[{"id":"paper-depil-nat-rev-drug-discov","kind":"paper","name":"'Off-the-shelf' allogeneic CAR T cells: development and challenges","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 31900462 and published in Nature Reviews Drug Discovery; the citing page links this DOI, which is how the record was matched.","summary":"Autologous chimeric antigen receptor (CAR) T cells have changed the therapeutic landscape in haematological malignancies. Nevertheless, the use of allogeneic CAR T cells from donors has many potential advantages over autologous approaches, such as the immediate availability of cryopreserved batches for patient treatment, possible standardization of the CAR-T cell product, time for multiple cell modifications, redosing or combination of CAR T cells directed against different targets, and decreased cost using an industrialized process. However, allogeneic CAR T cells may cause life-threatening graft-versus-host disease and may be rapidly eliminated by the host immune system. The development of next-generation allogeneic CAR T cells to address these issues is an active area of research. In this Review, we analyse the different sources of T cells for optimal allogeneic CAR-T cell therapy and describe the different technological approaches, mainly based on gene editing, to produce allogeneic CAR T cells with limited potential for graft-versus-host disease. These improved allogeneic CAR-T cell products will pave the way for further breakthroughs in the treatment of cancer.\n\nIndexed on Europe PMC as PubMed record 31900462 (DOI 10.1038/s41573-019-0051-2). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Drug Discov 2020","url":"https://doi.org/10.1038/s41573-019-0051-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31900462/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31900462"}],"tags":["europepmc-ingest"],"related":["allogeneic-cell-therapy"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-drug-discovery"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Drug Discovery","year":2020,"doi":"10.1038/s41573-019-0051-2","pmid":"31900462","authors":"Depil S, Duchateau P, Grupp SA, et al.","paperType":"review","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-capivasertib-breast-hr-positive-breast-2022","kind":"paper","name":"\"The emerging role of capivasertib in breast cancer\"","aka":[],"tldr":"Review on Capivasertib in HR-positive / HER2-negative breast cancer, in The Breast (2022), one of the most cited Europe PMC records with Capivasertib in its title.","summary":"Over 50% of breast tumors harbor alterations in one or more genes of the phosphatidylinositol 3-kinase (PI3K) pathway including PIK3CA mutations (31%), PTEN loss (34%), PTEN mutations (5%) and AKT1 mutations (3%). While PI3K and mTOR inhibitors are already approved in advanced breast cancer, AKT inhibitors have been recently developed as a new therapeutic approach. Capivasertib (AZD5363) is a novel, selective ATP-competitive pan-AKT kinase inhibitor that exerts similar activity against the three AKT isoforms, AKT1, AKT2, and AKT3. Preclinical studies demonstrated efficacy of capivasertib in breast cancer cell lines as a single agent or in combination with anti-HER2 agents and endocrine treatment, especially in tumors with PIK3CA or MTOR alterations. Phase I/II studies demonstrated greater efficacy when capivasertib was co-administered with paclitaxel, fulvestrant in hormone receptor (HR)-positive, HER2-negative breast cancer or olaparib. The recommended phase II dose of capivasertib as monotherapy was 480 mg bid on a 4-days-on, 3-days-off dosing schedule. Toxicity profile proved to be manageable with hyperglycemia (20-24%), diarrhea (14-17%) and maculopapular rash (11-16%) being the most common grade ≥3 adverse events. Ongoing Phase III trials of capivasertib in combination with fulvestrant (CAPItello-291), CDK4/6 inhibitor palbociclib (CAPItello-292) and paclitaxel (CAPItello- 290) will better clarify the therapeutic role of capivasertib in breast cancer.\n\nIndexed on Europe PMC as PubMed record 35398754 (DOI 10.1016/j.breast.2022.03.018). Its title names Capivasertib and its text names HR-positive / HER2-negative breast cancer; PubMed types it as a review (review-article, Review). It was matched automatically to the idea \"Molecular-progression switching beyond ESR1\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Breast 2022","url":"https://doi.org/10.1016/j.breast.2022.03.018"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35398754/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35398754"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["the-breast"],"dependsOn":[],"notes":[],"journal":"The Breast","year":2022,"doi":"10.1016/j.breast.2022.03.018","pmid":"35398754","authors":"Andrikopoulou A, Chatzinikolaou S, Panourgias E, et al.","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for Capivasertib in HR-positive / HER2-negative breast cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Capivasertib in the title and HR-positive / HER2-negative breast cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-psmaddition-lancet-2026","kind":"paper","name":"[ 177 Lu]Lu-PSMA-617 in patients with PSMA-positive metastatic androgen pathway modulator-naive/sensitive prostate cancer (PSMAddition): a phase 3 randomised, controlled trial","aka":[],"tldr":"Published report from the PSMAddition trial registered as NCT04720157, in The Lancet (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: A contemporary standard of care for patients with metastatic androgen pathway modulator-naive/sensitive (APMN/S) prostate cancer (also known as metastatic hormone-sensitive prostate cancer) is androgen deprivation therapy (ADT) plus an androgen receptor pathway inhibitor (ARPI) until progression. PSMAddition aimed to evaluate the efficacy and safety of [ 177 Lu]Lu-PSMA-617 ( 177 Lu-PSMA-617) combined with ADT plus ARPI in prostate-specific membrane antigen (PSMA)-positive metastatic APMN/S prostate cancer.\n\nMethods: PSMAddition is an ongoing, randomised, controlled, phase 3 superiority trial conducted at 169 sites across 20 countries, including hospitals, medical centres, and specialist cancer centres. Eligible male patients had treatment-naive or minimally treated metastatic APMN/S prostate cancer diagnosed by CT, MRI, or bone scan and one or more PSMA-positive metastatic lesion on centrally read baseline [ 68 Ga]Ga-PSMA-11 PET. Patients were randomly assigned 1:1 to open-label, intravenous 177 Lu-PSMA-617 (7·4 GBq [200 mCi] ±10% every 6 weeks for up to six cycles) with ADT plus ARPI ( 177 Lu-PSMA-617 arm) or ADT plus ARPI (control arm). ADT and ARPI were investigator-chosen according to local authorisation and administered per local product labelling. Control arm patients with centrally confirmed radiographic progression could cross over to 177 Lu-PSMA-617. The primary endpoint was radiographic progression-free survival (centrally assessed per Prostate Cancer Clinical Trials Working Group 3-modified RECIST 1.1 or death); secondary endpoints included safety and tolerability. We report the second interim analysis of radiographic progression-free survival in the intention-to-treat population (all randomly assigned participants; data cutoff Jan 13, 2025). Safety was assessed in all patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT04720157, and is ongoing.\n\nFindings: From June 15, 2021, to July 25, 2023, 1529 patients were screened and 1144 were randomly assigned (n=572 per arm; 1144 [100%] male, 572 [50%] with de novo metastatic APMN/S prostate cancer, 779 [68%] with high-volume disease; median age 68·0 years [IQR 62·0-73·0]). Baseline characteristics were balanced between arms. At second interim analysis for radiographic progression-free survival (median time from randomisation to data cutoff 23·6 months [IQR 20·3-29·2]; median radiographic progression-free survival follow-up time 19·6 months [IQR 14·0-24·1]), 139 (24%) of 572 participants in the 177 Lu-PSMA-617 arm and 172 (30%) of 572 participants in the control arm had radiographic disease progression or death. Radiographic progression-free survival was significantly improved in the 177 Lu-PSMA-617 arm versus the control arm, with a 28% reduction in the relative risk of radiographic progression or death (HR 0·72 [95% CI 0·58-0·90]; p=0·0021; median radiographic progression-free survival not reached in either arm). The primary endpoint was thus met. Grade 3 or worse adverse events occurred in 286 (51%) of 564 patients in the 177 Lu-PSMA-617 arm and 243 (43%) of 565 patients in the control arm. Serious adverse events occurred in 180 (32%) of 564 patients in the 177 Lu-PSMA-617 arm and 162 (29%) of 565 in the control arm; of which 17 (3%) in the 177 Lu-PSMA-617 arm were 177 Lu-PSMA-617-related. The most common adverse event was dry mouth, in 258 (46%) patients in the 177 Lu-PSMA-617 arm and 21 (4%) patients in the control arm; all were grade 1 or 2 and none were serious. Other common adverse events with higher incidence in the 177 Lu-PSMA-617 arm included cytopenias and gastrointestinal disturbances.\n\nInterpretation: Combining 177 Lu-PSMA-617 with ADT plus ARPI prolonged radiographic progression-free survival in patients with PSMA-positive metastatic APMN/S prostate cancer. Although adverse events were more frequent, there were no unexpected safety findings associated with the drug combination. Therefore, combining 177 Lu-PSMA-617 with ADT plus ARPI might be a new treatment option in metastatic APMN/S prostate cancer.\n\nFunding: Novartis.\n\nIndexed on Europe PMC as PubMed record 42561994 (DOI 10.1016/s0140-6736(26)01092-5). Its abstract cites the registry id NCT04720157, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet 2026","url":"https://doi.org/10.1016/s0140-6736(26)01092-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42561994/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42561994"},{"label":"ClinicalTrials.gov NCT04720157","url":"https://clinicaltrials.gov/study/NCT04720157"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["psmaddition"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2026,"doi":"10.1016/s0140-6736(26)01092-5","pmid":"42561994","authors":"Tagawa ST, Sartor O, Piulats JM, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04720157 with the most citations, so it is the natural first reading for anyone following the PSMAddition trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-therap-lancet-2021","kind":"paper","name":"[ 177 Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial","aka":[],"tldr":"Published report from the TheraP trial registered as NCT03392428, in The Lancet (2021), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Lutetium-177 [ 177 Lu]Lu-PSMA-617 is a radiolabelled small molecule that delivers β radiation to cells expressing prostate-specific membrane antigen (PSMA), with activity and safety in patients with metastatic castration-resistant prostate cancer. We aimed to compare [ 177 Lu]Lu-PSMA-617 with cabazitaxel in patients with metastatic castration-resistant prostate cancer.\n\nMethods: We did this multicentre, unblinded, randomised phase 2 trial at 11 centres in Australia. We recruited men with metastatic castration-resistant prostate cancer for whom cabazitaxel was considered the next appropriate standard treatment. Participants were required to have adequate renal, haematological, and liver function, and an Eastern Cooperative Oncology Group performance status of 0-2. Previous treatment with androgen receptor-directed therapy was allowed. Men underwent gallium-68 [ 68 Ga]Ga-PSMA-11 and 2-flourine-18[ 18 F]fluoro-2-deoxy-D-glucose (FDG) PET-CT scans. PET eligibility criteria for the trial were PSMA-positive disease, and no sites of metastatic disease with discordant FDG-positive and PSMA-negative findings. Men were randomly assigned (1:1) to [ 177 Lu]Lu-PSMA-617 (6·0-8·5 GBq intravenously every 6 weeks for up to six cycles) or cabazitaxel (20 mg/m 2 intravenously every 3 weeks for up to ten cycles). The primary endpoint was prostate-specific antigen (PSA) response defined by a reduction of at least 50% from baseline. This trial is registered with ClinicalTrials.gov, NCT03392428.\n\nFindings: Between Feb 6, 2018, and Sept 3, 2019, we screened 291 men, of whom 200 were eligible on PET imaging. Study treatment was received by 98 (99%) of 99 men randomly assigned to [ 177 Lu]Lu-PSMA-617 versus 85 (84%) of 101 randomly assigned to cabazitaxel. PSA responses were more frequent among men in the [ 177 Lu]Lu-PSMA-617 group than in the cabazitaxel group (65 vs 37 PSA responses; 66% vs 37% by intention to treat; difference 29% (95% CI 16-42; p<0·0001; and 66% vs 44% by treatment received; difference 23% [9-37]; p=0·0016). Grade 3-4 adverse events occurred in 32 (33%) of 98 men in the [ 177 Lu]Lu-PSMA-617 group versus 45 (53%) of 85 men in the cabazitaxel group. No deaths were attributed to [ 177 Lu]Lu-PSMA-617.\n\nInterpretation: [ 177 Lu]Lu-PSMA-617 compared with cabazitaxel in men with metastatic castration-resistant prostate cancer led to a higher PSA response and fewer grade 3 or 4 adverse events. [ 177 Lu]Lu-PSMA-617 is a new effective class of therapy and a potential alternative to cabazitaxel.\n\nFunding: Prostate Cancer Foundation of Australia, Endocyte (a Novartis company), Australian Nuclear Science and Technology Organization, Movember, The Distinguished Gentleman's Ride, It's a Bloke Thing, and CAN4CANCER.\n\nIndexed on Europe PMC as PubMed record 33581798 (DOI 10.1016/s0140-6736(21)00237-3). Its abstract cites the registry id NCT03392428, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet 2021","url":"https://doi.org/10.1016/s0140-6736(21)00237-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33581798/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33581798"},{"label":"ClinicalTrials.gov NCT03392428","url":"https://clinicaltrials.gov/study/NCT03392428"}],"tags":["europepmc-ingest"],"related":["prostate-roadmap","paper-de-bono-tropic-cabazitaxel-lancet-2010","idea-prostate-randomise-the-sequence-not-only-the-drugs"],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["psma-pet","radioligand-therapy"],"targets":["psma"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["theranostics","psa50"],"trials":["therap"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2021,"doi":"10.1016/s0140-6736(21)00237-3","pmid":"33581798","authors":"Hofman MS, Emmett L, Sandhu S, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03392428 with the most citations, so it is the natural first reading for anyone following the TheraP trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-shuch-lancet-oncol","kind":"paper","name":"[ 89 Zr]Zr-girentuximab for PET-CT imaging of clear-cell renal cell carcinoma: a prospective, open-label, multicentre, phase 3 trial","aka":[],"tldr":"Paper cited by one technology page and one idea page, indexed on Europe PMC as PubMed record 39270701 and published in The Lancet Oncology; the citing pages link this DOI, which is how the record was matched.","summary":"Background: With limitations of conventional imaging and biopsy, accurate, non-invasive techniques to detect clear-cell renal cell carcinoma in patients with renal masses remain an unmet need. 89 Zr-labelled monoclonal antibody ([ 89 Zr]Zr-girentuximab) has high affinity for carbonic anhydrase 9, a tumour antigen highly expressed in clear-cell renal cell carcinoma. We aimed to evaluate [ 89 Zr]Zr-girentuximab PET-CT imaging for detection and characterisation of clear-cell renal cell carcinoma.\n\nMethods: ZIRCON was a prospective, open-label, multicentre, phase 3 trial conducted at 36 research hospitals and practices across nine countries (the USA, Australia, Canada, the UK, Türkiye, Belgium, the Netherlands, Spain, and France). Patients aged 18 years or older with an indeterminate renal mass 7 cm or smaller (cT1) suspicious for clear-cell renal cell carcinoma and scheduled for nephrectomy received a single dose of [ 89 Zr]Zr-girentuximab (37 MBq ±10%; 10 mg girentuximab) intravenously followed by abdominal PET-CT imaging 5 days (±2 days) later. Surgery was performed no later than 90 days after administration of [ 89 Zr]Zr-girentuximab. Blinded central review, conducted by three independent readers, determined the histology from surgical samples. The coprimary endpoints, determined for each individual reader, were the sensitivity and specificity of [ 89 Zr]Zr-girentuximab PET-CT imaging to detect clear-cell renal cell carcinoma, with histopathological confirmation as standard of truth. Analyses were on the full analysis set of patients, defined as patients who had evaluable PET-CT imaging and a confirmed histopathological diagnosis. The trial is registered with ClinicalTrials.gov, NCT03849118, and EUDRA Clinical Trials Register, 2018-002773-21, and is closed to enrolment.\n\nFindings: Between Aug 14, 2019, and July 8, 2022, 371 patients were screened for eligibility, 332 of whom were enrolled. 300 patients received [ 89 Zr]Zr-girentuximab (214 [71%] male and 86 [29%] female). 284 (95%) evaluable patients were included in the primary analysis. The mean sensitivity was 85·5% (95% CI 81·5-89·6) and mean specificity was 87·0% (81·0-93·1). No safety signals were observed. Most adverse events were not or were unlikely to be related to [ 89 Zr]Zr-girentuximab, with most (193 [74%] of 261 events) occurring during or after surgery. The most common grade 3 or worse adverse events were post-procedural haemorrhage (in six [2%] of 261 patients), urinary retention (three [1%]), and hypertension (three [1%]). In 25 (8%) of 300 patients, 52 serious adverse events were reported, of which 51 (98%) occurred after surgery. There were no treatment-related deaths.\n\nInterpretation: Our results suggest that [ 89 Zr]Zr-girentuximab PET-CT has a favourable safety profile and is a highly accurate, non-invasive imaging modality for the detection and characterisation of clear-cell renal cell carcinoma, which has the potential to be practice changing.\n\nFunding: Telix Pharmaceuticals.\n\nIndexed on Europe PMC as PubMed record 39270701 (DOI 10.1016/s1470-2045(24)00402-9). Matched by DOI alone: one technology page and one idea page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2024","url":"https://doi.org/10.1016/s1470-2045(24)00402-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39270701/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39270701"}],"tags":["europepmc-ingest"],"related":["caix-pet","idea-caix-theranostics"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2024,"doi":"10.1016/s1470-2045(24)00402-9","pmid":"39270701","authors":"Shuch B, Pantuck AJ, Bernhard JC, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page and one idea page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-hera-b31-n9831-lancet-2017-update","kind":"paper","name":"11 years' follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial","aka":[],"tldr":"Later report from the HERA trial registered as NCT00045032, in The Lancet (2017); its title describes an updated or longer-term analysis.","summary":"Background: Clinical trials have shown that trastuzumab, a recombinant monoclonal antibody against HER2 receptor, significantly improves overall survival and disease-free survival in women with HER2-positive early breast cancer, but long-term follow-up data are needed. We report the results of comparing observation with two durations of trastuzumab treatment at a median follow-up of 11 years, for patients enrolled in the HERA (HERceptin Adjuvant) trial.\n\nMethods: HERA (BIG 1-01) is an international, multicentre, open-label, phase 3 randomised trial of 5102 women with HER2-positive early breast cancer, who were enrolled from hospitals in 39 countries between Dec 7, 2001, and June 20, 2005. After completion of all primary therapy (including, surgery, chemotherapy, and radiotherapy as indicated), patients were randomly assigned (1:1:1) to receive trastuzumab for 1 year (once at 8 mg/kg of bodyweight intravenously, then 6 mg/kg once every 3 weeks) or for 2 years (with the same dose schedule), or to the observation group. Primary endpoint is disease-free survival, and analyses are in the intention-to-treat population. Hazard ratios (HRs) were estimated from Cox models, and survival curves were estimated by the Kaplan-Meier method. Comparison of 2 years versus 1 year of trastuzumab is based on 366-day landmark analyses. This study is registered with ClinicalTrials.gov (NCT00045032).\n\nFindings: Of the 5102 women randomly assigned in the HERA trial, three patients had no evidence of having provided written informed consent to participate. We followed up the intention-to-treat population of 5099 patients (1697 in observation, 1702 in 1-year trastuzumab, and 1700 in 2-years trastuzumab groups). After a median follow-up of 11 years (IQR 10·09-11·53), random assignment to 1 year of trastuzumab significantly reduced the risk of a disease-free survival event (HR 0·76, 95% CI 0·68-0·86) and death (0·74, 0·64-0·86) compared with observation. 2 years of adjuvant trastuzumab did not improve disease free-survival outcomes compared with 1 year of this drug (HR 1·02, 95% CI 0·89-1·17). Estimates of 10-year disease-free survival were 63% for observation, 69% for 1 year of trastuzumab, and 69% for 2 years of trastuzumab. 884 (52%) patients assigned to the observation group selectively crossed over to receive trastuzumab. Cardiac toxicity remained low in all groups and occurred mostly during the treatment phase. The incidence of secondary cardiac endpoints was 122 (7·3%) in the 2-years trastuzumab group, 74 (4·4%) in the 1-year trastuzumab group, and 15 (0·9%) in the observation group.\n\nInterpretation: 1 year of adjuvant trastuzumab after chemotherapy for patients with HER2-positive early breast cancer significantly improves long-term disease-free survival, compared with observation. 2 years of trastuzumab had no additional benefit.\n\nFunding: F Hoffmann-La Roche (Roche).\n\nIndexed on Europe PMC as PubMed record 28215665 (DOI 10.1016/s0140-6736(16)32616-2). Its abstract cites the registry id NCT00045032, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet 2017","url":"https://doi.org/10.1016/s0140-6736(16)32616-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28215665/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28215665"},{"label":"ClinicalTrials.gov NCT00045032","url":"https://clinicaltrials.gov/study/NCT00045032"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["hera-b31-n9831"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2017,"doi":"10.1016/s0140-6736(16)32616-2","pmid":"28215665","authors":"Cameron D, Piccart-Gebhart MJ, Gelber RD, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the HERA trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-psmafore-lancet-2024","kind":"paper","name":"177 Lu-PSMA-617 versus a change of androgen receptor pathway inhibitor therapy for taxane-naive patients with progressive metastatic castration-resistant prostate cancer (PSMAfore): a phase 3, randomised, controlled trial","aka":[],"tldr":"Published report from the PSMAfore trial registered as NCT04689828, in The Lancet (2024), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: [ 177 Lu]Lu-PSMA-617 ( 177 Lu-PSMA-617) prolongs radiographic progression-free survival and overall survival in patients with metastatic castration-resistant prostate cancer previously treated with androgen receptor pathway inhibitor (ARPI) and taxane therapy. We aimed to investigate the efficacy of 177 Lu-PSMA-617 in patients with taxane-naive metastatic castration-resistant prostate cancer.\n\nMethods: In this phase 3, randomised, controlled trial conducted at 74 sites across Europe and North America, taxane-naive patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer who had progressed once on a previous ARPI were randomly allocated (1:1) to open-label, intravenous 177 Lu-PSMA-617 at a dosage of 7·4 GBq (200 mCi) ± 10% once every 6 weeks for six cycles, or a change of ARPI (to abiraterone or enzalutamide, administered orally on a continuous basis per product labelling). Crossover from ARPI change to 177 Lu-PSMA-617 was allowed after centrally confirmed radiographic progression. The primary endpoint was radiographic progression-free survival, defined as the time from randomisation until radiographic progression or death, assessed in the intention-to-treat population. Safety was a secondary endpoint. This study is registered with ClinicalTrials.gov (NCT04689828) and is ongoing. In this primary report of the study, we present primary (first data cutoff) and updated (third data cutoff) analyses of radiographic progression-free survival; all other data are based on the third data cutoff.\n\nFindings: Overall, of the 585 patients screened, 468 met all eligibility criteria and were randomly allocated between June 15, 2021 and Oct 7, 2022 to receive 177 Lu-PSMA-617 (234 [50%] patients) or ARPI change (234 [50%]). Baseline characteristics were mostly similar between groups; median number of 177 Lu-PSMA-617 cycles was 6·0 (IQR 4·0-6·0). Of patients assigned to ARPI change, 134 (57%) crossed over to receive 177 Lu-PSMA-617. In the primary analysis (median time from randomisation to first data cutoff 7·26 months [IQR 3·38-10·55]), the median radiographic progression-free survival was 9·30 months (95% CI 6·77-not estimable) in the 177 Lu-PSMA-617 group versus 5·55 months (4·04-5·95) in the ARPI change group (hazard ratio [HR] 0·41 [95% CI 0·29-0·56]; p<0·0001). In the updated analysis at time of the third data cutoff (median time from randomisation to third data cutoff 24·11 months [IQR 20·24-27·40]), median radiographic progression-free survival was 11·60 months (95% CI 9·30-14·19) in the 177 Lu-PSMA-617 group versus 5·59 months (4·21-5·95) in the ARPI change group (HR 0·49 [95% CI 0·39-0·61]). The incidence of grade 3-5 adverse events was lower in the 177 Lu-PSMA-617 group (at least one event in 81 [36%] of 227 patients; four [2%] grade 5 [none treatment related]) than the ARPI change group (112 [48%] of 232; five [2%] grade 5 [one treatment related]).\n\nInterpretation: 177 Lu-PSMA-617 prolonged radiographic progression-free survival relative to ARPI change, with a favourable safety profile. For patients with PSMA-positive metastatic castration-resistant prostate cancer who are being considered for a change of ARPI after progression on a previous ARPI, 177 Lu-PSMA-617 may be an effective treatment alternative.\n\nFunding: Novartis.\n\nIndexed on Europe PMC as PubMed record 39293462 (DOI 10.1016/s0140-6736(24)01653-2). Its abstract cites the registry id NCT04689828, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet 2024","url":"https://doi.org/10.1016/s0140-6736(24)01653-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39293462/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39293462"},{"label":"ClinicalTrials.gov NCT04689828","url":"https://clinicaltrials.gov/study/NCT04689828"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["psmafore"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2024,"doi":"10.1016/s0140-6736(24)01653-2","pmid":"39293462","authors":"Morris MJ, Castellano D, Herrmann K, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04689828 with the most citations, so it is the natural first reading for anyone following the PSMAfore trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-pan-n-engl-j-med","kind":"paper","name":"20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years","aka":[],"tldr":"Paper cited by one term page and one bottleneck page, indexed on Europe PMC as PubMed record 29117498 and published in New England Journal of Medicine; the citing pages link this DOI, which is how the record was matched.","summary":"Background: The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)-positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment.\n\nMethods: In this meta-analysis of the results of 88 trials involving 62,923 women with ER-positive breast cancer who were disease-free after 5 years of scheduled endocrine therapy, we used Kaplan-Meier and Cox regression analyses, stratified according to trial and treatment, to assess the associations of tumor diameter and nodal status (TN), tumor grade, and other factors with patients' outcomes during the period from 5 to 20 years.\n\nResults: Breast-cancer recurrences occurred at a steady rate throughout the study period from 5 to 20 years. The risk of distant recurrence was strongly correlated with the original TN status. Among the patients with stage T1 disease, the risk of distant recurrence was 13% with no nodal involvement (T1N0), 20% with one to three nodes involved (T1N1-3), and 34% with four to nine nodes involved (T1N4-9); among those with stage T2 disease, the risks were 19% with T2N0, 26% with T2N1-3, and 41% with T2N4-9. The risk of death from breast cancer was similarly dependent on TN status, but the risk of contralateral breast cancer was not. Given the TN status, the factors of tumor grade (available in 43,590 patients) and Ki-67 status (available in 7692 patients), which are strongly correlated with each other, were of only moderate independent predictive value for distant recurrence, but the status regarding the progesterone receptor (in 54,115 patients) and human epidermal growth factor receptor type 2 (HER2) (in 15,418 patients in trials with no use of trastuzumab) was not predictive. During the study period from 5 to 20 years, the absolute risk of distant recurrence among patients with T1N0 breast cancer was 10% for low-grade disease, 13% for moderate-grade disease, and 17% for high-grade disease; the corresponding risks of any recurrence or a contralateral breast cancer were 17%, 22%, and 26%, respectively.\n\nConclusions: After 5 years of adjuvant endocrine therapy, breast-cancer recurrences continued to occur steadily throughout the study period from 5 to 20 years. The risk of distant recurrence was strongly correlated with the original TN status, with risks ranging from 10 to 41%, depending on TN status and tumor grade. (Funded by Cancer Research UK and others.).\n\nIndexed on Europe PMC as PubMed record 29117498 (DOI 10.1056/nejmoa1701830). Matched by DOI alone: one term page and one bottleneck page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2017","url":"https://doi.org/10.1056/nejmoa1701830"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29117498/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29117498"}],"tags":["europepmc-ingest"],"related":["late-recurrence","b-dormancy-mrd"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2017,"doi":"10.1056/nejmoa1701830","pmid":"29117498","authors":"Pan H, Gray R, Braybrooke J, et al.","paperType":"meta-analysis","findings":[],"whatItMeans":"One term page and one bottleneck page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-ata-2015-thyroid-nodules-dtc-haugen-thyroid-2016","kind":"paper","name":"2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer","aka":[],"tldr":"The 2015 American Thyroid Association guideline moved differentiated thyroid cancer towards less treatment: lobectomy rather than total thyroidectomy for many low-risk cancers, selective rather than routine radioactive iodine, and active surveillance for small papillary cancers.","summary":"Comprehensive guideline covering evaluation of thyroid nodules, ultrasound risk stratification, molecular testing, extent of surgery, risk stratification for recurrence, radioactive iodine indications, TSH suppression, follow-up, and management of recurrent and metastatic differentiated thyroid cancer including kinase inhibitors.","asOf":"2026-09-17","links":[{"label":"Thyroid 2016","url":"https://doi.org/10.1089/thy.2015.0020"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26462967/"}],"tags":[],"related":[],"cancers":["follicular-thyroid-cancer","papillary-thyroid-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["bryan-haugen"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Thyroid","year":2016,"doi":"10.1089/thy.2015.0020","pmid":"26462967","authors":"Haugen BR, Alexander EK, Bible KC, et al.","paperType":"guideline","findings":[],"whatItMeans":"The follicular and papillary thyroid cancer pages' recommendations for lobectomy, selective iodine and surveillance of microcarcinoma follow this guideline.","caveats":["Under revision; ESTIMABL2 and IoN have since supported omitting iodine in low-risk disease."],"changedPractice":true},{"id":"paper-ata-anaplastic-thyroid-guideline-bible-thyroid-2021","kind":"paper","name":"2021 American Thyroid Association guidelines for management of patients with anaplastic thyroid cancer","aka":[],"tldr":"The updated American guideline for anaplastic thyroid cancer stresses molecular testing within days of diagnosis, BRAF-MEK inhibitors for BRAF-mutant disease including before surgery, multimodal therapy for resectable disease, and early goals-of-care discussions.","summary":"Evidence-based guideline covering rapid diagnosis and staging, airway management, molecular testing, surgery, radiotherapy with or without chemotherapy, BRAF-directed and other targeted therapy, immunotherapy, and palliative and supportive care for anaplastic thyroid cancer.","asOf":"2026-09-17","links":[{"label":"Thyroid 2021","url":"https://doi.org/10.1089/thy.2020.0944"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33728999/"}],"tags":[],"related":[],"cancers":["anaplastic-thyroid-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["keith-bible"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Thyroid","year":2021,"doi":"10.1089/thy.2020.0944","pmid":"33728999","authors":"Bible KC, Kebebew E, Brierley J, et al.","paperType":"guideline","findings":[],"whatItMeans":"The anaplastic thyroid cancer page's emphasis on speed, BRAF testing and neoadjuvant targeted therapy follows this guideline.","caveats":["Evidence for most recommendations is from small series."],"changedPractice":true},{"id":"paper-heuser-blood","kind":"paper","name":"2021 Update on MRD in acute myeloid leukemia: a consensus document from the European LeukemiaNet MRD Working Party","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 34724563 and published in Blood; the citing page links this DOI, which is how the record was matched.","summary":"Measurable residual disease (MRD) is an important biomarker in acute myeloid leukemia (AML) that is used for prognostic, predictive, monitoring, and efficacy-response assessments. The European LeukemiaNet (ELN) MRD Working Party evaluated standardization and harmonization of MRD in an ongoing manner and has updated the 2018 ELN MRD recommendations based on significant developments in the field. New and revised recommendations were established during in-person and online meetings, and a 2-stage Delphi poll was conducted to optimize consensus. All recommendations are graded by levels of evidence and agreement. Major changes include technical specifications for next-generation sequencing-based MRD testing and integrative assessments of MRD irrespective of technology. Other topics include use of MRD as a prognostic and surrogate end point for drug testing; selection of the technique, material, and appropriate time points for MRD assessment; and clinical implications of MRD assessment. In addition to technical recommendations for flow- and molecular-MRD analysis, we provide MRD thresholds and define MRD response, and detail how MRD results should be reported and combined if several techniques are used. MRD assessment in AML is complex and clinically relevant, and standardized approaches to application, interpretation, technical conduct, and reporting are of critical importance.\n\nIndexed on Europe PMC as PubMed record 34724563 (DOI 10.1182/blood.2021013626). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Blood 2021","url":"https://doi.org/10.1182/blood.2021013626"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34724563/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34724563"}],"tags":["europepmc-ingest"],"related":["mrd-negative-cr"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["blood"],"dependsOn":[],"notes":[],"journal":"Blood","year":2021,"doi":"10.1182/blood.2021013626","pmid":"34724563","authors":"Heuser M, Freeman SD, Ossenkoppele GJ, et al.","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-lyon-eur-heart-j","kind":"paper","name":"2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS)","aka":[],"tldr":"Paper cited by two technology pages, indexed on Europe PMC as PubMed record 36017568 and published in European heart journal; the citing pages link this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 36017568 (DOI 10.1093/eurheartj/ehac244). Matched by DOI alone: two technology pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Eur Heart J 2022","url":"https://doi.org/10.1093/eurheartj/ehac244"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36017568/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36017568"}],"tags":["europepmc-ingest"],"related":["strain-echocardiography-gls","cardiac-biomarker-monitoring"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"European heart journal","year":2022,"doi":"10.1093/eurheartj/ehac244","pmid":"36017568","authors":"Lyon AR, López-Fernández T, Couch LS, et al.","paperType":"observational","findings":[],"whatItMeans":"Two technology pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-rxponder-n-engl-j-med-2021","kind":"paper","name":"21-Gene Assay to Inform Chemotherapy Benefit in Node-Positive Breast Cancer","aka":[],"tldr":"Published report from the RxPONDER trial registered as NCT01272037, in New England Journal of Medicine (2021), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: The recurrence score based on the 21-gene breast-cancer assay has been clinically useful in predicting a chemotherapy benefit in hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, axillary lymph-node-negative breast cancer. In women with positive lymph-node disease, the role of the recurrence score with respect to predicting a benefit of adjuvant chemotherapy is unclear.\n\nMethods: In a prospective trial, we randomly assigned women with hormone-receptor-positive, HER2-negative breast cancer, one to three positive axillary lymph nodes, and a recurrence score of 25 or lower (scores range from 0 to 100, with higher scores indicating a worse prognosis) to endocrine therapy only or to chemotherapy plus endocrine (chemoendocrine) therapy. The primary objective was to determine the effect of chemotherapy on invasive disease-free survival and whether the effect was influenced by the recurrence score. Secondary end points included distant relapse-free survival.\n\nResults: A total of 5083 women (33.2% premenopausal and 66.8% postmenopausal) underwent randomization, and 5018 participated in the trial. At the prespecified third interim analysis, the chemotherapy benefit with respect to increasing invasive disease-free survival differed according to menopausal status (P = 0.008 for the comparison of chemotherapy benefit in premenopausal and postmenopausal participants), and separate prespecified analyses were conducted. Among postmenopausal women, invasive disease-free survival at 5 years was 91.9% in the endocrine-only group and 91.3% in the chemoendocrine group, with no chemotherapy benefit (hazard ratio for invasive disease recurrence, new primary cancer [breast cancer or another type], or death, 1.02; 95% confidence interval [CI], 0.82 to 1.26; P = 0.89). Among premenopausal women, invasive disease-free survival at 5 years was 89.0% with endocrine-only therapy and 93.9% with chemoendocrine therapy (hazard ratio, 0.60; 95% CI, 0.43 to 0.83; P = 0.002), with a similar increase in distant relapse-free survival (hazard ratio, 0.58; 95% CI, 0.39 to 0.87; P = 0.009). The relative chemotherapy benefit did not increase as the recurrence score increased.\n\nConclusions: Among premenopausal women with one to three positive lymph nodes and a recurrence score of 25 or lower, those who received chemoendocrine therapy had longer invasive disease-free survival and distant relapse-free survival than those who received endocrine-only therapy, whereas postmenopausal women with similar characteristics did not benefit from adjuvant chemotherapy. (Funded by the National Cancer Institute and others; RxPONDER ClinicalTrials.gov number, NCT01272037.).\n\nIndexed on Europe PMC as PubMed record 34914339 (DOI 10.1056/nejmoa2108873). Its abstract cites the registry id NCT01272037, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2021","url":"https://doi.org/10.1056/nejmoa2108873"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34914339/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34914339"},{"label":"ClinicalTrials.gov NCT01272037","url":"https://clinicaltrials.gov/study/NCT01272037"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["rxponder"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2021,"doi":"10.1056/nejmoa2108873","pmid":"34914339","authors":"Kalinsky K, Barlow WE, Gralow JR, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT01272037 with the most citations, so it is the natural first reading for anyone following the RxPONDER trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-phergain-lancet-2024-update","kind":"paper","name":"3-year invasive disease-free survival with chemotherapy de-escalation using an 18 F-FDG-PET-based, pathological complete response-adapted strategy in HER2-positive early breast cancer (PHERGain): a randomised, open-label, phase 2 trial","aka":[],"tldr":"Later report from the PHERGain trial registered as NCT03161353, in The Lancet (2024); its title describes an updated or longer-term analysis.","summary":"Background: PHERGain was designed to assess the feasibility, safety, and efficacy of a chemotherapy-free treatment based on a dual human epidermal growth factor receptor 2 (HER2) blockade with trastuzumab and pertuzumab in patients with HER2-positive early breast cancer (EBC). It used an 18 fluorine-fluorodeoxyglucose-PET-based, pathological complete response (pCR)-adapted strategy.\n\nMethods: PHERGain was a randomised, open-label, phase 2 trial that took place in 45 hospitals in seven European countries. It randomly allocated patients in a 1:4 ratio with centrally confirmed, HER2-positive, stage I-IIIA invasive, operable breast cancer with at least one PET-evaluable lesion to either group A, where patients received docetaxel (75 mg/m 2, intravenous), carboplatin (area under the curve 6 mg/mL per min, intravenous), trastuzumab (600 mg fixed dose, subcutaneous), and pertuzumab (840 mg loading dose followed by 420 mg maintenance doses, intravenous; TCHP), or group B, where patients received trastuzumab and pertuzumab with or without endocrine therapy, every 3 weeks. Random allocation was stratified by hormone receptor status. Centrally reviewed PET was conducted at baseline and after two treatment cycles. Patients in group B were treated according to on-treatment PET results. Patients in group B who were PET-responders continued with trastuzumab and pertuzumab with or without endocrine therapy for six cycles, while PET-non-responders were switched to receive six cycles of TCHP. After surgery, patients in group B who were PET-responders who did not achieve a pCR received six cycles of TCHP, and all patients completed up to 18 cycles of trastuzumab and pertuzumab. The primary endpoints were pCR in patients who were group B PET-responders after two treatment cycles (the results for which have been reported previously) and 3-year invasive disease-free survival (iDFS) in patients in group B. The study is registered with ClinicalTrials.gov (NCT03161353) and is ongoing.\n\nFindings: Between June 26, 2017, and April 24, 2019, a total of 356 patients were randomly allocated (71 patients in group A and 285 patients in group B), and 63 (89%) and 267 (94%) patients proceeded to surgery in groups A and B, respectively. At this second analysis (data cutoff: Nov 4, 2022), the median duration of follow-up was 43·3 months (range 0·0-63·0). In group B, the 3-year iDFS rate was 94·8% (95% CI 91·4-97·1; p=0·001), meeting the primary endpoint. No new safety signals were identified. Treatment-related adverse events and serious adverse events (SAEs) were numerically higher in patients allocated to group A than to group B (grade ≥3 62% vs 33%; SAEs 28% vs 14%). Group B PET-responders with pCR presented the lowest incidence of treatment-related grade 3 or higher adverse events (1%) without any SAEs.\n\nInterpretation: Among HER2-positive EBC patients, a PET-based, pCR-adapted strategy was associated with an excellent 3-year iDFS. This strategy identified about a third of patients who had HER2-positive EBC who could safely omit chemotherapy.\n\nFunding: F Hoffmann-La Roche.\n\nIndexed on Europe PMC as PubMed record 38582092 (DOI 10.1016/s0140-6736(24)00054-0). Its abstract cites the registry id NCT03161353, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet 2024","url":"https://doi.org/10.1016/s0140-6736(24)00054-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38582092/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38582092"},{"label":"ClinicalTrials.gov NCT03161353","url":"https://clinicaltrials.gov/study/NCT03161353"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["phergain"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2024,"doi":"10.1016/s0140-6736(24)00054-0","pmid":"38582092","authors":"Pérez-García JM, Cortés J, Ruiz-Borrego M, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the PHERGain trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-neosphere-lancet-oncol-2016-update","kind":"paper","name":"5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial","aka":[],"tldr":"Later report from the NeoSphere trial registered as NCT00545688, in The Lancet Oncology (2016); its title describes an updated or longer-term analysis.","summary":"Background: In the primary analysis of the NeoSphere trial, patients given neoadjuvant pertuzumab, trastuzumab, and docetaxel showed a significantly improved pathological complete response compared with those given trastuzumab and docetaxel after surgery. Here, we report 5-year progression-free survival, disease-free survival, and safety.\n\nMethods: In this multicentre, open-label, phase 2 randomised trial in hospitals and medical clinics, treatment-naive adults with locally advanced, inflammatory, or early-stage HER2-positive breast cancer were randomly assigned (1:1:1:1) to receive four neoadjuvant cycles of trastuzumab (8 mg/kg loading dose, followed by 6 mg/kg every 3 weeks) plus docetaxel (75 mg/m(2) every 3 weeks, increasing to 100 mg/m(2) from cycle 2 if tolerated; group A), pertuzumab (840 mg loading dose, followed by 420 mg every 3 weeks) and trastuzumab plus docetaxel (group B), pertuzumab and trastuzumab (group C), or pertuzumab and docetaxel (group D). After surgery, patients received three cycles of FEC (fluorouracil 600 mg/m(2), epirubicin 90 mg/m(2), and cyclophosphamide 600 mg/m(2)) every 3 weeks (patients in group C received four cycles of docetaxel prior to FEC), and trastuzumab 6 mg/kg every 3 weeks to complete 1 year's treatment (17 cycles in total). Randomisation was done by a central centre using dynamic allocation, stratified by operable, locally advanced, and inflammatory breast cancer, and by oestrogen and/or progesterone receptor positivity. Safety analyses were done according to treatment received. The primary endpoint (pathological complete response) was previously reported; secondary endpoints reported here are 5-year progression-free survival (analysed in the intention-to-treat population) and disease-free survival (analysed in patients who had surgery). Secondary and exploratory analyses were not powered for formal statistical hypothesis testing, and therefore results are for descriptive purposes only. The study ended on Sept 22, 2014 (last patient, last visit). This study is registered with ClinicalTrials.gov, number NCT00545688.\n\nFindings: Between Dec 17, 2007, and Dec 22, 2009, 417 eligible patients were randomly assigned to group A (107 patients), group B (107 patients), group C (107 patients), or group D (96 patients). One patient in group A withdrew before treatment. One patient assigned to group D received group A treatment, one patient assigned to group D received group B treatment, and one patient assigned to group B received group C treatment. At clinical cutoff, 87 patients had progressed or died. 5-year progression-free survival rates were 81% (95% CI 71-87) for group A, 86% (77-91) for group B, 73% (64-81) for group C, and 73% (63-81) for group D (hazard ratios 0·69 [95% CI 0·34-1·40] group B vs group A, 1·25 [0·68-2·30] group C vs group A, and 2·05 [1·07-3·93] group D vs group B). Disease-free survival results were consistent with progression-free survival results and were 81% (95% CI 72-88) for group A, 84% (72-91) for group B, 80% (70-86) for group C, and 75% (64-83) for group D. Patients who achieved total pathological complete response (all groups combined) had longer progression-free survival compared with patients who did not (85% [76-91] in patients who achieved total pathological response vs 76% [71-81] in patients who did not achieve total pathological response; hazard ratio 0·54 [95% CI 0·29-1·00]). There were no new or long-term safety concerns and tolerability was similar across groups (neoadjuvant and adjuvant treatment periods combined). The most common grade 3 or worse adverse events were neutropenia (group A: 71 [66%] of 107 patients; group B: 59 [55%] of 107; group C: 40 [37%] of 108; group D: 60 [64%] of 94), febrile neutropenia (group A: 10 [9%]; group B: 12 [11%]; group C: 5 [5%]; group D: 15 [16%]), and leucopenia (group A: 13 [12%]; group B: 6 [6%]; group C: 4 [4%]; group D: 8 [9%]). The number of patients with one or more serious adverse event was similar across groups (19-22 serious adverse events per group in 18-22% of patients).\n\nInterpretation: Progression-free survival and disease-free survival at 5-year follow-up show large and overlapping CIs, but support the primary endpoint (pathological complete response) and suggest that neoadjuvant pertuzumab is beneficial when combined with trastuzumab and docetaxel. Additionally, they suggest that total pathological complete response could be an early indicator of long-term outcome in early-stage HER2-positive breast cancer.\n\nFunding: F Hoffmann-La Roche.\n\nIndexed on Europe PMC as PubMed record 27179402 (DOI 10.1016/s1470-2045(16)00163-7). Its abstract cites the registry id NCT00545688, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2016","url":"https://doi.org/10.1016/s1470-2045(16)00163-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27179402/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27179402"},{"label":"ClinicalTrials.gov NCT00545688","url":"https://clinicaltrials.gov/study/NCT00545688"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["neosphere"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2016,"doi":"10.1016/s1470-2045(16)00163-7","pmid":"27179402","authors":"Gianni L, Pienkowski T, Im YH, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the NeoSphere trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-persephone-lancet-2019","kind":"paper","name":"6 versus 12 months of adjuvant trastuzumab for HER2-positive early breast cancer (PERSEPHONE): 4-year disease-free survival results of a randomised phase 3 non-inferiority trial","aka":[],"tldr":"Published report from the PERSEPHONE trial registered as NCT00712140, in The Lancet (2019), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Adjuvant trastuzumab significantly improves outcomes for patients with HER2-positive early breast cancer. The standard treatment duration is 12 months but shorter treatment could provide similar efficacy while reducing toxicities and cost. We aimed to investigate whether 6-month adjuvant trastuzumab treatment is non-inferior to the standard 12-month treatment regarding disease-free survival.\n\nMethods: This study is an open-label, randomised phase 3 non-inferiority trial. Patients were recruited from 152 centres in the UK. We randomly assigned patients with HER2-positive early breast cancer, aged 18 years or older, and with a clear indication for chemotherapy, by a computerised minimisation process (1:1), to receive either 6-month or 12-month trastuzumab delivered every 3 weeks intravenously (loading dose of 8 mg/kg followed by maintenance doses of 6 mg/kg) or subcutaneously (600 mg), given in combination with chemotherapy (concurrently or sequentially). The primary endpoint was disease-free survival, analysed by intention to treat, with a non-inferiority margin of 3% for 4-year disease-free survival. Safety was analysed in all patients who received trastuzumab. This trial is registered with EudraCT (number 2006-007018-39), ISRCTN (number 52968807), and ClinicalTrials.gov (number NCT00712140).\n\nFindings: Between Oct 4, 2007, and July 31, 2015, 2045 patients were assigned to 12-month trastuzumab treatment and 2044 to 6-month treatment (one patient was excluded because they were double randomised). Median follow-up was 5·4 years (IQR 3·6-6·7) for both treatment groups, during which a disease-free survival event occurred in 265 (13%) of 2043 patients in the 6-month group and 247 (12%) of 2045 patients in the 12-month group. 4-year disease-free survival was 89·4% (95% CI 87·9-90·7) in the 6-month group and 89·8% (88·3-91·1) in the 12-month group (hazard ratio 1·07 [90% CI 0·93-1·24], non-inferiority p=0·011), showing non-inferiority of the 6-month treatment. 6-month trastuzumab treatment resulted in fewer patients reporting severe adverse events (373 [19%] of 1939 patients vs 459 [24%] of 1894 patients, p=0·0002) or stopping early because of cardiotoxicity (61 [3%] of 1939 patients vs 146 [8%] of 1894 patients, p<0·0001).\n\nInterpretation: We have shown that 6-month trastuzumab treatment is non-inferior to 12-month treatment in patients with HER2-positive early breast cancer, with less cardiotoxicity and fewer severe adverse events. These results support consideration of reduced duration trastuzumab for women at similar risk of recurrence as to those included in the trial.\n\nFunding: UK National Institute for Health Research, Health Technology Assessment Programme.\n\nIndexed on Europe PMC as PubMed record 31178152 (DOI 10.1016/s0140-6736(19)30650-6). Its abstract cites the registry id NCT00712140, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet 2019","url":"https://doi.org/10.1016/s0140-6736(19)30650-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31178152/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31178152"},{"label":"ClinicalTrials.gov NCT00712140","url":"https://clinicaltrials.gov/study/NCT00712140"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["persephone"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2019,"doi":"10.1016/s0140-6736(19)30650-6","pmid":"31178152","authors":"Earl HM, Hiller L, Vallier AL, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT00712140 with the most citations, so it is the natural first reading for anyone following the PERSEPHONE trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-kratochwil-j-nucl-med","kind":"paper","name":"68 Ga-FAPI PET/CT: Tracer Uptake in 28 Different Kinds of Cancer","aka":[],"tldr":"Paper cited by one idea page, indexed on Europe PMC as PubMed record 30954939 and published in Journal of Nuclear Medicine; the citing page links this DOI, which is how the record was matched.","summary":"The recent development of quinoline-based PET tracers that act as fibroblast-activation-protein inhibitors (FAPIs) demonstrated promising preclinical and clinical results. FAP is overexpressed by cancer-associated fibroblasts of several tumor entities. Here, we quantify the tumor uptake on 68 Ga-FAPI PET/CT of various primary and metastatic tumors to identify the most promising indications for future application. Methods: 68 Ga-FAPI PET/CT scans were requested by various referring physicians according to individual clinical indications that were considered insufficiently covered by 18 F-FDG PET/CT or other imaging modalities. All PET/CT was performed 1 h after injection of 122-312 MBq of 68 Ga-FAPI-04. We retrospectively identified 80 patients with histopathologically proven primary tumors or metastases or radiologically unequivocal metastatic lesions of histologically proven primary tumors. Tumor uptake was quantified by SUV max and SUV mean (60% isocontour). Results: Eighty patients with 28 different tumor entities (54 primary tumors and 229 metastases) were evaluated. The highest average SUV max (>12) was found in sarcoma, esophageal, breast, cholangiocarcinoma, and lung cancer. The lowest 68 Ga-FAPI uptake (average SUV max < 6) was observed in pheochromocytoma, renal cell, differentiated thyroid, adenoid cystic, and gastric cancer. The average SUV max of hepatocellular, colorectal, head-neck, ovarian, pancreatic, and prostate cancer was intermediate (SUV 6-12). SUV varied across and within all tumor entities. Because of low background in muscle and blood pool (SUV max < 2), the tumor-to-background contrast ratios were more than 3-fold in the intermediate and more than 6-fold in the high-intensity uptake group. Conclusion: Several highly prevalent cancers presented with remarkably high uptake and image contrast on 68 Ga-FAPI PET/CT. The high and rather selective tumor uptake may open up new applications for noninvasive tumor characterization, staging examinations, or radioligand therapy.\n\nIndexed on Europe PMC as PubMed record 30954939 (DOI 10.2967/jnumed.119.227967). Matched by DOI alone: one idea page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Nucl Med 2019","url":"https://doi.org/10.2967/jnumed.119.227967"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30954939/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30954939"}],"tags":["europepmc-ingest"],"related":["idea-fap-theranostics-pancancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-nuclear-medicine"],"dependsOn":[],"notes":[],"journal":"Journal of Nuclear Medicine","year":2019,"doi":"10.2967/jnumed.119.227967","pmid":"30954939","authors":"Kratochwil C, Flechsig P, Lindner T, et al.","paperType":"basic","findings":[],"whatItMeans":"One idea page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-piccart-lancet-oncol","kind":"paper","name":"70-gene signature as an aid for treatment decisions in early breast cancer: updated results of the phase 3 randomised MINDACT trial with an exploratory analysis by age","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 33721561 and published in The Lancet Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background: The MINDACT trial showed excellent 5-year distant metastasis-free survival of 94·7% (95% CI 92·5-96·2) in patients with breast cancer of high clinical and low genomic risk who did not receive chemotherapy. We present long-term follow-up results together with an exploratory analysis by age.\n\nMethods: MINDACT was a multicentre, randomised, phase 3 trial done in 112 academic and community hospitals in nine European countries. Patients aged 18-70 years, with histologically confirmed primary invasive breast cancer (stage T1, T2, or operable T3) with up to three positive lymph nodes, no distant metastases, and a WHO performance status of 0-1 were enrolled and their genomic risk (using the MammaPrint 70-gene signature) and clinical risk (using a modified version of Adjuvant! Online) were determined. Patients with low clinical and low genomic risk results did not receive chemotherapy, and patients with high clinical and high genomic risk did receive chemotherapy (mostly anthracycline-based or taxane-based, or a combination thereof). Patients with discordant risk results (ie, patients with high clinical risk but low genomic risk, and those with low clinical risk but high genomic risk) were randomly assigned (1:1) to receive chemotherapy or not based on either the clinical risk or the genomic risk. Randomisation was done centrally and used a minimisation technique that was stratified by institution, risk group, and clinical-pathological characteristics. Treatment allocation was not masked. The primary endpoint was to test whether the distant metastasis-free survival rate at 5 years in patients with high clinical risk and low genomic risk not receiving chemotherapy had a lower boundary of the 95% CI above the predefined non-inferiority boundary of 92%. In the primary test population of patients with high clinical risk and low genomic risk who adhered to the treatment allocation of no chemotherapy and had no change in risk post-enrolment. Here, we present updated follow-up as well as an exploratory analysis of a potential age effect (≤50 years vs >50 years) and an analysis by nodal status for patients with hormone receptor-positive and HER2-negative disease. These analyses were done in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT00433589, and the European Clinical Trials database, EudraCT2005-002625-31. Recruitment is complete and further long-term follow-up is ongoing.\n\nFindings: Between Feb 8, 2007, and July 11, 2011, 6693 patients were enrolled. On Feb 26, 2020, median follow-up was 8·7 years (IQR 7·8-9·7). The updated 5-year distant metastasis-free survival rate for patients with high clinical risk and low genomic risk receiving no chemotherapy (primary test population, n=644) was 95·1% (95% CI 93·1-96·6), which is above the predefined non-inferiority boundary of 92%, supporting the previous analysis and proving MINDACT as a positive de-escalation trial. Patients with high clinical risk and low genomic risk were randomly assigned to receive chemotherapy (n=749) or not (n=748); this was the intention-to-treat population. The 8-year estimates for distant metastasis-free survival in the intention-to-treat population were 92·0% (95% CI 89·6-93·8) for chemotherapy versus 89·4% (86·8-91·5) for no chemotherapy (hazard ratio 0·66; 95% CI 0·48-0·92). An exploratory analysis confined to the subset of patients with hormone receptor-positive, HER2-negative disease (1358 [90.7%] of 1497 randomly assigned patients, of whom 676 received chemotherapy and 682 did not) shows different effects of chemotherapy administration on 8-year distant metastasis-free survival according to age: 93·6% (95% CI 89·3-96·3) with chemotherapy versus 88·6% (83·5-92·3) without chemotherapy in 464 women aged 50 years or younger (absolute difference 5·0 percentage points [SE 2·8, 95% CI -0·5 to 10·4]) and 90·2% (86·8-92·7) versus 90·0% (86·6-92·6) in 894 women older than 50 years (absolute difference 0·2 percentage points [2·1, -4·0 to 4·4]). The 8-year distant metastasis-free survival in the exploratory analysis by nodal status in these patients was 91·7% (95% CI 88·1-94·3) with chemotherapy and 89·2% (85·2-92·2) without chemotherapy in 699 node-negative patients (absolute difference 2·5 percentage points [SE 2·3, 95% CI -2·1 to 7·2]) and 91·2% (87·2-94·0) versus 89·9% (85·8-92·8) for 658 patients with one to three positive nodes (absolute difference 1·3 percentage points [2·4, -3·5 to 6·1]).\n\nInterpretation: With a more mature follow-up approaching 9 years, the 70-gene signature shows an intact ability of identifying among women with high clinical risk, a subgroup, namely patients with a low genomic risk, with an excellent distant metastasis-free survival when treated with endocrine therapy alone. For these women the magnitude of the benefit from adding chemotherapy to endocrine therapy remains small (2·6 percentage points) and is not enhanced by nodal positivity. However, in an underpowered exploratory analysis this benefit appears to be age-dependent, as it is only seen in women younger than 50 years where it reaches a clinically relevant threshold of 5 percentage points. Although, possibly due to chemotherapy-induced ovarian function suppression, it should be part of informed, shared decision making. Further study is needed in younger women, who might need reinforced endocrine therapy to forego chemotherapy.\n\nFunding: European Commission Sixth Framework Programme.\n\nIndexed on Europe PMC as PubMed record 33721561 (DOI 10.1016/s1470-2045(21)00007-3). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2021","url":"https://doi.org/10.1016/s1470-2045(21)00007-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33721561/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33721561"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["mindact"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2021,"doi":"10.1016/s1470-2045(21)00007-3","pmid":"33721561","authors":"Piccart M, van 't Veer LJ, Poncet C, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-cardoso-n-engl-j-med","kind":"paper","name":"70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 27557300 and published in New England Journal of Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Background: The 70-gene signature test (MammaPrint) has been shown to improve prediction of clinical outcome in women with early-stage breast cancer. We sought to provide prospective evidence of the clinical utility of the addition of the 70-gene signature to standard clinical-pathological criteria in selecting patients for adjuvant chemotherapy.\n\nMethods: In this randomized, phase 3 study, we enrolled 6693 women with early-stage breast cancer and determined their genomic risk (using the 70-gene signature) and their clinical risk (using a modified version of Adjuvant! Online). Women at low clinical and genomic risk did not receive chemotherapy, whereas those at high clinical and genomic risk did receive such therapy. In patients with discordant risk results, either the genomic risk or the clinical risk was used to determine the use of chemotherapy. The primary goal was to assess whether, among patients with high-risk clinical features and a low-risk gene-expression profile who did not receive chemotherapy, the lower boundary of the 95% confidence interval for the rate of 5-year survival without distant metastasis would be 92% (i.e., the noninferiority boundary) or higher.\n\nResults: A total of 1550 patients (23.2%) were deemed to be at high clinical risk and low genomic risk. At 5 years, the rate of survival without distant metastasis in this group was 94.7% (95% confidence interval, 92.5 to 96.2) among those not receiving chemotherapy. The absolute difference in this survival rate between these patients and those who received chemotherapy was 1.5 percentage points, with the rate being lower without chemotherapy. Similar rates of survival without distant metastasis were reported in the subgroup of patients who had estrogen-receptor-positive, human epidermal growth factor receptor 2-negative, and either node-negative or node-positive disease.\n\nConclusions: Among women with early-stage breast cancer who were at high clinical risk and low genomic risk for recurrence, the receipt of no chemotherapy on the basis of the 70-gene signature led to a 5-year rate of survival without distant metastasis that was 1.5 percentage points lower than the rate with chemotherapy. Given these findings, approximately 46% of women with breast cancer who are at high clinical risk might not require chemotherapy. (Funded by the European Commission Sixth Framework Program and others; ClinicalTrials.gov number, NCT00433589; EudraCT number, 2005-002625-31.).\n\nIndexed on Europe PMC as PubMed record 27557300 (DOI 10.1056/nejmoa1602253). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2016","url":"https://doi.org/10.1056/nejmoa1602253"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27557300/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27557300"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["mindact"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2016,"doi":"10.1056/nejmoa1602253","pmid":"27557300","authors":"Cardoso F, van't Veer LJ, Bogaerts J, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-bensch-nat-med","kind":"paper","name":"89 Zr-atezolizumab imaging as a non-invasive approach to assess clinical response to PD-L1 blockade in cancer","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 30478423 and published in Nature Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Programmed cell death protein-1/ligand-1 (PD-1/PD-L1) blockade is effective in a subset of patients with several tumor types, but predicting patient benefit using approved diagnostics is inexact, as some patients with PD-L1-negative tumors also show clinical benefit 1,2. Moreover, all biopsy-based tests are subject to the errors and limitations of invasive tissue collection 3-11. Preclinical studies of positron-emission tomography (PET) imaging with antibodies to PD-L1 suggested that this imaging method might be an approach to selecting patients 12,13. Such a technique, however, requires substantial clinical development and validation. Here we present the initial results from a first-in-human study to assess the feasibility of imaging with zirconium-89-labeled atezolizumab (anti-PD-L1), including biodistribution, and secondly test its potential to predict response to PD-L1 blockade (ClinicalTrials.gov identifiers NCT02453984 and NCT02478099). We imaged 22 patients across three tumor types before the start of atezolizumab therapy. The PET signal, a function of tracer exposure and target expression, was high in lymphoid tissues and at sites of inflammation. In tumors, uptake was generally high but heterogeneous, varying within and among lesions, patients, and tumor types. Intriguingly, clinical responses in our patients were better correlated with pretreatment PET signal than with immunohistochemistry- or RNA-sequencing-based predictive biomarkers, encouraging further development of molecular PET imaging for assessment of PD-L1 status and clinical response prediction.\n\nIndexed on Europe PMC as PubMed record 30478423 (DOI 10.1038/s41591-018-0255-8). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Med 2018","url":"https://doi.org/10.1038/s41591-018-0255-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30478423/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30478423"}],"tags":["europepmc-ingest"],"related":["immuno-pet"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2018,"doi":"10.1038/s41591-018-0255-8","pmid":"30478423","authors":"Bensch F, van der Veen EL, Lub-de Hooge MN, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-chun-ajcc-8th-edition-hepatobiliary-aso-2018","kind":"paper","name":"8th Edition of the AJCC Cancer Staging Manual: Pancreas and Hepatobiliary Cancers","aka":[],"tldr":"The editorial announcing the 2017 staging changes for pancreas, liver and biliary cancers, including the split of muscle-invading gallbladder cancer into a free-side and a liver-side category.","summary":"Editorial in Annals of Surgical Oncology by AJCC hepatobiliary panel members introducing the eighth edition changes. Europe PMC indexes no abstract for this article, so OnCo carries no figures from it. For gallbladder cancer the edition subdivided T2 into T2a (peritoneal side) and T2b (hepatic side), following the Shindoh 2015 multicentre study, and reclassified N stage by the number of positive nodes rather than their location (as the validation study linked here describes).","asOf":"2026-09-24","links":[{"label":"Ann Surg Oncol 2018","url":"https://doi.org/10.1245/s10434-017-6025-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28752469/"}],"tags":["gallbladder-evidence"],"related":["paper-shindoh-t2-gallbladder-cancer-tumour-location-ann-surg-2015","paper-giannis-ajcc8-gallbladder-staging-validation-cancers-2021"],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tnm-staging","t2a-versus-t2b"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-surgical-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Surgical Oncology","year":2018,"doi":"10.1245/s10434-017-6025-x","pmid":"28752469","authors":"Chun YS, Pawlik TM, Vauthey JN.","paperType":"review","findings":["No abstract is indexed on Europe PMC; the T2a/T2b subdivision is documented in the validation and meta-analysis papers linked from this record."],"whatItMeans":"The staging change UK pathology reports now carry. Validation against the US National Cancer Database (Giannis 2021) found the eighth edition no better than the seventh at predicting survival overall.","caveats":["Editorial without indexed abstract.","The N-stage change did not improve prognostic performance in validation."],"changedPractice":true},{"id":"paper-hugosson-eur-urol","kind":"paper","name":"A 16-yr Follow-up of the European Randomized study of Screening for Prostate Cancer","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 30824296 and published in European Urology; the citing page links this DOI, which is how the record was matched.","summary":"Background: The European Randomized study of Screening for Prostate Cancer (ERSPC) has previously demonstrated that prostate-specific antigen (PSA) screening decreases prostate cancer (PCa) mortality.\n\nObjective: To determine whether PSA screening decreases PCa mortality for up to 16yr and to assess results following adjustment for nonparticipation and the number of screening rounds attended.\n\nDesign, setting, and participants: This multicentre population-based randomised screening trial was conducted in eight European countries. Report includes 182160 men, followed up until 2014 (maximum of 16yr), with a predefined core age group of 162389 men (55-69yr), selected from population registry.\n\nOutcome measurements and statistical analysis: The outcome was PCa mortality, also assessed with adjustment for nonparticipation and the number of screening rounds attended.\n\nResults and limitations: The rate ratio of PCa mortality was 0.80 (95% confidence interval [CI] 0.72-0.89, p<0.001) at 16yr. The difference in absolute PCa mortality increased from 0.14% at 13yr to 0.18% at 16yr. The number of men needed to be invited for screening to prevent one PCa death was 570 at 16yr compared with 742 at 13yr. The number needed to diagnose was reduced to 18 from 26 at 13yr. Men with PCa detected during the first round had a higher prevalence of PSA >20ng/ml (9.9% compared with 4.1% in the second round, p<0.001) and higher PCa mortality (hazard ratio=1.86, p<0.001) than those detected subsequently.\n\nConclusions: Findings corroborate earlier results that PSA screening significantly reduces PCa mortality, showing larger absolute benefit with longer follow-up and a reduction in excess incidence. Repeated screening may be important to reduce PCa mortality on a population level.\n\nPatient summary: In this report, we looked at the outcomes from prostate cancer in a large European population. We found that repeated screening reduces the risk of dying from prostate cancer.\n\nIndexed on Europe PMC as PubMed record 30824296 (DOI 10.1016/j.eururo.2019.02.009). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Eur Urol 2019","url":"https://doi.org/10.1016/j.eururo.2019.02.009"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30824296/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30824296"}],"tags":["europepmc-ingest"],"related":["prostate-screening-psa-mri","prostate-roadmap","paper-schroder-erspc-screening-mortality-nejm-2009","paper-draisma-lead-time-overdiagnosis-psa-jnci-2009"],"cancers":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["number-needed-to-screen"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["european-urology"],"dependsOn":[],"notes":[],"journal":"European Urology","year":2019,"doi":"10.1016/j.eururo.2019.02.009","pmid":"30824296","authors":"Hugosson J, Roobol MJ, Månsson M, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-sottoriva-nat-genet","kind":"paper","name":"A Big Bang model of human colorectal tumor growth","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 25665006 and published in Nature Genetics; the citing page links this DOI, which is how the record was matched.","summary":"What happens in early, still undetectable human malignancies is unknown because direct observations are impractical. Here we present and validate a 'Big Bang' model, whereby tumors grow predominantly as a single expansion producing numerous intermixed subclones that are not subject to stringent selection and where both public (clonal) and most detectable private (subclonal) alterations arise early during growth. Genomic profiling of 349 individual glands from 15 colorectal tumors showed an absence of selective sweeps, uniformly high intratumoral heterogeneity (ITH) and subclone mixing in distant regions, as postulated by our model. We also verified the prediction that most detectable ITH originates from early private alterations and not from later clonal expansions, thus exposing the profile of the primordial tumor. Moreover, some tumors appear 'born to be bad', with subclone mixing indicative of early malignant potential. This new model provides a quantitative framework to interpret tumor growth dynamics and the origins of ITH, with important clinical implications.\n\nIndexed on Europe PMC as PubMed record 25665006 (DOI 10.1038/ng.3214). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Genet 2015","url":"https://doi.org/10.1038/ng.3214"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25665006/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25665006"}],"tags":["europepmc-ingest"],"related":["clonal-evolution-theory"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":2015,"doi":"10.1038/ng.3214","pmid":"25665006","authors":"Sottoriva A, Kang H, Ma Z, et al.","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-lapidot-nature","kind":"paper","name":"A cell initiating human acute myeloid leukaemia after transplantation into SCID mice","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 7509044 and published in Nature; the citing page links this DOI, which is how the record was matched.","summary":"Most human acute myeloid leukaemia (AML) cells have limited proliferative capacity, suggesting that the leukaemic clone may be maintained by a rare population of stem cells. This putative leukaemic stem cell has not been characterized because the available in vitro assays can only detect progenitors with limited proliferative and replating potential. We have now identified an AML-initiating cell by transplantation into severe combined immune-deficient (SCID) mice. These cells homed to the bone marrow and proliferated extensively in response to in vivo cytokine treatment, resulting in a pattern of dissemination and leukaemic cell morphology similar to that seen in the original patients. Limiting dilution analysis showed that the frequency of these leukaemia-initiating cells in the peripheral blood of AML patients was one engraftment unit in 250,000 cells. We fractionated AML cells on the basis of cell-surface-marker expression and found that the leukaemia-initiating cells that could engraft SCID mice to produce large numbers of colony-forming progenitors were CD34+ CD38-; however, the CD34+ CD38+ and CD34- fractions contained no cells with these properties. This in vivo model replicates many aspects of human AML and defines a new leukaemia-initiating cell which is less mature than colony-forming cells.\n\nIndexed on Europe PMC as PubMed record 7509044 (DOI 10.1038/367645a0). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 1994","url":"https://doi.org/10.1038/367645a0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/7509044/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/7509044"}],"tags":["europepmc-ingest"],"related":["cancer-stem-cell-theory"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":1994,"doi":"10.1038/367645a0","pmid":"7509044","authors":"Lapidot T, Sirard C, Vormoor J, et al.","paperType":"basic","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-eclipse-shield-n-engl-j-med-2024","kind":"paper","name":"A Cell-free DNA Blood-Based Test for Colorectal Cancer Screening","aka":[],"tldr":"Published report from the ECLIPSE trial registered as NCT04136002, in New England Journal of Medicine (2024), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Colorectal cancer is the third most diagnosed cancer in adults in the United States. Early detection could prevent more than 90% of colorectal cancer-related deaths, yet more than one third of the screening-eligible population is not up to date with screening despite multiple available tests. A blood-based test has the potential to improve screening adherence, detect colorectal cancer earlier, and reduce colorectal cancer-related mortality.\n\nMethods: We assessed the performance characteristics of a cell-free DNA (cfDNA) blood-based test in a population eligible for colorectal cancer screening. The coprimary outcomes were sensitivity for colorectal cancer and specificity for advanced neoplasia (colorectal cancer or advanced precancerous lesions) relative to screening colonoscopy. The secondary outcome was sensitivity to detect advanced precancerous lesions.\n\nResults: The clinical validation cohort included 10,258 persons, 7861 of whom met eligibility criteria and were evaluable. A total of 83.1% of the participants with colorectal cancer detected by colonoscopy had a positive cfDNA test and 16.9% had a negative test, which indicates a sensitivity of the cfDNA test for detection of colorectal cancer of 83.1% (95% confidence interval [CI], 72.2 to 90.3). Sensitivity for stage I, II, or III colorectal cancer was 87.5% (95% CI, 75.3 to 94.1), and sensitivity for advanced precancerous lesions was 13.2% (95% CI, 11.3 to 15.3). A total of 89.6% of the participants without any advanced colorectal neoplasia (colorectal cancer or advanced precancerous lesions) identified on colonoscopy had a negative cfDNA blood-based test, whereas 10.4% had a positive cfDNA blood-based test, which indicates a specificity for any advanced neoplasia of 89.6% (95% CI, 88.8 to 90.3). Specificity for negative colonoscopy (no colorectal cancer, advanced precancerous lesions, or nonadvanced precancerous lesions) was 89.9% (95% CI, 89.0 to 90.7).\n\nConclusions: In an average-risk screening population, this cfDNA blood-based test had 83% sensitivity for colorectal cancer, 90% specificity for advanced neoplasia, and 13% sensitivity for advanced precancerous lesions. (Funded by Guardant Health; ECLIPSE ClinicalTrials.gov number, NCT04136002.).\n\nIndexed on Europe PMC as PubMed record 38477985 (DOI 10.1056/nejmoa2304714). Its abstract cites the registry id NCT04136002, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2024","url":"https://doi.org/10.1056/nejmoa2304714"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38477985/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38477985"},{"label":"ClinicalTrials.gov NCT04136002","url":"https://clinicaltrials.gov/study/NCT04136002"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["eclipse-shield"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2024,"doi":"10.1056/nejmoa2304714","pmid":"38477985","authors":"Chung DC, Gray DM, Singh H, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04136002 with the most citations, so it is the natural first reading for anyone following the ECLIPSE trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-sharma-cell","kind":"paper","name":"A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 20371346 and published in Cell; the citing page links this DOI, which is how the record was matched.","summary":"Accumulating evidence implicates heterogeneity within cancer cell populations in the response to stressful exposures, including drug treatments. While modeling the acute response to various anticancer agents in drug-sensitive human tumor cell lines, we consistently detected a small subpopulation of reversibly \"drug-tolerant\" cells. These cells demonstrate >100-fold reduced drug sensitivity and maintain viability via engagement of IGF-1 receptor signaling and an altered chromatin state that requires the histone demethylase RBP2/KDM5A/Jarid1A. This drug-tolerant phenotype is transiently acquired and relinquished at low frequency by individual cells within the population, implicating the dynamic regulation of phenotypic heterogeneity in drug tolerance. The drug-tolerant subpopulation can be selectively ablated by treatment with IGF-1 receptor inhibitors or chromatin-modifying agents, potentially yielding a therapeutic opportunity. Together, these findings suggest that cancer cell populations employ a dynamic survival strategy in which individual cells transiently assume a reversibly drug-tolerant state to protect the population from eradication by potentially lethal exposures.\n\nIndexed on Europe PMC as PubMed record 20371346 (DOI 10.1016/j.cell.2010.02.027). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cell 2010","url":"https://doi.org/10.1016/j.cell.2010.02.027"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20371346/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/20371346"}],"tags":["europepmc-ingest"],"related":["drug-tolerant-persisters"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Cell","year":2010,"doi":"10.1016/j.cell.2010.02.027","pmid":"20371346","authors":"Sharma SV, Lee DY, Li B, et al.","paperType":"basic","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-cd19-multiple-myeloma-lancet-haematol-2019","kind":"paper","name":"A combination of humanised anti-CD19 and anti-BCMA CAR T cells in patients with relapsed or refractory multiple myeloma: a single-arm, phase 2 trial","aka":[],"tldr":"Phase 2 or 3 results paper on CD19 in Multiple myeloma, in The Lancet Haematology (2019), one of the most cited Europe PMC records with CD19 in its title.","summary":"Background: Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy has been shown to have activity in patients with relapsed or refractory multiple myeloma. Reports have suggested that a small subgroup of less differentiated myeloma clones express CD19 and anti-CD19 CAR T-cell therapy has shown activity in some of these patients. We aimed to assess the activity and safety of a combination of humanised anti-CD19 and anti-BCMA CAR T cells in patients with relapsed or refractory multiple myeloma.\n\nMethods: We did a single-centre, single-arm, phase 2 trial at the Affiliated Hospital of Xuzhou Medical University in China. Patients were eligible if they were aged 18-69 years, had histologically confirmed multiple myeloma, a Karnofsky Performance Score of 50 points or more, and met the International Myeloma Working Group diagnostic criteria for relapsed or refractory disease. Fludarabine (three daily doses of 30mg/m 2) and cyclophosphamide (one daily dose of 750 mg/m 2) were used to deplete lymphocytes before infusion of humanised anti-CD19 CAR T cells (1 × 10 6 cells per kg) and murine anti-BCMA CAR T cells (1 × 10 6 cells per kg). The primary outcome was the proportion of patients who achieved an overall response. Responses were assessed according to the International Myeloma Working Group criteria. This study is registered with the Chinese Clinical Trial Registration Center, number ChiCTR-OIC-17011272.\n\nFindings: From May 1, 2017, to Jan 20, 2019, 22 patients were enrolled and 21 received an infusion of CAR T cells and were evaluable for safety and activity analyses. At a median follow-up of 179 days (IQR 72-295), 20 (95%) of 21 patients had an overall response, including nine (43%) stringent complete responses, three (14%) complete responses, five (24%) very good partial responses, and three (14%) partial responses. The most common adverse events included cytokine release syndrome (19 [90%] of 21), including 18 patients (86%) with grade 1-2 cytokine release syndrome. The most common serious adverse events were haematological toxicities, which occurred in 20 (95%) of 21 patients. Common grade 3 or higher adverse events included neutropenia (18 [86%]), anaemia (13 [62%]), and thrombocytopenia (13 [62%]). One patient died due to cerebral hemorrhage, which was considered related to sustained thrombocytopenia. No deaths were judged to be treatment-related.\n\nInterpretation: Our results confirm that combined infusion of humanised anti-CD19 and anti-BCMA CAR T cells is feasible in patients with relapsed or refractory multiple myeloma, and the preliminary activity observed warrants further investigation in randomised trials. This dual CAR-T cell combinations might be a promising treatment option for relapsed or refractory multiple myeloma.\n\nFunding: National Natural Science Foundation of China, Natural Science Foundation, Key Research and Development Plan of Jiangsu.\n\nIndexed on Europe PMC as PubMed record 31378662 (DOI 10.1016/s2352-3026(19)30115-2). Its title names CD19 and its text names Multiple myeloma; PubMed types it as a clinical trial report (Clinical Trial, Phase II). It was matched automatically to the idea \"In vivo CAR-T manufactured and priced like a generic biologic\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Haematol 2019","url":"https://doi.org/10.1016/s2352-3026(19)30115-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31378662/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31378662"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-haematology"],"dependsOn":[],"notes":[],"journal":"The Lancet Haematology","year":2019,"doi":"10.1016/s2352-3026(19)30115-2","pmid":"31378662","authors":"Yan Z, Cao J, Cheng H, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for CD19 in Multiple myeloma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by CD19 in the title and Multiple myeloma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-springer-pancreatic-cyst-molecular-classification-gastroenterology-2015","kind":"paper","name":"A combination of molecular markers and clinical features improve the classification of pancreatic cysts","aka":[],"tldr":"Testing cyst fluid for a panel of gene mutations alongside the clinical picture classified 130 removed pancreatic cysts almost perfectly and would have avoided nine in ten of the operations that turned out to be unnecessary.","summary":"Multicentre retrospective study of 130 patients with resected pancreatic cystic neoplasms (12 serous cystadenomas, 10 solid pseudopapillary neoplasms, 12 mucinous cystic neoplasms, 96 IPMNs). Cyst fluid was analysed for mutations in BRAF, CDKN2A, CTNNB1, GNAS, KRAS, NRAS, PIK3CA, RNF43, SMAD4, TP53 and VHL, loss of heterozygosity at CDKN2A, RNF43, SMAD4, TP53 and VHL, and aneuploidy. Molecular markers with clinical features classified cyst type with 90 to 100% sensitivity and 92 to 98% specificity; the marker panel correctly identified 67 of the 74 patients who did not need surgery, a potential 91% reduction in unnecessary operations.","asOf":"2026-09-24","links":[{"label":"Springer et al., Gastroenterology 2015: molecular markers plus clinical features classify 130 resected cysts","url":"https://doi.org/10.1053/j.gastro.2015.07.041"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26253305/"}],"tags":[],"related":[],"cancers":["pancreatic","ipmn-cystic-precursors"],"sections":[],"technologies":[],"targets":["gnas","kras","rnf43","ctnnb1","smad4","tp53","cdkn2a"],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":[],"terms":["biopsy"],"trials":[],"people":["bert-vogelstein","luis-diaz"],"bottlenecks":[],"keyPapers":[],"journals":["gastroenterology"],"dependsOn":[],"notes":[],"journal":"Gastroenterology","year":2015,"doi":"10.1053/j.gastro.2015.07.041","pmid":"26253305","authors":"Springer S, Wang Y, Dal Molin M, et al.","paperType":"observational","findings":["Cyst type classified with 90 to 100% sensitivity and 92 to 98% specificity.","Would have avoided 91% of the unnecessary operations in the cohort."],"whatItMeans":"The evidence that molecular cyst-fluid testing can spare operations, now part of specialist practice although not a universal standard.","caveats":["Retrospective on resected cysts, so selection is towards operated lesions.","Prospective validation of the composite classifier is limited."],"changedPractice":false,"participants":130},{"id":"paper-rindi-common-classification-framework-mod-pathol-2018","kind":"paper","name":"A common classification framework for neuroendocrine neoplasms (IARC and WHO expert consensus)","aka":[],"tldr":"This consensus proposed a uniform way of classifying neuroendocrine neoplasms at every body site, separating well-differentiated neuroendocrine tumours (graded 1 to 3) from poorly differentiated neuroendocrine carcinomas, which became the basis of the WHO 2019 and 2022 classifications.","summary":"Expert consensus from the International Agency for Research on Cancer and WHO proposing that neuroendocrine neoplasms across organs be divided into well-differentiated neuroendocrine tumours graded 1 to 3 by proliferation and poorly differentiated small- and large-cell neuroendocrine carcinomas, with mixed neuroendocrine-non-neuroendocrine neoplasms as a third family.","asOf":"2026-09-17","links":[{"label":"Mod Pathol 2018","url":"https://doi.org/10.1038/s41379-018-0110-y"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30140036/"}],"tags":[],"related":[],"cancers":["extrapulmonary-nec","grade-3-net"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Modern Pathology","year":2018,"doi":"10.1038/s41379-018-0110-y","pmid":"30140036","authors":"Rindi G, Klimstra DS, Abedi-Ardekani B, et al.","paperType":"guideline","findings":[],"whatItMeans":"The grade 3 neuroendocrine tumour category, treated differently from neuroendocrine carcinoma, exists because of this framework.","caveats":["Lung neuroendocrine tumours retain older terminology (typical and atypical carcinoid) in the 2021 thoracic classification."],"changedPractice":true},{"id":"paper-carboplatin-glioblastoma-eur-j-cancer-2017","kind":"paper","name":"A European randomised controlled trial of the addition of etoposide to standard vincristine and carboplatin induction as part of an 18-month treatment programme for childhood (≤16 years) low grade glioma - A final report","aka":[],"tldr":"Phase 2 or 3 results paper on Carboplatin in Glioma & glioblastoma, in European Journal of Cancer (2017), one of the most cited Europe PMC records with Carboplatin in its title.","summary":"Background: The use of chemotherapy to manage newly diagnosed low grade glioma (LGG) was first introduced in the 1980s. One randomised trial has studied two- versus four-drug regimens with a duration of 12 months of treatment after resection.\n\nMethods: Within the European comprehensive treatment strategy for childhood LGG, the International Society of Paediatric Oncology-Low Grade Glioma (SIOP LGG) Committee launched a randomised trial involving 118 institutions and 11 countries to investigate the addition of etoposide (100 mg/m 2, days 1, 2 & 3) to a four-course induction of vincristine (1.5 mg/m 2 × 10 wkly) and carboplatin (550 mg/m 2 q 3 weekly) as part of 18-month continuing treatment programme. Patients were recruited after imaging diagnosis, resection or biopsy with progressive disease/symptoms. Some 497 newly diagnosed patients (M/F 231/266; median age 4.26 years (interquartile range (IQR) 2.02-7.06)) were randomised to receive vincristine carboplatin (VC) (n = 249) or VC plus etoposide (VCE) during induction (n = 248), stratified by age and tumour site.\n\nFindings: No differences between the two arms were found in term of survival and radiological response. Response and non-progression rates at 24 weeks for VC and VCE, were 46% versus 41%, and 93% versus 91% respectively; 5-year Progression-Free Survival (PFS) and Overall Survival (OS) were 46% (StDev 3.5) versus 45% (StDev 3.5) and 89% (StDev 2.1) versus 89% (StDev 2.1) respectively. Age and diencephalic syndrome are adverse clinical risk factors for PFS and OS. 5-year OS for patients in early progression at week 24 were 46% (StDev 13.8) and 49% (StDev 16.5) in the two arms, respectively.\n\nInterpretation: The addition of etoposide to VC did not improve PFS or OS. High non-progression rates at 24 weeks justify retaining VC as standard first-line therapy. Infants with diencephalic syndrome and early progression need new treatments to be tested. Future trials should use neurological/visual and toxicity outcomes and be designed to discriminate between the impact on disease outcomes of 'duration of therapy' and 'age at stopping therapy'.\n\nIndexed on Europe PMC as PubMed record 28649001 (DOI 10.1016/j.ejca.2017.04.019). Its title names Carboplatin and its text names Glioma & glioblastoma; PubMed types it as a clinical trial report (Research Support, Non-U.S. Gov't, research-article, Randomized Controlled Trial). It was matched automatically to the idea \"A skull ultrasound implant that opens the barrier at every cycle\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Eur J Cancer 2017","url":"https://doi.org/10.1016/j.ejca.2017.04.019"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28649001/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28649001"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["european-journal-of-cancer"],"dependsOn":[],"notes":[],"journal":"European Journal of Cancer","year":2017,"doi":"10.1016/j.ejca.2017.04.019","pmid":"28649001","authors":"Gnekow AK, Walker DA, Kandels D, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Carboplatin in Glioma & glioblastoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Carboplatin in the title and Glioma & glioblastoma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-nct05933265-invest-new-drugs-2026","kind":"paper","name":"A first-in-human phase 1a study of LP-184, a tumor-site activated novel alkylating agent, in patients with advanced solid tumors","aka":[],"tldr":"Published report from the trial registered as NCT05933265, in Investigational new drugs (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"LP-184 is a novel acylfulvene pro-drug that alkylates DNA after bioactivation by the intracellular oxidoreductase prostaglandin reductase 1 (PTGR1). In preclinical studies, potent growth inhibition has been observed against a wide variety of solid tumor models, particularly those carrying DNA damage repair deficiency. Here, we report results of the first-in-human dose escalation trial of LP-184 in advanced solid tumors. A dose escalation Bayesian optimal interval design was used with a starting dose of 0.01 mg/kg. Eligible patients with advanced refractory solid tumors were enrolled to receive LP-184 intravenously on days 1 and 8 of each 21-day cycle. Sixty-three patients were enrolled, with a median age of 62 years. Twelve dose levels (DLs) were evaluated with one dose-limiting toxicity (DLT) at DL11 (0.49 mg/kg; grade 4 platelet count decreased) and two DLTs at DL12 (0.61 mg/kg; grade 3 alanine aminotransferase increased and acute liver injury). The most common (≥ 20%) treatment-related adverse events of any grade included nausea, vomiting, fatigue, and platelet count decreased. No treatment-related deaths occurred during the study. Best response to monotherapy LP-184 was stable disease (SD), which was observed in 22 (40%) of the evaluable patients. Three patients experienced SD that lasted more than 12 months. LP-184 was safe and tolerable in the Phase 1a trial in patients with advanced refractory solid tumors. The maximum tolerated dose (MTD) of LP-184 is 0.49 mg/kg. Registry: ClinicalTrials.gov, TRN: NCT05933265, Registration date: June 23, 2023.\n\nIndexed on Europe PMC as PubMed record 42410111 (DOI 10.1007/s10637-026-01626-y). Its abstract cites the registry id NCT05933265, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Invest New Drugs 2026","url":"https://doi.org/10.1007/s10637-026-01626-y"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42410111/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42410111"},{"label":"ClinicalTrials.gov NCT05933265","url":"https://clinicaltrials.gov/study/NCT05933265"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05933265"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Investigational new drugs","year":2026,"doi":"10.1007/s10637-026-01626-y","pmid":"42410111","authors":"Mahadevan D, Parekh J, Beck JT, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05933265 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-vorontsov-nat-med","kind":"paper","name":"A foundation model for clinical-grade computational pathology and rare cancers detection","aka":[],"tldr":"Paper cited by two technology pages, indexed on Europe PMC as PubMed record 39039250 and published in Nature Medicine; the citing pages link this DOI, which is how the record was matched.","summary":"The analysis of histopathology images with artificial intelligence aims to enable clinical decision support systems and precision medicine. The success of such applications depends on the ability to model the diverse patterns observed in pathology images. To this end, we present Virchow, the largest foundation model for computational pathology to date. In addition to the evaluation of biomarker prediction and cell identification, we demonstrate that a large foundation model enables pan-cancer detection, achieving 0.95 specimen-level area under the (receiver operating characteristic) curve across nine common and seven rare cancers. Furthermore, we show that with less training data, the pan-cancer detector built on Virchow can achieve similar performance to tissue-specific clinical-grade models in production and outperform them on some rare variants of cancer. Virchow's performance gains highlight the value of a foundation model and open possibilities for many high-impact applications with limited amounts of labeled training data.\n\nIndexed on Europe PMC as PubMed record 39039250 (DOI 10.1038/s41591-024-03141-0). Matched by DOI alone: two technology pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Med 2024","url":"https://doi.org/10.1038/s41591-024-03141-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39039250/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39039250"}],"tags":["europepmc-ingest"],"related":["pathology-foundation-model","virchow"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2024,"doi":"10.1038/s41591-024-03141-0","pmid":"39039250","authors":"Vorontsov E, Bozkurt A, Casson A, et al.","paperType":"observational","findings":[],"whatItMeans":"Two technology pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-sahai-nat-rev-cancer","kind":"paper","name":"A framework for advancing our understanding of cancer-associated fibroblasts","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 31980749 and published in Nature Reviews Cancer; the citing page links this DOI, which is how the record was matched.","summary":"Cancer-associated fibroblasts (CAFs) are a key component of the tumour microenvironment with diverse functions, including matrix deposition and remodelling, extensive reciprocal signalling interactions with cancer cells and crosstalk with infiltrating leukocytes. As such, they are a potential target for optimizing therapeutic strategies against cancer. However, many challenges are present in ongoing attempts to modulate CAFs for therapeutic benefit. These include limitations in our understanding of the origin of CAFs and heterogeneity in CAF function, with it being desirable to retain some antitumorigenic functions. On the basis of a meeting of experts in the field of CAF biology, we summarize in this Consensus Statement our current knowledge and present a framework for advancing our understanding of this critical cell type within the tumour microenvironment.\n\nIndexed on Europe PMC as PubMed record 31980749 (DOI 10.1038/s41568-019-0238-1). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Cancer 2020","url":"https://doi.org/10.1038/s41568-019-0238-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31980749/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31980749"}],"tags":["europepmc-ingest"],"related":["caf-activation-desmoplasia"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Cancer","year":2020,"doi":"10.1038/s41568-019-0238-1","pmid":"31980749","authors":"Sahai E, Astsaturov I, Cukierman E, et al.","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-kralovics-n-engl-j-med","kind":"paper","name":"A gain-of-function mutation of JAK2 in myeloproliferative disorders","aka":[],"tldr":"Paper cited by one target page, indexed on Europe PMC as PubMed record 15858187 and published in New England Journal of Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Background: Polycythemia vera, essential thrombocythemia, and idiopathic myelofibrosis are clonal myeloproliferative disorders arising from a multipotent progenitor. The loss of heterozygosity (LOH) on the short arm of chromosome 9 (9pLOH) in myeloproliferative disorders suggests that 9p harbors a mutation that contributes to the cause of clonal expansion of hematopoietic cells in these diseases.\n\nMethods: We performed microsatellite mapping of the 9pLOH region and DNA sequencing in 244 patients with myeloproliferative disorders (128 with polycythemia vera, 93 with essential thrombocythemia, and 23 with idiopathic myelofibrosis).\n\nResults: Microsatellite mapping identified a 9pLOH region that included the Janus kinase 2 (JAK2) gene. In patients with 9pLOH, JAK2 had a homozygous G-->T transversion, causing phenylalanine to be substituted for valine at position 617 of JAK2 (V617F). All 51 patients with 9pLOH had the V617F mutation. Of 193 patients without 9pLOH, 66 were heterozygous for V617F and 127 did not have the mutation. The frequency of V617F was 65 percent among patients with polycythemia vera (83 of 128), 57 percent among patients with idiopathic myelofibrosis (13 of 23), and 23 percent among patients with essential thrombocythemia (21 of 93). V617F is a somatic mutation present in hematopoietic cells. Mitotic recombination probably causes both 9pLOH and the transition from heterozygosity to homozygosity for V617F. Genetic evidence and in vitro functional studies indicate that V617F gives hematopoietic precursors proliferative and survival advantages. Patients with the V617F mutation had a significantly longer duration of disease and a higher rate of complications (fibrosis, hemorrhage, and thrombosis) and treatment with cytoreductive therapy than patients with wild-type JAK2.\n\nConclusions: A high proportion of patients with myeloproliferative disorders carry a dominant gain-of-function mutation of JAK2.\n\nIndexed on Europe PMC as PubMed record 15858187 (DOI 10.1056/nejmoa051113). Matched by DOI alone: one target page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2005","url":"https://doi.org/10.1056/nejmoa051113"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/15858187/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/15858187"}],"tags":["europepmc-ingest"],"related":["jak2"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2005,"doi":"10.1056/nejmoa051113","pmid":"15858187","authors":"Kralovics R, Passamonti F, Buser AS, et al.","paperType":"basic","findings":[],"whatItMeans":"One target page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-fearon-cell","kind":"paper","name":"A genetic model for colorectal tumorigenesis","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 2188735 and published in Cell; the citing page links this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 2188735 (DOI 10.1016/0092-8674(90)90186-i). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cell 1990","url":"https://doi.org/10.1016/0092-8674(90)90186-i"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/2188735/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/2188735"}],"tags":["europepmc-ingest"],"related":["somatic-mutation-theory","colorectal-roadmap","paper-vogelstein-genetic-alterations-colorectal-tumor-development-nejm-1988"],"cancers":["colorectal"],"sections":[],"technologies":[],"targets":["apc","kras","tp53","smad4"],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":["colorectal-cancer-signalling","chromosomal-instability","clonal-evolution"],"terms":["driver-mutation"],"trials":[],"people":["bert-vogelstein","eric-fearon"],"bottlenecks":[],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Cell","year":1990,"doi":"10.1016/0092-8674(90)90186-i","pmid":"2188735","authors":"Fearon ER, Vogelstein B","paperType":"review","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-donenberg-bahamas-brca1-founder-bcrt-2011","kind":"paper","name":"A high prevalence of BRCA1 mutations among breast cancer patients from the Bahamas","aka":[],"tldr":"Nearly a quarter of 214 Bahamian women with breast cancer, chosen without regard to age or family history, carried one of six BRCA1 founder mutations, the highest national prevalence recorded.","summary":"214 Bahamian women with invasive breast cancer, unselected for age or family history, were screened for six BRCA1 mutations previously reported in Bahamian cancer families. A mutation was identified in 49 (23%); frequency was 33% in women diagnosed before 50, 41% with a first-degree relative with breast or ovarian cancer and 58% with bilateral disease. About 23% of unselected breast cancers in the Bahamas are attributable to a BRCA1 founder mutation.","asOf":"2026-09-24","links":[{"label":"Donenberg et al., Breast Cancer Res Treat 2011: BRCA1 founder mutations in 214 Bahamian breast cancer patients","url":"https://doi.org/10.1007/s10549-010-1156-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20838878/"}],"tags":[],"related":[],"cancers":["tnbc","breast-cancer"],"sections":[],"technologies":[],"targets":["brca"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["gbrca-mutation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["breast-cancer-research-and-treatment"],"dependsOn":[],"notes":[],"journal":"Breast Cancer Research and Treatment","year":2011,"doi":"10.1007/s10549-010-1156-9","pmid":"20838878","authors":"Donenberg T, Lunn J, Curling D, et al.","paperType":"observational","findings":["BRCA1 founder mutation in 49 of 214 unselected patients, 23%.","33% under age 50, 41% with an affected first-degree relative, 58% with bilateral disease."],"whatItMeans":"Founder-mutation screening of every breast cancer patient is justified in the Bahamas, and the finding explains part of the early-onset, BRCA1-driven triple-negative burden across Afro-Caribbean populations.","caveats":["Only the six known founder alleles were tested; full sequencing would find more.","Receptor status was not the focus of the study."],"changedPractice":false,"participants":214},{"id":"paper-devita-cancer-res","kind":"paper","name":"A history of cancer chemotherapy","aka":[],"tldr":"Paper cited by one roadmap page, indexed on Europe PMC as PubMed record 18974103 and published in Cancer Research; the citing page links this DOI, which is how the record was matched.","summary":"The use of chemotherapy to treat cancer began at the start of the 20th century with attempts to narrow the universe of chemicals that might affect the disease by developing methods to screen chemicals using transplantable tumors in rodents. It was, however, four World War II-related programs, and the effects of drugs that evolved from them, that provided the impetus to establish in 1955 the national drug development effort known as the Cancer Chemotherapy National Service Center. The ability of combination chemotherapy to cure acute childhood leukemia and advanced Hodgkin's disease in the 1960s and early 1970s overcame the prevailing pessimism about the ability of drugs to cure advanced cancers, facilitated the study of adjuvant chemotherapy, and helped foster the national cancer program. Today, chemotherapy has changed as important molecular abnormalities are being used to screen for potential new drugs as well as for targeted treatments.\n\nIndexed on Europe PMC as PubMed record 18974103 (DOI 10.1158/0008-5472.can-07-6611). Matched by DOI alone: one roadmap page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer Res 2008","url":"https://doi.org/10.1158/0008-5472.can-07-6611"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/18974103/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/18974103"}],"tags":["europepmc-ingest"],"related":["chemotherapy-roadmap"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-research"],"dependsOn":[],"notes":[],"journal":"Cancer Research","year":2008,"doi":"10.1158/0008-5472.can-07-6611","pmid":"18974103","authors":"DeVita VT, Chu E","paperType":"observational","findings":[],"whatItMeans":"One roadmap page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-bertotti-xenopatients-her2-cetuximab-resistant-colorectal-cancer-discov-2011","kind":"paper","name":"A molecularly annotated platform of patient-derived xenografts identifies HER2 as an effective therapeutic target in cetuximab-resistant colorectal cancer","aka":[],"tldr":"Growing 85 patients' bowel cancers in mice and treating them like a clinical trial reproduced the pattern seen in people, and revealed that the tumours resisting cetuximab despite normal RAS often have extra copies of HER2.","summary":"Large xenograft cohorts were produced from 85 patient-derived, genetically characterised metastatic colorectal cancer samples. Serially passaged tumours retained the morphological and genomic features of their originals, and a validation trial confirmed that they responded to cetuximab with rates and extents analogous to those seen in the clinic, and could be prospectively stratified as responders or non-responders using predictive biomarkers. Genotype-response correlations indicated HER2 amplification specifically in a subset of cetuximab-resistant, KRAS, NRAS, BRAF and PIK3CA wild-type cases, and HER2 amplification was also enriched among clinically non-responding KRAS wild-type patients. A proof-of-concept, multi-arm study in HER2-amplified xenopatients showed that combined inhibition of HER2 and EGFR induced overt, long-lasting tumour regression.","asOf":"2026-09-24","links":[{"label":"Bertotti et al., Cancer Discov 2011: xenopatients identify HER2 amplification in cetuximab-resistant colorectal cancer","url":"https://doi.org/10.1158/2159-8290.CD-11-0109"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22586653/"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["organoids"],"targets":["her2","egfr","kras"],"drugs":["cetuximab","trastuzumab","lapatinib"],"companies":[],"institutions":["candiolo"],"pathways":["rtk-activation","ras-mapk"],"terms":["wild-type","gene-amplification"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-discovery"],"dependsOn":[],"notes":[],"journal":"Cancer Discovery","year":2011,"doi":"10.1158/2159-8290.CD-11-0109","pmid":"22586653","authors":"Bertotti A, Migliardi G, Galimi F, et al.","paperType":"translational","findings":["Patient-derived xenografts reproduced clinical cetuximab response rates and biomarker stratification.","HER2 amplification enriched in cetuximab-resistant, quadruple wild-type cases.","Dual HER2 and EGFR inhibition produced long-lasting regressions in HER2-amplified xenografts."],"whatItMeans":"It is where HER2-directed colorectal therapy came from: the xenopatient result led directly to HERACLES and therefore to every HER2 regimen now used in the disease.","caveats":["Mouse models without an immune system.","Small numbers of HER2-amplified cases, as in patients.","The clinical benefit of dual blockade has been shorter-lived than the xenograft regressions suggested."],"changedPractice":false,"participants":85},{"id":"paper-peter-thuss-patience-ann-oncol-2019","kind":"paper","name":"A multicentre, phase IIa study of zolbetuximab as a single agent in patients with recurrent or refractory advanced adenocarcinoma of the stomach or lower oesophagus: the MONO study","aka":[],"tldr":"Paper by Peter Thuss-Patience indexed on Europe PMC as PubMed record 31240302, in Annals of Oncology (2019), one of the most cited records naming an author with this name at Charité Universitätsmedizin Berlin.","summary":"Background: Claudin 18.2 (CLDN18.2) is physiologically confined to gastric mucosa tight junctions; however, upon malignant transformation, perturbations in cell polarity lead to CLDN18.2 epitopes being exposed on the cancer cell surface. The first-in-class monoclonal antibody, zolbetuximab (formerly known as IMAB362), binds to CLDN18.2 and can induce immune-mediated lysis of CLDN18.2-positive cells.\n\nPatients and methods: Patients with advanced gastric, gastro-oesophageal junction (GEJ) or oesophageal adenocarcinomas with moderate-to-strong CLDN18.2 expression in ≥50% of tumour cells received zolbetuximab intravenously every 2 weeks for five planned infusions. At least three patients were enrolled in two sequential cohorts (cohort 1300 mg/m2; cohort 2600 mg/m2); additional patients were enrolled into a dose-expansion cohort (cohort 3600 mg/m2). The primary end point was the objective response rate [ORR: complete and partial response (PR)]; secondary end points included clinical benefit [ORR+stable disease (SD)], progression-free survival, safety/tolerability, and zolbetuximab pharmacokinetic profile.\n\nResults: From September 2010 to September 2012, 54 patients were enrolled (cohort 1, n = 4; cohort 2, n = 6; cohort 3, n = 44). Three patients in cohort 1 and 25 patients in cohorts 2/3 received at least 5 infusions. Antitumour activity data were available for 43 patients, of whom 4 achieved PR (ORR 9%) and 6 (14%) had SD for a clinical benefit rate of 23%. In a subgroup of patients with moderate-to-high CLDN18.2 expression in ≥70% of tumour cells, ORR was 14% (n = 4/29). Treatment-related adverse events occurred in 81.5% (n = 44/54) patients; nausea (61%), vomiting (50%), and fatigue (22%) were the most frequent.\n\nConclusions: Zolbetuximab monotherapy was well tolerated and exhibited antitumour activity in patients with CLDN18.2-positive advanced gastric or GEJ adenocarcinomas, with response rates similar to those reported for single-agent targeted agents in gastric/GEJ cancer trials.\n\nClinicaltrials.gov number: NCT01197885.\n\nIndexed on Europe PMC as PubMed record 31240302 (DOI 10.1093/annonc/mdz199). Its author list gives \"Thuss-Patience P\" with the affiliation \"Charite University Medicine Berlin, Medical Clinic of Hematology, Oncology and Tumor Immunology, Berlin\", which names Charité Universitätsmedizin Berlin; that is how the record was matched to Peter Thuss-Patience, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Ann Oncol 2019","url":"https://doi.org/10.1093/annonc/mdz199"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31240302/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31240302"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["peter-thuss-patience"],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2019,"doi":"10.1093/annonc/mdz199","pmid":"31240302","authors":"Türeci O, Sahin U, Schulze-Bergkamen H, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Peter Thuss-Patience at Charité Universitätsmedizin Berlin, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-pramesh-ncg-pooled-procurement-2023","kind":"paper","name":"A National Cancer Grid pooled procurement initiative, India","aka":[],"tldr":"When 23 Indian cancer centres bought 40 cancer drugs together instead of separately, prices fell by a median of 82%, saving about 13 billion rupees against list prices.","summary":"Report in the Bulletin of the World Health Organization of the National Cancer Grid's pooled procurement pilot: 40 anticancer drugs, pooled demand from 23 cancer centres worth about 15.6 billion Indian rupees (197 million dollars) at maximum retail price, and a negotiated cost reduction of about 13.2 billion rupees (166.7 million dollars). Savings ranged from 23% to 99% per drug (median 82%), larger for generics than for innovator or newly patented drugs, and were achieved through group negotiation of fixed prices and uniform contracts with standardised terms.","asOf":"2026-09-10","links":[{"label":"Bull WHO 2023","url":"https://doi.org/10.2471/BLT.23.289714"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["global-oncology-access"],"targets":[],"drugs":[],"companies":[],"institutions":["national-cancer-grid","tata-memorial"],"pathways":[],"terms":[],"trials":[],"people":["pramesh-c-s"],"bottlenecks":["b-drug-pricing","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Bulletin of the World Health Organization","year":2023,"doi":"10.2471/BLT.23.289714","authors":"Pramesh CS, Sengar M, Patankar S, et al.","paperType":"real-world","findings":["40 drugs, 23 centres, pooled demand of about 15.6 billion rupees at maximum retail price.","Cost reduction of about 13.2 billion rupees (166.7 million dollars).","Savings per drug 23% to 99%, median 82%; larger for generics than innovator drugs.","Mechanism: group negotiation, fixed prices, uniform contracts with standardised terms."],"whatItMeans":"Buying power, not new science, is the fastest lever on cancer drug prices in a decentralised, under-funded system. The Grid's model is being extended across its 360-plus centres and offers a template for other middle-income countries and for pooled buying of newer, patented drugs.","caveats":["Savings are measured against maximum retail price, which overstates the gain versus prices large centres already negotiated.","Innovator and patented drugs saw far smaller discounts; the model works best for generics.","Sustaining supply quality and adherence to contracts across many hospitals is an ongoing task."],"changedPractice":true},{"id":"paper-yeh-ca19-9-lewis-negative-fut3-cutoff-ccr-2026","kind":"paper","name":"A new CA19-9 cutoff value identifies Lewis antigen status and refines prognostic stratification in PDAC","aka":[],"tldr":"Genotyping 615 patients showed that about one in ten cannot make CA 19-9, that their outlook is as poor as patients with very high readings, and that a value of 7 or below is a practical way to spot them without a genetic test.","summary":"Germline whole-exome sequencing in a multicentre cohort of 615 patients with pancreatic ductal adenocarcinoma determined FUT2 and FUT3 genotypes. Receiver operating characteristic analysis identified the optimal CA 19-9 cut-off for FUT3-null status and maximally selected rank statistics derived cut-offs stratifying overall survival in a training set (307) tested in a validation set (308). FUT3-null patients had similar demographics but a much lower median baseline CA 19-9 (2.4 against 496 U/mL) and a median overall survival of 13.5 months, comparable with FUT3-intact patients above 200 U/mL (12.9 months). A cut-off of 7 U/mL identified FUT3-null status with positive predictive value 95.1% and accuracy 87.9%. Using 7 and 200 U/mL without genotyping gave four prognostic groups: above 7 to 37 (23.2 months), above 37 to 200 (22 months), above 200 (12.8 months) and 7 or below, likely FUT3-null (13.5 months).","asOf":"2026-09-24","links":[{"label":"Yeh et al., Clin Cancer Res 2026: FUT3-null (Lewis-negative) patients and a CA 19-9 cut-off in 615 patients","url":"https://doi.org/10.1158/1078-0432.ccr-25-4564"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42162970/"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":["germline-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ca19-9","founder-mutation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2026,"doi":"10.1158/1078-0432.ccr-25-4564","pmid":"42162970","authors":"Yeh CM, Yu CC, Lee AF, et al.","paperType":"observational","findings":["About 10% of patients are FUT3-null non-producers with median CA 19-9 2.4 against 496 U/mL.","CA 19-9 of 7 U/mL or below identifies them with 95.1% positive predictive value.","Non-producers have the same short survival as patients above 200 U/mL."],"whatItMeans":"A very low CA 19-9 is not reassurance: it marks the non-producer group whose outlook matches the highest-marker group, and it gives clinics a rule they can apply without genotyping.","caveats":["Taiwanese multicentre cohort; the 10% non-producer share varies by ancestry.","Retrospective derivation and validation within one cohort."],"changedPractice":false,"participants":615},{"id":"paper-errani-wwtr1-camta1-ehe-gcc-2011","kind":"paper","name":"A novel WWTR1-CAMTA1 gene fusion is a consistent abnormality in epithelioid haemangioendothelioma","aka":[],"tldr":"This study identified the WWTR1-CAMTA1 gene fusion in nearly every epithelioid haemangioendothelioma from any body site, giving this rare vascular tumour a defining molecular marker.","summary":"Molecular study identifying a t(1;3) translocation fusing WWTR1 (encoding TAZ) to CAMTA1 in epithelioid haemangioendothelioma of soft tissue, bone, liver and lung, present in almost all cases and absent from other vascular tumours.","asOf":"2026-09-17","links":[{"label":"Genes Chromosomes Cancer 2011","url":"https://doi.org/10.1002/gcc.20886"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21584898/"}],"tags":[],"related":[],"cancers":["epithelioid-haemangioendothelioma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["genes-chromosomes-and-cancer"],"dependsOn":[],"notes":[],"journal":"Genes, chromosomes & cancer","year":2011,"doi":"10.1002/gcc.20886","pmid":"21584898","authors":"Errani C, Zhang L, Sung YS, et al.","paperType":"basic","findings":["WWTR1-CAMTA1 fusion in the vast majority of epithelioid haemangioendotheliomas across sites."],"whatItMeans":"CAMTA1 immunohistochemistry and fusion testing confirm the diagnosis, and the TAZ-CAMTA1 fusion protein's dependence on the Hippo pathway is guiding drug development.","caveats":["A minority of cases carry an alternative YAP1-TFE3 fusion."],"changedPractice":true},{"id":"paper-wang-nature","kind":"paper","name":"A pathology foundation model for cancer diagnosis and prognosis prediction","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 39232164 and published in Nature; the citing page links this DOI, which is how the record was matched.","summary":"Histopathology image evaluation is indispensable for cancer diagnoses and subtype classification. Standard artificial intelligence methods for histopathology image analyses have focused on optimizing specialized models for each diagnostic task 1,2. Although such methods have achieved some success, they often have limited generalizability to images generated by different digitization protocols or samples collected from different populations 3. Here, to address this challenge, we devised the Clinical Histopathology Imaging Evaluation Foundation (CHIEF) model, a general-purpose weakly supervised machine learning framework to extract pathology imaging features for systematic cancer evaluation. CHIEF leverages two complementary pretraining methods to extract diverse pathology representations: unsupervised pretraining for tile-level feature identification and weakly supervised pretraining for whole-slide pattern recognition. We developed CHIEF using 60,530 whole-slide images spanning 19 anatomical sites. Through pretraining on 44 terabytes of high-resolution pathology imaging datasets, CHIEF extracted microscopic representations useful for cancer cell detection, tumour origin identification, molecular profile characterization and prognostic prediction. We successfully validated CHIEF using 19,491 whole-slide images from 32 independent slide sets collected from 24 hospitals and cohorts internationally. Overall, CHIEF outperformed the state-of-the-art deep learning methods by up to 36.1%, showing its ability to address domain shifts observed in samples from diverse populations and processed by different slide preparation methods. CHIEF provides a generalizable foundation for efficient digital pathology evaluation for patients with cancer.\n\nIndexed on Europe PMC as PubMed record 39232164 (DOI 10.1038/s41586-024-07894-z). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2024","url":"https://doi.org/10.1038/s41586-024-07894-z"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39232164/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39232164"}],"tags":["europepmc-ingest"],"related":["chief"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2024,"doi":"10.1038/s41586-024-07894-z","pmid":"39232164","authors":"Wang X, Zhao J, Marostica E, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-stock-blood","kind":"paper","name":"A pediatric regimen for older adolescents and young adults with acute lymphoblastic leukemia: results of CALGB 10403","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 30658992 and published in Blood; the citing page links this DOI, which is how the record was matched.","summary":"Retrospective studies have suggested that older adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL) have better survival rates when treated using a pediatric ALL regimen administered by pediatric treatment teams. To address the feasibility and efficacy of using a pediatric treatment regimen for AYA patients with newly diagnosed ALL administered by adult treatment teams, we performed a prospective study, CALGB 10403, with doses and schedule identical to those in the Children's Oncology Group study AALL0232. From 2007 to 2012, 318 patients were enrolled; 295 were eligible and evaluable for response. Median age was 24 years (range, 17-39 years). Use of the pediatric regimen was safe; overall treatment-related mortality was 3%, and there were only 2 postremission deaths. Median event-free survival (EFS) was 78.1 months (95% confidence interval [CI], 41.8 to not reached), more than double the historical control of 30 months (95% CI, 22-38 months); 3-year EFS was 59% (95% CI, 54%-65%). Median overall survival (OS) was not reached. Estimated 3-year OS was 73% (95% CI, 68%-78%). Pretreatment risk factors associated with worse treatment outcomes included obesity and presence of the Philadelphia-like gene expression signature. Use of a pediatric regimen for AYAs with ALL up to age 40 years was feasible and effective, resulting in improved survival rates compared with historical controls. CALGB 10403 can be considered a new treatment standard upon which to build for improving survival for AYAs with ALL. This trial was registered at www.clinicaltrials.gov as #NCT00558519.\n\nIndexed on Europe PMC as PubMed record 30658992 (DOI 10.1182/blood-2018-10-881961). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Blood 2019","url":"https://doi.org/10.1182/blood-2018-10-881961"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30658992/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30658992"}],"tags":["europepmc-ingest"],"related":["aya-oncology"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["blood"],"dependsOn":[],"notes":[],"journal":"Blood","year":2019,"doi":"10.1182/blood-2018-10-881961","pmid":"30658992","authors":"Stock W, Luger SM, Advani AS, et al.","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-cd47-neuroblastoma-curr-oncol-2024","kind":"paper","name":"A Perspective on the CD47-SIRPA Axis in High-Risk Neuroblastoma","aka":[],"tldr":"Review on CD47 in Neuroblastoma, in Current oncology (2024), one of the most cited Europe PMC records with CD47 in its title.","summary":"Neuroblastoma is a pediatric cancer with significant clinical heterogeneity. Despite extensive efforts, it is still difficult to cure children with high-risk neuroblastoma. Immunotherapy is a promising approach to treat children with this devastating disease. We have previously reported that macrophages are important effector cells in high-risk neuroblastoma. In this perspective article, we discuss the potential function of the macrophage inhibitory receptor SIRPA in the homeostasis of tumor-associated macrophages in high-risk neuroblastoma. The ligand of SIRPA is CD47, known as a \"don't eat me\" signal, which is highly expressed on cancer cells compared to normal cells. CD47 is expressed on both tumor and stroma cells, whereas SIRPA expression is restricted to macrophages in high-risk neuroblastoma tissues. Notably, high SIRPA expression is associated with better disease outcome. According to the current paradigm, the interaction between CD47 on tumor cells and SIRPA on macrophages leads to the inhibition of tumor phagocytosis. However, data from recent clinical trials have called into question the use of anti-CD47 antibodies for the treatment of adult and pediatric cancers. The restricted expression of SIRPA on macrophages in many tissues argues for targeting SIRPA on macrophages rather than CD47 in CD47/SIRPA blockade therapy. Based on the data available to date, we propose that disruption of the CD47-SIRPA interaction by anti-CD47 antibody would shift the macrophage polarization status from M1 to M2, which is inferred from the 1998 study by Timms et al. In contrast, the anti-SIRPA F(ab') 2 lacking Fc binds to SIRPA on the macrophage, mimics the CD47-SIRPA interaction, and thus maintains M1 polarization. Anti-SIRPA F(ab') 2 also prevents the binding of CD47 to SIRPA, thereby blocking the \"don't eat me\" signal. The addition of tumor-opsonizing and macrophage-activating antibodies is expected to enhance active tumor phagocytosis.\n\nIndexed on Europe PMC as PubMed record 38920727 (DOI 10.3390/curroncol31060243). Its title names CD47 and its text names Neuroblastoma; PubMed types it as a review (other, Review). It was matched automatically to the idea \"Can MYC be drugged directly, and will patients tolerate it?\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Curr Oncol 2024","url":"https://doi.org/10.3390/curroncol31060243"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38920727/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38920727"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["current-oncology-mdpi"],"dependsOn":[],"notes":[],"journal":"Current oncology","year":2024,"doi":"10.3390/curroncol31060243","pmid":"38920727","authors":"Tang XX, Shimada H, Ikegaki N","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for CD47 in Neuroblastoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by CD47 in the title and Neuroblastoma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-makvandi-j-clin-invest","kind":"paper","name":"A PET imaging agent for evaluating PARP-1 expression in ovarian cancer","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 29509546 and published in Journal of Clinical Investigation; the citing page links this DOI, which is how the record was matched.","summary":"Background: Poly(ADP-ribose) polymerase (PARP) inhibitors are effective in a broad population of patients with ovarian cancer; however, resistance caused by low enzyme expression of the drug target PARP-1 remains to be clinically evaluated in this context. We hypothesize that PARP-1 expression is variable in ovarian cancer and can be quantified in primary and metastatic disease using a novel PET imaging agent.\n\nMethods: We used a translational approach to describe the significance of PET imaging of PARP-1 in ovarian cancer. First, we produced PARP1-KO ovarian cancer cell lines using CRISPR/Cas9 gene editing to test the loss of PARP-1 as a resistance mechanism to all clinically used PARP inhibitors. Next, we performed preclinical microPET imaging studies using ovarian cancer patient-derived xenografts in mouse models. Finally, in a phase I PET imaging clinical trial we explored PET imaging as a regional marker of PARP-1 expression in primary and metastatic disease through correlative tissue histology.\n\nResults: We found that deletion of PARP1 causes resistance to all PARP inhibitors in vitro, and microPET imaging provides proof of concept as an approach to quantify PARP-1 in vivo. Clinically, we observed a spectrum of standard uptake values (SUVs) ranging from 2-12 for PARP-1 in tumors. In addition, we found a positive correlation between PET SUVs and fluorescent immunohistochemistry for PARP-1 (r2 = 0.60).\n\nConclusion: This work confirms the translational potential of a PARP-1 PET imaging agent and supports future clinical trials to test PARP-1 expression as a method to stratify patients for PARP inhibitor therapy.\n\nTrial registration: Clinicaltrials.gov NCT02637934.\n\nFunding: Research reported in this publication was supported by the Department of Defense OC160269, a Basser Center team science grant, NIH National Cancer Institute R01CA174904, a Department of Energy training grant DE-SC0012476, Abramson Cancer Center Radiation Oncology pilot grants, the Marsha Rivkin Foundation, Kaleidoscope of Hope Foundation, and Paul Calabresi K12 Career Development Award 5K12CA076931.\n\nIndexed on Europe PMC as PubMed record 29509546 (DOI 10.1172/jci97992). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Invest 2018","url":"https://doi.org/10.1172/jci97992"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29509546/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29509546"}],"tags":["europepmc-ingest"],"related":["parp-pet"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jci"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Investigation","year":2018,"doi":"10.1172/jci97992","pmid":"29509546","authors":"Makvandi M, Pantel A, Schwartz L, et al.","paperType":"basic","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nct05751798-eur-j-cancer-2026","kind":"paper","name":"A Phase 1 dose-escalation study to evaluate safety, pharmacokinetics, and pharmacodynamics of OSE-279, an anti-PD-1 monoclonal antibody in patients with advanced solid tumours","aka":[],"tldr":"Published report from the trial registered as NCT05751798, in European Journal of Cancer (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: OSE-279 is a high affinity humanized monoclonal bivalent antibody against PD-1 with potent antitumor activity in vivo in syngeneic non-clinical models.\n\nMethods: This phase I study assessed the safety, pharmacokinetics, pharmacodynamics and antitumor activity of OSE-279 in advanced solid tumours.\n\nResults: Twenty patients received OSE-279 intravenously at 100 mg q3w (n = 2), 300 mg q3w (n = 7) and 600 mg q6w (n = 11). Median age was 61.5 (range 3-81) years, 50% were female, median number of prior metastatic lines was 2 (range 1-6). Most frequent tumour types were soft tissue sarcoma (n = 4) and anal squamous cell carcinoma (n = 3). OSE-279 monotherapy was safe. Two recommended phase 2 doses were established: 300 mg q3w and 600 mg q6w. The most common (≥10%) related TEAEs were diarrhoea, dry mouth, pruritus, chills, fatigue, headache, dysgeusia and hyperthyroidism. OSE-279 PK exhibited linear dose proportionality and mean receptor occupancy was maintained above 80% in all tested doses. There were 1 CR at 300 mg q3w, 4 PRs at 600 mg q6w and 7 SD with response duration ranging from 6.8 to 18.4 months.\n\nConclusion: OSE-279 monotherapy was well tolerated with durable responses in patients with advanced solid tumours. The trial is continuing with OSE-279 combined with OSE2101, a therapeutic cancer vaccine in 1st line HLA-A2 positive PD-L1 ≥ 50% NSCLC. CLINICAL TRIAL REGISTRATION (NCT NUMBER: NCT05751798).\n\nIndexed on Europe PMC as PubMed record 42034003 (DOI 10.1016/j.ejca.2026.116729). Its abstract cites the registry id NCT05751798, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Eur J Cancer 2026","url":"https://doi.org/10.1016/j.ejca.2026.116729"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42034003/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42034003"},{"label":"ClinicalTrials.gov NCT05751798","url":"https://clinicaltrials.gov/study/NCT05751798"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05751798"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["european-journal-of-cancer"],"dependsOn":[],"notes":[],"journal":"European Journal of Cancer","year":2026,"doi":"10.1016/j.ejca.2026.116729","pmid":"42034003","authors":"Robert M, Kotecki N, Gomez-Roca C, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05751798 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-zhao-j-hematol-oncol","kind":"paper","name":"A phase 1, open-label study of LCAR-B38M, a chimeric antigen receptor T cell therapy directed against B cell maturation antigen, in patients with relapsed or refractory multiple myeloma","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 30572922 and published in Journal of hematology & oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background: Chimeric antigen receptor (CAR) T cell therapy has demonstrated proven efficacy in some hematologic cancers. We evaluated the safety and efficacy of LCAR-B38M, a dual epitope-binding CAR T cell therapy directed against 2 distinct B cell maturation antigen epitopes, in patients with relapsed/refractory (R/R) multiple myeloma (MM).\n\nMethods: This ongoing phase 1, single-arm, open-label, multicenter study enrolled patients (18 to 80 years) with R/R MM. Lymphodepletion was performed using cyclophosphamide 300 mg/m 2. LCAR-B38M CAR T cells (median CAR+ T cells, 0.5 × 10 6 cells/kg [range, 0.07 to 2.1 × 10 6 ]) were infused in 3 separate infusions. The primary objective is to evaluate the safety of LCAR-B38M CAR T cells; the secondary objective is to evaluate the antimyeloma response of the treatment based on the general guidelines of the International Myeloma Working Group.\n\nResults: At data cutoff, 57 patients had received LCAR-B38M CAR T cells. All patients experienced ≥ 1 adverse events (AEs). Grade ≥ 3 AEs were reported in 37/57 patients (65%); most common were leukopenia (17/57; 30%), thrombocytopenia (13/57; 23%), and aspartate aminotransferase increased (12/57; 21%). Cytokine release syndrome occurred in 51/57 patients (90%); 4/57 (7%) had grade ≥ 3 cases. One patient reported neurotoxicity of grade 1 aphasia, agitation, and seizure-like activity. The overall response rate was 88% (95% confidence interval [CI], 76 to 95); 39/57 patients (68%) achieved a complete response, 3/57 (5%) achieved a very good partial response, and 8/57 (14%) achieved a partial response. Minimal residual disease was negative for 36/57 (63%) patients. The median time to response was 1 month (range, 0.4 to 3.5). At a median follow-up of 8 months, median progression-free survival was 15 months (95% CI, 11 to not estimable). Median overall survival for all patients was not reached.\n\nConclusions: LCAR-B38M CAR T cell therapy displayed a manageable safety profile and demonstrated deep and durable responses in patients with R/R MM.\n\nTrial registration: ClinicalTrials.gov, NCT03090659; Registered on March 27, 2017, retrospectively registered.\n\nIndexed on Europe PMC as PubMed record 30572922 (DOI 10.1186/s13045-018-0681-6). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Hematol Oncol 2018","url":"https://doi.org/10.1186/s13045-018-0681-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30572922/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30572922"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["legend-2"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-hematology-and-oncology"],"dependsOn":[],"notes":[],"journal":"Journal of hematology & oncology","year":2018,"doi":"10.1186/s13045-018-0681-6","pmid":"30572922","authors":"Zhao WH, Liu J, Wang BY, et al.","paperType":"observational","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-empower-cscc-1-j-am-acad-dermatol-2025-update","kind":"paper","name":"A phase 2 open-label study of cemiplimab in patients with advanced cutaneous squamous cell carcinoma (EMPOWER-CSCC-1): Final long-term analysis of groups 1, 2, and 3, and primary analysis of fixed-dose treatment group 6","aka":[],"tldr":"Later report from the EMPOWER-CSCC-1 trial registered as NCT02760498, in Journal of the American Academy of Dermatology (2025); its title describes an updated or longer-term analysis.","summary":"Background: In the phase 2 EMPOWER-CSCC-1 study (NCT02760498), cemiplimab demonstrated antitumor activity against metastatic cutaneous squamous cell carcinoma (mCSCC) and locally advanced cutaneous squamous cell carcinoma (laCSCC).\n\nObjectives: To report final analysis of weight-based cemiplimab in mCSCC and laCSCC (groups 1 and 2), fixed-dose cemiplimab in mCSCC (group 3), and primary analysis of fixed-dose cemiplimab in mCSCC/laCSCC (group 6).\n\nMethods: Patients received cemiplimab (3 mg/kg intravenously every 2 weeks [groups 1 and 2]) or cemiplimab (350 mg intravenously [groups 3 and 6]) every 3 weeks. The primary end point was objective response rate (ORR). Duration of response (DOR) and progression-free survival (PFS) are presented per protocol, according to post-hoc sensitivity analyses that only include the period of protocol-mandated imaging assessments.\n\nResults: At 42.5 months, ORR for groups 1-3 (n = 193) was 47.2%, estimated 12-month DOR was 88.3%, and median PFS was 26.0 months. At 8.7 months, ORR for group 6 (n = 165 patients) was 44.8%; median DOR and median PFS were not reached. Serious treatment-emergent adverse event rates (grade ≥3) were groups 1-3: 31.1% and group 6: 34.5%.\n\nLimitations: Nonrandomized study, nonsurvival primary end point.\n\nConclusion: EMPOWER-CSCC-1 provides the largest prospective data on long-term efficacy and safety for anti-programmed cell death-1 therapy in advanced CSCC.\n\nIndexed on Europe PMC as PubMed record 39245360 (DOI 10.1016/j.jaad.2024.06.108). Its abstract cites the registry id NCT02760498, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Am Acad Dermatol 2025","url":"https://doi.org/10.1016/j.jaad.2024.06.108"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39245360/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39245360"},{"label":"ClinicalTrials.gov NCT02760498","url":"https://clinicaltrials.gov/study/NCT02760498"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["empower-cscc-1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of the American Academy of Dermatology","year":2025,"doi":"10.1016/j.jaad.2024.06.108","pmid":"39245360","authors":"Hughes BGM, Guminski A, Bowyer S, et al.","paperType":"observational","findings":[],"whatItMeans":"A second publication from the EMPOWER-CSCC-1 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-nct05195632-lung-cancer-2026","kind":"paper","name":"A phase 2 study of encorafenib in combination with binimetinib for Chinese participants with BRAF V600E mutated metastatic non-small cell lung cancer: Results from the OCEAN II study","aka":[],"tldr":"Published report from the OCEANII trial registered as NCT05195632, in Lung cancer (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Purpose: The ongoing OCEAN II study (ClinicalTrials.gov identifier: NCT05195632) evaluates encorafenib in combination with binimetinib (E+B) in Chinese participants with BRAF V600E -mutated metastatic non-small cell lung cancer (NSCLC).\n\nMethods: Participants with metastatic unresectable stage IV BRAF V600E -mutated NSCLC (treatment-naïve or with prior systemic therapy excluding BRAF/MEK-inhibitors), were enrolled in a phase 2 study with two parts: safety lead-in (SLI) and pivotal part (PP). Participants received daily oral encorafenib (450mg) and twice daily oral binimetinib (90mg total). Primary endpoints were dose-limiting toxicities (DLT) during SLI and confirmed objective response rate by independent central review (cORR-ICR) during PP. Secondary endpoints were other measures of efficacy, safety, and pharmacokinetics.\n\nResults: In total, 63 participants were enrolled. One DLT (non-serious Grade 3 lipase increased) during SLI considered possibly related to E+B resolved without intervention, supporting initiation of PP. Pre-defined statistical efficacy criteria on the first 50 participants were met. In the main analysis, cORR-ICRwas59% (95%CI 45-72). At a later ad hoc analysis, cORR-ICR was 61% (95%CI 47-74), disease control rate 87% (95%CI 75-95). Medians (95%CI) were, time-to-response 1.8 months, duration of response 17.5 months, progression-free survival 13.8 months (7.5-not estimable), overall survival 27.9 months (14.7-30.0). 98.4% of participants experienced ≥1 treatment-related TEAE, and 55.6% had any Grade ≥3 TEAE. Nine (14.3%) participants discontinued any drug due to adverse events.\n\nConclusion: These data confirm the clinical benefit of E+B in Chinese participants with BRAF V600E -mNSCLC, a population with distinct genomic and disease characteristics. No new safety concerns were identified in Chinese participants.\n\nIndexed on Europe PMC as PubMed record 42612509 (DOI 10.1016/j.lungcan.2026.109580). Its abstract cites the registry id NCT05195632, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lung Cancer 2026","url":"https://doi.org/10.1016/j.lungcan.2026.109580"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42612509/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42612509"},{"label":"ClinicalTrials.gov NCT05195632","url":"https://clinicaltrials.gov/study/NCT05195632"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05195632"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lung-cancer-journal"],"dependsOn":[],"notes":[],"journal":"Lung cancer","year":2026,"doi":"10.1016/j.lungcan.2026.109580","pmid":"42612509","authors":"Zhou H, Zhou Q, Guo Q, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05195632 with the most citations, so it is the natural first reading for anyone following the OCEANII trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-mansoori-mebendazole-gi-cancer-phase-2a-sci-rep-2021","kind":"paper","name":"A phase 2a clinical study on the safety and efficacy of individualized dosed mebendazole in patients with advanced gastrointestinal cancer","aka":[],"tldr":"A Swedish trial gave mebendazole to ten people with advanced bowel and stomach cancers that had stopped responding to treatment; it was safe, but every patient's cancer kept growing, four of them unusually fast.","summary":"Patients with treatment-refractory gastrointestinal cancer received mebendazole at individually adjusted doses up to 4 g a day aiming at a serum level of 300 ng/mL; 11 were included and 10 started treatment (Mebendazole phase 2a 2021). Two stopped before and the remaining eight after the eight-week CT scan, all for progressive disease, four met suggested criteria for hyperprogression, only five reached the target level, and no severe adverse effects were observed; the authors conclude that new approaches such as prodrugs or combinations would be needed for further exploration (Mebendazole phase 2a 2021).","asOf":"2026-09-24","links":[{"label":"Mebendazole phase 2a 2021","url":"https://doi.org/10.1038/s41598-021-88433-y"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33903692/"}],"tags":[],"related":[],"cancers":["colorectal","gastric"],"sections":[],"technologies":["drug-repurposing"],"targets":[],"drugs":["mebendazole"],"companies":[],"institutions":[],"pathways":[],"terms":["single-arm"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo agent (Claude Fable 5.1)","editedOn":"2026-09-24","note":"Written from cached ClinicalTrials.gov v2, Europe PMC, DailyMed, Drugs@FDA and WHO eEML responses; no figure appears without its source link."},"journal":"Scientific Reports","year":2021,"doi":"10.1038/s41598-021-88433-y","pmid":"33903692","authors":"Mansoori S, Fryknäs M, Alvfors C, Loskog A, Larsson R, Nygren P.","paperType":"translational","findings":["10 treated; all 10 stopped for progressive disease by the eight-week scan; four met hyperprogression criteria.","No severe adverse effects; only five reached the target serum concentration."],"whatItMeans":"The only completed efficacy study of an internet-famous dewormer in cancer patients found no benefit in anyone. It is the clearest human result in this whole story.","caveats":["Small single-arm study in heavily pretreated patients; drug exposure was below target in half of them."],"changedPractice":false,"participants":11},{"id":"paper-msb-gvhd001-bbmt-2020","kind":"paper","name":"A phase 3, single-arm, prospective study of remestemcel-L, ex vivo culture-expanded adult human mesenchymal stromal cells for the treatment of pediatric patients who failed to respond to steroid treatment for acute graft-versus-host disease","aka":[],"tldr":"The primary report of MSB-GVHD001: seven in ten children with steroid-refractory acute graft-versus-host disease responded to remestemcel-L by day 28, well above the 45 percent historical rate, and responders were far more likely to be alive at six months.","summary":"Phase 3, prospective, single-arm, multicentre study (NCT02336230) in 54 children with primary steroid-refractory acute graft-versus-host disease who were naive to other immunosuppressant therapies for it, treated with remestemcel-L at 2 million cells per kilogram twice weekly for 4 weeks.\n\nRemestemcel-L significantly improved day 28 overall response rate compared with the prespecified control value of 45 percent (70.4 percent versus 45 percent, P = .0003). The response was sustained through day 100, with complete response rising from 29.6 percent at day 28 to 44.4 percent at day 100. Overall survival was 74.1 percent at day 100 and 68.5 percent at day 180. Day 28 response predicted survival: 86.8 versus 47.1 percent at day 100 (P = .0001) and 78.9 versus 43.8 percent at day 180 (P = .003) for responders and nonresponders. No infusion-related toxicities or other safety concerns were identified.","asOf":"2026-09-24","links":[{"label":"Biology of Blood and Marrow Transplantation 2020","url":"https://doi.org/10.1016/j.bbmt.2020.01.018"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32018062/"},{"label":"ClinicalTrials.gov NCT02336230","url":"https://clinicaltrials.gov/study/NCT02336230"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["remestemcel-l"],"companies":["mesoblast"],"institutions":[],"pathways":[],"terms":["gvhd","allogeneic-transplant"],"trials":["msb-gvhd001"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Biology of Blood and Marrow Transplantation","year":2020,"doi":"10.1016/j.bbmt.2020.01.018","pmid":"32018062","authors":"Kurtzberg J, Abdel-Azim H, Carpenter P, et al.","paperType":"observational","findings":["Day 28 overall response 70.4% against a prespecified control of 45% (P = .0003); complete response 29.6% at day 28 and 44.4% at day 100.","Overall survival 74.1% at day 100 and 68.5% at day 180.","Survival at day 180 78.9% in day 28 responders vs 43.8% in nonresponders (P = .003); no infusion-related toxicities."],"whatItMeans":"This is the study behind the December 2024 US approval of remestemcel-L (Ryoncil), the first mesenchymal stromal cell therapy approved in the United States, for children whose acute graft-versus-host disease has not settled on steroids. The label reports the same 54 children as a 70 percent response.","caveats":["Single arm, judged against a historical 45% response rate rather than a concurrent control.","54 children; the registry full analysis set counts 55.","Do not confuse with the adult placebo-controlled remestemcel-L study (Kebriaei 2020), a different trial."],"changedPractice":true,"participants":54},{"id":"paper-adusumilli-cancer-discov","kind":"paper","name":"A Phase I Trial of Regional Mesothelin-Targeted CAR T-cell Therapy in Patients with Malignant Pleural Disease, in Combination with the Anti-PD-1 Agent Pembrolizumab","aka":[],"tldr":"Paper cited by one idea page, indexed on Europe PMC as PubMed record 34266984 and published in Cancer Discovery; the citing page links this DOI, which is how the record was matched.","summary":"Malignant pleural diseases, comprising metastatic lung and breast cancers and malignant pleural mesothelioma (MPM), are aggressive solid tumors with poor therapeutic response. We developed and conducted a first-in-human, phase I study of regionally delivered, autologous, mesothelin-targeted chimeric antigen receptor (CAR) T-cell therapy. Intrapleural administration of 0.3M to 60M CAR T cells/kg in 27 patients (25 with MPM) was safe and well tolerated. CAR T cells were detected in peripheral blood for >100 days in 39% of patients. Following our demonstration that PD-1 blockade enhances CAR T-cell function in mice, 18 patients with MPM also received pembrolizumab safely. Among those patients, median overall survival from CAR T-cell infusion was 23.9 months (1-year overall survival, 83%). Stable disease was sustained for ≥6 months in 8 patients; 2 exhibited complete metabolic response on PET scan. Combination immunotherapy with CAR T cells and PD-1 blockade agents should be further evaluated in patients with solid tumors. SIGNIFICANCE: Regional delivery of mesothelin-targeted CAR T-cell therapy followed by pembrolizumab administration is feasible, safe, and demonstrates evidence of antitumor efficacy in patients with malignant pleural diseases. Our data support the investigation of combination immunotherapy with CAR T cells and PD-1 blockade agents in solid tumors. See related commentary by Aldea et al., p. 2674. This article is highlighted in the In This Issue feature, p. 2659.\n\nIndexed on Europe PMC as PubMed record 34266984 (DOI 10.1158/2159-8290.cd-21-0407). Matched by DOI alone: one idea page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer Discov 2021","url":"https://doi.org/10.1158/2159-8290.cd-21-0407"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34266984/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34266984"}],"tags":["europepmc-ingest"],"related":["idea-mesothelin-car-t-regional"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-discovery"],"dependsOn":[],"notes":[],"journal":"Cancer Discovery","year":2021,"doi":"10.1158/2159-8290.cd-21-0407","pmid":"34266984","authors":"Adusumilli PS, Zauderer MG, Rivière I, et al.","paperType":"basic","findings":[],"whatItMeans":"One idea page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nct04454437-int-j-cancer-2023","kind":"paper","name":"A Phase IIb, single arm, multicenter trial of sacituzumab govitecan in Chinese patients with metastatic triple-negative breast cancer who received at least two prior treatments","aka":[],"tldr":"Published report from the trial registered as NCT04454437, in International journal of cancer (2023), chosen as the most cited paper whose own text cites the registry id.","summary":"Refractory or relapsing metastatic triple-negative breast cancer (mTNBC) has a poor prognosis. Sacituzumab govitecan (SG) is a novel antibody-drug conjugate, targeting human trophoblast cell-surface antigen 2 (Trop-2). This is the first report of SG's efficacy and safety in Chinese patients with mTNBC. EVER-132-001 (NCT04454437) was a multicenter, single-arm, Phase IIb study in Chinese patients with mTNBC who failed ≥2 prior chemotherapy regimens. Eligible patients received 10 mg/kg SG on Days 1 and 8 of each 21-day treatment cycle, until disease progression/unacceptable toxicity. The primary endpoint was objective response rate (ORR) assessed by the Independent Review Committee. Secondary endpoints included: duration of response (DOR), clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS) and safety. Eighty female Chinese patients (median age 47.6 years; range 24-69.9 years) received ≥1 SG dose with a median of 8 treatment cycles by the cutoff date (August 6, 2021). Median number of prior systemic cancer treatments was 4.0 (range 2.0-8.0). ORR and CBR were reported 38.8% (95% confidence interval [CI]: 28.06-50.30) and 43.8% (95% CI, 32.68-55.30) of patients, respectively. The median PFS was 5.55 months (95% CI, 4.14-N/A). SG-related Grade ≥3 treatment-emergent adverse events (TEAEs) were reported in 71.3%, the most common were neutrophil count decreased (62.5%), white blood cell count decreased (48.8%) and anemia (21.3%); 6.3% discontinued SG because of TEAEs. SG demonstrated substantial clinical activity in heavily pretreated Chinese patients with mTNBC. The observed safety profile was generally manageable.\n\nIndexed on Europe PMC as PubMed record 36621000 (DOI 10.1002/ijc.34424). Its abstract cites the registry id NCT04454437, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Int J Cancer 2023","url":"https://doi.org/10.1002/ijc.34424"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36621000/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36621000"},{"label":"ClinicalTrials.gov NCT04454437","url":"https://clinicaltrials.gov/study/NCT04454437"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04454437"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["international-journal-of-cancer"],"dependsOn":[],"notes":[],"journal":"International journal of cancer","year":2023,"doi":"10.1002/ijc.34424","pmid":"36621000","authors":"Xu B, Ma F, Wang T, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04454437 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-polcagb-protocol-bmj-open-2019","kind":"paper","name":"A phase III randomised clinical trial of perioperative therapy (neoadjuvant chemotherapy versus chemoradiotherapy) in locally advanced gallbladder cancers (POLCAGB): study protocol","aka":[],"tldr":"The plan for an Indian trial comparing chemotherapy with chemotherapy plus radiotherapy before surgery for gallbladder cancer that has grown beyond the gallbladder wall.","summary":"Protocol from Tata Memorial Hospital for a randomised trial in biopsy-proven locally advanced (T3 to T4) gallbladder cancer without metastases, comparing gemcitabine-based neoadjuvant chemotherapy with neoadjuvant chemoradiation. The primary endpoint is overall survival; secondary endpoints include progression-free survival, R0 resection rate, toxicity, complications and quality of life. The design targets a 5.5-month improvement in median survival (11 months in the control arm, hazard ratio 0.7) with 80 percent power, requiring 314 patients (157 per arm) over five years with 10 percent attrition. Registered as CTRI/2016/08/007199 and NCT02867865.","asOf":"2026-09-24","links":[{"label":"BMJ Open 2019","url":"https://doi.org/10.1136/bmjopen-2018-028147"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31253621/"},{"label":"ClinicalTrials.gov NCT02867865","url":"https://clinicaltrials.gov/study/NCT02867865"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["tata-memorial"],"pathways":[],"terms":["chemoradiation","neoadjuvant-adjuvant"],"trials":["polcagb"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"BMJ Open","year":2019,"doi":"10.1136/bmjopen-2018-028147","pmid":"31253621","authors":"Engineer R, Patkar S, Lewis SC, et al.","paperType":"methods","findings":["Planned sample 314 (157 per arm) to detect a 5.5-month gain in median overall survival, hazard ratio 0.7, 80 percent power.","Primary endpoint overall survival; the registry now lists 124 actual participants."],"whatItMeans":"India carries a large share of the world's gallbladder cancer and this is the only randomised test of radiotherapy's role before surgery; the registry's actual enrolment of 124 against a plan of 314 means the answer will be less certain than designed.","caveats":["Protocol paper; no results.","Single-institution design."],"changedPractice":false,"participants":314},{"id":"paper-yurkovetskiy-cancer-res","kind":"paper","name":"A Polymer-Based Antibody-Vinca Drug Conjugate Platform: Characterization and Preclinical Efficacy","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 26113086 and published in Cancer Research; the citing page links this DOI, which is how the record was matched.","summary":"Antibody-drug conjugates (ADC) are an emerging drug class that uses antibodies to improve cytotoxic drug targeting for cancer treatment. ADCs in current clinical trials achieve a compromise between potency and physicochemical/pharmacokinetic properties by conjugating potent cytotoxins directly to an antibody at a 4:1 or less stoichiometric ratio. Herein, we report a novel, polyacetal polymer-based platform for creating ADC that use poly-1-hydroxymethylethylene hydroxymethyl-formal (PHF), also known as Fleximer. The high hydrophilicity and polyvalency properties of the Fleximer polymer can be used to produce ADC with high drug loading without compromising physicochemical and pharmacokinetic properties. Using trastuzumab and a vinca drug derivative to demonstrate the utility of this platform, a novel Fleximer-based ADC was prepared and characterized in vivo. The ADC prepared had a vinca-antibody ratio of 20:1. It exhibited a high antigen-binding affinity, an excellent pharmacokinetic profile and antigen-dependent efficacy, and tumor accumulation in multiple tumor xenograft models. Our findings illustrate the robust utility of the Fleximer platform as a highly differentiated alternative to the conjugation platforms used to create ADC currently in clinical development.\n\nIndexed on Europe PMC as PubMed record 26113086 (DOI 10.1158/0008-5472.can-15-0129). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer Res 2015","url":"https://doi.org/10.1158/0008-5472.can-15-0129"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26113086/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26113086"}],"tags":["europepmc-ingest"],"related":["hydrophilic-next-gen"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-research"],"dependsOn":[],"notes":[],"journal":"Cancer Research","year":2015,"doi":"10.1158/0008-5472.can-15-0129","pmid":"26113086","authors":"Yurkovetskiy AV, Yin M, Bodyak N, et al.","paperType":"basic","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-braun-n-engl-j-med","kind":"paper","name":"A pooled analysis of bone marrow micrometastasis in breast cancer","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 16120859 and published in New England Journal of Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Background: We assessed the prognostic significance of the presence of micrometastasis in the bone marrow at the time of diagnosis of breast cancer by means of a pooled analysis.\n\nMethods: We combined individual patient data from nine studies involving 4703 patients with stage I, II, or III breast cancer. We evaluated patient outcomes over a 10-year follow-up period (median, 5.2 years), using a multivariable piecewise Cox regression model.\n\nResults: Micrometastasis was detected in 30.6 percent of the patients. As compared with women without bone marrow micrometastasis, patients with bone marrow micrometastasis had larger tumors and tumors with a higher histologic grade and more often had lymph-node metastases and hormone receptor-negative tumors (P<0.001 for all variables). The presence of micrometastasis was a significant prognostic factor with respect to poor overall survival and breast-cancer-specific survival (univariate mortality ratios, 2.15 and 2.44, respectively; P<0.001 for both outcomes) and poor disease-free survival and distant-disease-free survival during the 10-year observation period (incidence-rate ratios, 2.13 and 2.33, respectively; P<0.001 for both outcomes). In the multivariable analysis, micrometastasis was an independent predictor of a poor outcome. In the univariate subgroup analysis, breast-cancer-specific survival among patients with micrometastasis was significantly shortened (P<0.001 for all comparisons) among those receiving adjuvant endocrine treatment (mortality ratio, 3.22) or cytotoxic therapy (mortality ratio, 2.32) and among patients who had tumors no larger than 2 cm in diameter without lymph-node metastasis and who did not receive systemic adjuvant therapy (mortality ratio, 3.65).\n\nConclusions: The presence of micrometastasis in the bone marrow at the time of diagnosis of breast cancer is associated with a poor prognosis.\n\nIndexed on Europe PMC as PubMed record 16120859 (DOI 10.1056/nejmoa050434). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2005","url":"https://doi.org/10.1056/nejmoa050434"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/16120859/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/16120859"}],"tags":["europepmc-ingest"],"related":["disseminated-tumor-cells"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2005,"doi":"10.1056/nejmoa050434","pmid":"16120859","authors":"Braun S, Vogl FD, Naume B, et al.","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-wright-lymphgen-genetic-subtypes-dlbcl-cancer-cell-2020","kind":"paper","name":"A probabilistic classification tool for genetic subtypes of diffuse large B cell lymphoma with therapeutic implications","aka":["LymphGen","Wright 2020","Seven genetic subtypes of diffuse large B-cell lymphoma"],"tldr":"A tool that takes one patient's tumour genetics and gives the probability that it belongs to each of seven genetic groups, rather than sorting whole cohorts into clusters.","summary":"Clustering methods classify a cohort. A patient needs a classification of their own tumour, with a statement of how confident it is. LymphGen is the algorithm that provides it: it returns the probability that a given lymphoma belongs to each of seven genetic subtypes on the basis of its genetic features.\n\nThe classification extends the four subtypes of the 2018 National Cancer Institute paper and revealed genetic similarities between diffuse large B-cell lymphoma subtypes and various indolent and extranodal lymphoma types, which suggests a shared pathogenesis and is one of the stronger arguments that the current histological boundaries do not cut the disease at its joints. The subtypes have distinct gene-expression profiles, distinct immune microenvironments and distinct outcomes after immunochemotherapy, and functional analysis of subtype models showed distinct vulnerabilities to targeted therapy.\n\nLymphGen is now the classifier used to select patients in genetics-directed trials in this disease, which is the practical reason it belongs on this list rather than in a methods appendix.","asOf":"2026-10-01","links":[{"label":"Cancer Cell 2020","url":"https://doi.org/10.1016/j.ccell.2020.03.015"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32289277/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32289277"}],"tags":["lymphoma-evidence"],"related":["paper-schmitz-genetics-pathogenesis-dlbcl-nejm-2018","paper-chapuy-molecular-subtypes-dlbcl-nat-med-2018","lymphoma-roadmap"],"cancers":["dlbcl","non-hodgkin-lymphoma","primary-cns-lymphoma","primary-mediastinal-b-cell-lymphoma","marginal-zone-lymphoma"],"sections":["diagnostics","ai-computation","targeted-therapy"],"technologies":["wes-wgs","ngs"],"targets":["myd88","cd79b","bcl2","bcl6","ezh2","notch1","notch2","tp53"],"drugs":[],"companies":[],"institutions":["nci"],"pathways":[],"terms":["cell-of-origin"],"trials":[],"people":["louis-staudt"],"bottlenecks":["b-biomarker-validation","b-trial-design","b-data-silos"],"keyPapers":[],"journals":["cancer-cell"],"dependsOn":[],"notes":[],"journal":"Cancer Cell","year":2020,"doi":"10.1016/j.ccell.2020.03.015","pmid":"32289277","authors":"Wright GW, Huang DW, Phelan JD, et al.","paperType":"methods","findings":["An algorithm was described that returns the probability that an individual patient's lymphoma belongs to each of seven genetic subtypes, based on its genetic features.","The classification revealed genetic similarities between these subtypes and various indolent and extranodal lymphoma types, suggesting shared pathogenesis.","The genetic subtypes have distinct gene-expression profiles, distinct immune microenvironments and distinct outcomes after immunochemotherapy.","Functional analysis of genetic subtype models highlighted distinct vulnerabilities to targeted therapy."],"whatItMeans":"The piece that turns a research classification into something a trial can use on one person's biopsy, with a probability attached rather than a flat label. It is the reason genetics-directed lymphoma trials became possible at all.","caveats":["A classification tool, not a clinical trial: no randomised evidence yet shows that treating by LymphGen subtype improves outcomes.","It needs comprehensive genetic data, including copy number and structural variants, which most routine panels do not generate.","A proportion of cases remain unclassified by design, and that proportion is larger in cohorts with less complete sequencing.","Subtype boundaries still depend on the training cohorts, which were largely of European ancestry."],"changedPractice":false},{"id":"paper-rimm-pd-l1-assay-comparison-jama-oncol-2017","kind":"paper","name":"A prospective, multi-institutional, pathologist-based assessment of 4 immunohistochemistry assays for PD-L1 expression in non-small cell lung cancer","aka":[],"tldr":"Thirteen pathologists scored four different stains for the same protein on ninety lung cancers. They agreed well on the cancer cells and hardly at all on the immune cells, and one of the four stains consistently read lower than the others.","summary":"Four serial histological sections from 90 archival non-small-cell lung cancers were distributed to three sites, which performed immunohistochemistry with the 28-8 and 22C3 antibodies on the Dako Link 48 platform, SP142 on the Ventana Benchmark platform and E1L3N on the Leica Bond platform. Slides were scanned and scored by 13 pathologists estimating the percentage of malignant and immune cells expressing PD-L1. SP142 was an outlier with significantly lower mean scores in both compartments (tumour cells 1.99 against 2.96 for 22C3, 3.26 for 28-8 and 3.20 for E1L3N). Interassay concordance for tumour-cell scoring was high, 0.813, and low for immune-cell scoring, 0.277.","asOf":"2026-09-25","links":[{"label":"Rimm et al., JAMA Oncol 2017: 13 pathologists scoring four PD-L1 assays on 90 non-small-cell lung cancers","url":"https://doi.org/10.1001/jamaoncol.2017.0013"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28278348/"}],"tags":[],"related":["pd-l1-tps","pd-l1-tc-score","pd-l1-ic-score"],"cancers":["nsclc"],"sections":[],"technologies":["histopathology-ihc"],"targets":["pdl1"],"drugs":[],"companies":[],"institutions":["yale-cancer-center","md-anderson"],"pathways":["pd1-checkpoint"],"terms":["ihc"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2017,"doi":"10.1001/jamaoncol.2017.0013","pmid":"28278348","authors":"Rimm DL, Han G, Taube JM, et al.","paperType":"methods","findings":["SP142 gives significantly lower scores than 22C3, 28-8 and E1L3N in both compartments.","28-8 and a laboratory-developed E1L3N test were statistically indistinguishable.","Interassay concordance 0.813 for tumour cells and 0.277 for immune cells.","Pathologist variability is the larger source of error for immune cells."],"whatItMeans":"Together with the Blueprint work it establishes that a PD-L1 percentage reports the assay as much as it reports the tumour, so the threshold and the antibody have to be quoted together.","caveats":["Archival tissue from 2008 to 2010, where antigen may have degraded.","Scoring was on scanned images rather than at the microscope.","A laboratory-developed test was included, which is not equivalent to a regulated assay."],"changedPractice":false,"participants":90},{"id":"paper-swanson-cell-prolif","kind":"paper","name":"A quantitative model for differential motility of gliomas in grey and white matter","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 11063134 and published in Cell proliferation; the citing page links this DOI, which is how the record was matched.","summary":"We have extended a mathematical model of gliomas based on proliferation and diffusion rates to incorporate the effects of augmented cell motility in white matter as compared to grey matter. Using a detailed mapping of the white and grey matter in the brain developed for a MRI simulator, we have been able to simulate model tumours on an anatomically accurate brain domain. Our simulations show good agreement with clinically observed tumour geometries and suggest paths of submicroscopic tumour invasion not detectable on CT or MRI images. We expect this model to give insight into microscopic and submicroscopic invasion of the human brain by glioma cells. This method gives insight in microscopic and submicroscopic invasion of the human brain by glioma cells. Additionally, the model can be useful in defining expected pathways of invasion by glioma cells and thereby identify regions of the brain on which to focus treatments.\n\nIndexed on Europe PMC as PubMed record 11063134 (DOI 10.1046/j.1365-2184.2000.00177.x). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cell Prolif 2000","url":"https://doi.org/10.1046/j.1365-2184.2000.00177.x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/11063134/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/11063134"}],"tags":["europepmc-ingest"],"related":["reaction-diffusion-glioma-model"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Cell proliferation","year":2000,"doi":"10.1046/j.1365-2184.2000.00177.x","pmid":"11063134","authors":"Swanson KR, Alvord EC, Murray JD","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-castroviejo-bermejo-embo-mol-med","kind":"paper","name":"A RAD51 assay feasible in routine tumor samples calls PARP inhibitor response beyond BRCA mutation","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 30377213 and published in EMBO molecular medicine; the citing page links this DOI, which is how the record was matched.","summary":"Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) are effective in cancers with defective homologous recombination DNA repair (HRR), including BRCA1/2-related cancers. A test to identify additional HRR-deficient tumors will help to extend their use in new indications. We evaluated the activity of the PARPi olaparib in patient-derived tumor xenografts (PDXs) from breast cancer (BC) patients and investigated mechanisms of sensitivity through exome sequencing, BRCA1 promoter methylation analysis, and immunostaining of HRR proteins, including RAD51 nuclear foci. In an independent BC PDX panel, the predictive capacity of the RAD51 score and the homologous recombination deficiency (HRD) score were compared. To examine the clinical feasibility of the RAD51 assay, we scored archival breast tumor samples, including PALB2-related hereditary cancers. The RAD51 score was highly discriminative of PARPi sensitivity versus PARPi resistance in BC PDXs and outperformed the genomic test. In clinical samples, all PALB2-related tumors were classified as HRR-deficient by the RAD51 score. The functional biomarker RAD51 enables the identification of PARPi-sensitive BC and broadens the population who may benefit from this therapy beyond BRCA1/2-related cancers.\n\nIndexed on Europe PMC as PubMed record 30377213 (DOI 10.15252/emmm.201809172). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"EMBO Mol Med 2018","url":"https://doi.org/10.15252/emmm.201809172"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30377213/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30377213"}],"tags":["europepmc-ingest"],"related":["rad51-foci-assay"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"EMBO molecular medicine","year":2018,"doi":"10.15252/emmm.201809172","pmid":"30377213","authors":"Castroviejo-Bermejo M, Cruz C, Llop-Guevara A, et al.","paperType":"basic","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-montgomery-j-natl-cancer-inst","kind":"paper","name":"A randomized clinical trial of a brief hypnosis intervention to control side effects in breast surgery patients","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 17728216 and published in JNCI: Journal of the National Cancer Institute; the citing page links this DOI, which is how the record was matched.","summary":"Background: Breast cancer surgery is associated with side effects, including postsurgical pain, nausea, and fatigue. We carried out a randomized clinical trial to test the hypotheses that a brief presurgery hypnosis intervention would decrease intraoperative anesthesia and analgesic use and side effects associated with breast cancer surgery and that it would be cost effective.\n\nMethods: We randomly assigned 200 patients who were scheduled to undergo excisional breast biopsy or lumpectomy (mean age 48.5 years) to a 15-minute presurgery hypnosis session conducted by a psychologist or nondirective empathic listening (attention control). Patients were not blinded to group assignment. Intraoperative anesthesia use (i.e., of the analgesics lidocaine and fentanyl and the sedatives propofol and midazolam) was assessed. Patient-reported pain and other side effects as measured on a visual analog scale (0-100) were assessed at discharge, as was use of analgesics in the recovery room. Institutional costs and time in the operating room were assessed via chart review.\n\nResults: Patients in the hypnosis group required less propofol (means = 64.01 versus 96.64 microg; difference = 32.63; 95% confidence interval [CI] = 3.95 to 61.30) and lidocaine (means = 24.23 versus 31.09 mL; difference = 6.86; 95% CI = 3.05 to 10.68) than patients in the control group. Patients in the hypnosis group also reported less pain intensity (means = 22.43 versus 47.83; difference = 25.40; 95% CI = 17.56 to 33.25), pain unpleasantness (means = 21.19 versus 39.05; difference = 17.86; 95% CI = 9.92 to 25.80), nausea (means = 6.57 versus 25.49; difference = 18.92; 95% CI = 12.98 to 24.87), fatigue (means = 29.47 versus 54.20; difference = 24.73; 95% CI = 16.64 to 32.83), discomfort (means = 23.01 versus 43.20; difference = 20.19; 95% CI = 12.36 to 28.02), and emotional upset (means = 8.67 versus 33.46; difference = 24.79; 95% CI = 18.56 to 31.03). No statistically significant differences were seen in the use of fentanyl, midazolam, or recovery room analgesics. Institutional costs for surgical breast cancer procedures were $8561 per patient at Mount Sinai School of Medicine. Patients in the hypnosis group cost the institution $772.71 less per patient than those in the control group (95% CI = 75.10 to 1469.89), mainly due to reduced surgical time.\n\nConclusions: Hypnosis was superior to attention control regarding propofol and lidocaine use; pain, nausea, fatigue, discomfort, and emotional upset at discharge; and institutional cost. Overall, the present data support the use of hypnosis with breast cancer surgery patients.\n\nIndexed on Europe PMC as PubMed record 17728216 (DOI 10.1093/jnci/djm106). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Natl Cancer Inst 2007","url":"https://doi.org/10.1093/jnci/djm106"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/17728216/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/17728216"}],"tags":["europepmc-ingest"],"related":["hypnosis-cancer-care"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jnci"],"dependsOn":[],"notes":[],"journal":"JNCI: Journal of the National Cancer Institute","year":2007,"doi":"10.1093/jnci/djm106","pmid":"17728216","authors":"Montgomery GH, Bovbjerg DH, Schnur JB, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-overgaard-radiother-oncol","kind":"paper","name":"A randomized double-blind phase III study of nimorazole as a hypoxic radiosensitizer of primary radiotherapy in supraglottic larynx and pharynx carcinoma. Results of the Danish Head and Neck Cancer Study (DAHANCA) Protocol 5-85","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 9510041 and published in Radiotherapy and Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: A multicenter randomized and balanced double-blind trial with the objective of assessing the efficacy and tolerance of nimorazole given as a hypoxic radiosensitizer in conjunction with primary radiotherapy of invasive carcinoma of the supraglottic larynx and pharynx.\n\nPatients and treatment: Between January 1986 and September 1990, 422 patients (414 eligible) with pharynx and supraglottic larynx carcinoma were double-blind randomized to receive the hypoxic cell radiosensitizer nimorazole, or placebo, in association with conventional primary radiotherapy (62-68 Gy, 2 Gy per fraction, five fractions per week). The median observation time was 112 months.\n\nResults: Univariate analysis showed that the outcome (5-year actuarial loco-regional tumor control) was significantly related to T-classification (T1-T2 48% versus T3-T4 36%, P = 0.0008), neck-nodes (N- 53% versus N+ 33%), pre-irradiation hemoglobin (Hb) concentration (high 46% versus low 37%, P = 0.02) and sex (females 51% versus males 38%, P = 0.03). Overall the nimorazole group showed a significantly better loco-regional control rate than the placebo group (49 versus 33%, P = 0.002). A similar significant benefit of nimorazole was observed for the end-points of final loco-regional control (including surgical salvage) and cancer-related deaths (52 versus 41%, P = 0.002). This trend was also found in the overall survival but to a lesser, non-significant extent (26 versus 16%, 10-year actuarial values, P = 0.32). Cox multivariate regression analysis showed the most important prognostic parameters for loco-regional control to be positive neck nodes (relative risk 1.84 (1.38-2.45)), T3-T4 tumor (relative risk 1.65 (1.25-2.17)) and nimorazole (relative risk 0.69 (0.52-0.90)). The same parameters were also significantly related to the probability of dying from cancer. The compliance to radiotherapy was good and 98% of the patients received the planned dose. Late radiation-related morbidity was observed in 10% of the patients, irrespective of nimorazole treatment. Drug-related side-effects were minor and tolerable with transient nausea and vomiting being the most frequent complications.\n\nConclusion: Nimorazole significantly improves the effect of radiotherapeutic management of supraglottic and pharynx tumors and can be given without major side-effects.\n\nIndexed on Europe PMC as PubMed record 9510041 (DOI 10.1016/s0167-8140(97)00220-x). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Radiother Oncol 1998","url":"https://doi.org/10.1016/s0167-8140(97)00220-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/9510041/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/9510041"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["dahanca-5"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["radiotherapy-and-oncology"],"dependsOn":[],"notes":[],"journal":"Radiotherapy and Oncology","year":1998,"doi":"10.1016/s0167-8140(97)00220-x","pmid":"9510041","authors":"Overgaard J, Hansen HS, Overgaard M, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-tam-blood","kind":"paper","name":"A randomized phase 3 trial of zanubrutinib vs ibrutinib in symptomatic Waldenström macroglobulinemia: the ASPEN study","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 32731259 and published in Blood; the citing page links this DOI, which is how the record was matched.","summary":"Bruton tyrosine kinase (BTK) inhibition is an effective treatment approach for patients with Waldenström macroglobulinemia (WM). The phase 3 ASPEN study compared the efficacy and safety of ibrutinib, a first-generation BTK inhibitor, with zanubrutinib, a novel highly selective BTK inhibitor, in patients with WM. Patients with MYD88L265P disease were randomly assigned 1:1 to treatment with ibrutinib or zanubrutinib. The primary end point was the proportion of patients achieving a complete response (CR) or a very good partial response (VGPR) by independent review. Key secondary end points included major response rate (MRR), progression-free survival (PFS), duration of response (DOR), disease burden, and safety. A total of 201 patients were randomized, and 199 received ≥1 dose of study treatment. No patient achieved a CR. Twenty-nine (28%) zanubrutinib patients and 19 (19%) ibrutinib patients achieved a VGPR, a nonstatistically significant difference (P =.09). MRRs were 77% and 78%, respectively. Median DOR and PFS were not reached; 84% and 85% of ibrutinib and zanubrutinib patients were progression free at 18 months. Atrial fibrillation, contusion, diarrhea, peripheral edema, hemorrhage, muscle spasms, and pneumonia, as well as adverse events leading to treatment discontinuation, were less common among zanubrutinib recipients. Incidence of neutropenia was higher with zanubrutinib, although grade ≥3 infection rates were similar in both arms (1.2 and 1.1 events per 100 person-months). These results demonstrate that zanubrutinib and ibrutinib are highly effective in the treatment of WM, but zanubrutinib treatment was associated with a trend toward better response quality and less toxicity, particularly cardiovascular toxicity.\n\nIndexed on Europe PMC as PubMed record 32731259 (DOI 10.1182/blood.2020006844). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Blood 2020","url":"https://doi.org/10.1182/blood.2020006844"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32731259/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32731259"}],"tags":["europepmc-ingest"],"related":["waldenstrom"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["blood"],"dependsOn":[],"notes":[],"journal":"Blood","year":2020,"doi":"10.1182/blood.2020006844","pmid":"32731259","authors":"Tam CS, Opat S, D'Sa S, et al.","paperType":"rct","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nct02152631-front-oncol-2020","kind":"paper","name":"A Randomized Phase III Study of Abemaciclib Versus Erlotinib in Patients with Stage IV Non-small Cell Lung Cancer With a Detectable KRAS Mutation Who Failed Prior Platinum-Based Therapy: JUNIPER","aka":[],"tldr":"Published report from the JUNIPER trial registered as NCT02152631, in Frontiers in oncology (2020), chosen as the most cited paper whose own text cites the registry id.","summary":"Introduction: JUNIPER compared the efficacy and safety of abemaciclib, a selective cyclin-dependent kinase 4 and 6 inhibitor, with erlotinib in patients with non-small cell lung cancer (NSCLC) harboring a Kirsten rat sarcoma ( KRAS) mutation.\n\nMethods: JUNIPER was a Phase III, multicenter, randomized, open-label trial of abemaciclib versus erlotinib in patients with stage IV NSCLC and a detectable mutation in codons 12 or 13 of the KRAS oncogene, who progressed after platinum-based chemotherapy and 1 additional therapy (could include immune checkpoint inhibitor therapy). Randomized patients (3:2) received either 200 mg abemaciclib twice daily or 150 mg erlotinib once daily with best supportive care until disease progression or unacceptable toxicity. The primary endpoint was overall survival (OS); secondary endpoints included overall response rate (ORR), progression-free survival (PFS), and safety.\n\nResults: Between December 2014 and April 2017, 453 patients were randomly assigned to receive abemaciclib (N = 270) or erlotinib (N = 183). Median OS was 7.4 months (95% confidence interval [CI]: 6.5, 8.8) with abemaciclib and 7.8 months (95% CI: 6.4, 9.5) with erlotinib (hazard ratio [HR] = 0.968 [95% CI: 0.768, 1.219]; p =.77). Median PFS was 3.6 months (95% CI: 2.8, 3.8) with abemaciclib and 1.9 months (95% CI: 1.9, 2.0) with erlotinib (HR = 0.583 [95% CI: 0.470, 0.723]; p <.000001). ORR was 8.9% and 2.7% (p =.010), and the disease control rate was 54.4% and 31.7% (p <.001) with abemaciclib and erlotinib, respectively. Safety results reflected the known safety profiles of abemaciclib and erlotinib.\n\nConclusions: In this study, the primary endpoint of OS was not met; PFS and ORR were improved with manageable toxicity in the abemaciclib arm. The increases in response rates and PFS support further investigation of abemaciclib in other NSCLC subpopulations or in combination with other agents.\n\nClinical trial registration: www.ClinicalTrials.gov, identifier: NCT02152631.\n\nIndexed on Europe PMC as PubMed record 33194700 (DOI 10.3389/fonc.2020.578756). Its abstract cites the registry id NCT02152631, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Front Oncol 2020","url":"https://doi.org/10.3389/fonc.2020.578756"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33194700/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33194700"},{"label":"ClinicalTrials.gov NCT02152631","url":"https://clinicaltrials.gov/study/NCT02152631"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct02152631"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Frontiers in oncology","year":2020,"doi":"10.3389/fonc.2020.578756","pmid":"33194700","authors":"Goldman JW, Mazieres J, Barlesi F, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02152631 with the most citations, so it is the natural first reading for anyone following the JUNIPER trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-espac-1-chemoradiotherapy-chemotherapy-resected-pancreatic-nejm-2004","kind":"paper","name":"A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer","aka":[],"tldr":"The 2004 European trial that showed chemotherapy after pancreatic cancer surgery doubled five-year survival, while adding radiotherapy to the chemotherapy made survival worse, a result that split European and American practice for a decade.","summary":"ESPAC-1 used a two-by-two factorial design to randomise 289 patients with resected pancreatic ductal adenocarcinoma: 73 to chemoradiotherapy alone (20 Gy over two weeks plus fluorouracil), 75 to chemotherapy alone (fluorouracil), 72 to both and 69 to observation. With 237 deaths and a median follow-up of 47 months, the estimated five-year survival was 10 percent among patients assigned chemoradiotherapy and 20 percent among those who did not receive it (P = 0.05), and 21 percent among those who received chemotherapy against 8 percent among those who did not (P = 0.009); the chemotherapy benefit persisted after adjustment for prognostic factors. The authors concluded that adjuvant chemotherapy has a significant survival benefit whereas adjuvant chemoradiotherapy has a deleterious effect.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2004","url":"https://doi.org/10.1056/NEJMoa032295"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/15028824/"}],"tags":["pancreatic-evidence"],"related":["paper-espac-3-fluorouracil-vs-gemcitabine-adjuvant-neoptolemos-jama-2010","paper-conko-001-adjuvant-gemcitabine-observation-jama-2007","chemotherapy-roadmap"],"cancers":["pancreatic","resectable-pdac"],"sections":["chemotherapy","radiation"],"technologies":["cytotoxic-chemotherapy"],"targets":[],"drugs":["fluorouracil"],"companies":[],"institutions":[],"pathways":[],"terms":["neoadjuvant-adjuvant"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2004,"doi":"10.1056/NEJMoa032295","pmid":"15028824","authors":"Neoptolemos JP, Stocken DD, Friess H, et al.","paperType":"rct","findings":["289 resected patients in a two-by-two factorial design; 237 deaths at 47 months median follow-up.","Five-year survival 21 percent with chemotherapy against 8 percent without (P = 0.009).","Five-year survival 10 percent with chemoradiotherapy against 20 percent without (P = 0.05)."],"whatItMeans":"The origin of the European position that adjuvant treatment means chemotherapy alone; CONKO-001, ESPAC-3, ESPAC-4 and PRODIGE 24 all built on it, and the role of radiotherapy remains contested (LAP07, PREOPANC).","caveats":["The factorial design allowed clinician choice of randomisation options and background treatment, criticised at the time.","Split-course radiotherapy at 20 Gy is not modern chemoradiotherapy; the harm may not generalise."],"changedPractice":true,"participants":289},{"id":"paper-wattel-blood","kind":"paper","name":"A randomized trial of hydroxyurea versus VP16 in adult chronic myelomonocytic leukemia. Groupe Français des Myélodysplasies and European CMML Group","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 8839839 and published in Blood; the citing page links this DOI, which is how the record was matched.","summary":"We performed a randomized study of hydroxyurea (HY) versus VP16 in advanced chronic myelomonocytic leukemia (CMML) patients with CMML (according to French-American-British group criteria) and either documented visceral involvement (excluding liver and spleen infiltration) or at least 2 of the following: (1) neutrophils > 16 x 10(9)/I (2) Hemoglobin < 10 g/dL (3) platelets < 100 x 10(9)/L (4) marrow blasts > 5% (5) spleen > 5 cm below costal margin were eligible for this trial. Initial dosage was 1 g/d for HY and 150 mg/week for VP16, orally (doubled in case of visceral involvement). Doses were scheduled to be escalated up to HY 4 g/d and VP16 600 mg/week in the absence of response, and finally adjusted to maintain white blood cells (WBCs) between 5 and 10 x 10(9)/L. Crossing over was scheduled only in case of life threatening visceral involvement or major progression. The major endpoint of the study was survival. The study was closed on first interim analysis that showed a superiority of HY over VP16, after inclusion of 105 pts (HY arm: 53, VP16 arm: 52). Results of the second interim analysis, performed 7 months later, are presented here. Median age was 71 (range 38 to 91), median WBC count 20.10(9)/L (range 10 to 187). Thirteen pts had visceral involvement (3 serous effusions, 8 cutaneous infiltrations, 1 kidney, 1 bone infiltrations). Initial characteristics were similar in the HY and VP16 groups. Median follow up was 11 months in both groups (range 1 to 43+). Response to treatment was seen in 60% of the pts in the HY group, versus 36%, respectively, in the VP16 group (P =.02). Time to response was significantly shorter in the HY group (2.1 v 3.5 months, in the VP16 group, P =.003) and response duration was significantly longer in the HY group (median 24 v 9 months, in the VP16 group, P =.0004). The response rate of patients with visceral involvement was 3 out of 7 in the VP16 arm versus 5 out of 6 in the HY group. Three of the 10 pts crossed over from HY to VP16 responded as compared to 6 pts of the 11 pts crossed over from VP16 to HY. HY yielded better response on leukocytosis (P =.002). The effect on splenomegaly platelets, on hemoglobin level and transfusion requirement was similar in the 2 treatment groups. A significantly higher incidence of alopecia was noted in the VP16 arm (20% v 3%, P =.03). Fourteen (27%) and 20 (38%) patients in the HY and the VP16 group respectively, progressed to acute myeloid leukemia (difference NS). Twenty five (53%) and 44 (83%) patients in the HY and the VP16 group, respectively, had died (P =.002). Median actuarial survival was 20 months in the HY arm, versus 9 months in the VP16 arm (P < 10(-4)). Main factors associated with poor survival were allocation to the VP16 arm, \"unfavorable\" karyotype (ie, monosomy 7 or complex abnormalities) and anemia. In the HY group, unfavorable karyotype (P =.006), and low hemoglobin level (P =.004) were significantly associated with low response rates. Prognostic factors for poor survival in the HY group were also unfavorable karyotype (P =.001), and low hemoglobin level (P < 10(-4). In conclusion, we found that HY gave higher response rates and better survival than VP16 in advanced CMML. However, even with HY responses were only partial and survival was generally poor. This stresses the need for new agents in the treatment of CMML, that will have to be compared with HY in future randomized studies.\n\nIndexed on Europe PMC as PubMed record 8839839 (DOI 10.1182/blood.v88.7.2480.bloodjournal8872480). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Blood 1996","url":"https://doi.org/10.1182/blood.v88.7.2480.bloodjournal8872480"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/8839839/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/8839839"}],"tags":["europepmc-ingest"],"related":["cmml"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["blood"],"dependsOn":[],"notes":[],"journal":"Blood","year":1996,"doi":"10.1182/blood.v88.7.2480.bloodjournal8872480","pmid":"8839839","authors":"Wattel E, Guerci A, Hecquet B, et al.","paperType":"rct","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-duvic-j-am-acad-dermatol","kind":"paper","name":"A randomized trial of minoxidil in chemotherapy-induced alopecia","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 8682968 and published in Journal of the American Academy of Dermatology; the citing page links this DOI, which is how the record was matched.","summary":"Background: Hair loss is a side effect of many chemotherapeutic agents, and patients have even refused possibly palliative or lifesaving drugs because they could not accept temporary or prolonged baldness. Topical minoxidil has been shown to be effective for androgenetic alopecia and alopecia areata.\n\nObjective: Our purpose was to investigate the value and safety of minoxidil in chemotherapy-induced hair loss.\n\nMethods: Twenty-two women who were facing adjuvant chemotherapy after breast surgery were registered in a protocol that used a 2% minoxidil topical solution or a placebo in a randomized double-blind trial.\n\nResults: There was a statistically significant difference (favoring minoxidil) in the interval from maximal hair loss to first regrowth. Thus the period of baldness was shortened (mean, 50.2 days) in the minoxidil group.\n\nConclusion: Minoxidil decreased the duration of alopecia caused by chemotherapy. There were no significant side effects.\n\nIndexed on Europe PMC as PubMed record 8682968 (DOI 10.1016/s0190-9622(96)90500-9). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Am Acad Dermatol 1996","url":"https://doi.org/10.1016/s0190-9622(96)90500-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/8682968/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/8682968"}],"tags":["europepmc-ingest"],"related":["minoxidil-chemotherapy-alopecia"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of the American Academy of Dermatology","year":1996,"doi":"10.1016/s0190-9622(96)90500-9","pmid":"8682968","authors":"Duvic M, Lemak NA, Valero V, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-carboplatin-glioblastoma-neuro-oncol-2003","kind":"paper","name":"A randomized, double-blind, placebo-controlled, phase 2 study of RMP-7 in combination with carboplatin administered intravenously for the treatment of recurrent malignant glioma","aka":[],"tldr":"Phase 2 or 3 results paper on Carboplatin in Glioma & glioblastoma, in Neuro-Oncology (2003), one of the most cited Europe PMC records with Carboplatin in its title.","summary":"RMP-7, a bradykinin analog, temporarily increases the permeability of the blood-brain tumor barrier to chemotherapy drugs like carboplatin. We conducted a randomized, controlled trial of carboplatin and RMP-7 versus carboplatin and placebo in patients with recurrent malignant glioma. The primary outcome measure was time to tumor progression (TTP). Adults with recurrent glioblastoma multiforme or anaplastic glioma were randomized in a 1:1 ratio to receive carboplatin and either RMP-7 or placebo. Radiation therapy had failed in all patients, and they may have received prior chemotherapy. Carboplatin (dosed to achieve an area under the curve of 5 mg/ml x time for patients who had received prior chemotherapy, or 7 mg/ml x time for those who had not) was given intravenously every 4 weeks, followed by intravenous infusion of either RMP-7 or placebo (300 ng/kg). TTP, tumor response, neuropsychological assessments, functional independence, and quality of life assessments were analyzed every 4 weeks. There were 122 patients enrolled, 62 in the RMP-7 and carboplatin group and 60 in the placebo and carboplatin group. Median TTP was 9.7 weeks (95% CI, 8.3-12.6 weeks) for the RMP-7 and carboplatin group and 8.0 weeks (95% CI, 7.4-12.6 weeks) for the placebo and carboplatin group. Median survival times were 26.9 weeks (95% CI, 21.3-37.6 weeks) for the RMP-7 group and 19.9 weeks (95% CI, 15.0-31.3 weeks) for the placebo group. No differences were noted for time to worsening of neuropsychological assessments, functional independence, or quality of life assessments. The use of RMP-7 had no effect on the pharmacokinetics or toxicity of carboplatin. At the dose and schedule used in this trial, RMP-7 did not improve the efficacy of carboplatin. Recent preclinical pharmacokinetic modeling of RMP-7 suggests that higher doses of RMP-7 may be required to increase carboplatin delivery to tumor.\n\nIndexed on Europe PMC as PubMed record 12672281 (DOI 10.1093/neuonc/5.2.96). Its title names Carboplatin and its text names Glioma & glioblastoma; PubMed types it as a clinical trial report (Clinical Trial, Phase II, Comparative Study, Clinical Trial, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, research-article, Multicenter Study, Randomized Controlled Trial). It was matched automatically to the idea \"A skull ultrasound implant that opens the barrier at every cycle\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Neuro Oncol 2003","url":"https://doi.org/10.1093/neuonc/5.2.96"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/12672281/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/12672281"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["neuro-oncology"],"dependsOn":[],"notes":[],"journal":"Neuro-Oncology","year":2003,"doi":"10.1093/neuonc/5.2.96","pmid":"12672281","authors":"Prados MD, Schold SC, Fine HA, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Carboplatin in Glioma & glioblastoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Carboplatin in the title and Glioma & glioblastoma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-notta-punctuated-evolution-pancreatic-nature-2016","kind":"paper","name":"A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns","aka":[],"tldr":"Tracking chromosome damage in tumour-enriched genomes showed that pancreatic cancer often does not acquire its driver mutations one at a time: in two-thirds of tumours a catastrophic mitotic error knocks out several at once, so the disease can become invasive in a jump.","summary":"Using new informatics tools, changes in DNA copy number and associated rearrangements were tracked in tumour-enriched genomes. The prevailing model predicts a particular sequence (KRAS, then CDKN2A, then TP53 and SMAD4) acquired gradually. Two-thirds of tumours harboured complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory; in a subset the consequence was the simultaneous rather than sequential knockout of canonical preneoplastic drivers, likely setting off invasive growth.","asOf":"2026-09-24","links":[{"label":"Notta et al., Nature 2016: a renewed, punctuated model of pancreatic cancer evolution","url":"https://doi.org/10.1038/nature19823"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27732578/"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":["wes-wgs"],"targets":["kras","tp53","cdkn2a","smad4"],"drugs":[],"companies":[],"institutions":["oicr","princess-margaret"],"pathways":["chromosomal-instability","clonal-evolution"],"terms":["whole-genome-doubling"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2016,"doi":"10.1038/nature19823","pmid":"27732578","authors":"Notta F, Chan-Seng-Yue M, Lemire M, et al.","paperType":"translational","findings":["Two-thirds of tumours show complex rearrangements from mitotic errors.","Canonical drivers can be knocked out simultaneously rather than in sequence."],"whatItMeans":"The textbook PanIN-to-cancer ladder is only part of the story, and a screening programme cannot assume years of orderly progression in every patient.","caveats":["Inference from bulk copy-number and rearrangement patterns.","The proportion of cancers arising by each route is uncertain."],"changedPractice":false},{"id":"paper-basturk-baltimore-consensus-precursor-lesions-ajsp-2015","kind":"paper","name":"A revised classification system and recommendations from the Baltimore consensus meeting for neoplastic precursor lesions in the pancreas","aka":[],"tldr":"An international panel simplified precursor grading to low grade and high grade, reserving high grade for carcinoma in situ, and set rules for margins, small intraductal lesions and simple mucinous cysts.","summary":"International experts revised the 2004 recommendations for assessing and reporting precursor lesions of the pancreas, including PanIN, IPMN, mucinous cystic neoplasm and others. A two-tiered system (low versus high grade) is proposed for all precursor lesions, with former PanIN-2 and intermediate-grade neoplasms categorised as low grade and high-grade dysplasia reserved for carcinoma in situ-type lesions. PanIN of any grade at a resection margin has no prognostic implication. Intraductal lesions of 0.5 to 1 cm may be large PanINs or small IPMNs, with 'incipient IPMN' reserved for those with intestinal or oncocytic papillae or GNAS mutations. Distance between IPMN and invasive carcinoma should be measured to assess concomitant versus associated status. 'Intraductal spread of invasive carcinoma' and 'simple mucinous cyst' are defined.","asOf":"2026-09-24","links":[{"label":"Basturk et al., Am J Surg Pathol 2015: Baltimore consensus, two-tier grading of precursor lesions","url":"https://doi.org/10.1097/PAS.0000000000000533"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26559377/"}],"tags":[],"related":[],"cancers":["pancreatic","ipmn-cystic-precursors"],"sections":[],"technologies":[],"targets":["gnas"],"drugs":[],"companies":[],"institutions":["mskcc","johns-hopkins"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"American Journal of Surgical Pathology","year":2015,"doi":"10.1097/PAS.0000000000000533","pmid":"26559377","authors":"Basturk O, Hong SM, Wood LD, et al.","paperType":"guideline","findings":["Two-tier grading (low versus high) for all pancreatic precursor lesions.","PanIN at a margin carries no prognostic implication; GNAS mutation defines incipient IPMN."],"whatItMeans":"The reporting standard behind every modern precursor study and the reason a pathology report now says low or high grade rather than PanIN-2.","caveats":["Consensus, not evidence from outcome data.","Clinical significance of dysplasia at a margin in non-invasive IPMN is unresolved."],"changedPractice":true},{"id":"paper-burkitt-sarcoma-involving-jaws-african-children-br-j-surg-1958","kind":"paper","name":"A sarcoma involving the jaws in African children","aka":["Burkitt 1958","The first description of Burkitt lymphoma"],"tldr":"A surgeon working in Uganda described a tumour of the jaw in children that nobody had named, and the pattern of where it occurred led, six years later, to the discovery of the first human cancer virus.","summary":"Denis Burkitt was a surgeon at Mulago Hospital in Kampala. His 1958 report in the British Journal of Surgery described a tumour involving the jaws in African children as a distinct entity. Europe PMC indexes no abstract for the paper, so no figure from it is quoted here; the record exists because of what followed from it.\n\nWhat followed was the beginning of viral oncology. Burkitt's mapping of where the tumour occurred, and the correspondence of that distribution with climate, prompted the search for an infectious cause. In 1964 Epstein, Achong and Barr found virus particles in lymphoblasts cultured from one of Burkitt's biopsies, the first human tumour virus. The lymphoma now carries Burkitt's name, is defined by the MYC translocation, and is one of the few aggressive lymphomas curable with chemotherapy alone in a high proportion of patients.\n\nThe paper was reprinted in 1972 in the Classics in Oncology series of CA: A Cancer Journal for Clinicians, which is the version many readers encounter.","asOf":"2026-10-01","links":[{"label":"British Journal of Surgery 1958","url":"https://doi.org/10.1002/bjs.18004619704"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/13628987/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/13628987"}],"tags":["lymphoma-evidence"],"related":["paper-epstein-virus-particles-burkitt-lymphoblasts-lancet-1964","lymphoma-roadmap"],"cancers":["burkitt-lymphoma","non-hodgkin-lymphoma"],"sections":["diagnostics","prevention"],"technologies":[],"targets":["myc"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-global-access","b-rare-cancers"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"British Journal of Surgery","year":1958,"doi":"10.1002/bjs.18004619704","pmid":"13628987","authors":"Burkitt D.","paperType":"observational","findings":["Described a tumour involving the jaws in African children as a distinct clinical entity.","Europe PMC indexes no abstract for this record, so no figure from the paper is quoted here.","The paper was reprinted in 1972 in the Classics in Oncology series of CA: A Cancer Journal for Clinicians (PubMed 4632235)."],"whatItMeans":"The clinical description that set off the search for a cancer virus. It is also an argument for geographic epidemiology: Burkitt found the cause by asking where the disease was, not by looking down a microscope.","caveats":["A clinical case description from 1958, with no abstract indexed and no modern diagnostic criteria; the entity was defined histologically and then genetically much later.","The association with Epstein-Barr virus and with holoendemic malaria was established by others over the following two decades, not in this paper."],"changedPractice":true},{"id":"paper-den-boer-bcr-abl1-like-all-lancet-oncol-2009","kind":"paper","name":"A subtype of childhood acute lymphoblastic leukaemia with poor outcome: genome-wide classification study (BCR-ABL1-like ALL)","aka":[],"tldr":"Gene expression profiling identified a group of childhood leukaemias that look like Philadelphia-positive disease without the fusion gene, later called Ph-like or BCR-ABL1-like ALL, with a high relapse rate and frequent IKZF1 deletions.","summary":"Genome-wide expression classification of 190 childhood B-ALL cases identifying a novel subtype in about 15 percent of B-other cases with a signature resembling BCR-ABL1-positive ALL, frequent IKZF1 deletions, and poor five-year disease-free survival (about 60 percent) validated in independent cohorts.","asOf":"2026-09-17","links":[{"label":"Lancet Oncol 2009","url":"https://doi.org/10.1016/S1470-2045(08)70339-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19138562/"}],"tags":[],"related":[],"cancers":["all-ph-like"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2009,"doi":"10.1016/S1470-2045(08)70339-5","pmid":"19138562","authors":"Den Boer ML, van Slegtenhorst M, De Menezes RX, et al.","paperType":"translational","findings":["BCR-ABL1-like subtype in about 15 percent of B-other childhood ALL.","Five-year disease-free survival about 60 percent, similar to BCR-ABL1-positive ALL."],"whatItMeans":"This discovery, made simultaneously with the American Children's Oncology Group finding, created the Ph-like ALL category now screened for in high-risk protocols.","caveats":["Discovery study without kinase lesion characterisation, which came with later sequencing."],"changedPractice":true,"participants":190},{"id":"paper-johnson-sleep-med-rev","kind":"paper","name":"A systematic review and meta-analysis of randomized controlled trials of cognitive behavior therapy for insomnia (CBT-I) in cancer survivors","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 26434673 and published in Sleep medicine reviews; the citing page links this DOI, which is how the record was matched.","summary":"This review examined the efficacy of cognitive behavior therapy for insomnia (CBT-I) in people diagnosed with cancer. Studies were identified through November 2014 using multiple databases, clinical trial records, and bibliography searches. Inclusion was limited to randomized controlled trials of CBT-I conducted in individuals with a cancer diagnosis who had clinically relevant insomnia. The primary outcome variable was sleep efficiency (SE) as measured by sleep diary. Eight studies including data from 752 cancer survivors met inclusion criteria. CBT-I resulted in a 15.5% improvement in SE relative to control conditions (6.1%) from pre- to post-intervention, with a medium effect size (ES: d = 0.53). Overall, sleep latency was reduced by 22 min with an ES of d = 0.43, compared to a reduction of 8 min in the control conditions. Wake after sleep onset was reduced by 30 min with an ES of d = 0.41, compared to 13 min in the control conditions. Large effect sizes were observed for self-reported insomnia severity (d = 0.77) for those patients who received CBT-I, representing a clinically relevant eight point reduction. Effects were durable up to 6 mo. The quality of the evidence supports a strong recommendation for the use of CBT-I among cancer survivors.\n\nIndexed on Europe PMC as PubMed record 26434673 (DOI 10.1016/j.smrv.2015.07.001). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Sleep Med Rev 2016","url":"https://doi.org/10.1016/j.smrv.2015.07.001"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26434673/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26434673"}],"tags":["europepmc-ingest"],"related":["cbt-insomnia-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Sleep medicine reviews","year":2016,"doi":"10.1016/j.smrv.2015.07.001","pmid":"26434673","authors":"Johnson JA, Rash JA, Campbell TS, et al.","paperType":"meta-analysis","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-hayashi-squamous-basal-like-pancreatic-nat-cancer-2020","kind":"paper","name":"A unifying paradigm for transcriptional heterogeneity and squamous features in pancreatic ductal adenocarcinoma","aka":[],"tldr":"Sampling several regions of metastatic pancreatic cancers showed that squamous-looking areas are the tissue form of the basal-like gene signature, usually a subclone inside an otherwise classical tumour, and that such cancers carry chromatin-gene mutations and uneven MYC gain.","summary":"Evolutionary analysis and expression profiling were integrated in multiregion-sampled metastatic pancreatic cancers. Squamous features were the histological correlate of the RNA-seq-defined basal-like subtype. In patients with coexisting basal-squamous and classical-glandular morphology, phylogenetics showed squamous morphology as a subclonal population within an otherwise classical tumour. Cancers with squamous features were more likely to have clonal mutations in chromatin modifiers, intercellular heterogeneity for MYC amplification and entosis.","asOf":"2026-09-24","links":[{"label":"Hayashi et al., Nat Cancer 2020: squamous features are the histological correlate of basal-like expression","url":"https://doi.org/10.1038/s43018-019-0010-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35118421/"}],"tags":[],"related":[],"cancers":["pancreatic","metastatic-pdac"],"sections":[],"technologies":[],"targets":["myc-gene","kdm6a"],"drugs":[],"companies":[],"institutions":["mskcc"],"pathways":["myc","clonal-evolution","swi-snf-chromatin"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Cancer","year":2020,"doi":"10.1038/s43018-019-0010-1","pmid":"35118421","authors":"Hayashi A, Fan J, Chen R, et al.","paperType":"translational","findings":["Squamous histology is the tissue correlate of basal-like expression and usually subclonal.","Squamous-feature cancers carry clonal chromatin-modifier mutations and heterogeneous MYC amplification."],"whatItMeans":"It joins the pathology (adenosquamous), the transcriptome (basal-like) and the genome (KDM6A, MYC) into one account of the chemotherapy-resistant subtype, and shows a single biopsy can miss it.","caveats":["Rapid-autopsy metastatic cohort.","Entosis and MYC heterogeneity are descriptive findings."],"changedPractice":false},{"id":"paper-vasan-nature","kind":"paper","name":"A view on drug resistance in cancer","aka":[],"tldr":"Paper cited by one pathway page and one bottleneck page, indexed on Europe PMC as PubMed record 31723286 and published in Nature; the citing pages link this DOI, which is how the record was matched.","summary":"The problem of resistance to therapy in cancer is multifaceted. Here we take a reductionist approach to define and separate the key determinants of drug resistance, which include tumour burden and growth kinetics; tumour heterogeneity; physical barriers; the immune system and the microenvironment; undruggable cancer drivers; and the many consequences of applying therapeutic pressures. We propose four general solutions to drug resistance that are based on earlier detection of tumours permitting cancer interception; adaptive monitoring during therapy; the addition of novel drugs and improved pharmacological principles that result in deeper responses; and the identification of cancer cell dependencies by high-throughput synthetic lethality screens, integration of clinico-genomic data and computational modelling. These different approaches could eventually be synthesized for each tumour at any decision point and used to inform the choice of therapy.\n\nIndexed on Europe PMC as PubMed record 31723286 (DOI 10.1038/s41586-019-1730-1). Matched by DOI alone: one pathway page and one bottleneck page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2019","url":"https://doi.org/10.1038/s41586-019-1730-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31723286/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31723286"}],"tags":["europepmc-ingest"],"related":["resistance-routes-map","b-resistance"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2019,"doi":"10.1038/s41586-019-1730-1","pmid":"31723286","authors":"Vasan N, Baselga J, Hyman DM","paperType":"review","findings":[],"whatItMeans":"One pathway page and one bottleneck page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-xiang-nature","kind":"paper","name":"A vision-language foundation model for precision oncology","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 39779851 and published in Nature; the citing page links this DOI, which is how the record was matched.","summary":"Clinical decision-making is driven by multimodal data, including clinical notes and pathological characteristics. Artificial intelligence approaches that can effectively integrate multimodal data hold significant promise in advancing clinical care 1,2. However, the scarcity of well-annotated multimodal datasets in clinical settings has hindered the development of useful models. In this study, we developed the Multimodal transformer with Unified maSKed modeling (MUSK), a vision-language foundation model designed to leverage large-scale, unlabelled, unpaired image and text data. MUSK was pretrained on 50 million pathology images from 11,577 patients and one billion pathology-related text tokens using unified masked modelling. It was further pretrained on one million pathology image-text pairs to efficiently align the vision and language features. With minimal or no further training, MUSK was tested in a wide range of applications and demonstrated superior performance across 23 patch-level and slide-level benchmarks, including image-to-text and text-to-image retrieval, visual question answering, image classification and molecular biomarker prediction. Furthermore, MUSK showed strong performance in outcome prediction, including melanoma relapse prediction, pan-cancer prognosis prediction and immunotherapy response prediction in lung and gastro-oesophageal cancers. MUSK effectively combined complementary information from pathology images and clinical reports and could potentially improve diagnosis and precision in cancer therapy.\n\nIndexed on Europe PMC as PubMed record 39779851 (DOI 10.1038/s41586-024-08378-w). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2025","url":"https://doi.org/10.1038/s41586-024-08378-w"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39779851/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39779851"}],"tags":["europepmc-ingest"],"related":["musk"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2025,"doi":"10.1038/s41586-024-08378-w","pmid":"39779851","authors":"Xiang J, Wang X, Zhang X, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-lu-nat-med","kind":"paper","name":"A visual-language foundation model for computational pathology","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 38504017 and published in Nature Medicine; the citing page links this DOI, which is how the record was matched.","summary":"The accelerated adoption of digital pathology and advances in deep learning have enabled the development of robust models for various pathology tasks across a diverse array of diseases and patient cohorts. However, model training is often difficult due to label scarcity in the medical domain, and a model's usage is limited by the specific task and disease for which it is trained. Additionally, most models in histopathology leverage only image data, a stark contrast to how humans teach each other and reason about histopathologic entities. We introduce CONtrastive learning from Captions for Histopathology (CONCH), a visual-language foundation model developed using diverse sources of histopathology images, biomedical text and, notably, over 1.17 million image-caption pairs through task-agnostic pretraining. Evaluated on a suite of 14 diverse benchmarks, CONCH can be transferred to a wide range of downstream tasks involving histopathology images and/or text, achieving state-of-the-art performance on histology image classification, segmentation, captioning, and text-to-image and image-to-text retrieval. CONCH represents a substantial leap over concurrent visual-language pretrained systems for histopathology, with the potential to directly facilitate a wide array of machine learning-based workflows requiring minimal or no further supervised fine-tuning.\n\nIndexed on Europe PMC as PubMed record 38504017 (DOI 10.1038/s41591-024-02856-4). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Med 2024","url":"https://doi.org/10.1038/s41591-024-02856-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38504017/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38504017"}],"tags":["europepmc-ingest"],"related":["uni-conch"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2024,"doi":"10.1038/s41591-024-02856-4","pmid":"38504017","authors":"Lu MY, Chen B, Williamson DFK, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-xu-nature","kind":"paper","name":"A whole-slide foundation model for digital pathology from real-world data","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 38778098 and published in Nature; the citing page links this DOI, which is how the record was matched.","summary":"Digital pathology poses unique computational challenges, as a standard gigapixel slide may comprise tens of thousands of image tiles 1-3. Prior models have often resorted to subsampling a small portion of tiles for each slide, thus missing the important slide-level context 4. Here we present Prov-GigaPath, a whole-slide pathology foundation model pretrained on 1.3 billion 256 × 256 pathology image tiles in 171,189 whole slides from Providence, a large US health network comprising 28 cancer centres. The slides originated from more than 30,000 patients covering 31 major tissue types. To pretrain Prov-GigaPath, we propose GigaPath, a novel vision transformer architecture for pretraining gigapixel pathology slides. To scale GigaPath for slide-level learning with tens of thousands of image tiles, GigaPath adapts the newly developed LongNet 5 method to digital pathology. To evaluate Prov-GigaPath, we construct a digital pathology benchmark comprising 9 cancer subtyping tasks and 17 pathomics tasks, using both Providence and TCGA data 6. With large-scale pretraining and ultra-large-context modelling, Prov-GigaPath attains state-of-the-art performance on 25 out of 26 tasks, with significant improvement over the second-best method on 18 tasks. We further demonstrate the potential of Prov-GigaPath on vision-language pretraining for pathology 7,8 by incorporating the pathology reports. In sum, Prov-GigaPath is an open-weight foundation model that achieves state-of-the-art performance on various digital pathology tasks, demonstrating the importance of real-world data and whole-slide modelling.\n\nIndexed on Europe PMC as PubMed record 38778098 (DOI 10.1038/s41586-024-07441-w). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2024","url":"https://doi.org/10.1038/s41586-024-07441-w"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38778098/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38778098"}],"tags":["europepmc-ingest"],"related":["prov-gigapath"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2024,"doi":"10.1038/s41586-024-07441-w","pmid":"38778098","authors":"Xu H, Usuyama N, Bagga J, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-a3961-intermediate-risk-neuroblastoma-baker-nejm-2010","kind":"paper","name":"A3961: outcome after reduced chemotherapy for intermediate-risk neuroblastoma","aka":[],"tldr":"Cutting chemotherapy to four or eight cycles based on tumour biology kept three-year survival above 96 percent in intermediate-risk neuroblastoma, showing these children could be safely treated with substantially less.","summary":"Children's Oncology Group prospective study of 479 children with intermediate-risk neuroblastoma treated with four cycles (favourable biology) or eight cycles (unfavourable biology) of carboplatin, etoposide, cyclophosphamide and doxorubicin, with surgery and no radiotherapy for most.\n\nThree-year event-free survival was 88 percent and overall survival 96 percent, similar to historical results with more intensive therapy, with excellent outcomes in the favourable biology group (96 percent overall survival).","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2010","url":"https://doi.org/10.1056/NEJMoa1001527"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20879880/"}],"tags":[],"related":[],"cancers":["neuroblastoma-intermediate-risk"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2010,"doi":"10.1056/NEJMoa1001527","pmid":"20879880","authors":"Baker DL, Schmidt ML, Cohn SL, et al.","paperType":"observational","findings":["Three-year overall survival 96 percent; event-free survival 88 percent.","Four cycles sufficient for favourable biology."],"whatItMeans":"Biology-based reduction of chemotherapy is the standard for intermediate-risk neuroblastoma, and the successor trial ANBL0531 reduced it further.","caveats":["Non-randomised comparison with historical controls."],"changedPractice":true,"participants":479},{"id":"paper-aall0031-imatinib-ph-positive-all-schultz-jco-2009","kind":"paper","name":"AALL0031: imatinib with intensive chemotherapy for Philadelphia chromosome-positive acute lymphoblastic leukaemia in children","aka":[],"tldr":"Adding continuous imatinib to intensive chemotherapy more than doubled three-year event-free survival in childhood Philadelphia-positive leukaemia compared with historical controls and matched the results of transplant, changing the standard of care.","summary":"Children's Oncology Group study of 92 children with Ph-positive ALL treated with intensive chemotherapy plus imatinib for increasing durations across cohorts, with transplant for those with a sibling donor.\n\nThree-year event-free survival in the cohort with continuous imatinib was 80 percent, more than double the 35 percent of historical controls, and no worse than with sibling donor transplant; toxicity was not increased.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2009","url":"https://doi.org/10.1200/JCO.2008.21.2514"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19805687/"}],"tags":[],"related":[],"cancers":["all-paediatric-ph-positive"],"sections":[],"technologies":[],"targets":[],"drugs":["imatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2009,"doi":"10.1200/JCO.2008.21.2514","pmid":"19805687","authors":"Schultz KR, Bowman WP, Aledo A, et al.","paperType":"observational","findings":["Three-year event-free survival 80 percent with continuous imatinib vs 35 percent in historical controls.","Chemotherapy plus imatinib comparable to sibling donor transplant."],"whatItMeans":"A tyrosine kinase inhibitor throughout chemotherapy is the standard for childhood Ph-positive ALL, and transplant in first remission is no longer routine.","caveats":["Non-randomised comparison with historical controls; small cohorts."],"changedPractice":true,"participants":92},{"id":"paper-aall0232-larsen-jco-2016","kind":"paper","name":"AALL0232: dexamethasone and high-dose methotrexate improve outcome in high-risk B-cell acute lymphoblastic leukaemia in children and young adults","aka":[],"tldr":"In high-risk childhood B-cell acute lymphoblastic leukaemia, high-dose methotrexate beat escalating-dose methotrexate, and dexamethasone beat prednisone in children under 10, defining the backbone still used in Children's Oncology Group trials.","summary":"Phase 3 factorial trial of 3,154 patients aged 1 to 30 with high-risk B-ALL randomised to dexamethasone or prednisone during induction and to high-dose methotrexate or Capizzi escalating methotrexate with asparaginase during interim maintenance.\n\nFive-year event-free survival was 79.6 percent with high-dose methotrexate against 75.2 percent with Capizzi methotrexate; dexamethasone improved event-free survival in patients under 10 (91.2 versus 83.2 percent) but increased osteonecrosis in older patients.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2016","url":"https://doi.org/10.1200/JCO.2015.62.4544"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27114587/"}],"tags":[],"related":[],"cancers":["all-paediatric-high-risk"],"sections":[],"technologies":[],"targets":[],"drugs":["dexamethasone","methotrexate"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2016,"doi":"10.1200/JCO.2015.62.4544","pmid":"27114587","authors":"Larsen EC, Devidas M, Chen S, et al.","paperType":"rct","findings":["Five-year event-free survival 79.6 percent (high-dose methotrexate) vs 75.2 percent (Capizzi).","Dexamethasone benefit in patients under 10; more osteonecrosis in those 10 and over."],"whatItMeans":"High-dose methotrexate interim maintenance and age-adapted steroid choice are standard in high-risk paediatric B-ALL protocols.","caveats":["Large factorial design with interactions between the two randomisations."],"changedPractice":true,"participants":3154},{"id":"paper-aall0434-nelarabine-t-all-dunsmore-jco-2020","kind":"paper","name":"AALL0434: nelarabine in newly diagnosed T-cell acute lymphoblastic leukaemia in children and young adults","aka":[],"tldr":"Adding the T-cell-specific drug nelarabine to intensive chemotherapy improved disease-free survival in childhood T-cell acute lymphoblastic leukaemia and cut central nervous system relapses, in the largest T-ALL trial ever run.","summary":"Phase 3 trial of 1,895 patients with T-ALL of whom 1,562 were randomised in a factorial design to Capizzi or high-dose methotrexate and, for intermediate- and high-risk patients, to nelarabine or not.\n\nFive-year disease-free survival was 88.2 percent with nelarabine against 82.1 percent without, with fewer central nervous system relapses; Capizzi methotrexate was superior to high-dose methotrexate in this T-cell population, the opposite of B-ALL.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2020","url":"https://doi.org/10.1200/JCO.20.00256"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32813610/"}],"tags":[],"related":[],"cancers":["all-paediatric-high-risk"],"sections":[],"technologies":[],"targets":[],"drugs":["nelarabine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["aall0434"],"people":["kimberly-dunsmore"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/JCO.20.00256","pmid":"32813610","authors":"Dunsmore KP, Winter SS, Devidas M, et al.","paperType":"rct","findings":["Five-year disease-free survival 88.2 percent with nelarabine vs 82.1 percent without.","Overall five-year survival 90.2 percent for the whole T-ALL cohort."],"whatItMeans":"Nelarabine is part of standard therapy for intermediate- and high-risk childhood T-ALL, and Capizzi methotrexate is preferred in T-ALL.","caveats":["Neurotoxicity of nelarabine requires monitoring.","Cranial irradiation was still used for many patients; its omission was tested later."],"changedPractice":true,"participants":1562},{"id":"paper-aall1231-bortezomib-t-all-teachey-jco-2022","kind":"paper","name":"AALL1231: bortezomib in newly diagnosed T-cell acute lymphoblastic leukaemia and lymphoma, with cranial radiotherapy removed","aka":[],"tldr":"In children with T-cell leukaemia or lymphoma, adding bortezomib to chemotherapy did not significantly improve survival for the whole group but did for those with lymphoma, and the intensified chemotherapy let more than nine in ten avoid radiotherapy to the brain without more relapses.","summary":"Children's Oncology Group phase 3 trial: 824 eligible children and young adults with T-cell acute lymphoblastic leukaemia or lymphoblastic lymphoma enrolled between 2014 and 2017 were randomised to a modified augmented BFM regimen with or without bortezomib during induction and delayed intensification; the backbone was intensified so that prophylactic cranial radiotherapy was scheduled for only 9.5 percent of patients.\n\nFour-year event-free survival was 80.1 percent without and 83.8 percent with bortezomib (p 0.131); overall survival 85.7 and 88.3 percent (p 0.085). Patients with lymphoblastic lymphoma had significantly better event-free (86.4 against 76.5 percent) and overall survival (89.5 against 78.3 percent) with bortezomib. Patients spared cranial radiotherapy did as well as comparable irradiated patients in the predecessor trial AALL0434.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2022","url":"https://doi.org/10.1200/JCO.21.02678"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35271306/"}],"tags":[],"related":[],"cancers":["all-paediatric-high-risk","all-leukemia"],"sections":[],"technologies":[],"targets":[],"drugs":["bortezomib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["aall1231"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2022,"doi":"10.1200/JCO.21.02678","pmid":"35271306","authors":"Teachey DT, Devidas M, Wood BL, et al.","paperType":"rct","findings":["Four-year event-free survival 83.8 percent with bortezomib versus 80.1 percent without (p 0.131); overall survival 88.3 versus 85.7 percent (p 0.085).","T-lymphoblastic lymphoma: four-year event-free survival 86.4 versus 76.5 percent (p 0.041) and overall survival 89.5 versus 78.3 percent (p 0.009).","Cranial radiotherapy scheduled for 9.5 percent of patients against 90.8 percent in AALL0434, with no difference in event-free or overall survival."],"whatItMeans":"Prophylactic cranial radiotherapy can be limited to central nervous system involvement and the highest-risk patients in childhood T-ALL, and bortezomib is a reasonable addition for T-lymphoblastic lymphoma.","caveats":["The primary comparison across all patients was not significant; the lymphoma benefit is a subgroup result.","Open-label design."],"changedPractice":true,"participants":824},{"id":"paper-aall1331-low-risk-hogan-jco-2023","kind":"paper","name":"AALL1331: blinatumomab added to chemotherapy in low-risk first relapse of childhood B-ALL","aka":[],"tldr":"In children with a late, low-risk relapse of leukaemia, adding three blocks of blinatumomab did not change survival overall, but for the two thirds whose relapse involved the bone marrow it cut relapses and deaths enough to become their new standard.","summary":"Report of the low-risk stratum of the Children's Oncology Group AALL1331 trial: 255 patients aged 1 to 30 with low-risk first relapse of B-cell acute lymphoblastic leukaemia were randomised after reinduction to standard chemotherapy or chemotherapy with three blinatumomab blocks intercalated.\n\nFour-year disease-free and overall survival were 61.2 and 90.4 percent with blinatumomab against 49.5 and 79.6 percent with chemotherapy (p 0.089 and 0.11). For the 174 patients with bone marrow relapse (with or without extramedullary disease) the differences were significant (disease-free survival 72.7 against 53.7 percent, overall survival 97.1 against 84.8 percent), while the 81 patients with isolated extramedullary relapse did poorly in both arms.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2023","url":"https://doi.org/10.1200/JCO.22.02200"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37257143/"}],"tags":[],"related":[],"cancers":["all-paediatric-relapsed","all-leukemia"],"sections":[],"technologies":[],"targets":[],"drugs":["blinatumomab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["aall1331"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2023,"doi":"10.1200/JCO.22.02200","pmid":"37257143","authors":"Hogan LE, Brown PA, Ji L, et al.","paperType":"rct","findings":["Four-year disease-free survival 61.2 versus 49.5 percent and overall survival 90.4 versus 79.6 percent overall (not significant).","Bone marrow relapse: four-year disease-free survival 72.7 versus 53.7 percent (p 0.015) and overall survival 97.1 versus 84.8 percent (p 0.020).","Isolated extramedullary relapse: no difference, with four-year disease-free survival under 40 percent in both arms."],"whatItMeans":"Blinatumomab belongs in the treatment of low-risk marrow relapse in children; isolated extramedullary relapse needs new approaches.","caveats":["The overall comparison was not statistically significant; the marrow-relapse benefit is a subgroup finding.","Patients with central nervous system leukaemia received cranial radiotherapy in both arms."],"changedPractice":true,"participants":255},{"id":"paper-aall1331-brown-jama-2021","kind":"paper","name":"AALL1331: blinatumomab versus chemotherapy consolidation in high- and intermediate-risk first relapse of childhood B-ALL","aka":[],"tldr":"Children whose leukaemia relapsed did better when two cycles of the antibody blinatumomab replaced intensive chemotherapy before transplant: more were alive two years later and far fewer had serious infections, although the disease-free survival difference did not reach the trial's statistical threshold.","summary":"Randomised phase 3 trial of the Children's Oncology Group at 155 hospitals: 208 patients aged 1 to 30 with high- or intermediate-risk first relapse of B-cell acute lymphoblastic leukaemia were randomised after reinduction to two cycles of blinatumomab or two cycles of multi-agent chemotherapy, each followed by transplant.\n\nTwo-year disease-free survival was 54.4 percent with blinatumomab against 39.0 percent with chemotherapy (hazard ratio 0.70, one-sided p 0.03), two-year overall survival 71.3 against 58.4 percent (hazard ratio 0.62), and serious infection, febrile neutropenia, sepsis and mucositis were several times less common with blinatumomab. Randomisation was closed early on the monitoring committee's recommendation, so the primary endpoint was underpowered.","asOf":"2026-09-22","links":[{"label":"JAMA 2021","url":"https://doi.org/10.1001/jama.2021.0669"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33651090/"}],"tags":[],"related":[],"cancers":["all-paediatric-relapsed","all-leukemia"],"sections":[],"technologies":[],"targets":[],"drugs":["blinatumomab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["aall1331"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2021,"doi":"10.1001/jama.2021.0669","pmid":"33651090","authors":"Brown PA, Ji L, Xu X, et al.","paperType":"rct","findings":["Two-year disease-free survival 54.4 percent with blinatumomab versus 39.0 percent with chemotherapy (hazard ratio 0.70, 95% CI 0.47 to 1.03; one-sided p 0.03).","Two-year overall survival 71.3 versus 58.4 percent (hazard ratio 0.62, 95% CI 0.39 to 0.98).","Serious infection 15 versus 65 percent, febrile neutropenia 5 versus 58 percent, sepsis 2 versus 27 percent, mucositis 1 versus 28 percent."],"whatItMeans":"Blinatumomab consolidation is a safer bridge to transplant for children with higher-risk relapsed B-ALL and improved survival; it is the basis for using blinatumomab in place of chemotherapy blocks after relapse.","caveats":["Early closure with 80 of 131 planned events; the disease-free survival difference was not statistically significant at the prespecified threshold.","Patients with Down syndrome, Philadelphia-positive disease or prior transplant were excluded."],"changedPractice":true,"participants":208},{"id":"paper-aaml0531-gemtuzumab-gamis-jco-2014","kind":"paper","name":"AAML0531: gemtuzumab ozogamicin added to chemotherapy for children and adolescents with acute myeloid leukaemia","aka":[],"tldr":"Adding the CD33-targeted antibody-drug conjugate gemtuzumab ozogamicin to two courses of chemotherapy reduced relapses in childhood acute myeloid leukaemia, most clearly in the high-risk group, and it was later restored to the paediatric label.","summary":"Phase 3 trial of 1,022 children, adolescents and young adults with newly diagnosed AML randomised to standard chemotherapy with or without gemtuzumab ozogamicin in induction and intensification.\n\nEvent-free survival at three years was 53.1 versus 46.9 percent (hazard ratio 0.83) with relapse risk reduced from 41 to 33 percent; overall survival was not significantly different (69.4 versus 65.4 percent), and benefit was greatest in high-risk patients and those with high CD33 expression.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2014","url":"https://doi.org/10.1200/JCO.2014.55.3628"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25092781/"}],"tags":[],"related":[],"cancers":["aml-paediatric"],"sections":[],"technologies":[],"targets":[],"drugs":["gemtuzumab-ozogamicin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["aaml0531"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2014,"doi":"10.1200/JCO.2014.55.3628","pmid":"25092781","authors":"Gamis AS, Alonzo TA, Meshinchi S, et al.","paperType":"rct","findings":["Three-year event-free survival 53.1 percent vs 46.9 percent; relapse risk 32.8 percent vs 41.3 percent.","Overall survival 69.4 percent vs 65.4 percent (not significant)."],"whatItMeans":"Gemtuzumab ozogamicin is part of standard induction for CD33-positive childhood AML in Children's Oncology Group protocols.","caveats":["Higher treatment-related mortality offset part of the relapse reduction.","Benefit depends on CD33 expression and splicing genotype."],"changedPractice":true,"participants":1022},{"id":"paper-aaml1031-bortezomib-aplenc-haematologica-2020","kind":"paper","name":"AAML1031: bortezomib with standard chemotherapy for children with acute myeloid leukaemia does not improve outcomes","aka":[],"tldr":"Adding the proteasome inhibitor bortezomib to standard chemotherapy for children with newly diagnosed acute myeloid leukaemia did not help them live longer or relapse less, and it caused more nerve damage and intensive care admissions.","summary":"Report of the randomised bortezomib question in the Children's Oncology Group phase 3 AAML1031 trial: 1,097 patients under 30 with de novo acute myeloid leukaemia were randomised to standard chemotherapy with (n 555) or without (n 542) bortezomib 1.3 mg/m2 on days 1, 4 and 8 of each course.\n\nRemission induction rates were the same (89 against 91 percent), three-year event-free survival was 44.8 against 47.0 percent and overall survival 63.6 against 67.2 percent. Bortezomib was associated with more peripheral neuropathy and intensive care unit admissions during the first course.","asOf":"2026-09-22","links":[{"label":"Haematologica 2020","url":"https://doi.org/10.3324/haematol.2019.220962"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32029509/"}],"tags":[],"related":[],"cancers":["aml-paediatric","aml"],"sections":[],"technologies":[],"targets":[],"drugs":["bortezomib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["aaml1031"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["haematologica"],"dependsOn":[],"notes":[],"journal":"Haematologica","year":2020,"doi":"10.3324/haematol.2019.220962","pmid":"32029509","authors":"Aplenc R, Meshinchi S, Sung L, et al.","paperType":"rct","findings":["Complete remission 89 percent with bortezomib versus 91 percent without (p 0.531).","Three-year event-free survival 44.8 versus 47.0 percent (p 0.236) and overall survival 63.6 versus 67.2 percent (p 0.356).","More peripheral neuropathy (p 0.006) and intensive care admissions (p 0.025) with bortezomib."],"whatItMeans":"Bortezomib should not be added to standard chemotherapy for childhood acute myeloid leukaemia; the trial's FLT3-ITD sorafenib cohorts were reported separately.","caveats":["Open-label randomisation; the trial's high allelic ratio FLT3-ITD patients were treated in non-randomised sorafenib cohorts and excluded from this comparison."],"changedPractice":false,"participants":1097},{"id":"paper-aaml1031-sorafenib-flt3-pollard-jco-2022","kind":"paper","name":"AAML1031: sorafenib combined with chemotherapy for children with high allelic ratio FLT3-ITD acute myeloid leukaemia","aka":[],"tldr":"Adding the kinase inhibitor sorafenib to chemotherapy improved event-free survival in children with high allelic ratio FLT3-ITD acute myeloid leukaemia compared with matched historical controls, the first FLT3-targeted result in paediatric leukaemia.","summary":"Non-randomised cohort within the AAML1031 trial of 92 children with high allelic ratio FLT3-ITD AML treated with sorafenib during induction, consolidation and maintenance, compared with 76 concurrent and historical controls treated without sorafenib.\n\nThree-year event-free survival was 55.9 versus 31.9 percent and relapse risk lower with sorafenib; benefit was concentrated in patients who received it from the first induction course, and toxicity was mostly rash and hand-foot syndrome.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2022","url":"https://doi.org/10.1200/JCO.21.01612"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35349331/"}],"tags":[],"related":[],"cancers":["aml-paediatric"],"sections":[],"technologies":[],"targets":[],"drugs":["sorafenib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2022,"doi":"10.1200/JCO.21.01612","pmid":"35349331","authors":"Pollard JA, Alonzo TA, Gerbing R, et al.","paperType":"observational","findings":["Three-year event-free survival 55.9 percent vs 31.9 percent.","Three-year relapse risk 22.8 percent vs 55.5 percent."],"whatItMeans":"FLT3 inhibitors are now incorporated into frontline paediatric AML therapy for FLT3-ITD, with gilteritinib being studied in the successor trial.","caveats":["Non-randomised comparison; sorafenib patients more often had haematopoietic stem cell transplant."],"changedPractice":true,"participants":92},{"id":"paper-al-hallaq-med-phys","kind":"paper","name":"AAPM task group report 302: Surface-guided radiotherapy","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 35179229 and published in Medical physics; the citing page links this DOI, which is how the record was matched.","summary":"The clinical use of surface imaging has increased dramatically, with demonstrated utility for initial patient positioning, real-time motion monitoring, and beam gating in a variety of anatomical sites. The Therapy Physics Subcommittee and the Imaging for Treatment Verification Working Group of the American Association of Physicists in Medicine commissioned Task Group 302 to review the current clinical uses of surface imaging and emerging clinical applications. The specific charge of this task group was to provide technical guidelines for clinical indications of use for general positioning, breast deep-inspiration breath hold treatment, and frameless stereotactic radiosurgery. Additionally, the task group was charged with providing commissioning and on-going quality assurance (QA) requirements for surface-guided radiation therapy (SGRT) as part of a comprehensive QA program including risk assessment. Workflow considerations for other anatomic sites and for computed tomography simulation, including motion management, are also discussed. Finally, developing clinical applications, such as stereotactic body radiotherapy (SBRT) or proton radiotherapy, are presented. The recommendations made in this report, which are summarized at the end of the report, are applicable to all video-based SGRT systems available at the time of writing.\n\nIndexed on Europe PMC as PubMed record 35179229 (DOI 10.1002/mp.15532). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Med Phys 2022","url":"https://doi.org/10.1002/mp.15532"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35179229/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35179229"}],"tags":["europepmc-ingest"],"related":["patient-positioning-surface-guidance-systems"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Medical physics","year":2022,"doi":"10.1002/mp.15532","pmid":"35179229","authors":"Al-Hallaq HA, Cerviño L, Gutierrez AN, et al.","paperType":"review","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-aaronson-eortc-qlq-c30-jnci-1993","kind":"paper","name":"Aaronson 1993: the EORTC QLQ-C30 quality of life questionnaire","aka":[],"tldr":"The 30-question form that lets cancer trials measure how patients feel and function, tested first in lung cancer patients across 13 countries and now used in thousands of studies.","summary":"Aaronson and the EORTC Study Group on Quality of Life designed a core questionnaire for use in international cancer trials and tested it in 305 patients with non-resectable lung cancer in 13 countries before and during treatment. The QLQ-C30 covers five functioning scales (physical, role, cognitive, emotional and social), symptom scales for fatigue, pain and nausea and vomiting, single items for other common symptoms and financial impact, and a global health and quality of life scale. Its scales showed acceptable reliability, distinguished patients by performance status and weight loss, and changed with clinical status over time.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1093/jnci/85.5.365"},{"label":"EORTC Quality of Life Group","url":"https://qol.eortc.org/"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["quality-of-life","qol-pro"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"JNCI: Journal of the National Cancer Institute","year":1993,"doi":"10.1093/jnci/85.5.365","authors":"Aaronson NK, Ahmedzai S, Bergman B, et al.","paperType":"methods","findings":["Field-tested in 305 lung cancer patients from 13 countries, before and during treatment.","Thirty items forming five functioning scales, three symptom scales, six single items and a global quality of life scale.","Scales were reliable, distinguished clinically distinct patient groups and responded to change in clinical status."],"whatItMeans":"The QLQ-C30 made patient-reported quality of life a standard trial endpoint and is the instrument behind many of the quality of life claims on drug labels and in health technology assessments. Cancer-specific modules were later added on top of the core questionnaire.","caveats":["Validated first in lung cancer; later modules extend it to other cancers.","Quality of life data in trials are often incomplete because sicker patients stop filling in forms."],"changedPractice":true},{"id":"paper-kuhl-j-clin-oncol","kind":"paper","name":"Abbreviated breast magnetic resonance imaging (MRI): first postcontrast subtracted images and maximum-intensity projection-a novel approach to breast cancer screening with MRI","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 24958821 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: We investigated whether an abbreviated protocol (AP), consisting of only one pre- and one postcontrast acquisition and their derived images (first postcontrast subtracted [FAST] and maximum-intensity projection [MIP] images), was suitable for breast magnetic resonance imaging (MRI) screening.\n\nMethods: We conducted a prospective observational reader study in 443 women at mildly to moderately increased risk who underwent 606 screening MRIs. Eligible women had normal or benign digital mammograms and, for those with heterogeneously dense or extremely dense breasts (n = 427), normal or benign ultrasounds. Expert radiologists reviewed the MIP image first to search for significant enhancement and then reviewed the complete AP (consisting of MIP and FAST images and optionally their nonsubtracted source images) to characterize enhancement and establish a diagnosis. Only thereafter was the regular full diagnostic protocol (FDP) analyzed.\n\nResults: MRI acquisition time for FDP was 17 minutes, versus 3 minutes for the AP. Average time to read the single MIP and complete AP was 2.8 and 28 seconds, respectively. Eleven breast cancers (four ductal carcinomas in situ and seven invasive cancers; all T1N0 intermediate or high grade) were diagnosed, for an additional cancer yield of 18.2 per 1,000. MIP readings were positive in 10 (90.9%) of 11 cancers and allowed establishment of the absence of breast cancer, with a negative predictive value (NPV) of 99.8% (418 of 419). Interpretation of the complete AP, as with the FDP, allowed diagnosis of all cancers (11 [100%] of 11). Specificity and positive predictive value (PPV) of AP versus FDP were equivalent (94.3% v 93.9% and 24.4% v 23.4%, respectively).\n\nConclusion: An MRI acquisition time of 3 minutes and an expert radiologist MIP image reading time of 3 seconds are sufficient to establish the absence of breast cancer, with an NPV of 99.8%. With a reading time < 30 seconds for the complete AP, diagnostic accuracy was equivalent to that of the FDP and resulted in an additional cancer yield of 18.2 per 1,000.\n\nIndexed on Europe PMC as PubMed record 24958821 (DOI 10.1200/jco.2013.52.5386). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2014","url":"https://doi.org/10.1200/jco.2013.52.5386"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24958821/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/24958821"}],"tags":["europepmc-ingest"],"related":["breast-mri-coils-abbreviated-mri"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2014,"doi":"10.1200/jco.2013.52.5386","pmid":"24958821","authors":"Kuhl CK, Schrading S, Strobel K, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-abc-02-gemcitabine-cisplatin-nejm-2010","kind":"paper","name":"ABC-02: cisplatin plus gemcitabine versus gemcitabine alone for biliary tract cancer","aka":[],"tldr":"Adding cisplatin to gemcitabine lengthened survival by more than three months in advanced bile duct and gallbladder cancer without extra serious toxicity, establishing the chemotherapy standard for the disease.","summary":"Phase 3 trial of 410 patients with locally advanced or metastatic cholangiocarcinoma, gallbladder or ampullary cancer randomised to cisplatin plus gemcitabine or gemcitabine alone for up to 24 weeks.\n\nMedian overall survival was 11.7 versus 8.1 months (hazard ratio 0.64) and progression-free survival 8.0 versus 5.0 months, with similar rates of grade 3 to 4 adverse events.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2010","url":"https://doi.org/10.1056/NEJMoa0908721"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20375404/"}],"tags":[],"related":[],"cancers":["extrahepatic-cholangiocarcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":["cisplatin","gemcitabine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["abc-02"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2010,"doi":"10.1056/NEJMoa0908721","pmid":"20375404","authors":"Valle J, Wasan H, Palmer DH, et al.","paperType":"rct","findings":["Median overall survival 11.7 vs 8.1 months; hazard ratio 0.64.","Median progression-free survival 8.0 vs 5.0 months."],"whatItMeans":"Gemcitabine-cisplatin is the backbone of first-line treatment for advanced biliary tract cancer, now combined with durvalumab or pembrolizumab.","caveats":["Treatment was capped at eight cycles.","Heterogeneous population across biliary sites."],"changedPractice":true,"participants":410},{"id":"paper-nct03706365-lancet-oncol-2025","kind":"paper","name":"Abemaciclib plus abiraterone in patients with metastatic castration-resistant prostate cancer (CYCLONE 2): a randomised, double-blind, placebo-controlled, phase 3 trial","aka":[],"tldr":"Published report from the CYCLONE 2 trial registered as NCT03706365, in The Lancet Oncology (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Abemaciclib, a potent CDK4 and CDK6 inhibitor, has shown antitumour activity in prostate cancer models and in patients with metastatic castration-resistant prostate cancer (mCRPC) who have been heavily treated. We aimed to evaluate the safety and efficacy of abemaciclib in combination with abiraterone in patients with mCRPC.\n\nMethods: CYCLONE 2 was a randomised, double-blind, placebo-controlled, phase 3 study done in 89 hospitals and academic and private research centres in 12 countries. All study parts had identical eligibility criteria, and used block randomisation with the same stratification factors (previous docetaxel treatment, presence of measurable disease, and type of progression). Participants were adults aged 18 years and older with histologically confirmed adenocarcinoma of the prostate and metastatic disease as documented by bone scans, CT scans, or MRI scans, and radiographic or PSA progression during continuous androgen deprivation therapy. Previous docetaxel for metastatic castration-sensitive prostate cancer was permitted; previous abiraterone, apalutamide, enzalutamide, darolutamide, or CDK4 and CDK6 inhibitors were exclusionary. The trial was conducted in three parts. Part 1 was a four-arm, placebo-controlled safety and dose-finding lead-in to determine the recommended phase 2 dose of abemaciclib with abiraterone. Participants were randomly assigned (2:2:1:1) to receive abiraterone (1000 mg orally once daily) and prednisone or prednisolone (5 mg orally twice daily) with either abemaciclib at 150 mg or 200 mg orally twice daily or with matching placebo (150 mg or 200 mg twice daily). In part 2 and part 3, patients were randomly assigned (1:1) to standard abiraterone and prednisone or prednisolone plus either abemaciclib at the recommended phase 2 dose or matching placebo. Patients, investigators, and sponsor were masked to treatment assignment. The primary outcome, investigator-assessed radiographic progression-free survival, was analysed in the intention-to-treat (participants from all study parts) population. Patients who received at least one dose of abiraterone, abemaciclib, or placebo were included in the safety population. This trial is registered at ClinicalTrials.gov, NCT03706365, and is completed.\n\nFindings: Between Nov 26, 2018, and July 20, 2022, 515 patients were screened for eligibility, 393 of whom were randomly assigned, 206 patients to abemaciclib plus abiraterone and 187 to placebo plus abiraterone. The median age was 70·0 years (IQR 63·0-76·0). 289 (74%) of 393 patients identified as White, 80 (20%) as Asian, 17 (4%) as Black or African American, and seven (2%) as multiple race or not reported. The highest tested dose of 200 mg abemaciclib administered twice daily was chosen as the recommended phase 2 dose. The median follow-up time was 26·3 months (IQR 22·1-48·2) for the abemaciclib plus abiraterone group and 25·6 months (22·1-40·8) for the placebo plus abiraterone group. The primary endpoint of radiographic progression-free survival was not met: radiographic progression-free survival events were reported in 92 (45%) of 206 patients in the abemaciclib plus abiraterone group and 95 (51%) of 187 patients in the placebo plus abiraterone group (HR 0·83 [95% CI 0·62-1·11]; p=0·21). Median radiographic progression-free survival was 22·0 months (95% CI 19·3-27·5) for abemaciclib plus abiraterone and 20·3 months (16·5-24·4) for placebo plus abiraterone. The most common grade 3 or higher adverse events reported in the abemaciclib plus abiraterone group were anaemia (28 [14%] of 206 vs eight [4%] of 185 in the placebo plus abiraterone group), neutropenia (26 [13%] vs one [1%]), and alanine aminotransferase increase (18 [9%] vs 12 [6%]). Serious adverse events occurred in 91 (44%) of 206 patients in the abemaciclib plus abiraterone group and in 68 (37%) of 185 patients in the placebo plus abiraterone group. There were three treatment-related deaths due to interstitial lung disease in the abemaciclib plus abiraterone group.\n\nInterpretation: Dual inhibition of CDK4 and CDK6 and the androgen receptor pathway with abemaciclib plus abiraterone did not improve radiographic progression-free survival compared with abiraterone alone in the CYCLONE 2 study population with mCRPC. Safety of the combination was consistent with the previously reported safety of the individual drugs. Additional research is required to identify effective combination therapies for patients with mCRPC, especially in those presenting with adverse prognostic characteristics.\n\nFunding: Eli Lilly.\n\nIndexed on Europe PMC as PubMed record 41167216 (DOI 10.1016/s1470-2045(25)00475-9). Its abstract cites the registry id NCT03706365, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2025","url":"https://doi.org/10.1016/s1470-2045(25)00475-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41167216/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41167216"},{"label":"ClinicalTrials.gov NCT03706365","url":"https://clinicaltrials.gov/study/NCT03706365"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct03706365"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2025,"doi":"10.1016/s1470-2045(25)00475-9","pmid":"41167216","authors":"Smith M, Piulats J, Todenhöfer T, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03706365 with the most citations, so it is the natural first reading for anyone following the CYCLONE 2 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-monarche-lancet-oncol-2023","kind":"paper","name":"Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): results from a preplanned interim analysis of a randomised, open-label, phase 3 trial","aka":[],"tldr":"Published report from the monarchE trial registered as NCT03155997, in The Lancet Oncology (2023), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Adjuvant abemaciclib plus endocrine therapy previously showed a significant improvement in invasive disease-free survival and distant relapse-free survival in hormone receptor-positive, human epidermal growth factor receptor 2 (HER2; also known as ERBB2)-negative, node-positive, high-risk, early breast cancer. Here, we report updated results from an interim analysis to assess overall survival as well as invasive disease-free survival and distant relapse-free survival with additional follow-up.\n\nMethods: In monarchE, an open-label, randomised, phase 3 trial, adult patients (aged ≥18 years) who had hormone receptor-positive, HER2-negative, node-positive, early breast cancer at a high risk of recurrence with an Eastern Cooperative Oncology Group performance status of 0 or 1 were recruited from 603 sites including hospitals and academic and community centres in 38 countries. Patients were randomly assigned (1:1) by means of an interactive web-based response system (block size of 4), stratified by previous chemotherapy, menopausal status, and region, to receive standard-of-care endocrine therapy of physician's choice for up to 10 years with or without abemaciclib 150 mg orally twice a day for 2 years (treatment period). All therapies were administered in an open-label manner without masking. High-risk disease was defined as either four or more positive axillary lymph nodes, or between one and three positive axillary lymph nodes and either grade 3 disease or tumour size of 5 cm or larger (cohort 1). A smaller group of patients were enrolled with between one and three positive axillary lymph nodes and Ki-67 of at least 20% as an additional risk feature (cohort 2). This was a prespecified overall survival interim analysis planned to occur 2 years after the primary outcome analysis for invasive disease-free survival. Efficacy was assessed in the intention-to-treat population. Safety was assessed in all treated patients. The study is registered with ClinicalTrials.gov, NCT03155997, and is ongoing.\n\nFindings: Between July 17, 2017, and Aug 12, 2019, 5637 patients were randomly assigned (5601 [99·4%] were women and 36 [0·6%] were men). 2808 were assigned to receive abemaciclib plus endocrine therapy and 2829 were assigned to receive endocrine therapy alone. At a median follow-up of 42 months (IQR 37-47), median invasive disease-free survival was not reached in either group and the invasive disease-free survival benefit previously reported was sustained: HR 0·664 (95% CI 0·578-0·762, nominal p<0·0001). At 4 years, the absolute difference in invasive disease-free survival between the groups was 6·4% (85·8% [95% CI 84·2-87·3] in the abemaciclib plus endocrine therapy group vs 79·4% [77·5-81·1] in the endocrine therapy alone group). 157 (5·6%) of 2808 patients in the abemaciclib plus endocrine therapy group died compared with 173 (6·1%) of 2829 patients in the endocrine therapy alone group (HR 0·929, 95% CI 0·748-1·153; p=0·50). The most common grade 3-4 adverse events were neutropenia (in 548 [19·6%] of 2791 patients receiving abemaciclib plus endocrine therapy vs 24 [0·9%] of 2800 patients in the endocrine therapy alone group), leukopenia (318 [11·4%] vs 11 [0·4%]), and diarrhoea (218 [7·8%] vs six [0·2%]). Serious adverse events occurred in 433 (15·5%) of 2791 patients receiving abemaciclib plus endocrine therapy versus 256 (9·1%) of 2800 receiving endocrine therapy. There were two treatment-related deaths in the abemaciclib plus endocrine therapy group (diarrhoea and pneumonitis) and none in the endocrine therapy alone group.\n\nInterpretation: Adjuvant abemaciclib reduces the risk of recurrence. The benefit is sustained beyond the completion of treatment with an absolute increase at 4 years, further supporting the use of abemaciclib in patients with high-risk hormone receptor-positive, HER2-negative early breast cancer. Further follow-up is needed to establish whether overall survival can be improved with abemaciclib plus endocrine therapy in these patients.\n\nFunding: Eli Lilly.\n\nIndexed on Europe PMC as PubMed record 36493792 (DOI 10.1016/s1470-2045(22)00694-5). Its abstract cites the registry id NCT03155997, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2023","url":"https://doi.org/10.1016/s1470-2045(22)00694-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36493792/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36493792"},{"label":"ClinicalTrials.gov NCT03155997","url":"https://clinicaltrials.gov/study/NCT03155997"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["monarche"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2023,"doi":"10.1016/s1470-2045(22)00694-5","pmid":"36493792","authors":"Johnston SRD, Toi M, O'Shaughnessy J, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03155997 with the most citations, so it is the natural first reading for anyone following the monarchE trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-abiraterone-acetate-prostate-lancet-oncol-2012","kind":"paper","name":"Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study","aka":[],"tldr":"Phase 2 or 3 results paper on Abiraterone acetate in Prostate cancer, in The Lancet Oncology (2012), one of the most cited Europe PMC records with Abiraterone acetate in its title.","summary":"Background: Abiraterone acetate improved overall survival in metastatic castration-resistant prostate cancer at a preplanned interim analysis of the COU-AA-301 double-blind, placebo-controlled phase 3 study. Here, we present the final analysis of the study before crossover from placebo to abiraterone acetate (after 775 of the prespecified 797 death events).\n\nMethods: Between May 8, 2008, and July 28, 2009, this study enrolled 1195 patients at 147 sites in 13 countries. Patients were eligible if they had metastatic castration-resistant prostate cancer progressing after docetaxel. Patients were stratified according to baseline Eastern Cooperative Oncology Group (ECOG) performance status, worst pain over the past 24 h on the Brief Pain Inventory-Short Form, number of previous chemotherapy regimens, and type of progression. Patients were randomly assigned (ratio 2:1) to receive either abiraterone acetate (1000 mg, once daily and orally) plus prednisone (5 mg, orally twice daily) or placebo plus prednisone with a permuted block method via an interactive web response system. The primary endpoint was overall survival, analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00091442.\n\nFindings: Of the 1195 eligible patients, 797 were randomly assigned to receive abiraterone acetate plus prednisone (abiraterone group) and 398 to receive placebo plus prednisone (placebo group). At median follow-up of 20·2 months (IQR 18·4-22·1), median overall survival for the abiraterone group was longer than in the placebo group (15·8 months [95% CI 14·8-17·0] vs 11·2 months [10·4-13·1]; hazard ratio [HR] 0·74, 95% CI 0·64-0·86; p<0·0001). Median time to PSA progression (8·5 months, 95% CI 8·3-11·1, in the abiraterone group vs 6·6 months, 5·6-8·3, in the placebo group; HR 0·63, 0·52-0·78; p<0·0001), median radiologic progression-free survival (5·6 months, 5·6-6·5, vs 3·6 months, 2·9-5·5; HR 0·66, 0·58-0·76; p<0·0001), and proportion of patients who had a PSA response (235 [29·5%] of 797 patients vs 22 [5·5%] of 398; p<0·0001) were all improved in the abiraterone group compared with the placebo group. The most common grade 3-4 adverse events were fatigue (72 [9%] of 791 patients in the abiraterone group vs 41 [10%] of 394 in the placebo group), anaemia (62 [8%] vs 32 [8%]), back pain (56 [7%] vs 40 [10%]), and bone pain (51 [6%] vs 31 [8%]).\n\nInterpretation: This final analysis confirms that abiraterone acetate significantly prolongs overall survival in patients with metastatic castration-resistant prostate cancer who have progressed after docetaxel treatment. No new safety signals were identified with increased follow-up.\n\nIndexed on Europe PMC as PubMed record 22995653 (DOI 10.1016/s1470-2045(12)70379-0). Its title names Abiraterone acetate and its text names Prostate cancer; PubMed types it as a clinical trial report (Clinical Trial, Phase III, Research Support, Non-U.S. Gov't, Randomized Controlled Trial). It was matched automatically to the idea \"Prescribe a quarter dose of abiraterone with breakfast\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2012","url":"https://doi.org/10.1016/s1470-2045(12)70379-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22995653/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/22995653"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2012,"doi":"10.1016/s1470-2045(12)70379-0","pmid":"22995653","authors":"Fizazi K, Scher HI, Molina A, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Abiraterone acetate in Prostate cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Abiraterone acetate in the title and Prostate cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-attard-lancet-oncol","kind":"paper","name":"Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 37142371 and published in The Lancet Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background: Abiraterone acetate plus prednisolone (herein referred to as abiraterone) or enzalutamide added at the start of androgen deprivation therapy improves outcomes for patients with metastatic prostate cancer. Here, we aimed to evaluate long-term outcomes and test whether combining enzalutamide with abiraterone and androgen deprivation therapy improves survival.\n\nMethods: We analysed two open-label, randomised, controlled, phase 3 trials of the STAMPEDE platform protocol, with no overlapping controls, conducted at 117 sites in the UK and Switzerland. Eligible patients (no age restriction) had metastatic, histologically-confirmed prostate adenocarcinoma; a WHO performance status of 0-2; and adequate haematological, renal, and liver function. Patients were randomly assigned (1:1) using a computerised algorithm and a minimisation technique to either standard of care (androgen deprivation therapy; docetaxel 75 mg/m 2 intravenously for six cycles with prednisolone 10 mg orally once per day allowed from Dec 17, 2015) or standard of care plus abiraterone acetate 1000 mg and prednisolone 5 mg (in the abiraterone trial) orally or abiraterone acetate and prednisolone plus enzalutamide 160 mg orally once a day (in the abiraterone and enzalutamide trial). Patients were stratified by centre, age, WHO performance status, type of androgen deprivation therapy, use of aspirin or non-steroidal anti-inflammatory drugs, pelvic nodal status, planned radiotherapy, and planned docetaxel use. The primary outcome was overall survival assessed in the intention-to-treat population. Safety was assessed in all patients who started treatment. A fixed-effects meta-analysis of individual patient data was used to compare differences in survival between the two trials. STAMPEDE is registered with ClinicalTrials.gov (NCT00268476) and ISRCTN (ISRCTN78818544).\n\nFindings: Between Nov 15, 2011, and Jan 17, 2014, 1003 patients were randomly assigned to standard of care (n=502) or standard of care plus abiraterone (n=501) in the abiraterone trial. Between July 29, 2014, and March 31, 2016, 916 patients were randomly assigned to standard of care (n=454) or standard of care plus abiraterone and enzalutamide (n=462) in the abiraterone and enzalutamide trial. Median follow-up was 96 months (IQR 86-107) in the abiraterone trial and 72 months (61-74) in the abiraterone and enzalutamide trial. In the abiraterone trial, median overall survival was 76·6 months (95% CI 67·8-86·9) in the abiraterone group versus 45·7 months (41·6-52·0) in the standard of care group (hazard ratio [HR] 0·62 [95% CI 0·53-0·73]; p<0·0001). In the abiraterone and enzalutamide trial, median overall survival was 73·1 months (61·9-81·3) in the abiraterone and enzalutamide group versus 51·8 months (45·3-59·0) in the standard of care group (HR 0·65 [0·55-0·77]; p<0·0001). We found no difference in the treatment effect between these two trials (interaction HR 1·05 [0·83-1·32]; p interaction =0·71) or between-trial heterogeneity (I 2 p=0·70). In the first 5 years of treatment, grade 3-5 toxic effects were higher when abiraterone was added to standard of care (271 [54%] of 498 vs 192 [38%] of 502 with standard of care) and the highest toxic effects were seen when abiraterone and enzalutamide were added to standard of care (302 [68%] of 445 vs 204 [45%] of 454 with standard of care). Cardiac causes were the most common cause of death due to adverse events (five [1%] with standard of care plus abiraterone and enzalutamide [two attributed to treatment] and one (<1%) with standard of care in the abiraterone trial).\n\nInterpretation: Enzalutamide and abiraterone should not be combined for patients with prostate cancer starting long-term androgen deprivation therapy. Clinically important improvements in survival from addition of abiraterone to androgen deprivation therapy are maintained for longer than 7 years.\n\nFunding: Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Janssen, and Astellas.\n\nIndexed on Europe PMC as PubMed record 37142371 (DOI 10.1016/s1470-2045(23)00148-1). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2023","url":"https://doi.org/10.1016/s1470-2045(23)00148-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37142371/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37142371"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["stampede"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2023,"doi":"10.1016/s1470-2045(23)00148-1","pmid":"37142371","authors":"Attard G, Murphy L, Clarke NW, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-latitude-lancet-oncol-2019-update","kind":"paper","name":"Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomised, double-blind, phase 3 trial","aka":[],"tldr":"Later report from the LATITUDE trial registered as NCT01715285, in The Lancet Oncology (2019); its title describes an updated or longer-term analysis.","summary":"Background: In the interim analyses of the LATITUDE study, the addition of abiraterone acetate plus prednisone to androgen deprivation therapy (ADT) led to a significant improvement in overall survival and radiographic progression-free survival compared with placebos plus ADT in men with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (mCSPC). Here, we present long-term survival outcomes and safety of abiraterone acetate plus prednisone and ADT from the final analysis of the LATITUDE study.\n\nMethods: This is a multicentre, randomised, double-blind, phase 3 trial done at 235 sites in 34 countries. Eligible patients (men aged ≥18 years) had newly diagnosed, histologically or cytologically confirmed prostate cancer with metastases, Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, and at least two of the three high-risk prognostic factors (Gleason score of ≥8, presence of three or more lesions on bone scan, or presence of measurable visceral metastasis except lymph node metastasis). Patients were randomly assigned (1:1) to receive abiraterone acetate (1000 mg) once daily orally plus prednisone (5 mg) once daily orally and ADT (abiraterone acetate plus prednisone group) or matching placebos plus ADT (placebo group); each treatment cycle was 28 days. Randomisation was done by a centralised interactive web response system in a country-by-country scheme using permuted block randomisation, stratified by presence of visceral disease and ECOG performance status. The coprimary endpoint of overall survival was assessed in the intention-to-treat population. This study is registered at ClinicalTrials.gov, number NCT01715285 and is complete.\n\nFindings: Between Feb 12, 2013, and Dec 11, 2014, 1209 patients were screened, of whom ten were ineligible because of study site violations. 1199 patients were randomly assigned to either the abiraterone acetate plus prednisone group (n=597) or placebo group (n=602). After the results of the first interim analysis (cutoff date Oct 31, 2016), the study was unmasked to patients and investigators, and patients in the placebo group were allowed to cross over to receive abiraterone acetate and prednisone plus ADT treatment as per a protocol amendment (Feb 15, 2017) in an open-label extension phase of the study (up to 18 months from the protocol amendment). This final analysis (data cutoff Aug 15, 2018) was done after a median follow-up of 51·8 months (IQR 47·2-57·0) and 618 deaths (275 [46%] of 597 in the abiraterone acetate plus prednisone group and 343 [57%] of 602 in the placebo group). Overall survival was significantly longer in the abiraterone acetate plus prednisone group (median 53·3 months [95% CI 48·2-not reached]) than in the placebo group (36·5 months [33·5-40·0]), with a hazard ratio of 0·66 (95% CI 0·56-0·78; p<0·0001). The most common grade 3-4 adverse events were hypertension (125 [21%] in the abiraterone acetate plus prednisone group vs 60 [10%] in the placebo group vs three [4%] in the 72 patients who crossed over from placebo to abiraterone acetate plus prednisone) and hypokalaemia (70 [12%] vs ten [2%] vs two [3%]). Serious adverse events of any grade occurred in 192 (32%) of 597 patients in the abiraterone acetate plus prednisone group, 151 (25%) of 602 in the placebo group, and four (6%) of 72 in the crossover group. The most common treatment-related serious adverse event was hypokalaemia (four [1%] patients in the abiraterone acetate plus prednisone group and none in the other groups). Treatment-related deaths occurred in three (<1%) patients each in the abiraterone acetate plus prednisone group (gastric ulcer perforation, sudden death, and cerebrovascular accident) and the placebo group (sudden death, cerebrovascular accident, and pneumonia), with none in the crossover group.\n\nInterpretation: The combination of abiraterone acetate plus prednisone with ADT was associated with significantly longer overall survival than placebos plus ADT in men with newly diagnosed high-risk mCSPC and had a manageable safety profile. These findings support the use of abiraterone acetate plus prednisone as a standard of care in patients with high-risk mCSPC.\n\nFunding: Janssen Research & Development.\n\nIndexed on Europe PMC as PubMed record 30987939 (DOI 10.1016/s1470-2045(19)30082-8). Its abstract cites the registry id NCT01715285, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2019","url":"https://doi.org/10.1016/s1470-2045(19)30082-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30987939/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30987939"},{"label":"ClinicalTrials.gov NCT01715285","url":"https://clinicaltrials.gov/study/NCT01715285"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["latitude"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2019,"doi":"10.1016/s1470-2045(19)30082-8","pmid":"30987939","authors":"Fizazi K, Tran N, Fein L, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the LATITUDE trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-abiraterone-acetate-prostate-lancet-oncol-2015","kind":"paper","name":"Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study","aka":[],"tldr":"Phase 2 or 3 results paper on Abiraterone acetate in Prostate cancer, in The Lancet Oncology (2015), one of the most cited Europe PMC records with Abiraterone acetate in its title.","summary":"Background: Abiraterone acetate plus prednisone significantly improved radiographic progression-free survival compared with placebo plus prednisone in men with chemotherapy-naive castration-resistant prostate cancer at the interim analyses of the COU-AA-302 trial. Here, we present the prespecified final analysis of the trial, assessing the effect of abiraterone acetate plus prednisone on overall survival, time to opiate use, and use of other subsequent therapies.\n\nMethods: In this placebo-controlled, double-blind, randomised phase 3 study, 1088 asymptomatic or mildly symptomatic patients with chemotherapy-naive prostate cancer stratified by Eastern Cooperative Oncology performance status (0 vs 1) were randomly assigned with a permuted block allocation scheme via a web response system in a 1:1 ratio to receive either abiraterone acetate (1000 mg once daily) plus prednisone (5 mg twice daily; abiraterone acetate group) or placebo plus prednisone (placebo group). Coprimary endpoints were radiographic progression-free survival and overall survival analysed in the intention-to-treat population. The study is registered with ClinicalTrials.gov, number NCT00887198.\n\nFindings: At a median follow-up of 49.2 months (IQR 47.0-51.8), 741 (96%) of the prespecified 773 death events for the final analysis had been observed: 354 (65%) of 546 patients in the abiraterone acetate group and 387 (71%) of 542 in the placebo group. 238 (44%) patients initially receiving prednisone alone subsequently received abiraterone acetate plus prednisone as crossover per protocol (93 patients) or as subsequent therapy (145 patients). Overall, 365 (67%) patients in the abiraterone acetate group and 435 (80%) in the placebo group received subsequent treatment with one or more approved agents. Median overall survival was significantly longer in the abiraterone acetate group than in the placebo group (34.7 months [95% CI 32.7-36.8] vs 30.3 months [28.7-33.3]; hazard ratio 0.81 [95% CI 0.70-0.93]; p=0.0033). The most common grade 3-4 adverse events of special interest were cardiac disorders (41 [8%] of 542 patients in the abiraterone acetate group vs 20 [4%] of 540 patients in the placebo group), increased alanine aminotransferase (32 [6%] vs four [<1%]), and hypertension (25 [5%] vs 17 [3%]).\n\nInterpretation: In this randomised phase 3 trial with a median follow-up of more than 4 years, treatment with abiraterone acetate prolonged overall survival compared with prednisone alone by a margin that was both clinically and statistically significant. These results further support the favourable safety profile of abiraterone acetate in patients with chemotherapy-naive metastatic castration-resistant prostate cancer.\n\nFunding: Janssen Research & Development.\n\nIndexed on Europe PMC as PubMed record 25601341 (DOI 10.1016/s1470-2045(14)71205-7). Its title names Abiraterone acetate and its text names Prostate cancer; PubMed types it as a clinical trial report (Clinical Trial, Phase III, Comparative Study, Research Support, Non-U.S. Gov't, Multicenter Study, Randomized Controlled Trial). It was matched automatically to the idea \"Prescribe a quarter dose of abiraterone with breakfast\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2015","url":"https://doi.org/10.1016/s1470-2045(14)71205-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25601341/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25601341"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2015,"doi":"10.1016/s1470-2045(14)71205-7","pmid":"25601341","authors":"Ryan CJ, Smith MR, Fizazi K, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Abiraterone acetate in Prostate cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Abiraterone acetate in the title and Prostate cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-clarke-nejm-evid","kind":"paper","name":"Abiraterone and Olaparib for Metastatic Castration-Resistant Prostate Cancer","aka":[],"tldr":"Paper cited by one pairing page, indexed on Europe PMC as PubMed record 38319800 and published in NEJM Evidence; the citing page links this DOI, which is how the record was matched.","summary":"BACKGROUND: Preclinical studies and results of a phase 2 trial of abiraterone and olaparib suggest a combined antitumor effect when the poly(adenosine diphosphate[ADP]-ribose) polymerase inhibitor olaparib is combined with next-generation hormonal agent abiraterone to treat metastatic castration-resistant prostate cancer (mCRPC). METHODS: We conducted a double-blind, phase 3 trial of abiraterone and olaparib versus abiraterone and placebo in patients with mCRPC in the first-line setting. Patients were enrolled regardless of homologous recombination repair gene mutation (HRRm) status. HRRm status was determined following enrollment by tumor tissue and circulating tumor DNA tests. Patients were randomly assigned (1:1) to receive abiraterone (1000 mg once daily) plus prednisone or prednisolone with either olaparib (300 mg twice daily) or placebo. The primary end point was imaging-based progression-free survival (ibPFS) by investigator assessment. Overall survival was among the secondary end points. RESULTS: At this planned primary analysis at the first data cutoff, median ibPFS was significantly longer in the abiraterone and olaparib arm than in the abiraterone and placebo arm (24.8 vs. 16.6 months; hazard ratio, 0.66; 95% confidence interval [CI], 0.54 to 0.81; P<0.001) and was consistent with blinded independent central review (hazard ratio, 0.61; 95% CI, 0.49 to 0.74). At this data cutoff, overall survival data were immature (28.6% maturity; hazard ratio, 0.86; 95% CI, 0.66 to 1.12; P=0.29). The safety profile of olaparib and abiraterone was consistent with the known safety profiles of the individual drugs. The most common adverse events in the abiraterone and olaparib arm were anemia, fatigue/asthenia, and nausea. CONCLUSIONS: At primary analysis at this first data cutoff, abiraterone combined with olaparib significantly prolonged ibPFS compared with abiraterone and placebo as first-line treatment for patients with mCRPC enrolled irrespective of HRRm status. (Funded by AstraZeneca and Merck Sharp & Dohme, LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; ClinicalTrials.gov number, NCT03732820.)\n\nIndexed on Europe PMC as PubMed record 38319800 (DOI 10.1056/evidoa2200043). Matched by DOI alone: one pairing page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"NEJM Evid 2022","url":"https://doi.org/10.1056/evidoa2200043"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38319800/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38319800"}],"tags":["europepmc-ingest"],"related":["parp-plus-arpi"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm-evidence"],"dependsOn":[],"notes":[],"journal":"NEJM Evidence","year":2022,"doi":"10.1056/evidoa2200043","pmid":"38319800","authors":"Clarke NW, Armstrong AJ, Thiery-Vuillemin A, et al.","paperType":"observational","findings":[],"whatItMeans":"One pairing page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-abiraterone-acetate-prostate-n-engl-j-med-2013","kind":"paper","name":"Abiraterone in metastatic prostate cancer without previous chemotherapy","aka":[],"tldr":"Phase 2 or 3 results paper on Abiraterone acetate in Prostate cancer, in New England Journal of Medicine (2013), one of the most cited Europe PMC records with Abiraterone acetate in its title.","summary":"Background: Abiraterone acetate, an androgen biosynthesis inhibitor, improves overall survival in patients with metastatic castration-resistant prostate cancer after chemotherapy. We evaluated this agent in patients who had not received previous chemotherapy.\n\nMethods: In this double-blind study, we randomly assigned 1088 patients to receive abiraterone acetate (1000 mg) plus prednisone (5 mg twice daily) or placebo plus prednisone. The coprimary end points were radiographic progression-free survival and overall survival.\n\nResults: The study was unblinded after a planned interim analysis that was performed after 43% of the expected deaths had occurred. The median radiographic progression-free survival was 16.5 months with abiraterone-prednisone and 8.3 months with prednisone alone (hazard ratio for abiraterone-prednisone vs. prednisone alone, 0.53; 95% confidence interval [CI], 0.45 to 0.62; P<0.001). Over a median follow-up period of 22.2 months, overall survival was improved with abiraterone-prednisone (median not reached, vs. 27.2 months for prednisone alone; hazard ratio, 0.75; 95% CI, 0.61 to 0.93; P=0.01) but did not cross the efficacy boundary. Abiraterone-prednisone showed superiority over prednisone alone with respect to time to initiation of cytotoxic chemotherapy, opiate use for cancer-related pain, prostate-specific antigen progression, and decline in performance status. Grade 3 or 4 mineralocorticoid-related adverse events and abnormalities on liver-function testing were more common with abiraterone-prednisone.\n\nConclusions: Abiraterone improved radiographic progression-free survival, showed a trend toward improved overall survival, and significantly delayed clinical decline and initiation of chemotherapy in patients with metastatic castration-resistant prostate cancer. (Funded by Janssen Research and Development, formerly Cougar Biotechnology; ClinicalTrials.gov number, NCT00887198.).\n\nIndexed on Europe PMC as PubMed record 23228172 (DOI 10.1056/nejmoa1209096). Its title names Abiraterone acetate and its text names Prostate cancer; PubMed types it as a clinical trial report (Research Support, Non-U.S. Gov't, research-article, Multicenter Study, Randomized Controlled Trial). It was matched automatically to the idea \"Prescribe a quarter dose of abiraterone with breakfast\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2013","url":"https://doi.org/10.1056/nejmoa1209096"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23228172/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/23228172"}],"tags":["europepmc-ingest"],"related":["prostate-roadmap","paper-cou-aa-301-abiraterone-de-bono-nejm-2011","paper-beer-prevail-enzalutamide-nejm-2014","paper-attard-abiraterone-phase-1-cyp17-jco-2008"],"cancers":["prostate","prostate-mcrpc"],"sections":["hormonal","targeted-therapy"],"technologies":[],"targets":["androgen-receptor"],"drugs":["abiraterone","prednisone"],"companies":[],"institutions":[],"pathways":[],"terms":["castration-resistance","psa","radiographic-progression-free-survival"],"trials":[],"people":[],"bottlenecks":["b-resistance"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2013,"doi":"10.1056/nejmoa1209096","pmid":"23228172","authors":"Ryan CJ, Smith MR, de Bono JS, et al.","paperType":"rct","findings":["Median radiographic progression-free survival 16.5 months with abiraterone and prednisone against 8.3 months with prednisone alone (hazard ratio 0.53; 95 percent confidence interval 0.45 to 0.62; P less than 0.001), in 1,088 chemotherapy-naive patients.","Over a median follow-up of 22.2 months, overall survival was improved with abiraterone and prednisone (median not reached against 27.2 months; hazard ratio 0.75; 0.61 to 0.93; P equals 0.01) but did not cross the pre-specified efficacy boundary.","Abiraterone and prednisone were superior for time to initiation of cytotoxic chemotherapy, opiate use for cancer-related pain, prostate-specific antigen progression and decline in performance status.","Grade 3 or 4 mineralocorticoid-related adverse events and liver-function abnormalities were more common with abiraterone and prednisone."],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Abiraterone acetate in Prostate cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Abiraterone acetate in the title and Prostate cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."],"changedPractice":true,"participants":1088},{"id":"paper-peace-1-lancet-2022","kind":"paper","name":"Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design","aka":[],"tldr":"Published report from the PEACE-1 trial registered as NCT01957436, in The Lancet (2022), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Current standard of care for metastatic castration-sensitive prostate cancer supplements androgen deprivation therapy with either docetaxel, second-generation hormonal therapy, or radiotherapy. We aimed to evaluate the efficacy and safety of abiraterone plus prednisone, with or without radiotherapy, in addition to standard of care.\n\nMethods: We conducted an open-label, randomised, phase 3 study with a 2 × 2 factorial design (PEACE-1) at 77 hospitals across Belgium, France, Ireland, Italy, Romania, Spain, and Switzerland. Eligible patients were male, aged 18 years or older, with histologically confirmed or cytologically confirmed de novo metastatic prostate adenocarcinoma, and an Eastern Cooperative Oncology Group performance status of 0-1 (or 2 due to bone pain). Participants were randomly assigned (1:1:1:1) to standard of care (androgen deprivation therapy alone or with intravenous docetaxel 75 mg/m 2 once every 3 weeks), standard of care plus radiotherapy, standard of care plus abiraterone (oral 1000 mg abiraterone once daily plus oral 5 mg prednisone twice daily), or standard of care plus radiotherapy plus abiraterone. Neither the investigators nor the patients were masked to treatment allocation. The coprimary endpoints were radiographic progression-free survival and overall survival. Abiraterone efficacy was first assessed in the overall population and then in the population who received androgen deprivation therapy with docetaxel as standard of care (population of interest). This study is ongoing and is registered with ClinicalTrials.gov, NCT01957436.\n\nFindings: Between Nov 27, 2013, and Dec 20, 2018, 1173 patients were enrolled (one patient subsequently withdrew consent for analysis of his data) and assigned to receive standard of care (n=296), standard of care plus radiotherapy (n=293), standard of care plus abiraterone (n=292), or standard of care plus radiotherapy plus abiraterone (n=291). Median follow-up was 3·5 years (IQR 2·8-4·6) for radiographic progression-free survival and 4·4 years (3·5-5·4) for overall survival. Adjusted Cox regression modelling revealed no interaction between abiraterone and radiotherapy, enabling the pooled analysis of abiraterone efficacy. In the overall population, patients assigned to receive abiraterone (n=583) had longer radiographic progression-free survival (hazard ratio [HR] 0·54, 99·9% CI 0·41-0·71; p<0·0001) and overall survival (0·82, 95·1% CI 0·69-0·98; p=0·030) than patients who did not receive abiraterone (n=589). In the androgen deprivation therapy with docetaxel population (n=355 in both with abiraterone and without abiraterone groups), the HRs were consistent (radiographic progression-free survival 0·50, 99·9% CI 0·34-0·71; p<0·0001; overall survival 0·75, 95·1% CI 0·59-0·95; p=0·017). In the androgen deprivation therapy with docetaxel population, grade 3 or worse adverse events occurred in 217 (63%) of 347 patients who received abiraterone and 181 (52%) of 350 who did not; hypertension had the largest difference in occurrence (76 [22%] patients and 45 [13%], respectively). Addition of abiraterone to androgen deprivation therapy plus docetaxel did not increase the rates of neutropenia, febrile neutropenia, fatigue, or neuropathy compared with androgen deprivation therapy plus docetaxel alone.\n\nInterpretation: Combining androgen deprivation therapy, docetaxel, and abiraterone in de novo metastatic castration-sensitive prostate cancer improved overall survival and radiographic progression-free survival with a modest increase in toxicity, mostly hypertension. This triplet therapy could become a standard of care for these patients.\n\nFunding: Janssen-Cilag, Ipsen, Sanofi, and the French Government.\n\nIndexed on Europe PMC as PubMed record 35405085 (DOI 10.1016/s0140-6736(22)00367-1). Its abstract cites the registry id NCT01957436, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet 2022","url":"https://doi.org/10.1016/s0140-6736(22)00367-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35405085/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35405085"},{"label":"ClinicalTrials.gov NCT01957436","url":"https://clinicaltrials.gov/study/NCT01957436"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["peace-1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2022,"doi":"10.1016/s0140-6736(22)00367-1","pmid":"35405085","authors":"Fizazi K, Foulon S, Carles J, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT01957436 with the most citations, so it is the natural first reading for anyone following the PEACE-1 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-acalabrutinib-cll-n-engl-j-med-2016","kind":"paper","name":"Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia","aka":[],"tldr":"Phase 2 or 3 results paper on Acalabrutinib in Chronic lymphocytic leukaemia, in New England Journal of Medicine (2016), one of the most cited Europe PMC records with Acalabrutinib in its title.","summary":"Background: Irreversible inhibition of Bruton's tyrosine kinase (BTK) by ibrutinib represents an important therapeutic advance for the treatment of chronic lymphocytic leukemia (CLL). However, ibrutinib also irreversibly inhibits alternative kinase targets, which potentially compromises its therapeutic index. Acalabrutinib (ACP-196) is a more selective, irreversible BTK inhibitor that is specifically designed to improve on the safety and efficacy of first-generation BTK inhibitors.\n\nMethods: In this uncontrolled, phase 1-2, multicenter study, we administered oral acalabrutinib to 61 patients who had relapsed CLL to assess the safety, efficacy, pharmacokinetics, and pharmacodynamics of acalabrutinib. Patients were treated with acalabrutinib at a dose of 100 to 400 mg once daily in the dose-escalation (phase 1) portion of the study and 100 mg twice daily in the expansion (phase 2) portion.\n\nResults: The median age of the patients was 62 years, and patients had received a median of three previous therapies for CLL; 31% had chromosome 17p13.1 deletion, and 75% had unmutated immunoglobulin heavy-chain variable genes. No dose-limiting toxic effects occurred during the dose-escalation portion of the study. The most common adverse events observed were headache (in 43% of the patients), diarrhea (in 39%), and increased weight (in 26%). Most adverse events were of grade 1 or 2. At a median follow-up of 14.3 months, the overall response rate was 95%, including 85% with a partial response and 10% with a partial response with lymphocytosis; the remaining 5% of patients had stable disease. Among patients with chromosome 17p13.1 deletion, the overall response rate was 100%. No cases of Richter's transformation (CLL that has evolved into large-cell lymphoma) and only one case of CLL progression have occurred.\n\nConclusions: In this study, the selective BTK inhibitor acalabrutinib had promising safety and efficacy profiles in patients with relapsed CLL, including those with chromosome 17p13.1 deletion. (Funded by the Acerta Pharma and others; ClinicalTrials.gov number, NCT02029443.).\n\nIndexed on Europe PMC as PubMed record 26641137 (DOI 10.1056/nejmoa1509981). Its title names Acalabrutinib and its text names Chronic lymphocytic leukaemia; PubMed types it as a clinical trial report (Clinical Trial, Phase II, Research Support, Non-U.S. Gov't, research-article, Multicenter Study, Clinical Trial, Phase I, Research Support, N.I.H., Extramural). It was matched automatically to the idea \"BTK degraders to pre-empt resistance in frontline CLL\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2016","url":"https://doi.org/10.1056/nejmoa1509981"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26641137/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26641137"},{"label":"ClinicalTrials.gov NCT02029443","url":"https://clinicaltrials.gov/study/NCT02029443"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct02029443"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2016,"doi":"10.1056/nejmoa1509981","pmid":"26641137","authors":"Byrd JC, Harrington B, O'Brien S, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Acalabrutinib in Chronic lymphocytic leukaemia, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Acalabrutinib in the title and Chronic lymphocytic leukaemia in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-echo-acalabrutinib-bendamustine-rituximab-mantle-cell-jco-2025","kind":"paper","name":"Acalabrutinib plus bendamustine-rituximab in untreated mantle cell lymphoma","aka":["ECHO","Wang 2025","Acalabrutinib with bendamustine and rituximab"],"tldr":"Repeating the SHINE design with a more selective targeted tablet gave another seventeen months before relapse, and again did not extend life.","summary":"A randomised trial in patients aged 65 or over with previously untreated mantle cell lymphoma, designed to test whether acalabrutinib, more selective and better tolerated than ibrutinib, would do in this setting what ibrutinib had not. Patients received acalabrutinib 100 mg twice daily or placebo until progression or unacceptable toxicity, plus six cycles of bendamustine 90 mg per square metre on days 1 and 2 and rituximab 375 mg per square metre on day 1, followed by two years of rituximab maintenance in responders. Crossover to acalabrutinib at progression was permitted. The primary endpoint was progression-free survival by independent review committee.\n\n598 patients were randomised, 299 per arm. At a median follow-up of 49.8 months by the reverse Kaplan-Meier method, median progression-free survival was 66.4 months with acalabrutinib against 49.6 months with placebo (hazard ratio 0.73, 95 per cent confidence interval 0.57 to 0.94, p = 0.0160), with benefit across all subgroups including those with high-risk features. Overall response and complete response rates were 91.0 and 66.6 per cent with acalabrutinib against 88.0 and 53.5 per cent. Overall survival was not significantly different (hazard ratio 0.86, 0.65 to 1.13, p = 0.27). Grade 3 or greater adverse events occurred in 88.9 and 88.2 per cent.","asOf":"2026-10-01","links":[{"label":"Journal of Clinical Oncology 2025","url":"https://doi.org/10.1200/JCO-25-00690"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40311141/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40311141"}],"tags":["lymphoma-evidence"],"related":["lymphoma-roadmap"],"cancers":["mantle-cell-lymphoma","non-hodgkin-lymphoma"],"sections":["targeted-therapy","chemotherapy"],"technologies":[],"targets":["btk","cd20","ccnd1"],"drugs":["acalabrutinib","bendamustine","rituximab"],"companies":["astrazeneca"],"institutions":[],"pathways":["bcr-signalling"],"terms":[],"trials":["nct02972840","shine","enrich"],"people":["michael-wang","martin-dreyling"],"bottlenecks":["b-aging-comorbidity","b-toxicity-qol"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2025,"doi":"10.1200/JCO-25-00690","pmid":"40311141","authors":"Wang M, Salek D, Belada D, et al.","paperType":"rct","findings":["Median progression-free survival was 66.4 months with acalabrutinib against 49.6 months with placebo (hazard ratio 0.73, 95 per cent confidence interval 0.57 to 0.94, p = 0.0160).","Overall response and complete response rates were 91.0 and 66.6 per cent with acalabrutinib against 88.0 and 53.5 per cent with placebo.","Overall survival was not significantly different (hazard ratio 0.86, 0.65 to 1.13, p = 0.27).","Grade 3 or greater adverse events were reported in 88.9 per cent with acalabrutinib and 88.2 per cent with placebo.","Benefit was seen across all subgroups, including those with high-risk features."],"whatItMeans":"A second randomised confirmation that adding a Bruton tyrosine kinase inhibitor to first-line bendamustine-rituximab delays progression in older patients with mantle cell lymphoma, with a toxicity profile that did not improve as much as the drug's selectivity promised.","caveats":["No overall survival benefit, as in SHINE; crossover at progression was permitted, which makes a survival difference harder to detect.","Grade 3 or greater adverse events in roughly 89 per cent of both arms shows how much of the burden comes from the chemotherapy backbone rather than the inhibitor.","The trial recruited through the COVID-19 pandemic, which the investigators have discussed as affecting early mortality in both arms.","Indefinite acalabrutinib until progression, with the cost and adherence implications that carries."],"changedPractice":true,"participants":598},{"id":"paper-acalabrutinib-cll-j-clin-oncol-2021","kind":"paper","name":"Acalabrutinib Versus Ibrutinib in Previously Treated Chronic Lymphocytic Leukemia: Results of the First Randomized Phase III Trial","aka":[],"tldr":"Phase 2 or 3 results paper on Acalabrutinib in Chronic lymphocytic leukaemia, in Journal of Clinical Oncology (2021), one of the most cited Europe PMC records with Acalabrutinib in its title.","summary":"Purpose: Among Bruton's tyrosine kinase inhibitors, acalabrutinib has greater selectivity than ibrutinib, which we hypothesized would improve continuous therapy tolerability. We conducted an open-label, randomized, noninferiority, phase III trial comparing acalabrutinib and ibrutinib in patients with chronic lymphocytic leukemia (CLL).\n\nMethods: Patients with previously treated CLL with centrally confirmed del(17)(p13.1) or del(11)(q22.3) were randomly assigned to oral acalabrutinib 100 mg twice daily or ibrutinib 420 mg once daily until progression or unacceptable toxicity. The primary end point was independent review committee-assessed noninferiority of progression-free survival (PFS).\n\nResults: Overall, 533 patients (acalabrutinib, n = 268; ibrutinib, n = 265) were randomly assigned. At the data cutoff, 124 (46.3%) acalabrutinib patients and 109 (41.1%) ibrutinib patients remained on treatment. After a median follow-up of 40.9 months, acalabrutinib was determined to be noninferior to ibrutinib with a median PFS of 38.4 months in both arms (95% CI acalabrutinib, 33.0 to 38.6 and ibrutinib, 33.0 to 41.6; hazard ratio: 1.00; 95% CI, 0.79 to 1.27). All-grade atrial fibrillation/atrial flutter incidence was significantly lower with acalabrutinib versus ibrutinib (9.4% v 16.0%; P =.02); among other selected secondary end points, grade 3 or higher infections (30.8% v 30.0%) and Richter transformations (3.8% v 4.9%) were comparable between groups and median overall survival was not reached in either arm (hazard ratio, 0.82; 95% CI, 0.59 to 1.15), with 63 (23.5%) deaths with acalabrutinib and 73 (27.5%) with ibrutinib. Treatment discontinuations because of adverse events occurred in 14.7% of acalabrutinib-treated patients and 21.3% of ibrutinib-treated patients.\n\nConclusion: In this first direct comparison of less versus more selective Bruton's tyrosine kinase inhibitors in CLL, acalabrutinib demonstrated noninferior PFS with fewer cardiovascular adverse events.\n\nIndexed on Europe PMC as PubMed record 34310172 (DOI 10.1200/jco.21.01210). Its title names Acalabrutinib and its text names Chronic lymphocytic leukaemia; PubMed types it as a clinical trial report (Clinical Trial, Phase III, Comparative Study, Equivalence Trial, Research Support, Non-U.S. Gov't, research-article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural). It was matched automatically to the idea \"BTK degraders to pre-empt resistance in frontline CLL\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2021","url":"https://doi.org/10.1200/jco.21.01210"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34310172/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34310172"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2021,"doi":"10.1200/jco.21.01210","pmid":"34310172","authors":"Byrd JC, Byrd JC, Hillmen P, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Acalabrutinib in Chronic lymphocytic leukaemia, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Acalabrutinib in the title and Chronic lymphocytic leukaemia in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-wilson-lancet","kind":"paper","name":"Access to pathology and laboratory medicine services: a crucial gap","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 29550029 and published in The Lancet; the citing page links this DOI, which is how the record was matched.","summary":"As global efforts accelerate to implement the Sustainable Development Goals and, in particular, universal health coverage, access to high-quality and timely pathology and laboratory medicine (PALM) services will be needed to support health-care systems that are tasked with achieving these goals. This access will be most challenging to achieve in low-income and middle-income countries (LMICs), which have a disproportionately large share of the global burden of disease but a disproportionately low share of global health-care resources, particularly PALM services. In this first in a Series of three papers on PALM in LMICs, we describe the crucial and central roles of PALM services in the accurate diagnosis and detection of disease, informing prognosis and guiding treatment, contributing to disease screening, public health surveillance and disease registries, and supporting medical-legal systems. We also describe how, even though data are sparse, these services are of both insufficient scope and inadequate quality to play their key role in health-care systems in LMICs. Lastly, we identify four key barriers to the provision of optimal PALM services in resource-limited settings: insufficient human resources or workforce capacity, inadequate education and training, inadequate infrastructure, and insufficient quality, standards, and accreditation.\n\nIndexed on Europe PMC as PubMed record 29550029 (DOI 10.1016/s0140-6736(18)30458-6). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet 2018","url":"https://doi.org/10.1016/s0140-6736(18)30458-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29550029/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29550029"}],"tags":["europepmc-ingest"],"related":["oncology-workforce"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2018,"doi":"10.1016/s0140-6736(18)30458-6","pmid":"29550029","authors":"Wilson ML, Fleming KA, Kuti MA, et al.","paperType":"review","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-halder-lancet-reg-health-southeast-asia","kind":"paper","name":"Access to timely cancer treatment initiation in India: extent, determinants and trends","aka":[],"tldr":"Paper cited by one institution page, indexed on Europe PMC as PubMed record 39802701 and published in The Lancet regional health. Southeast Asia; the citing page links this DOI, which is how the record was matched.","summary":"Background: Treatment delays are significantly associated with advanced stage, poor response to treatment, increased mortality risk, poor health outcomes, increased healthcare expenditures among cancer patients. However, factors associated with these delays have not yet been robustly evaluated. In order to bridge this gap, we determined the delayed time to treatment initiation (TTI) among cancer patients in India, ascertained its determinants, and assessed the trends of delayed TTI.\n\nMethods: We analysed data collected from 6695 cancer patients seeking outpatient/daycare treatment, recruited at purposively selected seven healthcare facilities across six states of India. Data on socio-demographic and clinical characteristics including date of cancer diagnosis, date of treatment initiation, cancer site, stage and type of treatment were collected to determine the median TTI and ascertain its determinants among cancer patients in India. Time to treatment initiation was calculated as the duration (days) between diagnosis of cancer (histologically/clinically) and date of initiation of treatment. Multi-variable logistic regression was employed to analyse the relationship between the outcome variable (TTI) and each explanatory variable. A Cox Proportional Hazard (CPH) model was used to conduct time-to-event analysis, and to assess the impact of government-funded health insurance on timely cancer treatment initiation.\n\nFindings: The median (IQR) overall TTI was 20 (7-39) days, with a mean of 53.7 days (SD, 192.9). The TTI was higher for those having head and neck cancer (median TTI: 29 days, IQR: 10.5-55.5) and those receiving radiotherapy as initial treatment (27.5 days, IQR: 10-49.5). Younger patients, those educated up to graduation level and males had significantly lower odds of delayed TTI. As compared to patients who were diagnosed between 1995 and 2017, those diagnosed after 2018 had a 36% (26-46%) higher odds of timely initiation of treatment within 30 days. Upon stratifying by enrolment under PMJAY, we found that while the access for timely treatment initiation increased by 33% for those who were not enrolled, vs. 90% among those enrolled under PM-JAY. Overall, this shows significant improvement in timely initiation of cancer treatment as a result of introduction of PM-JAY.\n\nInterpretation: The study highlights the positive impact of government-funded health insurance schemes on the timely access to cancer treatment in India. Our study recommends expanding AB PM-JAY cancer packages to include cost-effective treatments, increasing population coverage under screening programs and promoting e-RUPI to reduce financial constraints associated with diagnostic services to address delayed treatment initiation due to unknown cancer stages.\n\nFunding: Department of Health Research, Ministry of Health and Family Welfare, New Delhi, India.\n\nIndexed on Europe PMC as PubMed record 39802701 (DOI 10.1016/j.lansea.2024.100514). Matched by DOI alone: one institution page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Reg Health Southeast Asia 2025","url":"https://doi.org/10.1016/j.lansea.2024.100514"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39802701/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39802701"}],"tags":["europepmc-ingest"],"related":["nha-pmjay"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Lancet regional health. Southeast Asia","year":2025,"doi":"10.1016/j.lansea.2024.100514","pmid":"39802701","authors":"Halder P, Dixit J, Gupta N, et al.","paperType":"observational","findings":[],"whatItMeans":"One institution page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-hanahan-cancer-cell","kind":"paper","name":"Accessories to the crime: functions of cells recruited to the tumor microenvironment","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 22439926 and published in Cancer Cell; the citing page links this DOI, which is how the record was matched.","summary":"Mutationally corrupted cancer (stem) cells are the driving force of tumor development and progression. Yet, these transformed cells cannot do it alone. Assemblages of ostensibly normal tissue and bone marrow-derived (stromal) cells are recruited to constitute tumorigenic microenvironments. Most of the hallmarks of cancer are enabled and sustained to varying degrees through contributions from repertoires of stromal cell types and distinctive subcell types. Their contributory functions to hallmark capabilities are increasingly well understood, as are the reciprocal communications with neoplastic cancer cells that mediate their recruitment, activation, programming, and persistence. This enhanced understanding presents interesting new targets for anticancer therapy.\n\nIndexed on Europe PMC as PubMed record 22439926 (DOI 10.1016/j.ccr.2012.02.022). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer Cell 2012","url":"https://doi.org/10.1016/j.ccr.2012.02.022"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22439926/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/22439926"}],"tags":["europepmc-ingest"],"related":["microenvironment-inflammation-theory"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-cell"],"dependsOn":[],"notes":[],"journal":"Cancer Cell","year":2012,"doi":"10.1016/j.ccr.2012.02.022","pmid":"22439926","authors":"Hanahan D, Coussens LM","paperType":"review","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-fendler-psma-pet-biochemical-recurrence-jama-oncol-2019","kind":"paper","name":"Accuracy of gallium-68 PSMA-11 PET in localising recurrent prostate cancer: a prospective single-arm clinical trial","aka":[],"tldr":"In 635 men whose PSA had started rising again, a PSMA scan found where the cancer was in three quarters of them, and the chance of finding it rose steeply with the PSA level.","summary":"In a single-arm prospective trial at two universities, 635 men with biochemically recurrent prostate cancer after prostatectomy (262, 41%), radiation therapy (169, 27%) or both (204, 32%) underwent gallium-68 PSMA-11 PET, with the presence of prostate cancer recorded by three blinded readers on a per-patient and per-region basis and lesions validated by histopathology and by a composite reference standard. Median age was 69 years. Positive predictive value was 0.84 by histopathological validation in 87 men and 0.92 by the composite reference standard in 217 men. The scan localised recurrent prostate cancer in 475 of 635 men, 75%, and detection rates rose significantly with PSA: 38% below 0.5 ng/mL in 136 men, 57% at 0.5 to under 1.0 in 79, 84% at 1.0 to under 2.0 in 89, 86% at 2.0 to under 5.0 in 158 and 97% at 5.0 or above in 173. Interreader reproducibility was substantial, Fleiss kappa 0.65 to 0.78, and there were no serious adverse events. PET-directed focal therapy alone led to a PSA drop of 50% or more in 31 of 39 men, 80%.","asOf":"2026-09-25","links":[{"label":"Fendler et al., JAMA Oncol 2019: prospective accuracy of gallium-68 PSMA-11 PET in 635 men with biochemically recurrent prostate cancer","url":"https://doi.org/10.1001/jamaoncol.2019.0096"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30920593/"}],"tags":[],"related":[],"cancers":["prostate"],"sections":[],"technologies":["psma-pet","pet-ct"],"targets":["psma"],"drugs":[],"companies":[],"institutions":[],"pathways":["prostate-cancer-signalling"],"terms":["biochemical-recurrence","psa","theranostics"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2019,"doi":"10.1001/jamaoncol.2019.0096","pmid":"30920593","authors":"Fendler WP, Calais J, Eiber M, et al.","paperType":"observational","findings":["Recurrence localised in 475 of 635 men, 75%.","Detection rate 38% below PSA 0.5 ng/mL, rising to 97% at 5.0 or above.","Positive predictive value 0.84 by histopathology and 0.92 by composite reference standard.","PSA fall of at least half in 31 of 39 men treated with PET-directed focal therapy alone."],"whatItMeans":"It is the evidence behind using PSMA PET when PSA rises after treatment, and it quantifies the limit that matters most: below PSA 0.5 ng/mL, where salvage radiotherapy works best, the scan is negative in nearly two men in three, so a negative scan is not a reason to wait.","caveats":["Two academic centres with experienced readers, so performance elsewhere may be lower.","Histopathological validation was available for only 87 of 635 men.","The PSA responses to focal therapy show the scan pointed at real disease, not that focal therapy cures."],"changedPractice":true,"participants":635},{"id":"paper-cheng-science","kind":"paper","name":"Accurate proteome-wide missense variant effect prediction with AlphaMissense","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 37733863 and published in Science; the citing page links this DOI, which is how the record was matched.","summary":"The vast majority of missense variants observed in the human genome are of unknown clinical significance. We present AlphaMissense, an adaptation of AlphaFold fine-tuned on human and primate variant population frequency databases to predict missense variant pathogenicity. By combining structural context and evolutionary conservation, our model achieves state-of-the-art results across a wide range of genetic and experimental benchmarks, all without explicitly training on such data. The average pathogenicity score of genes is also predictive for their cell essentiality, capable of identifying short essential genes that existing statistical approaches are underpowered to detect. As a resource to the community, we provide a database of predictions for all possible human single amino acid substitutions and classify 89% of missense variants as either likely benign or likely pathogenic.\n\nIndexed on Europe PMC as PubMed record 37733863 (DOI 10.1126/science.adg7492). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Science 2023","url":"https://doi.org/10.1126/science.adg7492"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37733863/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37733863"}],"tags":["europepmc-ingest"],"related":["alphamissense"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2023,"doi":"10.1126/science.adg7492","pmid":"37733863","authors":"Cheng J, Novati G, Pan J, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-abramson-nature","kind":"paper","name":"Accurate structure prediction of biomolecular interactions with AlphaFold 3","aka":[],"tldr":"Paper cited by one technology page and one roadmap page, indexed on Europe PMC as PubMed record 38718835 and published in Nature; the citing pages link this DOI, which is how the record was matched.","summary":"The introduction of AlphaFold 2 1 has spurred a revolution in modelling the structure of proteins and their interactions, enabling a huge range of applications in protein modelling and design 2-6. Here we describe our AlphaFold 3 model with a substantially updated diffusion-based architecture that is capable of predicting the joint structure of complexes including proteins, nucleic acids, small molecules, ions and modified residues. The new AlphaFold model demonstrates substantially improved accuracy over many previous specialized tools: far greater accuracy for protein-ligand interactions compared with state-of-the-art docking tools, much higher accuracy for protein-nucleic acid interactions compared with nucleic-acid-specific predictors and substantially higher antibody-antigen prediction accuracy compared with AlphaFold-Multimer v.2.3 7,8. Together, these results show that high-accuracy modelling across biomolecular space is possible within a single unified deep-learning framework.\n\nIndexed on Europe PMC as PubMed record 38718835 (DOI 10.1038/s41586-024-07487-w). Matched by DOI alone: one technology page and one roadmap page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2024","url":"https://doi.org/10.1038/s41586-024-07487-w"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38718835/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38718835"}],"tags":["europepmc-ingest"],"related":["alphafold3","drug-discovery-roadmap"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2024,"doi":"10.1038/s41586-024-07487-w","pmid":"38718835","authors":"Abramson J, Adler J, Dunger J, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page and one roadmap page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-acns0121-ependymoma-conformal-radiotherapy-merchant-jco-2019","kind":"paper","name":"ACNS0121: conformal radiotherapy for paediatric ependymoma, chemotherapy for incompletely resected tumours and observation after complete resection","aka":[],"tldr":"In the largest trial of childhood ependymoma, radiotherapy focused on the tumour bed straight after surgery cured about two thirds of children, worked as well in those under three as in older children, and children whose tumour could not be fully removed fared much worse.","summary":"Children's Oncology Group phase 2 trial of 378 children aged 1 to 21 with newly diagnosed ependymoma, assigned by extent of resection and histology to observation (complete resection of differentiated supratentorial tumours), immediate post-operative conformal radiotherapy (near-total or gross-total resection) or chemotherapy before second surgery and radiotherapy (subtotal resection).\n\nFive-year event-free survival was 68.5 percent after immediate conformal radiotherapy, 61.4 percent with observation and 37.2 percent after subtotal resection. Outcomes differed by tumour grade but not by age, location, RELA fusion or posterior fossa subgroup; 1q gain predicted relapse in infratentorial tumours (five-year event-free survival 47.4 against 82.8 percent).","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2019","url":"https://doi.org/10.1200/JCO.18.01765"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30811284/"}],"tags":[],"related":[],"cancers":["ependymoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["acns0121"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2019,"doi":"10.1200/JCO.18.01765","pmid":"30811284","authors":"Merchant TE, Bendel AE, Sabin ND, et al.","paperType":"observational","findings":["Five-year event-free survival 68.5 percent (95% CI 62.8 to 74.2) with immediate conformal radiotherapy, 61.4 percent with observation, 37.2 percent after subtotal resection.","No difference in event-free survival by age, so children under three benefit from immediate radiotherapy.","1q gain in infratentorial tumours: five-year event-free survival 47.4 versus 82.8 percent (p 0.0013)."],"whatItMeans":"Maximal resection followed by conformal radiotherapy is the mainstay for most childhood ependymoma, including in very young children; incompletely resected tumours need better approaches.","caveats":["Non-randomised assignment by resection status.","The observation arm was small and its confidence interval wide."],"changedPractice":true,"participants":378},{"id":"paper-acns0331-michalski-jco-2021","kind":"paper","name":"ACNS0331: reduced-dose and reduced-volume radiotherapy with chemotherapy for average-risk medulloblastoma","aka":[],"tldr":"Reducing the radiotherapy boost to the tumour bed instead of the whole posterior fossa was safe in average-risk medulloblastoma, but lowering the craniospinal dose from 23.4 to 18 Gy in young children led to more relapses, so the standard dose was kept.","summary":"Children's Oncology Group phase 3 trial of 464 children with average-risk medulloblastoma randomised to involved-field (tumour bed) versus whole posterior fossa boost, and, for children aged 3 to 7, to low-dose (18 Gy) versus standard-dose (23.4 Gy) craniospinal irradiation.\n\nFive-year event-free survival was 82.5 percent with involved-field boost versus 80.5 percent with posterior fossa boost (non-inferior), but 71.4 percent with 18 Gy against 82.9 percent with 23.4 Gy craniospinal irradiation (inferior); WNT tumours did well regardless.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2021","url":"https://doi.org/10.1200/JCO.20.02730"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34110925/"}],"tags":[],"related":[],"cancers":["medulloblastoma-group-3-4","medulloblastoma-wnt"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["acns0331"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2021,"doi":"10.1200/JCO.20.02730","pmid":"34110925","authors":"Michalski JM, Janss AJ, Vezina LG, et al.","paperType":"rct","findings":["Involved-field boost non-inferior: five-year event-free survival 82.5 percent vs 80.5 percent.","18 Gy craniospinal irradiation inferior: 71.4 percent vs 82.9 percent."],"whatItMeans":"Tumour-bed boost is standard in average-risk medulloblastoma, while craniospinal dose reduction is reserved for the WNT-activated subgroup in trials.","caveats":["Molecular subgroup was determined retrospectively.","Neurocognitive outcomes were somewhat better with lower dose, highlighting the trade-off."],"changedPractice":true,"participants":464},{"id":"paper-acns0332-leary-jama-oncol-2021","kind":"paper","name":"ACNS0332: carboplatin during radiotherapy and isotretinoin maintenance in high-risk medulloblastoma","aka":[],"tldr":"Adding daily carboplatin during craniospinal radiotherapy improved event-free survival in children with high-risk group 3 medulloblastoma, but not in other subgroups, while isotretinoin maintenance did not help.","summary":"Children's Oncology Group phase 3 trial of 261 children with high-risk medulloblastoma randomised to 36 Gy craniospinal radiotherapy with or without daily carboplatin, and to maintenance isotretinoin or not (the isotretinoin randomisation was stopped early for futility).\n\nCarboplatin improved five-year event-free survival in group 3 tumours (73.2 versus 53.7 percent) but not overall or in group 4, and molecular subgroup was strongly prognostic.","asOf":"2026-09-17","links":[{"label":"JAMA Oncol 2021","url":"https://doi.org/10.1001/jamaoncol.2021.2224"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34292305/"}],"tags":[],"related":[],"cancers":["medulloblastoma-group-3-4"],"sections":[],"technologies":[],"targets":[],"drugs":["carboplatin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["acns0332"],"people":["sarah-leary"],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2021,"doi":"10.1001/jamaoncol.2021.2224","pmid":"34292305","authors":"Leary SES, Packer RJ, Li Y, et al.","paperType":"rct","findings":["Group 3: five-year event-free survival 73.2 percent with carboplatin vs 53.7 percent without.","No benefit from isotretinoin maintenance."],"whatItMeans":"Carboplatin radiosensitisation is used for high-risk group 3 medulloblastoma, an example of subgroup-directed therapy.","caveats":["Subgroup analysis; overall effect of carboplatin was not significant."],"changedPractice":true,"participants":261},{"id":"paper-acns0333-atrt-high-dose-chemotherapy-reddy-jco-2020","kind":"paper","name":"ACNS0333: high-dose chemotherapy and three-dimensional conformal radiation for atypical teratoid/rhabdoid tumour","aka":[],"tldr":"The first trial designed for atypical teratoid/rhabdoid tumour, a brain cancer of infants, showed that intensive chemotherapy with stem cell rescue and focused radiotherapy cut the risk of relapse or death by more than half compared with how children had been treated before.","summary":"Children's Oncology Group trial ACNS0333: patients from birth to 22 years with atypical teratoid/rhabdoid tumour had surgery, two courses of multi-agent induction chemotherapy, three courses of high-dose chemotherapy with peripheral blood stem cell rescue, and involved-field radiotherapy timed by age and disease extent. SMARCB1 testing was mandatory. The primary analysis compared event-free survival in children under 36 months with a historical cooperative group cohort.\n\nOf 65 evaluable patients, 54 were under 36 months; the regimen significantly reduced the hazard of an event (hazard rate 0.43). Four-year event-free and overall survival for the whole cohort were 37 and 43 percent; 91 percent of relapses occurred within two years and four patients died of treatment.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2020","url":"https://doi.org/10.1200/JCO.19.01776"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32105509/"}],"tags":[],"related":[],"cancers":["atrt"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["acns0333"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/JCO.19.01776","pmid":"32105509","authors":"Reddy AT, Strother DR, Judkins AR, et al.","paperType":"observational","findings":["Hazard rate for an event 0.43 (95% CI 0.28 to 0.66; p < 0.0005) against the historical cohort in children under 36 months.","Four-year event-free survival 37 percent (95% CI 25 to 49) and overall survival 43 percent (31 to 55).","Timing of radiotherapy did not affect survival; four treatment-related deaths."],"whatItMeans":"ACNS0333 established the treatment backbone for atypical teratoid/rhabdoid tumour and the platform on which new agents are being tested.","caveats":["Non-randomised comparison with historical controls.","Molecular subgroup and clinical features suggest prognostic differences that the trial was not powered to test."],"changedPractice":true,"participants":65},{"id":"paper-acns1123-nggct-reduced-radiotherapy-fangusaro-jco-2019","kind":"paper","name":"ACNS1123: response-based reduced radiotherapy for localised CNS non-germinomatous germ cell tumours","aka":[],"tldr":"Children whose non-germinomatous germ cell tumour of the brain responded to chemotherapy did well with radiotherapy limited to the ventricles rather than the whole brain and spine, but the few who relapsed all relapsed in the spine, so the smaller field carries a specific risk.","summary":"Children's Oncology Group phase 2 trial: 107 patients aged 3 to 21 with localised non-germinomatous germ cell tumours received six cycles of carboplatin, etoposide and ifosfamide; the 66 with a complete or partial response received 30.6 Gy whole-ventricular irradiation with a boost to 54 Gy instead of craniospinal irradiation.\n\nThree-year progression-free survival was 87.8 percent and overall survival 92.4 percent, compared with 92 and 94.1 percent in ACNS0122 with full-dose craniospinal irradiation. Ten recurrences prompted early closure; on central review eight of 66 reduced-radiotherapy patients progressed, six with isolated spinal relapse and two with combined local and spinal relapse.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2019","url":"https://doi.org/10.1200/JCO.19.00701"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31545689/"}],"tags":[],"related":[],"cancers":["cns-germ-cell-tumours","paediatric-germ-cell-tumours"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["acns1123","acns0122"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2019,"doi":"10.1200/JCO.19.00701","pmid":"31545689","authors":"Fangusaro J, Wu S, MacDonald S, et al.","paperType":"observational","findings":["66 of 107 patients (61.7 percent) reached a complete or partial response and proceeded to reduced radiotherapy.","Three-year progression-free survival 87.8 percent and overall survival 92.4 percent, against 92 and 94.1 percent in ACNS0122.","All eight relapses after reduced radiotherapy involved the spine."],"whatItMeans":"Whole-ventricular irradiation with a boost is a reasonable option after a good response to chemotherapy, but the spinal failure pattern shaped the next trial and keeps craniospinal irradiation as an alternative.","caveats":["Single-arm comparison with a historical trial; the stratum closed early after recurrences.","Tumour markers did not predict progression."],"changedPractice":true,"participants":107},{"id":"paper-acns1123-germinoma-neuro-oncology-2022","kind":"paper","name":"ACNS1123: response-based reduced-dose whole-ventricular radiotherapy for localised germinoma","aka":[],"tldr":"In children with localised germinoma who responded completely to chemotherapy, lowering the whole-ventricular radiotherapy dose to 18 Gy kept cure rates above 90 percent, allowing less radiation to the developing brain.","summary":"Children's Oncology Group phase 2 trial of 137 patients with localised germinoma treated with carboplatin and etoposide induction; complete responders received reduced-dose whole-ventricular irradiation (18 Gy) with a 12 Gy boost, while partial responders received 24 Gy plus boost.\n\nThree-year progression-free survival was 94.5 percent in the reduced-dose group and overall survival 100 percent, with the trial meeting its goal of maintaining outcomes with less radiation.","asOf":"2026-09-17","links":[{"label":"Neuro Oncol 2022","url":"https://doi.org/10.1093/neuonc/noab270"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34850169/"}],"tags":[],"related":[],"cancers":["cns-germ-cell-tumours"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["neuro-oncology"],"dependsOn":[],"notes":[],"journal":"Neuro-Oncology","year":2022,"doi":"10.1093/neuonc/noab270","pmid":"34850169","authors":"Bartels U, Onar-Thomas A, Patel SK, et al.","paperType":"observational","findings":["Three-year progression-free survival 94.5 percent with 18 Gy whole-ventricular irradiation after complete response.","Overall survival 100 percent."],"whatItMeans":"Response-adapted, reduced-dose whole-ventricular radiotherapy after chemotherapy is now a standard for localised germinoma in North American protocols.","caveats":["Single-arm trial; late neurocognitive outcomes are still being followed.","The non-germinomatous stratum of the same trial had a different, less favourable result."],"changedPractice":true,"participants":137},{"id":"paper-thress-nat-med","kind":"paper","name":"Acquired EGFR C797S mutation mediates resistance to AZD9291 in non-small cell lung cancer harboring EGFR T790M","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 25939061 and published in Nature Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Here we studied cell-free plasma DNA (cfDNA) collected from subjects with advanced lung cancer whose tumors had developed resistance to the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) AZD9291. We first performed next-generation sequencing of cfDNA from seven subjects and detected an acquired EGFR C797S mutation in one; expression of this mutant EGFR construct in a cell line rendered it resistant to AZD9291. We then performed droplet digital PCR on serial cfDNA specimens collected from 15 AZD9291-treated subjects. All were positive for the T790M mutation before treatment, but upon developing AZD9291 resistance three molecular subtypes emerged: six cases acquired the C797S mutation, five cases maintained the T790M mutation but did not acquire the C797S mutation and four cases lost the T790M mutation despite the presence of the underlying EGFR activating mutation. Our findings provide insight into the diversity of mechanisms through which tumors acquire resistance to AZD9291 and highlight the need for therapies that are able to overcome resistance mediated by the EGFR C797S mutation.\n\nIndexed on Europe PMC as PubMed record 25939061 (DOI 10.1038/nm.3854). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Med 2015","url":"https://doi.org/10.1038/nm.3854"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25939061/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25939061"}],"tags":["europepmc-ingest"],"related":["c797s","egfr-c797s","egfr-t790m"],"cancers":["nsclc"],"sections":[],"technologies":["liquid-biopsy","cgp"],"targets":["egfr"],"drugs":[],"companies":[],"institutions":[],"pathways":["resistance-routes-map","rtk-activation"],"terms":["resistance","egfr-mutation-subtypes","ctdna"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2015,"doi":"10.1038/nm.3854","pmid":"25939061","authors":"Thress KS, Paweletz CP, Felip E, et al.","paperType":"basic","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-pao-egfr-t790m-acquired-resistance-plos-med-2005","kind":"paper","name":"Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain","aka":[],"tldr":"Published within weeks of the single-patient report, this study found the same resistance change in several more patients and showed it was not there before treatment, so the drug had selected it.","summary":"In two of five patients with acquired resistance to gefitinib or erlotinib, the progressing tumours contained, in addition to a primary drug-sensitive EGFR mutation, a secondary mutation in exon 20 leading to substitution of methionine for threonine at position 790. Tumour cells from a sixth patient with a drug-sensitive mutation whose tumour progressed on adjuvant gefitinib after complete resection also contained T790M. The mutation was not detected in untreated tumour samples. No tumour with acquired resistance carried a KRAS mutation. Biochemical analyses of transfected cells and growth inhibition studies in lung cancer cell lines showed that T790M confers resistance to EGFR mutants otherwise sensitive to either drug. An analogous mutation had been observed in another kinase with acquired resistance to imatinib.","asOf":"2026-09-25","links":[{"label":"Pao et al., PLoS Med 2005: a second EGFR kinase-domain mutation in lung adenocarcinomas with acquired resistance to gefitinib or erlotinib","url":"https://doi.org/10.1371/journal.pmed.0020073"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/15737014/"}],"tags":[],"related":["egfr-t790m"],"cancers":["nsclc"],"sections":[],"technologies":[],"targets":["egfr","kras"],"drugs":["gefitinib","erlotinib"],"companies":[],"institutions":["mskcc"],"pathways":["rtk-activation","resistance-routes-map","clonal-evolution"],"terms":["resistance","egfr-mutation-subtypes"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["plos-medicine"],"dependsOn":[],"notes":[],"journal":"PLOS Medicine","year":2005,"doi":"10.1371/journal.pmed.0020073","pmid":"15737014","authors":"Pao W, Miller VA, Politi KA, et al.","paperType":"translational","findings":["T790M found in resistant tumours from three of six patients and absent from untreated samples.","No KRAS mutations in the resistant tumours, distinguishing acquired from primary resistance.","Cell line work confirmed the mutation confers resistance.","The gatekeeper position parallels imatinib resistance in another kinase."],"whatItMeans":"It generalised the single-patient finding and made the point that drug-resistant subclones are selected by treatment rather than created by it, which is the model the whole field now works with.","caveats":["Six patients.","Detection methods of the time could not exclude pre-existing low-frequency T790M.","Only tumours that could be rebiopsied were studied, which selects for accessible disease."],"changedPractice":true,"participants":6},{"id":"paper-act-ii-anal-cancer-chemoradiation-lancet-oncol-2013","kind":"paper","name":"ACT II: mitomycin or cisplatin chemoradiation with or without maintenance chemotherapy for squamous cell carcinoma of the anus","aka":[],"tldr":"The largest anal cancer trial ever run found that swapping mitomycin for cisplatin during radiotherapy did not help, that extra chemotherapy afterwards added nothing, and that tumours keep shrinking for months, so the decision to operate should wait until 26 weeks.","summary":"Randomised 2 by 2 factorial phase 3 trial of 940 patients with anal squamous cell carcinoma treated with radiotherapy (50.4 Gy in 28 fractions) plus fluorouracil, comparing concurrent mitomycin with cisplatin, and two cycles of maintenance cisplatin and fluorouracil with no maintenance.\n\nComplete response rates at 26 weeks were about 90 percent in both chemotherapy arms and three-year progression-free survival was about 74 percent with and without maintenance. Because many tumours that had not fully responded at 11 weeks had done so by 26 weeks, the trial changed the timing of response assessment before salvage surgery.","asOf":"2026-09-18","links":[{"label":"Lancet Oncol 2013","url":"https://doi.org/10.1016/S1470-2045(13)70086-X"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23578724/"}],"tags":[],"related":[],"cancers":["localised-anal-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["fluorouracil","mitomycin","cisplatin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["act-ii"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2013,"doi":"10.1016/S1470-2045(13)70086-X","pmid":"23578724","authors":"James RD, Glynne-Jones R, Meadows HM, et al.","paperType":"rct","findings":["Complete response at 26 weeks in about 90 percent of patients whether mitomycin or cisplatin was given with fluorouracil.","Maintenance chemotherapy did not improve three-year progression-free survival (about 74 versus 73 percent).","Complete response rates rose from about 64 percent at 11 weeks to about 85 percent at 26 weeks in the same patients."],"whatItMeans":"Fluorouracil and mitomycin with radiotherapy remains the standard for localised anal cancer, without maintenance, and patients whose tumour has not vanished at three months should be watched to six months rather than sent straight to surgery.","caveats":["Radiotherapy was two-dimensional or three-dimensional rather than intensity-modulated, and used a single dose for all stages.","Open-label design; the co-primary endpoint of complete response used clinical assessment."],"changedPractice":true,"participants":940},{"id":"paper-actg-a5263-kaposi-sarcoma-resource-limited-krown-lancet-2020","kind":"paper","name":"ACTG A5263/AMC 066: three chemotherapy regimens with antiretroviral therapy for advanced AIDS-associated Kaposi sarcoma in resource-limited settings","aka":[],"tldr":"For people with HIV and advanced Kaposi sarcoma in Africa and Brazil, paclitaxel with antiretroviral therapy kept far more patients free of progression at a year than either oral etoposide or bleomycin with vincristine, both of which were stopped early for being worse.","summary":"Three-arm open-label randomised non-inferiority trial in 334 adults with advanced AIDS-associated Kaposi sarcoma at sites in Kenya, Malawi, South Africa, Uganda, Zimbabwe and Brazil, randomised to antiretroviral therapy with paclitaxel, oral etoposide, or bleomycin plus vincristine. The primary endpoint was progression-free survival at week 48.\n\nThe etoposide arm closed for inferiority in 2016 and the bleomycin-vincristine arm in 2018. Week-48 progression-free survival was 50 percent with paclitaxel against 20 percent with etoposide (difference -30 percentage points, 95% CI -52 to -8) and 64 percent against 44 percent with bleomycin-vincristine (difference -20, 95% CI -33 to -7). Adverse events were similar across arms.","asOf":"2026-09-22","links":[{"label":"Lancet 2020","url":"https://doi.org/10.1016/S0140-6736(19)33222-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32145827/"}],"tags":[],"related":[],"cancers":["kaposi-sarcoma"],"sections":[],"technologies":[],"targets":[],"drugs":["paclitaxel","etoposide","bleomycin","vincristine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["actg-a5263"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2020,"doi":"10.1016/S0140-6736(19)33222-2","pmid":"32145827","authors":"Krown SE, Moser CB, MacPhail P, et al.","paperType":"rct","findings":["Week-48 progression-free survival 50 percent with paclitaxel versus 20 percent with etoposide (difference -30 percentage points, 95% CI -52 to -8).","Week-48 progression-free survival 64 percent with paclitaxel versus 44 percent with bleomycin plus vincristine (difference -20, 95% CI -33 to -7).","Both investigational arms closed early for inferiority; neutropenia, low albumin, weight loss and anaemia were the common adverse events."],"whatItMeans":"Paclitaxel with antiretroviral therapy is the treatment to supply for advanced AIDS-associated Kaposi sarcoma in resource-limited settings; cheaper regimens are inferior.","caveats":["Open-label; the non-inferiority margins were not met rather than superiority being the design."],"changedPractice":true,"participants":334},{"id":"paper-parsons-j-clin-oncol","kind":"paper","name":"Actionable Tumor Alterations and Treatment Protocol Enrollment of Pediatric and Young Adult Patients With Refractory Cancers in the National Cancer Institute-Children's Oncology Group Pediatric MATCH Trial","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 35353553 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: The National Cancer Institute-Children's Oncology Group Pediatric MATCH trial aimed to facilitate evaluation of molecular-targeted therapies in biomarker-selected cohorts of childhood and young adult patients with cancer by screening tumors for actionable alterations.\n\nPatients and methods: Tumors from patients age 1-21 years with refractory solid tumors, lymphomas, or histiocytic disorders were subjected to cancer gene panel sequencing and limited immunohistochemistry to identify actionable alterations for assignment to phase II treatment arms. The rates of treatment arm assignment and enrollment were compared between clinical and demographic groups.\n\nResults: Testing was completed for 94.7% of tumors submitted. Actionable alterations were detected in 31.5% of the first 1,000 tumors screened, with treatment arm assignment and enrollment occurring in 28.4% and 13.1% of patients, respectively. Assignment rates varied by tumor histology and were higher for patients with CNS tumors or enrolled at Pediatric Early Phase Clinical Trials Network sites. A reported history of prior clinical molecular testing was associated with higher assignment and enrollment rates. Actionable alterations in the mitogen-activated protein kinase signaling pathway were most frequent (11.2%). The most common reasons provided for not enrolling on treatment arms were patients receiving other treatment or poor clinical status.\n\nConclusion: The Pediatric MATCH trial has proven the feasibility of a nationwide screening Protocol for identification of actionable genetic alterations and assignment of pediatric and young adult patients with refractory cancers to trials of molecularly targeted therapies. These data support the early use of tumor molecular screening for childhood patients with cancer whose tumors have not responded to standard treatments.\n\nIndexed on Europe PMC as PubMed record 35353553 (DOI 10.1200/jco.21.02838). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2022","url":"https://doi.org/10.1200/jco.21.02838"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35353553/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35353553"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["pediatric-match"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2022,"doi":"10.1200/jco.21.02838","pmid":"35353553","authors":"Parsons DW, Janeway KA, Patton DR, et al.","paperType":"observational","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-durham-nat-med","kind":"paper","name":"Activating mutations in CSF1R and additional receptor tyrosine kinases in histiocytic neoplasms","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 31768065 and published in Nature Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Histiocytoses are clonal hematopoietic disorders frequently driven by mutations mapping to the BRAF and MEK1 and MEK2 kinases. Currently, however, the developmental origins of histiocytoses in patients are not well understood, and clinically meaningful therapeutic targets outside of BRAF and MEK are undefined. In this study, we uncovered activating mutations in CSF1R and rearrangements in RET and ALK that conferred dramatic responses to selective inhibition of RET (selpercatinib) and crizotinib, respectively, in patients with histiocytosis.\n\nIndexed on Europe PMC as PubMed record 31768065 (DOI 10.1038/s41591-019-0653-6). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Med 2019","url":"https://doi.org/10.1038/s41591-019-0653-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31768065/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31768065"}],"tags":["europepmc-ingest"],"related":["histiocytoses"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2019,"doi":"10.1038/s41591-019-0653-6","pmid":"31768065","authors":"Durham BH, Lopez Rodrigo E, Picarsic J, et al.","paperType":"observational","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-lynch-egfr-activating-mutations-gefitinib-nejm-2004","kind":"paper","name":"Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib","aka":[],"tldr":"A drug that worked spectacularly in about one patient in ten and did nothing in the rest. Sequencing the tumours of nine responders found the answer: eight of them had a mutation in the gene the drug targets.","summary":"Lynch, Bell, Sordella and colleagues at Massachusetts General Hospital, with Haber as senior author, searched for mutations in EGFR in primary tumours from patients who had responded to gefitinib, patients who had not, and patients never exposed to it, then expressed the mutant proteins in cultured cells to test their function.\n\nIt appeared on the same day as Paez and colleagues' independent report in Science (paper-paez-egfr-mutations-gefitinib-science-2004). Together they are the founding papers of precision oncology in solid tumours: not a new drug, but an explanation of why an existing drug worked in a minority, which converted a failure into a triumph by changing who received it.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2004","url":"https://doi.org/10.1056/NEJMoa040938"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/15118073/"}],"tags":["lung-evidence"],"related":["paper-paez-egfr-mutations-gefitinib-science-2004","paper-mok-ipass-gefitinib-pulmonary-adenocarcinoma-nejm-2009","paper-kobayashi-egfr-t790m-gefitinib-resistance-nejm-2005","targeted-therapy-roadmap"],"cancers":["lung-cancer","nsclc","egfr-mutant-nsclc","lung-adenocarcinoma"],"sections":["targeted-therapy","diagnostics"],"technologies":["ngs"],"targets":["egfr"],"drugs":["gefitinib","erlotinib"],"companies":[],"institutions":["mgh"],"pathways":["ras-mapk","pi3k-akt-mtor"],"terms":["driver-mutation","oncogene-addiction"],"trials":[],"people":["thomas-lynch","lecia-sequist"],"bottlenecks":["b-biomarker-validation","b-undruggable-targets","b-translational-valley"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2004,"doi":"10.1056/NEJMoa040938","pmid":"15118073","authors":"Lynch TJ, Bell DW, Sordella R, et al.","paperType":"translational","findings":["Somatic mutations in the tyrosine kinase domain of EGFR were identified in eight of nine patients with gefitinib-responsive lung cancer and in none of the seven patients with no response.","The mutations led to increased growth factor signalling and conferred susceptibility to the inhibitor when the mutant proteins were expressed in cultured cells.","The authors conclude that screening for such mutations may identify the patients who will respond."],"whatItMeans":"The template for every driver mutation since: find the responders, sequence them, and give the drug only to people whose tumour carries the lesion it was built for. Gefitinib had been close to abandonment on the strength of unselected trials.","caveats":["Sixteen patients in the response comparison; the effect size was obvious but the sample was tiny.","It predicts response, not survival: the randomised evidence that selecting by mutation improves outcomes came five years later with IPASS.","The same mutations that confer sensitivity set up the T790M resistance mutation described the following year."],"changedPractice":true},{"id":"paper-comet-dcis-jama-2025","kind":"paper","name":"Active Monitoring With or Without Endocrine Therapy for Low-Risk Ductal Carcinoma In Situ: The COMET Randomized Clinical Trial","aka":[],"tldr":"Published report from the COMET trial registered as NCT02926911, in JAMA (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Importance: Active monitoring for low-risk ductal carcinoma in situ (DCIS) of the breast has been proposed as an alternative to guideline-concordant care, but the safety of this approach is unknown.\n\nObjective: To compare rates of invasive cancer in patients with low-risk DCIS receiving active monitoring vs guideline-concordant care.\n\nDesign, setting, and participants: Prospective, randomized noninferiority trial enrolling 995 women aged 40 years or older with a new diagnosis of hormone receptor-positive grade 1 or grade 2 DCIS without invasive cancer at 100 US Alliance Cancer Cooperative Group clinical trial sites from 2017 to 2023.\n\nInterventions: Participants were randomized to receive active monitoring (follow-up every 6 months with breast imaging and physical examination; n = 484) or guideline-concordant care (surgery with or without radiation therapy; n = 473).\n\nMain outcomes and measures: The primary outcome was 2-year cumulative risk of ipsilateral invasive cancer diagnosis, according to planned intention-to-treat and per-protocol analyses, with a noninferiority bound of 5%.\n\nResults: The median age of the 957 participants analyzed was 63.6 (95% CI, 55.5-70.5) years in the guideline-concordant care group and 63.7 (95% CI, 60.0-71.6) years in the active monitoring group. Overall, 15.7% of participants were Black and 75.0% were White. In this prespecified primary analysis, median follow-up was 36.9 months; 346 patients had surgery for DCIS, 264 in the guideline-concordant care group and 82 in the active monitoring group. Forty-six women were diagnosed with invasive cancer, 19 in the active monitoring group and 27 in the guideline-concordant care group. The 2-year Kaplan-Meier cumulative rate of ipsilateral invasive cancer was 4.2% in the active monitoring group vs 5.9% in the guideline-concordant care group, a difference of -1.7% (upper limit of the 95% CI, 0.95%), indicating that active monitoring is not inferior to guideline-concordant care. Invasive tumor characteristics did not differ significantly between groups.\n\nConclusions and relevance: Women with low-risk DCIS randomized to active monitoring did not have a higher rate of invasive cancer in the same breast at 2 years compared with those randomized to guideline-concordant care.\n\nTrial registration: ClinicalTrials.gov Identifier: NCT02926911.\n\nIndexed on Europe PMC as PubMed record 39665585 (DOI 10.1001/jama.2024.26698). Its abstract cites the registry id NCT02926911, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"JAMA 2025","url":"https://doi.org/10.1001/jama.2024.26698"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39665585/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39665585"},{"label":"ClinicalTrials.gov NCT02926911","url":"https://clinicaltrials.gov/study/NCT02926911"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["comet-dcis"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2025,"doi":"10.1001/jama.2024.26698","pmid":"39665585","authors":"Hwang ES, Hyslop T, Lynch T, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02926911 with the most citations, so it is the natural first reading for anyone following the COMET trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-timbergen-eur-j-cancer","kind":"paper","name":"Active surveillance in desmoid-type fibromatosis: A systematic literature review","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 32738571 and published in European Journal of Cancer; the citing page links this DOI, which is how the record was matched.","summary":"Background: This study evaluates the results of the active surveillance (AS) approach in adult patients with desmoid-type fibromatosis (DTF) because AS is advocated as a front-line approach for DTF in the European consensus guidelines.\n\nMethods: A systematic literature search was conducted (December 19th, 2019, updated on April 14th, 2020). Studies describing the outcomes of the AS approach were included. The PRISMA guidelines were used.\n\nResults: Twenty-five articles were included for data retrieval. Forty-two percent of reported patients (1480 of 3527 patients) received AS, the majority were women and the majority had a primary tumour. The median age at diagnosis ranged from 28 to 59 years. Common tumour sites were the extremities/girdles (n = 273), the abdominal wall (n = 253) and the trunk (n = 153). The median reported percentage of progressive disease, stable disease and partial response was 20% (interquartile range [IQR]: 13-35%), 59% (IQR: 37-69%) and 19% (IQR 3-23%), respectively. In 640 patients, the outcome was not specified. The median reported percentage of shifting to an active form of treatment was 29%, most commonly to systemic treatment (n = 195) and surgery (n = 107). The reported median follow-up time ranged between 8 and 73 months. The reported median time to progression and/or initiation of the subgroup shifting from AS to 'active' therapy ranged from 6.3 months to 19.7 months.\n\nConclusion: The majority of patients undergoing AS have either stable disease or a partial response, and about one-third of patients shift to an active form of treatment. Selecting patients who will benefit from active surveillance upfront should be the priority of future studies.\n\nIndexed on Europe PMC as PubMed record 32738571 (DOI 10.1016/j.ejca.2020.06.022). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Eur J Cancer 2020","url":"https://doi.org/10.1016/j.ejca.2020.06.022"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32738571/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32738571"}],"tags":["europepmc-ingest"],"related":["desmoid-tumour"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["european-journal-of-cancer"],"dependsOn":[],"notes":[],"journal":"European Journal of Cancer","year":2020,"doi":"10.1016/j.ejca.2020.06.022","pmid":"32738571","authors":"Timbergen MJM, Schut AW, Grünhagen DJ, et al.","paperType":"review","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-ito-kuma-active-surveillance-microcarcinoma-thyroid-2014","kind":"paper","name":"Active surveillance of papillary thyroid microcarcinoma at Kuma Hospital: patient age and progression","aka":[],"tldr":"Following more than 1,200 patients with small papillary thyroid cancers under observation, the Kuma Hospital group found that only 8 percent grew and under 4 percent developed node metastases over ten years, with the lowest risk in older patients, establishing surveillance as a safe alternative to surgery.","summary":"Prospective observational cohort of 1,235 patients with low-risk papillary thyroid microcarcinoma managed by active surveillance between 1993 and 2011, analysing tumour enlargement and nodal metastasis by age.\n\nTen-year rates of tumour enlargement of 3 mm or more and of new node metastases were 8.0 and 3.8 percent; progression was most frequent in patients under 40 and rarest in those over 60, and no patient died of thyroid cancer or developed distant metastases.","asOf":"2026-09-17","links":[{"label":"Thyroid 2014","url":"https://doi.org/10.1089/thy.2013.0367"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24001104/"}],"tags":[],"related":[],"cancers":["papillary-thyroid-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Thyroid","year":2014,"doi":"10.1089/thy.2013.0367","pmid":"24001104","authors":"Ito Y, Miyauchi A, Kihara M, et al.","paperType":"observational","findings":["Ten-year tumour enlargement 8.0 percent; nodal metastasis 3.8 percent.","Progression more frequent under 40 (about 22 percent at ten years) than over 60 (about 3 percent)."],"whatItMeans":"Active surveillance is a guideline-endorsed option for papillary microcarcinoma, adopted in Japan, the United States and elsewhere, especially for older patients.","caveats":["Single-centre Japanese cohort with expert ultrasound; selection excluded tumours near the trachea or nerve."],"changedPractice":true,"participants":1235},{"id":"paper-sirolimus-ehe-stacchiotti-cancer-2021","kind":"paper","name":"Activity of sirolimus in progressive epithelioid haemangioendothelioma (Italian Rare Cancer Network)","aka":[],"tldr":"In patients with progressing epithelioid haemangioendothelioma, the mTOR inhibitor sirolimus stabilised the disease in most, with a median progression-free survival of about a year, but did not help patients who had developed serosal effusions.","summary":"Retrospective case series of 38 patients with progressive epithelioid haemangioendothelioma treated with sirolimus within the Italian Rare Cancer Network.\n\nBest response was partial response in 11 percent and stable disease in 71 percent, with median progression-free survival of 13 months and median overall survival of 19 months in patients with serosal effusions against not reached in those without.","asOf":"2026-09-17","links":[{"label":"Cancer 2021","url":"https://doi.org/10.1002/cncr.33247"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33107985/"}],"tags":[],"related":[],"cancers":["epithelioid-haemangioendothelioma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-wiley"],"dependsOn":[],"notes":[],"journal":"Cancer","year":2021,"doi":"10.1002/cncr.33247","pmid":"33107985","authors":"Stacchiotti S, Simeone N, Lo Vullo S, et al.","paperType":"observational","findings":["Partial response 11 percent; stable disease 71 percent; median progression-free survival 13 months.","Poor outcome with serosal effusions."],"whatItMeans":"Sirolimus is the first-choice systemic therapy for progressing EHE, ideally started before pleural or peritoneal effusions develop.","caveats":["Retrospective series without a comparator."],"changedPractice":true,"participants":38},{"id":"paper-ezzo-cochrane-database-syst-rev","kind":"paper","name":"Acupuncture-point stimulation for chemotherapy-induced nausea or vomiting","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 16625560 and published in The Cochrane database of systematic reviews; the citing page links this DOI, which is how the record was matched.","summary":"Background: There have been recent advances in chemotherapy-induced nausea and vomiting using 5-HT(3) inhibitors and dexamethasone. However, many still experience these symptoms, and expert panels encourage additional methods to reduce these symptoms.\n\nObjectives: The objective was to assess the effectiveness of acupuncture-point stimulation on acute and delayed chemotherapy-induced nausea and vomiting in cancer patients.\n\nSearch strategy: We searched MEDLINE, EMBASE, PsycLIT, MANTIS, Science Citation Index, CCTR (Cochrane Controlled Trials Registry), Cochrane Complementary Medicine Field Trials Register, Cochrane Pain, Palliative Care and Supportive Care Specialized Register, Cochrane Cancer Specialized Register, and conference abstracts.\n\nSelection criteria: Randomized trials of acupuncture-point stimulation by any method (needles, electrical stimulation, magnets, or acupressure) and assessing chemotherapy-induced nausea or vomiting, or both.\n\nData collection and analysis: Data were provided by investigators of the original trials and pooled using a fixed effect model. Relative risks were calculated on dichotomous data. Standardized mean differences were calculated for nausea severity. Weighted mean differences were calculated for number of emetic episodes.\n\nMain results: Eleven trials (N = 1247) were pooled. Overall, acupuncture-point stimulation of all methods combined reduced the incidence of acute vomiting (RR = 0.82; 95% confidence interval 0.69 to 0.99; P = 0.04), but not acute or delayed nausea severity compared to control. By modality, stimulation with needles reduced proportion of acute vomiting (RR = 0.74; 95% confidence interval 0.58 to 0.94; P = 0.01), but not acute nausea severity. Electroacupuncture reduced the proportion of acute vomiting (RR = 0.76; 95% confidence interval 0.60 to 0.97; P = 0.02), but manual acupuncture did not; delayed symptoms for acupuncture were not reported. Acupressure reduced mean acute nausea severity (SMD = -0.19; 95% confidence interval -0.37 to -0.01; P = 0.04) but not acute vomiting or delayed symptoms. Noninvasive electrostimulation showed no benefit for any outcome. All trials used concomitant pharmacologic antiemetics, and all, except electroacupuncture trials, used state-of-the-art antiemetics.\n\nAuthors' conclusions: This review complements data on post-operative nausea and vomiting suggesting a biologic effect of acupuncture-point stimulation. Electroacupuncture has demonstrated benefit for chemotherapy-induced acute vomiting, but studies combining electroacupuncture with state-of-the-art antiemetics and in patients with refractory symptoms are needed to determine clinical relevance. Self-administered acupressure appears to have a protective effect for acute nausea and can readily be taught to patients though studies did not involve placebo control. Noninvasive electrostimulation appears unlikely to have a clinically relevant impact when patients are given state-of-the-art pharmacologic antiemetic therapy.\n\nIndexed on Europe PMC as PubMed record 16625560 (DOI 10.1002/14651858.cd002285.pub2). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cochrane Database Syst Rev 2006","url":"https://doi.org/10.1002/14651858.cd002285.pub2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/16625560/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/16625560"}],"tags":["europepmc-ingest"],"related":["acupuncture-nausea"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Cochrane database of systematic reviews","year":2006,"doi":"10.1002/14651858.cd002285.pub2","pmid":"16625560","authors":"Ezzo JM, Richardson MA, Vickers A, et al.","paperType":"meta-analysis","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-hunger-mullighan-all-children-nejm-2015","kind":"paper","name":"Acute lymphoblastic leukaemia in children (review)","aka":[],"tldr":"This review summarises how childhood acute lymphoblastic leukaemia became curable in nine of ten children through risk-adapted chemotherapy, and how genomic subtypes such as Ph-like and infant leukaemia are shaping the next generation of targeted treatment.","summary":"Review of the epidemiology, genomic classification (including Ph-like ALL, IKZF1 alterations, KMT2A rearrangements, hypodiploidy), risk stratification by measurable residual disease, treatment phases, outcomes approaching 90 percent survival, late effects, relapse and emerging immunotherapies for childhood ALL.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2015","url":"https://doi.org/10.1056/NEJMra1400972"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26465987/"}],"tags":[],"related":[],"cancers":["all-paediatric-high-risk","all-ph-like","all-infant"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2015,"doi":"10.1056/NEJMra1400972","pmid":"26465987","authors":"Hunger SP, Mullighan CG.","paperType":"review","findings":[],"whatItMeans":"The structure of the paediatric ALL subtype pages, from risk groups to new targeted and immune therapies, follows the framework in this review.","caveats":["Predates blinatumomab and CAR-T results in frontline therapy."],"changedPractice":false},{"id":"paper-dohner-n-engl-j-med","kind":"paper","name":"Acute Myeloid Leukemia","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 26376137 and published in New England Journal of Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 26376137 (DOI 10.1056/nejmra1406184). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2015","url":"https://doi.org/10.1056/nejmra1406184"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26376137/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26376137"}],"tags":["europepmc-ingest"],"related":["aml-signalling"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2015,"doi":"10.1056/nejmra1406184","pmid":"26376137","authors":"Döhner H, Weisdorf DJ, Bloomfield CD","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nct03785249-n-engl-j-med-2022","kind":"paper","name":"Adagrasib in Non-Small-Cell Lung Cancer Harboring a KRAS G12C Mutation","aka":[],"tldr":"Published report from the Phase 1 trial registered as NCT03785249, in New England Journal of Medicine (2022), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Adagrasib, a KRAS G12C inhibitor, irreversibly and selectively binds KRAS G12C, locking it in its inactive state. Adagrasib showed clinical activity and had an acceptable adverse-event profile in the phase 1-1b part of the KRYSTAL-1 phase 1-2 study.\n\nMethods: In a registrational phase 2 cohort, we evaluated adagrasib (600 mg orally twice daily) in patients with KRAS G12C -mutated non-small-cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy and anti-programmed death 1 or programmed death ligand 1 therapy. The primary end point was objective response assessed by blinded independent central review. Secondary end points included the duration of response, progression-free survival, overall survival, and safety.\n\nResults: at October 15, 2021, a total of 116 patients with KRAS G12C -mutated NSCLC had been treated (median follow-up, 12.9 months); 98.3% had previously received both chemotherapy and immunotherapy. Of 112 patients with measurable disease at baseline, 48 (42.9%) had a confirmed objective response. The median duration of response was 8.5 months (95% confidence interval [CI], 6.2 to 13.8), and the median progression-free survival was 6.5 months (95% CI, 4.7 to 8.4). at January 15, 2022 (median follow-up, 15.6 months), the median overall survival was 12.6 months (95% CI, 9.2 to 19.2). Among 33 patients with previously treated, stable central nervous system metastases, the intracranial confirmed objective response rate was 33.3% (95% CI, 18.0 to 51.8). Treatment-related adverse events occurred in 97.4% of the patients - grade 1 or 2 in 52.6% and grade 3 or higher in 44.8% (including two grade 5 events) - and resulted in drug discontinuation in 6.9% of patients.\n\nConclusions: In patients with previously treated KRAS G12C -mutated NSCLC, adagrasib showed clinical efficacy without new safety signals. (Funded by Mirati Therapeutics; ClinicalTrials.gov number, NCT03785249.).\n\nIndexed on Europe PMC as PubMed record 35658005 (DOI 10.1056/nejmoa2204619). Its abstract cites the registry id NCT03785249, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2022","url":"https://doi.org/10.1056/nejmoa2204619"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35658005/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35658005"},{"label":"ClinicalTrials.gov NCT03785249","url":"https://clinicaltrials.gov/study/NCT03785249"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct03785249"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/nejmoa2204619","pmid":"35658005","authors":"Jänne PA, Riely GJ, Gadgeel SM, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03785249 with the most citations, so it is the natural first reading for anyone following the Phase 1 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-alexander-clin-cancer-res","kind":"paper","name":"Adaptive Global Innovative Learning Environment for Glioblastoma: GBM AGILE","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 28814435 and published in Clinical Cancer Research; the citing page links this DOI, which is how the record was matched.","summary":"Glioblastoma (GBM) is a deadly disease with few effective therapies. Although much has been learned about the molecular characteristics of the disease, this knowledge has not been translated into clinical improvements for patients. At the same time, many new therapies are being developed. Many of these therapies have potential biomarkers to identify responders. The result is an enormous amount of testable clinical questions that must be answered efficiently. The GBM Adaptive Global Innovative Learning Environment (GBM AGILE) is a novel, multi-arm, platform trial designed to address these challenges. It is the result of the collective work of over 130 oncologists, statisticians, pathologists, neurosurgeons, imagers, and translational and basic scientists from around the world. GBM AGILE is composed of two stages. The first stage is a Bayesian adaptively randomized screening stage to identify effective therapies based on impact on overall survival compared with a common control. This stage also finds the population in which the therapy shows the most promise based on clinical indication and biomarker status. Highly effective therapies transition in an inferentially seamless manner in the identified population to a second confirmatory stage. The second stage uses fixed randomization to confirm the findings from the first stage to support registration. Therapeutic arms with biomarkers may be added to the trial over time, while others complete testing. The design of GBM AGILE enables rapid clinical testing of new therapies and biomarkers to speed highly effective therapies to clinical practice. Clin Cancer Res; 24(4); 737-43. ©2017 AACR.\n\nIndexed on Europe PMC as PubMed record 28814435 (DOI 10.1158/1078-0432.ccr-17-0764). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Clin Cancer Res 2018","url":"https://doi.org/10.1158/1078-0432.ccr-17-0764"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28814435/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28814435"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["gbm-agile"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2018,"doi":"10.1158/1078-0432.ccr-17-0764","pmid":"28814435","authors":"Alexander BM, Ba S, Berger MS, et al.","paperType":"review","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-gatenby-cancer-res","kind":"paper","name":"Adaptive therapy","aka":[],"tldr":"Paper cited by one technology page and one term page, indexed on Europe PMC as PubMed record 19487300 and published in Cancer Research; the citing pages link this DOI, which is how the record was matched.","summary":"A number of successful systemic therapies are available for treatment of disseminated cancers. However, tumor response is often transient, and therapy frequently fails due to emergence of resistant populations. The latter reflects the temporal and spatial heterogeneity of the tumor microenvironment as well as the evolutionary capacity of cancer phenotypes to adapt to therapeutic perturbations. Although cancers are highly dynamic systems, cancer therapy is typically administered according to a fixed, linear protocol. Here we examine an adaptive therapeutic approach that evolves in response to the temporal and spatial variability of tumor microenvironment and cellular phenotype as well as therapy-induced perturbations. Initial mathematical models find that when resistant phenotypes arise in the untreated tumor, they are typically present in small numbers because they are less fit than the sensitive population. This reflects the \"cost\" of phenotypic resistance such as additional substrate and energy used to up-regulate xenobiotic metabolism, and therefore not available for proliferation, or the growth inhibitory nature of environments (i.e., ischemia or hypoxia) that confer resistance on phenotypically sensitive cells. Thus, in the Darwinian environment of a cancer, the fitter chemosensitive cells will ordinarily proliferate at the expense of the less fit chemoresistant cells. The models show that, if resistant populations are present before administration of therapy, treatments designed to kill maximum numbers of cancer cells remove this inhibitory effect and actually promote more rapid growth of the resistant populations. We present an alternative approach in which treatment is continuously modulated to achieve a fixed tumor population. The goal of adaptive therapy is to enforce a stable tumor burden by permitting a significant population of chemosensitive cells to survive so that they, in turn, suppress proliferation of the less fit but chemoresistant subpopulations. Computer simulations show that this strategy can result in prolonged survival that is substantially greater than that of high dose density or metronomic therapies. The feasibility of adaptive therapy is supported by in vivo experiments. [Cancer Res 2009;69(11):4894-903] Major FindingsWe present mathematical analysis of the evolutionary dynamics of tumor populations with and without therapy. Analytic solutions and numerical simulations show that, with pretreatment, therapy-resistant cancer subpopulations are present due to phenotypic or microenvironmental factors; maximum dose density chemotherapy hastens rapid expansion of resistant populations. The models predict that host survival can be maximized if \"treatment-for-cure strategy\" is replaced by \"treatment-for-stability.\" Specifically, the models predict that an optimal treatment strategy will modulate therapy to maintain a stable population of chemosensitive cells that can, in turn, suppress the growth of resistant populations under normal tumor conditions (i.e., when therapy-induced toxicity is absent). In vivo experiments using OVCAR xenografts treated with carboplatin show that adaptive therapy is feasible and, in this system, can produce long-term survival.\n\nIndexed on Europe PMC as PubMed record 19487300 (DOI 10.1158/0008-5472.can-08-3658). Matched by DOI alone: one technology page and one term page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer Res 2009","url":"https://doi.org/10.1158/0008-5472.can-08-3658"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19487300/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/19487300"}],"tags":["europepmc-ingest"],"related":["adaptive-therapy-dynamics","clonal-evolution-theory"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-research"],"dependsOn":[],"notes":[],"journal":"Cancer Research","year":2009,"doi":"10.1158/0008-5472.can-08-3658","pmid":"19487300","authors":"Gatenby RA, Silva AS, Gillies RJ, et al.","paperType":"basic","findings":[],"whatItMeans":"One technology page and one term page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-adaura-8-year-os-jto-2026","kind":"paper","name":"ADAURA: exploratory eight-year overall survival update for adjuvant osimertinib in resected EGFR-mutated stage IB to IIIA lung cancer","aka":[],"tldr":"Eight years after surgery, about three in four patients who took osimertinib for three years were still alive, compared with under six in ten on placebo: the longest survival follow-up from any global adjuvant trial in EGFR-mutated lung cancer.","summary":"Post hoc exploratory analysis of long-term overall survival in ADAURA, the phase 3 trial that randomised 682 patients with resected EGFR-mutated stage IB to IIIA non-small-cell lung cancer to three years of adjuvant osimertinib or placebo. Survival data were collected from 431 of the 558 patients alive at the planned final overall survival analysis (data cut-off 27 January 2023) through yearly follow-up to a new cut-off of 4 May 2026; the 127 patients without further follow-up stayed censored at the earlier cut-off.\n\nIn the stage II to IIIA population the overall survival hazard ratio was 0.53 (95 percent CI 0.38 to 0.75) and eight-year survival was 74 percent with osimertinib against 58 percent with placebo. In the stage IB to IIIA population the hazard ratio was 0.52 (95 percent CI 0.39 to 0.71) with eight-year survival of 79 percent against 64 percent. Hazard ratios by mutation were 0.45 for exon 19 deletions and 0.72 (95 percent CI 0.46 to 1.11) for L858R, and the benefit was seen across subgroups.","asOf":"2026-09-21","links":[{"label":"J Thorac Oncol 2026","url":"https://doi.org/10.1016/j.jtho.2026.104179"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42732874/"},{"label":"ClinicalTrials.gov NCT02511106","url":"https://clinicaltrials.gov/study/NCT02511106"}],"tags":[],"related":[],"cancers":["nsclc","egfr-mutant-nsclc","resectable-nsclc"],"sections":[],"technologies":[],"targets":["egfr"],"drugs":["osimertinib"],"companies":["astrazeneca"],"institutions":[],"pathways":[],"terms":["os","neoadjuvant-adjuvant","data-maturity"],"trials":["adaura"],"people":["wu-yi-long","lu-shun","roy-herbst"],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-thoracic-oncology"],"dependsOn":[],"notes":[],"journal":"Journal of Thoracic Oncology","year":2026,"doi":"10.1016/j.jtho.2026.104179","pmid":"42732874","authors":"Wu YL, Majem M, John T, et al.","paperType":"rct","findings":["Stage II to IIIA: eight-year overall survival 74 percent with osimertinib vs 58 percent with placebo; hazard ratio 0.53 (95 percent CI 0.38 to 0.75); median follow-up 92.0 vs 68.5 months.","Stage IB to IIIA: eight-year overall survival 79 percent vs 64 percent; hazard ratio 0.52 (95 percent CI 0.39 to 0.71); median follow-up 93.3 vs 79.6 months.","Overall survival hazard ratio 0.45 (95 percent CI 0.29 to 0.68) for exon 19 deletion and 0.72 (95 percent CI 0.46 to 1.11) for L858R."],"whatItMeans":"The survival benefit first reported in 2023 has held five years after the last dose of adjuvant osimertinib, which answers the worry that a three-year course only delays relapse. Patients with an exon 19 deletion gained most; the L858R estimate crosses one and is less certain. Nothing here changes the recommendation, which already rests on the 2023 analysis, but it tightens the case for testing every resected non-squamous tumour for EGFR mutations.","caveats":["Post hoc exploratory analysis, not a prespecified endpoint, with unequal follow-up between arms.","Follow-up was obtained for 431 of 558 patients alive at the 2023 cut-off; the remaining 127 were censored at the earlier date, so the eight-year estimates rest on partial ascertainment.","The L858R hazard ratio (0.72, 95 percent CI 0.46 to 1.11) is not statistically significant on its own."],"changedPractice":false,"participants":682},{"id":"paper-adaura-nejm-2020","kind":"paper","name":"ADAURA: three years of osimertinib after surgery for EGFR-mutated lung cancer","aka":[],"tldr":"After surgery for early-stage EGFR-mutated lung cancer, three years of osimertinib cut recurrences by about 80% and later reduced deaths by half.","summary":"Double-blind, placebo-controlled phase 3 trial of 682 patients with completely resected stage IB-IIIA EGFR-mutated NSCLC, with or without adjuvant chemotherapy, randomised to three years of osimertinib or placebo. Primary endpoint was disease-free survival in stage II-IIIA.\n\nThe trial was unblinded early: DFS HR 0.17 in stage II-IIIA and 0.20 overall, with 24-month DFS 89% vs 52%. The 2023 overall survival report showed 5-year OS 88% vs 78% (HR 0.49). It made adjuvant osimertinib standard and established EGFR testing of resected tumours.","asOf":"2026-09-08","links":[{"label":"NEJM 2020","url":"https://doi.org/10.1056/NEJMoa2027071"},{"label":"ClinicalTrials.gov NCT02511106","url":"https://clinicaltrials.gov/study/NCT02511106"}],"tags":[],"related":["lung-cancer-evidence-roadmap","paper-wu-alina-adjuvant-alectinib-nejm-2024","paper-lace-adjuvant-cisplatin-pooled-analysis-jco-2008"],"cancers":["nsclc","lung-cancer"],"sections":[],"technologies":["kinase-inhibitors"],"targets":["egfr"],"drugs":["osimertinib"],"companies":["astrazeneca"],"institutions":[],"pathways":[],"terms":["neoadjuvant-adjuvant","oncogene-addiction","mrd"],"trials":["adaura"],"people":["wu-yi-long","he-jie","lu-shun"],"bottlenecks":["b-dormancy-mrd","b-drug-pricing"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2020,"doi":"10.1056/NEJMoa2027071","authors":"Wu YL, Tsuboi M, He J, et al.","paperType":"rct","findings":["Stage II-IIIA: 24-month disease-free survival 90% vs 44%; HR 0.17 (99.06% CI 0.11-0.26).","Overall population (IB-IIIA): 24-month DFS 89% vs 52%; HR 0.20.","CNS recurrence or death HR 0.18.","Overall survival (2023): 5-year OS 88% vs 78% overall, HR 0.49; stage II-IIIA 85% vs 73%.","Benefit was seen with or without prior adjuvant chemotherapy."],"whatItMeans":"Every resected non-squamous lung cancer should be tested for EGFR mutations, because patients who carry one live longer if they take osimertinib for three years after surgery. The trial does not tell us whether adjuvant chemotherapy can be omitted, nor what happens on relapse after osimertinib, and the three-year duration was chosen empirically.","caveats":["Early unblinding after a dramatic DFS effect meant the trial was stopped before the planned analysis.","Recurrences resumed after osimertinib stopped, raising the question of whether it delays rather than prevents relapse in some patients; OS benefit argues it does more than delay.","Optimal duration (three years vs indefinite) is untested.","Cost of three years of therapy is very high."],"changedPractice":true,"participants":682},{"id":"paper-zammarchi-blood","kind":"paper","name":"ADCT-402, a PBD dimer-containing antibody drug conjugate targeting CD19-expressing malignancies","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 29298756 and published in Blood; the citing page links this DOI, which is how the record was matched.","summary":"Human CD19 antigen is a 95-kDa type I membrane glycoprotein in the immunoglobulin superfamily whose expression is limited to the various stages of B-cell development and differentiation and is maintained in the majority of B-cell malignancies, including leukemias and non-Hodgkin lymphomas of B-cell origin. Coupled with its differential and favorable expression profile, CD19 has rapid internalization kinetics and is not shed into the circulation, making it an ideal target for the development of antibody-drug conjugates (ADCs) to treat B-cell malignancies. ADCT-402 (loncastuximab tesirine) is a novel CD19-targeted ADC delivering SG3199, a highly cytotoxic DNA minor groove interstrand crosslinking pyrrolobenzodiazepine (PDB) dimer warhead. It showed potent and highly targeted in vitro cytotoxicity in CD19-expressing human cell lines. ADCT-402 was specifically bound, internalized, and trafficked to lysosomes in CD19-expressing cells and, following release of the PBD warhead, resulted in formation of DNA crosslinks that persisted for 36 hours. Bystander killing of CD19 - cells by ADCT-402 was also observed. In vivo, single doses of ADCT-402 resulted in highly potent, dose-dependent antitumor activity in several subcutaneous and disseminated human tumor models with marked superiority to comparator ADCs delivering tubulin inhibitors. Dose-dependent DNA crosslinks and γ-H2AX DNA damage response were measured in tumors by 24 hours after single dose administration, whereas matched peripheral blood mononuclear cells showed no evidence of DNA damage. Pharmacokinetic analysis in rat and cynomolgus monkey showed excellent stability and tolerability of ADCT-402 in vivo. Together, these impressive data were used to support the clinical testing of this novel ADC in patients with CD19-expressing B-cell malignancies.\n\nIndexed on Europe PMC as PubMed record 29298756 (DOI 10.1182/blood-2017-10-813493). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Blood 2018","url":"https://doi.org/10.1182/blood-2017-10-813493"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29298756/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29298756"}],"tags":["europepmc-ingest"],"related":["val-ala"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["blood"],"dependsOn":[],"notes":[],"journal":"Blood","year":2018,"doi":"10.1182/blood-2017-10-813493","pmid":"29298756","authors":"Zammarchi F, Corbett S, Adams L, et al.","paperType":"basic","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-stampede-lancet-2016","kind":"paper","name":"Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial","aka":[],"tldr":"Published report from the STAMPEDE trial registered as NCT00268476, in The Lancet (2016), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Long-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy. We report primary survival results for three research comparisons testing the addition of zoledronic acid, docetaxel, or their combination to standard of care versus standard of care alone.\n\nMethods: Standard of care was hormone therapy for at least 2 years; radiotherapy was encouraged for men with N0M0 disease to November, 2011, then mandated; radiotherapy was optional for men with node-positive non-metastatic (N+M0) disease. Stratified randomisation (via minimisation) allocated men 2:1:1:1 to standard of care only (SOC-only; control), standard of care plus zoledronic acid (SOC + ZA), standard of care plus docetaxel (SOC + Doc), or standard of care with both zoledronic acid and docetaxel (SOC + ZA + Doc). Zoledronic acid (4 mg) was given for six 3-weekly cycles, then 4-weekly until 2 years, and docetaxel (75 mg/m(2)) for six 3-weekly cycles with prednisolone 10 mg daily. There was no blinding to treatment allocation. The primary outcome measure was overall survival. Pairwise comparisons of research versus control had 90% power at 2·5% one-sided α for hazard ratio (HR) 0·75, requiring roughly 400 control arm deaths. Statistical analyses were undertaken with standard log-rank-type methods for time-to-event data, with hazard ratios (HRs) and 95% CIs derived from adjusted Cox models. This trial is registered at ClinicalTrials.gov (NCT00268476) and ControlledTrials.com (ISRCTN78818544).\n\nFindings: 2962 men were randomly assigned to four groups between Oct 5, 2005, and March 31, 2013. Median age was 65 years (IQR 60-71). 1817 (61%) men had M+ disease, 448 (15%) had N+/X M0, and 697 (24%) had N0M0. 165 (6%) men were previously treated with local therapy, and median prostate-specific antigen was 65 ng/mL (IQR 23-184). Median follow-up was 43 months (IQR 30-60). There were 415 deaths in the control group (347 [84%] prostate cancer). Median overall survival was 71 months (IQR 32 to not reached) for SOC-only, not reached (32 to not reached) for SOC + ZA (HR 0·94, 95% CI 0·79-1·11; p=0·450), 81 months (41 to not reached) for SOC + Doc (0·78, 0·66-0·93; p=0·006), and 76 months (39 to not reached) for SOC + ZA + Doc (0·82, 0·69-0·97; p=0·022). There was no evidence of heterogeneity in treatment effect (for any of the treatments) across prespecified subsets. Grade 3-5 adverse events were reported for 399 (32%) patients receiving SOC, 197 (32%) receiving SOC + ZA, 288 (52%) receiving SOC + Doc, and 269 (52%) receiving SOC + ZA + Doc.\n\nInterpretation: Zoledronic acid showed no evidence of survival improvement and should not be part of standard of care for this population. Docetaxel chemotherapy, given at the time of long-term hormone therapy initiation, showed evidence of improved survival accompanied by an increase in adverse events. Docetaxel treatment should become part of standard of care for adequately fit men commencing long-term hormone therapy.\n\nFunding: Cancer Research UK, Medical Research Council, Novartis, Sanofi-Aventis, Pfizer, Janssen, Astellas, NIHR Clinical Research Network, Swiss Group for Clinical Cancer Research.\n\nIndexed on Europe PMC as PubMed record 26719232 (DOI 10.1016/s0140-6736(15)01037-5). Its abstract cites the registry id NCT00268476, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet 2016","url":"https://doi.org/10.1016/s0140-6736(15)01037-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26719232/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26719232"},{"label":"ClinicalTrials.gov NCT00268476","url":"https://clinicaltrials.gov/study/NCT00268476"}],"tags":["europepmc-ingest"],"related":["prostate-roadmap","paper-gravis-getug-afu-15-docetaxel-lancet-oncol-2013","paper-vale-stopcap-docetaxel-bisphosphonates-lancet-oncol-2016"],"cancers":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["stampede"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2016,"doi":"10.1016/s0140-6736(15)01037-5","pmid":"26719232","authors":"James ND, Sydes MR, Clarke NW, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT00268476 with the most citations, so it is the natural first reading for anyone following the STAMPEDE trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-brightness-lancet-oncol-2018","kind":"paper","name":"Addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to standard neoadjuvant chemotherapy in triple-negative breast cancer (BrighTNess): a randomised, phase 3 trial","aka":[],"tldr":"Published report from the BrighTNess trial registered as NCT02032277, in The Lancet Oncology (2018), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Although several randomised trials in patients with triple-negative breast cancer have shown that the addition of carboplatin, with or without poly(ADP-ribose) polymerase (PARP) inhibitors, to neoadjuvant chemotherapy increases the likelihood of achieving a pathological complete response, the use of these therapies in this setting has remained controversial. The BrighTNess trial was designed to assess the addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to standard neoadjuvant chemotherapy in triple-negative breast cancer.\n\nMethods: We did a phase 3, randomised, double-blind, placebo-controlled trial (BrighTNess) across 145 sites in 15 countries. Patients aged 18 years and older with previously untreated histologically or cytologically confirmed clinical stage II-III triple-negative breast cancer, who were candidates for potentially curative surgery and had an Eastern Cooperative Oncology Group performance status of 0 or 1, were randomly assigned (2:1:1) by an interactive response technology system via permuted blocks (block size of four) within strata to receive one of three segment 1 regimens: paclitaxel (80 mg/m 2 intravenously weekly for 12 doses) plus carboplatin (area under the curve 6 mg/mL per min, intravenously every 3 weeks, for four cycles) plus veliparib (50 mg orally, twice a day); paclitaxel plus carboplatin plus veliparib placebo (twice a day); or paclitaxel plus carboplatin placebo (every 3 weeks for four cycles) plus veliparib placebo. Following segment 1, all patients were assigned to segment 2 in which they received doxorubicin and cyclophosphamide every 2-3 weeks for four cycles. Randomisation for segment 1 was stratified by germline BRCA mutation status, nodal stage, and planned schedule of doxorubicin and cyclophosphamide administration. The primary endpoint was pathological complete response in breast and lymph nodes as determined by site pathologists following completion of neoadjuvant therapy. Efficacy analyses were done by intention to treat and safety analyses included all patients who received at least one dose of study treatment. These are the first results of an ongoing clinical trial; the data cutoff for the analyses presented was Dec 8, 2016. This study is registered with ClinicalTrials.gov, number NCT02032277.\n\nFindings: Between April 4, 2014, and March 18, 2016, 634 patients were randomly assigned: 316 to paclitaxel plus carboplatin plus veliparib, 160 to paclitaxel plus carboplatin, and 158 to paclitaxel alone. The proportion of patients who achieved a pathological complete response was higher in the paclitaxel, carboplatin, and veliparib group than in patients receiving paclitaxel alone (168 [53%] of 316 patients vs 49 [31%] of 158, p<0·0001), but not compared with patients receiving paclitaxel plus carboplatin (92 [58%] of 160 patients, p=0·36). Grade 3 or 4 toxicities, and serious adverse events were more common in patients receiving carboplatin, whereas veliparib did not substantially increase toxicity. The most common grade 3 or 4 events overall were neutropenia (352 [56%] of 628 patients), anaemia (180 [29%]), and thrombocytopenia (75 [12%]) through complete treatment, and febrile neutropenia (88 [15%] of 601 patients) during segment 2. The most common serious adverse events were febrile neutropenia (80 [13%] of 628 patients) and anaemia (20 [3%]).\n\nInterpretation: Although the addition of veliparib and carboplatin to paclitaxel followed by doxorubicin and cyclophosphamide improved the proportion of patients with triple-negative breast cancer who achieved a pathological complete response, the addition of veliparib to carboplatin and paclitaxel did not. Increased toxicities with the addition of carboplatin (with or without veliparib) to paclitaxel were manageable and did not substantially affect treatment delivery of paclitaxel followed by doxorubicin and cyclophosphamide. Given the consistent results with previous studies, the addition of carboplatin appears to have a favourable risk to benefit profile and might be considered as a potential component of neoadjuvant chemotherapy for patients with high-risk, triple-negative breast cancer.\n\nFunding: AbbVie.\n\nIndexed on Europe PMC as PubMed record 29501363 (DOI 10.1016/s1470-2045(18)30111-6). Its abstract cites the registry id NCT02032277, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2018","url":"https://doi.org/10.1016/s1470-2045(18)30111-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29501363/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29501363"},{"label":"ClinicalTrials.gov NCT02032277","url":"https://clinicaltrials.gov/study/NCT02032277"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["brightness"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2018,"doi":"10.1016/s1470-2045(18)30111-6","pmid":"29501363","authors":"Loibl S, O'Shaughnessy J, Untch M, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02032277 with the most citations, so it is the natural first reading for anyone following the BrighTNess trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-capstone-1-lancet-oncol-2022","kind":"paper","name":"Adebrelimab or placebo plus carboplatin and etoposide as first-line treatment for extensive-stage small-cell lung cancer (CAPSTONE-1): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial","aka":[],"tldr":"Published report from the CAPSTONE-1 trial registered as NCT03711305, in The Lancet Oncology (2022), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Extensive-stage small-cell lung cancer (ES-SCLC) is associated with poor prognosis and treatment options are scarce. Immunotherapy has shown robust clinical activity in ES-SCLC in previous phase 3 trials. We aimed to assess the efficacy and safety of adebrelimab (SHR-1316), a novel anti-PD-L1 antibody, with standard chemotherapy as a first-line treatment for ES-SCLC.\n\nMethods: The CAPSTONE-1 study was a randomised, double-blind, placebo-controlled, phase 3 trial, done in 47 tertiary hospitals in China. Key inclusion criteria were patients aged 18-75 years, with previously untreated histologically or cytologically confirmed ES-SCLC and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Eligible patients were randomly assigned (1:1) to receive four to six cycles of carboplatin (area under the curve of 5 mg/mL per min, day 1 of each cycle) and etoposide (100 mg/m 2 of body-surface area, on days 1-3 of each cycle) with either adebrelimab (20 mg/kg, day 1 of each cycle) or matching placebo, followed by maintenance therapy with adebrelimab or placebo. All treatments were given intravenously in 21-day cycles. Randomisation was done using a centralised interactive web response system with a block size of four, stratified by liver metastases, brain metastases, and lactate dehydrogenase concentration. The primary endpoint was overall survival in patients who received at least one dose of study medication. Safety was analysed in the as-treated population. This study is complete and registered with ClinicalTrials.gov, NCT03711305.\n\nFindings: Between Dec 26, 2018, and Sept 4, 2020, 462 eligible patients were enrolled and randomly assigned: 230 (50%) patients received adebrelimab plus chemotherapy (adebrelimab group) and 232 (50%) patients received placebo plus chemotherapy (placebo group). At data cutoff (Oct 8, 2021), median follow-up was 13·5 months (IQR 8·9-20·1). Median overall survival was significantly improved in the adebrelimab group (median 15·3 months [95% CI 13·2-17·5]) compared with the placebo group (12·8 months [11·3-13·7]; hazard ratio 0·72 [95% CI 0·58-0·90]; one-sided p=0·0017). The most common treatment-related grade 3 or 4 adverse events were decreased neutrophil count (174 [76%] patients in the adebrelimab group and 175 [75%] patients in the placebo group), decreased white blood cell count (106 [46%] and 88 [38%]), decreased platelet count (88 [38%] and 78 [34%]), and anaemia (64 [28%] and 66 [28%]). Treatment-related serious adverse events occurred in 89 (39%) patients in the adebrelimab group and 66 (28%) patients in the placebo group. Four treatment-related deaths were reported: two each in the adebrelimab group (respiratory failure and interstitial lung disease and pneumonia) and placebo group (multiple organ dysfunction and unknown cause of death).\n\nInterpretation: Adding adebrelimab to chemotherapy significantly improved overall survival with an acceptable safety profile in patients with ES-SCLC, supporting this combination as a new first-line treatment option for this population.\n\nFunding: Jiangsu Hengrui Pharmaceuticals.\n\nIndexed on Europe PMC as PubMed record 35576956 (DOI 10.1016/s1470-2045(22)00224-8). Its abstract cites the registry id NCT03711305, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2022","url":"https://doi.org/10.1016/s1470-2045(22)00224-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35576956/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35576956"},{"label":"ClinicalTrials.gov NCT03711305","url":"https://clinicaltrials.gov/study/NCT03711305"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["capstone-1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2022,"doi":"10.1016/s1470-2045(22)00224-8","pmid":"35576956","authors":"Wang J, Zhou C, Yao W, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03711305 with the most citations, so it is the natural first reading for anyone following the CAPSTONE-1 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-herbst-diethylstilbestrol-vaginal-adenocarcinoma-nejm-1971","kind":"paper","name":"Adenocarcinoma of the vagina: association of maternal stilbestrol therapy with tumour appearance in young women","aka":[],"tldr":"Eight young women in Boston developed a vaginal cancer almost never seen at their age; seven of their mothers had taken the synthetic oestrogen diethylstilbestrol in pregnancy. It was the first proof that a drug given to a mother could cause cancer in her child decades later.","summary":"Case-control study of eight women aged 15 to 22 with clear cell adenocarcinoma of the vagina diagnosed in Boston between 1966 and 1969, each matched to four controls born in the same hospital within days.\n\nSeven of the eight mothers had taken diethylstilbestrol (DES) during the first trimester, against none of the 32 control mothers. The finding led to the withdrawal of DES in pregnancy and to the recognition of transplacental carcinogenesis.","asOf":"2026-09-18","links":[{"label":"N Engl J Med 1971","url":"https://doi.org/10.1056/NEJM197104222841604"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/5549830/"}],"tags":[],"related":[],"cancers":["vaginal-adenocarcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":1971,"doi":"10.1056/NEJM197104222841604","pmid":"5549830","authors":"Herbst AL, Ulfelder H, Poskanzer DC.","paperType":"observational","findings":["Maternal DES exposure in the first trimester in 7 of 8 cases versus 0 of 32 matched controls."],"whatItMeans":"Clear cell adenocarcinoma of the vagina is the archetype of a cancer caused by exposure before birth; DES-exposed daughters still need lifelong gynaecological surveillance, and the paper is the reason drugs in pregnancy are now scrutinised for effects on the child.","caveats":["Eight cases; the association was confirmed by registries over the following decades.","Most vaginal adenocarcinomas today arise without DES exposure."],"changedPractice":true,"participants":40},{"id":"paper-adiuvo-adjuvant-mitotane-low-grade-acc-terzolo-lancet-diabetes-endocrinol-2023","kind":"paper","name":"ADIUVO: adjuvant mitotane versus surveillance in low-grade, localised adrenocortical carcinoma","aka":[],"tldr":"After complete removal of a low-grade adrenal cancer, two years of mitotane did not significantly reduce recurrence or improve survival compared with surveillance, and every patient on it had side effects.","summary":"International multicentre open-label randomised phase 3 trial with a parallel observational study: 91 patients with completely resected low- to intermediate-risk adrenocortical carcinoma were randomised to adjuvant mitotane (45) or surveillance (46) between 2008 and 2018, when the trial closed for slow recruitment.\n\nFive-year recurrence-free survival was 79 percent with mitotane against 75 percent with surveillance (hazard ratio 0.74, 95% CI 0.30 to 1.85); five-year overall survival 95 against 86 percent with two and five deaths. All 42 treated patients had adverse events and 19 percent discontinued.","asOf":"2026-09-22","links":[{"label":"Lancet Diabetes Endocrinol 2023","url":"https://doi.org/10.1016/S2213-8587(23)00193-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37619579/"}],"tags":[],"related":[],"cancers":["localised-adrenocortical-carcinoma","adrenocortical"],"sections":[],"technologies":[],"targets":[],"drugs":["mitotane"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["adiuvo"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Lancet Diabetes and Endocrinology","year":2023,"doi":"10.1016/S2213-8587(23)00193-6","pmid":"37619579","authors":"Terzolo M, Fassnacht M, Perotti P, et al.","paperType":"rct","findings":["Five-year recurrence-free survival 79 percent (95% CI 67 to 94) versus 75 percent (63 to 90); hazard ratio 0.74 (0.30 to 1.85).","Five-year overall survival 95 percent (89 to 100) versus 86 percent (74 to 100), not significant.","Adverse events in all 42 treated patients; 19 percent discontinued mitotane."],"whatItMeans":"Adjuvant mitotane may be withheld in low-grade localised adrenocortical carcinoma, given the good prognosis and the drug's toxicity.","caveats":["Underpowered after early closure, so a treatment effect cannot be excluded."],"changedPractice":true,"participants":91},{"id":"paper-felip-impower010-adjuvant-atezolizumab-lancet-2021","kind":"paper","name":"Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010)","aka":[],"tldr":"The first trial to show that immunotherapy after lung cancer surgery delays recurrence. The benefit was concentrated in patients whose tumours expressed PD-L1.","summary":"The IMpower010 investigators, reported by Felip, Altorki, Zhou and colleagues with Wakelee as senior author, randomised 1,005 of 1,280 enrolled patients with completely resected stage IB (tumours 4 cm or larger) to IIIA non-small-cell lung cancer, after one to four cycles of adjuvant platinum chemotherapy, to atezolizumab 1200 mg every 21 days for 16 cycles or a year (507) or best supportive care (498), across 227 sites in 22 countries.\n\nThe hierarchical testing order is the result. The PD-L1-positive stage II to IIIA group cleared the bar comfortably, the whole stage II to IIIA group marginally, and the intention-to-treat population barely, which is why regulators restricted the indication to PD-L1-positive stage II to IIIA disease rather than granting what the trial nominally showed.","asOf":"2026-09-25","links":[{"label":"Lancet 2021","url":"https://doi.org/10.1016/S0140-6736(21)02098-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34555333/"},{"label":"ClinicalTrials.gov NCT02486718","url":"https://clinicaltrials.gov/study/NCT02486718"},{"label":"Lancet 2021","url":"https://doi.org/10.1016/s0140-6736(21)02098-5"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34555333"}],"tags":["lung-evidence"],"related":["paper-lace-adjuvant-cisplatin-pooled-analysis-jco-2008","paper-checkmate-816-nejm-2022","paper-heymach-aegean-perioperative-durvalumab-nejm-2023","paper-keynote-671-n-engl-j-med-2023"],"cancers":["lung-cancer","nsclc","resectable-nsclc","pdl1-high-nsclc"],"sections":["immunotherapy","surgery"],"technologies":["ihc","checkpoint-inhibitor"],"targets":["pd1"],"drugs":["atezolizumab","cisplatin","carboplatin"],"companies":["roche-genentech"],"institutions":[],"pathways":["immune-checkpoint"],"terms":["neoadjuvant-adjuvant","pdl1"],"trials":["nct02486718"],"people":[],"bottlenecks":["b-dormancy-mrd","b-immunotherapy-response","b-biomarker-validation"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2021,"doi":"10.1016/S0140-6736(21)02098-5","pmid":"34555333","authors":"Felip E, Altorki N, Zhou C, et al.","paperType":"rct","findings":["Stage II to IIIA patients whose tumours expressed PD-L1 on 1 percent or more of tumour cells: disease-free survival hazard ratio 0.66 (95 percent confidence interval 0.50 to 0.88; p equals 0.0039).","All stage II to IIIA patients: hazard ratio 0.79 (0.64 to 0.96; p equals 0.020).","Intention-to-treat population (stage IB to IIIA): hazard ratio 0.81 (0.67 to 0.99; p equals 0.040).","Median follow-up 32.2 months in the stage II to IIIA population.","Atezolizumab-related grade 3 and 4 adverse events in 53 of 495 patients (11 percent) and grade 5 events in 4 patients (1 percent)."],"whatItMeans":"Adjuvant immunotherapy entered lung cancer here, and with it the question that still divides practice: whether it is better given before the operation, after it, or on both sides.","caveats":["Disease-free survival, with overall survival immature at this report; treatment-related deaths occurred in 1 percent.","Best supportive care rather than placebo, in an open-label trial where recurrence detection depends on scan frequency.","Everyone had already received adjuvant chemotherapy, so it does not say what atezolizumab does on its own."],"changedPractice":true,"participants":1005},{"id":"paper-early-breast-cancer-trialists-collaborative-group-ebctcg-lancet","kind":"paper","name":"Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials","aka":[],"tldr":"Paper cited by one technology page and one term page, indexed on Europe PMC as PubMed record 26211824 and published in The Lancet; the citing pages link this DOI, which is how the record was matched.","summary":"Background: Bisphosphonates have profound effects on bone physiology, and could modify the process of metastasis. We undertook collaborative meta-analyses to clarify the risks and benefits of adjuvant bisphosphonate treatment in breast cancer.\n\nMethods: We sought individual patient data from all unconfounded trials in early breast cancer that randomised between bisphosphonate and control. Primary outcomes were recurrence, distant recurrence, and breast cancer mortality. Primary subgroup investigations were site of first distant recurrence (bone or other), menopausal status (postmenopausal [combining natural and artificial] or not), and bisphosphonate class (aminobisphosphonate [eg, zoledronic acid, ibandronate, pamidronate] or other [ie, clodronate]). Intention-to-treat log-rank methods yielded bisphosphonate versus control first-event rate ratios (RRs).\n\nFindings: We received data on 18,766 women (18,206 [97%] in trials of 2-5 years of bisphosphonate) with median follow-up 5·6 woman-years, 3453 first recurrences, and 2106 subsequent deaths. Overall, the reductions in recurrence (RR 0·94, 95% CI 0·87-1·01; 2p=0·08), distant recurrence (0·92, 0·85-0·99; 2p=0·03), and breast cancer mortality (0·91, 0·83-0·99; 2p=0·04) were of only borderline significance, but the reduction in bone recurrence was more definite (0·83, 0·73-0·94; 2p=0·004). Among premenopausal women, treatment had no apparent effect on any outcome, but among 11 767 postmenopausal women it produced highly significant reductions in recurrence (RR 0·86, 95% CI 0·78-0·94; 2p=0·002), distant recurrence (0·82, 0·74-0·92; 2p=0·0003), bone recurrence (0·72, 0·60-0·86; 2p=0·0002), and breast cancer mortality (0·82, 0·73-0·93; 2p=0·002). Even for bone recurrence, however, the heterogeneity of benefit was barely significant by menopausal status (2p=0·06 for trend with menopausal status) or age (2p=0·03), and it was non-significant by bisphosphonate class, treatment schedule, oestrogen receptor status, nodes, tumour grade, or concomitant chemotherapy. No differences were seen in non-breast cancer mortality. Bone fractures were reduced (RR 0·85, 95% CI 0·75-0·97; 2p=0·02).\n\nInterpretation: Adjuvant bisphosphonates reduce the rate of breast cancer recurrence in the bone and improve breast cancer survival, but there is definite benefit only in women who were postmenopausal when treatment began.\n\nFunding: Cancer Research UK, Medical Research Council.\n\nIndexed on Europe PMC as PubMed record 26211824 (DOI 10.1016/s0140-6736(15)60908-4). Matched by DOI alone: one technology page and one term page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet 2015","url":"https://doi.org/10.1016/s0140-6736(15)60908-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26211824/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26211824"}],"tags":["europepmc-ingest"],"related":["bone-modifying-agents","seed-and-soil-hypothesis"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2015,"doi":"10.1016/s0140-6736(15)60908-4","pmid":"26211824","authors":"Early Breast Cancer Trialists' Collaborative Group (EBCTCG)","paperType":"meta-analysis","findings":[],"whatItMeans":"One technology page and one term page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-create-x-adjuvant-capecitabine-nejm-2017","kind":"paper","name":"Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy","aka":[],"tldr":"The Japanese and Korean trial of 910 women whose tumours had survived pre-surgery chemotherapy, in which six months of capecitabine tablets cut deaths by 41 percent, and by 48 percent in the triple-negative group; the first treatment ever shown to help after residual disease.","summary":"CREATE-X (Masuda, Lee, Ohtani, Im and colleagues) randomised 910 patients with HER2-negative residual invasive breast cancer after anthracycline- and/or taxane-containing neoadjuvant chemotherapy to standard post-surgical treatment with or without capecitabine; the primary endpoint was disease-free survival and the trial stopped early after a pre-specified interim analysis met it. Five-year disease-free survival was 74.1 versus 67.6 percent (hazard ratio 0.70, 95 percent confidence interval 0.53 to 0.92, p=0.01) and overall survival 89.2 versus 83.6 percent (hazard ratio 0.59, 0.39 to 0.90, p=0.01). Among triple-negative patients disease-free survival was 69.8 versus 56.1 percent (hazard ratio 0.58, 0.39 to 0.87) and overall survival 78.8 versus 70.3 percent (0.52, 0.30 to 0.90). Hand-foot syndrome occurred in 73.4 percent of the capecitabine group. Registered as UMIN000000843.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2017","url":"https://doi.org/10.1056/NEJMoa1612645"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28564564/"},{"label":"UMIN Clinical Trials Registry UMIN000000843","url":"https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000001028"},{"label":"N Engl J Med 2017","url":"https://doi.org/10.1056/nejmoa1612645"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28564564"}],"tags":["tnbc-evidence"],"related":["paper-liedtke-neoadjuvant-response-survival-tnbc-jco-2008","tnbc-early"],"cancers":["tnbc","breast-hr-positive"],"sections":[],"technologies":[],"targets":[],"drugs":["capecitabine"],"companies":[],"institutions":[],"pathways":[],"terms":["rcb","neoadjuvant-adjuvant","hazard-ratio"],"trials":[],"people":[],"bottlenecks":["b-dormancy-mrd"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2017,"doi":"10.1056/NEJMoa1612645","pmid":"28564564","authors":"Masuda N, Lee SJ, Ohtani S, et al.","paperType":"rct","findings":["Five-year disease-free survival 74.1 vs 67.6 percent; hazard ratio 0.70 (95 percent CI 0.53 to 0.92), p=0.01.","Five-year overall survival 89.2 vs 83.6 percent; hazard ratio 0.59 (0.39 to 0.90), p=0.01.","Triple-negative subgroup: disease-free survival 69.8 vs 56.1 percent (hazard ratio 0.58); overall survival 78.8 vs 70.3 percent (0.52).","Hand-foot syndrome in 73.4 percent on capecitabine."],"whatItMeans":"Established that residual disease after neoadjuvant chemotherapy is a treatable state, the principle behind OlympiA and the post-neoadjuvant antibody-drug conjugate trials; capecitabine remains the option for residual triple-negative disease without a BRCA variant in ESMO, NCCN and UK practice.","caveats":["East Asian population with different capecitabine pharmacology and tolerance from Western patients; a US confirmatory trial was never completed.","Stopped early at interim analysis, which tends to overstate effects.","Pre-immunotherapy: whether capecitabine adds to adjuvant pembrolizumab is unknown."],"changedPractice":true,"participants":910},{"id":"paper-quasar-adjuvant-chemotherapy-vs-observation-lancet-2007","kind":"paper","name":"Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study (QUASAR)","aka":[],"tldr":"The trial that measured how small the benefit of chemotherapy is for node-negative bowel cancer: about 3.6 people in every 100 avoid dying, which is why the decision is a conversation rather than a rule.","summary":"QUASAR set out to determine the size and duration of any survival benefit from adjuvant chemotherapy in patients at low risk of recurrence, for whom the indication was unclear. After apparently curative resection, 3,239 patients from 150 centres in 19 countries were randomised to fluorouracil and folinic acid or to observation with chemotherapy considered on recurrence; 2,963 (91 percent) had stage II node-negative disease and 2,291 (71 percent) had colon rather than rectal cancer, with a median age of 63. Until 1997 levamisole or placebo was added; after 1997 the chemotherapy arm received fluorouracil and low-dose folinic acid only. The primary outcome was all-cause mortality, analysed by intention to treat.\n\nTreatment efficacy did not differ significantly by tumour site, stage, sex, age or chemotherapy schedule.","asOf":"2026-09-24","links":[{"label":"Lancet 2007","url":"https://doi.org/10.1016/S0140-6736(07)61866-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/18083404/"}],"tags":["colorectal-evidence"],"related":["paper-dynamic-nejm-2022","paper-moertel-levamisole-fluorouracil-adjuvant-colon-nejm-1990"],"cancers":["colorectal","colon-cancer"],"sections":["chemotherapy"],"technologies":["cytotoxic-chemotherapy"],"targets":[],"drugs":["fluorouracil","leucovorin"],"companies":[],"institutions":["oxford-cancer"],"pathways":[],"terms":["neoadjuvant-adjuvant","msi"],"trials":[],"people":["richard-gray"],"bottlenecks":["b-toxicity-qol","b-trial-design"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2007,"doi":"10.1016/S0140-6736(07)61866-2","pmid":"18083404","authors":"Quasar Collaborative Group, Gray R, Barnwell J, et al.","paperType":"rct","findings":["After a median 5.5 years, 311 deaths on chemotherapy against 370 on observation: relative risk of death 0.82 (95 percent CI 0.70 to 0.95, p=0.008).","293 recurrences against 359: relative risk 0.78 (0.67 to 0.91, p=0.001).","Assuming 20 percent five-year mortality without chemotherapy, the absolute survival improvement is 3.6 percent (95 percent CI 1.0 to 6.0).","Eight chemotherapy-group and four observation-group patients died of non-colorectal causes within 30 weeks; one death was deemed possibly chemotherapy related."],"whatItMeans":"The number every stage II conversation still uses. It is also the baseline against which ctDNA-guided de-escalation is judged: DYNAMIC halved chemotherapy use in exactly this group without losing recurrence-free survival.","caveats":["Fluorouracil and folinic acid alone; the trial says nothing about whether adding oxaliplatin changes the stage II calculus.","Enrolment ran from 1994 to 2003, before mismatch repair status was routinely known, and mismatch repair-deficient stage II tumours are now known not to benefit.","The 3.6 percent figure is a modelled absolute benefit conditional on an assumed baseline mortality."],"changedPractice":true,"participants":3239},{"id":"paper-conko-001-adjuvant-gemcitabine-observation-jama-2007","kind":"paper","name":"Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial","aka":[],"tldr":"The 2007 German and Austrian trial in which six months of gemcitabine after surgery roughly doubled the time before the cancer came back, making gemcitabine the standard after resection until 2017.","summary":"CONKO-001 randomised 368 patients with gross complete (R0 or R1) resection and no prior radiation or chemotherapy at 88 centres in Germany and Austria between 1998 and 2004 to six cycles of gemcitabine on days 1, 8 and 15 every four weeks (179) or observation (175). More than 80 percent had R0 resection. Grade 3 or 4 toxicities were rare and quality of life did not differ. At 53 months median follow-up, 74 percent of the gemcitabine group and 92 percent of controls had recurred; median disease-free survival was 13.4 months against 6.9 months. The 2013 long-term report (recorded separately) showed the overall survival gain.","asOf":"2026-09-24","links":[{"label":"JAMA 2007","url":"https://doi.org/10.1001/jama.297.3.267"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/17227978/"}],"tags":["pancreatic-evidence"],"related":["paper-conko-001-adjuvant-gemcitabine-long-term-oettle-jama-2013","paper-espac-1-chemoradiotherapy-chemotherapy-resected-pancreatic-nejm-2004"],"cancers":["pancreatic","resectable-pdac"],"sections":[],"technologies":["cytotoxic-chemotherapy"],"targets":[],"drugs":["gemcitabine"],"companies":[],"institutions":["charite"],"pathways":[],"terms":[],"trials":["conko-001"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2007,"doi":"10.1001/jama.297.3.267","pmid":"17227978","authors":"Oettle H, Post S, Neuhaus P, et al.","paperType":"rct","findings":["368 patients; six cycles of adjuvant gemcitabine versus observation.","Median disease-free survival 13.4 versus 6.9 months.","Recurrence in 74 percent versus 92 percent at 53 months; grade 3 or 4 toxicity rare."],"whatItMeans":"The trial that made adjuvant gemcitabine standard in Europe and the control arm PRODIGE 24 and ESPAC-4 later beat.","caveats":["Disease-free survival was the primary endpoint; overall survival benefit came in the 2013 update.","Registered with ISRCTN (ISRCTN34802808), not ClinicalTrials.gov."],"changedPractice":true,"participants":368},{"id":"paper-soft-text-j-clin-oncol-2023-update","kind":"paper","name":"Adjuvant Endocrine Therapy in Premenopausal Breast Cancer: 12-Year Results From SOFT","aka":[],"tldr":"Later report from the SOFT trial registered as NCT00066690, in Journal of Clinical Oncology (2023); its title describes an updated or longer-term analysis.","summary":"Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. The Suppression of Ovarian Function Trial (SOFT; ClinicalTrials.gov identifier: NCT00066690) randomly assigned premenopausal women with hormone receptor-positive breast cancer to 5 years of adjuvant tamoxifen, tamoxifen plus ovarian function suppression (OFS), or exemestane plus OFS. The primary analysis compared disease-free survival (DFS) between tamoxifen plus OFS versus tamoxifen alone; exemestane plus OFS versus tamoxifen was a secondary objective. After 8 years, SOFT reported a significant reduction in recurrence and improved overall survival (OS) with adjuvant tamoxifen plus OFS versus tamoxifen alone. Here, we report outcomes after median follow-up of 12 years. DFS remained significantly improved with tamoxifen plus OFS versus tamoxifen (hazard ratio, 0.82; 95% CI, 0.69 to 0.98) with a 12-year DFS of 71.9% with tamoxifen, 76.1% with tamoxifen plus OFS, and 79.0% with exemestane plus OFS. OS was improved with tamoxifen plus OFS versus tamoxifen (hazard ratio, 0.78; 95% CI, 0.60 to 1.01) and was 86.8% with tamoxifen, 89.0% with tamoxifen plus OFS, and 89.4% with exemestane plus OFS at 12 years. Among those who received prior chemotherapy for human epidermal growth factor receptor-2-negative tumors, OS was 78.8% with tamoxifen, 81.1% with tamoxifen plus OFS, and 84.4% with exemestane plus OFS. In conclusion, after 12 years, there remains a benefit from including OFS in adjuvant endocrine therapy, with an absolute improvement in OS more apparent with higher baseline risk of recurrence.[Media: see text].\n\nIndexed on Europe PMC as PubMed record 36493334 (DOI 10.1200/jco.22.01065). Its abstract cites the registry id NCT00066690, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2023","url":"https://doi.org/10.1200/jco.22.01065"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36493334/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36493334"},{"label":"ClinicalTrials.gov NCT00066690","url":"https://clinicaltrials.gov/study/NCT00066690"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["soft-text"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2023,"doi":"10.1200/jco.22.01065","pmid":"36493334","authors":"Francis PA, Fleming GF, Láng I, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the SOFT trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-relativity-098-nat-med-2025","kind":"paper","name":"Adjuvant nivolumab and relatlimab in stage III/IV melanoma: the randomized phase 3 RELATIVITY-098 trial","aka":[],"tldr":"Published report from the RELATIVITY-098 trial registered as NCT05002569, in Nature Medicine (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Based on RELATIVITY-047, nivolumab plus relatlimab is approved for advanced melanoma. Here, to address a current unmet need for more efficacious adjuvant regimens for completely resected melanoma, the phase 3, double-blind RELATIVITY-098 trial compared adjuvant nivolumab plus relatlimab to nivolumab after complete resection of stage III/IV melanoma. Patients were randomized 1:1 to receive nivolumab 480 mg plus relatlimab 160 mg (n = 547) or nivolumab 480 mg (n = 546) intravenously every 4 weeks for ≤1 year; safety populations totaled 543 and 545 patients, respectively. The primary endpoint was recurrence-free survival (RFS), and the key secondary was overall survival; translational endpoints were exploratory. There was no difference in RFS for nivolumab plus relatlimab versus nivolumab (hazard ratio = 1.01; 95% confidence interval: 0.83-1.22; P = 0.928); therefore, overall survival was not tested. Translational data across trials showed lower circulating LAG-3 + T cells in the adjuvant setting (RELATIVITY-098) versus advanced melanoma (RELATIVITY-047), where LAG-3 + T cells were enriched in tumor versus blood. The absence of macroscopic tumor and reduced peripheral LAG-3 + T cells may explain the lack of added benefit of nivolumab plus relatlimab over nivolumab in resected versus metastatic melanoma. ClinicalTrials.gov identifier: NCT05002569.\n\nIndexed on Europe PMC as PubMed record 41109920 (DOI 10.1038/s41591-025-04032-8). Its abstract cites the registry id NCT05002569, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Nat Med 2025","url":"https://doi.org/10.1038/s41591-025-04032-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41109920/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41109920"},{"label":"ClinicalTrials.gov NCT05002569","url":"https://clinicaltrials.gov/study/NCT05002569"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["relativity-098"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2025,"doi":"10.1038/s41591-025-04032-8","pmid":"41109920","authors":"Long GV, Garnett-Benson C, Dolfi S, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05002569 with the most citations, so it is the natural first reading for anyone following the RELATIVITY-098 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-checkmate-238-lancet-oncol-2020-update","kind":"paper","name":"Adjuvant nivolumab versus ipilimumab in resected stage IIIB-C and stage IV melanoma (CheckMate 238): 4-year results from a multicentre, double-blind, randomised, controlled, phase 3 trial","aka":[],"tldr":"Later report from the CheckMate 238 trial registered as NCT02388906, in The Lancet Oncology (2020); its title describes an updated or longer-term analysis.","summary":"Background: Previously, findings from CheckMate 238, a double-blind, phase 3 adjuvant trial in patients with resected stage IIIB-C or stage IV melanoma, showed significant improvements in recurrence-free survival and distant metastasis-free survival with nivolumab versus ipilimumab. This report provides updated 4-year efficacy, initial overall survival, and late-emergent safety results.\n\nMethods: This multicentre, double-blind, randomised, controlled, phase 3 trial was done in 130 academic centres, community hospitals, and cancer centres across 25 countries. Patients aged 15 years or older with resected stage IIIB-C or IV melanoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned (1:1) to receive nivolumab or ipilimumab via an interactive voice response system and stratified according to disease stage and baseline PD-L1 status of tumour cells. Patients received intravenous nivolumab 3 mg/kg every 2 weeks or intravenous ipilimumab 10 mg/kg every 3 weeks for four doses, and then every 12 weeks until 1 year of treatment, disease recurrence, unacceptable toxicity, or withdrawal of consent. The primary endpoint was recurrence-free survival by investigator assessment, and overall survival was a key secondary endpoint. Efficacy analyses were done in the intention-to-treat population (all randomly assigned patients). All patients who received at least one dose of study treatment were included in the safety analysis. The results presented in this report reflect the 4-year update of the ongoing study with a database lock date of Jan 30, 2020. This study is registered with ClinicalTrials.gov, NCT02388906.\n\nFindings: Between March 30 and Nov 30, 2015, 906 patients were assigned to nivolumab (n=453) or ipilimumab (n=453). Median follow-up was 51·1 months (IQR 41·6-52·7) with nivolumab and 50·9 months (36·2-52·3) with ipilimumab; 4-year recurrence-free survival was 51·7% (95% CI 46·8-56·3) in the nivolumab group and 41·2% (36·4-45·9) in the ipilimumab group (hazard ratio [HR] 0·71 [95% CI 0·60-0·86]; p=0·0003). With 211 (100 [22%] of 453 patients in the nivolumab group and 111 [25%] of 453 patients in the ipilimumab group) of 302 anticipated deaths observed (about 73% of the originally planned 88% power needed for significance), 4-year overall survival was 77·9% (95% CI 73·7-81·5) with nivolumab and 76·6% (72·2-80·3) with ipilimumab (HR 0·87 [95% CI 0·66-1·14]; p=0·31). Late-emergent grade 3-4 treatment-related adverse events were reported in three (1%) of 452 and seven (2%) of 453 patients. The most common late-emergent treatment-related grade 3 or 4 adverse events reported were diarrhoea, diabetic ketoacidosis, and pneumonitis (one patient each) in the nivolumab group, and colitis (two patients) in the ipilimumab group. Two previously reported treatment-related deaths in the ipilimumab group were attributed to study drug toxicity (marrow aplasia in one patient and colitis in one patient); no further treatment-related deaths were reported.\n\nInterpretation: At a minimum of 4 years' follow-up, nivolumab demonstrated sustained recurrence-free survival benefit versus ipilimumab in resected stage IIIB-C or IV melanoma indicating a long-term treatment benefit with nivolumab. With fewer deaths than anticipated, overall survival was similar in both groups. Nivolumab remains an efficacious adjuvant treatment for patients with resected high-risk melanoma, with a safety profile that is more tolerable than that of ipilimumab.\n\nFunding: Bristol Myers Squibb and Ono Pharmaceutical.\n\nIndexed on Europe PMC as PubMed record 32961119 (DOI 10.1016/s1470-2045(20)30494-0). Its abstract cites the registry id NCT02388906, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2020","url":"https://doi.org/10.1016/s1470-2045(20)30494-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32961119/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32961119"},{"label":"ClinicalTrials.gov NCT02388906","url":"https://clinicaltrials.gov/study/NCT02388906"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-238"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2020,"doi":"10.1016/s1470-2045(20)30494-0","pmid":"32961119","authors":"Ascierto PA, Del Vecchio M, Mandalá M, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the CheckMate 238 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-soft-text-n-engl-j-med-2015","kind":"paper","name":"Adjuvant ovarian suppression in premenopausal breast cancer","aka":[],"tldr":"Published report from the SOFT trial registered as NCT00066690, in New England Journal of Medicine (2015), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Suppression of ovarian estrogen production reduces the recurrence of hormone-receptor-positive early breast cancer in premenopausal women, but its value when added to tamoxifen is uncertain.\n\nMethods: We randomly assigned 3066 premenopausal women, stratified according to prior receipt or nonreceipt of chemotherapy, to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression. The primary analysis tested the hypothesis that tamoxifen plus ovarian suppression would improve disease-free survival, as compared with tamoxifen alone. In the primary analysis, 46.7% of the patients had not received chemotherapy previously, and 53.3% had received chemotherapy and remained premenopausal.\n\nResults: After a median follow-up of 67 months, the estimated disease-free survival rate at 5 years was 86.6% in the tamoxifen-ovarian suppression group and 84.7% in the tamoxifen group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.83; 95% confidence interval [CI], 0.66 to 1.04; P=0.10). Multivariable allowance for prognostic factors suggested a greater treatment effect with tamoxifen plus ovarian suppression than with tamoxifen alone (hazard ratio, 0.78; 95% CI, 0.62 to 0.98). Most recurrences occurred in patients who had received prior chemotherapy, among whom the rate of freedom from breast cancer at 5 years was 82.5% in the tamoxifen-ovarian suppression group and 78.0% in the tamoxifen group (hazard ratio for recurrence, 0.78; 95% CI, 0.60 to 1.02). At 5 years, the rate of freedom from breast cancer was 85.7% in the exemestane-ovarian suppression group (hazard ratio for recurrence vs. tamoxifen, 0.65; 95% CI, 0.49 to 0.87).\n\nConclusions: Adding ovarian suppression to tamoxifen did not provide a significant benefit in the overall study population. However, for women who were at sufficient risk for recurrence to warrant adjuvant chemotherapy and who remained premenopausal, the addition of ovarian suppression improved disease outcomes. Further improvement was seen with the use of exemestane plus ovarian suppression. (Funded by Pfizer and others; SOFT ClinicalTrials.gov number, NCT00066690.).\n\nIndexed on Europe PMC as PubMed record 25495490 (DOI 10.1056/nejmoa1412379). Its abstract cites the registry id NCT00066690, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2015","url":"https://doi.org/10.1056/nejmoa1412379"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25495490/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25495490"},{"label":"ClinicalTrials.gov NCT00066690","url":"https://clinicaltrials.gov/study/NCT00066690"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["soft-text"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2015,"doi":"10.1056/nejmoa1412379","pmid":"25495490","authors":"Francis PA, Regan MM, Fleming GF, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT00066690 with the most citations, so it is the natural first reading for anyone following the SOFT trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-apt-trial-lancet-oncol-2023-update","kind":"paper","name":"Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer: final 10-year analysis of the open-label, single-arm, phase 2 APT trial","aka":[],"tldr":"Later report from the trial registered as NCT00542451, in The Lancet Oncology (2023); its title describes an updated or longer-term analysis.","summary":"Background: We aimed to report on long-term outcomes of patients with small, node-negative, HER2-positive breast cancer treated with adjuvant paclitaxel and trastuzumab and to establish potential biomarkers to predict prognosis.\n\nMethods: In this open-label, single-arm, phase 2 study, patients aged 18 years or older, with small (≤3 cm), node-negative, HER2-positive breast cancer, and an Eastern Cooperative Oncology Group performance status of 0-1, were recruited from 16 institutions in 13 cities in the USA. Eligible patients were given intravenous paclitaxel (80 mg/m 2) with intravenous trastuzumab (loading dose of 4 mg/kg, subsequent doses 2 mg/kg) weekly for 12 weeks, followed by trastuzumab (weekly at 2 mg/kg or once every 3 weeks at 6 mg/kg) for 40 weeks to complete a full year of trastuzumab. The primary endpoint was 3-year invasive disease-free survival. Here, we report 10-year survival outcomes, assessed in all participants who received protocol-defined treatment, with exploratory analyses using the HER2DX genomic tool. This study is registered on ClinicalTrials.gov, NCT00542451, and is closed to accrual.\n\nFindings: Between Oct 29, 2007, and Sept 3, 2010, 410 patients were enrolled and 406 were given adjuvant paclitaxel and trastuzumab and included in the analysis. Mean age at enrolment was 55 years (SD 10·5), 405 (99·8%) of 406 patients were female and one (0·2%) was male, 350 (86·2%) were White, 28 (6·9%) were Black or African American, and 272 (67·0%) had hormone receptor-positive disease. After a median follow-up of 10·8 years (IQR 7·1-11·4), among 406 patients included in the analysis population, we observed 31 invasive disease-free survival events, of which six (19·4%) were locoregional ipsilateral recurrences, nine (29·0%) were new contralateral breast cancers, six (19·4%) were distant recurrences, and ten (32·3%) were all-cause deaths. 10-year invasive disease-free survival was 91·3% (95% CI 88·3-94·4), 10-year recurrence-free interval was 96·3% (95% CI 94·3-98·3), 10-year overall survival was 94·3% (95% CI 91·8-96·8), and 10-year breast cancer-specific survival was 98·8% (95% CI 97·6-100). HER2DX risk score as a continuous variable was significantly associated with invasive disease-free survival (hazard ratio [HR] per 10-unit increment 1·24 [95% CI 1·00-1·52]; p=0·047) and recurrence-free interval (1·45 [1·09-1·93]; p=0·011).\n\nInterpretation: Adjuvant paclitaxel and trastuzumab is a reasonable treatment standard for patients with small, node-negative, HER2-positive breast cancer. The HER2DX genomic tool might help to refine the prognosis for this population.\n\nFunding: Genentech.\n\nIndexed on Europe PMC as PubMed record 36858723 (DOI 10.1016/s1470-2045(23)00051-7). Its abstract cites the registry id NCT00542451, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2023","url":"https://doi.org/10.1016/s1470-2045(23)00051-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36858723/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36858723"},{"label":"ClinicalTrials.gov NCT00542451","url":"https://clinicaltrials.gov/study/NCT00542451"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["apt-trial"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2023,"doi":"10.1016/s1470-2045(23)00051-7","pmid":"36858723","authors":"Tolaney SM, Tarantino P, Graham N, et al.","paperType":"observational","findings":[],"whatItMeans":"A second publication from the trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-nct02362594-lancet-oncol-2021-update","kind":"paper","name":"Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): distant metastasis-free survival results from a double-blind, randomised, controlled, phase 3 trial","aka":[],"tldr":"Later report from the KEYNOTE-054 trial registered as NCT02362594, in The Lancet Oncology (2021); its title describes an updated or longer-term analysis.","summary":"Background: The European Organisation for Research and Treatment of Cancer (EORTC) 1325/KEYNOTE-054 trial assessed pembrolizumab versus placebo in patients with resected high-risk stage III melanoma. At 15-month median follow-up, pembrolizumab improved recurrence-free survival (hazard ratio [HR] 0·57 [98·4% CI 0·43-0·74], p<0·0001) compared with placebo, leading to its approval in the USA and Europe. This report provides the final results for the secondary efficacy endpoint, distant metastasis-free survival and an update of the recurrence-free survival results.\n\nMethods: This double-blind, randomised, controlled, phase 3 trial was done at 123 academic centres and community hospitals across 23 countries. Patients aged 18 years or older with complete resection of cutaneous melanoma metastatic to lymph node, classified as American Joint Committee on Cancer staging system, seventh edition (AJCC-7) stage IIIA (at least one lymph node metastasis >1 mm), IIIB, or IIIC (without in-transit metastasis), and with an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible. Patients were randomly assigned (1:1) via a central interactive voice response system to receive intravenous pembrolizumab 200 mg or placebo every 3 weeks for up to 18 doses or until disease recurrence or unacceptable toxicity. Randomisation was stratified according to disease stage and region, using a minimisation technique, and clinical investigators, patients, and those collecting or analysing the data were masked to treatment assignment. The two coprimary endpoints were recurrence-free survival in the intention-to-treat (ITT) population and in patients with PD-L1-positive tumours. The secondary endpoint reported here was distant metastasis-free survival in the ITT and PD-L1-positive populations. This study is registered with ClinicalTrials.gov, NCT02362594, and EudraCT, 2014-004944-37.\n\nFindings: Between Aug 26, 2015, and Nov 14, 2016, 1019 patients were assigned to receive either pembrolizumab (n=514) or placebo (n=505). At an overall median follow-up of 42·3 months (IQR 40·5-45·9), 3·5-year distant metastasis-free survival was higher in the pembrolizumab group than in the placebo group in the ITT population (65·3% [95% CI 60·9-69·5] in the pembrolizumab group vs 49·4% [44·8-53·8] in the placebo group; HR 0·60 [95% CI 0·49-0·73]; p<0·0001). In the 853 patients with PD-L1-positive tumours, 3·5-year distant metastasis-free survival was 66·7% (95% CI 61·8-71·2) in the pembrolizumab group and 51·6% (46·6-56·4) in the placebo group (HR 0·61 [95% CI 0·49-0·76]; p<0·0001). Recurrence-free survival remained longer in the pembrolizumab group 59·8% (95% CI 55·3-64·1) than the placebo group 41·4% (37·0-45·8) at this 3·5-year follow-up in the ITT population (HR 0·59 [95% CI 0·49-0·70]) and in those with PD-L1-positive tumours 61·4% (56·3-66·1) in the pembrolizumab group and 44·1% (39·2-48·8) in the placebo group (HR 0·59 [95% CI 0·49-0·73]).\n\nInterpretation: Pembrolizumab adjuvant therapy provided a significant and clinically meaningful improvement in distant metastasis-free survival at a 3·5-year median follow-up, which was consistent with the improvement in recurrence-free survival. Therefore, the results of this trial support the indication to use adjuvant pembrolizumab therapy in patients with resected high risk stage III cutaneous melanoma.\n\nFunding: Merck Sharp & Dohme.\n\nIndexed on Europe PMC as PubMed record 33857412 (DOI 10.1016/s1470-2045(21)00065-6). Its abstract cites the registry id NCT02362594, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2021","url":"https://doi.org/10.1016/s1470-2045(21)00065-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33857412/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33857412"},{"label":"ClinicalTrials.gov NCT02362594","url":"https://clinicaltrials.gov/study/NCT02362594"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct02362594"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2021,"doi":"10.1016/s1470-2045(21)00065-6","pmid":"33857412","authors":"Eggermont AMM, Blank CU, Mandalà M, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the KEYNOTE-054 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-aphinity-j-clin-oncol-2024-update","kind":"paper","name":"Adjuvant Pertuzumab and Trastuzumab in Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer in the APHINITY Trial: Third Interim Overall Survival Analysis With Efficacy Update","aka":[],"tldr":"Later report from the APHINITY trial registered as NCT01358877, in Journal of Clinical Oncology (2024); its title describes an updated or longer-term analysis.","summary":"Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. The APHINITY trial (ClinicalTrials.gov identifier: NCT01358877) previously demonstrated that pertuzumab added to adjuvant trastuzumab and chemotherapy improved invasive disease-free survival (iDFS) for patients with early human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC). Here, we report the preplanned third interim analysis of overall survival (OS) and a descriptive updated iDFS analysis with 8.4 years of median follow-up of 4,804 patients in the intent-to-treat population. The 8-year OS was 92.7% in the pertuzumab versus 92.0% in the placebo group (hazard ratio [HR], 0.83 [95% CI, 0.68 to 1.02]; P =.078, above the 0.006 significance threshold). The HR was 0.80 [95% CI 0.63 to 1.00] in the node-positive cohort and 0.99 [95% CI, 0.64 to 1.55] in the node-negative cohort. Updated results of 8-year iDFS in the node-positive cohort showed an absolute improvement of 4.9% favoring pertuzumab (86.1% v 81.2%; HR, 0.72 [95% CI, 0.60 to 0.87]). The node-negative cohort did well without adding pertuzumab (8-year iDFS and OS in the placebo group were 93.3% and 96.4%, respectively). The iDFS benefit was seen in the hormone receptor-negative (HR, 0.82 [95% CI, 0.64 to 1.06]) and HR+ cohorts (HR of 0.75 [95% CI, 0.61 to 0.92]). Despite improvement in overall iDFS, the addition of pertuzumab did not improve OS at this third interim analysis.\n\nIndexed on Europe PMC as PubMed record 39259927 (DOI 10.1200/jco.23.02505). Its abstract cites the registry id NCT01358877, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2024","url":"https://doi.org/10.1200/jco.23.02505"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39259927/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39259927"},{"label":"ClinicalTrials.gov NCT01358877","url":"https://clinicaltrials.gov/study/NCT01358877"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["aphinity"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2024,"doi":"10.1200/jco.23.02505","pmid":"39259927","authors":"Loibl S, Jassem J, Sonnenblick A, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the APHINITY trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-lian-adjuvant-temozolomide-cisplatin-mucosal-melanoma-ccr-2013","kind":"paper","name":"Adjuvant temozolomide plus cisplatin versus high-dose interferon versus observation in resected mucosal melanoma","aka":[],"tldr":"In this Chinese randomised trial, chemotherapy with temozolomide and cisplatin after surgery for mucosal melanoma lengthened relapse-free and overall survival compared with interferon or observation, the only positive adjuvant trial specific to mucosal disease.","summary":"Phase 2 randomised trial of 189 patients with resected mucosal melanoma assigned to observation, high-dose interferon alfa-2b for one year, or six cycles of temozolomide plus cisplatin.\n\nMedian relapse-free survival was 5.4 months with observation, 9.4 months with interferon and 20.8 months with chemotherapy, and median overall survival 21.2, 40.4 and 48.7 months respectively.","asOf":"2026-09-17","links":[{"label":"Clin Cancer Res 2013","url":"https://doi.org/10.1158/1078-0432.CCR-13-0739"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23833309/"}],"tags":[],"related":[],"cancers":["mucosal-melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":["cisplatin","temozolomide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2013,"doi":"10.1158/1078-0432.CCR-13-0739","pmid":"23833309","authors":"Lian B, Si L, Cui C, et al.","paperType":"rct","findings":["Median relapse-free survival 20.8 months (chemotherapy) vs 9.4 (interferon) vs 5.4 (observation).","Median overall survival 48.7 vs 40.4 vs 21.2 months."],"whatItMeans":"Adjuvant temozolomide-cisplatin is used in China for resected mucosal melanoma; elsewhere anti-PD-1 therapy is extrapolated from cutaneous disease, and the two have since been compared directly.","caveats":["Single-country phase 2 trial in a largely Asian population.","Predates adjuvant immunotherapy."],"changedPractice":true,"participants":189},{"id":"paper-trastuzumab-breast-her2-positive-n-engl-j-med-2011","kind":"paper","name":"Adjuvant trastuzumab in HER2-positive breast cancer","aka":[],"tldr":"Phase 2 or 3 results paper on Trastuzumab in HER2-positive breast cancer, in New England Journal of Medicine (2011), one of the most cited Europe PMC records with Trastuzumab in its title.","summary":"Background: Trastuzumab improves survival in the adjuvant treatment of HER-positive breast cancer, although combined therapy with anthracycline-based regimens has been associated with cardiac toxicity. We wanted to evaluate the efficacy and safety of a new nonanthracycline regimen with trastuzumab.\n\nMethods: We randomly assigned 3222 women with HER2-positive early-stage breast cancer to receive doxorubicin and cyclophosphamide followed by docetaxel every 3 weeks (AC-T), the same regimen plus 52 weeks of trastuzumab (AC-T plus trastuzumab), or docetaxel and carboplatin plus 52 weeks of trastuzumab (TCH). The primary study end point was disease-free survival. Secondary end points were overall survival and safety.\n\nResults: At a median follow-up of 65 months, 656 events triggered this protocol-specified analysis. The estimated disease-free survival rates at 5 years were 75% among patients receiving AC-T, 84% among those receiving AC-T plus trastuzumab, and 81% among those receiving TCH. Estimated rates of overall survival were 87%, 92%, and 91%, respectively. No significant differences in efficacy (disease-free or overall survival) were found between the two trastuzumab regimens, whereas both were superior to AC-T. The rates of congestive heart failure and cardiac dysfunction were significantly higher in the group receiving AC-T plus trastuzumab than in the TCH group (P<0.001). Eight cases of acute leukemia were reported: seven in the groups receiving the anthracycline-based regimens and one in the TCH group subsequent to receiving an anthracycline outside the study.\n\nConclusions: The addition of 1 year of adjuvant trastuzumab significantly improved disease-free and overall survival among women with HER2-positive breast cancer. The risk-benefit ratio favored the nonanthracycline TCH regimen over AC-T plus trastuzumab, given its similar efficacy, fewer acute toxic effects, and lower risks of cardiotoxicity and leukemia. (Funded by Sanofi-Aventis and Genentech; BCIRG-006 ClinicalTrials.gov number, NCT00021255.).\n\nIndexed on Europe PMC as PubMed record 21991949 (DOI 10.1056/nejmoa0910383). Its title names Trastuzumab and its text names HER2-positive breast cancer; PubMed types it as a clinical trial report (Research Support, Non-U.S. Gov't, research-article, Multicenter Study, Randomized Controlled Trial, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural). It was matched automatically to the idea \"Can T-DXd alone cure early HER2-positive disease?\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2011","url":"https://doi.org/10.1056/nejmoa0910383"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21991949/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/21991949"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2011,"doi":"10.1056/nejmoa0910383","pmid":"21991949","authors":"Slamon D, Eiermann W, Robert N, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Trastuzumab in HER2-positive breast cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Trastuzumab in the title and HER2-positive breast cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-admiral-gilteritinib-flt3-nejm-2019","kind":"paper","name":"ADMIRAL: gilteritinib pills versus chemotherapy for relapsed FLT3-mutated acute myeloid leukaemia","aka":[],"tldr":"An oral FLT3 inhibitor extended survival compared with salvage chemotherapy in relapsed AML with a FLT3 mutation, doubling the remission rate.","summary":"ADMIRAL randomised 371 adults with relapsed or refractory FLT3-mutated AML in a 2:1 ratio to gilteritinib 120 mg daily or investigator-chosen salvage chemotherapy (high- or low-intensity). Primary endpoints were overall survival and the rate of complete remission or remission with partial haematological recovery. Median OS was 9.3 versus 5.6 months (hazard ratio 0.64) and one-year survival 37.1% versus 16.7%; CR/CRh was 34.0% versus 15.3%. More patients on gilteritinib proceeded to transplant, and toxicity was lower than with chemotherapy. It established single-agent targeted therapy as a standard in relapsed FLT3-mutated AML.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa1902688"},{"label":"ClinicalTrials.gov NCT02421939","url":"https://clinicaltrials.gov/study/NCT02421939"}],"tags":[],"related":["paper-quantum-first-quizartinib-lancet-2023"],"cancers":["aml"],"sections":[],"technologies":["allogeneic-hsct"],"targets":["flt3"],"drugs":["gilteritinib","midostaurin","quizartinib"],"companies":["astellas"],"institutions":[],"pathways":[],"terms":["os"],"trials":["admiral"],"people":[],"bottlenecks":["b-resistance"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2019,"doi":"10.1056/NEJMoa1902688","authors":"Perl AE, Martinelli G, Cortes JE, et al.","paperType":"rct","findings":["371 patients with relapsed/refractory FLT3-mutated AML; gilteritinib vs salvage chemotherapy (2:1).","Median OS 9.3 vs 5.6 months; hazard ratio 0.64.","1-year overall survival 37.1% vs 16.7%.","CR/CRh 34.0% vs 15.3%; complete remission 21.1% vs 10.5%.","Fewer grade 3 or higher adverse events per exposure-adjusted analysis with gilteritinib."],"whatItMeans":"ADMIRAL showed that a targeted oral drug can beat chemotherapy outright in relapsed AML, and made gilteritinib the standard bridge to transplant for FLT3-mutated relapse. Its success also underpinned FLT3 inhibitor use in first-line combinations. Resistance through FLT3-independent clones and RAS pathway mutations limits durability without transplant.","caveats":["Modest absolute survival gain; most patients not transplanted eventually relapsed.","Open-label with heterogeneous chemotherapy comparators.","Excluded patients previously treated with certain FLT3 inhibitors; prior midostaurin exposure was uncommon.","Differentiation syndrome and QT prolongation require monitoring."],"changedPractice":true,"participants":371},{"id":"paper-besser-til-melanoma-intent-to-treat-ccr-2013","kind":"paper","name":"Adoptive transfer of tumor-infiltrating lymphocytes in patients with metastatic melanoma: intent-to-treat analysis and efficacy after failure to prior immunotherapies","aka":[],"tldr":"Sheba's decade of growing melanoma patients' own tumour-fighting cells and giving them back, reported honestly: counting everyone who enrolled, not only those who made it to treatment.","summary":"The Ella Lemelbaum Institute at Sheba Medical Center began treating metastatic melanoma with autologous tumour-infiltrating lymphocytes in 2006, more than a decade before any regulator approved the approach. This report is the intent-to-treat analysis of the first 80 patients with stage IV disease enrolled in the programme.\n\nTumour-infiltrating lymphocyte cultures could be established for 72 of the 80. Fifty-seven were treated with unselected or young lymphocytes and high-dose interleukin-2 after non-myeloablative lymphodepleting conditioning. Twenty-three were withdrawn, mostly because they deteriorated clinically during the weeks the cells were being grown, which is the cost of a manufacturing step that cannot be hurried.\n\nThe overall response rate was 29 percent and median survival 9.8 months counting everyone enrolled; 40 percent and 15.2 months counting those actually treated. Five patients achieved complete and 18 partial remission. Every complete responder remained in unmaintained remission at a median follow-up of 28 months, and three-year survival among responders was 78 percent. On multivariate analysis, lactate dehydrogenase, sex, days of culture and the total number of infused CD8-positive cells independently predicted outcome. Thirty-two patients received ipilimumab before or after the cells; patients who had not responded to ipilimumab or interleukin-2 did about as well on cell therapy as those who had.","asOf":"2026-09-25","links":[{"label":"Clin Cancer Res 2013","url":"https://doi.org/10.1158/1078-0432.ccr-13-0380"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23690483/"}],"tags":[],"related":[],"cancers":["melanoma"],"sections":["cell-therapy"],"technologies":["til-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":["sheba"],"pathways":[],"terms":[],"trials":[],"people":["michal-besser","jacob-schachter","gal-markel"],"bottlenecks":["b-manufacturing-cell-therapy"],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2013,"doi":"10.1158/1078-0432.ccr-13-0380","pmid":"23690483","authors":"Besser MJ, Shapira-Frommer R, Itzhaki O, Treves AJ, Zippel DB, Levy D, Kubi A, Shoshani N, Zikich D, Ohayon Y, Ohayon D, Shalmon B, Markel G, Yerushalmi R, Apter S, Ben-Nun A, Schachter J, et al.","paperType":"observational","findings":["Cultures established for 72 of 80 enrolled patients; 57 treated; 23 withdrawn, mainly through clinical deterioration during manufacture.","Overall response rate 29 percent and median survival 9.8 months on intent to treat; 40 percent and 15.2 months among treated patients.","Five complete and 18 partial remissions; all complete responders in unmaintained remission at a median 28 months; three-year survival among responders 78 percent.","Lactate dehydrogenase, sex, days of cells in culture and total infused CD8-positive cells were independent predictors of outcome.","Failure of prior ipilimumab or interleukin-2 did not predict failure of cell therapy."],"whatItMeans":"It showed that a single academic centre outside the United States could run tumour-infiltrating lymphocyte therapy at scale and get durable remissions, and it quantified the attrition that intent-to-treat reporting exposes and single-arm treated-patient reporting hides.","caveats":["Single-arm, single-centre and not randomised, in an era before checkpoint inhibitors became standard first-line treatment, so the comparison group is historical.","High-dose interleukin-2 and lymphodepletion make the regimen unsuitable for frail patients, and the three-week manufacturing window excluded nearly a third of those enrolled."],"participants":80},{"id":"paper-zahalka-science","kind":"paper","name":"Adrenergic nerves activate an angio-metabolic switch in prostate cancer","aka":[],"tldr":"Paper cited by one idea page, indexed on Europe PMC as PubMed record 29051371 and published in Science; the citing page links this DOI, which is how the record was matched.","summary":"Nerves closely associate with blood vessels and help to pattern the vasculature during development. Recent work suggests that newly formed nerve fibers may regulate the tumor microenvironment, but their exact functions are unclear. Studying mouse models of prostate cancer, we show that endothelial β-adrenergic receptor signaling via adrenergic nerve-derived noradrenaline in the prostate stroma is critical for activation of an angiogenic switch that fuels exponential tumor growth. Mechanistically, this occurs through alteration of endothelial cell metabolism. Endothelial cells typically rely on aerobic glycolysis for angiogenesis. We found that the loss of endothelial Adrb2, the gene encoding the β 2 -adrenergic receptor, leads to inhibition of angiogenesis through enhancement of endothelial oxidative phosphorylation. Codeletion of Adrb2 and Cox10, a gene encoding a cytochrome IV oxidase assembly factor, prevented the metabolic shift induced by Adrb2 deletion and rescued prostate cancer progression. This cross-talk between nerves and endothelial metabolism could potentially be targeted as an anticancer therapy.\n\nIndexed on Europe PMC as PubMed record 29051371 (DOI 10.1126/science.aah5072). Matched by DOI alone: one idea page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Science 2017","url":"https://doi.org/10.1126/science.aah5072"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29051371/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29051371"}],"tags":["europepmc-ingest"],"related":["idea-nerve-tumour-blockade"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2017,"doi":"10.1126/science.aah5072","pmid":"29051371","authors":"Zahalka AH, Arnal-Estapé A, Maryanovich M, et al.","paperType":"observational","findings":[],"whatItMeans":"One idea page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-adriatic-nejm-2024","kind":"paper","name":"ADRIATIC: durvalumab after chemoradiotherapy for limited-stage small-cell lung cancer","aka":[],"tldr":"For small-cell lung cancer confined to the chest, adding two years of durvalumab after chemoradiotherapy extended median survival from under three years to over four and a half, the first advance in this setting in decades.","summary":"Double-blind, placebo-controlled phase 3 trial of 730 patients with limited-stage small-cell lung cancer who had not progressed after concurrent platinum-etoposide chemoradiotherapy, randomised to durvalumab, durvalumab plus tremelimumab, or placebo for up to 24 months. Primary endpoints were overall survival and PFS for durvalumab versus placebo.\n\nMedian overall survival was 55.9 vs 33.4 months (HR 0.73) and median PFS 16.6 vs 9.2 months (HR 0.76). It applied the PACIFIC consolidation model to small-cell lung cancer and became the new standard for limited-stage disease.","asOf":"2026-09-08","links":[{"label":"NEJM 2024","url":"https://doi.org/10.1056/NEJMoa2404873"},{"label":"ClinicalTrials.gov NCT03703297","url":"https://clinicaltrials.gov/study/NCT03703297"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39268857/"}],"tags":[],"related":["paper-turrisi-twice-daily-thoracic-radiotherapy-limited-sclc-nejm-1999","paper-spigel-pacific-five-year-survival-jco-2022","paper-paz-ares-caspian-durvalumab-es-sclc-lancet-2019"],"cancers":["sclc","lung-cancer","limited-stage-sclc"],"sections":["immunotherapy","radiation"],"technologies":["checkpoint-inhibitor","imrt-igrt","platinum","radiotherapy"],"targets":["pdl1","pd1"],"drugs":["durvalumab","tremelimumab"],"companies":["astrazeneca"],"institutions":[],"pathways":["immune-checkpoint"],"terms":["os","pfs","standard-of-care","chemoradiation","prophylactic-cranial-irradiation"],"trials":["adriatic"],"people":["cho-byoung-chul"],"bottlenecks":["b-immunotherapy-response","b-surgery-radiation-innovation","b-rare-cancers","b-biomarker-validation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2024,"doi":"10.1056/NEJMoa2404873","pmid":"39268857","authors":"Cheng Y, Spigel DR, Cho BC, et al.","paperType":"rct","findings":["Median overall survival 55.9 vs 33.4 months; HR 0.73 (98.321% CI 0.54-0.98); 36-month OS 56.5% vs 47.6%.","Median PFS 16.6 vs 9.2 months; HR 0.76; 24-month PFS 46.2% vs 34.2%.","Grade 3-4 adverse events 24.4% vs 24.2%; pneumonitis or radiation pneumonitis of any grade 38.2% vs 30.2%.","Benefit was consistent regardless of whether prophylactic cranial irradiation had been given."],"whatItMeans":"Patients with limited-stage small-cell lung cancer who complete chemoradiotherapy without progression should now be offered up to two years of durvalumab consolidation, which extends life by almost two years on average. This is the first survival improvement for limited-stage disease since twice-daily radiotherapy and prophylactic cranial irradiation, and small-cell lung cancer is no longer a disease where immunotherapy gives only marginal gains.","caveats":["The durvalumab plus tremelimumab arm has not shown clear additional benefit and its role is unclear.","Radiotherapy schedules varied (once or twice daily) and prophylactic cranial irradiation was optional, adding heterogeneity.","Only patients without progression after chemoradiotherapy were eligible, as in PACIFIC.","No biomarker predicts benefit; PD-L1 is not useful in small-cell lung cancer."],"changedPractice":true,"participants":730},{"id":"paper-hinuma-adult-t-cell-leukaemia-antigen-pnas-1981","kind":"paper","name":"Adult T-cell leukemia: antigen in an ATL cell line and detection of antibodies to the antigen in human sera","aka":["Hinuma 1981","ATLA antigen","Seroepidemiology of HTLV-1 in Japan"],"tldr":"Japanese researchers found an antigen in cells from a patient with an unusual leukaemia, then found antibodies to it in every one of 44 patients with that leukaemia and in a quarter of healthy adults where the disease clusters.","summary":"Yorio Hinuma and colleagues used indirect immunofluorescence to detect an antigen in the cytoplasm of 1 to 5 per cent of cells of MT-1, a T-cell line from a patient with adult T-cell leukaemia, a disease endemic in southwestern Japan. The antigen was absent from six other T-cell lines, seven B-cell lines and four non-T non-B lines, and did not cross-react with Epstein-Barr virus, herpes simplex virus, cytomegalovirus, varicella-zoster virus, herpesvirus saimiri or Marek disease virus. Culturing with 5-iodo-2'-deoxyuridine increased the proportion of antigen-bearing cells roughly fivefold, and electron microscopy of those cultures showed extracellular type C virus particles.\n\nThe serology is what made the case. Antibodies against the antigen were found in all 44 patients with adult T-cell leukaemia examined, in 32 of 40 patients with malignant T-cell lymphomas resembling it, in 26 per cent of healthy adults from endemic areas, and in only a few of those from non-endemic areas.\n\nTogether with Poiesz's isolation of the virus in the United States the year before, this established human T-lymphotropic virus type 1 as the cause of adult T-cell leukaemia/lymphoma, a disease the OnCo corpus does not yet hold as a record of its own.","asOf":"2026-10-01","links":[{"label":"Proceedings of the National Academy of Sciences 1981","url":"https://doi.org/10.1073/pnas.78.10.6476"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/7031654/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/7031654"}],"tags":["lymphoma-evidence"],"related":["paper-poiesz-htlv-retrovirus-cutaneous-t-cell-lymphoma-pnas-1980","lymphoma-roadmap"],"cancers":["peripheral-t-cell-lymphoma","non-hodgkin-lymphoma"],"sections":["prevention","diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["jcog9801"],"people":[],"bottlenecks":["b-prevention-adoption","b-global-access"],"keyPapers":[],"journals":["pnas"],"dependsOn":[],"notes":[],"journal":"Proceedings of the National Academy of Sciences","year":1981,"doi":"10.1073/pnas.78.10.6476","pmid":"7031654","authors":"Hinuma Y, Nagata K, Hanaoka M, et al.","paperType":"basic","findings":["An antigen was detected by indirect immunofluorescence in the cytoplasm of 1 to 5 per cent of cells of the MT-1 T-cell line from a patient with adult T-cell leukaemia.","The antigen was absent from six other T-cell lines, seven B-cell lines and four non-T non-B cell lines, and showed no cross-reactivity with six herpesviruses including Epstein-Barr virus.","Antibodies to the antigen were found in all 44 patients with adult T-cell leukaemia examined and in 32 of 40 patients with similar malignant T-cell lymphomas.","Antibodies were present in 26 per cent of healthy adults from endemic areas but in only a few from non-endemic areas.","Electron microscopy of induced MT-1 cultures showed extracellular type C virus particles."],"whatItMeans":"The seroepidemiology that tied a virus to a cancer across a population rather than in one patient. It is the reason blood donations are screened for human T-lymphotropic virus type 1 in Japan and elsewhere, and the reason breastfeeding advice is part of cancer prevention in endemic regions.","caveats":["Antibody prevalence of 26 per cent in healthy adults from endemic areas against a lifetime leukaemia risk of a few per cent shows that infection is far from sufficient to cause disease.","The assay detected an antigen rather than isolating the virus; the isolation was Poiesz's the year before.","Sample sizes are small by modern standards, and the comparison areas were not matched for anything other than endemicity."],"changedPractice":true},{"id":"paper-cardenas-semin-radiat-oncol","kind":"paper","name":"Advances in Auto-Segmentation","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 31027636 and published in Seminars in radiation oncology; the citing page links this DOI, which is how the record was matched.","summary":"Manual image segmentation is a time-consuming task routinely performed in radiotherapy to identify each patient's targets and anatomical structures. The efficacy and safety of the radiotherapy plan requires accurate segmentations as these regions of interest are generally used to optimize and assess the quality of the plan. However, reports have shown that this process can be subject to significant inter- and intraobserver variability. Furthermore, the quality of the radiotherapy treatment, and subsequent analyses (ie, radiomics, dosimetric), can be subject to the accuracy of these manual segmentations. Automatic segmentation (or auto-segmentation) of targets and normal tissues is, therefore, preferable as it would address these challenges. Previously, auto-segmentation techniques have been clustered into 3 generations of algorithms, with multiatlas based and hybrid techniques (third generation) being considered the state-of-the-art. More recently, however, the field of medical image segmentation has seen accelerated growth driven by advances in computer vision, particularly through the application of deep learning algorithms, suggesting we have entered the fourth generation of auto-segmentation algorithm development. In this paper, the authors review traditional (nondeep learning) algorithms particularly relevant for applications in radiotherapy. Concepts from deep learning are introduced focusing on convolutional neural networks and fully-convolutional networks which are generally used for segmentation tasks. Furthermore, the authors provide a summary of deep learning auto-segmentation radiotherapy applications reported in the literature. Lastly, considerations for clinical deployment (commissioning and QA) of auto-segmentation software are provided.\n\nIndexed on Europe PMC as PubMed record 31027636 (DOI 10.1016/j.semradonc.2019.02.001). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Semin Radiat Oncol 2019","url":"https://doi.org/10.1016/j.semradonc.2019.02.001"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31027636/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31027636"}],"tags":["europepmc-ingest"],"related":["auto-contouring-ai"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["seminars-in-radiation-oncology"],"dependsOn":[],"notes":[],"journal":"Seminars in radiation oncology","year":2019,"doi":"10.1016/j.semradonc.2019.02.001","pmid":"31027636","authors":"Cardenas CE, Yang J, Anderson BM, et al.","paperType":"review","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-aeneas-j-clin-oncol-2022","kind":"paper","name":"AENEAS: A Randomized Phase III Trial of Aumolertinib Versus Gefitinib as First-Line Therapy for Locally Advanced or MetastaticNon-Small-Cell Lung Cancer With EGFR Exon 19 Deletion or L858R Mutations","aka":[],"tldr":"Published report from the AENEAS trial registered as NCT03849768, in Journal of Clinical Oncology (2022), chosen as the most cited paper whose own text cites the registry id.","summary":"Purpose: Aumolertinib (formerly almonertinib; HS-10296) is a novel third-generation epidermal growth factor receptor tyrosine kinase inhibitor approved in China. This double-blind phase III trial evaluated the efficacy and safety of aumolertinib compared with gefitinib as a first-line treatment for locally advanced or metastatic EGFR -mutated non-small-cell lung cancer (NSCLC; ClinicalTrials.gov identifier: NCT03849768).\n\nMethods: Patients at 53 sites in China were randomly assigned 1:1 to receive either aumolertinib (110 mg) or gefitinib (250 mg) once daily. The primary end point was progression-free survival (PFS) per investigator assessment.\n\nResults: A total of 429 patients who were naïve to treatment for locally advanced or metastatic NSCLC were enrolled. PFS was significantly longer with aumolertinib compared with gefitinib (hazard ratio, 0.46; 95% CI, 0.36 to 0.60; P <.0001). The median PFS with aumolertinib was 19.3 months (95% CI, 17.8 to 20.8) versus 9.9 months with gefitinib (95% CI, 8.3 to 12.6). Objective response rate and disease control rate were similar in the aumolertinib and gefitinib groups (objective response rate, 73.8% and 72.1%, respectively; disease control rate, 93.0% and 96.7%, respectively). The median duration of response was 18.1 months (95% CI, 15.2 to not applicable) with aumolertinib versus 8.3 months (95% CI, 6.9 to 11.1) with gefitinib. Adverse events of grade ≥ 3 severity (any cause) were observed in 36.4% and 35.8% of patients in the aumolertinib and gefitinib groups, respectively. Rash and diarrhea (any grade) were observed in 23.4% and 16.4% of patients who received aumolertinib compared with 41.4% and 35.8% of those who received gefitinib, respectively.\n\nConclusion: Aumolertinib is a well-tolerated third-generation epidermal growth factor receptor tyrosine kinase inhibitor that could serve as a treatment option for EGFR -mutant NSCLC in the first-line setting.\n\nIndexed on Europe PMC as PubMed record 35580297 (DOI 10.1200/jco.21.02641). Its abstract cites the registry id NCT03849768, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2022","url":"https://doi.org/10.1200/jco.21.02641"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35580297/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35580297"},{"label":"ClinicalTrials.gov NCT03849768","url":"https://clinicaltrials.gov/study/NCT03849768"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["aeneas"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2022,"doi":"10.1200/jco.21.02641","pmid":"35580297","authors":"Lu S, Dong X, Jian H, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03849768 with the most citations, so it is the natural first reading for anyone following the AENEAS trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-aethera-brentuximab-consolidation-after-asct-hodgkin-lancet-2015","kind":"paper","name":"AETHERA: brentuximab vedotin consolidation after autologous stem cell transplantation in Hodgkin lymphoma at risk of relapse","aka":[],"tldr":"Giving the antibody-drug conjugate brentuximab vedotin for up to a year after a stem cell transplant roughly doubled the time before Hodgkin lymphoma came back in patients at high risk of relapse.","summary":"International randomised double-blind placebo-controlled phase 3 trial of 329 patients with Hodgkin lymphoma at high risk of relapse after autologous stem cell transplantation (primary refractory disease, relapse within twelve months, or extranodal relapse), assigned to up to 16 cycles of brentuximab vedotin or placebo starting 30 to 45 days after transplant.\n\nMedian progression-free survival by independent review was 42.9 months with brentuximab vedotin against 24.1 months with placebo (hazard ratio 0.57); peripheral neuropathy was the main toxicity. Overall survival did not differ, partly because placebo patients received brentuximab at relapse.","asOf":"2026-09-18","links":[{"label":"Lancet 2015","url":"https://doi.org/10.1016/S0140-6736(15)60165-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25796459/"}],"tags":[],"related":[],"cancers":["relapsed-refractory-hodgkin-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["brentuximab-vedotin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["aethera"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2015,"doi":"10.1016/S0140-6736(15)60165-9","pmid":"25796459","authors":"Moskowitz CH, Nademanee A, Masszi T, et al.","paperType":"rct","findings":["Median progression-free survival 42.9 months with brentuximab vedotin versus 24.1 months with placebo; hazard ratio 0.57.","Peripheral sensory neuropathy in about two thirds of treated patients, mostly reversible."],"whatItMeans":"Patients at high risk of relapse after autologous transplant are offered brentuximab vedotin consolidation; the benefit is largest in those with two or more risk factors.","caveats":["No overall survival benefit, with crossover at relapse.","Patients who had already received brentuximab before transplant were excluded, which now describes many candidates."],"changedPractice":true,"participants":329},{"id":"paper-aews0031-interval-compressed-chemotherapy-ewing-womer-jco-2012","kind":"paper","name":"AEWS0031: randomised trial of interval-compressed chemotherapy for localised Ewing sarcoma","aka":[],"tldr":"Giving the standard Ewing sarcoma chemotherapy every two weeks rather than every three cured more patients, 73 against 65 percent free of events at five years, with no more side effects.","summary":"Children's Oncology Group phase 3 trial: 587 patients with localised Ewing sarcoma (568 eligible, 284 per arm) were randomised to alternating vincristine-doxorubicin-cyclophosphamide and ifosfamide-etoposide every 21 days or every 14 days with filgrastim.\n\nThe median cycle interval achieved was 21 days (standard) and 15 days (intensified). Event-free survival at a median of five years was 65 percent in the standard arm and 73 percent in the intensified arm (p 0.048); toxicity was similar.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2012","url":"https://doi.org/10.1200/JCO.2011.41.5703"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23091096/"}],"tags":[],"related":[],"cancers":["ewing-sarcoma","sarcoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["aews0031"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2012,"doi":"10.1200/JCO.2011.41.5703","pmid":"23091096","authors":"Womer RB, West DC, Krailo MD, et al.","paperType":"rct","findings":["Five-year event-free survival 73 percent with interval-compressed chemotherapy versus 65 percent with standard timing (p 0.048).","Median cycle interval 15 versus 21 days; toxicity similar."],"whatItMeans":"Interval-compressed VDC/IE is the standard first-line chemotherapy for localised Ewing sarcoma in North America; Euro Ewing 2012 later adopted it in Europe.","caveats":["Localised disease only; the benefit in metastatic disease was not tested here."],"changedPractice":true,"participants":587},{"id":"paper-scher-affirm-enzalutamide-nejm-2012","kind":"paper","name":"AFFIRM: increased survival with enzalutamide in prostate cancer after chemotherapy","aka":["AFFIRM","Scher 2012 enzalutamide","MDV3100 AFFIRM"],"tldr":"Enzalutamide, an oral tablet that blocks the androgen receptor at several points at once, added nearly five months to median survival in men whose cancer had already been through chemotherapy. More than half had their PSA halve, against two percent on placebo.","summary":"Howard Scher and the AFFIRM investigators randomised 1,199 men with castration-resistant prostate cancer who had already had chemotherapy, in a 2 to 1 ratio, to 160 mg of enzalutamide daily or placebo. The trial was stopped at a planned interim analysis after 520 deaths.\n\nEnzalutamide came out of the Sawyers laboratory as a direct answer to the biology described in Chen 2004: a compound that stays an antagonist when the androgen receptor is abundant, and that also blocks nuclear translocation and DNA binding. AFFIRM is the clinical proof that the design brief was right. Every secondary endpoint moved in the same direction, which is unusual, and the effect size on prostate-specific antigen (54 percent against 2 percent) is among the largest in solid tumour oncology.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2012","url":"https://doi.org/10.1056/nejmoa1207506"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22894553/"},{"label":"ClinicalTrials.gov NCT00974311","url":"https://clinicaltrials.gov/study/NCT00974311"}],"tags":["prostate-evidence"],"related":["paper-beer-prevail-enzalutamide-nejm-2014","paper-chen-androgen-receptor-overexpression-antiandrogen-resistance-nat-med-2004","paper-cou-aa-301-abiraterone-de-bono-nejm-2011","prostate-roadmap"],"cancers":["prostate","prostate-mcrpc"],"sections":["hormonal","targeted-therapy"],"technologies":[],"targets":["androgen-receptor"],"drugs":["enzalutamide"],"companies":["astellas","pfizer"],"institutions":[],"pathways":[],"terms":["castration-resistance","psa","quality-of-life","radiographic-progression-free-survival"],"trials":[],"people":["howard-scher","karim-fizazi"],"bottlenecks":["b-resistance","b-toxicity-qol"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2012,"doi":"10.1056/nejmoa1207506","pmid":"22894553","authors":"Scher HI, Fizazi K, Saad F, et al.","paperType":"rct","findings":["Median overall survival 18.4 months (95 percent confidence interval 17.3 to not yet reached) with enzalutamide against 13.6 months (11.3 to 15.8) with placebo; hazard ratio for death 0.63 (0.53 to 0.75; P less than 0.001).","A reduction in prostate-specific antigen of 50 percent or more in 54 percent against 2 percent (P less than 0.001).","Soft-tissue response rate 29 percent against 4 percent; quality-of-life response rate 43 percent against 18 percent (P less than 0.001 for both).","Radiographic progression-free survival 8.3 against 2.9 months (hazard ratio 0.40; P less than 0.001); time to first skeletal-related event 16.7 against 13.3 months (hazard ratio 0.69).","Seizures were reported in five patients (0.6 percent) receiving enzalutamide; fatigue, diarrhoea and hot flushes were more common."],"whatItMeans":"An oral drug that works after chemotherapy has failed, in a disease where the previous option was more chemotherapy. Together with abiraterone it moved castration-resistant prostate cancer from a chemotherapy disease to a hormonal one, and set up the sequencing questions the field is still arguing about.","caveats":["Placebo-controlled in a post-chemotherapy population, so it does not say how enzalutamide compares with abiraterone, cabazitaxel or radioligand therapy.","The 0.6 percent seizure rate excluded men with a history of seizure from the trial, so the real-world rate in unselected patients is not established here.","Cross-resistance with abiraterone was not tested; the CARD trial later showed that switching from one androgen receptor drug to the other is worse than moving to cabazitaxel."],"changedPractice":true,"participants":1199},{"id":"paper-martini-african-ancestry-tnbc-cancer-discov-2022","kind":"paper","name":"African ancestry-associated gene expression profiles in triple-negative breast cancer underlie altered tumor biology and clinical outcome in women of African descent","aka":[],"tldr":"RNA sequencing of triple-negative tumours from African Americans, West Africans and East Africans, with ancestry measured genetically rather than self-reported, found hundreds of genes tied to African ancestry and a distinct immune landscape in the tumours.","summary":"RNA sequencing was performed on an international cohort of African Americans and West and East Africans with TNBC, with comprehensive genetic ancestry estimation. Expression of 613 genes was associated with African ancestry and more than 2,000 with regional African ancestry; a subset also differed in normal breast tissue. Pathway enrichment and deconvolution of tumour cellular composition revealed distinct tumour-associated immunological profiles in patients of African descent.","asOf":"2026-09-24","links":[{"label":"Martini et al., Cancer Discov 2022: African ancestry-associated expression profiles in TNBC","url":"https://doi.org/10.1158/2159-8290.CD-22-0138"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36121736/"}],"tags":[],"related":[],"cancers":["tnbc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["tumor-microenvironment"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-discovery"],"dependsOn":[],"notes":[],"journal":"Cancer Discovery","year":2022,"doi":"10.1158/2159-8290.CD-22-0138","pmid":"36121736","authors":"Martini R, Delpe P, Chu TR, et al.","paperType":"translational","findings":["613 genes associated with African ancestry and over 2,000 with regional African ancestry in TNBC.","Tumour immune profiles differ by ancestry after quantified admixture."],"whatItMeans":"It replaces self-reported race with measured ancestry and shows the immune microenvironment of TNBC differs with it, a variable immunotherapy trials have not stratified on.","caveats":["Cohort size and clinical outcome data are limited; expression associations are not yet causal.","Social determinants and ancestry remain entangled in outcome comparisons."],"changedPractice":false},{"id":"paper-fruhwald-neuro-oncol","kind":"paper","name":"Age and DNA methylation subgroup as potential independent risk factors for treatment stratification in children with atypical teratoid/rhabdoid tumors","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 31883020 and published in Neuro-Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background: Controversy exists as to what may be defined as standard of care (including markers for stratification) for patients with atypical teratoid/rhabdoid tumors (ATRTs). The European Rhabdoid Registry (EU-RHAB) recruits uniformly treated patients and offers standardized genetic and DNA methylation analyses.\n\nMethods: Clinical, genetic, and treatment data of 143 patients from 13 European countries were analyzed (2009-2017). Therapy consisted of surgery, anthracycline-based induction, and either radiotherapy or high dose chemotherapy following a consensus among European experts. Fluorescence in situ hybridization, multiplex ligation-dependent probe amplification, and sequencing were employed for assessment of somatic and germline mutations in SWItch/sucrose nonfermentable related, matrix associated, actin dependent regulator of chromatin, subfamily B (SMARCB1). Molecular subgroups (ATRT-SHH, ATRT-TYR, and ATRT-MYC) were determined using DNA methylation arrays, resulting in profiles of 84 tumors.\n\nResults: Median age at diagnosis of 67 girls and 76 boys was 29.5 months. Five-year overall survival (OS) and event-free survival (EFS) were 34.7 ± 4.5% and 30.5 ± 4.2%, respectively. Tumors displayed allelic partial/whole gene deletions (66%; 122/186 alleles) or single nucleotide variants (34%; 64/186 alleles) of SMARCB1. Germline mutations were detected in 26% of ATRTs (30/117). The patient cohort consisted of 47% ATRT-SHH (39/84), 33% ATRT-TYR (28/84), and 20% ATRT-MYC (17/84). Age <1 year, non-TYR signature (ATRT-SHH or -MYC), metastatic or synchronous tumors, germline mutation, incomplete remission, and omission of radiotherapy were negative prognostic factors in univariate analyses (P < 0.05). An adjusted multivariate model identified age <1 year and a non-TYR signature as independent negative predictors of OS: high risk (<1 y + non-TYR; 5-y OS = 0%), intermediate risk (<1 y + ATRT-TYR or ≥1 y + non-TYR; 5-y OS = 32.5 ± 8.7%), and standard risk (≥1 y + ATRT-TYR, 5-y OS = 71.5 ± 12.2%).\n\nConclusions: Age and molecular subgroup status are independent risk factors for survival in children with ATRT. Our model warrants validation within future clinical trials.\n\nIndexed on Europe PMC as PubMed record 31883020 (DOI 10.1093/neuonc/noz244). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Neuro Oncol 2020","url":"https://doi.org/10.1093/neuonc/noz244"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31883020/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31883020"}],"tags":["europepmc-ingest"],"related":["atrt"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["neuro-oncology"],"dependsOn":[],"notes":[],"journal":"Neuro-Oncology","year":2020,"doi":"10.1093/neuonc/noz244","pmid":"31883020","authors":"Frühwald MC, Hasselblatt M, Nemes K, et al.","paperType":"observational","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-agile-ivosidenib-azacitidine-nejm-2022","kind":"paper","name":"AGILE: ivosidenib plus azacitidine for newly diagnosed IDH1-mutated AML in patients unfit for intensive chemotherapy","aka":[],"tldr":"Adding the IDH1 inhibitor ivosidenib to azacitidine tripled median survival, from 7.9 to 24 months, in older patients with IDH1-mutated AML.","summary":"AGILE randomised 146 patients with newly diagnosed IDH1-mutated AML who were ineligible for intensive induction to ivosidenib plus azacitidine or placebo plus azacitidine. The primary endpoint was event-free survival. EFS favoured ivosidenib (hazard ratio 0.33), complete remission was 47% versus 15%, and median overall survival was 24.0 versus 7.9 months (hazard ratio 0.44). Differentiation syndrome occurred in 14% of ivosidenib patients; febrile neutropenia and infections were less frequent than with azacitidine alone, partly because of faster count recovery. The result established a mutation-directed doublet for this subgroup.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa2117344"},{"label":"ClinicalTrials.gov NCT03173248","url":"https://clinicaltrials.gov/study/NCT03173248"}],"tags":[],"related":["paper-viale-a-venetoclax-azacitidine-nejm-2020"],"cancers":["aml"],"sections":[],"technologies":[],"targets":[],"drugs":["ivosidenib","azacitidine","venetoclax"],"companies":["servier"],"institutions":[],"pathways":[],"terms":["efs","os"],"trials":["agile"],"people":[],"bottlenecks":["b-rare-cancers","b-trial-enrolment"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/NEJMoa2117344","authors":"Montesinos P, Recher C, Vives S, et al.","paperType":"rct","findings":["146 patients with untreated IDH1-mutated AML unfit for intensive chemotherapy; ivosidenib + azacitidine vs placebo + azacitidine.","Event-free survival hazard ratio 0.33.","Complete remission 47% vs 15%.","Median OS 24.0 vs 7.9 months; hazard ratio 0.44.","Differentiation syndrome 14%; fewer infections and febrile neutropenia than the control arm."],"whatItMeans":"AGILE showed that for the roughly 6-10% of AML patients with an IDH1 mutation, a targeted doublet produces survival in the range of two years, an outcome previously unimaginable in unfit patients. Ivosidenib-azacitidine is approved and is one option alongside venetoclax-azacitidine for these patients. Which regimen, or triplet, is best for IDH1-mutated disease has not been settled by a randomised trial.","caveats":["Small trial that stopped enrolment early; wide confidence intervals.","Enrolled before venetoclax-azacitidine became standard, so the comparator is azacitidine alone.","Restricted to IDH1; IDH2-mutated AML is treated with enasidenib or venetoclax-based regimens.","Differentiation syndrome needs prompt recognition."],"changedPractice":true,"participants":146},{"id":"paper-nct01436968-lancet-oncol-2026","kind":"paper","name":"Aglatimagene besadenovec (CAN-2409) with radiotherapy for patients with localised prostate cancer: a phase 3, multicentre, randomised, double-blind, placebo-controlled trial","aka":[],"tldr":"Published report from the trial registered as NCT01436968, in The Lancet Oncology (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: About 30% of men with localised prostate cancer undergoing radiotherapy with curative intent have disease recurrence associated with progression-related symptoms and substantial toxicity of salvage therapies. Previous studies with aglatimagene besadenovec (CAN-2409, hereafter referred to as aglatimagene) showed synergy with radiation and immune-mediated cytotoxicity in patients with prostate cancer. We aimed to assess whether addition of aglatimagene plus prodrug (valacyclovir) to standard-of-care external beam radiation therapy (EBRT) could improve disease-free survival in this population.\n\nMethods: We conducted a phase 3, randomised, double-blind, placebo-controlled trial at 51 medical centres (26 community and 25 institutional or military) across the USA and Puerto Rico in patients with intermediate or high-risk prostate cancer. Patients aged at least 18 years who were planning to undergo EBRT and with an Eastern Cooperative Oncology Group score of 0-2 were eligible. Patients were randomly assigned (2:1) via central block-randomisation to receive either three courses of intraprostatic aglatimagene (5 × 10 11 viral particles) plus valacyclovir or placebo plus valacyclovir, with randomisation stratified by risk category and androgen deprivation therapy (ADT) use. Patients received standard-of-care EBRT (78 Gy in 2 Gy fractions) or hypofractionated EBRT (60 Gy in 3 Gy fractions or 70 Gy in 2·5 Gy fractions) with optional ADT. The primary endpoint was disease-free survival, defined as time-from-randomisation to prostate cancer recurrence or death in the intent-to-treat population (all randomly assigned patients). Safety was assessed in all individuals who received at least one injection. The trial is registered at ClinicalTrials.gov, NCT01436968, and long-term follow-up is ongoing.\n\nFindings: Between Feb 21, 2012, and Sept 9, 2021, 745 men (591 [79%] White, 121 [16%] Black) were randomly assigned to receive aglatimagene plus valacyclovir (n=496) or placebo plus valacyclovir (n=249). After a median follow-up of 50·3 months (IQR 35·2-63·3), median disease-free survival was not reached (95% CI 121·78 to not reached) in the aglatimagene plus valacyclovir group versus 86·1 (IQR 29·7-143·0) months in the placebo plus valacyclovir group (hazard ratio 0·70, 95% CI 0·52-0·94; p=0·016). Treatment-emergent adverse events (TEAEs) of grade 3 or worse occurred in 40 (8%) of 479 patients in the aglatimagene group and 17 (7%)of 232 patients in the placebo group. The most common TEAE of grade 3 or worse was acute kidney injury in both the aglatimagene group (nine [2%] of 479 patients) and the placebo group (four [2%] of 232 patients). Serious adverse events occurred in 28 (6%) of 479 patients in the aglatimagene group and 17 (7%) of 232 in the placebo group. Treatment-related serious adverse events occurred in eight (2%) patients in the aglatimagene group (four acute kidney injury, two pyrexia, and one each influenza-like symptoms and urinary retention) and five (2%) in the placebo group (four acute kidney injury, and one each increased creatinine levels and skin rash; one patient reported two serious adverse events). No treatment-related deaths were reported.\n\nInterpretation: Aglatimagene plus valacyclovir was associated with longer disease-free survival than placebo plus valacyclovir when added to standard of radiotherapy for the treatment of localised prostate cancer, offering a meaningful benefit without increasing clinically significant toxicity.\n\nFunding: Candel Therapeutics and US National Institutes of Health.\n\nIndexed on Europe PMC as PubMed record 42225101 (DOI 10.1016/s1470-2045(26)00071-9). Its abstract cites the registry id NCT01436968, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2026","url":"https://doi.org/10.1016/s1470-2045(26)00071-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42225101/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42225101"},{"label":"ClinicalTrials.gov NCT01436968","url":"https://clinicaltrials.gov/study/NCT01436968"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct01436968"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2026,"doi":"10.1016/s1470-2045(26)00071-9","pmid":"42225101","authors":"DeWeese TL, Manzanera A, Sylvester J, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT01436968 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-ahod1331-brentuximab-vedotin-paediatric-hodgkin-castellino-nejm-2022","kind":"paper","name":"AHOD1331: brentuximab vedotin with chemotherapy in paediatric high-risk Hodgkin lymphoma","aka":[],"tldr":"Swapping bleomycin for the antibody-drug conjugate brentuximab vedotin in children's chemotherapy for advanced Hodgkin lymphoma cut the risk of relapse or death by 59 percent with no extra toxicity.","summary":"Open-label multicentre randomised phase 3 trial: 600 patients aged 2 to 21 with untreated high-risk classical Hodgkin lymphoma were assigned to five cycles of brentuximab vedotin with doxorubicin, vincristine, etoposide, prednisone and cyclophosphamide or to standard ABVE-PC, with PET-directed involved-site radiotherapy to slow-responding lesions.\n\nAt a median follow-up of 42.1 months three-year event-free survival was 92.1 percent with brentuximab vedotin against 82.5 percent with standard care (hazard ratio 0.41). Radiotherapy use (53.4 against 56.8 percent) and toxic effects were similar; three-year overall survival was 99.3 and 98.5 percent.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2022","url":"https://doi.org/10.1056/NEJMoa2206660"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36322844/"}],"tags":[],"related":[],"cancers":["hodgkin-lymphoma","advanced-stage-classical-hodgkin-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["brentuximab-vedotin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["ahod1331"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/NEJMoa2206660","pmid":"36322844","authors":"Castellino SM, Pei Q, Parsons SK, et al.","paperType":"rct","findings":["Three-year event-free survival 92.1 percent (95% CI 88.4 to 94.7) versus 82.5 percent (77.4 to 86.5); hazard ratio 0.41 (0.25 to 0.67), p < 0.001.","Three-year overall survival 99.3 versus 98.5 percent.","Involved-site radiotherapy given to 53.4 versus 56.8 percent; toxic effects similar."],"whatItMeans":"Brentuximab vedotin with AVEPC is the new standard for high-risk paediatric Hodgkin lymphoma and led to the first paediatric approval of the drug in November 2022.","caveats":["Open-label; the trial did not reduce radiotherapy use, which later trials are testing."],"changedPractice":true,"participants":600},{"id":"paper-al-hajj-breast-cancer-stem-cells-pnas-2003","kind":"paper","name":"Al-Hajj 2003: prospective identification of tumorigenic breast cancer cells","aka":[],"tldr":"The first demonstration in a solid tumour that only a small, marker-defined fraction of breast cancer cells can regrow the cancer: a few hundred cells with one surface profile formed tumours in mice while tens of thousands of the other cells did not.","summary":"Al-Hajj, Wicha, Clarke and colleagues separated cells from human breast cancers, mostly metastatic fluid collections and one primary tumour, by surface markers and injected them into immunodeficient mice. Cells that were CD44-positive and CD24-negative or low, and lacked lineage markers, formed tumours from as few as 100 cells in eight of nine patients' samples, whereas tens of thousands of cells with other profiles did not. The resulting tumours reproduced the mixture of cell types of the original cancer and could be passaged serially, the defining behaviour of a cancer stem cell.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1073/pnas.0530291100"}],"tags":[],"related":["paper-reya-cancer-stem-cells-nature-2001"],"cancers":["breast-hr-positive","breast-her2-positive","tnbc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["michigan-rogel"],"pathways":[],"terms":["stem-cell","relapse-recurrence"],"trials":[],"people":["max-wicha"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Proceedings of the National Academy of Sciences","year":2003,"doi":"10.1073/pnas.0530291100","authors":"Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF.","paperType":"basic","findings":["Tumorigenic cells from human breast cancers were enriched in the CD44-positive, CD24-negative or low, lineage-negative fraction.","As few as 100 such cells formed tumours in NOD/SCID mice; tens of thousands of cells with other marker profiles did not.","Tumours from the sorted cells reproduced the original tumour's heterogeneity and could be passaged repeatedly."],"whatItMeans":"This paper extended the cancer stem cell concept from leukaemia to a common solid tumour and started the search for tumour-initiating cells across cancers. It underpins research on why cancers relapse after treatments that shrink them and on therapies aimed at the cells that regrow disease.","caveats":["Samples were mostly metastatic effusions rather than primary tumours.","Transplantation into mice measures what survives the assay and may not reflect behaviour in patients.","The markers are not universal across breast cancer subtypes."],"changedPractice":false},{"id":"paper-alcanza-brentuximab-vedotin-lancet-2017","kind":"paper","name":"ALCANZA: brentuximab vedotin versus physician's choice in CD30-positive cutaneous T-cell lymphoma","aka":[],"tldr":"In CD30-expressing mycosis fungoides and primary cutaneous anaplastic large cell lymphoma, the antibody-drug conjugate brentuximab vedotin produced lasting responses in more than half of patients, far more than methotrexate or bexarotene.","summary":"Phase 3 trial of 131 patients with CD30-positive mycosis fungoides or primary cutaneous anaplastic large cell lymphoma previously treated with systemic therapy, randomised to brentuximab vedotin or physician's choice of methotrexate or bexarotene.\n\nObjective response lasting at least four months was 56.3 versus 12.5 percent, median progression-free survival 16.7 versus 3.5 months, and peripheral neuropathy occurred in two thirds of brentuximab patients.","asOf":"2026-09-17","links":[{"label":"Lancet 2017","url":"https://doi.org/10.1016/S0140-6736(17)31266-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28600132/"}],"tags":[],"related":["lymphoma-roadmap","lymphoma-ev-randomised-evidence-for-the-t-cell-lymphomas"],"cancers":["cutaneous-t-cell-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["brentuximab-vedotin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["alcanza"],"people":["miles-prince"],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2017,"doi":"10.1016/S0140-6736(17)31266-7","pmid":"28600132","authors":"Prince HM, Kim YH, Horwitz SM, et al.","paperType":"rct","findings":["Objective response lasting four months or more: 56.3 percent vs 12.5 percent.","Median progression-free survival 16.7 vs 3.5 months."],"whatItMeans":"Brentuximab vedotin is a standard for CD30-positive cutaneous T-cell lymphoma requiring systemic therapy, including large cell transformation.","caveats":["Peripheral neuropathy in 67 percent, mostly reversible.","CD30 expression threshold for benefit is low and variable."],"changedPractice":true,"participants":131},{"id":"paper-alcohol-cancer-burden-lancet-oncol-2021","kind":"paper","name":"Alcohol caused an estimated 741,000 cancers worldwide in 2020","aka":[],"tldr":"Building on the IARC classification of alcohol as a Group 1 carcinogen, this global modelling study attributed 4.1% of all new cancers in 2020 to drinking, three-quarters of them in men and the largest numbers in oesophageal, liver and breast cancer.","summary":"IARC Monographs volumes 44, 96 and 100E established alcoholic beverages, and the acetaldehyde derived from them, as Group 1 carcinogens with sufficient evidence for cancers of the oral cavity, pharynx, larynx, oesophagus (squamous), liver, colorectum and female breast. Rumgay and colleagues combined per-capita alcohol consumption estimates (with a 10-year lag) and relative risks from meta-analyses with GLOBOCAN 2020 incidence to estimate the attributable burden by country, sex and site.\n\nAn estimated 741,300 new cancers (4.1% of all cases) were attributable to alcohol in 2020; 76.7% were in men. Oesophageal (189,700), liver (154,700) and breast (98,300) cancers had the largest numbers. Heavy drinking accounted for most of the burden, but moderate drinking (up to two drinks a day) contributed around 100,000 cases.\n\nThe paper drove policy interest in alcohol labelling and pricing, and the 2023 WHO and 2025 US Surgeon General statements on alcohol and cancer.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1016/S1470-2045(21)00279-5"},{"label":"IARC Monographs Volume 100E","url":"https://publications.iarc.who.int/122"}],"tags":[],"related":["idea-prev-alcohol-cancer-warning-labels","idea-prev-pharmacy-prevention-hub"],"cancers":["esophageal","hcc","breast-hr-positive","colorectal","head-and-neck"],"sections":["prevention"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["iarc"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-misinformation","b-incentive-misalignment"],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"Lancet Oncology","year":2021,"doi":"10.1016/S1470-2045(21)00279-5","pmid":"34270924","authors":"Rumgay H, Shield K, Charvat H, et al.","paperType":"observational","findings":["741,300 alcohol-attributable new cancers globally in 2020 (95% uncertainty interval 558,500-951,200), 4.1% of all cancers","76.7% of attributable cases were in men","Largest contributions: oesophagus 189,700; liver 154,700; female breast 98,300","Moderate drinking (less than 20 g/day) accounted for an estimated 103,100 cases (13.9% of the alcohol burden)"],"whatItMeans":"There is no safe level of alcohol for cancer risk, and the risk is highest for cancers of the mouth, throat, oesophagus, liver, bowel and breast. Public awareness is low; most people do not know alcohol causes breast cancer. Warning labels and minimum pricing are the policy levers being debated.","caveats":["Modelled estimates depend on consumption data of uneven quality and on relative risks from observational meta-analyses","Unrecorded alcohol consumption is poorly captured in many countries","Does not account for former drinkers or interactions with smoking","Population-level estimates say nothing about individual risk trajectories"],"changedPractice":false},{"id":"paper-wu-alina-adjuvant-alectinib-nejm-2024","kind":"paper","name":"Alectinib in resected ALK-positive non-small-cell lung cancer","aka":[],"tldr":"After surgery for ALK-positive lung cancer, two years of alectinib kept 93.8 percent of patients disease-free at two years against 63.0 percent on chemotherapy.","summary":"The ALINA investigators, reported by Wu, Dziadziuszko, Ahn and colleagues with Solomon as senior author, randomised 257 patients with completely resected ALK-positive non-small-cell lung cancer of stage IB (tumours 4 cm or larger), II or IIIA to oral alectinib 600 mg twice daily for 24 months or four 21-day cycles of intravenous platinum-based chemotherapy. The primary endpoint was disease-free survival, tested hierarchically in stage II or IIIA and then in the intention-to-treat population.\n\nWith ADAURA for EGFR, ALINA completes the move of targeted therapy from the metastatic setting into the operating theatre's aftermath. The open question both share is whether an effect on disease-free survival becomes an effect on cure or only postpones recurrence until the drug stops.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2024","url":"https://doi.org/10.1056/NEJMoa2310532"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38598794/"},{"label":"ClinicalTrials.gov NCT03456076","url":"https://clinicaltrials.gov/study/NCT03456076"},{"label":"N Engl J Med 2024","url":"https://doi.org/10.1056/nejmoa2310532"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38598794"}],"tags":["lung-evidence"],"related":["paper-adaura-nejm-2020","paper-lace-adjuvant-cisplatin-pooled-analysis-jco-2008","paper-peters-alex-alectinib-crizotinib-nejm-2017"],"cancers":["lung-cancer","nsclc","alk-positive-nsclc","resectable-nsclc"],"sections":["targeted-therapy","surgery"],"technologies":[],"targets":["alk"],"drugs":["alectinib","cisplatin","carboplatin"],"companies":["roche-genentech"],"institutions":[],"pathways":[],"terms":["neoadjuvant-adjuvant","brain-metastases","mrd"],"trials":["alina"],"people":[],"bottlenecks":["b-dormancy-mrd","b-biomarker-validation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2024,"doi":"10.1056/NEJMoa2310532","pmid":"38598794","authors":"Wu YL, Dziadziuszko R, Ahn JS, et al.","paperType":"rct","findings":["Among patients with stage II or IIIA disease, 93.8 percent were alive and disease-free at 2 years with alectinib against 63.0 percent with chemotherapy: hazard ratio for disease recurrence or death 0.24 (95 percent confidence interval 0.13 to 0.45).","257 patients were randomised, 130 to alectinib and 127 to platinum-based chemotherapy.","Other endpoints included central nervous system disease-free survival, overall survival and safety."],"whatItMeans":"Adjuvant treatment for lung cancer is now chosen by genotype. A resected ALK-positive tumour is treated with two years of a tablet instead of four cycles of platinum, which is a different life as well as a different outcome.","caveats":["Disease-free survival, not overall survival, and follow-up is short for a curative-intent question.","Chemotherapy comparator rather than chemotherapy plus alectinib, and no answer to the duration question: 24 months is a convention, not a result.","257 patients is small, and an ALK-positive resected population has to be found by testing early-stage tumours, which is not yet universal."],"changedPractice":true,"participants":257},{"id":"paper-peters-alex-alectinib-crizotinib-nejm-2017","kind":"paper","name":"Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer","aka":[],"tldr":"A newer ALK drug that gets into the brain beat the original one, and did it with fewer side effects. ALEX is why nobody starts an ALK-positive patient on crizotinib any more.","summary":"The ALEX trial investigators, reported by Peters, Camidge, Shaw and colleagues, randomised 303 patients with previously untreated advanced ALK-positive non-small-cell lung cancer, including those with asymptomatic central nervous system disease, to alectinib 600 mg twice daily or crizotinib 250 mg twice daily. The primary endpoint was investigator-assessed progression-free survival; time to central nervous system progression was a secondary endpoint.\n\nThe design deliberately admitted patients with brain metastases rather than excluding them, which is why the trial could show what the next generation of ALK inhibitors was actually for. It is the pattern later followed by CROWN with lorlatinib.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2017","url":"https://doi.org/10.1056/NEJMoa1704795"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28586279/"},{"label":"ClinicalTrials.gov NCT02075840","url":"https://clinicaltrials.gov/study/NCT02075840"},{"label":"N Engl J Med 2017","url":"https://doi.org/10.1056/nejmoa1704795"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28586279"}],"tags":["lung-evidence"],"related":["paper-kwak-crizotinib-alk-nsclc-nejm-2010","paper-shaw-crown-lorlatinib-crizotinib-nejm-2020","paper-wu-alina-adjuvant-alectinib-nejm-2024"],"cancers":["lung-cancer","nsclc","alk-positive-nsclc"],"sections":["targeted-therapy"],"technologies":["kinase-inhibitors"],"targets":["alk"],"drugs":["alectinib","crizotinib"],"companies":["roche-genentech"],"institutions":[],"pathways":[],"terms":["brain-metastases","driver-mutation"],"trials":["alex"],"people":["solange-peters","alice-shaw","tony-mok"],"bottlenecks":["b-brain-delivery","b-resistance"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2017,"doi":"10.1056/NEJMoa1704795","pmid":"28586279","authors":"Peters S, Camidge DR, Shaw AT, et al.","paperType":"rct","findings":["Twelve-month event-free survival 68.4 percent (95 percent confidence interval 61.0 to 75.9) with alectinib against 48.7 percent (40.4 to 56.9) with crizotinib.","Hazard ratio for disease progression or death 0.47 (0.34 to 0.65).","Progression or death occurred in 62 of 152 patients (41 percent) on alectinib and 102 of 151 (68 percent) on crizotinib, at a median follow-up of 18.6 and 17.6 months.","Alectinib showed superior efficacy and lower toxicity than crizotinib in primary treatment of ALK-positive disease."],"whatItMeans":"First-line ALK treatment moved to a drug designed for the brain, and brain metastasis prevention became an explicit design goal rather than a hoped-for side effect. ALK-positive lung cancer is now among the longest-surviving metastatic solid tumours.","caveats":["Open-label design with investigator-assessed primary endpoint, though an independent review committee endpoint agreed.","Asymptomatic central nervous system disease was allowed but symptomatic disease was not, so the hardest patients were not tested.","Superseded in first line by lorlatinib on progression-free survival grounds (CROWN), without a head-to-head overall survival comparison."],"changedPractice":true,"participants":303},{"id":"paper-hillmen-j-clin-oncol","kind":"paper","name":"Alemtuzumab compared with chlorambucil as first-line therapy for chronic lymphocytic leukemia","aka":[],"tldr":"Paper cited by one target page, indexed on Europe PMC as PubMed record 17984186 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: We conducted a randomized trial to evaluate the efficacy and safety of intravenous alemtuzumab compared with chlorambucil in first-line treatment of chronic lymphocytic leukemia (CLL).\n\nPatients and methods: Patients received alemtuzumab (30 mg three times per week, for up to 12 weeks) or chlorambucil (40 mg/m(2) every 28 days, for up to 12 months). The primary end point was progression-free survival (PFS). Secondary end points included overall response rate (ORR), complete response (CR), time to alternative therapy, safety, and overall survival.\n\nResults: We randomly assigned 297 patients, 149 to alemtuzumab and 148 to chlorambucil. Alemtuzumab had superior PFS, with a 42% reduction in risk of progression or death (hazard ratio [HR] = 0.58; P =.0001), and a median time to alternative treatment of 23.3 versus 14.7 months for chlorambucil (HR = 0.54; P =.0001). The ORR was 83% with alemtuzumab (24% CR) versus 55% with chlorambucil (2% CR); differences in ORR and CR were highly statistically significant (P <.0001). Elimination of minimal residual disease occurred in 11 of 36 complete responders to alemtuzumab versus none to chlorambucil. Adverse events profiles were similar, except for more infusion-related and cytomegalovirus (CMV) events with alemtuzumab and more nausea and vomiting with chlorambucil. CMV events had no apparent impact on efficacy.\n\nConclusion: As first-line treatment for patients with CLL, alemtuzumab demonstrated significantly improved PFS, time to alternative treatment, ORR and CR, and minimal residual disease-negative remissions compared with chlorambucil, with predictable and manageable toxicity.\n\nIndexed on Europe PMC as PubMed record 17984186 (DOI 10.1200/jco.2007.12.9098). Matched by DOI alone: one target page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2007","url":"https://doi.org/10.1200/jco.2007.12.9098"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/17984186/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/17984186"}],"tags":["europepmc-ingest"],"related":["cd52"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2007,"doi":"10.1200/jco.2007.12.9098","pmid":"17984186","authors":"Hillmen P, Skotnicki AB, Robak T, et al.","paperType":"rct","findings":[],"whatItMeans":"One target page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-shaw-alk-resistance-mutations-lorlatinib-jco-2019","kind":"paper","name":"ALK resistance mutations and efficacy of lorlatinib in advanced anaplastic lymphoma kinase-positive non-small-cell lung cancer","aka":[],"tldr":"In patients whose cancer had already outgrown a second ALK drug, the third-generation drug worked in seven out of ten of those whose tumour carried a resistance mutation and in fewer than three out of ten of those whose tumour did not.","summary":"Baseline plasma and tumour tissue samples were collected from 198 patients with ALK-positive non-small-cell lung cancer in the registrational phase 2 study of lorlatinib. Plasma DNA was analysed for ALK mutations with a commercial assay and tumour tissue DNA with an ALK mutation-focused next-generation sequencing assay. About a quarter of patients had ALK mutations detected by plasma or tissue genotyping. In patients with crizotinib-resistant disease, lorlatinib efficacy was comparable with and without ALK mutations. In patients who had failed one or more second-generation inhibitors, objective response was higher with ALK mutations, 62% against 32% by plasma and 69% against 27% by tissue, and progression-free survival was similar by plasma genotyping (7.3 against 5.5 months, hazard ratio 0.81) but significantly longer by tissue genotyping (11.0 against 5.4 months, hazard ratio 0.47).","asOf":"2026-09-25","links":[{"label":"Shaw et al., J Clin Oncol 2019: ALK resistance mutations and the efficacy of lorlatinib in 198 patients","url":"https://doi.org/10.1200/JCO.18.02236"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30892989/"}],"tags":[],"related":["alk-fusion"],"cancers":["nsclc"],"sections":[],"technologies":["kinase-inhibitors","liquid-biopsy","cgp"],"targets":["alk","ros1"],"drugs":["lorlatinib","crizotinib","guardant360-cdx"],"companies":[],"institutions":["mgh"],"pathways":["resistance-routes-map","rtk-activation"],"terms":["resistance","gene-fusion","ctdna"],"trials":[],"people":["alice-shaw"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2019,"doi":"10.1200/JCO.18.02236","pmid":"30892989","authors":"Shaw AT, Solomon BJ, Besse B, et al.","paperType":"rct","findings":["About a quarter of previously treated patients carried a detectable ALK resistance mutation.","After a second-generation inhibitor, response was 69% with an ALK mutation on tissue against 27% without.","Progression-free survival 11.0 against 5.4 months by tissue genotyping, hazard ratio 0.47.","After crizotinib alone, mutation status made no difference."],"whatItMeans":"It turned the laboratory prediction into a clinical rule: after a second-generation ALK inhibitor, genotype the tumour, and treat the absence of an ALK mutation as evidence that the cancer has stopped depending on ALK.","caveats":["A single-arm registrational study, so the comparison is between subgroups rather than between treatments.","Tissue and plasma disagreed, and the tissue result separated the groups more sharply.","Not all patients had both sample types."],"changedPractice":true,"participants":198},{"id":"paper-all-r3-mitoxantrone-relapsed-childhood-all-parker-lancet-2010","kind":"paper","name":"ALL R3: mitoxantrone versus idarubicin in first relapse of childhood acute lymphoblastic leukaemia","aka":[],"tldr":"Children whose leukaemia had come back were far more likely to survive without further relapse if their first block of treatment used mitoxantrone instead of idarubicin, an unexpected finding that changed the standard reinduction treatment.","summary":"Open-label randomised trial in 22 centres in the United Kingdom and Ireland and nine in Australia and New Zealand: 216 of 239 registered children aged 1 to 18 with first relapse of acute lymphoblastic leukaemia were randomised to idarubicin or mitoxantrone during induction, with later chemotherapy or transplant decided by risk group and measurable residual disease.\n\nThree-year progression-free survival was 64.6 percent with mitoxantrone against 35.9 percent with idarubicin (p 0.0004), and three-year overall survival 69.0 against 45.2 percent (p 0.004). The difference came from fewer disease events rather than fewer treatment-related deaths.","asOf":"2026-09-22","links":[{"label":"Lancet 2010","url":"https://doi.org/10.1016/S0140-6736(10)62002-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21131038/"}],"tags":[],"related":[],"cancers":["all-paediatric-relapsed","all-leukemia"],"sections":[],"technologies":[],"targets":[],"drugs":["mitoxantrone","idarubicin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["ukallr3"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2010,"doi":"10.1016/S0140-6736(10)62002-8","pmid":"21131038","authors":"Parker C, Waters R, Leighton C, et al.","paperType":"rct","findings":["Three-year progression-free survival 64.6 percent (95% CI 54.2 to 73.2) with mitoxantrone versus 35.9 percent (25.9 to 45.9) with idarubicin (p 0.0004).","Three-year overall survival 69.0 versus 45.2 percent (p 0.004).","Disease events reduced (hazard ratio 0.56, 95% CI 0.34 to 0.92) without an increase in adverse treatment effects."],"whatItMeans":"Mitoxantrone-based reinduction became the reference treatment for relapsed childhood ALL and the control arm of later international relapse trials.","caveats":["The randomisation stopped early after the unexpected difference, with 212 patients analysed.","The mechanism of mitoxantrone's advantage is not established."],"changedPractice":true,"participants":216},{"id":"paper-allemani-concord-3-lancet-2018","kind":"paper","name":"Allemani 2018: CONCORD-3, global surveillance of cancer survival 2000 to 2014","aka":[],"tldr":"The largest comparison of cancer survival between countries, covering 37.5 million patients in 71 countries, found survival rising for most cancers but with very wide gaps between countries, especially for children's cancers and cancers that depend on early diagnosis and good treatment access.","summary":"CONCORD-3 analysed individual records for 37.5 million patients diagnosed with one of 18 cancers between 2000 and 2014, supplied by 322 population-based registries in 71 countries and territories, and estimated five-year net survival by country and period. Survival was rising for most cancers in most countries, including steep rises for liver and lung cancers in some countries, but international differences remained very wide. The paper documented, for example, breast cancer survival in the high 80s and 90s of percent in Australia and the United States against the mid-60s in India, and childhood brain tumour survival ranging from under 40% to over 80%.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1016/S0140-6736(17)33326-3"},{"label":"CONCORD programme","url":"https://csg.lshtm.ac.uk/research/themes/concord-programme/"}],"tags":[],"related":["paper-bray-globocan-2018-cacancer-2018"],"cancers":["breast-hr-positive","colorectal","nsclc","hcc","pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["prognosis","mortality"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2018,"doi":"10.1016/S0140-6736(17)33326-3","authors":"Allemani C, Matsuda T, Di Carlo V, et al.","paperType":"observational","findings":["37.5 million patient records for 18 cancers from 322 registries in 71 countries, diagnosed 2000 to 2014.","Five-year net survival increased for most cancers in most countries over the period.","Five-year breast cancer survival about 90% in the United States and Australia versus about 66% in India; childhood brain tumour survival ranged from under 40% to over 80% between countries.","Survival for oesophageal, liver, lung and pancreatic cancers remained low almost everywhere."],"whatItMeans":"CONCORD is the evidence base for national cancer plans and for the statement that where you live changes your chance of surviving cancer. Its country tables are the benchmark health systems use to judge early diagnosis and treatment access.","caveats":["Registry coverage and data quality vary widely; some countries contributed only regional registries.","Net survival compares against general population mortality and is affected by screening-detected, slow-growing cancers."],"changedPractice":false},{"id":"paper-knaul-lancet","kind":"paper","name":"Alleviating the access abyss in palliative care and pain relief-an imperative of universal health coverage: the Lancet Commission report","aka":[],"tldr":"Paper cited by one technology page and one bottleneck page, indexed on Europe PMC as PubMed record 29032993 and published in The Lancet; the citing pages link this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 29032993 (DOI 10.1016/s0140-6736(17)32513-8). Matched by DOI alone: one technology page and one bottleneck page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet 2018","url":"https://doi.org/10.1016/s0140-6736(17)32513-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29032993/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29032993"}],"tags":["europepmc-ingest"],"related":["palliative-care","b-palliative"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2018,"doi":"10.1016/s0140-6736(17)32513-8","pmid":"29032993","authors":"Knaul FM, Farmer PE, Krakauer EL, et al.","paperType":"review","findings":[],"whatItMeans":"One technology page and one bottleneck page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-alliance-a021501-mfolfirinox-radiotherapy-borderline-resectable-jama-oncol-2022","kind":"paper","name":"Alliance A021501: preoperative modified FOLFIRINOX with or without hypofractionated radiotherapy for borderline resectable pancreatic cancer","aka":[],"tldr":"In the first randomised US trial of neoadjuvant treatment for borderline resectable pancreatic cancer, eight cycles of modified FOLFIRINOX alone gave two-thirds of patients an 18-month survival, while replacing the last cycle with short-course radiotherapy did worse and that arm was stopped early.","summary":"Multicentre randomised phase 2 trial in 126 patients with borderline resectable pancreatic ductal adenocarcinoma, assigned to eight cycles of modified FOLFIRINOX or to seven cycles followed by stereotactic body radiotherapy or hypofractionated image-guided radiotherapy, then surgery and adjuvant FOLFOX. The radiotherapy arm was closed at a planned interim analysis for futility.\n\nEighteen-month overall survival was 66.7 percent with chemotherapy alone and 47.3 percent with chemotherapy and radiotherapy; median overall survival was 29.8 against 17.1 months. The chemotherapy-alone arm met its prespecified benchmark against historical controls.","asOf":"2026-09-21","links":[{"label":"JAMA Oncol 2022","url":"https://doi.org/10.1001/jamaoncol.2022.2319"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35834226/"}],"tags":[],"related":[],"cancers":["borderline-resectable-pdac","pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":["folfirinox"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2022,"doi":"10.1001/jamaoncol.2022.2319","pmid":"35834226","authors":"Katz MHG, Shi Q, Meyers J, et al.","paperType":"rct","findings":["Eighteen-month overall survival 66.7 percent with modified FOLFIRINOX alone versus 47.3 percent with added radiotherapy.","Median overall survival 29.8 versus 17.1 months; the radiotherapy arm was closed early for futility."],"whatItMeans":"Neoadjuvant modified FOLFIRINOX without routine radiotherapy became the reference approach for borderline resectable disease in North America; radiotherapy is reserved for selected patients or trials.","caveats":["The two arms were not formally compared with each other; each was judged against a historical benchmark.","Only about half of patients in each arm went on to resection, and the radiotherapy arm was small after early closure."],"changedPractice":true,"participants":126},{"id":"paper-a071401-brastianos-jco-2023","kind":"paper","name":"Alliance A071401: phase II trial of focal adhesion kinase inhibition in meningiomas with somatic NF2 mutations","aka":[],"tldr":"In the first trial to match meningioma patients to a drug by their tumour's mutation, a FAK-blocking tablet kept 83 percent of low-grade and 33 percent of higher-grade NF2-mutant tumours from progressing for six months, clearing the bar the trial had set.","summary":"Report of the NF2 cohort of Alliance A071401 (NCT02523014), the first genomically driven phase 2 study in recurrent or progressive grade 1 to 3 meningioma. Patients whose tumours screened positive for NF2 mutations received the focal adhesion kinase inhibitor GSK2256098, 750 mg orally twice daily, until progression. Coprimary endpoints were progression-free survival at six months, evaluated separately in grade 1 and grade 2 or 3 tumours, and response rate by Macdonald criteria; the drug would be considered promising if either met its decision criterion.\n\nOf 322 patients screened for all mutation cohorts, 36 eligible and evaluable patients with NF2 mutations were enrolled and treated (12 grade 1, 24 grade 2 or 3). One patient had a partial response and 24 had stable disease. Six-month progression-free survival was 83 percent in grade 1 (10 of 12; 95 percent CI 52 to 98) and 33 percent in grade 2 or 3 (8 of 24; 16 to 55), meeting the endpoint in both cohorts. Seven patients had a maximum grade 3 adverse event at least possibly related to treatment; there were no grade 4 or 5 events.","asOf":"2026-09-24","links":[{"label":"Journal of Clinical Oncology 2023","url":"https://doi.org/10.1200/JCO.21.02371"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36288512/"},{"label":"ClinicalTrials.gov NCT02523014","url":"https://clinicaltrials.gov/study/NCT02523014"}],"tags":[],"related":[],"cancers":["meningioma"],"sections":[],"technologies":[],"targets":["fak"],"drugs":["gsk2256098"],"companies":["alliance-oncology"],"institutions":[],"pathways":[],"terms":[],"trials":["a071401"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2023,"doi":"10.1200/JCO.21.02371","pmid":"36288512","authors":"Brastianos PK, Twohy EL, Gerstner ER, et al.","paperType":"observational","findings":["Six-month progression-free survival 83 percent (10 of 12) in grade 1 and 33 percent (8 of 24) in grade 2 or 3 NF2-mutant meningioma; both met the decision criteria.","One partial response and 24 stable disease among 36 patients.","Seven grade 3 adverse events at least possibly related; no grade 4 or 5."],"whatItMeans":"Meningioma had no systemic therapy with proven activity; this cohort shows that matching a drug to the NF2 mutation can slow progression, and it validates the synthetic-lethal idea that NF2-deficient cells depend on FAK. It is a signal-finding result against historical controls, not yet a change to standard care.","caveats":["Single-arm cohort compared with historical controls; no randomised comparison.","Small numbers, especially in the grade 1 group (12 patients), so the confidence intervals are wide.","Response by Macdonald criteria was rare (one partial response); the benefit is disease stabilisation."],"changedPractice":false,"participants":36},{"id":"paper-alliance-n0574-brown-jama-2016","kind":"paper","name":"Alliance N0574: radiosurgery alone versus radiosurgery plus whole-brain radiotherapy for one to three brain metastases","aka":[],"tldr":"Adding whole-brain radiotherapy to focused radiosurgery for a few brain metastases caused more memory and thinking problems without lengthening life, so radiosurgery alone became standard for limited brain metastases.","summary":"Phase 3 trial of 213 patients with one to three brain metastases randomised to stereotactic radiosurgery alone or radiosurgery plus whole-brain radiotherapy, with cognitive decline at three months as the primary endpoint.\n\nCognitive deterioration was more frequent with whole-brain radiotherapy (91.7 versus 63.5 percent) despite better intracranial control, and median overall survival did not differ (10.4 versus 7.4 months, not significant).","asOf":"2026-09-17","links":[{"label":"JAMA 2016","url":"https://doi.org/10.1001/jama.2016.9839"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27458945/"}],"tags":[],"related":[],"cancers":["secondary-brain-tumours"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["alliance-n0574"],"people":["paul-brown"],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2016,"doi":"10.1001/jama.2016.9839","pmid":"27458945","authors":"Brown PD, Jaeckle K, Ballman KV, et al.","paperType":"rct","findings":["Cognitive deterioration at three months 91.7 percent vs 63.5 percent.","Intracranial control at one year better with whole-brain radiotherapy (85 vs 51 percent) without a survival difference."],"whatItMeans":"Patients with a limited number of brain metastases are treated with radiosurgery alone and surveillance, accepting more new brain lesions in return for preserved cognition.","caveats":["Cognitive testing only assessed to three months in the primary endpoint.","Modern hippocampal-avoidance whole-brain radiotherapy was not used."],"changedPractice":true,"participants":213},{"id":"paper-solar-1-ann-oncol-2021-update","kind":"paper","name":"Alpelisib plus fulvestrant for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: final overall survival results from SOLAR-1","aka":[],"tldr":"Later report from the SOLAR-1 trial registered as NCT02437318, in Annals of Oncology (2021); its title describes an updated or longer-term analysis.","summary":"Background: Activation of the phosphatidylinositol-3-kinase (PI3K) pathway via PIK3CA mutations occurs in 28%-46% of hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) advanced breast cancers (ABCs) and is associated with poor prognosis. The SOLAR-1 trial showed that the addition of alpelisib to fulvestrant treatment provided statistically significant and clinically meaningful progression-free survival (PFS) benefit in PIK3CA-mutated, HR+, HER2- ABC.\n\nPatients and methods: Men and postmenopausal women with HR+, HER2- ABC whose disease progressed on or after aromatase inhibitor (AI) were randomized 1: 1 to receive alpelisib (300 mg/day) plus fulvestrant (500 mg every 28 days and once on day 15) or placebo plus fulvestrant. Overall survival (OS) in the PIK3CA-mutant cohort was evaluated by Kaplan-Meier methodology and a one-sided stratified log-rank test was carried out with an O'Brien-Fleming efficacy boundary of P ≤ 0.0161.\n\nResults: In the PIK3CA-mutated cohort (n = 341), median OS [95% confidence interval (CI)] was 39.3 months (34.1-44.9) for alpelisib-fulvestrant and 31.4 months (26.8-41.3) for placebo-fulvestrant [hazard ratio (HR) = 0.86 (95% CI, 0.64-1.15; P = 0.15)]. OS results did not cross the prespecified efficacy boundary. Median OS (95% CI) in patients with lung and/or liver metastases was 37.2 months (28.7-43.6) and 22.8 months (19.0-26.8) in the alpelisib-fulvestrant and placebo-fulvestrant arms, respectively [HR = 0.68 (0.46-1.00)]. Median times to chemotherapy (95% CI) for the alpelisib-fulvestrant and placebo-fulvestrant arms were 23.3 months (15.2-28.4) and 14.8 months (10.5-22.6), respectively [HR = 0.72 (0.54-0.95)]. No new safety signals were observed with longer follow-up.\n\nConclusions: Although the analysis did not cross the prespecified boundary for statistical significance, there was a 7.9-month numeric improvement in median OS when alpelisib was added to fulvestrant treatment of patients with PIK3CA-mutated, HR+, HER2- ABC. Overall, these results further support the statistically significant prolongation of PFS observed with alpelisib plus fulvestrant in this population, which has a poor prognosis due to a PIK3CA mutation. CLINICALTRIALS.\n\nGov id: NCT02437318.\n\nIndexed on Europe PMC as PubMed record 33246021 (DOI 10.1016/j.annonc.2020.11.011). Its abstract cites the registry id NCT02437318, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2021","url":"https://doi.org/10.1016/j.annonc.2020.11.011"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33246021/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33246021"},{"label":"ClinicalTrials.gov NCT02437318","url":"https://clinicaltrials.gov/study/NCT02437318"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["solar-1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2021,"doi":"10.1016/j.annonc.2020.11.011","pmid":"33246021","authors":"André F, Ciruelos EM, Juric D, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the SOLAR-1 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-alphafold2-jumper-nature-2021","kind":"paper","name":"AlphaFold 2: predicting protein structures to near-experimental accuracy","aka":[],"tldr":"DeepMind's neural network predicted protein structures at CASP14 with a median backbone error of under 1 angstrom, comparable to experimental methods, and the team released predicted structures for essentially every human protein within a year.","summary":"AlphaFold 2 combines multiple-sequence alignments, an attention-based Evoformer network and an equivariant structure module trained end to end on the Protein Data Bank. At the blind CASP14 assessment in 2020 it achieved a median GDT of about 92 and a median backbone RMSD95 of 0.96 angstrom on the hardest targets, versus 2.8 angstrom for the next-best method.\n\nThe model provides per-residue confidence estimates (pLDDT), enabling users to distinguish reliable regions from disordered or uncertain ones. The accompanying AlphaFold Protein Structure Database, built with EMBL-EBI, released predicted structures for the human proteome and later for more than 200 million proteins.\n\nFor cancer drug discovery, AlphaFold accelerated structure-based design for targets without crystal structures and, with AlphaFold 3 (2024) extending to protein-ligand and protein-nucleic acid complexes, is now a routine part of the target-to-lead pipeline.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1038/s41586-021-03819-2"},{"label":"AlphaFold Protein Structure Database","url":"https://alphafold.ebi.ac.uk"}],"tags":[],"related":["alphafold3","de-novo-protein-design","idea-multimodal-foundation-model"],"cancers":[],"sections":["drug-discovery","ai-computation"],"technologies":["ai-drug-design","structural-biology-infrastructure"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets","b-translational-valley","b-ai-validation"],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2021,"doi":"10.1038/s41586-021-03819-2","pmid":"34265844","authors":"Jumper J, Evans R, Pritzel A, et al.","paperType":"methods","findings":["CASP14: median backbone RMSD95 of 0.96 angstrom (95% CI 0.85-1.16) vs 2.8 angstrom for the next-best method","Median GDT score around 92 across CASP14 targets, the first time a computational method reached experimental-grade accuracy","Per-residue confidence (pLDDT) reliably flags disordered and low-confidence regions","Predicted structures for the entire human proteome released in 2021; over 200 million proteins by 2022"],"whatItMeans":"The shape of nearly every protein is now available to any researcher in seconds instead of years, which shortens the path from a cancer target to a designed molecule. It does not by itself produce drugs: binding pockets, dynamics and cellular context still need experiment.","caveats":["Predicts single static conformations; many drug targets (kinases, GPCRs, KRAS) move between states","Accuracy is lower for proteins without evolutionary homologues, disordered regions and multi-protein complexes","Does not predict effects of point mutations or ligand binding (AlphaFold 3 and other tools partly address this)","The 2021 model was released with a non-commercial licence for weights, later loosened"],"changedPractice":false},{"id":"paper-alsympca-radium-223-nejm-2013","kind":"paper","name":"ALSYMPCA: alpha emitter radium-223 and survival in metastatic prostate cancer with bone metastases","aka":[],"tldr":"Radium-223, an injected alpha-emitting radioisotope that homes to bone, lengthened survival and delayed skeletal complications in men with castration-resistant prostate cancer that had spread to bone but not to organs.","summary":"Phase 3 placebo-controlled trial of 921 men with castration-resistant prostate cancer, symptomatic bone metastases and no visceral disease, randomised 2:1 to six injections of radium-223 or placebo with best standard of care.\n\nMedian overall survival was 14.9 versus 11.3 months (hazard ratio 0.70), time to first symptomatic skeletal event was delayed (15.6 versus 9.8 months) and myelosuppression was mild.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2013","url":"https://doi.org/10.1056/NEJMoa1213755"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23863050/"}],"tags":[],"related":[],"cancers":["prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["alsympca"],"people":["chris-parker"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2013,"doi":"10.1056/NEJMoa1213755","pmid":"23863050","authors":"Parker C, Nilsson S, Heinrich D, et al.","paperType":"rct","findings":["Median overall survival 14.9 vs 11.3 months; hazard ratio 0.70.","Time to first symptomatic skeletal event 15.6 vs 9.8 months."],"whatItMeans":"Radium-223 is an option for symptomatic bone-predominant castration-resistant prostate cancer, now less used since lutetium-PSMA, and should not be combined with abiraterone after the ERA 223 fracture signal.","caveats":["No effect on PSA or soft tissue disease.","Combination with abiraterone increased fractures and deaths in ERA 223."],"changedPractice":true,"participants":921},{"id":"paper-trigos-proc-natl-acad-sci-u-s-a","kind":"paper","name":"Altered interactions between unicellular and multicellular genes drive hallmarks of transformation in a diverse range of solid tumors","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 28484005 and published in Proceedings of the National Academy of Sciences; the citing page links this DOI, which is how the record was matched.","summary":"Tumors of distinct tissues of origin and genetic makeup display common hallmark cellular phenotypes, including sustained proliferation, suppression of cell death, and altered metabolism. These phenotypic commonalities have been proposed to stem from disruption of conserved regulatory mechanisms evolved during the transition to multicellularity to control fundamental cellular processes such as growth and replication. Dating the evolutionary emergence of human genes through phylostratigraphy uncovered close association between gene age and expression level in RNA sequencing data from The Cancer Genome Atlas for seven solid cancers. Genes conserved with unicellular organisms were strongly up-regulated, whereas genes of metazoan origin were primarily inactivated. These patterns were most consistent for processes known to be important in cancer, implicating both selection and active regulation during malignant transformation. The coordinated expression of strongly interacting multicellularity and unicellularity processes was lost in tumors. This separation of unicellular and multicellular functions appeared to be mediated by 12 highly connected genes, marking them as important general drivers of tumorigenesis. Our findings suggest common principles closely tied to the evolutionary history of genes underlie convergent changes at the cellular process level across a range of solid cancers. We propose altered activity of genes at the interfaces between multicellular and unicellular regions of human gene regulatory networks activate primitive transcriptional programs, driving common hallmark features of cancer. Manipulation of cross-talk between biological processes of different evolutionary origins may thus present powerful and broadly applicable treatment strategies for cancer.\n\nIndexed on Europe PMC as PubMed record 28484005 (DOI 10.1073/pnas.1617743114). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Proc Natl Acad Sci U S A 2017","url":"https://doi.org/10.1073/pnas.1617743114"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28484005/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28484005"}],"tags":["europepmc-ingest"],"related":["atavistic-theory-of-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["pnas"],"dependsOn":[],"notes":[],"journal":"Proceedings of the National Academy of Sciences","year":2017,"doi":"10.1073/pnas.1617743114","pmid":"28484005","authors":"Trigos AS, Pearson RB, Papenfuss AT, et al.","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-fraass-med-phys","kind":"paper","name":"American Association of Physicists in Medicine Radiation Therapy Committee Task Group 53: quality assurance for clinical radiotherapy treatment planning","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 9800687 and published in Medical physics; the citing page links this DOI, which is how the record was matched.","summary":"In recent years, the sophistication and complexity of clinical treatment planning and treatment planning systems has increased significantly, particularly including three-dimensional (3D) treatment planning systems, and the use of conformal treatment planning and delivery techniques. This has led to the need for a comprehensive set of quality assurance (QA) guidelines that can be applied to clinical treatment planning. This document is the report of Task Group 53 of the Radiation Therapy Committee of the American Association of Physicists in Medicine. The purpose of this report is to guide and assist the clinical medical physicist in developing and implementing a comprehensive but viable program of quality assurance for modern radiotherapy treatment planning. The scope of the QA needs for treatment planning is quite broad, encompassing image-based definition of patient anatomy, 3D beam descriptions for complex beams including multileaf collimator apertures, 3D dose calculation algorithms, and complex plan evaluation tools including dose volume histograms. The Task Group recommends an organizational framework for the task of creating a QA program which is individualized to the needs of each institution and addresses the issues of acceptance testing, commissioning the planning system and planning process, routine quality assurance, and ongoing QA of the planning process. This report, while not prescribing specific QA tests, provides the framework and guidance to allow radiation oncology physicists to design comprehensive and practical treatment planning QA programs for their clinics.\n\nIndexed on Europe PMC as PubMed record 9800687 (DOI 10.1118/1.598373). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Med Phys 1998","url":"https://doi.org/10.1118/1.598373"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/9800687/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/9800687"}],"tags":["europepmc-ingest"],"related":["treatment-planning-systems"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Medical physics","year":1998,"doi":"10.1118/1.598373","pmid":"9800687","authors":"Fraass B, Doppke K, Hunt M, et al.","paperType":"review","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-rock-ca-cancer-j-clin","kind":"paper","name":"American Cancer Society guideline for diet and physical activity for cancer prevention","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 32515498 and published in CA: A Cancer Journal for Clinicians; the citing page links this DOI, which is how the record was matched.","summary":"The American Cancer Society (ACS) publishes the Diet and Physical Activity Guideline to serve as a foundation for its communication, policy, and community strategies and, ultimately, to affect dietary and physical activity patterns among Americans. This guideline is developed by a national panel of experts in cancer research, prevention, epidemiology, public health, and policy, and reflects the most current scientific evidence related to dietary and activity patterns and cancer risk. The ACS guideline focuses on recommendations for individual choices regarding diet and physical activity patterns, but those choices occur within a community context that either facilitates or creates barriers to healthy behaviors. Therefore, this committee presents recommendations for community action to accompany the 4 recommendations for individual choices to reduce cancer risk. These recommendations for community action recognize that a supportive social and physical environment is indispensable if individuals at all levels of society are to have genuine opportunities to choose healthy behaviors. This 2020 ACS guideline is consistent with guidelines from the American Heart Association and the American Diabetes Association for the prevention of coronary heart disease and diabetes as well as for general health promotion, as defined by the 2015 to 2020 Dietary Guidelines for Americans and the 2018 Physical Activity Guidelines for Americans.\n\nIndexed on Europe PMC as PubMed record 32515498 (DOI 10.3322/caac.21591). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"CA Cancer J Clin 2020","url":"https://doi.org/10.3322/caac.21591"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32515498/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32515498"}],"tags":["europepmc-ingest"],"related":["mediterranean-plant-forward-diet"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["ca-cancer-journal"],"dependsOn":[],"notes":[],"journal":"CA: A Cancer Journal for Clinicians","year":2020,"doi":"10.3322/caac.21591","pmid":"32515498","authors":"Rock CL, Thomson C, Gansler T, et al.","paperType":"guideline","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-asco-cap-er-pr-testing-guideline-jco-2010","kind":"paper","name":"American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer","aka":[],"tldr":"The 2010 rule that fixed the line between hormone receptor-positive and negative breast cancer at 1 percent of stained tumour nuclei, after finding that up to a fifth of receptor tests worldwide might be wrong; it is the threshold that defines triple-negative disease.","summary":"ASCO and College of American Pathologists guideline by Hammond, Hayes, Dowsett, Allred and colleagues, developed with Cancer Care Ontario from a systematic review. Up to 20 percent of immunohistochemical oestrogen and progesterone receptor determinations worldwide may be inaccurate, mostly through variation in pre-analytic handling, positivity thresholds and interpretation. The panel recommends that receptor status be determined on all invasive breast cancers and recurrences, proposes a testing algorithm with specified elements to reduce assay variation, and recommends that assays be considered positive if at least 1 percent of tumour nuclei stain in the presence of expected internal and external control reactivity. The absence of endocrine therapy benefit in receptor-negative disease has been confirmed in large overviews of randomised trials.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2010","url":"https://doi.org/10.1200/JCO.2009.25.6529"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20404251/"}],"tags":["tnbc-evidence"],"related":[],"cancers":["tnbc","breast-hr-positive"],"sections":[],"technologies":["digital-pathology-ai"],"targets":[],"drugs":[],"companies":[],"institutions":["asco"],"pathways":[],"terms":["ihc"],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2010,"doi":"10.1200/JCO.2009.25.6529","pmid":"20404251","authors":"Hammond ME, Hayes DF, Dowsett M, et al.","paperType":"guideline","findings":["Up to 20 percent of immunohistochemical oestrogen and progesterone receptor determinations worldwide may be inaccurate.","Positive defined as at least 1 percent of tumour nuclei staining with expected control reactivity."],"whatItMeans":"Triple-negative is a laboratory definition; this guideline wrote the oestrogen and progesterone half of it, and the 1 to 10 percent low-positive band it created is still argued over.","caveats":["Immunohistochemistry thresholds are conventions; tumours with 1 to 10 percent staining behave more like receptor-negative disease in several series.","Predates the HER2-low and HER2-ultralow categories."],"changedPractice":true},{"id":"paper-park-j-clin-oncol","kind":"paper","name":"Amivantamab in EGFR Exon 20 Insertion-Mutated Non-Small-Cell Lung Cancer Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 34339292 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: Non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor ( EGFR) exon 20 insertion (Exon20ins) mutations exhibits inherent resistance to approved tyrosine kinase inhibitors. Amivantamab, an EGFR-MET bispecific antibody with immune cell-directing activity, binds to each receptor's extracellular domain, bypassing resistance at the tyrosine kinase inhibitor binding site.\n\nMethods: CHRYSALIS is a phase I, open-label, dose-escalation, and dose-expansion study, which included a population with EGFR Exon20ins NSCLC. The primary end points were dose-limiting toxicity and overall response rate. We report findings from the postplatinum EGFR Exon20ins NSCLC population treated at the recommended phase II dose of 1,050 mg amivantamab (1,400 mg, ≥ 80 kg) given once weekly for the first 4 weeks and then once every 2 weeks starting at week 5.\n\nResults: In the efficacy population (n = 81), the median age was 62 years (range, 42-84 years); 40 patients (49%) were Asian, and the median number of previous lines of therapy was two (range, 1-7). The overall response rate was 40% (95% CI, 29 to 51), including three complete responses, with a median duration of response of 11.1 months (95% CI, 6.9 to not reached). The median progression-free survival was 8.3 months (95% CI, 6.5 to 10.9). In the safety population (n = 114), the most common adverse events were rash in 98 patients (86%), infusion-related reactions in 75 (66%), and paronychia in 51 (45%). The most common grade 3-4 adverse events were hypokalemia in six patients (5%) and rash, pulmonary embolism, diarrhea, and neutropenia in four (4%) each. Treatment-related dose reductions and discontinuations were reported in 13% and 4% of patients, respectively.\n\nConclusion: Amivantamab, via its novel mechanism of action, yielded robust and durable responses with tolerable safety in patients with EGFR Exon20ins mutations after progression on platinum-based chemotherapy.\n\nIndexed on Europe PMC as PubMed record 34339292 (DOI 10.1200/jco.21.00662). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2021","url":"https://doi.org/10.1200/jco.21.00662"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34339292/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34339292"}],"tags":["europepmc-ingest"],"related":["egfr-exon20-insertion"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2021,"doi":"10.1200/jco.21.00662","pmid":"34339292","authors":"Park K, Haura EB, Leighl NB, et al.","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nct05379595-j-clin-oncol-2026","kind":"paper","name":"Amivantamab Monotherapy in Chemorefractory RAS / BRAF Wild-Type Metastatic Colorectal Cancer: Results From OrigAMI-1, an Open-Label, Phase Ib/II Study","aka":[],"tldr":"Published report from the OrigAMI-1 trial registered as NCT05379595, in Journal of Clinical Oncology (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Purpose: Amivantamab, an EGFR-MET bispecific antibody with immune cell-directing activity, is approved in non-small cell lung cancer (NSCLC). Effective treatments are limited for chemorefractory metastatic colorectal cancer (mCRC).\n\nMethods: OrigAMI-1 (ClinicalTrials.gov identifier: NCT05379595) is a phase Ib/II study evaluating amivantamab monotherapy in chemorefractory (2-3 prior lines) mCRC. Participants had centrally confirmed RAS / BRAF / EGFR ectodomain wild-type status, without ERBB2 / HER2 amplification. Participants with left-sided mCRC without (cohort A) or with (cohort B) prior anti-EGFR antibody treatment, or right-sided mCRC (cohort C) regardless of prior anti-EGFR treatment, received intravenous amivantamab 1,050 mg (1,400 mg for ≥80 kg) once every 2 weeks. The primary end point was objective response rate (ORR) per RECIST v1.1.\n\nResults: By October 31, 2024, 94 participants received amivantamab monotherapy (median follow-up, 11.9 months). The median age was 60 years, and 65% of participants were male, with a median of 2 prior lines (94%, prior bevacizumab). In left-sided cohorts, the ORR was 29% (5 of 17) in cohort A and 19% (10 of 54) in cohort B; the median duration of response (DoR) was 9.0 months and 6.1 months, and the median progression-free survival (PFS) was 5.7 months and 4.6 months, respectively. In the right-sided cohort, the ORR was 22% (10 of 23; 43% had prior anti-EGFR), the median DoR was 9.8 months, and the median PFS was 3.7 months. Most frequent treatment-related grade ≥3 adverse events (AEs) were rash (7%), dermatitis acneiform (4%), and hypoalbuminemia (4%). One participant discontinued amivantamab because of a treatment-related AE.\n\nConclusion: Amivantamab monotherapy demonstrated promising, durable antitumor activity in chemorefractory mCRC, regardless of prior anti-EGFR therapy and the primary tumor location. The amivantamab safety profile in mCRC is consistent with experience in NSCLC. Amivantamab plus chemotherapy is currently being explored in two phase III studies in first-line and second-line mCRCs.\n\nIndexed on Europe PMC as PubMed record 42013403 (DOI 10.1200/jco-25-02187). Its abstract cites the registry id NCT05379595, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2026","url":"https://doi.org/10.1200/jco-25-02187"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42013403/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42013403"},{"label":"ClinicalTrials.gov NCT05379595","url":"https://clinicaltrials.gov/study/NCT05379595"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05379595"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2026,"doi":"10.1200/jco-25-02187","pmid":"42013403","authors":"Oberstein PE, Hecht JR, Raghav K, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05379595 with the most citations, so it is the natural first reading for anyone following the OrigAMI-1 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-nct04538664-n-engl-j-med-2023","kind":"paper","name":"Amivantamab plus Chemotherapy in NSCLC with EGFR Exon 20 Insertions","aka":[],"tldr":"Published report from the PAPILLON trial registered as NCT04538664, in New England Journal of Medicine (2023), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Amivantamab has been approved for the treatment of patients with advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor ( EGFR) exon 20 insertions who have had disease progression during or after platinum-based chemotherapy. Phase 1 data showed the safety and antitumor activity of amivantamab plus carboplatin-pemetrexed (chemotherapy). Additional data on this combination therapy are needed.\n\nMethods: In this phase 3, international, randomized trial, we assigned in a 1:1 ratio patients with advanced NSCLC with EGFR exon 20 insertions who had not received previous systemic therapy to receive intravenous amivantamab plus chemotherapy (amivantamab-chemotherapy) or chemotherapy alone. The primary outcome was progression-free survival according to blinded independent central review. Patients in the chemotherapy group who had disease progression were allowed to cross over to receive amivantamab monotherapy.\n\nResults: A total of 308 patients underwent randomization (153 to receive amivantamab-chemotherapy and 155 to receive chemotherapy alone). Progression-free survival was significantly longer in the amivantamab-chemotherapy group than in the chemotherapy group (median, 11.4 months and 6.7 months, respectively; hazard ratio for disease progression or death, 0.40; 95% confidence interval [CI], 0.30 to 0.53; P<0.001). At 18 months, progression-free survival was reported in 31% of the patients in the amivantamab-chemotherapy group and in 3% in the chemotherapy group; a complete or partial response at data cutoff was reported in 73% and 47%, respectively (rate ratio, 1.50; 95% CI, 1.32 to 1.68; P<0.001). In the interim overall survival analysis (33% maturity), the hazard ratio for death for amivantamab-chemotherapy as compared with chemotherapy was 0.67 (95% CI, 0.42 to 1.09; P = 0.11). The predominant adverse events associated with amivantamab-chemotherapy were reversible hematologic and EGFR-related toxic effects; 7% of patients discontinued amivantamab owing to adverse reactions.\n\nConclusions: The use of amivantamab-chemotherapy resulted in superior efficacy as compared with chemotherapy alone as first-line treatment of patients with advanced NSCLC with EGFR exon 20 insertions. (Funded by Janssen Research and Development; PAPILLON ClinicalTrials.gov number, NCT04538664.).\n\nIndexed on Europe PMC as PubMed record 37870976 (DOI 10.1056/nejmoa2306441). Its abstract cites the registry id NCT04538664, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2023","url":"https://doi.org/10.1056/nejmoa2306441"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37870976/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37870976"},{"label":"ClinicalTrials.gov NCT04538664","url":"https://clinicaltrials.gov/study/NCT04538664"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04538664"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/nejmoa2306441","pmid":"37870976","authors":"Zhou C, Tang KJ, Cho BC, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04538664 with the most citations, so it is the natural first reading for anyone following the PAPILLON trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-chrysalis-nat-med-2023","kind":"paper","name":"Amivantamab plus lazertinib in osimertinib-relapsed EGFR-mutant advanced non-small cell lung cancer: a phase 1 trial","aka":[],"tldr":"Published report from the CHRYSALIS trial registered as NCT02609776, in Nature Medicine (2023), chosen as the most cited paper whose own text cites the registry id.","summary":"Patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) often develop resistance to current standard third-generation EGFR tyrosine kinase inhibitors (TKIs); no targeted treatments are approved in the osimertinib-relapsed setting. In this open-label, dose-escalation and dose-expansion phase 1 trial, the potential for improved anti-tumor activity by combining amivantamab, an EGFR-MET bispecific antibody, with lazertinib, a third-generation EGFR TKI, was evaluated in patients with EGFR-mutant NSCLC whose disease progressed on third-generation TKI monotherapy but were chemotherapy naive (CHRYSALIS cohort E). In the dose-escalation phase, the recommended phase 2 combination dose was established; in the dose-expansion phase, the primary endpoints were safety and overall response rate, and key secondary endpoints included progression-free survival and overall survival. The safety profile of amivantamab and lazertinib was generally consistent with previous experience of each agent alone, with 4% experiencing grade ≥3 events; no new safety signals were identified. In an exploratory cohort of 45 patients who were enrolled without biomarker selection, the primary endpoint of investigator-assessed overall response rate was 36% (95% confidence interval, 22-51). The median duration of response was 9.6 months, and the median progression-free survival was 4.9 months. Next-generation sequencing and immunohistochemistry analyses identified high EGFR and/or MET expression as potential predictive biomarkers of response, which will need to be validated with prospective assessment. ClinicalTrials.gov identifier: NCT02609776.\n\nIndexed on Europe PMC as PubMed record 37710001 (DOI 10.1038/s41591-023-02554-7). Its abstract cites the registry id NCT02609776, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Nat Med 2023","url":"https://doi.org/10.1038/s41591-023-02554-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37710001/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37710001"},{"label":"ClinicalTrials.gov NCT02609776","url":"https://clinicaltrials.gov/study/NCT02609776"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["chrysalis"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2023,"doi":"10.1038/s41591-023-02554-7","pmid":"37710001","authors":"Cho BC, Kim DW, Spira AI, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02609776 with the most citations, so it is the natural first reading for anyone following the CHRYSALIS trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-ampect-nab-sirolimus-pecoma-wagner-jco-2021","kind":"paper","name":"AMPECT: nab-sirolimus for malignant perivascular epithelioid cell tumours","aka":[],"tldr":"Albumin-bound sirolimus shrank tumours in about four in ten patients with malignant PEComa, with responses lasting years and best results in tumours with TSC2 mutations, and became the first approved treatment for the disease.","summary":"Phase 2 study of 34 patients with malignant PEComa treated with intravenous nab-sirolimus weekly for two of every three weeks.\n\nObjective response by independent review was 39 percent with a median duration of response not reached (over 2.5 years), median progression-free survival 10.6 months; 89 percent of TSC2-mutant tumours responded. Stomatitis, myelosuppression and hyperglycaemia were manageable.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2021","url":"https://doi.org/10.1200/JCO.21.01728"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34637337/"}],"tags":[],"related":[],"cancers":["pecoma"],"sections":[],"technologies":[],"targets":[],"drugs":["sirolimus-albumin-bound"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["ampect"],"people":["andrew-wagner"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2021,"doi":"10.1200/JCO.21.01728","pmid":"34637337","authors":"Wagner AJ, Ravi V, Riedel RF, et al.","paperType":"observational","findings":["Objective response 39 percent; 89 percent in TSC2-mutant tumours.","Median duration of response not reached at 2.5 years."],"whatItMeans":"Nab-sirolimus is the approved first-line treatment for advanced malignant PEComa, and TSC1/TSC2 testing helps predict response.","caveats":["Single-arm study in a rare tumour; comparison with oral mTOR inhibitors is indirect."],"changedPractice":true,"participants":34},{"id":"paper-amplify-acalabrutinib-venetoclax-nejm-2025","kind":"paper","name":"AMPLIFY: fixed-duration acalabrutinib plus venetoclax, with or without obinutuzumab, versus chemo-immunotherapy in fit CLL patients","aka":[],"tldr":"In AMPLIFY, an all-oral, 14-month course of acalabrutinib plus venetoclax beat FCR or BR chemo-immunotherapy in fit CLL patients, offering a time-limited alternative to indefinite pills.","summary":"AMPLIFY randomised 867 fit, previously untreated patients with CLL without del(17p) or TP53 mutation to acalabrutinib plus venetoclax (AV), acalabrutinib plus venetoclax plus obinutuzumab (AVO), or investigator's choice of FCR or bendamustine-rituximab. The primary endpoint was PFS for AV versus chemo-immunotherapy. Estimated 36-month PFS was 76.5% with AV, 83.1% with AVO and 66.5% with chemo-immunotherapy (hazard ratios 0.65 and 0.42 respectively). Overall survival favoured AV, driven largely by deaths from COVID-19 in the chemo-immunotherapy arm during the pandemic. AVO produced the deepest MRD responses but more infections and neutropenia.","asOf":"2026-09-08","links":[{"label":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=AMPLIFY%20acalabrutinib%20venetoclax%20obinutuzumab%20Brown%20NEJM%202025"},{"label":"ClinicalTrials.gov NCT03836261","url":"https://clinicaltrials.gov/study/NCT03836261"}],"tags":[],"related":["btki-plus-venetoclax-fixed-duration"],"cancers":["cll"],"sections":[],"technologies":[],"targets":["btk","bcl2","cd20"],"drugs":["acalabrutinib","venetoclax","obinutuzumab"],"companies":["astrazeneca","abbvie"],"institutions":[],"pathways":[],"terms":["mrd","pfs","del17p-tp53"],"trials":["amplify","cll13-gaia","glow"],"people":[],"bottlenecks":["b-combination-space","b-drug-pricing"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2025,"doi":"10.1056/NEJMoa2409804","pmid":"39976417","authors":"Brown JR, Seymour JF, Jurczak W, et al.","paperType":"rct","findings":["867 fit patients without TP53 aberration; 14 cycles of AV or AVO vs 6 cycles of FCR or BR.","36-month PFS: 76.5% (AV), 83.1% (AVO), 66.5% (chemo-immunotherapy); HR 0.65 for AV and 0.42 for AVO vs chemo-immunotherapy.","Overall survival better with AV than chemo-immunotherapy, but many chemo-immunotherapy deaths were from COVID-19.","Undetectable MRD rates were highest with AVO; AV produced a lower MRD-negativity rate than AVO or venetoclax-obinutuzumab in other trials.","Grade 3 or higher neutropenia and infections were more frequent with AVO than AV."],"whatItMeans":"AMPLIFY delivered the first all-oral, fixed-duration doublet for front-line CLL and supported its approval, giving fit patients a way to avoid both chemotherapy and years of continuous BTK inhibitor. It does not settle whether a doublet or triplet is best, or how AV compares with venetoclax-obinutuzumab. Patients with TP53 aberration were excluded and still need different strategies.","caveats":["Chemo-immunotherapy is no longer the preferred comparator in many countries; the relevant question is AV versus venetoclax-obinutuzumab or continuous BTKi.","The OS signal is confounded by pandemic-era deaths.","Excluded del(17p)/TP53-mutated patients.","AV MRD-negativity was lower than with AVO; long-term durability is still maturing."],"changedPractice":true,"participants":867},{"id":"paper-nct05415072-nat-med-2026","kind":"paper","name":"An anti-PMEL antibody-drug conjugate with a G q/1 1 inhibitor payload in GNAQ/GNA11-mutant melanomas: a phase 1 trial","aka":[],"tldr":"Published report from the trial registered as NCT05415072, in Nature Medicine (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Metastatic uveal melanoma (mUM) is an aggressive cancer with limited treatment options; 85-90% of tumors harbor activating GNAQ and GNA11 mutations. Uveal melanoma cells also express PMEL (also known as PMEL17 or gp100), a melanocyte lineage antigen. DYP688, a novel biology-matched antibody-drug conjugate, binds surface PMEL and delivers the potent Gα q /Gα 11 (G q/11) inhibitor SDZ475 as payload by internalization. This dose-escalating first-in-human phase 1 study of DYP688 in patients with metastatic uveal melanoma and other GNAQ/GNA11-mutant melanomas assessed safety as the primary endpoint and pharmacokinetics and preliminary antitumor activity as secondary endpoints. Sixty-six patients received varying DYP688 doses and schedules. Grade 3 treatment-related adverse events occurred in five patients (7.6%), including one dose-limiting toxicity of grade 3 hypotension. Objective responses were seen in 13 out of 66 patients (19.7%) and tumor reduction in 47 out of 66 patients (71.2%). Median progression-free survival was 7.2 (95% CI: 5.3-7.8) months. In summary, DYP688 was well tolerated and showed preliminary efficacy, supporting this novel therapeutic approach. ClinicalTrials.gov identifier: NCT05415072.\n\nIndexed on Europe PMC as PubMed record 42443515 (DOI 10.1038/s41591-026-04518-z). Its abstract cites the registry id NCT05415072, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Nat Med 2026","url":"https://doi.org/10.1038/s41591-026-04518-z"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42443515/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42443515"},{"label":"ClinicalTrials.gov NCT05415072","url":"https://clinicaltrials.gov/study/NCT05415072"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05415072"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2026,"doi":"10.1038/s41591-026-04518-z","pmid":"42443515","authors":"Carlino MS, Kapiteijn E, Piperno-Neumann S, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05415072 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-moore-israel-cancer-registry-completeness-imaj-2021","kind":"paper","name":"An assessment of the completeness and timeliness of the Israel National Cancer Registry","aka":[],"tldr":"The registry checked its own work by sending people to 39 hospitals and laboratories to count the cancers by hand, then seeing how many were in the database. About one in sixteen was not.","summary":"The Israel National Cancer Registry was established in 1960 and notification has been compulsory since 1982. Reportable disease covers all invasive and in-situ malignancies and neoplasms of uncertain behaviour, and benign as well as malignant tumours of the brain and central nervous system, but excludes basal and squamous cell carcinomas of the skin, which is why Israel's non-melanoma skin cancer figures should not be read as a count.\n\nTo measure its own completeness the registry sent abstractors into the medical records departments, pathology and cytology laboratories and oncology and haematology institutes of 39 Israeli medical facilities to identify every reportable case diagnosed or treated in 2005, then linked those cases to the registry database by national identity number. Completeness was the proportion of independently identified reportable cases that the registry already held; timeliness was the proportion of 2005 cases in the database by 31 December 2007.\n\nCompleteness was 93.7 percent for all reportable disease, 96.8 percent for invasive solid tumours and 88.0 percent for haematopoietic tumours. Cases diagnosed in the index year were less likely to be in the database than older ones, which is what a reporting lag looks like. The authors judge both measures to meet international guidelines and argue for fully automated reporting.","asOf":"2026-09-25","links":[{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33443338/"},{"label":"Israel Medical Association Journal","url":"https://www.ima.org.il/MedicineIMAJ/"}],"tags":[],"related":[],"cancers":[],"sections":["prevention"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["incidence-vs-prevalence"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Israel Medical Association Journal","year":2021,"pmid":"33443338","authors":"Moore E, Silverman BG, Fishler Y, Ben-Adiva E, Davidov O, Dichtiar R, Edri H, Zatlawi M, Keinan-Boker L","paperType":"methods","findings":["Completeness against an independent case-finding survey of 39 facilities: 93.7 percent for all reportable disease, 96.8 percent for invasive solid tumours, 88.0 percent for haematopoietic tumours.","Notification has been mandatory since 1982; the registry was founded in 1960.","Basal and squamous cell carcinomas of the skin are not reportable, so they are absent from Israeli registry counts.","Cases from the index diagnosis year were less likely to be present than older cases, the signature of a reporting lag."],"whatItMeans":"It is the number to quote when using Israeli registry data, and the reason to treat the most recent year in any registry report as provisional. It also explains why haematological malignancies are the weakest part of the count, and why Israeli non-melanoma skin cancer statistics are not comparable with countries that register it.","caveats":["The audit covers cases diagnosed or treated in 2005; completeness and timeliness since then are not measured by this paper, and the authors expected automated reporting to change both.","Completeness is measured against what abstractors could find in 39 facilities, which is itself an incomplete frame."]},{"id":"paper-sanai-j-neurosurg","kind":"paper","name":"An extent of resection threshold for newly diagnosed glioblastomas","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 21417701 and published in Journal of neurosurgery; the citing page links this DOI, which is how the record was matched.","summary":"Object: The value of extent of resection (EOR) in improving survival in patients with glioblastoma multiforme (GBM) remains controversial. Specifically, it is unclear what proportion of contrast-enhancing tumor must be resected for a survival advantage and how much survival improves beyond this threshold. The authors attempt to define these values for the patient with newly diagnosed GBM in the modern neurosurgical era.\n\nMethods: The authors identified 500 consecutive newly diagnosed patients with supratentorial GBM treated at the University of California, San Francisco between 1997 and 2009. Clinical, radiographic, and outcome parameters were measured for each case, including MR imaging-based volumetric tumor analysis.\n\nResults: The patients had a median age of 60 years and presented with a median Karnofsky Performance Scale (KPS) score of 80. The mean clinical follow-up period was 15.3 months, and no patient was unaccounted for. All patients underwent resection followed by chemotherapy and radiation therapy. The median postoperative tumor volume was 2.3 cm(3), equating to a 96% EOR. The median overall survival was 12.2 months. Using Cox proportional hazards analysis, age, KPS score, and EOR were predictive of survival (p < 0.0001). A significant survival advantage was seen with as little as 78% EOR, and stepwise improvement in survival was evident even in the 95%-100% EOR range. A recursive partitioning analysis validated these findings and provided additional risk stratification parameters related to age, EOR, and tumor burden.\n\nConclusions: For patients with newly diagnosed GBMs, aggressive EOR equates to improvement in overall survival, even at the highest levels of resection. Interestingly, subtotal resections as low as 78% also correspond to a survival benefit.\n\nIndexed on Europe PMC as PubMed record 21417701 (DOI 10.3171/2011.2.jns10998). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Neurosurg 2011","url":"https://doi.org/10.3171/2011.2.jns10998"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21417701/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/21417701"}],"tags":["europepmc-ingest"],"related":["extent-of-resection"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of neurosurgery","year":2011,"doi":"10.3171/2011.2.jns10998","pmid":"21417701","authors":"Sanai N, Polley MY, McDermott MW, et al.","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-hu-j-natl-cancer-inst","kind":"paper","name":"An Observational Study of Deep Learning and Automated Evaluation of Cervical Images for Cancer Screening","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 30629194 and published in JNCI: Journal of the National Cancer Institute; the citing page links this DOI, which is how the record was matched.","summary":"Background: Human papillomavirus vaccination and cervical screening are lacking in most lower resource settings, where approximately 80% of more than 500 000 cancer cases occur annually. Visual inspection of the cervix following acetic acid application is practical but not reproducible or accurate. The objective of this study was to develop a \"deep learning\"-based visual evaluation algorithm that automatically recognizes cervical precancer/cancer.\n\nMethods: A population-based longitudinal cohort of 9406 women ages 18-94 years in Guanacaste, Costa Rica was followed for 7 years (1993-2000), incorporating multiple cervical screening methods and histopathologic confirmation of precancers. Tumor registry linkage identified cancers up to 18 years. Archived, digitized cervical images from screening, taken with a fixed-focus camera (\"cervicography\"), were used for training/validation of the deep learning-based algorithm. The resultant image prediction score (0-1) could be categorized to balance sensitivity and specificity for detection of precancer/cancer. All statistical tests were two-sided.\n\nResults: Automated visual evaluation of enrollment cervigrams identified cumulative precancer/cancer cases with greater accuracy (area under the curve [AUC] = 0.91, 95% confidence interval [CI] = 0.89 to 0.93) than original cervigram interpretation (AUC = 0.69, 95% CI = 0.63 to 0.74; P <.001) or conventional cytology (AUC = 0.71, 95% CI = 0.65 to 0.77; P <.001). A single visual screening round restricted to women at the prime screening ages of 25-49 years could identify 127 (55.7%) of 228 precancers (cervical intraepithelial neoplasia 2/cervical intraepithelial neoplasia 3/adenocarcinoma in situ [AIS]) diagnosed cumulatively in the entire adult population (ages 18-94 years) while referring 11.0% for management.\n\nConclusions: The results support consideration of automated visual evaluation of cervical images from contemporary digital cameras. If achieved, this might permit dissemination of effective point-of-care cervical screening.\n\nIndexed on Europe PMC as PubMed record 30629194 (DOI 10.1093/jnci/djy225). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Natl Cancer Inst 2019","url":"https://doi.org/10.1093/jnci/djy225"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30629194/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30629194"}],"tags":["europepmc-ingest"],"related":["colposcopes-digital-cervical-screening"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jnci"],"dependsOn":[],"notes":[],"journal":"JNCI: Journal of the National Cancer Institute","year":2019,"doi":"10.1093/jnci/djy225","pmid":"30629194","authors":"Hu L, Bell D, Antani S, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-quigley-brca2-reversion-cfdna-parp-resistance-cancer-discov-2017","kind":"paper","name":"Analysis of circulating cell-free DNA identifies multiclonal heterogeneity of BRCA2 reversion mutations associated with resistance to PARP inhibitors","aka":[],"tldr":"When PARP inhibitors stop working in prostate cancer, the tumour has repaired the broken gene, and a blood test shows it has done so in several different ways at once.","summary":"About 20% of metastatic prostate cancers carry mutations in genes required for DNA repair by homologous recombination, such as BRCA2, and those defects confer synthetic lethality to PARP inhibitors. In ovarian and breast cancer, olaparib resistance has been associated with restoration of homologous recombination, including by BRCA2 mutation reversion. This study identified BRCA2 reversion mutations associated with olaparib and talazoparib resistance in patients with prostate cancer. Analysis of circulating cell-free DNA revealed reversion mutation heterogeneity that was not discernible from a single solid-tumour biopsy, and suggested that cell-free DNA can be used to monitor for the emergence of PARP inhibitor resistance.","asOf":"2026-09-25","links":[{"label":"Quigley et al., Cancer Discov 2017: multiclonal BRCA2 reversion mutations in cell-free DNA and resistance to PARP inhibitors in prostate cancer","url":"https://doi.org/10.1158/2159-8290.CD-17-0146"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28450426/"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["liquid-biopsy"],"targets":["brca","parp"],"drugs":[],"companies":[],"institutions":[],"pathways":["homologous-recombination-repair","base-excision-repair-parp","synthetic-lethality-map","resistance-routes-map"],"terms":["brca-reversion-mutations","resistance","ctdna","cfdna","hrd"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-discovery"],"dependsOn":[],"notes":[],"journal":"Cancer Discovery","year":2017,"doi":"10.1158/2159-8290.CD-17-0146","pmid":"28450426","authors":"Quigley D, Alumkal JJ, Wyatt AW, et al.","paperType":"translational","findings":["BRCA2 reversion mutations identified in men with prostate cancer resistant to olaparib and to talazoparib.","Resistance was highly multiclonal, with several independent restoring events.","Cell-free DNA revealed heterogeneity a single solid-tumour biopsy could not show."],"whatItMeans":"It establishes that PARP inhibitor resistance in prostate cancer is a restored repair pathway rather than a bypass, which is why platinum and PARP inhibitors lose activity together, and it is the argument for sampling plasma rather than one lesion at progression.","caveats":["A small series of patients, published as a brief report.","No licensed assay reports reversion mutations.","Reversion is one mechanism among several and its frequency in prostate cancer has not been counted prospectively."],"changedPractice":false},{"id":"paper-reinert-ctdna-ultradeep-sequencing-colorectal-jama-oncol-2019","kind":"paper","name":"Analysis of plasma cell-free DNA by ultradeep sequencing in patients with stages I to III colorectal cancer","aka":[],"tldr":"Testing the same patients again and again after surgery, and after chemotherapy, and during follow-up, showed the blood test gets more powerful the later you use it, and found relapses up to 16 months before a scan did.","summary":"In a prospective, multicentre cohort study, circulating tumour DNA was quantified before and after surgery, during and after adjuvant chemotherapy and during surveillance in stage I to III colorectal cancer by personalised multiplex PCR-based next-generation sequencing. 130 patients were enrolled at three Danish hospitals from 2014 to 2017, with 829 plasma samples collected before surgery, at postoperative day 30 and every three months for up to three years; 125 were analysable. Preoperatively, ctDNA was detectable in 108 of 122 patients (88.5%). After definitive treatment, longitudinal analysis identified 14 of 16 relapses (87.5%). At postoperative day 30, ctDNA-positive patients were 7 times more likely to relapse (hazard ratio 7.2); shortly after adjuvant chemotherapy, 17 times (hazard ratio 17.5), and all 7 patients who were positive after chemotherapy relapsed. During surveillance, ctDNA-positive patients were more than 40 times more likely to recur (hazard ratio 43.5). ctDNA status was independently associated with relapse after adjustment for known risk factors, and serial analysis revealed recurrence up to 16.5 months ahead of standard imaging.","asOf":"2026-09-24","links":[{"label":"Reinert et al., JAMA Oncol 2019: ultradeep sequencing of plasma cell-free DNA in 130 stage I-III colorectal cancers","url":"https://doi.org/10.1001/jamaoncol.2019.0528"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31070691/"}],"tags":[],"related":["ctdna-mrd-positive"],"cancers":["colorectal"],"sections":[],"technologies":["mrd-testing","liquid-biopsy","continuous-ctdna-monitoring"],"targets":[],"drugs":["signatera"],"companies":[],"institutions":["aarhus-university-hospital"],"pathways":[],"terms":["mrd","ctdna","cfdna","tumour-informed-assay"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2019,"doi":"10.1001/jamaoncol.2019.0528","pmid":"31070691","authors":"Reinert T, Henriksen TV, Christensen E, et al.","paperType":"observational","findings":["Preoperative ctDNA detectable in 108 of 122 patients (88.5%).","Relapse hazard ratios 7.2 at day 30, 17.5 after adjuvant chemotherapy and 43.5 during surveillance.","Lead time over standard imaging of up to 16.5 months."],"whatItMeans":"It showed that serial rather than single testing is what makes residual disease detection work, and it set the sampling schedule most later studies have used.","caveats":["130 patients at three centres, with 16 relapses, so the confidence intervals are wide.","Tumour-informed assay requires tumour tissue and bespoke panel design.","Observational: no treatment decision was made on the result."],"changedPractice":false,"participants":130},{"id":"paper-chan-n-engl-j-med","kind":"paper","name":"Analysis of Plasma Epstein-Barr Virus DNA to Screen for Nasopharyngeal Cancer","aka":[],"tldr":"Paper cited by one cancer page and one term page, indexed on Europe PMC as PubMed record 28792880 and published in New England Journal of Medicine; the citing pages link this DOI, which is how the record was matched.","summary":"Background: Circulating cell-free Epstein-Barr virus (EBV) DNA is a biomarker for nasopharyngeal carcinoma. We conducted a prospective study to investigate whether EBV DNA in plasma samples would be useful to screen for early nasopharyngeal carcinoma in asymptomatic persons.\n\nMethods: We analyzed EBV DNA in plasma specimens to screen participants who did not have symptoms of nasopharyngeal carcinoma. Participants with initially positive results were retested approximately 4 weeks later, and those with persistently positive EBV DNA in plasma underwent nasal endoscopic examination and magnetic resonance imaging (MRI).\n\nResults: A total of 20,174 participants underwent screening. EBV DNA was detectable in plasma samples obtained from 1112 participants (5.5%), and 309 (1.5% of all participants and 27.8% of those who initially tested positive) had persistently positive results on the repeated sample. Among these 309 participants, 300 underwent endoscopic examination, and 275 underwent both endoscopic examination and MRI; of these participants, 34 had nasopharyngeal carcinoma. A significantly higher proportion of participants with nasopharyngeal carcinoma that was identified by screening had stage I or II disease than in a historical cohort (71% vs. 20%, P<0.001 by the chi-square test) and had superior 3-year progression-free survival (97% vs. 70%; hazard ratio, 0.10; 95% confidence interval, 0.05 to 0.18). Nine participants declined to undergo further testing, and 1 of them presented with advanced nasopharyngeal carcinoma 32 months after enrollment. Nasopharyngeal carcinoma developed in only 1 participant with negative EBV DNA in plasma samples within 1 year after testing. The sensitivity and specificity of EBV DNA in plasma samples in screening for nasopharyngeal carcinoma were 97.1% and 98.6%, respectively.\n\nConclusions: Analysis of EBV DNA in plasma samples was useful in screening for early asymptomatic nasopharyngeal carcinoma. Nasopharyngeal carcinoma was detected significantly earlier and outcomes were better in participants who were identified by screening than in those in a historical cohort. (Funded by the Kadoorie Charitable Foundation and the Research Grants Council of the Hong Kong government; ClinicalTrials.gov number, NCT02063399.).\n\nIndexed on Europe PMC as PubMed record 28792880 (DOI 10.1056/nejmoa1701717). Matched by DOI alone: one cancer page and one term page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2017","url":"https://doi.org/10.1056/nejmoa1701717"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28792880/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28792880"}],"tags":["europepmc-ingest"],"related":["nasopharyngeal","plasma-ebv-dna"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2017,"doi":"10.1056/nejmoa1701717","pmid":"28792880","authors":"Chan KCA, Woo JKS, King A, et al.","paperType":"observational","findings":[],"whatItMeans":"One cancer page and one term page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-yu-acquired-resistance-rebiopsy-egfr-ccr-2013","kind":"paper","name":"Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers","aka":[],"tldr":"Rebiopsying 155 patients whose targeted pill had stopped working put numbers on how they escape: about two thirds by one mutation, a few by making extra copies of another receptor, and a few by turning into a different kind of cancer altogether.","summary":"Patients with lung adenocarcinoma and acquired resistance to erlotinib or gefitinib enrolled in a prospective biopsy protocol and underwent rebiopsy after resistance developed. Histology was reviewed and samples genotyped for mutations in EGFR, AKT1, BRAF, ERBB2, KRAS, MEK1, NRAS and PIK3CA, with fluorescence in situ hybridisation for MET and HER2. Adequate samples were obtained in 155 patients. Ninety-eight had a second-site EGFR T790M mutation, 63%, and four had small-cell transformation, 3%. MET amplification was seen in 4 of 75, 5%, and HER2 amplification in 3 of 24, 13%. No acquired mutations were detected in PIK3CA, AKT1, BRAF, ERBB2, KRAS, MEK1 or NRAS among 88 tested. Overlap between mechanisms was seen in 4%.","asOf":"2026-09-25","links":[{"label":"Yu et al., Clin Cancer Res 2013: rebiopsy at acquired resistance in 155 patients with EGFR-mutant lung cancer","url":"https://doi.org/10.1158/1078-0432.CCR-12-2246"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23470965/"}],"tags":[],"related":["egfr-t790m","met-amplification-readout"],"cancers":["nsclc","sclc"],"sections":[],"technologies":["cytogenetics-fish","cgp"],"targets":["egfr","met","her2"],"drugs":["erlotinib","gefitinib"],"companies":[],"institutions":["mskcc"],"pathways":["resistance-routes-map","rtk-activation","lineage-plasticity-neuroendocrine"],"terms":["resistance","histologic-transformation","met-amplification","biopsy"],"trials":[],"people":["gregory-riely"],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2013,"doi":"10.1158/1078-0432.CCR-12-2246","pmid":"23470965","authors":"Yu HA, Arcila ME, Rekhtman N, et al.","paperType":"observational","findings":["T790M in 98 of 155 rebiopsied patients, 63%, the dominant mechanism.","MET amplification in 5% and HER2 amplification in 13% of those tested for them.","Small-cell transformation in 3%.","No acquired mutations in the downstream pathway genes tested."],"whatItMeans":"It is the reference frequency table for resistance to first-generation EGFR inhibitors, and it made rebiopsy at progression standard rather than exceptional, because the mechanism decides the next treatment and cannot be guessed.","caveats":["Only patients whose disease could be safely rebiopsied were included, which selects for accessible lesions.","A limited gene set was tested, so mechanisms outside it were not counted.","Single centre."],"changedPractice":true,"participants":155},{"id":"paper-romana-1-2-lancet-oncol-2016","kind":"paper","name":"Anamorelin in patients with non-small-cell lung cancer and cachexia (ROMANA 1 and ROMANA 2): results from two randomised, double-blind, phase 3 trials","aka":[],"tldr":"Published report from the ROMANA 1 trial registered as NCT01387269, in The Lancet Oncology (2016), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Patients with advanced cancer frequently experience anorexia and cachexia, which are associated with reduced food intake, altered body composition, and decreased functionality. We assessed anamorelin, a novel ghrelin-receptor agonist, on cachexia in patients with advanced non-small-cell lung cancer and cachexia.\n\nMethods: ROMANA 1 and ROMANA 2 were randomised, double-blind, placebo-controlled phase 3 trials done at 93 sites in 19 countries. Patients with inoperable stage III or IV non-small-cell lung cancer and cachexia (defined as ≥5% weight loss within 6 months or body-mass index <20 kg/m(2)) were randomly assigned 2:1 to anamorelin 100 mg orally once daily or placebo, with a computer-generated randomisation algorithm stratified by geographical region, cancer treatment status, and weight loss over the previous 6 months. Co-primary efficacy endpoints were the median change in lean body mass and handgrip strength over 12 weeks and were measured in all study participants (intention-to-treat population). Both trials are now completed and are registered with ClinicalTrials.gov, numbers NCT01387269 and NCT01387282.\n\nFindings: From July 8, 2011, to Jan 28, 2014, 484 patients were enrolled in ROMANA 1 (323 to anamorelin, 161 to placebo), and from July 14, 2011, to Oct 31, 2013, 495 patients were enrolled in ROMANA 2 (330 to anamorelin, 165 to placebo). Over 12 weeks, lean body mass increased in patients assigned to anamorelin compared with those assigned to placebo in ROMANA 1 (median increase 0·99 kg [95% CI 0·61 to 1·36] vs -0·47 kg [-1·00 to 0·21], p<0·0001) and ROMANA 2 (0·65 kg [0·38 to 0·91] vs -0·98 kg [-1·49 to -0·41], p<0·0001). We noted no difference in handgrip strength in ROMANA 1 (-1·10 kg [-1·69 to -0·40] vs -1·58 kg [-2·99 to -1·14], p=0·15) or ROMANA 2 (-1·49 kg [-2·06 to -0·58] vs -0·95 kg [-1·56 to 0·04], p=0·65). There were no differences in grade 3-4 treatment-related adverse events between study groups; the most common grade 3-4 adverse event was hyperglycaemia, occurring in one (<1%) of 320 patients given anamorelin in ROMANA 1 and in four (1%) of 330 patients given anamorelin in ROMANA 2.\n\nInterpretation: Anamorelin significantly increased lean body mass, but not handgrip, strength in patients with advanced non-small-cell lung cancer. Considering the unmet medical need for safe and effective treatments for cachexia, anamorelin might be a treatment option for patients with cancer anorexia and cachexia.\n\nFunding: Helsinn Therapeutics.\n\nIndexed on Europe PMC as PubMed record 26906526 (DOI 10.1016/s1470-2045(15)00558-6). Its abstract cites the registry id NCT01387269, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2016","url":"https://doi.org/10.1016/s1470-2045(15)00558-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26906526/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26906526"},{"label":"ClinicalTrials.gov NCT01387269","url":"https://clinicaltrials.gov/study/NCT01387269"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["romana-1-2"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2016,"doi":"10.1016/s1470-2045(15)00558-6","pmid":"26906526","authors":"Temel JS, Abernethy AP, Currow DC, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT01387269 with the most citations, so it is the natural first reading for anyone following the ROMANA 1 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","The abstract cites more than one registry id (NCT01387269, NCT01387282); it was kept because the trial's acronym appears in the title."]},{"id":"paper-kwak-crizotinib-alk-nsclc-nejm-2010","kind":"paper","name":"Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer","aka":[],"tldr":"1,500 tumours were screened to find 82 patients with an ALK fusion. Of those, 57 percent responded to crizotinib, a drug originally developed against a different target.","summary":"Kwak, Bang, Camidge, Shaw and colleagues screened tumour samples from approximately 1,500 patients with non-small-cell lung cancer for ALK rearrangements and enrolled 82 with advanced ALK-positive disease into an expanded cohort of the phase 1 study of crizotinib at 250 mg twice daily.\n\nThe screening ratio is the story as much as the response rate. Finding 82 eligible patients took 1,500 assays, which is the infrastructure cost of precision oncology stated plainly, and the reason molecular testing had to become routine rather than trial-specific.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2010","url":"https://doi.org/10.1056/NEJMoa1006448"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20979469/"},{"label":"ClinicalTrials.gov NCT00585195","url":"https://clinicaltrials.gov/study/NCT00585195"}],"tags":["lung-evidence"],"related":["paper-soda-eml4-alk-fusion-nature-2007","paper-alk-nsclc-n-engl-j-med-2013","paper-peters-alex-alectinib-crizotinib-nejm-2017","paper-shaw-crizotinib-ros1-nejm-2014"],"cancers":["lung-cancer","nsclc","alk-positive-nsclc"],"sections":["targeted-therapy"],"technologies":["fish","ngs","kinase-inhibitors"],"targets":["alk","met"],"drugs":["crizotinib"],"companies":["pfizer"],"institutions":["mgh"],"pathways":[],"terms":["driver-mutation","oncogene-addiction","brain-metastases"],"trials":[],"people":["alice-shaw"],"bottlenecks":["b-biomarker-validation","b-brain-delivery","b-trial-enrolment"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2010,"doi":"10.1056/NEJMoa1006448","pmid":"20979469","authors":"Kwak EL, Bang YJ, Camidge DR, et al.","paperType":"rct","findings":["Overall response rate 57 percent (47 of 82 patients: 46 confirmed partial responses and 1 confirmed complete response) at a mean treatment duration of 6.4 months.","27 patients (33 percent) had stable disease.","63 of 82 patients (77 percent) were still receiving crizotinib at data cutoff; estimated six-month progression-free survival 72 percent, with no median reached.","Side effects were mild grade 1 or 2 gastrointestinal events.","Approximately 1,500 patients were screened to identify the 82 with ALK rearrangements; those patients tended to be younger, with little or no tobacco exposure, and had adenocarcinomas."],"whatItMeans":"The trial that made ALK testing worth doing. It is also the clearest case in oncology of a drug finding its disease after the fact: crizotinib entered the clinic as a MET inhibitor and became an ALK drug because somebody checked.","caveats":["Single-arm expanded phase 1 cohort, not randomised; the randomised comparison against chemotherapy came in PROFILE 1007 (paper-alk-nsclc-n-engl-j-med-2013).","Median progression-free survival was not reached at 6.4 months of follow-up, so durability could not be judged.","Crizotinib penetrates the central nervous system poorly, and brain progression became the dominant failure pattern; the next-generation inhibitors were built for that."],"changedPractice":true,"participants":82},{"id":"paper-anbl00p2-expectant-observation-nuchtern-ann-surg-2012","kind":"paper","name":"ANBL00P2: expectant observation as primary therapy for neuroblastoma in young infants","aka":[],"tldr":"Small adrenal masses found in infants under six months could safely be watched rather than operated on: nearly half shrank or disappeared and the rest were removed later without any child dying of neuroblastoma.","summary":"Children's Oncology Group prospective study of 87 infants under six months with small (under 3.1 cm solid or 5 cm cystic) adrenal masses managed by observation with serial ultrasound and urinary catecholamines, with surgery for growth or progression.\n\nEighty-one percent avoided surgery; among those observed, 45 percent had complete or partial spontaneous resolution, and three-year event-free and overall survival were 97.7 and 100 percent.","asOf":"2026-09-17","links":[{"label":"Ann Surg 2012","url":"https://doi.org/10.1097/SLA.0b013e31826cbbbd"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22964741/"}],"tags":[],"related":[],"cancers":["neuroblastoma-low-risk"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Annals of Surgery","year":2012,"doi":"10.1097/SLA.0b013e31826cbbbd","pmid":"22964741","authors":"Nuchtern JG, London WB, Barnewolt CE, et al.","paperType":"observational","findings":["Surgery avoided in 81 percent of infants.","Three-year overall survival 100 percent."],"whatItMeans":"Observation without biopsy is standard for small adrenal masses in young infants, sparing them surgery for tumours that often regress.","caveats":["Applies only to small localised masses in infants under six months with defined imaging criteria."],"changedPractice":true,"participants":87},{"id":"paper-anbl0531-twist-jco-2019","kind":"paper","name":"ANBL0531: response- and biology-based therapy for intermediate-risk neuroblastoma","aka":[],"tldr":"Further reducing chemotherapy according to biology and response, including observation alone for some infants, maintained a three-year survival of 96 percent in intermediate-risk neuroblastoma.","summary":"Children's Oncology Group phase 3 study of 404 children with intermediate-risk neuroblastoma treated with two, four or eight cycles of chemotherapy depending on stage, age, biology and response, with some subgroups receiving surgery alone.\n\nThree-year event-free survival was 83.2 percent and overall survival 94.9 percent; 12q loss and 1p loss identified patients with more events, and reduced therapy was successful in most subgroups.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2019","url":"https://doi.org/10.1200/JCO.19.00919"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31386611/"}],"tags":[],"related":[],"cancers":["neuroblastoma-intermediate-risk"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2019,"doi":"10.1200/JCO.19.00919","pmid":"31386611","authors":"Twist CJ, Schmidt ML, Naranjo A, et al.","paperType":"observational","findings":["Three-year overall survival 94.9 percent; event-free survival 83.2 percent.","Reduced therapy safe in favourable biology subgroups."],"whatItMeans":"Current intermediate-risk neuroblastoma protocols minimise chemotherapy to two to eight cycles by response and biology, following this study.","caveats":["Some subgroups with unfavourable biology had lower event-free survival, prompting refinements."],"changedPractice":true,"participants":404},{"id":"paper-anbl0532-tandem-transplant-park-jama-2019","kind":"paper","name":"ANBL0532: tandem versus single autologous stem cell transplant for high-risk neuroblastoma","aka":[],"tldr":"Two consecutive high-dose chemotherapy courses with stem cell rescue improved three-year event-free survival compared with a single transplant in high-risk neuroblastoma, and the gain was largest in children who went on to receive anti-GD2 immunotherapy.","summary":"Children's Oncology Group phase 3 trial of 652 children with high-risk neuroblastoma, of whom 355 were randomised after induction to single transplant (carboplatin-etoposide-melphalan) or tandem transplant (thiotepa-cyclophosphamide followed by carboplatin-etoposide-melphalan).\n\nThree-year event-free survival was 61.6 versus 48.4 percent; overall survival did not differ significantly (74.1 versus 69.6 percent); among patients receiving immunotherapy, event-free survival was 73.7 versus 56.0 percent.","asOf":"2026-09-17","links":[{"label":"JAMA 2019","url":"https://doi.org/10.1001/jama.2019.11642"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31454045/"}],"tags":[],"related":[],"cancers":["neuroblastoma-high-risk"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["anbl0532"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2019,"doi":"10.1001/jama.2019.11642","pmid":"31454045","authors":"Park JR, Kreissman SG, London WB, et al.","paperType":"rct","findings":["Three-year event-free survival 61.6 percent vs 48.4 percent.","With post-consolidation immunotherapy: 73.7 percent vs 56.0 percent."],"whatItMeans":"Tandem transplant is the standard consolidation in North American protocols for high-risk neuroblastoma; Europe uses single busulfan-melphalan.","caveats":["Only about half of enrolled patients reached randomisation.","No significant overall survival benefit."],"changedPractice":true,"participants":355},{"id":"paper-anbl1221-expansion-dinutuximab-gm-csf-mody-jco-2020","kind":"paper","name":"ANBL1221 expansion: irinotecan, temozolomide and dinutuximab with GM-CSF in refractory or relapsed neuroblastoma","aka":[],"tldr":"Across 53 children treated with irinotecan, temozolomide and dinutuximab for relapsed neuroblastoma, four in ten had their tumours shrink and 85 percent were alive a year later, confirming the combination as the standard salvage treatment.","summary":"Report of the randomised and expansion cohorts of ANBL1221: 17 randomised and 36 non-randomly assigned patients received irinotecan, temozolomide, dinutuximab and GM-CSF.\n\nObjective responses occurred in 52.9 percent of randomised and 36.1 percent of expansion patients, 41.5 percent overall, with stable disease in a further 22 of 53. One-year progression-free and overall survival were 67.9 and 84.9 percent. Fever and infection, neutropenia, pain and diarrhoea were the common grade 3 or higher toxicities; higher dinutuximab trough levels were associated with response.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2020","url":"https://doi.org/10.1200/JCO.20.00203"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32343642/"}],"tags":[],"related":[],"cancers":["neuroblastoma-high-risk","neuroblastoma"],"sections":[],"technologies":[],"targets":[],"drugs":["dinutuximab","irinotecan","temozolomide","sargramostim"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["anbl1221"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/JCO.20.00203","pmid":"32343642","authors":"Mody R, Yu AL, Naranjo A, et al.","paperType":"observational","findings":["Objective response 41.5 percent (95% CI 28.2 to 54.8) in 53 patients; 52.9 percent in the randomised cohort and 36.1 percent in the expansion cohort.","One-year progression-free survival 67.9 percent and overall survival 84.9 percent.","Higher dinutuximab trough concentrations associated with response."],"whatItMeans":"Confirms irinotecan-temozolomide-dinutuximab as the reference salvage regimen and motivated frontline chemo-immunotherapy trials (ANBL17P1, ANBL1531).","caveats":["Single-arm expansion; response rate was lower in the expansion cohort than in the randomised cohort."],"changedPractice":true,"participants":53},{"id":"paper-anbl1221-irinotecan-temozolomide-dinutuximab-mody-lancet-oncol-2017","kind":"paper","name":"ANBL1221: irinotecan-temozolomide with temsirolimus or dinutuximab in relapsed or refractory neuroblastoma","aka":[],"tldr":"In children whose neuroblastoma had come back, adding the anti-GD2 antibody dinutuximab to irinotecan and temozolomide shrank the cancer in half of them, while adding temsirolimus almost never did.","summary":"Children's Oncology Group open-label randomised phase 2 selection trial: 35 eligible children with relapsed, refractory or progressive neuroblastoma were randomised to irinotecan and temozolomide with temsirolimus (n 18) or with dinutuximab plus GM-CSF (n 17).\n\nOne patient (6 percent) responded with temsirolimus against nine (53 percent, four partial and five complete responses) with dinutuximab. Pain, hypokalaemia, neutropenia, thrombocytopenia, anaemia, fever and hypoxia were the common grade 3 or worse events with dinutuximab; no deaths were attributed to treatment.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2017","url":"https://doi.org/10.1016/S1470-2045(17)30355-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28549783/"}],"tags":[],"related":[],"cancers":["neuroblastoma-high-risk","neuroblastoma"],"sections":[],"technologies":[],"targets":[],"drugs":["dinutuximab","irinotecan","temozolomide","temsirolimus"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["anbl1221"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2017,"doi":"10.1016/S1470-2045(17)30355-8","pmid":"28549783","authors":"Mody R, Naranjo A, Van Ryn C, et al.","paperType":"rct","findings":["Objective response 53 percent (95% CI 29.2 to 76.7) with irinotecan-temozolomide-dinutuximab versus 6 percent (0.0 to 16.1) with irinotecan-temozolomide-temsirolimus.","Grade 3 or worse pain in 44 percent and hypokalaemia in 38 percent of dinutuximab patients; one grade 4 hypoxia met unacceptable toxicity criteria."],"whatItMeans":"Chemo-immunotherapy with dinutuximab became the salvage standard for relapsed neuroblastoma and the regimen to move into first-line induction.","caveats":["Small randomised selection design intended to pick an arm for further study, not to prove superiority."],"changedPractice":true,"participants":35},{"id":"paper-bussey-proc-natl-acad-sci-u-s-a","kind":"paper","name":"Ancestral gene regulatory networks drive cancer","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 28584134 and published in Proceedings of the National Academy of Sciences; the citing page links this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 28584134 (DOI 10.1073/pnas.1706990114). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Proc Natl Acad Sci U S A 2017","url":"https://doi.org/10.1073/pnas.1706990114"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28584134/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28584134"}],"tags":["europepmc-ingest"],"related":["atavistic-theory-of-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["pnas"],"dependsOn":[],"notes":[],"journal":"Proceedings of the National Academy of Sciences","year":2017,"doi":"10.1073/pnas.1706990114","pmid":"28584134","authors":"Bussey KJ, Cisneros LH, Lineweaver CH, et al.","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-anchor-anal-hsil-treatment-nejm-2022","kind":"paper","name":"ANCHOR: treating anal high-grade squamous intraepithelial lesions to prevent anal cancer in people living with HIV","aka":[],"tldr":"Treating anal precancer, mostly by burning it off in the clinic, cut the number of people with HIV who went on to develop anal cancer by more than half compared with watching and waiting. It is the first randomised proof that treating an HPV precancer outside the cervix prevents cancer.","summary":"Randomised trial of 4,459 people living with HIV aged 35 or older with biopsy-proven anal high-grade squamous intraepithelial lesions (HSIL), assigned to treatment (office-based electrocautery or infrared coagulation, topical fluorouracil or imiquimod, or excision) or to active monitoring with high-resolution anoscopy every six months.\n\nThe trial was stopped early for efficacy: 9 participants in the treatment arm and 21 in the monitoring arm progressed to anal cancer, a rate of 173 against 402 per 100,000 person-years, a 57 percent reduction. The result made screening and treatment of anal HSIL a recommendation for people living with HIV.","asOf":"2026-09-18","links":[{"label":"N Engl J Med 2022","url":"https://doi.org/10.1056/NEJMoa2201048"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35704479/"}],"tags":[],"related":[],"cancers":["anal-hsil-precursor","anal"],"sections":[],"technologies":[],"targets":[],"drugs":["fluorouracil"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["anchor"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/NEJMoa2201048","pmid":"35704479","authors":"Palefsky JM, Lee JY, Jay N, et al.","paperType":"rct","findings":["Progression to anal cancer in 9 treated versus 21 monitored participants; 173 versus 402 cases per 100,000 person-years.","A 57 percent reduction in the rate of anal cancer, meeting the stopping boundary at a planned interim analysis."],"whatItMeans":"People living with HIV who have anal HSIL should be offered treatment rather than observation, and screening programmes to find those lesions are now justified. High-resolution anoscopy capacity is the limiting step.","caveats":["Only people living with HIV were enrolled; the benefit in other high-risk groups is inferred.","Recurrence of HSIL after treatment was common, so surveillance continues after treatment."],"changedPractice":true,"participants":4459},{"id":"paper-nct06015503-j-thorac-oncol-2026","kind":"paper","name":"Andamertinib in Advanced NSCLC With EGFR Exon 20 Insertions After Platinum-Based Chemotherapy or Immunotherapy: Results From the Phase 2 KANNON Study","aka":[],"tldr":"Published report from the KANNON trial registered as NCT06015503, in Journal of Thoracic Oncology (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Objectives: This study aimed to evaluate andamertinib, a selective and irreversible tyrosine kinase inhibitor, in pretreated advanced EGFR exon 20 insertion (ex20ins)-mutant NSCLC.\n\nMethods: In the phase 2, multicenter, single-arm KANNON study (NCT06015503), patients with locally advanced or metastatic NSCLC harboring EGFR ex20ins mutations who had progressed after platinum-based chemotherapy or immunotherapy received oral andamertinib 240 mg once daily in 28-day cycles. The primary end point was the confirmed objective response rate (ORR) assessed by independent review.\n\nResults: A total of 92 patients were enrolled and received daily 240 mg andamertinib, with nearly 30 different exon20ins subtypes included. The confirmed ORR was 42.7% (95% confidence interval [CI], 32.4-53.0), with a disease control rate of 86.5% and a median duration of response of 8.7 months (95% CI, 5.65-11.96). at September 6, 2025, with a median follow-up of 15.4 (range, 0.4-20.5) months, the median progression-free survival was 6.2 months (95% CI, 4.63-7.85) and median overall survival was not reached (95% CI, 13.93 mo to not estimable), with a 12-month survival rate of 70.5%. Among 38 patients with brain metastasis, the systemic confirmed ORR was 47.4% (95% CI, 31.5-63.2). Grade more than or equal to 3 treatment-related adverse events occurred in 40.2% of patients, and the most frequent events were diarrhea (12.0%) and rash (7.6%). No interstitial lung disease or grade more than or equal to 3 QT prolongation was reported.\n\nConclusions: Andamertinib at 240 mg once daily demonstrated efficacy with a manageable safety profile in previously treated patients with EGFR ex20ins-mutant NSCLC.\n\nIndexed on Europe PMC as PubMed record 41248848 (DOI 10.1016/j.jtho.2025.11.008). Its abstract cites the registry id NCT06015503, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Thorac Oncol 2026","url":"https://doi.org/10.1016/j.jtho.2025.11.008"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41248848/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41248848"},{"label":"ClinicalTrials.gov NCT06015503","url":"https://clinicaltrials.gov/study/NCT06015503"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct06015503"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-thoracic-oncology"],"dependsOn":[],"notes":[],"journal":"Journal of Thoracic Oncology","year":2026,"doi":"10.1016/j.jtho.2025.11.008","pmid":"41248848","authors":"Yang JJ, Mu Y, Wang ZH, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT06015503 with the most citations, so it is the natural first reading for anyone following the KANNON trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-androgen-receptor-prostate-endocr-rev-2004","kind":"paper","name":"Androgen receptor in prostate cancer","aka":[],"tldr":"Review on Androgen receptor in Prostate cancer, in Endocrine reviews (2004), one of the most cited Europe PMC records with Androgen receptor in its title.","summary":"The normal development and maintenance of the prostate is dependent on androgen acting through the androgen receptor (AR). AR remains important in the development and progression of prostate cancer. AR expression is maintained throughout prostate cancer progression, and the majority of androgen-independent or hormone refractory prostate cancers express AR. Mutation of AR, especially mutations that result in a relaxation of AR ligand specificity, may contribute to the progression of prostate cancer and the failure of endocrine therapy by allowing AR transcriptional activation in response to antiandrogens or other endogenous hormones. Similarly, alterations in the relative expression of AR coregulators have been found to occur with prostate cancer progression and may contribute to differences in AR ligand specificity or transcriptional activity. Prostate cancer progression is also associated with increased growth factor production and an altered response to growth factors by prostate cancer cells. The kinase signal transduction cascades initiated by mitogenic growth factors modulate the transcriptional activity of AR and the interaction between AR and AR coactivators. The inhibition of AR activity through mechanisms in addition to androgen ablation, such as modulation of signal transduction pathways, may delay prostate cancer progression.\n\nIndexed on Europe PMC as PubMed record 15082523 (DOI 10.1210/er.2002-0032). Its title names Androgen receptor and its text names Prostate cancer; PubMed types it as a review (Research Support, U.S. Gov't, P.H.S., Review). It was matched automatically to the idea \"Destroy the truncated androgen receptor that hormone drugs cannot touch\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Endocr Rev 2004","url":"https://doi.org/10.1210/er.2002-0032"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/15082523/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/15082523"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Endocrine reviews","year":2004,"doi":"10.1210/er.2002-0032","pmid":"15082523","authors":"Heinlein CA, Chang C","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for Androgen receptor in Prostate cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Androgen receptor in the title and Prostate cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-bluemn-double-negative-prostate-fgf-mapk-cancer-cell-2017","kind":"paper","name":"Androgen receptor pathway-independent prostate cancer is sustained through FGF signalling","aka":[],"tldr":"Over two decades a new kind of advanced prostate cancer appeared that uses neither the androgen receptor nor a neuroendocrine programme, and it runs on a growth factor pathway instead.","summary":"Androgen receptor signalling is the distinctive feature of prostate carcinoma and the major therapeutic target in metastatic disease, but androgen receptor antagonism can produce tumours that bypass a functional requirement for the receptor, often through neuroendocrine transdifferentiation. Through molecular assessment of metastatic prostate cancers over two decades, a phenotypic shift was found with the emergence of an androgen receptor-null, neuroendocrine-null phenotype. These double-negative prostate cancers showed elevated FGF and MAPK pathway activity, which can bypass androgen receptor dependence, and pharmacological inhibitors of MAPK or FGFR repressed their growth in vitro and in vivo.","asOf":"2026-09-25","links":[{"label":"Bluemn et al., Cancer Cell 2017: androgen receptor pathway-independent, neuroendocrine-null metastatic prostate cancer sustained by FGF and MAPK signalling","url":"https://doi.org/10.1016/j.ccell.2017.09.003"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29017058/"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc","prostate-nepc"],"sections":[],"technologies":[],"targets":["androgen-receptor","fgfr1","mek"],"drugs":[],"companies":[],"institutions":[],"pathways":["ar-signaling","fgfr-signalling","ras-mapk","lineage-plasticity-neuroendocrine","resistance-routes-map"],"terms":["resistance","castration-resistance","histologic-transformation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-cell"],"dependsOn":[],"notes":[],"journal":"Cancer Cell","year":2017,"doi":"10.1016/j.ccell.2017.09.003","pmid":"29017058","authors":"Bluemn EG, Coleman IM, Lucas JM, et al.","paperType":"basic","findings":["An androgen receptor-null, neuroendocrine-null phenotype has emerged in metastatic prostate cancer over two decades.","Double-negative tumours show elevated FGF and MAPK pathway activity.","MAPK or FGFR inhibition repressed growth of these tumours in vitro and in vivo."],"whatItMeans":"It shows that leaving androgen receptor dependence does not have to mean becoming neuroendocrine, and it names a treatable pathway for a group of men whose tumours would otherwise be described only by what they lack.","caveats":["A research autopsy and xenograft series rather than a prospective clinical cohort.","The phenotypic shift over time is inferred from samples collected under changing treatment practice.","No FGFR or MEK inhibitor is approved in prostate cancer."],"changedPractice":false},{"id":"paper-androgen-receptor-prostate-acta-pharmacol-sin-2015","kind":"paper","name":"Androgen receptor: structure, role in prostate cancer and drug discovery","aka":[],"tldr":"Review on Androgen receptor in Prostate cancer, in Acta pharmacologica Sinica (2015), one of the most cited Europe PMC records with Androgen receptor in its title.","summary":"Androgens and androgen receptors (AR) play a pivotal role in expression of the male phenotype. Several diseases, such as androgen insensitivity syndrome (AIS) and prostate cancer, are associated with alterations in AR functions. Indeed, androgen blockade by drugs that prevent the production of androgens and/or block the action of the AR inhibits prostate cancer growth. However, resistance to these drugs often occurs after 2-3 years as the patients develop castration-resistant prostate cancer (CRPC). In CRPC, a functional AR remains a key regulator. Early studies focused on the functional domains of the AR and its crucial role in the pathology. The elucidation of the structures of the AR DNA binding domain (DBD) and ligand binding domain (LBD) provides a new framework for understanding the functions of this receptor and leads to the development of rational drug design for the treatment of prostate cancer. An overview of androgen receptor structure and activity, its actions in prostate cancer, and how structural information and high-throughput screening have been or can be used for drug discovery are provided herein.\n\nIndexed on Europe PMC as PubMed record 24909511 (DOI 10.1038/aps.2014.18). Its title names Androgen receptor and its text names Prostate cancer; PubMed types it as a review (Research Support, Non-U.S. Gov't, review-article, Review, Research Support, N.I.H., Extramural). It was matched automatically to the idea \"Destroy the truncated androgen receptor that hormone drugs cannot touch\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Acta Pharmacol Sin 2015","url":"https://doi.org/10.1038/aps.2014.18"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24909511/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/24909511"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Acta pharmacologica Sinica","year":2015,"doi":"10.1038/aps.2014.18","pmid":"24909511","authors":"Tan MH, Li J, Xu HE, et al.","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for Androgen receptor in Prostate cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Androgen receptor in the title and Prostate cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-kindler-lancet-oncol","kind":"paper","name":"Anetumab ravtansine versus vinorelbine in patients with relapsed, mesothelin-positive malignant pleural mesothelioma (ARCS-M): a randomised, open-label phase 2 trial","aka":[],"tldr":"Paper cited by one trial page, one treatment page and one idea page, indexed on Europe PMC as PubMed record 35358455 and published in The Lancet Oncology; the citing pages link this DOI, which is how the record was matched.","summary":"Background: Few treatment options exist for second-line treatment of malignant pleural mesothelioma. We aimed to assess the antibody-drug conjugate anetumab ravtansine versus vinorelbine in patients with unresectable locally advanced or metastatic disease overexpressing mesothelin who had progressed on first-line platinum-pemetrexed chemotherapy with or without bevacizumab.\n\nMethods: In this phase 2, randomised, open-label study, done at 76 hospitals in 14 countries, we enrolled adults (aged ≥18 years) with unresectable locally advanced or metastatic malignant pleural mesothelioma, an Eastern Cooperative Oncology Group performance status of 0-1, and who had progressed on first-line platinum-pemetrexed chemotherapy with or without bevacizumab. Participants were prospectively screened for mesothelin overexpression (defined as 2+ or 3+ mesothelin membrane staining intensity on at least 30% of viable tumour cells by immunohistochemistry) and were randomly assigned (2:1), using an interactive voice and web response system provided by the sponsor, to receive intravenous anetumab ravtansine (6·5 mg/kg on day 1 of each 21-day cycle) or intravenous vinorelbine (30 mg/m 2 once every week) until progression, toxicity, or death. The primary endpoint was progression-free survival according to blinded central radiology review, assessed in the intention-to-treat population, with safety assessed in all participants who received any study treatment. This study is registered with ClinicalTrials.gov, NCT02610140, and is now completed.\n\nFindings: Between Dec 3, 2015, and May 31, 2017, 589 patients were enrolled and 248 mesothelin-overexpressing patients were randomly allocated to the two treatment groups (166 patients were randomly assigned to receive anetumab ravtansine and 82 patients were randomly assigned to receive vinorelbine). 105 (63%) of 166 patients treated with anetumab ravtansine (median follow-up 4·0 months [IQR 1·4-5·5]) versus 43 (52%) of 82 patients treated with vinorelbine (3·9 months [1·4-5·4]) had disease progression or died (median progression-free survival 4·3 months [95% CI 4·1-5·2] vs 4·5 months [4·1-5·8]; hazard ratio 1·22 [0·85-1·74]; log-rank p=0·86). The most common grade 3 or worse adverse events were neutropenia (one [1%] of 163 patients for anetumab ravtansine vs 28 [39%] of 72 patients for vinorelbine), pneumonia (seven [4%] vs five [7%]), neutrophil count decrease (two [1%] vs 12 [17%]), and dyspnoea (nine [6%] vs three [4%]). Serious drug-related treatment-emergent adverse events occurred in 12 (7%) patients treated with anetumab ravtansine and 11 (15%) patients treated with vinorelbine. Ten (6%) treatment-emergent deaths occurred with anetumab ravtansine: pneumonia (three [2%]), dyspnoea (two [1%]), sepsis (two [1%]), atrial fibrillation (one [1%]), physical deterioration (one [1%]), hepatic failure (one [1%]), mesothelioma (one [1%]), and renal failure (one [1%]; one patient had 3 events). One (1%) treatment-emergent death occurred in the vinorelbine group (pneumonia).\n\nInterpretation: Anetumab ravtansine showed a manageable safety profile and was not superior to vinorelbine. Further studies are needed to define active treatments in relapsed mesothelin-expressing malignant pleural mesothelioma.\n\nFunding: Bayer Healthcare Pharmaceuticals.\n\nIndexed on Europe PMC as PubMed record 35358455 (DOI 10.1016/s1470-2045(22)00061-4). Matched by DOI alone: one trial page, one treatment page and one idea page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2022","url":"https://doi.org/10.1016/s1470-2045(22)00061-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35358455/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35358455"}],"tags":["europepmc-ingest"],"related":["anetumab-ravtansine","idea-adc-for-mesothelioma"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["anetumab-vs-vinorelbine-mpm"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2022,"doi":"10.1016/s1470-2045(22)00061-4","pmid":"35358455","authors":"Kindler HL, Novello S, Bearz A, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page, one treatment page and one idea page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-golfier-mol-cancer-ther","kind":"paper","name":"Anetumab ravtansine: a novel mesothelin-targeting antibody-drug conjugate cures tumors with heterogeneous target expression favored by bystander effect","aka":[],"tldr":"Paper cited by one treatment page, indexed on Europe PMC as PubMed record 24714131 and published in Molecular Cancer Therapeutics; the citing page links this DOI, which is how the record was matched.","summary":"Mesothelin is a tumor differentiation antigen frequently overexpressed in tumors such as mesothelioma, ovarian, pancreatic, and lung adenocarcinomas while showing limited expression in nonmalignant tissues. Mesothelin is therefore an attractive target for cancer therapy using antibody-drug conjugates (ADC). This study describes the detailed characterization of anetumab ravtansine, here referred to as BAY 94-9343, a novel ADC consisting of a human anti-mesothelin antibody conjugated to the maytansinoid tubulin inhibitor DM4 via a disulfide-containing linker. Binding properties of the anti-mesothelin antibody were analyzed using surface plasmon resonance, immunohistochemistry, flow cytometry, and fluorescence microscopy. Effects of BAY 94-9343 on cell proliferation were first studied in vitro and subsequently in vivo using subcutaneous, orthotopic, and patient-derived xenograft tumor models. The antibody binds to human mesothelin with high affinity and selectivity, thereby inducing efficient antigen internalization. In vitro, BAY 94-9343 demonstrated potent and selective cytotoxicity of mesothelin-expressing cells with an IC(50) of 0.72 nmol/L, without affecting mesothelin-negative or nonproliferating cells. In vivo, BAY 94-9343 localized specifically to mesothelin-positive tumors and inhibited tumor growth in both subcutaneous and orthotopic xenograft models. In addition, BAY 94-9343 was able to induce a bystander effect on neighboring mesothelin-negative tumor cells. Antitumor efficacy of BAY 94-9343 correlated with the amount of mesothelin expressed and was generally superior to that of standard-of-care regimen resulting in complete tumor eradication in most of the models. BAY 94-9343 is a selective and highly potent ADC, and our data support its development for the treatment of patients with mesothelin-expressing tumors.\n\nIndexed on Europe PMC as PubMed record 24714131 (DOI 10.1158/1535-7163.mct-13-0926). Matched by DOI alone: one treatment page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Mol Cancer Ther 2014","url":"https://doi.org/10.1158/1535-7163.mct-13-0926"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24714131/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/24714131"}],"tags":["europepmc-ingest"],"related":["anetumab-ravtansine"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["molecular-cancer-therapeutics"],"dependsOn":[],"notes":[],"journal":"Molecular Cancer Therapeutics","year":2014,"doi":"10.1158/1535-7163.mct-13-0926","pmid":"24714131","authors":"Golfier S, Kopitz C, Kahnert A, et al.","paperType":"basic","findings":[],"whatItMeans":"One treatment page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-weaver-cancer-cell","kind":"paper","name":"Aneuploidy acts both oncogenically and as a tumor suppressor","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 17189716 and published in Cancer Cell; the citing page links this DOI, which is how the record was matched.","summary":"An abnormal chromosome number, aneuploidy, is a common characteristic of tumor cells. Boveri proposed nearly 100 years ago that aneuploidy causes tumorigenesis, but this has remained untested due to the difficulty of selectively generating aneuploidy. Cells and mice with reduced levels of the mitosis-specific, centromere-linked motor protein CENP-E are now shown to develop aneuploidy and chromosomal instability in vitro and in vivo. An increased rate of aneuploidy does drive an elevated level of spontaneous lymphomas and lung tumors in aged animals. Remarkably, however, in examples of chemically or genetically induced tumor formation, an increased rate of aneuploidy is a more effective inhibitor than initiator of tumorigenesis. These findings reveal a role of aneuploidy and chromosomal instability in preventing tumorigenesis.\n\nIndexed on Europe PMC as PubMed record 17189716 (DOI 10.1016/j.ccr.2006.12.003). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer Cell 2007","url":"https://doi.org/10.1016/j.ccr.2006.12.003"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/17189716/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/17189716"}],"tags":["europepmc-ingest"],"related":["aneuploidy-theory-of-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-cell"],"dependsOn":[],"notes":[],"journal":"Cancer Cell","year":2007,"doi":"10.1016/j.ccr.2006.12.003","pmid":"17189716","authors":"Weaver BA, Silk AD, Montagna C, et al.","paperType":"basic","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-young-angiosarcoma-review-lancet-oncol-2010","kind":"paper","name":"Angiosarcoma (review)","aka":[],"tldr":"This review summarises the epidemiology, subtypes (including radiation- and lymphoedema-associated forms), surgery, radiotherapy and chemotherapy of angiosarcoma, and why outcomes remain poor.","summary":"Review covering the presentation and risk factors of angiosarcoma at different sites, pathology, staging, wide surgical excision with radiotherapy, systemic therapy with anthracyclines and taxanes, anti-angiogenic agents, and prognostic factors.","asOf":"2026-09-17","links":[{"label":"Lancet Oncol 2010","url":"https://doi.org/10.1016/S1470-2045(10)70023-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20537949/"}],"tags":[],"related":[],"cancers":["angiosarcoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2010,"doi":"10.1016/S1470-2045(10)70023-1","pmid":"20537949","authors":"Young RJ, Brown NJ, Reed MW, et al.","paperType":"review","findings":[],"whatItMeans":"The angiosarcoma page's structure by site and by aetiology (cutaneous, radiation-associated breast, visceral) follows this review.","caveats":["Predates immunotherapy data in cutaneous angiosarcoma."],"changedPractice":false},{"id":"paper-angiotax-paclitaxel-angiosarcoma-penel-jco-2008","kind":"paper","name":"ANGIOTAX: phase 2 trial of weekly paclitaxel for unresectable angiosarcoma","aka":[],"tldr":"Weekly paclitaxel controlled angiosarcoma in three quarters of patients at two months and produced responses in about one in five, establishing it as a standard first-line chemotherapy for this vascular sarcoma, especially of the scalp and face.","summary":"Phase 2 study of 30 patients with unresectable angiosarcoma treated with weekly paclitaxel 80 mg per square metre.\n\nNon-progression at two months was 74 percent, objective response 19 percent, median progression-free survival 4 months and median overall survival 8 months; responses were more frequent in scalp and face angiosarcomas.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2008","url":"https://doi.org/10.1200/JCO.2008.17.3146"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/18809609/"}],"tags":[],"related":[],"cancers":["angiosarcoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["angiotax"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2008,"doi":"10.1200/JCO.2008.17.3146","pmid":"18809609","authors":"Penel N, Bui BN, Bay JO, et al.","paperType":"observational","findings":["Non-progression rate at two months 74 percent; objective response 19 percent.","Median overall survival 8 months."],"whatItMeans":"Weekly paclitaxel is a standard first-line option for angiosarcoma alongside doxorubicin, and it is also used with radiotherapy for unresectable scalp disease.","caveats":["Small single-arm study; survival remains poor.","The randomised ANNOUNCE and other trials have since compared taxanes with anthracyclines."],"changedPractice":true,"participants":30},{"id":"paper-chen-jama-oncol","kind":"paper","name":"Anlotinib for Refractory Advanced Non-Small Cell Lung Cancer in China","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 30489609 and published in JAMA Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 30489609 (DOI 10.1001/jamaoncol.2018.5526). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA Oncol 2019","url":"https://doi.org/10.1001/jamaoncol.2018.5526"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30489609/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30489609"}],"tags":["europepmc-ingest"],"related":["sinonasal"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2019,"doi":"10.1001/jamaoncol.2018.5526","pmid":"30489609","authors":"Chen XZ","paperType":"observational","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-cd30-hodgkin-lymphoma-j-clin-oncol-2020","kind":"paper","name":"Anti-CD30 CAR-T Cell Therapy in Relapsed and Refractory Hodgkin Lymphoma","aka":[],"tldr":"Phase 2 or 3 results paper on CD30 in Hodgkin lymphoma, in Journal of Clinical Oncology (2020), one of the most cited Europe PMC records with CD30 in its title.","summary":"Purpose: Chimeric antigen receptor (CAR) T-cell therapy of B-cell malignancies has proved to be effective. We show how the same approach of CAR T cells specific for CD30 (CD30.CAR-Ts) can be used to treat Hodgkin lymphoma (HL).\n\nMethods: We conducted 2 parallel phase I/II studies (ClinicalTrials.gov identifiers: NCT02690545 and NCT02917083) at 2 independent centers involving patients with relapsed or refractory HL and administered CD30.CAR-Ts after lymphodepletion with either bendamustine alone, bendamustine and fludarabine, or cyclophosphamide and fludarabine. The primary end point was safety.\n\nResults: Forty-one patients received CD30.CAR-Ts. Treated patients had a median of 7 prior lines of therapy (range, 2-23), including brentuximab vedotin, checkpoint inhibitors, and autologous or allogeneic stem cell transplantation. The most common toxicities were grade 3 or higher hematologic adverse events. Cytokine release syndrome was observed in 10 patients, all of which were grade 1. No neurologic toxicity was observed. The overall response rate in the 32 patients with active disease who received fludarabine-based lymphodepletion was 72%, including 19 patients (59%) with complete response. With a median follow-up of 533 days, the 1-year progression-free survival and overall survival for all evaluable patients were 36% (95% CI, 21% to 51%) and 94% (95% CI, 79% to 99%), respectively. CAR-T cell expansion in vivo was cell dose dependent.\n\nConclusion: Heavily pretreated patients with relapsed or refractory HL who received fludarabine-based lymphodepletion followed by CD30.CAR-Ts had a high rate of durable responses with an excellent safety profile, highlighting the feasibility of extending CAR-T cell therapies beyond canonical B-cell malignancies.\n\nIndexed on Europe PMC as PubMed record 32701411 (DOI 10.1200/jco.20.01342). Its title names CD30 and its text names Hodgkin lymphoma; PubMed types it as a clinical trial report (Clinical Trial, Phase II, Research Support, Non-U.S. Gov't, research-article, Multicenter Study, Clinical Trial, Phase I, Research Support, N.I.H., Extramural). It was matched automatically to the idea \"CD30 CAR-T for multiply relapsed Hodgkin lymphoma\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2020","url":"https://doi.org/10.1200/jco.20.01342"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32701411/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32701411"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/jco.20.01342","pmid":"32701411","authors":"Ramos CA, Grover NS, Beaven AW, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for CD30 in Hodgkin lymphoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by CD30 in the title and Hodgkin lymphoma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-yu-anti-gd2-neuroblastoma-nejm-2010","kind":"paper","name":"Anti-GD2 antibody with GM-CSF, interleukin-2 and isotretinoin for high-risk neuroblastoma (COG ANBL0032)","aka":[],"tldr":"Adding the anti-GD2 antibody ch14.18 with cytokines to isotretinoin after transplant improved two-year event-free survival in high-risk neuroblastoma from 46 to 66 percent, making immunotherapy a standard part of treatment.","summary":"Phase 3 trial of 226 children with high-risk neuroblastoma who had responded to induction and autologous transplant, randomised to isotretinoin alone or with five cycles of ch14.18 (dinutuximab) plus GM-CSF and interleukin-2.\n\nTwo-year event-free survival was 66 versus 46 percent and overall survival 86 versus 75 percent; pain, capillary leak and hypersensitivity were the main toxicities. Later follow-up confirmed the benefit.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2010","url":"https://doi.org/10.1056/NEJMoa0911123"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20879881/"}],"tags":[],"related":[],"cancers":["neuroblastoma-high-risk"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2010,"doi":"10.1056/NEJMoa0911123","pmid":"20879881","authors":"Yu AL, Gilman AL, Ozkaynak MF, et al.","paperType":"rct","findings":["Two-year event-free survival 66 percent vs 46 percent.","Two-year overall survival 86 percent vs 75 percent."],"whatItMeans":"Anti-GD2 immunotherapy after consolidation is standard for high-risk neuroblastoma worldwide; interleukin-2 was later dropped after the SIOPEN trial showed no added benefit.","caveats":["Trial stopped early at interim analysis.","Neuropathic pain and capillary leak syndrome are substantial toxicities."],"changedPractice":true,"participants":226},{"id":"paper-nakamura-anti-pd1-acral-melanoma-ann-oncol-2020","kind":"paper","name":"Anti-PD-1 checkpoint inhibitor therapy in acral melanoma: a multicentre study of 193 Japanese patients","aka":[],"tldr":"In the largest series of acral melanoma treated with anti-PD-1 antibodies, only about 17 percent responded, and melanomas of the nail apparatus responded least, showing that acral disease benefits less from immunotherapy than ordinary skin melanoma.","summary":"Retrospective multicentre study of 193 Japanese patients with advanced acral melanoma treated with nivolumab or pembrolizumab monotherapy.\n\nObjective response was 16.6 percent overall (21.3 percent for palm and sole melanoma, 8.3 percent for nail apparatus melanoma), with median progression-free survival of 3.5 months and overall survival of 18.1 months; a higher tumour burden and nail apparatus origin predicted poor outcome.","asOf":"2026-09-17","links":[{"label":"Ann Oncol 2020","url":"https://doi.org/10.1016/j.annonc.2020.05.031"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32522691/"}],"tags":[],"related":[],"cancers":["acral-melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2020,"doi":"10.1016/j.annonc.2020.05.031","pmid":"32522691","authors":"Nakamura Y, Namikawa K, Yoshino K, et al.","paperType":"real-world","findings":["Objective response 16.6 percent overall; 8.3 percent in nail apparatus melanoma.","Median overall survival 18.1 months."],"whatItMeans":"Acral melanoma needs its own treatment evidence: anti-PD-1 monotherapy has limited activity, so combination immunotherapy, KIT-directed therapy and trials of CDK4/6 inhibitors are important options.","caveats":["Retrospective Japanese cohort; many patients had prior chemotherapy."],"changedPractice":false,"participants":193},{"id":"paper-jain-cancer-cell","kind":"paper","name":"Antiangiogenesis strategies revisited: from starving tumors to alleviating hypoxia","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 25517747 and published in Cancer Cell; the citing page links this DOI, which is how the record was matched.","summary":"Ten antiangiogenic drugs targeting VEGF or its receptors are approved for cancer treatment. However, these agents, intended to block tumors' blood supply, may cause hypoxia, which may fuel tumor progression and treatment resistance. Emerging clinical data suggest that patients whose tumor perfusion or oxygenation increases in response to these agents may actually survive longer. Hence, strategies aimed at alleviating tumor hypoxia while improving perfusion may enhance the outcome of radiotherapy, chemotherapy, and immunotherapy. Here I summarize lessons learned from preclinical and clinical studies over the past decade and propose strategies for improving antiangiogenic therapy outcomes for malignant and nonmalignant diseases.\n\nIndexed on Europe PMC as PubMed record 25517747 (DOI 10.1016/j.ccell.2014.10.006). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer Cell 2014","url":"https://doi.org/10.1016/j.ccell.2014.10.006"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25517747/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25517747"}],"tags":["europepmc-ingest"],"related":["mechanical-theory-of-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-cell"],"dependsOn":[],"notes":[],"journal":"Cancer Cell","year":2014,"doi":"10.1016/j.ccell.2014.10.006","pmid":"25517747","authors":"Jain RK","paperType":"review","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-trastuzumab-deruxtecan-tnbc-expert-opin-biol-ther-2021","kind":"paper","name":"Antibody-drug conjugates in metastatic triple negative breast cancer: a spotlight on sacituzumab govitecan, ladiratuzumab vedotin, and trastuzumab deruxtecan","aka":[],"tldr":"Review on Trastuzumab deruxtecan in Triple-negative breast cancer, in Expert opinion on biological therapy (2021), one of the most cited Europe PMC records with Trastuzumab deruxtecan in its title.","summary":"Introduction: Metastatic triple-negative breast cancers (mTNBC) are characterized by aggressive behavior and worse clinical outcomes than other breast cancer subtypes, as well as poor response to cytotoxic chemotherapies. The use of antibody-drug conjugates (ADCs) has been investigated as a potential treatment strategy, particularly in heavily pretreated disease.\n\nAreas covered: This article reviews the preclinical and clinical data supporting the use of the ADCs sacituzumab govitecan (SG), ladiratuzumab vedotin (LV), and trastuzumab deruxtecan (T-DXd) in mTNBC, and highlights ongoing clinical trials and future clinical applications.\n\nExpert opinion: SG, LV, and T-DXd have demonstrated their potential to meaningfully improve clinical outcomes in patients with pretreated mTNBC, as demonstrated by notable response rates in phase I/II and, for SG, phase III clinical trials. Investigation of their use in combination with other agents, including PARP inhibitors and checkpoint inhibitors, is ongoing in the metastatic setting, and their application in early-stage TNBCs are under investigation. ADCs are therefore expected to redefine treatment paradigms in TNBC.\n\nIndexed on Europe PMC as PubMed record 33089726 (DOI 10.1080/14712598.2021.1840547). Its title names Trastuzumab deruxtecan and its text names Triple-negative breast cancer; PubMed types it as a review (Review). It was matched automatically to the idea \"AI quantification of HER2-low and HER2-ultralow\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Expert Opin Biol Ther 2021","url":"https://doi.org/10.1080/14712598.2021.1840547"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33089726/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33089726"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Expert opinion on biological therapy","year":2021,"doi":"10.1080/14712598.2021.1840547","pmid":"33089726","authors":"McGuinness JE, Kalinsky K","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for Trastuzumab deruxtecan in Triple-negative breast cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Trastuzumab deruxtecan in the title and Triple-negative breast cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-yamazaki-nat-commun","kind":"paper","name":"Antibody-drug conjugates with dual payloads for combating breast tumor heterogeneity and drug resistance","aka":[],"tldr":"Paper cited by one technology page and one idea page, indexed on Europe PMC as PubMed record 34112795 and published in Nature Communications; the citing pages link this DOI, which is how the record was matched.","summary":"Breast tumors generally consist of a diverse population of cells with varying gene expression profiles. Breast tumor heterogeneity is a major factor contributing to drug resistance, recurrence, and metastasis after chemotherapy. Antibody-drug conjugates (ADCs) are emerging chemotherapeutic agents with striking clinical success, including T-DM1 for HER2-positive breast cancer. However, these ADCs often suffer from issues associated with intratumor heterogeneity. Here, we show that homogeneous ADCs containing two distinct payloads are a promising drug class for addressing this clinical challenge. Our conjugates show HER2-specific cell killing potency, desirable pharmacokinetic profiles, minimal inflammatory response, and marginal toxicity at therapeutic doses. Notably, a dual-drug ADC exerts greater treatment effect and survival benefit than does co-administration of two single-drug variants in xenograft mouse models representing intratumor HER2 heterogeneity and elevated drug resistance. Our findings highlight the therapeutic potential of the dual-drug ADC format for treating refractory breast cancer and perhaps other cancers.\n\nIndexed on Europe PMC as PubMed record 34112795 (DOI 10.1038/s41467-021-23793-7). Matched by DOI alone: one technology page and one idea page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Commun 2021","url":"https://doi.org/10.1038/s41467-021-23793-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34112795/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34112795"}],"tags":["europepmc-ingest"],"related":["dual-payload-adc","idea-dual-payload-first"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-communications"],"dependsOn":[],"notes":[],"journal":"Nature Communications","year":2021,"doi":"10.1038/s41467-021-23793-7","pmid":"34112795","authors":"Yamazaki CM, Yamaguchi A, Anami Y, et al.","paperType":"basic","findings":[],"whatItMeans":"One technology page and one idea page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nct02489318-n-engl-j-med-2019","kind":"paper","name":"Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer","aka":[],"tldr":"Published report from the TITAN trial registered as NCT02489318, in New England Journal of Medicine (2019), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Apalutamide is an inhibitor of the ligand-binding domain of the androgen receptor. Whether the addition of apalutamide to androgen-deprivation therapy (ADT) would prolong radiographic progression-free survival and overall survival as compared with placebo plus ADT among patients with metastatic, castration-sensitive prostate cancer has not been determined.\n\nMethods: In this double-blind, phase 3 trial, we randomly assigned patients with metastatic, castration-sensitive prostate cancer to receive apalutamide (240 mg per day) or placebo, added to ADT. Previous treatment for localized disease and previous docetaxel therapy were allowed. The primary end points were radiographic progression-free survival and overall survival.\n\nResults: A total of 525 patients were assigned to receive apalutamide plus ADT and 527 to receive placebo plus ADT. The median age was 68 years. A total of 16.4% of the patients had undergone prostatectomy or received radiotherapy for localized disease, and 10.7% had received previous docetaxel therapy; 62.7% had high-volume disease, and 37.3% had low-volume disease. At the first interim analysis, with a median of 22.7 months of follow-up, the percentage of patients with radiographic progression-free survival at 24 months was 68.2% in the apalutamide group and 47.5% in the placebo group (hazard ratio for radiographic progression or death, 0.48; 95% confidence interval [CI], 0.39 to 0.60; P<0.001). Overall survival at 24 months was also greater with apalutamide than with placebo (82.4% in the apalutamide group vs. 73.5% in the placebo group; hazard ratio for death, 0.67; 95% CI, 0.51 to 0.89; P = 0.005). The frequency of grade 3 or 4 adverse events was 42.2% in the apalutamide group and 40.8% in the placebo group; rash was more common in the apalutamide group.\n\nConclusions: In this trial involving patients with metastatic, castration-sensitive prostate cancer, overall survival and radiographic progression-free survival were significantly longer with the addition of apalutamide to ADT than with placebo plus ADT, and the side-effect profile did not differ substantially between the two groups. (Funded by Janssen Research and Development; TITAN ClinicalTrials.gov number, NCT02489318.).\n\nIndexed on Europe PMC as PubMed record 31150574 (DOI 10.1056/nejmoa1903307). Its abstract cites the registry id NCT02489318, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2019","url":"https://doi.org/10.1056/nejmoa1903307"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31150574/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31150574"},{"label":"ClinicalTrials.gov NCT02489318","url":"https://clinicaltrials.gov/study/NCT02489318"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct02489318"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2019,"doi":"10.1056/nejmoa1903307","pmid":"31150574","authors":"Chi KN, Agarwal N, Bjartell A, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02489318 with the most citations, so it is the natural first reading for anyone following the TITAN trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-nct02257736-lancet-oncol-2021","kind":"paper","name":"Apalutamide plus abiraterone acetate and prednisone versus placebo plus abiraterone and prednisone in metastatic, castration-resistant prostate cancer (ACIS): a randomised, placebo-controlled, double-blind, multinational, phase 3 study","aka":[],"tldr":"Published report from the trial registered as NCT02257736, in The Lancet Oncology (2021), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: The majority of patients with metastatic castration-resistant prostate cancer (mCRPC) will have disease progression of a uniformly fatal disease. mCRPC is driven by both activated androgen receptors and elevated intratumoural androgens; however, the current standard of care is therapy that targets a single androgen signalling mechanism. We aimed to investigate the combination treatment using apalutamide plus abiraterone acetate, each of which suppresses the androgen signalling axis in a different way, versus standard care in mCRPC.\n\nMethods: ACIS was a randomised, placebo-controlled, double-blind, phase 3 study done at 167 hospitals in 17 countries in the USA, Canada, Mexico, Europe, the Asia-Pacific region, Africa, and South America. We included chemotherapy-naive men (aged ≥18 years) with mCRPC who had not been previously treated with androgen biosynthesis signalling inhibitors and were receiving ongoing androgen deprivation therapy, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and a Brief Pain Inventory-Short Form question 3 (ie, worst pain in the past 24 h) score of 3 or lower. Patients were randomly assigned (1:1) via a centralised interactive web response system with a permuted block randomisation scheme (block size 4) to oral apalutamide 240 mg once daily plus oral abiraterone acetate 1000 mg once daily and oral prednisone 5 mg twice daily (apalutamide plus abiraterone-prednisone group) or placebo plus abiraterone acetate and prednisone (abiraterone-prednisone group), in 28-day treatment cycles. Randomisation was stratified by presence or absence of visceral metastases, ECOG performance status, and geographical region. Patients, the investigators, study team, and the sponsor were masked to group assignments. An independent data-monitoring committee continually monitored data to ensure ongoing patient safety, and reviewed efficacy data. The primary endpoint was radiographic progression-free survival assessed in the intention-to-treat population. Safety was reported for all patients who received at least one dose of study drug. This study is completed and no longer recruiting and is registered with ClinicalTrials.gov, number NCT02257736.\n\nFindings: 982 men were enrolled and randomly assigned from Dec 10, 2014 to Aug 30, 2016 (492 to apalutamide plus abiraterone-prednisone; 490 to abiraterone-prednisone). At the primary analysis (median follow-up 25·7 months [IQR 23·0-28·9]), median radiographic progression-free survival was 22·6 months (95% CI 19·4-27·4) in the apalutamide plus abiraterone-prednisone group versus 16·6 months (13·9-19·3) in the abiraterone-prednisone group (hazard ratio [HR] 0·69, 95% CI 0·58-0·83; p<0·0001). At the updated analysis (final analysis for overall survival; median follow-up 54·8 months [IQR 51·5-58·4]), median radiographic progression-free survival was 24·0 months (95% CI 19·7-27·5) versus 16·6 months (13·9-19·3; HR 0·70, 95% CI 0·60-0·83; p<0·0001). The most common grade 3-4 treatment-emergent adverse event was hypertension (82 [17%] of 490 patients receiving apalutamide plus abiraterone-prednisone and 49 [10%] of 489 receiving abiraterone-prednisone). Serious treatment-emergent adverse events occurred in 195 (40%) patients receiving apalutamide plus abiraterone-prednisone and 181 (37%) patients receiving abiraterone-prednisone. Drug-related treatment-emergent adverse events with fatal outcomes occurred in three (1%) patients in the apalutamide plus abiraterone-prednisone group (2 pulmonary embolism, 1 cardiac failure) and five (1%) patients in the abiraterone-prednisone group (1 cardiac failure and 1 cardiac arrest, 1 mesenteric arterial occlusion, 1 seizure, and 1 sudden death).\n\nInterpretation: Despite the use of an active and established therapy as the comparator, apalutamide plus abiraterone-prednisone improved radiographic progression-free survival. Additional studies to identify subgroups of patients who might benefit the most from combination therapy are needed to further refine the treatment of mCRPC.\n\nFunding: Janssen Research & Development.\n\nIndexed on Europe PMC as PubMed record 34600602 (DOI 10.1016/s1470-2045(21)00402-2). Its abstract cites the registry id NCT02257736, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2021","url":"https://doi.org/10.1016/s1470-2045(21)00402-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34600602/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34600602"},{"label":"ClinicalTrials.gov NCT02257736","url":"https://clinicaltrials.gov/study/NCT02257736"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct02257736"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2021,"doi":"10.1016/s1470-2045(21)00402-2","pmid":"34600602","authors":"Saad F, Efstathiou E, Attard G, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02257736 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-aphinity-nejm-2017","kind":"paper","name":"APHINITY: adjuvant pertuzumab added to trastuzumab and chemotherapy in early HER2-positive breast cancer","aka":[],"tldr":"Adding a second HER2 antibody, pertuzumab, to a year of trastuzumab after surgery reduced recurrences modestly in early HER2-positive breast cancer, with the gain concentrated in women with lymph node involvement.","summary":"Phase 3 placebo-controlled trial of 4,805 patients with operable HER2-positive breast cancer randomised to chemotherapy plus trastuzumab with pertuzumab or placebo for one year.\n\nThree-year invasive disease-free survival was 94.1 percent with pertuzumab against 93.2 percent with placebo (hazard ratio 0.81); in node-positive disease the absolute gain grew to 4.5 percent at six years, with no benefit seen in node-negative disease. Diarrhoea was the main added toxicity.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2017","url":"https://doi.org/10.1056/NEJMoa1703643"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28581356/"}],"tags":[],"related":[],"cancers":["her2-positive-early-breast-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["pertuzumab","trastuzumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["aphinity"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2017,"doi":"10.1056/NEJMoa1703643","pmid":"28581356","authors":"von Minckwitz G, Procter M, de Azambuja E, et al.","paperType":"rct","findings":["Three-year invasive disease-free survival 94.1 percent vs 93.2 percent; hazard ratio 0.81.","Node-positive subgroup: six-year invasive disease-free survival 87.9 percent vs 83.4 percent."],"whatItMeans":"Dual HER2 blockade after surgery is reserved for node-positive or otherwise higher-risk disease, where the benefit is real but small; node-negative patients can be spared the extra drug.","caveats":["Absolute benefit is small and no overall survival difference has emerged.","Trial predates neoadjuvant therapy as the usual route for stage II to III disease."],"changedPractice":true,"participants":4805},{"id":"paper-apl0406-lo-coco-nejm-2013","kind":"paper","name":"APL0406: retinoic acid plus arsenic trioxide without chemotherapy for low- and intermediate-risk acute promyelocytic leukaemia","aka":[],"tldr":"Combining all-trans retinoic acid with arsenic trioxide cured almost every patient with lower-risk acute promyelocytic leukaemia without any conventional chemotherapy, and did so with fewer complications than the chemotherapy-based standard.","summary":"Phase 3 non-inferiority trial of 162 patients with non-high-risk APL randomised to all-trans retinoic acid plus arsenic trioxide or to retinoic acid plus idarubicin chemotherapy (AIDA).\n\nTwo-year event-free survival was 97 percent with the chemotherapy-free regimen against 86 percent with AIDA, and overall survival 99 versus 91 percent; the arsenic arm had less haematological toxicity and fewer infections but more liver enzyme rises and QT prolongation.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2013","url":"https://doi.org/10.1056/NEJMoa1300874"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23841729/"}],"tags":[],"related":[],"cancers":["apl"],"sections":[],"technologies":[],"targets":[],"drugs":["arsenic-trioxide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["apl0406"],"people":["francesco-lo-coco"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2013,"doi":"10.1056/NEJMoa1300874","pmid":"23841729","authors":"Lo-Coco F, Avvisati G, Vignetti M, et al.","paperType":"rct","findings":["Two-year event-free survival 97 percent vs 86 percent.","Two-year overall survival 99 percent vs 91 percent."],"whatItMeans":"Low- and intermediate-risk APL is now treated without cytotoxic chemotherapy. The regimen has become the standard worldwide and made APL the most curable adult acute leukaemia.","caveats":["High-risk patients (white count over 10,000) were excluded and still receive added chemotherapy or gemtuzumab.","Differentiation syndrome remains a risk with either regimen."],"changedPractice":true,"participants":162},{"id":"paper-apt-tolaney-nejm-2015","kind":"paper","name":"APT: adjuvant paclitaxel and trastuzumab for small, node-negative HER2-positive breast cancer","aka":[],"tldr":"Twelve weeks of paclitaxel with a year of trastuzumab, and no anthracycline, was enough to keep more than 98 percent of women with small node-negative HER2-positive breast cancers free of recurrence at three years.","summary":"Single-arm phase 2 study of 406 patients with node-negative HER2-positive breast cancer up to 3 cm treated with weekly paclitaxel for 12 weeks plus trastuzumab for one year.\n\nThree-year invasive disease-free survival was 98.7 percent, with only two distant recurrences, and seven-year follow-up confirmed durable results with minimal cardiac toxicity. It established a de-escalated regimen for stage I disease.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2015","url":"https://doi.org/10.1056/NEJMoa1406281"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25564897/"}],"tags":[],"related":[],"cancers":["her2-positive-early-breast-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["trastuzumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2015,"doi":"10.1056/NEJMoa1406281","pmid":"25564897","authors":"Tolaney SM, Barry WT, Dang CT, et al.","paperType":"observational","findings":["Three-year invasive disease-free survival 98.7 percent.","Seven-year disease-free survival 93 percent with 97.5 percent recurrence-free interval."],"whatItMeans":"Women with small HER2-positive tumours can avoid anthracyclines and multi-agent chemotherapy; the APT regimen is a guideline standard for stage I HER2-positive disease.","caveats":["Non-randomised; the excellent outcomes may partly reflect a favourable population.","Most tumours were under 2 cm and hormone receptor-positive."],"changedPractice":true,"participants":406},{"id":"paper-aquila-daratumumab-smouldering-nejm-2025","kind":"paper","name":"AQUILA: daratumumab versus active monitoring in high-risk smouldering multiple myeloma","aka":[],"tldr":"Giving daratumumab for up to three years to people with high-risk smouldering myeloma roughly halved the risk of progressing to active myeloma or death compared with watching and waiting.","summary":"Phase 3 trial of 390 patients with high-risk smouldering multiple myeloma randomised to subcutaneous daratumumab monotherapy for up to 36 months or active monitoring.\n\nFive-year progression-free survival was 63.1 percent with daratumumab against 40.8 percent with monitoring (hazard ratio 0.49), with a favourable trend in overall survival and a manageable toxicity profile.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2025","url":"https://doi.org/10.1056/NEJMoa2409029"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39652675/"}],"tags":[],"related":[],"cancers":["smouldering-myeloma"],"sections":[],"technologies":[],"targets":[],"drugs":["daratumumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["aquila"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2025,"doi":"10.1056/NEJMoa2409029","pmid":"39652675","authors":"Dimopoulos MA, Voorhees PM, Schjesvold F, et al.","paperType":"rct","findings":["Five-year progression-free survival 63.1 percent vs 40.8 percent; hazard ratio 0.49.","Five-year overall survival 93.0 percent vs 86.9 percent."],"whatItMeans":"Early single-agent treatment of high-risk smouldering myeloma is now an option with regulatory approval, though monitoring remains acceptable and the definition of high risk matters.","caveats":["Risk definitions at enrolment predate the 20/2/20 model, so some patients were lower risk than intended.","Whether early treatment improves survival compared with treating at progression remains unproven."],"changedPractice":true,"participants":390},{"id":"paper-antonarakis-ar-v7-resistance-nejm-2014","kind":"paper","name":"AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer","aka":["Antonarakis 2014","AR-V7","androgen receptor splice variant 7"],"tldr":"A short form of the androgen receptor, missing the part that the hormone drugs grab onto, can be detected in tumour cells circulating in the blood. Not one man whose cells carried it responded to either enzalutamide or abiraterone.","summary":"Emmanuel Antonarakis, Jun Luo and colleagues at Johns Hopkins used a quantitative reverse-transcriptase polymerase chain reaction assay for the androgen receptor splice variant 7 messenger RNA in circulating tumour cells from 62 men with metastatic castration-resistant prostate cancer starting enzalutamide or abiraterone.\n\nAR-V7 lacks the ligand-binding domain, which is exactly what both drugs target, so the prediction was mechanical and the result was categorical: 0 percent of AR-V7-positive men had a prostate-specific antigen response on either drug, against 53 percent and 68 percent of AR-V7-negative men. Every survival endpoint followed. A decade on, AR-V7 testing is available but little used, partly because a negative result does not guarantee response and partly because the alternatives the test would send a man to, taxanes and radioligand therapy, are used in the same sequence anyway.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2014","url":"https://doi.org/10.1056/nejmoa1315815"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25184630/"},{"label":"Antonarakis et al., N Engl J Med 2014: AR-V7 in circulating tumour cells and resistance to enzalutamide and abiraterone (62 patients)","url":"https://doi.org/10.1056/NEJMoa1315815"}],"tags":["prostate-evidence"],"related":["paper-chen-androgen-receptor-overexpression-antiandrogen-resistance-nat-med-2004","paper-mu-sox2-lineage-plasticity-science-2017","idea-bio1-arv7-degrader","prostate-roadmap"],"cancers":["prostate","prostate-mcrpc"],"sections":["diagnostics","hormonal"],"technologies":["liquid-biopsy"],"targets":["androgen-receptor"],"drugs":["enzalutamide","abiraterone"],"companies":[],"institutions":["johns-hopkins"],"pathways":["ar-signaling","rna-splicing","resistance-routes-map","intravasation-ctc-survival"],"terms":["castration-resistance","psa","ctdna","radiographic-progression-free-survival","neuroendocrine-differentiation","ar-v7","liquid-biopsy","resistance","psa50"],"trials":[],"people":[],"bottlenecks":["b-resistance","b-biomarker-validation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2014,"doi":"10.1056/nejmoa1315815","pmid":"25184630","authors":"Antonarakis ES, Lu C, Wang H, et al.","paperType":"observational","findings":["AR-V7 was detectable in circulating tumour cells from 39 percent of 31 enzalutamide-treated patients and 19 percent of 31 abiraterone-treated patients.","Among men receiving enzalutamide, AR-V7-positive patients had a prostate-specific antigen response rate of 0 percent against 53 percent in AR-V7-negative patients (P equals 0.004).","Among men receiving abiraterone, the prostate-specific antigen response rate was 0 percent against 68 percent (P equals 0.004).","Median prostate-specific antigen progression-free survival on enzalutamide was 1.4 against 6.0 months, clinical or radiographic progression-free survival 2.1 against 6.1 months, and overall survival 5.5 months against not reached (P equals 0.002).","The association between AR-V7 detection and therapeutic resistance was maintained after adjustment for expression of full-length androgen receptor messenger RNA."],"whatItMeans":"The first predictive resistance biomarker in prostate cancer, and a mechanism rather than a correlation: a receptor with no ligand-binding domain cannot be blocked by a drug that binds the ligand-binding domain. It is also the origin of the case for androgen receptor degraders, which destroy the protein rather than blocking a site the protein no longer has.","caveats":["62 patients, prospectively enrolled but not randomised, and the authors state that large-scale prospective validation is required.","A negative AR-V7 result does not predict response, only the absence of this particular resistance mechanism; most non-responders are AR-V7-negative.","Assay-dependent: messenger RNA and protein-based AR-V7 assays do not identify the same patients, and the test is not standardised across laboratories."],"changedPractice":false,"participants":62},{"id":"paper-aramis-nejm-2019","kind":"paper","name":"ARAMIS: darolutamide in non-metastatic castration-resistant prostate cancer","aka":[],"tldr":"Darolutamide, an androgen receptor inhibitor that barely enters the brain, delayed metastases by nearly two years in men with non-metastatic castration-resistant prostate cancer with side effects close to placebo, and later showed a survival benefit.","summary":"Phase 3 placebo-controlled trial of 1,509 men with non-metastatic castration-resistant prostate cancer and PSA doubling time of ten months or less randomised 2:1 to darolutamide or placebo with continued androgen deprivation.\n\nMedian metastasis-free survival was 40.4 versus 18.4 months (hazard ratio 0.41), three-year overall survival 83 versus 77 percent (hazard ratio 0.69 at final analysis), and adverse events including falls, fractures, seizures and cognitive impairment were similar to placebo.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2019","url":"https://doi.org/10.1056/NEJMoa1815671"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30763142/"}],"tags":[],"related":[],"cancers":["prostate-nmcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":["darolutamide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["aramis"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2019,"doi":"10.1056/NEJMoa1815671","pmid":"30763142","authors":"Fizazi K, Shore N, Tammela TL, et al.","paperType":"rct","findings":["Median metastasis-free survival 40.4 vs 18.4 months; hazard ratio 0.41.","Overall survival hazard ratio 0.69; adverse event rates close to placebo."],"whatItMeans":"Darolutamide is often preferred in older men or those with fall or cognitive concerns because of its favourable tolerability among the three approved agents.","caveats":["No head-to-head comparison with enzalutamide or apalutamide.","Non-metastatic by conventional imaging."],"changedPractice":true,"participants":1509},{"id":"paper-arasens-nejm-2022","kind":"paper","name":"ARASENS: darolutamide added to androgen deprivation and docetaxel in metastatic hormone-sensitive prostate cancer","aka":[],"tldr":"Adding the androgen receptor inhibitor darolutamide to hormone therapy and docetaxel chemotherapy cut deaths by a third in metastatic hormone-sensitive prostate cancer, establishing triplet therapy for men fit for chemotherapy.","summary":"Phase 3 placebo-controlled trial of 1,306 men with metastatic hormone-sensitive prostate cancer randomised to androgen deprivation plus docetaxel with darolutamide or placebo.\n\nFour-year overall survival was 62.7 versus 50.4 percent (hazard ratio 0.68), with delayed castration resistance, pain progression and skeletal events, and no meaningful increase in toxicity beyond docetaxel; benefit was seen in both high- and low-volume disease.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2022","url":"https://doi.org/10.1056/NEJMoa2119115"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35179323/"}],"tags":[],"related":[],"cancers":["prostate-mhspc"],"sections":[],"technologies":[],"targets":[],"drugs":["darolutamide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["arasens"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/NEJMoa2119115","pmid":"35179323","authors":"Smith MR, Hussain M, Saad F, et al.","paperType":"rct","findings":["Four-year overall survival 62.7 percent vs 50.4 percent; hazard ratio 0.68.","Time to castration-resistant disease hazard ratio 0.36."],"whatItMeans":"Triplet therapy with darolutamide is a standard for fit men with metastatic hormone-sensitive prostate cancer, particularly high-volume disease; PEACE-1 showed the same with abiraterone.","caveats":["No arm of androgen deprivation plus darolutamide without docetaxel, so the contribution of docetaxel is unproven.","Most patients had high-volume disease."],"changedPractice":true,"participants":1306},{"id":"paper-arches-eur-urol-2026-update","kind":"paper","name":"ARCHES 5-year Survival with Enzalutamide Plus Androgen-deprivation Therapy in Metastatic Hormone-sensitive Prostate Cancer Patients","aka":[],"tldr":"Later report from the ARCHES trial registered as NCT02677896, in European Urology (2026); its title describes an updated or longer-term analysis.","summary":"The ARCHES trial (NCT02677896) showed improved radiographic progression-free survival (primary analysis; 2018) and overall survival (prespecified analysis; 2021) with enzalutamide versus placebo, with concomitant androgen-deprivation therapy, in metastatic hormone-sensitive prostate cancer (mHSPC) patients. This post hoc analysis describes 5-yr efficacy and safety for all 1150 randomized patients (data cutoff: July 31, 2024). Patients were randomized 1:1 to receive enzalutamide or placebo (first patient randomized: March 21, 2016). After the primary analysis, ARCHES was unblinded (December 10, 2018); 65% and 32% of patients in the enzalutamide and placebo groups, respectively, enrolled in the open-label extension. After the 61.4-mo median follow-up, 5-yr survival probability was 66% with enzalutamide and 53% with placebo (median months not reached in either group; hazard ratio [HR]: 0.70; 95% confidence interval [CI]: 0.58, 0.85; p < 0.001; adjusted HR: 0.64; 95% CI: 0.51, 0.75). Patients with high-volume disease who received enzalutamide lived 36 mo longer than those who received placebo (HR: 0.70; 95% CI: 0.56, 0.88). No new safety signals emerged. As this was a post hoc, non-alpha protected analysis, the overall survival p value is nominal and should be interpreted cautiously. Overall, this study provides compelling long-term data demonstrating survival benefits with enzalutamide across diverse patient subgroups to guide clinical decision-making and establish prognostic expectations in the mHSPC setting.\n\nIndexed on Europe PMC as PubMed record 41633900 (DOI 10.1016/j.eururo.2025.12.021). Its abstract cites the registry id NCT02677896, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Eur Urol 2026","url":"https://doi.org/10.1016/j.eururo.2025.12.021"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41633900/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41633900"},{"label":"ClinicalTrials.gov NCT02677896","url":"https://clinicaltrials.gov/study/NCT02677896"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["arches"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["european-urology"],"dependsOn":[],"notes":[],"journal":"European Urology","year":2026,"doi":"10.1016/j.eururo.2025.12.021","pmid":"41633900","authors":"Armstrong AJ, Petrylak DP, Shore ND, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the ARCHES trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-arches-j-clin-oncol-2019","kind":"paper","name":"ARCHES: A Randomized, Phase III Study of Androgen Deprivation Therapy With Enzalutamide or Placebo in Men With Metastatic Hormone-Sensitive Prostate Cancer","aka":[],"tldr":"Published report from the ARCHES trial registered as NCT02677896, in Journal of Clinical Oncology (2019), chosen as the most cited paper whose own text cites the registry id.","summary":"Purpose: Enzalutamide, a potent androgen-receptor inhibitor, has demonstrated significant benefits in metastatic and nonmetastatic castration-resistant prostate cancer. We evaluated the efficacy and safety of enzalutamide in metastatic hormone-sensitive prostate cancer (mHSPC).\n\nMethods: ARCHES (ClinicalTrials.gov identifier: NCT02677896) is a multinational, double-blind, phase III trial, wherein 1,150 men with mHSPC were randomly assigned 1:1 to enzalutamide (160 mg/day) or placebo, plus androgen deprivation therapy (ADT), stratified by disease volume and prior docetaxel chemotherapy. The primary end point was radiographic progression-free survival.\n\nResults: at October 14, 2018, the risk of radiographic progression or death was significantly reduced with enzalutamide plus ADT versus placebo plus ADT (hazard ratio, 0.39; 95% CI, 0.30 to 0.50; P <.001; median not reached v 19.0 months). Similar significant improvements in radiographic progression-free survival were reported in prespecified subgroups on the basis of disease volume and prior docetaxel therapy. Enzalutamide plus ADT significantly reduced the risk of prostate-specific antigen progression, initiation of new antineoplastic therapy, first symptomatic skeletal event, castration resistance, and reduced risk of pain progression. More men achieved an undetectable prostate-specific antigen level and/or an objective response with enzalutamide plus ADT ( P <.001). Patients in both treatment groups reported a high baseline level of quality of life, which was maintained over time. Grade 3 or greater adverse events were reported in 24.3% of patients who received enzalutamide plus ADT versus 25.6% of patients who received placebo plus ADT, with no unexpected adverse events.\n\nConclusion: Enzalutamide with ADT significantly reduced the risk of metastatic progression or death over time versus placebo plus ADT in men with mHSPC, including those with low-volume disease and/or prior docetaxel, with a safety analysis that seems consistent with the safety profile of enzalutamide in previous clinical trials in castration-resistant prostate cancer.\n\nIndexed on Europe PMC as PubMed record 31329516 (DOI 10.1200/jco.19.00799). Its abstract cites the registry id NCT02677896, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2019","url":"https://doi.org/10.1200/jco.19.00799"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31329516/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31329516"},{"label":"ClinicalTrials.gov NCT02677896","url":"https://clinicaltrials.gov/study/NCT02677896"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["arches"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2019,"doi":"10.1200/jco.19.00799","pmid":"31329516","authors":"Armstrong AJ, Szmulewitz RZ, Petrylak DP, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02677896 with the most citations, so it is the natural first reading for anyone following the ARCHES trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-dillekas-cancer-med","kind":"paper","name":"Are 90% of deaths from cancer caused by metastases?","aka":[],"tldr":"Paper cited by one bottleneck page and 16 idea pages, indexed on Europe PMC as PubMed record 31397113 and published in Cancer medicine; the citing pages link this DOI, which is how the record was matched.","summary":"Numerous publications have stated that metastases are responsible for 90% of cancer deaths, but data underlying this assertion has been lacking. Our objective was to determine what proportions of cancer deaths are caused by metastases. Population-based data from the Cancer Registry of Norway for the years 2005-2015 was analyzed. We compared all deaths in the Norwegian population where a cancer diagnosis was registered as cause of death. Deaths caused by cancer, with and without metastases, were analyzed, by sex and tumor group. For solid tumors, 66.7% of cancer deaths were registered with metastases as a contributing cause. Proportions varied substantially between tumor groups. Our data support the idea that the majority of deaths from solid tumors are caused by metastases. Thus, a better understanding of the biology of metastases and identification of druggable targets involved in growth at the metastatic site is a promising strategy to reduce cancer mortality.\n\nIndexed on Europe PMC as PubMed record 31397113 (DOI 10.1002/cam4.2474). Matched by DOI alone: one bottleneck page and 16 idea pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer Med 2019","url":"https://doi.org/10.1002/cam4.2474"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31397113/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31397113"}],"tags":["europepmc-ingest"],"related":["b-metastasis-biology","idea-bio2-premetastatic-niche-assay","idea-bio2-oligometastatic-signature","idea-bio2-organotropism-atlas","idea-bio2-net-blockade-perioperative","idea-bio2-perioperative-betablocker-nsaid","idea-bio2-ctc-clearance-go-nogo","idea-bio2-cxcr4-mobilise-then-kill","idea-bio2-ctc-culture-functional-testing","idea-bio2-inhaled-lung-niche-immunotherapy","idea-bio2-metastasis-screen-standard","idea-moon-metastasis-prevention-indication","idea-bio2-brain-met-prevention-trials","idea-bio2-liver-niche-kupffer-reprogramming","idea-bio2-matrix-stiffness-prevention","idea-bio2-platelet-cloak-aspirin-mrd","idea-bio2-lymph-node-immune-priming"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-medicine"],"dependsOn":[],"notes":[],"journal":"Cancer medicine","year":2019,"doi":"10.1002/cam4.2474","pmid":"31397113","authors":"Dillekås H, Rogers MS, Straume O","paperType":"observational","findings":[],"whatItMeans":"One bottleneck page and 16 idea pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-wiegand-arid1a-clear-cell-nejm-2010","kind":"paper","name":"ARID1A mutations in endometriosis-associated ovarian carcinomas","aka":[],"tldr":"This study found that about half of ovarian clear cell carcinomas and a third of endometrioid carcinomas carry inactivating mutations in ARID1A, a chromatin remodelling gene, linking these endometriosis-associated cancers to a common driver.","summary":"Sequencing study identifying truncating ARID1A mutations in 46 percent of ovarian clear cell carcinomas and 30 percent of endometrioid carcinomas but not in high-grade serous carcinoma, with loss of the BAF250a protein in mutated tumours and evidence of the mutation in adjacent endometriosis.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2010","url":"https://doi.org/10.1056/NEJMoa1008433"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20942669/"}],"tags":[],"related":[],"cancers":["clear-cell-ovarian-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2010,"doi":"10.1056/NEJMoa1008433","pmid":"20942669","authors":"Wiegand KC, Shah SP, Al-Agha OM, et al.","paperType":"translational","findings":["ARID1A mutations in 46 percent of clear cell and 30 percent of endometrioid ovarian carcinomas.","No ARID1A mutations in high-grade serous carcinoma."],"whatItMeans":"ARID1A loss defines the biology of clear cell ovarian cancer and is the target of current trials of synthetic-lethal drugs such as ATR and EZH2 inhibitors.","caveats":["No ARID1A-directed therapy has yet been approved."],"changedPractice":true},{"id":"paper-arrow-pralsetinib-gainor-lancet-oncol-2021","kind":"paper","name":"ARROW: pralsetinib for RET fusion-positive non-small-cell lung cancer","aka":[],"tldr":"Pralsetinib, a second selective RET inhibitor, shrank tumours in 61 percent of previously treated and 70 percent of untreated patients with RET fusion-positive lung cancer, giving an alternative to selpercatinib.","summary":"Phase 1/2 study including 233 patients with RET fusion-positive non-small-cell lung cancer treated with pralsetinib 400 mg daily.\n\nObjective response was 61 percent in patients previously treated with platinum chemotherapy and 70 percent in treatment-naive patients, with median duration of response not reached in the latter; neutropenia, hypertension and liver enzyme rise were common.","asOf":"2026-09-17","links":[{"label":"Lancet Oncol 2021","url":"https://doi.org/10.1016/S1470-2045(21)00247-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34118197/"}],"tags":[],"related":[],"cancers":["ret-fusion-nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":["pralsetinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2021,"doi":"10.1016/S1470-2045(21)00247-3","pmid":"34118197","authors":"Gainor JF, Curigliano G, Kim DW, et al.","paperType":"observational","findings":["Objective response 61 percent (previously treated) and 70 percent (treatment-naive).","Grade 3 or worse neutropenia in about 18 percent."],"whatItMeans":"Pralsetinib is approved for RET fusion-positive lung cancer and is used where selpercatinib is unavailable or not tolerated.","caveats":["Single-arm; pneumonitis and haematological toxicity more frequent than with selpercatinib in cross-trial comparison."],"changedPractice":true,"participants":233},{"id":"paper-llovet-tace-lancet-2002","kind":"paper","name":"Arterial embolisation or chemoembolisation versus symptomatic treatment in unresectable hepatocellular carcinoma","aka":[],"tldr":"This Barcelona trial was the first to show that transarterial chemoembolisation lengthens survival in intermediate-stage liver cancer, with two-year survival of 63 percent against 27 percent with supportive care, making it the standard for this stage.","summary":"Randomised trial of 112 patients with unresectable hepatocellular carcinoma, Child-Pugh A or B cirrhosis and no vascular invasion or extrahepatic spread, randomised to arterial embolisation, chemoembolisation with doxorubicin, or conservative treatment; stopped early when chemoembolisation showed a survival benefit.\n\nSurvival at one and two years was 82 and 63 percent with chemoembolisation, 75 and 50 percent with embolisation, and 63 and 27 percent with conservative treatment (hazard ratio for chemoembolisation 0.47).","asOf":"2026-09-17","links":[{"label":"Lancet 2002","url":"https://doi.org/10.1016/S0140-6736(02)08649-X"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/12049862/"}],"tags":[],"related":[],"cancers":["hcc-intermediate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2002,"doi":"10.1016/S0140-6736(02)08649-X","pmid":"12049862","authors":"Llovet JM, Real MI, Montaña X, et al.","paperType":"rct","findings":["Two-year survival 63 percent (chemoembolisation) vs 27 percent (conservative).","Hazard ratio for death 0.47 with chemoembolisation."],"whatItMeans":"Transarterial chemoembolisation is the standard treatment for BCLC stage B hepatocellular carcinoma, now being combined with systemic therapy.","caveats":["Small trial stopped early; embolisation alone was not significantly better than control."],"changedPractice":true,"participants":112},{"id":"paper-screentrustcad-dembrower-lancet-digit-health-2023","kind":"paper","name":"Artificial intelligence for breast cancer detection in screening mammography in Sweden: a prospective, population-based, paired-reader, non-inferiority study (ScreenTrustCAD)","aka":[],"tldr":"Among 55,581 women screened in Stockholm, one radiologist working with Lunit's software found 261 cancers against 250 for two radiologists, and the software on its own found 246, so the AI could stand in for a second reader without missing cancers.","summary":"Primary publication of ScreenTrustCAD (NCT04778670), a prospective, population-based, paired-reader, non-inferiority study at Capio Sankt Göran Hospital, Stockholm. Consecutive women aged 40 to 74 without breast implants in population screening were included. The primary outcome was screen-detected breast cancer within three months of mammography; the primary analysis assessed non-inferiority (margin 0.15 relative reduction in diagnoses) of double reading by one radiologist plus AI against standard double reading by two radiologists, with single reading by AI and triple reading by two radiologists plus AI as further comparisons.\n\nFrom 1 April 2021 to 9 June 2022, 58,344 women underwent screening and 55,581 were included. 269 women (0.5 percent) had screen-detected cancer on an initial positive read. One radiologist plus AI was non-inferior to two radiologists (261 versus 250 detected cases; relative proportion 1.04, 95 percent CI 1.00 to 1.09). AI alone (246 versus 250; 0.98, 0.93 to 1.04) and two radiologists plus AI (269 versus 250; 1.08, 1.04 to 1.11) were also non-inferior. The authors conclude that replacing one radiologist with AI gave a 4 percent higher non-inferior detection rate and suggest controlled implementation with risk management and real-world follow-up. Funded by the Swedish Research Council, the Swedish Cancer Society, Region Stockholm and Lunit.","asOf":"2026-09-24","links":[{"label":"Lancet Digital Health 2023","url":"https://doi.org/10.1016/S2589-7500(23)00153-X"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37690911/"},{"label":"ClinicalTrials.gov NCT04778670","url":"https://clinicaltrials.gov/study/NCT04778670"}],"tags":[],"related":[],"cancers":["breast-hr-positive","tnbc"],"sections":[],"technologies":["mammography","radiology-ai-screening"],"targets":[],"drugs":["lunit-insight-mmg"],"companies":["lunit"],"institutions":["karolinska"],"pathways":[],"terms":[],"trials":["screentrustcad"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-digital-health"],"dependsOn":[],"notes":[],"journal":"The Lancet Digital Health","year":2023,"doi":"10.1016/S2589-7500(23)00153-X","pmid":"37690911","authors":"Dembrower K, Crippa A, Colón E, et al.","paperType":"observational","findings":["One radiologist plus AI detected 261 cancers vs 250 for two radiologists (relative proportion 1.04, 95 percent CI 1.00 to 1.09); non-inferior.","AI alone detected 246 (relative proportion 0.98, 0.93 to 1.04) and two radiologists plus AI 269 (1.08, 1.04 to 1.11); both non-inferior.","55,581 of 58,344 screened women were included; 269 (0.5 percent) had screen-detected cancer."],"whatItMeans":"Screening programmes short of radiologists can read this as prospective evidence that a well-validated AI reader can take the second reader's seat without lowering cancer detection. It is a paired-reader study in one hospital, not a randomised trial, so MASAI and real-world follow-up carry the argument further.","caveats":["Paired-reader design in a single hospital; the same women were read under every strategy rather than randomised between them.","The lower confidence bound of the primary relative proportion is 1.00, so the result sits at the edge of showing more detection rather than simply non-inferiority.","Interval cancers and overdiagnosis were not part of the primary analysis; Lunit part-funded the study."],"changedPractice":false,"participants":55581},{"id":"paper-nagendran-bmj","kind":"paper","name":"Artificial intelligence versus clinicians: systematic review of design, reporting standards, and claims of deep learning studies","aka":[],"tldr":"Paper cited by one bottleneck page, indexed on Europe PMC as PubMed record 32213531 and published in BMJ; the citing page links this DOI, which is how the record was matched.","summary":"Objective: To systematically examine the design, reporting standards, risk of bias, and claims of studies comparing the performance of diagnostic deep learning algorithms for medical imaging with that of expert clinicians.\n\nDesign: Systematic review.\n\nData sources: Medline, Embase, Cochrane Central Register of Controlled Trials, and the World Health Organization trial registry from 2010 to June 2019.\n\nEligibility criteria for selecting studies: Randomised trial registrations and non-randomised studies comparing the performance of a deep learning algorithm in medical imaging with a contemporary group of one or more expert clinicians. Medical imaging has seen a growing interest in deep learning research. The main distinguishing feature of convolutional neural networks (CNNs) in deep learning is that when CNNs are fed with raw data, they develop their own representations needed for pattern recognition. The algorithm learns for itself the features of an image that are important for classification rather than being told by humans which features to use. The selected studies aimed to use medical imaging for predicting absolute risk of existing disease or classification into diagnostic groups (eg, disease or non-disease). For example, raw chest radiographs tagged with a label such as pneumothorax or no pneumothorax and the CNN learning which pixel patterns suggest pneumothorax.\n\nReview methods: Adherence to reporting standards was assessed by using CONSORT (consolidated standards of reporting trials) for randomised studies and TRIPOD (transparent reporting of a multivariable prediction model for individual prognosis or diagnosis) for non-randomised studies. Risk of bias was assessed by using the Cochrane risk of bias tool for randomised studies and PROBAST (prediction model risk of bias assessment tool) for non-randomised studies.\n\nResults: Only 10 records were found for deep learning randomised clinical trials, two of which have been published (with low risk of bias, except for lack of blinding, and high adherence to reporting standards) and eight are ongoing. Of 81 non-randomised clinical trials identified, only nine were prospective and just six were tested in a real world clinical setting. The median number of experts in the comparator group was only four (interquartile range 2-9). Full access to all datasets and code was severely limited (unavailable in 95% and 93% of studies, respectively). The overall risk of bias was high in 58 of 81 studies and adherence to reporting standards was suboptimal (<50% adherence for 12 of 29 TRIPOD items). 61 of 81 studies stated in their abstract that performance of artificial intelligence was at least comparable to (or better than) that of clinicians. Only 31 of 81 studies (38%) stated that further prospective studies or trials were required.\n\nConclusions: Few prospective deep learning studies and randomised trials exist in medical imaging. Most non-randomised trials are not prospective, are at high risk of bias, and deviate from existing reporting standards. Data and code availability are lacking in most studies, and human comparator groups are often small. Future studies should diminish risk of bias, enhance real world clinical relevance, improve reporting and transparency, and appropriately temper conclusions.\n\nStudy registration: PROSPERO CRD42019123605.\n\nIndexed on Europe PMC as PubMed record 32213531 (DOI 10.1136/bmj.m689). Matched by DOI alone: one bottleneck page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"BMJ 2020","url":"https://doi.org/10.1136/bmj.m689"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32213531/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32213531"}],"tags":["europepmc-ingest"],"related":["b-ai-validation"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["bmj"],"dependsOn":[],"notes":[],"journal":"BMJ","year":2020,"doi":"10.1136/bmj.m689","pmid":"32213531","authors":"Nagendran M, Chen Y, Lovejoy CA, et al.","paperType":"review","findings":[],"whatItMeans":"One bottleneck page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-murray-nat-rev-cancer","kind":"paper","name":"Aryl hydrocarbon receptor ligands in cancer: friend and foe","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 25568920 and published in Nature Reviews Cancer; the citing page links this DOI, which is how the record was matched.","summary":"The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that is best known for mediating the toxicity and tumour-promoting properties of the carcinogen 2,3,7,8-tetrachlorodibenzo-p-dioxin, commonly referred to as ‘dioxin’. AHR influences the major stages of tumorigenesis, initiation, promotion, progression and metastasis, and physiologically relevant AHR ligands are often formed during disease states or during heightened innate and adaptive immune responses. Interestingly, ligand specificity and affinity vary between rodents and humans. Studies of aggressive tumours and tumour cell lines show increased levels of AHR and constitutive localization of this receptor in the nucleus. This suggests that the AHR is chronically activated in tumours, thus facilitating tumour progression. This Review discusses the role of AHR in tumorigenesis and the potential for therapeutic modulation of its activity in tumours.\n\nIndexed on Europe PMC as PubMed record 25568920 (DOI 10.1038/nrc3846). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Cancer 2014","url":"https://doi.org/10.1038/nrc3846"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25568920/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25568920"}],"tags":["europepmc-ingest"],"related":["chemical-carcinogenesis-receptor-activation"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Cancer","year":2014,"doi":"10.1038/nrc3846","pmid":"25568920","authors":"Murray IA, Patterson AD, Perdew GH","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-ascent-nejm-2021","kind":"paper","name":"ASCENT: sacituzumab govitecan doubles survival in heavily pretreated metastatic triple-negative breast cancer","aka":[],"tldr":"In triple-negative breast cancer that had already been through at least two treatments, the TROP2 antibody-drug conjugate sacituzumab govitecan roughly doubled the time patients lived compared with standard chemotherapy.","summary":"Open-label phase 3 trial of 529 patients with relapsed or refractory metastatic triple-negative breast cancer after two or more prior chemotherapy regimens, randomised to sacituzumab govitecan or single-agent chemotherapy (eribulin, vinorelbine, capecitabine or gemcitabine). The primary endpoint was PFS in the 468 patients without brain metastases.\n\nMedian PFS was 5.6 vs 1.7 months (HR 0.41) and median overall survival 12.1 vs 6.7 months (HR 0.48). It converted the 2020 accelerated approval into a full approval and was the first ADC to show a survival benefit in TNBC.","asOf":"2026-09-08","links":[{"label":"NEJM 2021","url":"https://doi.org/10.1056/NEJMoa2028485"},{"label":"ClinicalTrials.gov NCT02574455","url":"https://clinicaltrials.gov/study/NCT02574455"}],"tags":[],"related":["idea-post-neoadjuvant-adc","idea-trop2-pet-selection"],"cancers":["tnbc"],"sections":[],"technologies":["adc","topoisomerase-inhibitors"],"targets":["trop2"],"drugs":["sacituzumab-govitecan"],"companies":["gilead"],"institutions":[],"pathways":[],"terms":["linker","payload","orr","pfs","os","accelerated-approval"],"trials":["ascent","ascent-03","ascent-04"],"people":["sara-hurvitz","sara-tolaney","javier-cortes","martine-piccart","sibylle-loibl","hope-rugo"],"bottlenecks":["b-resistance","b-toxicity-qol"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2021,"doi":"10.1056/NEJMoa2028485","authors":"Bardia A, Hurvitz SA, Tolaney SM, et al.","paperType":"rct","findings":["Median PFS 5.6 vs 1.7 months; HR 0.41 (95% CI 0.32-0.52).","Median overall survival 12.1 vs 6.7 months; HR 0.48 (95% CI 0.38-0.59).","Objective response rate 35% vs 5%.","Grade 3 or higher neutropenia 51% vs 33% and diarrhoea 10% vs under 1%; UGT1A1 *28 homozygotes had more neutropenia.","Benefit was seen regardless of TROP2 expression level and in patients with germline BRCA mutations."],"whatItMeans":"Sacituzumab govitecan is a standard second-line or later treatment for metastatic triple-negative breast cancer, roughly doubling survival compared with the chemotherapies it was tested against. Patients should expect neutropenia and diarrhoea, which are manageable with growth factor support and loperamide. Trials are now testing it earlier, in first-line combinations with pembrolizumab and after surgery for residual disease.","caveats":["Open-label; PFS assessed by blinded review.","The control chemotherapies were of modest efficacy in this setting (ORR 5%).","Patients with brain metastases were excluded from the primary analysis and remain under-studied.","The relatively unstable linker releases SN-38 systemically, which contributes to neutropenia and diarrhoea."],"changedPractice":true,"participants":529},{"id":"paper-asco-irae-guideline-jco-2021","kind":"paper","name":"ASCO 2021 guideline: how to recognise and manage the immune-related side effects of checkpoint inhibitors","aka":[],"tldr":"The ASCO 2021 guideline is the consensus rulebook for checkpoint-inhibitor toxicity: grade the problem, hold or stop the drug, give steroids early, escalate to other immunosuppressants if they fail, and involve specialists.","summary":"This update of the 2018 ASCO guideline, developed with the National Comprehensive Cancer Network, provides organ-by-organ recommendations for immune-related adverse events (irAEs) of PD-1, PD-L1 and CTLA-4 inhibitors, based on systematic review and expert consensus. The general framework is graded: grade 1 events are usually managed with monitoring while continuing therapy (except some neurological, haematological and cardiac events); grade 2 events lead to holding the inhibitor and considering corticosteroids (prednisone 0.5-1 mg/kg/day); grade 3 events require holding therapy and high-dose corticosteroids (1-2 mg/kg/day) tapered over at least four to six weeks, with infliximab or other agents if no improvement in 48-72 hours; grade 4 events generally mandate permanent discontinuation, except endocrinopathies controlled by hormone replacement. Specific sections cover skin, gastrointestinal, hepatic, endocrine, pulmonary, rheumatological, renal, neurological, haematological, cardiovascular and ocular toxicities, and a companion ASCO guideline addresses CAR-T toxicities. The Society for Immunotherapy of Cancer published a parallel consensus in 2021.","asOf":"2026-09-08","links":[{"label":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Management%20of%20Immune-Related%20Adverse%20Events%20ASCO%20Guideline%20Update%20Schneider%20JCO%202021"},{"label":"ASCO guidelines","url":"https://www.asco.org/guidelines"}],"tags":[],"related":["paper-checkmate-067-10-year-nejm-2025","paper-hodi-ipilimumab-melanoma-nejm-2010","cardio-oncology"],"cancers":["melanoma","nsclc"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["pd1","ctla4"],"drugs":["nivolumab","ipilimumab","pembrolizumab","atezolizumab"],"companies":[],"institutions":["asco"],"pathways":[],"terms":["irae","crs","icans"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-knowledge-diffusion","b-care-fragmentation"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2021,"doi":"10.1200/JCO.21.01440","pmid":"34724392","authors":"Schneider BJ, Naidoo J, Santomasso BD, et al.","paperType":"guideline","findings":["Grade-based algorithm: grade 1 monitor and continue (with exceptions); grade 2 hold and consider steroids; grade 3 hold and give 1-2 mg/kg prednisone-equivalent; grade 4 permanently discontinue except endocrinopathies.","Steroid tapers should last at least 4-6 weeks; failure to improve within 48-72 hours should prompt infliximab (colitis, arthritis), mycophenolate (hepatitis) or other second-line immunosuppression.","Myocarditis is rare but has high mortality and warrants high-dose steroids and early cardiology involvement; troponin monitoring is discussed.","Hormone replacement, not steroids, is the treatment for most endocrinopathies, which are often permanent.","Rechallenge after grade 2-3 irAEs can be considered case by case once resolved to grade 1 or less; short steroid courses do not clearly reduce efficacy."],"whatItMeans":"Checkpoint inhibitors are now given to hundreds of thousands of patients a year, many in community clinics and emergency departments, so a common, explicit playbook for their autoimmune side effects saves lives. The guideline standardised when to stop, when to give steroids and when to escalate, and made multidisciplinary toxicity teams routine. It does not remove the judgement needed for rare events or for patients whose cancer is responding.","caveats":["Most recommendations rest on expert consensus and case series rather than randomised trials.","Steroid-sparing strategies and biomarkers for irAEs remain largely unstudied.","Guidance on rechallenge and on combination or adjuvant settings is limited.","Rapidly evolving; later ASCO and SITC updates modify specific sections (for example, myocarditis and CAR-T toxicity)."],"changedPractice":true},{"id":"paper-aspen-armstrong-lancet-oncol-2016","kind":"paper","name":"ASPEN: everolimus versus sunitinib in metastatic non-clear cell renal cell carcinoma","aka":[],"tldr":"In the first randomised trial dedicated to non-clear cell kidney cancers, sunitinib delayed progression more than everolimus overall, though chromophobe tumours appeared to fare better on everolimus.","summary":"Randomised phase 2 trial of 108 patients with metastatic papillary, chromophobe or unclassified renal cell carcinoma randomised to sunitinib or everolimus.\n\nMedian progression-free survival was 8.3 months with sunitinib against 5.6 months with everolimus (hazard ratio 1.41 for everolimus); in the small chromophobe subgroup everolimus gave longer progression-free survival (11.4 versus 5.5 months), while papillary tumours did better with sunitinib.","asOf":"2026-09-17","links":[{"label":"Lancet Oncol 2016","url":"https://doi.org/10.1016/S1470-2045(15)00515-X"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26794930/"}],"tags":[],"related":[],"cancers":["chromophobe-rcc","papillary-rcc"],"sections":[],"technologies":[],"targets":[],"drugs":["everolimus","sunitinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2016,"doi":"10.1016/S1470-2045(15)00515-X","pmid":"26794930","authors":"Armstrong AJ, Halabi S, Eisen T, et al.","paperType":"rct","findings":["Median progression-free survival 8.3 months (sunitinib) vs 5.6 months (everolimus).","Chromophobe subgroup: 11.4 months with everolimus vs 5.5 months with sunitinib."],"whatItMeans":"VEGF-directed therapy is the default for non-clear cell disease, with everolimus considered in chromophobe tumours; cabozantinib later became preferred for papillary disease.","caveats":["Small heterogeneous trial; subgroup findings are hypothesis-generating."],"changedPractice":true,"participants":108},{"id":"paper-valtorta-her2-scoring-colorectal-heracles-mod-pathol-2015","kind":"paper","name":"Assessment of a HER2 scoring system for colorectal cancer: results from a validation study","aka":[],"tldr":"Breast and stomach cancer HER2 scoring rules do not fit the bowel. This study wrote colorectal-specific criteria, tested them on more than a thousand samples, and produced the definition of HER2-positive that the trials have used ever since.","summary":"Criteria for ERBB2 (HER2) positivity in colorectal cancer were developed in two steps to allow accurate identification of amplified metastatic patients for the HERACLES trial. A consensus panel of pathologists first adapted existing breast and gastric protocols for colorectal use on an archival test cohort of 256 samples, producing specific recommendations for scoring. Those colorectal-specific protocols and criteria were then applied from September 2012 to January 2015 to centrally screen 830 KRAS wild-type patients for the trial. In both cohorts, 5% of KRAS wild-type patients were HER2-positive by the criteria. Positive tumours showed intense membranous HER2 protein expression corresponding to homogeneous amplification in more than 50% of cells; no immunohistochemistry 0 or 1+ case was amplified, and concordance between silver and fluorescence in situ hybridisation was 100%.","asOf":"2026-09-24","links":[{"label":"Valtorta et al., Mod Pathol 2015: the HERACLES HER2 scoring criteria for colorectal cancer (256 plus 830 samples)","url":"https://doi.org/10.1038/modpathol.2015.98"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26449765/"}],"tags":[],"related":["her2-ihc-3-plus","her2-ish-amplified"],"cancers":["colorectal"],"sections":[],"technologies":["histopathology-ihc","cytogenetics-fish"],"targets":["her2"],"drugs":[],"companies":[],"institutions":["niguarda-cancer-center","candiolo"],"pathways":[],"terms":["ihc","fish","gene-amplification"],"trials":[],"people":["andrea-sartore-bianchi","salvatore-siena"],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"Modern Pathology","year":2015,"doi":"10.1038/modpathol.2015.98","pmid":"26449765","authors":"Valtorta E, Martino C, Sartore-Bianchi A, et al.","paperType":"methods","findings":["HERACLES criteria: intense membranous HER2 staining in more than 50% of cells, corresponding to homogeneous amplification.","5% of KRAS wild-type patients HER2-positive in both the 256-sample test and 830-sample validation cohorts.","No immunohistochemistry 0 or 1+ case was amplified; silver and fluorescence in situ hybridisation agreed completely."],"whatItMeans":"It is the threshold behind the colorectal HER2 approvals: the more-than-50% rule, rather than the 10% used in gastric cancer, is what a pathologist applies when a bowel cancer is called HER2-positive.","caveats":["Developed on KRAS wild-type patients being screened for one trial, so it is a trial-defined rather than a population-defined threshold.","Later trials have used next-generation sequencing amplification calls alongside immunohistochemistry, and the equivalence between them is not exact."],"changedPractice":true,"participants":1086},{"id":"paper-garcia-murillas-molecular-relapse-detection-jama-oncol-2019","kind":"paper","name":"Assessment of molecular relapse detection in early-stage breast cancer","aka":[],"tldr":"In 101 women followed with blood tests every few months after treatment for early breast cancer, ctDNA appeared a median of 10.7 months before relapse showed on scans and caught 22 of 23 distant relapses outside the brain but only one of six brain-only relapses.","summary":"Prospective multicentre validation study at five UK centres (2011 to 2016) of women with early breast cancer of any subtype receiving neoadjuvant or adjuvant chemotherapy; 170 recruited, 101 with mutations identified formed the main cohort, and 144 the combined cohort. Personalised digital PCR assays tracked primary tumour mutations in plasma every three months for a year and six-monthly thereafter. ctDNA detection during follow-up was associated with relapse (HR 25.2; P less than .001), as was detection at diagnosis (HR 5.8). Median lead time was 10.7 months; distant extracranial relapse was detected by ctDNA in 22 of 23 (96%) but brain-only metastasis in 1 of 6 (17%).","asOf":"2026-09-24","links":[{"label":"Garcia-Murillas et al., JAMA Oncol 2019: molecular relapse detection in 101 early breast cancer patients","url":"https://doi.org/10.1001/jamaoncol.2019.1838"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31369045/"}],"tags":[],"related":["ctdna-mrd-positive"],"cancers":["tnbc","breast-cancer"],"sections":[],"technologies":["mrd-testing"],"targets":[],"drugs":[],"companies":[],"institutions":["icr-london","royal-marsden"],"pathways":[],"terms":["ctdna","mrd"],"trials":[],"people":["nicholas-turner"],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2019,"doi":"10.1001/jamaoncol.2019.1838","pmid":"31369045","authors":"Garcia-Murillas I, Chopra N, Comino-Mendez I, et al.","paperType":"observational","findings":["ctDNA during follow-up: relapse HR 25.2; at diagnosis HR 5.8.","Median lead time 10.7 months; extracranial relapse detected in 96%, brain-only in 17%."],"whatItMeans":"For TNBC, where brain metastases are common, the blind spot matters: a negative ctDNA test does not exclude intracranial relapse.","caveats":["All subtypes; TNBC-specific numbers are not in the abstract.","Digital PCR assays of a few variants."],"changedPractice":false,"participants":101},{"id":"paper-oxnard-osimertinib-resistance-mechanisms-jama-oncol-2018","kind":"paper","name":"Assessment of resistance mechanisms and clinical implications in patients with EGFR T790M-positive lung cancer and acquired resistance to osimertinib","aka":[],"tldr":"When the newest targeted pill stops working, what happens next depends on whether the tumour kept the mutation the pill was chosen for. Two thirds lost it, and those patients relapsed much sooner and by many different routes.","summary":"Patients with advanced non-small-cell lung cancer who received osimertinib for T790M-positive acquired resistance to a prior EGFR inhibitor were identified from a multi-institutional cohort of 143 and a confirmatory trial cohort of 110, with next-generation sequencing of tumour biopsies after resistance and plasma cell-free DNA genotyping as an orthogonal approach. Of 41 patients with tumour sequencing after resistance, 13, 32%, maintained T790M, and EGFR C797S was seen in 9, 22%. Among the 28, 68%, with loss of T790M, a range of competing mechanisms was detected including acquired KRAS mutations and targetable gene fusions. Time to treatment discontinuation was shorter with T790M loss, 6.1 against 15.2 months, suggesting emergence of pre-existing resistant clones, a finding confirmed in the plasma validation cohort. In serial plasma, loss of T790M at resistance was associated with a smaller decrease in the driver EGFR mutation level after one to three weeks of therapy, 100% against 83% decrease.","asOf":"2026-09-25","links":[{"label":"Oxnard et al., JAMA Oncol 2018: resistance mechanisms after osimertinib in T790M-positive lung cancer (143 and 110 patients)","url":"https://doi.org/10.1001/jamaoncol.2018.2969"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30073261/"}],"tags":[],"related":["egfr-t790m"],"cancers":["nsclc"],"sections":[],"technologies":["liquid-biopsy","cgp","continuous-ctdna-monitoring"],"targets":["egfr","kras","met"],"drugs":["osimertinib","guardant360-cdx"],"companies":[],"institutions":["dana-farber"],"pathways":["resistance-routes-map","clonal-evolution","drug-tolerant-persisters","rtk-activation"],"terms":["resistance","ctdna","cfdna","egfr-mutation-subtypes","biopsy"],"trials":[],"people":["pasi-janne"],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2018,"doi":"10.1001/jamaoncol.2018.2969","pmid":"30073261","authors":"Oxnard GR, Hu Y, Mileham KF, et al.","paperType":"observational","findings":["T790M maintained in 32% of resistant tumours, with C797S in 22%.","T790M lost in 68%, with heterogeneous competing mechanisms including KRAS mutation and new fusions.","Time to treatment discontinuation 6.1 months with T790M loss against 15.2 months when it was kept.","Early plasma kinetics separate the two groups within three weeks of starting treatment."],"whatItMeans":"It changed how resistance is investigated: the first question at progression on osimertinib is whether T790M is still there, because losing it means the tumour is no longer EGFR-driven in the growing compartment and another EGFR inhibitor will not help.","caveats":["Only 41 of 143 patients had tumour sequencing, so the mechanism frequencies rest on a subset.","Plasma and tissue detect partly different things.","Multi-institutional retrospective design."],"changedPractice":true,"participants":253},{"id":"paper-gyawali-jama-intern-med","kind":"paper","name":"Assessment of the Clinical Benefit of Cancer Drugs Receiving Accelerated Approval","aka":[],"tldr":"Paper cited by one bottleneck page and 15 idea pages, indexed on Europe PMC as PubMed record 31135808 and published in JAMA Internal Medicine; the citing pages link this DOI, which is how the record was matched.","summary":"Importance: The US Food and Drug Administration's (FDA's) accelerated approval pathway allows investigational cancer drugs to be approved by demonstrating a beneficial effect on a surrogate measure (eg, progression-free survival) that is expected to predict a real clinical benefit (eg, overall survival). However, these drugs must undergo postapproval confirmatory studies to evaluate their actual clinical benefits. In an assessment of the accelerated approval pathway published in 2018, the FDA concluded that this pathway was successful because only 5 (5%) of 93 accelerated drug approvals had been withdrawn or revoked over the last 25 years.\n\nObjective: To compare the end points used in preapproval trials leading to accelerated approval with the end points used in the required confirmatory trials that verified clinical benefit and to update the outcomes of accelerated approvals with confirmatory trials that were ongoing at the time of FDA's review.\n\nDesign, setting, and participants: A review of the literature on end points used in preapproval and confirmatory trials of cancer drugs that received accelerated approval and a review of the FDA's database of postmarketing requirements and commitments focused on the outcomes of confirmatory trials that were ongoing at the time of FDA's review of cancer drug approvals published in 2018.\n\nMain outcomes and measures: End points used as confirmation of clinical benefit in cancer drugs that received accelerated approval, updated status of the confirmatory trials, and regulatory outcomes for cancer drugs that did not meet expectations in the confirmatory trials.\n\nResults: The FDA published a review of 93 cancer drug indications for which accelerated approval was granted from December 11, 1992, through May 31, 2017. Of these approvals, the FDA reported that clinical benefit was adequately confirmed in 51 and confirmatory trials for 15 of these indications (16% of the main sample) accelerated approvals reported improvement in overall survival. For 19 approvals (37%), the confirmatory trials used surrogate measures that were the same as those used in the preapproval trials. In this updated review, confirmatory trials for 19 of 93 (20%) cancer drug approvals reported an improvement in overall survival, 19 (20%) reported improvement in the same surrogate used in the preapproval trial, and 20 (21%) reported improvement in a different surrogate. Five confirmatory trials were delayed, 10 were pending, and 9 were ongoing. For 3 recent approvals, the primary end points were not met in the confirmatory trials; however, 1 cancer drug indication still received full approval.\n\nConclusions and relevance: Confirmatory trials for one-fifth (n = 19 of 93) of cancer drug indications approved via the FDA's accelerated approval pathway demonstrated improvements in overall patient survival. Reassessment of the requirements for confirmatory trials may be necessary to obtain more clinically meaningful information.\n\nIndexed on Europe PMC as PubMed record 31135808 (DOI 10.1001/jamainternmed.2019.0462). Matched by DOI alone: one bottleneck page and 15 idea pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA Intern Med 2019","url":"https://doi.org/10.1001/jamainternmed.2019.0462"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31135808/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31135808"}],"tags":["europepmc-ingest"],"related":["b-real-world-evidence","idea-moon-federated-rwe-network","idea-data-sequencing-analysis-per-approval","idea-data-paediatric-rwe-consortium","idea-data-rwe-rct-calibration-library","idea-data-accelerated-approval-registry-condition","idea-data-registry-follow-up-of-trial-participants","idea-nl-bariatric-cancer-registry-linkage","idea-data-linked-pharmacovigilance-interactions","idea-data-excluded-populations-rwe-mandate","idea-data-access-programme-outcomes","idea-data-outcome-based-price-reassessment","idea-data-registry-based-rcts","idea-data-external-control-arm-standard","idea-data-rwpfs-validation-programme","idea-data-wearable-endpoints-validation"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-internal-medicine"],"dependsOn":[],"notes":[],"journal":"JAMA Internal Medicine","year":2019,"doi":"10.1001/jamainternmed.2019.0462","pmid":"31135808","authors":"Gyawali B, Hey SP, Kesselheim AS","paperType":"review","findings":[],"whatItMeans":"One bottleneck page and 15 idea pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-hu-germline-mutations-pancreatic-cancer-risk-jama-2018","kind":"paper","name":"Association Between Inherited Germline Mutations in Cancer Predisposition Genes and Risk of Pancreatic Cancer","aka":[],"tldr":"The 2018 Mayo Clinic study of 3,030 patients that found an inherited fault in one of six genes in 5.5 percent of all pancreatic cancers, including 5.2 percent of patients with no family history, which is why every patient is now offered a germline test.","summary":"Hu and colleagues sequenced 21 cancer predisposition genes in 3,030 adults with pancreatic cancer enrolled in a Mayo Clinic registry between 2000 and 2016 (43.2 percent female, 95.6 percent non-Hispanic white, mean age 65.3) and compared mutation frequencies with 123,136 gnomAD and 53,105 ExAC reference controls. Significant associations were found for CDKN2A (0.3 percent of cases, odds ratio 12.33), TP53 (0.2 percent, 6.70), MLH1 (0.13 percent, 6.66), BRCA2 (1.9 percent, 6.20), ATM (2.3 percent, 5.71) and BRCA1 (0.6 percent, 2.58). Mutations in the six genes were found in 5.5 percent of all patients, 7.9 percent of those with a family history of pancreatic cancer and 5.2 percent of those without.","asOf":"2026-09-24","links":[{"label":"JAMA 2018","url":"https://doi.org/10.1001/jama.2018.6228"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29922827/"}],"tags":["pancreatic-evidence"],"related":["paper-caps-consortium-surveillance-recommendations-gut-2020","paper-polo-olaparib-maintenance-gbrca-pancreatic-nejm-2019","brca-germline"],"cancers":["pancreatic","brca-palb2-pdac"],"sections":[],"technologies":["germline-testing","pancreatic-surveillance"],"targets":["brca","atm","cdkn2a","tp53","mlh1"],"drugs":[],"companies":[],"institutions":["mayo-clinic"],"pathways":["ddr"],"terms":["gbrca-mutation","germline-vs-somatic","hereditary-cancer-syndromes"],"trials":[],"people":[],"bottlenecks":["b-hereditary-risk"],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2018,"doi":"10.1001/jama.2018.6228","pmid":"29922827","authors":"Hu C, Hart SN, Polley EC, et al.","paperType":"observational","findings":["3,030 patients; six genes associated with pancreatic cancer: CDKN2A, TP53, MLH1, BRCA2, ATM, BRCA1.","BRCA2 in 1.9 percent of cases (odds ratio 6.20), ATM in 2.3 percent (5.71), CDKN2A in 0.3 percent (12.33).","5.5 percent of all patients carried a mutation, 7.9 percent with and 5.2 percent without a family history."],"whatItMeans":"Family history misses most carriers, so the NCCN and ASCO guidelines moved to testing every patient; each carrier found is a family that can be offered surveillance and a patient who may be eligible for platinum and PARP inhibition.","caveats":["95.6 percent non-Hispanic white; frequencies in other populations are less certain.","Odds ratios describe risk relative to population databases, not absolute lifetime risk."],"changedPractice":true,"participants":3030},{"id":"paper-qian-driver-genes-outcomes-resected-pancreatic-jama-oncol-2018","kind":"paper","name":"Association of alterations in main driver genes with outcomes of patients with resected pancreatic ductal adenocarcinoma","aka":[],"tldr":"In 356 patients whose pancreatic cancer was removed, the more of the four main driver genes were broken the worse the outcome, KRAS G12D was the worst allele, CDKN2A loss shortened survival, and SMAD4 status made no difference.","summary":"KRAS, CDKN2A, SMAD4 and TP53 were assessed by immunohistochemistry and next-generation sequencing in 356 resected pancreatic adenocarcinomas from Dana-Farber/Brigham, Rochester and Stanford. KRAS-mutant tumours had worse disease-free (12.3 versus 16.2 months) and overall survival (20.3 versus 38.6 months; 5-year 13.0% versus 30.2%) than wild-type; KRAS G12D carried median overall survival 15.3 months. Loss of CDKN2A expression gave disease-free survival 11.5 versus 14.8 and overall survival 19.7 versus 24.6 months. SMAD4 status was not associated with outcome; TP53 only with shorter disease-free survival (hazard ratio 1.33). Four altered genes against 0 to 2 gave a disease-free survival hazard ratio of 1.79; 5-year overall survival 18.4%, 14.1% and 8.2% for 0 to 2, 3 and 4 alterations.","asOf":"2026-09-24","links":[{"label":"Qian et al., JAMA Oncol 2018: the four driver genes and outcome in 356 resected cancers","url":"https://doi.org/10.1001/jamaoncol.2017.3420"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29098284/"}],"tags":[],"related":["kras-g12d"],"cancers":["pancreatic","resectable-pdac"],"sections":[],"technologies":[],"targets":["kras","cdkn2a","smad4","tp53"],"drugs":[],"companies":[],"institutions":["dana-farber","stanford"],"pathways":["p53-cell-cycle","ras-mapk"],"terms":["kras-mutation-subtypes"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2018,"doi":"10.1001/jamaoncol.2017.3420","pmid":"29098284","authors":"Qian ZR, Rubinson DA, Nowak JA, et al.","paperType":"observational","findings":["KRAS wild-type: overall survival 38.6 versus 20.3 months; G12D 15.3 months.","CDKN2A loss: overall survival 19.7 versus 24.6 months; SMAD4 not prognostic; TP53 disease-free only.","Four altered drivers: 5-year survival 8.2% versus 18.4%."],"whatItMeans":"The driver count is a prognostic score in itself, and the allele matters: G12D is the pancreatic allele with the worst outlook and the one the new selective inhibitors chase.","caveats":["Retrospective, three centres, mixed perioperative treatment.","SMAD4's metastatic-pattern effect (Iacobuzio-Donahue 2009) did not show as a survival difference here."],"changedPractice":false,"participants":356},{"id":"paper-aminian-jama","kind":"paper","name":"Association of Bariatric Surgery With Cancer Risk and Mortality in Adults With Obesity","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 35657620 and published in JAMA; the citing page links this DOI, which is how the record was matched.","summary":"Importance: Obesity increases the incidence and mortality from some types of cancer, but it remains uncertain whether intentional weight loss can decrease this risk.\n\nObjective: To investigate whether bariatric surgery is associated with lower cancer risk and mortality in patients with obesity.\n\nDesign, setting, and participants: In the SPLENDID (Surgical Procedures and Long-term Effectiveness in Neoplastic Disease Incidence and Death) matched cohort study, adult patients with a body mass index of 35 or greater who underwent bariatric surgery at a US health system between 2004 and 2017 were included. Patients who underwent bariatric surgery were matched 1:5 to patients who did not undergo surgery for their obesity, resulting in a total of 30 318 patients. Follow-up ended in February 2021.\n\nExposures: Bariatric surgery (n = 5053), including Roux-en-Y gastric bypass and sleeve gastrectomy, vs nonsurgical care (n = 25 265).\n\nMain outcomes and measures: Multivariable Cox regression analysis estimated time to incident obesity-associated cancer (a composite of 13 cancer types as the primary end point) and cancer-related mortality.\n\nResults: The study included 30 318 patients (median age, 46 years; median body mass index, 45; 77% female; and 73% White) with a median follow-up of 6.1 years (IQR, 3.8-8.9 years). The mean between-group difference in body weight at 10 years was 24.8 kg (95% CI, 24.6-25.1 kg) or a 19.2% (95% CI, 19.1%-19.4%) greater weight loss in the bariatric surgery group. During follow-up, 96 patients in the bariatric surgery group and 780 patients in the nonsurgical control group had an incident obesity-associated cancer (incidence rate of 3.0 events vs 4.6 events, respectively, per 1000 person-years). The cumulative incidence of the primary end point at 10 years was 2.9% (95% CI, 2.2%-3.6%) in the bariatric surgery group and 4.9% (95% CI, 4.5%-5.3%) in the nonsurgical control group (absolute risk difference, 2.0% [95% CI, 1.2%-2.7%]; adjusted hazard ratio, 0.68 [95% CI, 0.53-0.87], P =.002). Cancer-related mortality occurred in 21 patients in the bariatric surgery group and 205 patients in the nonsurgical control group (incidence rate of 0.6 events vs 1.2 events, respectively, per 1000 person-years). The cumulative incidence of cancer-related mortality at 10 years was 0.8% (95% CI, 0.4%-1.2%) in the bariatric surgery group and 1.4% (95% CI, 1.1%-1.6%) in the nonsurgical control group (absolute risk difference, 0.6% [95% CI, 0.1%-1.0%]; adjusted hazard ratio, 0.52 [95% CI, 0.31-0.88], P =.01).\n\nConclusions and relevance: Among adults with obesity, bariatric surgery compared with no surgery was associated with a significantly lower incidence of obesity-associated cancer and cancer-related mortality.\n\nIndexed on Europe PMC as PubMed record 35657620 (DOI 10.1001/jama.2022.9009). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA 2022","url":"https://doi.org/10.1001/jama.2022.9009"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35657620/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35657620"}],"tags":["europepmc-ingest"],"related":["bariatric-surgery-cancer-incidence"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2022,"doi":"10.1001/jama.2022.9009","pmid":"35657620","authors":"Aminian A, Wilson R, Al-Kurd A, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-dess-black-race-prostate-mortality-jama-oncol-2019","kind":"paper","name":"Association of Black race with prostate cancer-specific and other-cause mortality","aka":["Dess 2019","Black race prostate cancer mortality equal access"],"tldr":"Black men in the United States are more likely to die of prostate cancer. This study looked at registry data, an equal-access health system and randomised trials together, and found that once treatment and access were equal, the difference in prostate cancer deaths largely disappeared. The difference in dying of everything else did not.","summary":"Robert Dess, Daniel Spratt and colleagues assembled individual patient data on men with clinical T1 to T4, N0 to N1, M0 prostate cancer from three cohorts with progressively tighter control of access: the Surveillance, Epidemiology, and End Results registry (296,273 men), five equal-access Veterans Affairs medical centres (3,972 men, all treated surgically) and four pooled National Cancer Institute randomised radiotherapy trials (5,854 men). Inverse probability weighting was used to adjust for demographic, cancer and treatment differences.\n\nThe gradient across the three cohorts is the finding. In the registry, Black race carried an age-adjusted subdistribution hazard ratio for prostate cancer death of 1.30; after adjustment it fell to 1.09, with no significant difference in high-risk men. In the equal-access surgical cohort there was no significant difference, and in the randomised trials Black men had a significantly lower hazard. Other-cause mortality remained significantly higher in two of the three cohorts.","asOf":"2026-09-25","links":[{"label":"JAMA Oncol 2019","url":"https://doi.org/10.1001/jamaoncol.2019.0826"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31120534/"}],"tags":["prostate-evidence"],"related":["paper-conti-trans-ancestry-gwas-prostate-nat-genet-2021","paper-uspstf-prostate-screening-jama-2018","idea-acc-cardiometabolic-clinic-hormone-therapy","prostate-roadmap"],"cancers":["prostate","prostate-intermediate-risk","prostate-high-risk"],"sections":["early-detection","supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["screening","hazard-ratio","other-cause-mortality","polygenic-risk-score"],"trials":[],"people":[],"bottlenecks":["b-global-access","b-trial-diversity","b-care-fragmentation","b-survivorship","b-aging-comorbidity"],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2019,"doi":"10.1001/jamaoncol.2019.0826","pmid":"31120534","authors":"Dess RT, Hartman HE, Mahal BA, et al.","paperType":"observational","findings":["In the SEER cohort, Black race was associated with an age-adjusted subdistribution hazard ratio for prostate cancer-specific mortality of 1.30 (95 percent confidence interval 1.23 to 1.37; P less than 0.001).","After inverse probability weighting, the increase in prostate cancer-specific mortality at 10 years was 0.5 percentage points (0.2 to 0.9), subdistribution hazard ratio 1.09 (1.04 to 1.15), with no significant difference in high-risk men (1.04; 0.97 to 1.12; P equals 0.29).","No significant difference in prostate cancer-specific mortality in the weighted equal-access Veterans Affairs cohort (subdistribution hazard ratio 0.85; 0.56 to 1.30; P equals 0.46).","In the weighted randomised trial cohort, Black men had a significantly lower hazard of prostate cancer death (0.81; 0.66 to 0.99; P equals 0.04).","Other-cause mortality was significantly higher for Black men in the weighted SEER cohort (1.30; 1.27 to 1.34; P less than 0.001) and the weighted trial cohort (1.17; 1.06 to 1.29; P equals 0.002)."],"whatItMeans":"The disparity in prostate cancer death among Black men in the United States is, stage for stage and treatment for treatment, largely a disparity in getting standard care rather than in tumour biology. The disparity that survives equal access is in dying of everything else, which is the part a cancer service is least organised to fix and most able to measure.","caveats":["Retrospective, even with inverse probability weighting; unmeasured confounding remains, and the trial cohort is a selected population that consented to randomisation.","Higher incidence and younger age at presentation in Black men are not addressed here; the paper is about mortality after diagnosis at a given stage.","United States cohorts and United States health system; the access gradient in other systems is different."],"changedPractice":false,"participants":306100},{"id":"paper-radovich-ctdna-ctc-bre12-158-jama-oncol-2020","kind":"paper","name":"Association of Circulating Tumor DNA and Circulating Tumor Cells After Neoadjuvant Chemotherapy With Disease Recurrence in Patients With Triple-Negative Breast Cancer: Preplanned Secondary Analysis of the BRE12-158 Randomized Clinical Trial","aka":[],"tldr":"In 196 women with triple-negative breast cancer left with residual tumour after pre-surgery chemotherapy, finding tumour DNA in the blood after surgery tripled the risk of distant relapse and quadrupled the risk of death; at two years 56 percent versus 81 percent were free of distant disease.","summary":"Radovich, Jiang, Hancock, Chitambar and colleagues report a preplanned secondary analysis of BRE12-158, a phase 2 trial that randomised patients with early-stage triple-negative breast cancer and residual disease after neoadjuvant chemotherapy to genomically directed therapy or physician's choice; 196 patients had blood drawn at treatment assignment, with ctDNA (FoundationACT or FoundationOne Liquid) analysed for survival in 142 and circulating tumour cells in 123, median follow-up 17.2 months. ctDNA detection was associated with inferior distant disease-free survival (median 32.5 months versus not reached; hazard ratio 2.99, 95 percent confidence interval 1.38 to 6.48, p=0.006; two-year probability 56 versus 81 percent), disease-free survival (2.67) and overall survival (4.16, 1.66 to 10.42, p=0.002). Patients positive for both ctDNA and circulating tumour cells had a distant disease-free survival hazard ratio of 5.29 versus double-negative patients (two-year probability 52 versus 89 percent) and overall survival hazard ratio 8.60.","asOf":"2026-09-24","links":[{"label":"JAMA Oncol 2020","url":"https://doi.org/10.1001/jamaoncol.2020.2295"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32644110/"},{"label":"ClinicalTrials.gov NCT02101385","url":"https://clinicaltrials.gov/study/NCT02101385"}],"tags":["tnbc-evidence"],"related":["ctdna-tests","paper-turner-c-trak-tn-ctdna-pembrolizumab-ann-oncol-2023","ctdna-mrd-positive"],"cancers":["tnbc","tnbc-early"],"sections":[],"technologies":["liquid-biopsy","mrd-testing"],"targets":[],"drugs":["foundationone-cdx"],"companies":["foundation-medicine"],"institutions":[],"pathways":[],"terms":["ctdna","mrd","rcb","hazard-ratio"],"trials":[],"people":[],"bottlenecks":["b-dormancy-mrd","b-biomarker-validation"],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2020,"doi":"10.1001/jamaoncol.2020.2295","pmid":"32644110","authors":"Radovich M, Jiang G, Hancock BA, et al.","paperType":"rct","findings":["ctDNA detection after neoadjuvant chemotherapy: distant disease-free survival hazard ratio 2.99 (95 percent CI 1.38 to 6.48), p=0.006; two-year probability 56 vs 81 percent.","Overall survival hazard ratio 4.16 (1.66 to 10.42), p=0.002.","ctDNA and circulating tumour cell double positivity: distant disease-free survival hazard ratio 5.29; two-year probability 52 vs 89 percent."],"whatItMeans":"The proof that a blood test can split residual-disease patients into those likely to relapse and those likely cured, the premise of the ctDNA-guided adjuvant idea; no completed trial has yet acted on the result.","caveats":["Short follow-up (17.2 months) and a tumour-agnostic assay less sensitive than tumour-informed tests.","Secondary analysis of a trial whose primary comparison was negative."],"changedPractice":false,"participants":196},{"id":"paper-jensen-clonal-haematopoiesis-cfdna-interference-prostate-jama-oncol-2021","kind":"paper","name":"Association of clonal haematopoiesis in DNA repair genes with prostate cancer plasma cell-free DNA testing interference","aka":[],"tldr":"In one man in ten with advanced prostate cancer, a DNA repair fault found in a blood test came from his bone marrow rather than from his cancer, which could send him to the wrong drug.","summary":"A case series of 69 men with advanced prostate cancer, metastatic or with rising PSA after localised therapy, who had cell-free DNA variant testing with a large next-generation sequencing panel. To determine the source of variants in plasma, paired cell-free DNA and whole blood control samples were tested. Clonal haematopoiesis variants at 2% or more variant fraction were detected in cell-free DNA from 13 of the 69 men, 19%. Seven men, 10%, had clonal haematopoiesis variants in DNA repair genes used to determine PARP inhibitor candidacy, including ATM in 5, BRCA2 in 1 and CHEK2 in 1. Overall, clonal haematopoiesis variants accounted for almost half of the somatic DNA repair gene variants detected. Variants correlated exponentially with older age, and could be distinguished from prostate cancer variants using a paired whole blood control.","asOf":"2026-09-25","links":[{"label":"Jensen et al., JAMA Oncol 2021: clonal haematopoiesis in DNA repair genes interfering with prostate cancer plasma cell-free DNA testing (69 men, paired whole-blood control)","url":"https://doi.org/10.1001/jamaoncol.2020.5161"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33151258/"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["liquid-biopsy","cgp"],"targets":["atm","brca","chek2"],"drugs":[],"companies":[],"institutions":[],"pathways":["homologous-recombination-repair","clonal-haematopoiesis"],"terms":["ctdna","cfdna","germline-vs-somatic","vus"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2021,"doi":"10.1001/jamaoncol.2020.5161","pmid":"33151258","authors":"Jensen K, Konnick EQ, Schweizer MT, et al.","paperType":"observational","findings":["Clonal haematopoiesis variants at 2% or more in plasma from 13 of 69 men, 19%.","Seven men, 10%, had such a variant in a gene used to decide PARP inhibitor candidacy, most often ATM.","Clonal haematopoiesis accounted for almost half of all somatic DNA repair variants detected in plasma.","A paired whole blood control distinguishes them."],"whatItMeans":"It identifies a way that a good test produces a wrong answer, and it names the fix. Any plasma repair-gene result used to decide on a PARP inhibitor should be run with a paired blood control, or an older man may be treated for a marrow clone rather than for his prostate cancer.","caveats":["Sixty-nine men at one academic reference laboratory.","A 2% variant fraction threshold is a choice, and lower-level interference will be commoner still.","It does not quantify how often this has changed treatment in practice."],"changedPractice":true,"participants":69},{"id":"paper-connor-mutational-signatures-immune-pancreatic-jama-oncol-2017","kind":"paper","name":"Association of distinct mutational signatures with correlates of increased immune activity in pancreatic ductal adenocarcinoma","aka":[],"tldr":"Reading the mutation patterns in 255 whole genomes sorted pancreatic cancers into four types, and the two with broken DNA repair carried more mutations, more neoantigens and more signs of an immune response, suggesting who might respond to immunotherapy.","summary":"Retrospective ICGC cohort of resected pancreatic ductal adenocarcinoma: a discovery set of 160 tumour-enriched cases (154 patients) with whole-genome and RNA sequencing and a replication set of 95 bulk cases. Non-negative matrix factorisation measured signature contributions; hierarchical clustering gave five predominant mutational signatures in four subtypes: age-related, double-strand break repair, mismatch repair and unknown aetiology (signature 8), replicated and stable from primaries to matched metastases. Twelve of 27 (45%) double-strand break repair cases lacked germline or somatic events in BRCA1, BRCA2 or PALB2. Double-strand break repair and mismatch repair subtypes showed increased antitumour immunity expression (GZMA, PRF1) and regulatory molecules (CTLA-4, PD-1, IDO1), corresponding to higher somatic mutation and neoantigen frequency.","asOf":"2026-09-24","links":[{"label":"Connor et al., JAMA Oncol 2017: mutational signatures and immune activity in 160 plus 95 whole genomes","url":"https://doi.org/10.1001/jamaoncol.2016.3916"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27768182/"}],"tags":[],"related":["hrd-positive"],"cancers":["pancreatic"],"sections":[],"technologies":["wes-wgs"],"targets":["brca","palb2","mmr"],"drugs":[],"companies":[],"institutions":["oicr","princess-margaret"],"pathways":["mutagenesis-signatures","homologous-recombination-repair","antigen-presentation-immunoediting"],"terms":["mutational-signature","neoantigen"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2017,"doi":"10.1001/jamaoncol.2016.3916","pmid":"27768182","authors":"Connor AA, Denroche RE, Jang GH, et al.","paperType":"translational","findings":["Four signature subtypes: age-related, double-strand break repair, mismatch repair, signature 8.","45% of double-strand break repair cases had no BRCA1, BRCA2 or PALB2 event.","Repair-defective subtypes express more cytotoxic and checkpoint genes with more neoantigens."],"whatItMeans":"Signatures find repair-deficient tumours that gene panels miss, and they mark the minority in which checkpoint drugs have a rationale.","caveats":["Resected cohort; no immunotherapy outcomes.","Signature calling depends on tumour enrichment."],"changedPractice":false,"participants":255},{"id":"paper-ricciuti-tmb-pd-l1-levels-jama-oncol-2022","kind":"paper","name":"Association of high tumor mutation burden in non-small cell lung cancers with increased immune infiltration and improved clinical outcomes of PD-L1 blockade across PD-L1 expression levels","aka":[],"tldr":"Pooling more than fifteen hundred patients showed that the more mutations a lung cancer carries the better immunotherapy works, at every level of the PD-L1 stain, but the best dividing line was about twice the number the licensing authorities use.","summary":"A multicentre cohort study of patients with advanced non-small-cell lung cancer treated with PD-1 or PD-L1 inhibition without chemotherapy, drawn from three datasets, analysed the association between increasing tumour mutation burden and outcomes across clinically relevant PD-L1 levels. Among 1,552 patients, median age 66 years, a regression tree modelling response rate as a function of burden identified two groupings in the discovery cohort, low (19.0 or fewer mutations per megabase) and high (more than 19.0), which were associated with increasing improvements in response, progression-free survival and overall survival in the discovery cohort and in two independent cohorts. These levels were also associated with significant improvements within each PD-L1 subgroup of less than 1%, 1% to 49% and 50% or higher. Response was as high as 57% with high burden and PD-L1 50% or more and as low as 8.7% with low burden and PD-L1 under 1%. Multiplexed immunofluorescence and transcriptomic profiling linked high burden to greater immune infiltration.","asOf":"2026-09-25","links":[{"label":"Ricciuti et al., JAMA Oncol 2022: tumour mutational burden and PD-(L)1 blockade across PD-L1 levels in 1,552 patients","url":"https://doi.org/10.1001/jamaoncol.2022.1981"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35708671/"}],"tags":[],"related":["tmb-high","pd-l1-tps"],"cancers":["nsclc"],"sections":[],"technologies":["tmb-testing","cgp","checkpoint-inhibitor","single-cell-spatial"],"targets":["pdl1","pd1"],"drugs":[],"companies":[],"institutions":["dana-farber","mskcc"],"pathways":["cancer-immunity-cycle","pd1-checkpoint"],"terms":["tmb","neoantigen","cold-vs-hot"],"trials":[],"people":["matthew-hellmann"],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2022,"doi":"10.1001/jamaoncol.2022.1981","pmid":"35708671","authors":"Ricciuti B, Wang X, Alessi JV, et al.","paperType":"observational","findings":["The data-derived threshold was more than 19 mutations per megabase, not 10.","Burden predicted response, progression-free survival and overall survival within every PD-L1 stratum.","Response ranged from 57% with both markers high to 8.7% with both low.","High burden was accompanied by greater immune infiltration on imaging and transcriptomics."],"whatItMeans":"It is the strongest case that mutation burden is real biology in lung cancer and, at the same time, the clearest demonstration that its threshold is not fixed, which is why it never became a reliable selector.","caveats":["Retrospective across three cohorts with different panels and pipelines.","Patients received monotherapy, so the finding does not extend to chemo-immunotherapy.","A threshold found by regression tree in one cohort is at risk of overfitting even when it validates."],"changedPractice":false,"participants":1552},{"id":"paper-molinaro-jama-oncol","kind":"paper","name":"Association of Maximal Extent of Resection of Contrast-Enhanced and Non-Contrast-Enhanced Tumor With Survival Within Molecular Subgroups of Patients With Newly Diagnosed Glioblastoma","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 32027343 and published in JAMA Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Importance: Per the World Health Organization 2016 integrative classification, newly diagnosed glioblastomas are separated into isocitrate dehydrogenase gene 1 or 2 (IDH)-wild-type and IDH-mutant subtypes, with median patient survival of 1.2 and 3.6 years, respectively. Although maximal resection of contrast-enhanced (CE) tumor is associated with longer survival, the prognostic importance of maximal resection within molecular subgroups and the potential importance of resection of non-contrast-enhanced (NCE) disease is poorly understood.\n\nObjective: To assess the association of resection of CE and NCE tumors in conjunction with molecular and clinical information to develop a new road map for cytoreductive surgery.\n\nDesign, setting, and participants: This retrospective, multicenter cohort study included a development cohort from the University of California, San Francisco (761 patients diagnosed from January 1, 1997, through December 31, 2017, with 9.6 years of follow-up) and validation cohorts from the Mayo Clinic (107 patients diagnosed from January 1, 2004, through December 31, 2014, with 5.7 years of follow-up) and the Ohio Brain Tumor Study (99 patients with data collected from January 1, 2008, through December 31, 2011, with a median follow-up of 10.9 months). Image accessors were blinded to patient groupings. Eligible patients underwent surgical resection for newly diagnosed glioblastoma and had available survival, molecular, and clinical data and preoperative and postoperative magnetic resonance images. Data were analyzed from November 15, 2018, to March 15, 2019.\n\nMain outcomes and measures: Overall survival.\n\nResults: Among the 761 patients included in the development cohort (468 [61.5%] men; median age, 60 [interquartile range, 51.6-67.7] years), younger patients with IDH-wild-type tumors and aggressive resection of CE and NCE tumors had survival similar to that of patients with IDH-mutant tumors (median overall survival [OS], 37.3 [95% CI, 31.6-70.7] months). Younger patients with IDH-wild-type tumors and reduction of CE tumor but residual NCE tumors fared worse (median OS, 16.5 [95% CI, 14.7-18.3] months). Older patients with IDH-wild-type tumors benefited from reduction of CE tumor (median OS, 12.4 [95% CI, 11.4-14.0] months). The results were validated in the 2 external cohorts. The association between aggressive CE and NCE in patients with IDH-wild-type tumors was not attenuated by the methylation status of the promoter region of the DNA repair enzyme O6-methylguanine-DNA methyltransferase.\n\nConclusions and relevance: This study confirms an association between maximal resection of CE tumor and OS in patients with glioblastoma across all subgroups. In addition, maximal resection of NCE tumor was associated with longer OS in younger patients, regardless of IDH status, and among patients with IDH-wild-type glioblastoma regardless of the methylation status of the promoter region of the DNA repair enzyme O6-methylguanine-DNA methyltransferase. These conclusions may help reassess surgical strategies for individual patients with newly diagnosed glioblastoma.\n\nIndexed on Europe PMC as PubMed record 32027343 (DOI 10.1001/jamaoncol.2019.6143). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA Oncol 2020","url":"https://doi.org/10.1001/jamaoncol.2019.6143"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32027343/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32027343"}],"tags":["europepmc-ingest"],"related":["extent-of-resection"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2020,"doi":"10.1001/jamaoncol.2019.6143","pmid":"32027343","authors":"Molinaro AM, Hervey-Jumper S, Morshed RA, et al.","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-ethun-re-resection-timing-incidental-gallbladder-cancer-jama-surg-2017","kind":"paper","name":"Association of Optimal Time Interval to Re-resection for Incidental Gallbladder Cancer With Overall Survival: A Multi-Institution Analysis From the US Extrahepatic Biliary Malignancy Consortium","aka":[],"tldr":"Across ten US centres, people whose second operation for a chance-found gallbladder cancer happened four to eight weeks after the first lived longest; rushing back in under four weeks, or waiting beyond eight, went with shorter survival.","summary":"Cohort of 207 patients with incidentally discovered gallbladder cancer (46 percent of 449 gallbladder cancers) who underwent reoperation at 10 US academic institutions between 2000 and 2014, grouped by interval from cholecystectomy: under 4 weeks (25 patients, 12 percent), 4 to 8 weeks (91, 44 percent) and over 8 weeks (91, 44 percent). Groups were similar in demographics, extent of resection, residual disease, T stage, margins, nodes and complications. Median overall survival was 17.4, 40.4 and 22.4 months (log-rank p=0.03). On multivariable analysis the early (hazard ratio 2.63, 95 percent CI 1.25 to 5.54) and late (2.07, 1.17 to 3.66) intervals, R2 resection (2.69) and advanced T stage (1.85) remained associated with death.","asOf":"2026-09-24","links":[{"label":"JAMA Surg 2017","url":"https://doi.org/10.1001/jamasurg.2016.3642"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27784058/"}],"tags":["gallbladder-evidence"],"related":["paper-selvakumar-revision-surgery-timing-ipd-meta-analysis-hpb-2026"],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["incidental-gallbladder-cancer","radical-cholecystectomy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"JAMA Surgery","year":2017,"doi":"10.1001/jamasurg.2016.3642","pmid":"27784058","authors":"Ethun CG, Postlewait LM, Le N, et al.","paperType":"observational","findings":["Median overall survival 40.4 months for re-resection at 4 to 8 weeks vs 17.4 months under 4 weeks and 22.4 months over 8 weeks (p=0.03).","Multivariable hazard ratio 2.63 (95 percent CI 1.25 to 5.54) for under 4 weeks and 2.07 (1.17 to 3.66) for over 8 weeks, against 4 to 8 weeks."],"whatItMeans":"The origin of the widely quoted four-to-eight-week window for re-resection. A 2026 individual patient data meta-analysis found no survival difference by timing, so the window is a reasonable planning target rather than a proven rule.","caveats":["Retrospective; timing may reflect referral patterns and disease behaviour rather than cause survival.","Only 25 patients in the under-4-weeks group."],"changedPractice":true,"participants":207},{"id":"paper-brown-jama-oncol","kind":"paper","name":"Association of the Extent of Resection With Survival in Glioblastoma: A Systematic Review and Meta-analysis","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 27310651 and published in JAMA Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Importance: Glioblastoma multiforme (GBM) remains almost invariably fatal despite optimal surgical and medical therapy. The association between the extent of tumor resection (EOR) and outcome remains undefined, notwithstanding many relevant studies.\n\nObjective: To determine whether greater EOR is associated with improved 1- and 2-year overall survival and 6-month and 1-year progression-free survival in patients with GBM.\n\nData sources: Pubmed, CINAHL, and Web of Science (January 1, 1966, to December 1, 2015) were systematically reviewed with librarian guidance. Additional articles were included after consultation with experts and evaluation of bibliographies. Articles were collected from January 15 to December 1, 2015.\n\nStudy selection: Studies of adult patients with newly diagnosed supratentorial GBM comparing various EOR and presenting objective overall or progression-free survival data were included. Pediatric studies were excluded.\n\nData extraction and synthesis: Data were extracted from the text of articles or the Kaplan-Meier curves independently by investigators who were blinded to each other's results. Data were analyzed to assess mortality after gross total resection (GTR), subtotal resection (STR), and biopsy. The body of evidence was evaluated according to Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria and PRISMA guidelines.\n\nMain outcome and measures: Relative risk (RR) for mortality at 1 and 2 years and progression at 6 months and 1 year.\n\nResults: The search produced 37 studies suitable for inclusion (41 117 unique patients). The meta-analysis revealed decreased mortality for GTR compared with STR at 1 year (RR, 0.62; 95% CI, 0.56-0.69; P <.001; number needed to treat [NNT], 9) and 2 years (RR, 0.84; 95% CI, 0.79-0.89; P <.001; NNT, 17). The 1-year risk for mortality for STR compared with biopsy was reduced significantly (RR, 0.85; 95% CI, 0.80-0.91; P <.001). The risk for mortality was similarly decreased for any resection compared with biopsy at 1 year (RR, 0.77; 95% CI, 0.71-0.84; P <.001; NNT, 21) and 2 years (RR, 0.94; 95% CI, 0.89-1.00; P =.04; NNT, 593). The likelihood of disease progression was decreased with GTR compared with STR at 6 months (RR, 0.72; 95% CI, 0.48-1.09; P =.12; NNT, 14) and 1 year (RR, 0.66; 95% CI, 0.43-0.99; P <.001; NNT, 26). The quality of the body of evidence by the GRADE criteria was moderate to low.\n\nConclusion and relevance: This analysis represents the largest systematic review and only quantitative systematic review to date performed on this subject. Compared with STR, GTR substantially improves overall and progression-free survival, but the quality of the supporting evidence is moderate to low.\n\nIndexed on Europe PMC as PubMed record 27310651 (DOI 10.1001/jamaoncol.2016.1373). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA Oncol 2016","url":"https://doi.org/10.1001/jamaoncol.2016.1373"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27310651/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27310651"}],"tags":["europepmc-ingest"],"related":["extent-of-resection"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2016,"doi":"10.1001/jamaoncol.2016.1373","pmid":"27310651","authors":"Brown TJ, Brennan MC, Li M, et al.","paperType":"meta-analysis","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-keynote-042-tmb-mutations-ann-oncol-2023","kind":"paper","name":"Associations of tissue tumour mutational burden and mutational status with clinical outcomes in KEYNOTE-042","aka":[],"tldr":"In a large randomised trial of immunotherapy given alone, patients whose tumours carried more mutations did better on the drug than on chemotherapy, and patients with fewer mutations did not.","summary":"This retrospective exploratory analysis of the phase 3 KEYNOTE-042 trial assessed tissue tumour mutational burden and STK11, KEAP1 and KRAS mutations, determined by whole-exome sequencing of tumour and matched normal DNA, in patients with PD-L1-positive advanced non-small-cell lung cancer without EGFR or ALK alterations. Of 793 patients, 345, 43.5%, had a burden of 175 or more mutations per exome. No association was observed between PD-L1 expression and burden. Continuous burden was associated with improved overall and progression-free survival among patients receiving pembrolizumab but not chemotherapy. A burden of 175 or more favoured pembrolizumab over chemotherapy (overall survival hazard ratio 0.62) where a burden below 175 did not (1.09). Improved overall survival with pembrolizumab was seen regardless of STK11, KEAP1 or KRAS mutation status.","asOf":"2026-09-25","links":[{"label":"Mok et al., Ann Oncol 2023: tissue tumour mutational burden and mutation status in KEYNOTE-042 (793 patients)","url":"https://doi.org/10.1016/j.annonc.2023.01.011"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36709038/"}],"tags":[],"related":["tmb-high","pd-l1-tps"],"cancers":["nsclc"],"sections":[],"technologies":["tmb-testing","wes-wgs","checkpoint-inhibitor"],"targets":["pdl1","pd1","stk11","keap1","kras"],"drugs":["pembrolizumab"],"companies":[],"institutions":[],"pathways":["pd1-checkpoint","cancer-immunity-cycle"],"terms":["tmb","stk11-keap1"],"trials":[],"people":["tony-mok"],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2023,"doi":"10.1016/j.annonc.2023.01.011","pmid":"36709038","authors":"Mok TSK, Lopes G, Cho BC, et al.","paperType":"rct","findings":["Tissue burden of 175 or more mutations per exome identified benefit from pembrolizumab monotherapy (hazard ratio 0.62) where lower burden did not (1.09).","Burden and PD-L1 expression were uncorrelated.","Continuous burden tracked outcome on pembrolizumab and not on chemotherapy.","STK11, KEAP1 and KRAS status did not change the pembrolizumab benefit in this setting."],"whatItMeans":"It is the positive half of the tumour mutational burden story and it applies only to single-agent immunotherapy, which is the setting fewest patients are treated in.","caveats":["Retrospective exploratory analysis of a randomised trial with a prespecified cut point but no prospective validation.","Whole-exome sequencing is not the assay used in practice.","Only PD-L1-positive patients were enrolled."],"changedPractice":false,"participants":793},{"id":"paper-keynote-189-407-tmb-jtocrr-2023","kind":"paper","name":"Associations of tissue tumour mutational burden and mutational status with clinical outcomes with pembrolizumab plus chemotherapy versus chemotherapy for metastatic non-small-cell lung cancer","aka":[],"tldr":"In the two trials that established the treatment most patients with lung cancer actually receive, immunotherapy added to chemotherapy, the number of mutations in the tumour predicted nothing at all.","summary":"A retrospective exploratory analysis of the phase 3 KEYNOTE-189 (non-squamous) and KEYNOTE-407 (squamous) trials evaluated tissue tumour mutational burden and STK11, KEAP1 and KRAS mutation status, assessed by whole-exome sequencing with matched normal DNA, as biomarkers for pembrolizumab plus platinum-based chemotherapy. Among patients with evaluable data (293 in KEYNOTE-189 and 312 in KEYNOTE-407), no association was found between continuous burden and overall or progression-free survival for the pembrolizumab combination or for placebo plus chemotherapy in either histology. Pembrolizumab combination improved outcomes both above and below the prespecified cut point of 175 mutations per exome, and treatment outcomes were similar regardless of KEAP1, STK11 or KRAS mutation status.","asOf":"2026-09-25","links":[{"label":"Garassino et al., JTO Clin Res Rep 2023: tissue tumour mutational burden with pembrolizumab plus chemotherapy in KEYNOTE-189 and KEYNOTE-407","url":"https://doi.org/10.1016/j.jtocrr.2022.100431"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36793385/"}],"tags":[],"related":["tmb-high"],"cancers":["nsclc"],"sections":[],"technologies":["tmb-testing","wes-wgs","checkpoint-inhibitor"],"targets":["pdl1","pd1","stk11","keap1","kras"],"drugs":["pembrolizumab"],"companies":[],"institutions":[],"pathways":["pd1-checkpoint","cancer-immunity-cycle"],"terms":["tmb","stk11-keap1"],"trials":[],"people":["luis-paz-ares"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"JTO Clinical and Research Reports","year":2023,"doi":"10.1016/j.jtocrr.2022.100431","pmid":"36793385","authors":"Garassino MC, Gadgeel S, Novello S, et al.","paperType":"rct","findings":["No association between continuous tissue burden and survival with pembrolizumab plus chemotherapy in either histology.","Benefit was seen above and below the 175 mutations per exome cut point alike.","STK11, KEAP1 and KRAS status did not change the benefit of the combination.","The same held for the chemotherapy-alone arms."],"whatItMeans":"This is the result that ended tumour mutational burden as a practical selector in lung cancer: in the regimen most patients receive, it selects nobody, and neither do the co-mutations most often quoted as reasons to withhold immunotherapy.","caveats":["Exploratory analyses with sequencing available for roughly half of each trial population.","Whole-exome burden, not the panel-based measure used in clinics.","A negative finding within trials that were positive overall, so it cannot exclude small effects."],"changedPractice":false,"participants":605},{"id":"paper-lee-biol-blood-marrow-transplant","kind":"paper","name":"ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 30592986 and published in Biology of blood and marrow transplantation; the citing page links this DOI, which is how the record was matched.","summary":"Chimeric antigen receptor (CAR) T cell therapy is rapidly emerging as one of the most promising therapies for hematologic malignancies. Two CAR T products were recently approved in the United States and Europe for the treatment ofpatients up to age 25years with relapsed or refractory B cell acute lymphoblastic leukemia and/or adults with large B cell lymphoma. Many more CAR T products, as well as other immunotherapies, including various immune cell- and bi-specific antibody-based approaches that function by activation of immune effector cells, are in clinical development for both hematologic and solid tumor malignancies. These therapies are associated with unique toxicities of cytokine release syndrome (CRS) and neurologic toxicity. The assessment and grading of these toxicities vary considerably across clinical trials and across institutions, making it difficult to compare the safety of different products and hindering the ability to develop optimal strategies for management of these toxicities. Moreover, some aspects of these grading systems can be challenging to implement across centers. Therefore, in an effort to harmonize the definitions and grading systems for CRS and neurotoxicity, experts from all aspects of the field met on June 20 and 21, 2018, at a meeting supported by the American Society for Transplantation and Cellular Therapy (ASTCT; formerly American Society for Blood and Marrow Transplantation, ASBMT) in Arlington, VA. Here we report the consensus recommendations of that group and propose new definitions and grading for CRS and neurotoxicity that are objective, easy to apply, and ultimately more accurately categorize the severity of these toxicities. The goal is to provide a uniform consensus grading system for CRS and neurotoxicity associated with immune effector cell therapies, for use across clinical trials and in the postapproval clinical setting.\n\nIndexed on Europe PMC as PubMed record 30592986 (DOI 10.1016/j.bbmt.2018.12.758). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Biol Blood Marrow Transplant 2019","url":"https://doi.org/10.1016/j.bbmt.2018.12.758"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30592986/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30592986"}],"tags":["europepmc-ingest"],"related":["icans"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Biology of blood and marrow transplantation","year":2019,"doi":"10.1016/j.bbmt.2018.12.758","pmid":"30592986","authors":"Lee DW, Santomasso BD, Locke FL, et al.","paperType":"review","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-impassion130-n-engl-j-med-2018","kind":"paper","name":"Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer","aka":[],"tldr":"Published report from the IMpassion130 trial registered as NCT02425891, in New England Journal of Medicine (2018), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Unresectable locally advanced or metastatic triple-negative (hormone-receptor-negative and human epidermal growth factor receptor 2 [HER2]-negative) breast cancer is an aggressive disease with poor outcomes. Nanoparticle albumin-bound (nab)-paclitaxel may enhance the anticancer activity of atezolizumab.\n\nMethods: In this phase 3 trial, we randomly assigned (in a 1:1 ratio) patients with untreated metastatic triple-negative breast cancer to receive atezolizumab plus nab-paclitaxel or placebo plus nab-paclitaxel; patients continued the intervention until disease progression or an unacceptable level of toxic effects occurred. Stratification factors were the receipt or nonreceipt of neoadjuvant or adjuvant taxane therapy, the presence or absence of liver metastases at baseline, and programmed death ligand 1 (PD-L1) expression at baseline (positive vs. negative). The two primary end points were progression-free survival (in the intention-to-treat population and PD-L1-positive subgroup) and overall survival (tested in the intention-to-treat population; if the finding was significant, then it would be tested in the PD-L1-positive subgroup).\n\nResults: Each group included 451 patients (median follow-up, 12.9 months). In the intention-to-treat analysis, the median progression-free survival was 7.2 months with atezolizumab plus nab-paclitaxel, as compared with 5.5 months with placebo plus nab-paclitaxel (hazard ratio for progression or death, 0.80; 95% confidence interval [CI], 0.69 to 0.92; P=0.002); among patients with PD-L1-positive tumors, the median progression-free survival was 7.5 months and 5.0 months, respectively (hazard ratio, 0.62; 95% CI, 0.49 to 0.78; P<0.001). In the intention-to-treat analysis, the median overall survival was 21.3 months with atezolizumab plus nab-paclitaxel and 17.6 months with placebo plus nab-paclitaxel (hazard ratio for death, 0.84; 95% CI, 0.69 to 1.02; P=0.08); among patients with PD-L1-positive tumors, the median overall survival was 25.0 months and 15.5 months, respectively (hazard ratio, 0.62; 95% CI, 0.45 to 0.86). No new adverse effects were identified. Adverse events that led to the discontinuation of any agent occurred in 15.9% of the patients who received atezolizumab plus nab-paclitaxel and in 8.2% of those who received placebo plus nab-paclitaxel.\n\nConclusions: Atezolizumab plus nab-paclitaxel prolonged progression-free survival among patients with metastatic triple-negative breast cancer in both the intention-to-treat population and the PD-L1-positive subgroup. Adverse events were consistent with the known safety profiles of each agent. (Funded by F. Hoffmann-La Roche/Genentech; IMpassion130 ClinicalTrials.gov number, NCT02425891.).\n\nIndexed on Europe PMC as PubMed record 30345906 (DOI 10.1056/nejmoa1809615). Its abstract cites the registry id NCT02425891, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2018","url":"https://doi.org/10.1056/nejmoa1809615"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30345906/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30345906"},{"label":"ClinicalTrials.gov NCT02425891","url":"https://clinicaltrials.gov/study/NCT02425891"}],"tags":["europepmc-ingest"],"related":["pd-l1-ic-score"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["ventana-pd-l1-sp142"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["impassion130"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2018,"doi":"10.1056/nejmoa1809615","pmid":"30345906","authors":"Schmid P, Adams S, Rugo HS, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02425891 with the most citations, so it is the natural first reading for anyone following the IMpassion130 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-atezolizumab-alveolar-soft-part-sarcoma-chen-nejm-2023","kind":"paper","name":"Atezolizumab for advanced alveolar soft part sarcoma","aka":[],"tldr":"The PD-L1 antibody atezolizumab shrank tumours in about a quarter of patients with advanced alveolar soft part sarcoma, with responses lasting years in a disease resistant to chemotherapy, and became the first approved treatment for this sarcoma.","summary":"Phase 2 study of 52 patients aged 2 and older with advanced alveolar soft part sarcoma treated with atezolizumab every three weeks.\n\nObjective response was 24 percent (37 percent in an updated analysis with longer follow-up), with a median duration of response of over 16 months and stable disease in most others; toxicity was typical of PD-L1 blockade and low grade.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2023","url":"https://doi.org/10.1056/NEJMoa2303383"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37672694/"}],"tags":[],"related":[],"cancers":["alveolar-soft-part-sarcoma"],"sections":[],"technologies":[],"targets":[],"drugs":["atezolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["alice-chen"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/NEJMoa2303383","pmid":"37672694","authors":"Chen AP, Sharon E, O'Sullivan-Coyne G, et al.","paperType":"observational","findings":["Objective response 24 percent (37 percent with longer follow-up).","Median duration of response 16.5 months; many responses ongoing."],"whatItMeans":"Atezolizumab is the first-line systemic treatment for advanced alveolar soft part sarcoma, a rare, slow-growing but ultimately metastatic sarcoma of young adults for which chemotherapy never worked.","caveats":["Single-arm study in a rare disease; responses can take many months to appear."],"changedPractice":true,"participants":52},{"id":"paper-herbst-impower110-atezolizumab-pd-l1-nejm-2020","kind":"paper","name":"Atezolizumab for first-line treatment of PD-L1-selected patients with NSCLC","aka":[],"tldr":"In the patients whose tumours showed the most PD-L1, immunotherapy alone gave a median survival of 20.2 months against 13.1 on chemotherapy, with far fewer severe side effects.","summary":"Herbst, Giaccone, de Marinis and colleagues randomised 572 patients with metastatic non-squamous or squamous non-small-cell lung cancer, untreated and with PD-L1 expression on at least 1 percent of tumour cells or tumour-infiltrating immune cells by the SP142 assay, 1 to 1 between atezolizumab and platinum-based chemotherapy. Overall survival was tested hierarchically by PD-L1 status among patients whose tumours were EGFR and ALK wild-type.\n\nIMpower110 is the trial that generalised KEYNOTE-024's result to a second drug and a second assay, and in doing so exposed the assay problem: SP142, 22C3 and SP263 score different things and select different patients, so PD-L1 high means different populations in different trials.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2020","url":"https://doi.org/10.1056/NEJMoa1917346"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32997907/"},{"label":"ClinicalTrials.gov NCT02409342","url":"https://clinicaltrials.gov/study/NCT02409342"}],"tags":["lung-evidence"],"related":["paper-keynote-024-nejm-2016","paper-keynote-042-lancet-2019","paper-keynote-001-pembrolizumab-nsclc-nejm-2015","immunotherapy-roadmap","pd-l1-tc-score","pd-l1-ic-score","tmb-high"],"cancers":["lung-cancer","nsclc","pdl1-high-nsclc"],"sections":["immunotherapy","diagnostics"],"technologies":["ihc","checkpoint-inhibitor","histopathology-ihc"],"targets":["pd1"],"drugs":["atezolizumab","pembrolizumab","carboplatin","cisplatin","ventana-pd-l1-sp142"],"companies":["roche-genentech"],"institutions":[],"pathways":["immune-checkpoint","pd1-checkpoint"],"terms":["pdl1","tps","tmb","ihc"],"trials":[],"people":["roy-herbst"],"bottlenecks":["b-immunotherapy-response","b-biomarker-validation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2020,"doi":"10.1056/NEJMoa1917346","pmid":"32997907","authors":"Herbst RS, Giaccone G, de Marinis F, et al.","paperType":"rct","findings":["In EGFR and ALK wild-type patients with the highest PD-L1 expression (205 patients), median overall survival was 20.2 months with atezolizumab against 13.1 months with chemotherapy: hazard ratio for death 0.59 (P equals 0.01).","Adverse events occurred in 90.2 percent of patients on atezolizumab and 94.7 percent on chemotherapy.","Grade 3 or 4 adverse events occurred in 30.1 percent on atezolizumab and 52.5 percent on chemotherapy.","Overall and progression-free survival favoured atezolizumab in the subgroups with high blood-based tumour mutational burden."],"whatItMeans":"For the minority of patients whose tumours express a lot of PD-L1, a single antibody outperforms chemotherapy and is far easier to take. The word minority is the point: the same drug in the same disease at lower PD-L1 gives much less.","caveats":["The headline result is in 205 of 572 enrolled patients, the highest PD-L1 subgroup within the wild-type population; the hierarchical testing stopped there.","SP142 is not interchangeable with the 22C3 assay used in the KEYNOTE trials, so eligibility does not transfer between them.","Blood-based tumour mutational burden was exploratory and has not become a routine selection tool."],"changedPractice":true,"participants":572},{"id":"paper-raghav-atezolizumab-bevacizumab-peritoneal-mesothelioma-cancer-discov-2021","kind":"paper","name":"Atezolizumab plus bevacizumab in advanced malignant peritoneal mesothelioma","aka":[],"tldr":"In a small trial combining PD-L1 and VEGF blockade, four in ten patients with previously treated peritoneal mesothelioma responded, with responses lasting well over a year, the first dedicated prospective evidence for immunotherapy in this rare disease.","summary":"Single-centre phase 2 study of 20 patients with advanced unresectable peritoneal mesothelioma progressing after platinum-pemetrexed, treated with atezolizumab and bevacizumab.\n\nObjective response was 40 percent with a median duration of response of 12.8 months, one-year progression-free survival 61 percent and one-year overall survival 85 percent; biomarker analyses linked response to epithelial-mesenchymal transition and immune features.","asOf":"2026-09-17","links":[{"label":"Cancer Discov 2021","url":"https://doi.org/10.1158/2159-8290.CD-21-0331"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34261675/"}],"tags":[],"related":[],"cancers":["peritoneal-mesothelioma"],"sections":[],"technologies":[],"targets":[],"drugs":["atezolizumab","bevacizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-discovery"],"dependsOn":[],"notes":[],"journal":"Cancer Discovery","year":2021,"doi":"10.1158/2159-8290.CD-21-0331","pmid":"34261675","authors":"Raghav K, Liu S, Overman MJ, et al.","paperType":"observational","findings":["Objective response 40 percent; median duration of response 12.8 months.","One-year overall survival 85 percent."],"whatItMeans":"Immunotherapy combinations, largely extrapolated from pleural trials, now have direct supporting data in peritoneal mesothelioma and are used after or instead of chemotherapy in unresectable disease.","caveats":["Twenty patients at a single centre; no comparator."],"changedPractice":false,"participants":20},{"id":"paper-atomic-n-engl-j-med-2026","kind":"paper","name":"Atezolizumab plus FOLFOX for Stage III Mismatch Repair-Deficient Colon Cancer","aka":[],"tldr":"Published report from the ATOMIC trial registered as NCT02912559, in New England Journal of Medicine (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Standard adjuvant chemotherapy for stage III colon cancer consists of a fluoropyrimidine-plus-oxaliplatin regimen. Whether the addition of atezolizumab (an anti-programmed death ligand 1 agent) to a modified FOLFOX6 regimen (fluorouracil, oxaliplatin, and leucovorin; called mFOLFOX6) would improve outcomes in patients with stage III colon cancer with mismatch repair-deficient (dMMR) status is unclear.\n\nMethods: In a phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with resected stage III dMMR tumors to receive either adjuvant atezolizumab plus mFOLFOX6 for 6 months, with atezolizumab continued as monotherapy (for a total of 12 months of therapy), or mFOLFOX6 alone for 6 months. The primary end point was disease-free survival. Secondary end points were overall survival and the adverse-event profile.\n\nResults: A total of 355 patients were assigned to receive atezolizumab plus mFOLFOX6 and 357 to receive mFOLFOX6 alone. The median age of the patients was 64 years, 55.1% were women, and 53.9% had tumors that were T4, N2, or both (indicating high risk). At a median follow-up of 40.9 months, the 3-year disease-free survival was 86.3% (95% confidence interval [CI], 81.8 to 89.8) in the atezolizumab-mFOLFOX6 group, as compared with 76.2% (95% CI, 70.9 to 80.6) in the mFOLFOX6 group (hazard ratio for disease recurrence or death, 0.50; 95% CI, 0.35 to 0.73; P<0.001). Adverse events of grade 3 or 4 occurred in 84.1% of the patients who received atezolizumab plus mFOLFOX6 and in 71.9% of those who received mFOLFOX6 alone.\n\nConclusions: The addition of atezolizumab to mFOLFOX6 significantly improved disease-free survival among patients with stage III dMMR colon cancer. (Funded by the National Cancer Institute of the National Institutes of Health and Genentech; ATOMIC ClinicalTrials.gov number, NCT02912559.).\n\nIndexed on Europe PMC as PubMed record 41880612 (DOI 10.1056/nejmoa2507874). Its abstract cites the registry id NCT02912559, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2026","url":"https://doi.org/10.1056/nejmoa2507874"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41880612/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41880612"},{"label":"ClinicalTrials.gov NCT02912559","url":"https://clinicaltrials.gov/study/NCT02912559"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["atomic"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2026,"doi":"10.1056/nejmoa2507874","pmid":"41880612","authors":"Sinicrope FA, Ou FS, Arnold D, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02912559 with the most citations, so it is the natural first reading for anyone following the ATOMIC trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-impassion130-lancet-oncol-2020-update","kind":"paper","name":"Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial","aka":[],"tldr":"Later report from the IMpassion130 trial registered as NCT02425891, in The Lancet Oncology (2020); its title describes an updated or longer-term analysis.","summary":"Background: Immunotherapy in combination with chemotherapy has shown promising efficacy across many different tumour types. We report the prespecified second interim overall survival analysis of the phase 3 IMpassion130 study assessing the efficacy and safety of atezolizumab plus nab-paclitaxel in patients with unresectable, locally advanced or metastatic triple-negative breast cancer.\n\nMethods: In this randomised, placebo-controlled, double-blind, phase 3 trial, done in 246 academic centres and community oncology practices in 41 countries, patients aged 18 years or older, with previously untreated, histologically documented, locally advanced or metastatic triple-negative breast cancer, and Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible. Patients were randomly assigned (1:1) using a permuted block method (block size of four) and an interactive voice-web response system. Randomisation was stratified by previous taxane use, liver metastases, and PD-L1 expression on tumour-infiltrating immune cells. Patients received atezolizumab 840 mg or matching placebo intravenously on day 1 and day 15 of every 28-day cycle and nab-paclitaxel 100 mg/m 2 of body surface area intravenously on days 1, 8, and 15 until progression or unacceptable toxicity. Investigators, patients, and the funder were masked to treatment assignment. Coprimary endpoints were investigator-assessed progression-free survival per Response Evaluation Criteria in Solid Tumors version 1.1 and overall survival, assessed in the intention-to-treat population and in patients with PD-L1 immune cell-positive tumours (tumours with ≥1% PD-L1 expression). The final progression-free survival results were previously reported at the first interim overall survival analysis. The prespecified statistical testing hierarchy meant that overall survival in the subgroup of PD-L1 immune cell-positive patients could only be formally tested if overall survival was significantly different between the treatment groups in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02425891.\n\nFindings: Between June 23, 2015, and May 24, 2017, 902 patients were enrolled, of whom 451 were randomly assigned to receive atezolizumab plus nab-paclitaxel and 451 were assigned to receive placebo plus nab-paclitaxel (the intention-to-treat population). Six patients from each group did not receive treatment. At the second interim analysis (data cutoff Jan 2, 2019), median follow-up was 18·5 months (IQR 9·6-22·8) in the atezolizumab group and 17·5 months (8·4-22·4) in the placebo group. Median overall survival in the intention-to-treat patients was 21·0 months (95% CI 19·0-22·6) with atezolizumab and 18·7 months (16·9-20·3) with placebo (stratified hazard ratio [HR] 0·86, 95% CI 0·72-1·02, p=0·078). In the exploratory overall survival analysis in patients with PD-L1 immune cell-positive tumours, median overall survival was 25·0 months (95% CI 19·6-30·7) with atezolizumab versus 18·0 months (13·6-20·1) with placebo (stratified HR 0·71, 0·54-0·94]). at Sept 3, 2018 (the date up to which updated safety data were available), the most common grade 3-4 adverse events were neutropenia (38 [8%] of 453 patients in the atezolizumab group vs 36 [8%] of 437 patients in the placebo group), peripheral neuropathy (25 [6%] vs 12 [3%]), decreased neutrophil count (22 [5%] vs 16 [4%]), and fatigue (17 [4%] vs 15 [3%]). Treatment-related deaths occurred in two (<1%) patients in the atezolizumab group (autoimmune hepatitis related to atezolizumab [n=1] and septic shock related to nab-paclitaxel [n=1]) and one (<1%) patient in the placebo group (hepatic failure). No new treatment-related deaths have been reported since the primary clinical data cutoff date (April 17, 2018).\n\nInterpretation: Consistent with the first interim analysis, this second interim overall survival analysis of IMpassion130 indicates no significant difference in overall survival between the treatment groups in the intention-to-treat population but suggests a clinically meaningful overall survival benefit with atezolizumab plus nab-paclitaxel in patients with PD-L1 immune cell-positive disease. However, this positive result could not be formally tested due to the prespecified statistical testing hierarchy. For patients with PD-L1 immune cell-positive metastatic triple-negative breast cancer, atezolizumab plus nab-paclitaxel is an important therapeutic option in a disease with high unmet need.\n\nFunding: F Hoffmann-La Roche and Genentech.\n\nIndexed on Europe PMC as PubMed record 31786121 (DOI 10.1016/s1470-2045(19)30689-8). Its abstract cites the registry id NCT02425891, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2020","url":"https://doi.org/10.1016/s1470-2045(19)30689-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31786121/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31786121"},{"label":"ClinicalTrials.gov NCT02425891","url":"https://clinicaltrials.gov/study/NCT02425891"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["impassion130"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2020,"doi":"10.1016/s1470-2045(19)30689-8","pmid":"31786121","authors":"Schmid P, Rugo HS, Adams S, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the IMpassion130 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-friedman-cancer-discov","kind":"paper","name":"Atezolizumab Treatment of Tumors with High Tumor Mutational Burden from MyPathway, a Multicenter, Open-Label, Phase IIa Multiple Basket Study","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 34876409 and published in Cancer Discovery; the citing page links this DOI, which is how the record was matched.","summary":"High tumor mutational burden (TMB-H) correlates with improved immunotherapy response. We assessed atezolizumab 1,200 mg every 3 weeks for TMB-H tumors from MyPathway (NCT02091141), a phase IIa multibasket study. One hundred twenty-one patients had advanced solid tumors with TMB ≥10 mut/Mb by any Clinical Laboratory Improvement Amendments (CLIA)-certified assay. The preplanned primary endpoint was objective response rate (ORR) in patients with TMB ≥16 mut/Mb tumors by FoundationOne TMB testing [F1(CDx)]. Patients with F1(CDx) TMB ≥10 and <16 mut/Mb were also evaluated. Ninety patients with 19 tumor types and F1(CDx) TMB ≥10 mut/Mb were efficacy evaluable. In 42 patients with F1(CDx) TMB ≥16 mut/Mb, confirmed ORR was 38.1% [16/42; 95% confidence interval (CI), 23.6-54.4], and disease control rate was 61.9% (26/42; 95% CI, 45.6-76.4) versus 2.1% (1/48; 95% CI, 0.1-11.1) and 22.9% (11/48; 95% CI, 12.0-37.3) for 48 patients with TMB ≥10 and <16 mut/Mb. Responses were observed in nine different tumor types (47%; 9/19).\n\nSignificance: Atezolizumab monotherapy had promising, durable clinical activity across a variety of advanced solid tumor types in patients with TMB ≥16 mut/Mb tumors lacking other suitable treatment options and who were immunotherapy-naïve at enrollment, regardless of microsatellite instability status. Limited activity was observed in tumors with TMB ≥10 and <16 mut/Mb. See related commentary by Maron and Klempner, p. 602. This article is highlighted in the In This Issue feature, p. 587.\n\nIndexed on Europe PMC as PubMed record 34876409 (DOI 10.1158/2159-8290.cd-21-0450). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer Discov 2022","url":"https://doi.org/10.1158/2159-8290.cd-21-0450"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34876409/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34876409"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["mypathway"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-discovery"],"dependsOn":[],"notes":[],"journal":"Cancer Discovery","year":2022,"doi":"10.1158/2159-8290.cd-21-0450","pmid":"34876409","authors":"Friedman CF, Hainsworth JD, Kurzrock R, et al.","paperType":"observational","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nct03178552-nat-med-2022","kind":"paper","name":"Atezolizumab versus chemotherapy in advanced or metastatic NSCLC with high blood-based tumor mutational burden: primary analysis of BFAST cohort C randomized phase 3 trial","aka":[],"tldr":"Published report from the B-FAST trial registered as NCT03178552, in Nature Medicine (2022), chosen as the most cited paper whose own text cites the registry id.","summary":"Tumor mutational burden (TMB) is being explored as a predictive biomarker for cancer immunotherapy outcomes in non-small cell lung cancer. BFAST (NCT03178552)-an open-label, global, multicohort trial-evaluated the safety and efficacy of first-line targeted therapies or immunotherapy in patients with unresectable Stage IIIB or IV advanced or metastatic non-small cell lung cancer who were selected for biomarker status using blood-based targeted next-generation sequencing. In the Phase 3 cohort C evaluating blood-based (b)TMB as a biomarker of atezolizumab efficacy, patients with bTMB of ≥10 (N = 471) were randomized 1:1 to receive atezolizumab or platinum-based chemotherapy per local standard of care. Cohort C did not meet its primary endpoint of investigator-assessed progression-free survival in the population with bTMB of ≥16 (hazard ratio, 0.77; 95% confidence interval: 0.59, 1.00; P = 0.053). Adverse events leading to treatment withdrawal occurred in 10% of patients in the atezolizumab arm and 20% in the chemotherapy arm. Adverse events of special interest occurred in 42% of patients in the atezolizumab arm and 26% in the chemotherapy arm. A prespecified exploratory analysis compared the bTMB clinical trial assay with the FoundationOne Liquid Companion Diagnostic assay and showed high concordance between assays. Additional exploration of bTMB to identify optimal cutoffs, confounding factors, assay improvements or cooperative biomarkers is warranted.\n\nIndexed on Europe PMC as PubMed record 35995953 (DOI 10.1038/s41591-022-01933-w). Its abstract cites the registry id NCT03178552, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Nat Med 2022","url":"https://doi.org/10.1038/s41591-022-01933-w"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35995953/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35995953"},{"label":"ClinicalTrials.gov NCT03178552","url":"https://clinicaltrials.gov/study/NCT03178552"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct03178552"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2022,"doi":"10.1038/s41591-022-01933-w","pmid":"35995953","authors":"Peters S, Dziadziuszko R, Morabito A, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03178552 with the most citations, so it is the natural first reading for anyone following the B-FAST trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-keunchil-park-lancet-2016","kind":"paper","name":"Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial","aka":[],"tldr":"Paper by Keunchil Park indexed on Europe PMC as PubMed record 26970723, in The Lancet (2016), one of the most cited records naming an author with this name at Samsung Medical Center.","summary":"Background: Outcomes are poor for patients with previously treated, advanced or metastatic non-small-cell lung cancer (NSCLC). The anti-programmed death ligand 1 (PD-L1) antibody atezolizumab is clinically active against cancer, including NSCLC, especially cancers expressing PD-L1 on tumour cells, tumour-infiltrating immune cells, or both. We assessed efficacy and safety of atezolizumab versus docetaxel in previously treated NSCLC, analysed by PD-L1 expression levels on tumour cells and tumour-infiltrating immune cells and in the intention-to-treat population.\n\nMethods: In this open-label, phase 2 randomised controlled trial, patients with NSCLC who progressed on post-platinum chemotherapy were recruited in 61 academic medical centres and community oncology practices across 13 countries in Europe and North America. Key inclusion criteria were Eastern Cooperative Oncology Group performance status 0 or 1, measurable disease by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1), and adequate haematological and end-organ function. Patients were stratified by PD-L1 tumour-infiltrating immune cell status, histology, and previous lines of therapy, and randomly assigned (1:1) by permuted block randomisation (with a block size of four) using an interactive voice or web system to receive intravenous atezolizumab 1200 mg or docetaxel 75 mg/m(2) once every 3 weeks. Baseline PD-L1 expression was scored by immunohistochemistry in tumour cells (as percentage of PD-L1-expressing tumour cells TC3≥50%, TC2≥5% and <50%, TC1≥1% and <5%, and TC0<1%) and tumour-infiltrating immune cells (as percentage of tumour area: IC3≥10%, IC2≥5% and <10%, IC1≥1% and <5%, and IC0<1%). The primary endpoint was overall survival in the intention-to-treat population and PD-L1 subgroups at 173 deaths. Biomarkers were assessed in an exploratory analysis. We assessed safety in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT01903993.\n\nFindings: Patients were enrolled between Aug 5, 2013, and March 31, 2014. 144 patients were randomly allocated to the atezolizumab group, and 143 to the docetaxel group. 142 patients received at least one dose of atezolizumab and 135 received docetaxel. Overall survival in the intention-to-treat population was 12·6 months (95% CI 9·7-16·4) for atezolizumab versus 9·7 months (8·6-12·0) for docetaxel (hazard ratio [HR] 0·73 [95% CI 0·53-0·99]; p=0·04). Increasing improvement in overall survival was associated with increasing PD-L1 expression (TC3 or IC3 HR 0·49 [0·22-1·07; p=0·068], TC2/3 or IC2/3 HR 0·54 [0·33-0·89; p=0·014], TC1/2/3 or IC1/2/3 HR 0·59 [0·40-0·85; p=0·005], TC0 and IC0 HR 1·04 [0·62-1·75; p=0·871]). In our exploratory analysis, patients with pre-existing immunity, defined by high T-effector-interferon-γ-associated gene expression, had improved overall survival with atezolizumab. 11 (8%) patients in the atezolizumab group discontinued because of adverse events versus 30 (22%) patients in the docetaxel group. 16 (11%) patients in the atezolizumab group versus 52 (39%) patients in the docetaxel group had treatment-related grade 3-4 adverse events, and one (<1%) patient in the atezolizumab group versus three (2%) patients in the docetaxel group died from a treatment-related adverse event.\n\nInterpretation: Atezolizumab significantly improved survival compared with docetaxel in patients with previously treated NSCLC. Improvement correlated with PD-L1 immunohistochemistry expression on tumour cells and tumour-infiltrating immune cells, suggesting that PD-L1 expression is predictive for atezolizumab benefit. Atezolizumab was well tolerated, with a safety profile distinct from chemotherapy.\n\nFunding: F Hoffmann-La Roche/Genentech Inc.\n\nIndexed on Europe PMC as PubMed record 26970723 (DOI 10.1016/s0140-6736(16)00587-0). Its author list gives \"Park K\" with the affiliation \"Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul, South Korea\", which names Samsung Medical Center; that is how the record was matched to Keunchil Park, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet 2016","url":"https://doi.org/10.1016/s0140-6736(16)00587-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26970723/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26970723"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["keunchil-park"],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2016,"doi":"10.1016/s0140-6736(16)00587-0","pmid":"26970723","authors":"Fehrenbacher L, Spira A, Ballinger M, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Keunchil Park at Samsung Medical Center, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-keunchil-park-lancet-2017","kind":"paper","name":"Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial","aka":[],"tldr":"Paper by Keunchil Park indexed on Europe PMC as PubMed record 27979383, in The Lancet (2017), one of the most cited records naming an author with this name at Samsung Medical Center.","summary":"Background: Atezolizumab is a humanised antiprogrammed death-ligand 1 (PD-L1) monoclonal antibody that inhibits PD-L1 and programmed death-1 (PD-1) and PD-L1 and B7-1 interactions, reinvigorating anticancer immunity. We assessed its efficacy and safety versus docetaxel in previously treated patients with non-small-cell lung cancer.\n\nMethods: We did a randomised, open-label, phase 3 trial (OAK) in 194 academic or community oncology centres in 31 countries. We enrolled patients who had squamous or non-squamous non-small-cell lung cancer, were 18 years or older, had measurable disease per Response Evaluation Criteria in Solid Tumors, and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients had received one to two previous cytotoxic chemotherapy regimens (one or more platinum based combination therapies) for stage IIIB or IV non-small-cell lung cancer. Patients with a history of autoimmune disease and those who had received previous treatments with docetaxel, CD137 agonists, anti-CTLA4, or therapies targeting the PD-L1 and PD-1 pathway were excluded. Patients were randomly assigned (1:1) to intravenously receive either atezolizumab 1200 mg or docetaxel 75 mg/m 2 every 3 weeks by permuted block randomisation (block size of eight) via an interactive voice or web response system. Coprimary endpoints were overall survival in the intention-to-treat (ITT) and PD-L1-expression population TC1/2/3 or IC1/2/3 (≥1% PD-L1 on tumour cells or tumour-infiltrating immune cells). The primary efficacy analysis was done in the first 850 of 1225 enrolled patients. This study is registered with ClinicalTrials.gov, number NCT02008227.\n\nFindings: Between March 11, 2014, and April 29, 2015, 1225 patients were recruited. In the primary population, 425 patients were randomly assigned to receive atezolizumab and 425 patients were assigned to receive docetaxel. Overall survival was significantly longer with atezolizumab in the ITT and PD-L1-expression populations. In the ITT population, overall survival was improved with atezolizumab compared with docetaxel (median overall survival was 13·8 months [95% CI 11·8-15·7] vs 9·6 months [8·6-11·2]; hazard ratio [HR] 0·73 [95% CI 0·62-0·87], p=0·0003). Overall survival in the TC1/2/3 or IC1/2/3 population was improved with atezolizumab (n=241) compared with docetaxel (n=222; median overall survival was 15·7 months [95% CI 12·6-18·0] with atezolizumab vs 10·3 months [8·8-12·0] with docetaxel; HR 0·74 [95% CI 0·58-0·93]; p=0·0102). Patients in the PD-L1 low or undetectable subgroup (TC0 and IC0) also had improved survival with atezolizumab (median overall survival 12·6 months vs 8·9 months; HR 0·75 [95% CI 0·59-0·96]). Overall survival improvement was similar in patients with squamous (HR 0·73 [95% CI 0·54-0·98]; n=112 in the atezolizumab group and n=110 in the docetaxel group) or non-squamous (0·73 [0·60-0·89]; n=313 and n=315) histology. Fewer patients had treatment-related grade 3 or 4 adverse events with atezolizumab (90 [15%] of 609 patients) versus docetaxel (247 [43%] of 578 patients). One treatment-related death from a respiratory tract infection was reported in the docetaxel group.\n\nInterpretation: To our knowledge, OAK is the first randomised phase 3 study to report results of a PD-L1-targeted therapy, with atezolizumab treatment resulting in a clinically relevant improvement of overall survival versus docetaxel in previously treated non-small-cell lung cancer, regardless of PD-L1 expression or histology, with a favourable safety profile.\n\nFunding: F. Hoffmann-La Roche Ltd, Genentech, Inc.\n\nIndexed on Europe PMC as PubMed record 27979383 (DOI 10.1016/s0140-6736(16)32517-x). Its author list gives \"Park K\" with the affiliation \"Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea\", which names Samsung Medical Center; that is how the record was matched to Keunchil Park, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet 2017","url":"https://doi.org/10.1016/s0140-6736(16)32517-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27979383/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27979383"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["keunchil-park"],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2017,"doi":"10.1016/s0140-6736(16)32517-x","pmid":"27979383","authors":"Rittmeyer A, Barlesi F, Waterkamp D, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Keunchil Park at Samsung Medical Center, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-eng-imblaze370-atezolizumab-cobimetinib-colorectal-lancet-oncol-2019","kind":"paper","name":"Atezolizumab with or without cobimetinib versus regorafenib in previously treated metastatic colorectal cancer (IMblaze370)","aka":[],"tldr":"The phase 3 test of the idea that a MEK inhibitor could warm up an immunologically cold bowel cancer. It failed: neither immunotherapy alone nor the combination beat an existing pill.","summary":"IMblaze370 was a multicentre, open-label, phase 3, randomised, controlled trial at 73 centres in 11 countries. Patients with unresectable locally advanced or metastatic colorectal cancer who had progressed on or were intolerant of at least two previous chemotherapy regimens were assigned 2:1:1 to atezolizumab plus cobimetinib, atezolizumab monotherapy or regorafenib, stratified by extended RAS status and time since first metastasis; recruitment of high microsatellite instability patients was capped at 5%. Between July 2016 and January 2017, 363 patients were enrolled. Median overall survival was 8.87 months with atezolizumab plus cobimetinib, 7.10 months with atezolizumab and 8.51 months with regorafenib, with hazard ratios against regorafenib of 1.00 for the combination and 1.19 for atezolizumab. Grade 3 to 4 adverse events were common in the combination arm.","asOf":"2026-09-24","links":[{"label":"Eng et al., Lancet Oncol 2019: IMblaze370, atezolizumab with or without cobimetinib versus regorafenib (363 patients)","url":"https://doi.org/10.1016/S1470-2045(19)30027-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31003911/"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["pd1"],"drugs":["atezolizumab","regorafenib"],"companies":[],"institutions":[],"pathways":["pd1-checkpoint","ras-mapk","immune-desert-exclusion"],"terms":["mss-pmmr","cold-vs-hot"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"Lancet Oncology","year":2019,"doi":"10.1016/S1470-2045(19)30027-0","pmid":"31003911","authors":"Eng C, Kim TW, Bendell J, et al.","paperType":"rct","findings":["Median overall survival 8.87, 7.10 and 8.51 months for the combination, atezolizumab and regorafenib.","Hazard ratios against regorafenib 1.00 and 1.19; neither immunotherapy arm was better.","Trial capped microsatellite instability-high enrolment at 5%, so the result describes microsatellite-stable disease."],"whatItMeans":"It is the definitive negative result for unselected checkpoint blockade in microsatellite-stable colorectal cancer, and the reason later attempts have moved to Fc-enhanced CTLA-4 antibodies, TGF-beta blockade and vaccines rather than PD-L1 plus MEK.","caveats":["Third-line population, so the biology may differ from earlier lines.","Regorafenib is a modest comparator, which makes the failure starker rather than softer.","Cobimetinib dosing may not have achieved the immune priming seen in mice."],"changedPractice":false,"participants":363},{"id":"paper-imspire150-lancet-2020","kind":"paper","name":"Atezolizumab, vemurafenib, and cobimetinib as first-line treatment for unresectable advanced BRAF V600 mutation-positive melanoma (IMspire150): primary analysis of the randomised, double-blind, placebo-controlled, phase 3 trial","aka":[],"tldr":"Published report from the IMspire150 trial registered as NCT02908672, in The Lancet (2020), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: IMspire150 aimed to evaluate first-line combination treatment with BRAF plus MEK inhibitors and immune checkpoint therapy in BRAF V600 mutation-positive advanced or metastatic melanoma.\n\nMethods: IMspire150 was a randomised, double-blind, placebo-controlled phase 3 study done at 112 institutes in 20 countries. Patients with unresectable stage IIIc-IV, BRAF V600 mutation-positive melanoma were randomly assigned 1:1 to 28-day cycles of atezolizumab, vemurafenib, and cobimetinib (atezolizumab group) or atezolizumab placebo, vemurafenib, and cobimetinib (control group). In cycle 1, all patients received vemurafenib and cobimetinib only; atezolizumab placebo was added from cycle 2 onward. Randomisation was stratified by lactate dehydrogenase concentration and geographical region. Blinding for atezolizumab was achieved by means of an identical intravenous placebo, and blinding for vemurafenib was achieved by means of a placebo tablet. The primary outcome was investigator-assessed progression-free survival. This trial (ClinicalTrials.gov, NCT02908672) is ongoing but no longer recruiting patients.\n\nFindings: Between Jan 13, 2017, and April 26, 2018, 777 patients were screened and 514 were enrolled and randomly assigned to the atezolizumab group (n=256) or control group (n=258). At a median follow-up of 18·9 months (IQR 10·4-23·8), progression-free survival as assessed by the study investigator was significantly prolonged with atezolizumab versus control (15·1 vs 10·6 months; hazard ratio [HR] 0·78; 95% CI 0·63-0·97; p=0·025). Common treatment-related adverse events (>30%) in the atezolizumab and control groups were blood creatinine phosphokinase increased (51·3% vs 44·8%), diarrhoea (42·2% vs 46·6%), rash (40·9%, both groups), arthralgia (39·1% vs 28·1%), pyrexia (38·7% vs 26·0%), alanine aminotransferase increased (33·9% vs 22·8%), and lipase increased (32·2% vs 27·4%); 13% of patients in the atezolizumab group and 16% in the control group stopped all treatment because of adverse events.\n\nInterpretation: The addition of atezolizumab to targeted therapy with vemurafenib and cobimetinib was safe and tolerable and significantly increased progression-free survival in patients with BRAF V600 mutation-positive advanced melanoma.\n\nFunding: F Hoffmann-La Roche and Genentech.\n\nIndexed on Europe PMC as PubMed record 32534646 (DOI 10.1016/s0140-6736(20)30934-x). Its abstract cites the registry id NCT02908672, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet 2020","url":"https://doi.org/10.1016/s0140-6736(20)30934-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32534646/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32534646"},{"label":"ClinicalTrials.gov NCT02908672","url":"https://clinicaltrials.gov/study/NCT02908672"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["imspire150"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2020,"doi":"10.1016/s0140-6736(20)30934-x","pmid":"32534646","authors":"Gutzmer R, Stroyakovskiy D, Gogas H, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02908672 with the most citations, so it is the natural first reading for anyone following the IMspire150 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-augment-101-revumenib-menin-nature-2023","kind":"paper","name":"AUGMENT-101: revumenib, the first menin inhibitor, in relapsed leukaemias driven by KMT2A rearrangement or NPM1 mutation","aka":[],"tldr":"Blocking menin, a scaffold protein the leukaemia depends on, produced remissions in heavily pretreated patients with KMT2A-rearranged or NPM1-mutated acute leukaemia.","summary":"The phase 1 portion of AUGMENT-101 treated 68 adults and children with relapsed or refractory acute leukaemia carrying a KMT2A rearrangement or NPM1 mutation with oral revumenib (SNDX-5613), a small molecule that disrupts the menin-KMT2A interaction. Among 60 efficacy-evaluable patients the overall response rate was 53% and the rate of complete remission or remission with partial haematological recovery 30%, with most responders MRD-negative. QT prolongation was dose limiting and differentiation syndrome occurred in 16%. Resistance through MEN1 mutations was subsequently described. The phase 2 KMT2A-rearranged cohort met its primary endpoint and revumenib was approved in 2024 for KMT2A-rearranged acute leukaemia and in 2025 for NPM1-mutated AML, the first drugs in a new class.","asOf":"2026-09-08","links":[{"label":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=AUGMENT-101%20revumenib%20menin%20inhibitor%20KMT2A%20NPM1%20Issa%20Nature%202023"},{"label":"ClinicalTrials.gov NCT04065399","url":"https://clinicaltrials.gov/study/NCT04065399"}],"tags":[],"related":["menin-plus-venetoclax-hma"],"cancers":["aml","all-leukemia"],"sections":[],"technologies":[],"targets":["menin","kmt2a","npm1"],"drugs":["revumenib","ziftomenib"],"companies":["syndax","kura-oncology"],"institutions":["md-anderson"],"pathways":[],"terms":["mrd-negative-cr","orr"],"trials":["augment-101"],"people":[],"bottlenecks":["b-undruggable-targets","b-resistance"],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2023,"doi":"10.1038/s41586-023-05812-3","pmid":"36922593","authors":"Issa GC, Aldoss I, DiPersio J, et al.","paperType":"translational","findings":["68 patients treated (60 efficacy-evaluable) with relapsed/refractory KMT2A-rearranged or NPM1-mutated acute leukaemia.","Overall response 53%; CR/CRh 30%; most remissions MRD-negative.","Dose-limiting toxicity was QT prolongation; differentiation syndrome in 16%.","Responses in both KMT2A-rearranged and NPM1-mutated disease and in children and adults.","Phase 2 KMT2A-rearranged cohort: CR/CRh in roughly a fifth of patients, sufficient for regulatory approval; acquired MEN1 mutations identified as a resistance mechanism."],"whatItMeans":"Revumenib proved that a transcriptional dependency, rather than a kinase, can be drugged in leukaemia, opening treatment for two genetic subgroups that together cover roughly a third of AML plus most infant ALL. It is now approved and is being combined with venetoclax-azacitidine and intensive chemotherapy in front-line trials. Single-agent remissions are often short without transplant.","caveats":["Single-arm phase 1/2 in end-stage patients; no randomised data yet.","Modest CR/CRh rates as monotherapy; benefit likely to come from combinations and as a bridge to transplant.","QT prolongation and drug interactions with azoles require dose adjustment.","Resistance via MEN1 mutations emerges within months in some patients."],"changedPractice":true,"participants":68},{"id":"paper-augment-lenalidomide-rituximab-leonard-jco-2019","kind":"paper","name":"AUGMENT: lenalidomide plus rituximab versus rituximab alone in relapsed indolent lymphoma","aka":[],"tldr":"Adding lenalidomide to rituximab more than doubled the time to progression in relapsed follicular and marginal zone lymphoma compared with rituximab alone, establishing a chemotherapy-free option for relapsed indolent lymphoma.","summary":"Phase 3 trial of 358 patients with relapsed or refractory follicular (grade 1 to 3a) or marginal zone lymphoma randomised to lenalidomide plus rituximab (R2) or placebo plus rituximab for 12 cycles.\n\nMedian progression-free survival was 39.4 versus 14.1 months (hazard ratio 0.46) and response 78 versus 53 percent; the benefit was clear in follicular lymphoma while the marginal zone subgroup was small and inconclusive. Neutropenia was more frequent with lenalidomide.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2019","url":"https://doi.org/10.1200/JCO.19.00010"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30897038/"}],"tags":[],"related":[],"cancers":["marginal-zone-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["lenalidomide","rituximab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["augment"],"people":["john-leonard"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2019,"doi":"10.1200/JCO.19.00010","pmid":"30897038","authors":"Leonard JP, Trneny M, Izutsu K, et al.","paperType":"rct","findings":["Median progression-free survival 39.4 vs 14.1 months; hazard ratio 0.46.","Objective response 78 percent vs 53 percent."],"whatItMeans":"Lenalidomide-rituximab is approved for relapsed follicular and marginal zone lymphoma and is a standard chemotherapy-free choice, though marginal zone-specific evidence is thinner.","caveats":["Only 63 patients had marginal zone lymphoma, with no clear progression-free survival benefit in that subgroup."],"changedPractice":true,"participants":358},{"id":"paper-dix-j-clin-oncol","kind":"paper","name":"Augmentation of Therapy for Combined Loss of Heterozygosity 1p and 16q in Favorable Histology Wilms Tumor: A Children's Oncology Group AREN0532 and AREN0533 Study Report","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 31449468 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: In National Wilms Tumor Study 5 (NWTS-5), tumor-specific combined loss of heterozygosity of chromosomes 1p and 16q (LOH1p/16q) was associated with adverse outcomes in patients with favorable histology Wilms tumor. The AREN0533/AREN0532 studies assessed whether augmenting therapy improved event-free survival (EFS) for these patients. Patients with stage I/II disease received regimen DD4A (vincristine, dactinomycin and doxorubicin) but no radiation therapy. Patients with stage III/IV disease received regimen M (vincristine, dactinomycin, and doxorubicin alternating with cyclophosphamide and etoposide) and radiation therapy.\n\nMethods: Patients were enrolled through the AREN03B2 Biology study between October 2006 and October 2013; all underwent central review of pathology, surgical reports, and imaging. Tumors were evaluated for LOH1p/16q by microsatellite testing. EFS and overall survival were compared using the log-rank test between NWTS-5 and current studies.\n\nResults: LOH1p/16q was detected in 49 of 1,147 evaluable patients with stage I/II disease (4.27%) enrolled in AREN03B2; 32 enrolled in AREN0532. LOH1p/16q was detected in 82 of 1,364 evaluable patients with stage III/IV disease (6.01%) in AREN03B2; 51 enrolled in AREN0533. Median follow-up for 83 eligible patients enrolled in AREN0532/0533 was 5.73 years (range, 2.84 to 9.63 years). The 4-year EFS for patients with stage I/II and stage III/IV disease with LOH1p/16 was 87.3% (95% CI, 75.1% to 99.5%) and 90.2% (95% CI, 81.8% to 98.6%), respectively. These results are improved compared with the NWTS-5 updated 4-year EFS of 68.8% for patients with stage I/II disease ( P =.042), and 61.3% for patients with stage III/IV disease ( P =.001), with trends toward improved 4-year overall survival. The most common grade 3 or higher nonhematologic toxicities with regimen M were febrile neutropenia (39.2%) and infections (21.6%).\n\nConclusion: Augmentation of therapy improved EFS for patients with favorable histology Wilms tumor and LOH1p/16q compared with the historical NWTS-5 comparison group, with an expected toxicity profile.\n\nIndexed on Europe PMC as PubMed record 31449468 (DOI 10.1200/jco.18.01972). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2019","url":"https://doi.org/10.1200/jco.18.01972"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31449468/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31449468"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["aren0533"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2019,"doi":"10.1200/jco.18.01972","pmid":"31449468","authors":"Dix DB, Fernandez CV, Chi YY, et al.","paperType":"observational","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nct04687241-lancet-oncol-2026","kind":"paper","name":"Aumolertinib as adjuvant therapy in resected EGFR-mutated non-small-cell lung cancer (ARTS): a double-blind, multicentre, randomised, controlled, phase 3 trial","aka":[],"tldr":"Published report from the trial registered as NCT04687241, in The Lancet Oncology (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Patients with resectable non-small-cell lung cancer (NSCLC), particularly those with EGFR mutations, face a high risk of recurrence and mortality post-surgery. Aumolertinib, a third-generation EGFR tyrosine-kinase inhibitor, is approved in China for adjuvant treatment in patients with NSCLC harbouring EGFR with an exon 19 deletion (ex19del) or exon 21 substitution (Leu858Arg) mutation. The ARTS study aimed to evaluate the efficacy and safety of adjuvant therapy with aumolertinib in patients with stage II-IIIB EGFR-mutated NSCLC.\n\nMethods: This double-blind, multicentre, randomised, controlled, phase 3 trial enrolled patients from 48 hospitals in mainland China. Eligible patients were 18 years or older with stage II-IIIB NSCLC, had undergone a complete resection followed by standard adjuvant therapy, and had an EGFR ex19del or Leu858Arg mutation and an Eastern Cooperative Oncology Group performance status score of 0 or 1. Patients were stratified by EGFR mutation status and tumour stage and were randomly assigned (1:1) to receive aumolertinib 110 mg or placebo orally, once daily for 3 years or until disease recurrence or other discontinuation criteria were met. Patients were randomly allocated to groups using an interactive web response system; the double‑dummy technique masked patients, investigators, and assessors. The primary endpoint was disease-free survival in the modified intention-to treat (mITT) population (ie, all patients with stage II-IIIB NSCLC harbouring EGFR mutations who had undergone complete tumour resection and standard adjuvant therapy), assessed by blinded independent central review (BICR). Safety was assessed in all patients who received at least one dose of study treatment. Although the study is ongoing, with some patients remaining in follow-up, this analysis represents the protocol-specified primary analysis. This study is registered with ClinicalTrials.gov (NCT04687241).\n\nFindings: Between April 30, 2021, and May 17, 2022, 399 individuals were screened for study eligibility; of these, 214 patients were randomly assigned to receive aumolertinib or placebo (107 in each group). 120 (56%) patients were female, 94 (44%) were male, median age was 59 years (IQR 54-66), and all patients were Chinese. 204 (95%) of 214 patients had received prior adjuvant chemotherapy. One patient in the aumolertinib group and three patients in the placebo group had stage I disease; therefore, 106 patients in the aumolertinib group and 104 in the placebo group were included in the mITT (primary analysis) population. at the data cutoff date (April 15, 2024), the median duration of follow-up was 27·56 months (IQR 22·18-27·70) in the aumolertinib group and 27·63 months (22·18-27·79) in the placebo group. The BICR-assessed disease-free survival was significantly improved in the aumolertinib group compared with the placebo group, with an HR of 0·17 (95% CI 0·09-0·29, p<0·0001). The median disease-free survival per BICR in the aumolertinib group was not reached (95% CI 29·14 to not applicable), whereas it was 19·42 months (11·24-26·22) in the placebo group. The most common grade 3-4 adverse events in the aumolertinib group versus the placebo group were increased blood creatine phosphokinase (seven [7%] vs none), prolonged electrocardiogram QT interval (three [3%] vs three [3%]), hypertension (one [1%] vs five [5%]), and pneumonia (two [2%] vs three [3%]). Treatment-related serious adverse events occurred in one (1%) patient receiving aumolertinib and three (3%) patients receiving placebo. No treatment-related deaths occurred and no new safety signals were identified for aumolertinib.\n\nInterpretation: Aumolertinib showed substantial clinical benefits as adjuvant therapy in Chinese patients with stage II-IIIB EGFR-mutated NSCLC. The manageable safety profile of aumolertinib supports its suitability in the adjuvant setting.\n\nFunding: Hansoh Pharmaceutical Group.\n\nTranslation: For the Chinese translation of the abstract see Supplementary Materials section.\n\nIndexed on Europe PMC as PubMed record 41539318 (DOI 10.1016/s1470-2045(25)00643-6). Its abstract cites the registry id NCT04687241, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2026","url":"https://doi.org/10.1016/s1470-2045(25)00643-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41539318/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41539318"},{"label":"ClinicalTrials.gov NCT04687241","url":"https://clinicaltrials.gov/study/NCT04687241"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04687241"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2026,"doi":"10.1016/s1470-2045(25)00643-6","pmid":"41539318","authors":"Zhang L, Zhang X, Wu L, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04687241 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-nct04923906-lancet-oncol-2026","kind":"paper","name":"Aumolertinib with or without chemotherapy in EGFR-mutated advanced non-small-cell lung cancer (AENEAS2): an open-label, multicentre, randomised, controlled, phase 3 trial","aka":[],"tldr":"Published report from the trial registered as NCT04923906, in The Lancet Oncology (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Although third-generation epidermal growth-factor receptor (EGFR)-tyrosine-kinase inhibitors (TKIs) are standard first-line therapies for patients with advanced EGFR-mutated non-small-cell lung cancer (NSCLC), their effectiveness is often limited by the emergence of drug resistance and subsequent disease progression. Given the previously established clinical efficacy and adverse event profile of aumolertinib, we aimed to evaluate the efficacy and adverse event profile of aumolertinib in combination with platinum-based chemotherapy versus aumolertinib monotherapy as first-line treatment for patients with locally advanced or metastatic NSCLC patients with EGFR-sensitive mutations.\n\nMethods: The open-label, multicentre, randomised, controlled, phase 3 AENEAS2 trial was done across 60 hospitals in China. Patients aged at least 18 years with Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1; treatment-naive; histologically or cytologically confirmed locally advanced or metastatic NSCLC harbouring EGFR-sensitive mutations (ex19del/L858R with or without other EGFR mutations) were eligible. Brain metastases were allowed if neurologically stable. Previous EGFR-TKI therapy was an exclusion criterion. Patients were randomly assigned (1:1) with block randomisation (block size of 6), stratified by EGFR mutation type and baseline brain metastasis, to receive aumolertinib monotherapy (110 mg orally once a day) or combination therapy (aumolertinib 110 mg orally once a day plus pemetrexed 500 mg/m 2 intravenously with cisplatin [75 mg/m 2 ] or carboplatin [area under the plasma concentration-time curve 5] intravenously on day 1 of 21-day cycles for 4-6 cycles), followed by maintenance therapy (aumolertinib 110 mg orally once a day and pemetrexed 500 mg/m 2 intravenously once every 3 weeks). The primary endpoint was progression-free survival assessed by blinded independent central review (BICR; RECIST version 1.1). Efficacy was analysed in the full-analysis set, which included all randomly assigned patients, and safety was analysed in patients who received at least one dose of the actual trial treatment. The trial is registered at ClinicalTrials.gov, NCT04923906, and is ongoing, but closed to enrolment.\n\nFindings: Between Aug 4, 2021, to June 18, 2024, of 1011 patients assessed for eligibility, 624 randomly assigned patients (median age 59·0 years [IQR 52·0-66·0]; 337 [54%] were female, 287 [46%] were male) were randomly assigned. 310 (50%) patients received combination therapy and 314 (50%) received monotherapy. at the data cutoff date (June 18, 2024), the median follow-up was 23·4 months (IQR 20·5-26·5), In the full-analysis set, median BICR-assessed progression-free survival was 28·9 months (95% CI 26.3, NA) in the combination therapy versus 18·9 months (17·8-21·1) in the monotherapy (hazard ratio [HR] 0·47, 95% CI 0·37-0·60; log-rank p<0·0001). The most common grade 3-4 adverse events (occurring in at least 20% in any group) were neutrophil count decreased (168 [55%] of 304 in the combination group versus four [1%] of 316 in monotherapy group), white blood cell count decreased (103 [34%] vs one [<1%]), and platelet count decreased (62 [20%] vs two [1%]). Serious adverse events occurred in 109 (36%) patients in the combination group and 53 (17%) in the monotherapy group, the most common of which were platelet count decreased (22 [7%] vs 0), neutrophil count decreased (17 [6%] vs 0), white blood cell count decreased (13 [4%] vs 0), and anaemia (ten [3%] vs two [1%]). Treatment-related deaths occurred in one (<1%) patient in the combination group (encephalopathy) and two (1%) in the monotherapy group (pulmonary embolism and respiratory failure with circulatory collapse).\n\nInterpretation: Aumolertinib in combination with chemotherapy significantly improved progression-free survival. Although this regimen was associated with increased toxicity, the side-effects were managed with dose adjustment and supportive treatment aligned with clinical practice. Long-term follow-up is required to assess overall survival. The AENEAS2 study provides evidence to guide clinical practice regarding EGFR-TKIs and their combination use in treating patients with advanced EGFR-mutated NSCLC.\n\nFunding: Jiangsu Hansoh Pharmaceutical Group, and the Collaborative Innovation Center for Clinical and Translational Science by Ministry of Education & Shanghai.\n\nTranslations: For the Chinese translation of the abstract see Supplementary Materials section.\n\nIndexed on Europe PMC as PubMed record 42296979 (DOI 10.1016/s1470-2045(26)00090-2). Its abstract cites the registry id NCT04923906, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2026","url":"https://doi.org/10.1016/s1470-2045(26)00090-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42296979/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42296979"},{"label":"ClinicalTrials.gov NCT04923906","url":"https://clinicaltrials.gov/study/NCT04923906"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04923906"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2026,"doi":"10.1016/s1470-2045(26)00090-2","pmid":"42296979","authors":"Li Z, Hu J, Chen J, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04923906 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-aurelia-bevacizumab-platinum-resistant-ovarian-pujade-lauraine-jco-2014","kind":"paper","name":"AURELIA: bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer","aka":[],"tldr":"Adding bevacizumab to single-agent chemotherapy for platinum-resistant ovarian cancer doubled the time to progression and more than doubled the response rate, without a significant gain in survival.","summary":"Open-label randomised phase 3 trial: 361 women with platinum-resistant recurrent ovarian cancer received the investigator's choice of weekly paclitaxel, pegylated liposomal doxorubicin or topotecan, alone or with bevacizumab.\n\nMedian progression-free survival was 6.7 months with bevacizumab against 3.4 months (hazard ratio 0.48, p < 0.001); response rate 27.3 against 11.8 percent; median overall survival 16.6 against 13.3 months (hazard ratio 0.85, p 0.174). Grade 2 or higher hypertension and proteinuria were more common with bevacizumab; gastrointestinal perforation occurred in 2.2 percent.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2014","url":"https://doi.org/10.1200/JCO.2013.51.4489"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24637997/"}],"tags":[],"related":[],"cancers":["platinum-resistant-ovarian-cancer","ovarian"],"sections":[],"technologies":[],"targets":[],"drugs":["bevacizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["aurelia"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2014,"doi":"10.1200/JCO.2013.51.4489","pmid":"24637997","authors":"Pujade-Lauraine E, Hilpert F, Weber B, et al.","paperType":"rct","findings":["Median progression-free survival 6.7 versus 3.4 months; hazard ratio 0.48 (95% CI 0.38 to 0.60), p < 0.001.","Objective response 27.3 versus 11.8 percent (p 0.001).","Median overall survival 16.6 versus 13.3 months; hazard ratio 0.85 (0.66 to 1.08), not significant."],"whatItMeans":"Bevacizumab with weekly paclitaxel, liposomal doxorubicin or topotecan is a standard option in platinum-resistant ovarian cancer; approved in the United States in 2014.","caveats":["Open-label; patients with more than two prior regimens or bowel involvement at risk of perforation were excluded.","Crossover to bevacizumab at progression diluted the survival comparison."],"changedPractice":true,"participants":361},{"id":"paper-yamamoto-nature","kind":"paper","name":"Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 32376951 and published in Nature; the citing page links this DOI, which is how the record was matched.","summary":"Immune evasion is a major obstacle for cancer treatment. Common mechanisms of evasion include impaired antigen presentation caused by mutations or loss of heterozygosity of the major histocompatibility complex class I (MHC-I), which has been implicated in resistance to immune checkpoint blockade (ICB) therapy 1-3. However, in pancreatic ductal adenocarcinoma (PDAC), which is resistant to most therapies including ICB 4, mutations that cause loss of MHC-I are rarely found 5 despite the frequent downregulation of MHC-I expression 6-8. Here we show that, in PDAC, MHC-I molecules are selectively targeted for lysosomal degradation by an autophagy-dependent mechanism that involves the autophagy cargo receptor NBR1. PDAC cells display reduced expression of MHC-I at the cell surface and instead demonstrate predominant localization within autophagosomes and lysosomes. Notably, inhibition of autophagy restores surface levels of MHC-I and leads to improved antigen presentation, enhanced anti-tumour T cell responses and reduced tumour growth in syngeneic host mice. Accordingly, the anti-tumour effects of autophagy inhibition are reversed by depleting CD8 + T cells or reducing surface expression of MHC-I. Inhibition of autophagy, either genetically or pharmacologically with chloroquine, synergizes with dual ICB therapy (anti-PD1 and anti-CTLA4 antibodies), and leads to an enhanced anti-tumour immune response. Our findings demonstrate a role for enhanced autophagy or lysosome function in immune evasion by selective targeting of MHC-I molecules for degradation, and provide a rationale for the combination of autophagy inhibition and dual ICB therapy as a therapeutic strategy against PDAC.\n\nIndexed on Europe PMC as PubMed record 32376951 (DOI 10.1038/s41586-020-2229-5). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2020","url":"https://doi.org/10.1038/s41586-020-2229-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32376951/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32376951"}],"tags":["europepmc-ingest"],"related":["autophagy"],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":["pd1","ctla4"],"drugs":[],"companies":[],"institutions":[],"pathways":["antigen-presentation-immunoediting","autophagy","pd1-checkpoint"],"terms":["cold-vs-hot"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2020,"doi":"10.1038/s41586-020-2229-5","pmid":"32376951","authors":"Yamamoto K, Venida A, Yano J, et al.","paperType":"basic","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-davis-bmj","kind":"paper","name":"Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13","aka":[],"tldr":"Paper cited by two bottleneck pages and 15 idea pages, indexed on Europe PMC as PubMed record 28978555 and published in BMJ; the citing pages link this DOI, which is how the record was matched.","summary":"Objective To determine the availability of data on overall survival and quality of life benefits of cancer drugs approved in Europe. Design Retrospective cohort study. Setting Publicly accessible regulatory and scientific reports on cancer approvals by the European Medicines Agency (EMA) from 2009 to 2013. Main outcome measures Pivotal and postmarketing trials of cancer drugs according to their design features (randomisation, crossover, blinding), comparators, and endpoints. Availability and magnitude of benefit on overall survival or quality of life determined at time of approval and after market entry. Validated European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) used to assess the clinical value of the reported gains in published studies of cancer drugs. Results From 2009 to 2013, the EMA approved the use of 48 cancer drugs for 68 indications. Of these, eight indications (12%) were approved on the basis of a single arm study. At the time of market approval, there was significant prolongation of survival in 24 of the 68 (35%). The magnitude of the benefit on overall survival ranged from 1.0 to 5.8 months (median 2.7 months). At the time of market approval, there was an improvement in quality of life in seven of 68 indications (10%). Out of 44 indications for which there was no evidence of a survival gain at the time of market authorisation, in the subsequent postmarketing period there was evidence for extension of life in three (7%) and reported benefit on quality of life in five (11%). Of the 68 cancer indications with EMA approval, and with a median of 5.4 years' follow-up (minimum 3.3 years, maximum 8.1 years), only 35 (51%) had shown a significant improvement in survival or quality of life, while 33 (49%) remained uncertain. Of 23 indications associated with a survival benefit that could be scored with the ESMO-MCBS tool, the benefit was judged to be clinically meaningful in less than half (11/23, 48%). Conclusions This systematic evaluation of oncology approvals by the EMA in 2009-13 shows that most drugs entered the market without evidence of benefit on survival or quality of life. At a minimum of 3.3 years after market entry, there was still no conclusive evidence that these drugs either extended or improved life for most cancer indications. When there were survival gains over existing treatment options or placebo, they were often marginal.\n\nIndexed on Europe PMC as PubMed record 28978555 (DOI 10.1136/bmj.j4530). Matched by DOI alone: two bottleneck pages and 15 idea pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"BMJ 2017","url":"https://doi.org/10.1136/bmj.j4530"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28978555/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28978555"}],"tags":["europepmc-ingest"],"related":["b-toxicity-qol","b-trial-design","idea-tr1-window-of-opportunity-default","idea-tr1-tumour-agnostic-approval-standard","idea-tr1-aggregated-n-of-1-supportive-care","idea-tr1-ai-central-imaging-reads","idea-tr1-shrinkage-subgroup-analysis","idea-tr1-shared-control-arms-across-sponsors","idea-tr1-target-trial-emulation-to-prioritise-rcts","idea-tr1-crossover-adjusted-survival-standard","idea-tr1-immunotherapy-stop-trials","idea-tr1-randomised-phase-2-before-phase-3","idea-tr1-seamless-2-3-with-prespecified-go","idea-tr1-smart-designs-for-adaptive-strategies","idea-tr1-aggressive-futility-boundaries","idea-tr1-ctdna-guided-stop-in-metastatic-disease","idea-tr1-validate-real-world-progression-endpoints"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["bmj"],"dependsOn":[],"notes":[],"journal":"BMJ","year":2017,"doi":"10.1136/bmj.j4530","pmid":"28978555","authors":"Davis C, Naci H, Gurpinar E, et al.","paperType":"observational","findings":[],"whatItMeans":"Two bottleneck pages and 15 idea pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-roman-anderson-eclinicalmedicine-2025","kind":"paper","name":"Avasopasem manganese treatment for severe oral mucositis from chemoradiotherapy for locally advanced head and neck cancer: phase 3 randomized controlled trial (ROMAN)","aka":[],"tldr":"Giving avasopasem before each radiotherapy session lowered the share of head and neck cancer patients who got severe mouth ulcers from 64 to 54 percent and cut how long the ulcers lasted from 18 days to 8, but the gain was smaller than hoped and the FDA wanted another trial.","summary":"Primary publication of ROMAN (NCT03689712). Patients receiving 60 to 72 Gy of intensity-modulated radiotherapy (more than 50 Gy to at least two oral mucosal sites) plus cisplatin for locally advanced head and neck cancer were randomised 3:2 to avasopasem manganese 90 mg or placebo before each radiotherapy fraction. Severe oral mucositis (WHO grade 3 or 4) was assessed twice weekly during radiotherapy and weekly for two weeks after. The primary endpoint was the incidence of severe oral mucositis through the end of radiotherapy; secondary endpoints included its duration and onset, grade 4 incidence and duration, tumour outcomes and renal function.\n\n455 patients were randomised and 407 (241 avasopasem, 166 placebo) entered the primary analysis. Severe oral mucositis incidence was 54 percent versus 64 percent (relative risk 0.84; 95 percent CI 0.71 to 1.00; p = 0.045) and median duration 8 versus 18 days (p = 0.002); onset was nominally delayed (median 49 versus 38 days). Grade 4 incidence (27 percent, p = 0.052) and days (24 percent, p = 0.143) were not significantly reduced. Adverse-event frequencies were comparable; tumour outcomes were maintained at one year, and two-year overall survival was 89 percent (84 to 93) with avasopasem versus 93 percent (88 to 96) with placebo. The authors write that the incidence benefit was smaller than the phase 2b had predicted, that avasopasem's contribution to adverse events could not be excluded, and that ROMAN did not provide a sufficiently favourable benefit-risk determination for FDA approval; a confirmatory phase 3 trial was requested.","asOf":"2026-09-24","links":[{"label":"eClinicalMedicine 2025","url":"https://doi.org/10.1016/j.eclinm.2025.103539"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41127563/"},{"label":"ClinicalTrials.gov NCT03689712","url":"https://clinicaltrials.gov/study/NCT03689712"}],"tags":[],"related":[],"cancers":["head-and-neck"],"sections":[],"technologies":["radioprotectors"],"targets":[],"drugs":["avasopasem-manganese"],"companies":["galera-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":["roman"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"eClinicalMedicine","year":2025,"doi":"10.1016/j.eclinm.2025.103539","pmid":"41127563","authors":"Anderson C, Lee CM, Kelley JR, et al.","paperType":"rct","findings":["Severe oral mucositis incidence 54 percent with avasopasem vs 64 percent with placebo (relative risk 0.84; 95 percent CI 0.71 to 1.00; p = 0.045).","Median duration of severe oral mucositis 8 vs 18 days (p = 0.002); onset delayed to a median of 49 vs 38 days.","Grade 4 mucositis not significantly reduced; two-year overall survival 89 percent vs 93 percent."],"whatItMeans":"Severe mouth ulcers are the most disabling acute effect of head and neck chemoradiation and there is still no approved drug to prevent them. ROMAN shows that a radioprotector can reduce them, but by less than the phase 2b suggested, and the upper confidence limit of 1.00 plus the numerically lower two-year survival left the FDA unconvinced. The product stays investigational until a confirmatory trial reports.","caveats":["The confidence interval for the primary relative risk reaches 1.00, and the p value is 0.045.","Two-year overall survival was numerically lower on avasopasem (89 percent vs 93 percent); the confidence intervals overlap, but the authors say a contribution to adverse events could not be excluded.","The primary analysis population (407) is smaller than the randomised population (455).","Funded by Galera Therapeutics; published two years after the FDA complete response letter."],"changedPractice":false,"participants":455},{"id":"paper-javelin-merkel-200-lancet-oncol-2016","kind":"paper","name":"Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial","aka":[],"tldr":"Published report from the JAVELIN Merkel 200 trial registered as NCT02155647, in The Lancet Oncology (2016), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Merkel cell carcinoma is a rare, aggressive skin cancer with poor prognosis in patients with advanced disease. Current standard care uses various cytotoxic chemotherapy regimens, but responses are seldom durable. Tumour oncogenesis is linked to Merkel cell polyomavirus integration and ultraviolet-radiation-induced mutations, providing rationale for treatment with immunotherapy antibodies that target the PD-L1/PD-1 pathway. We assessed treatment with avelumab, an anti-PD-L1 monoclonal antibody, in patients with stage IV Merkel cell carcinoma that had progressed after cytotoxic chemotherapy.\n\nMethods: In this multicentre, international, prospective, single-group, open-label, phase 2 trial, patients with stage IV chemotherapy-refractory, histologically confirmed Merkel cell carcinoma (aged ≥18 years) were enrolled from 35 cancer treatment centres and academic hospitals in North America, Europe, Australia, and Asia. Key eligibility criteria were an ECOG performance status of 0 or 1, measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, adequate haematological, hepatic, and renal function, and immune-competent status (patients with HIV, immunosuppression, haematological malignancies, and previous organ transplantation were excluded). Patient selection was not based on PD-L1 expression or Merkel cell polyomavirus status. Collection of biopsy material or use of archival tissue for these assessments was mandatory. Avelumab was given intravenously at a dose of 10 mg/kg every 2 weeks. The primary endpoint was confirmed objective response (complete response or partial response) assessed according to RECIST version 1.1 by an independent review committee. Safety and clinical activity were assessed in all patients who received at least one dose of study drug (the modified intention-to-treat population). This trial is registered with ClinicalTrials.gov as NCT02155647.\n\nFindings: Between July 25, 2014, and Sept 3, 2015, 88 patients were enrolled and received at least one dose of avelumab. Patients were followed up for a median of 10·4 months (IQR 8·6-13·1). The proportion of patients who achieved an objective response was 28 (31·8% [95·9% CI 21·9-43·1]) of 88 patients, including eight complete responses and 20 partial responses. Responses were ongoing in 23 (82%) of 28 patients at the time of analysis. Five grade 3 treatment-related adverse events occurred in four (5%) patients: lymphopenia in two patients, blood creatine phosphokinase increase in one patient, aminotransferase increase in one patient, and blood cholesterol increase in one patient; there were no treatment-related grade 4 adverse events or treatment-related deaths. Serious treatment-related adverse events were reported in five patients (6%): enterocolitis, infusion-related reaction, aminotransferases increased, chondrocalcinosis, synovitis, and interstitial nephritis (n=1 each).\n\nInterpretation: Avelumab was associated with durable responses, most of which are still ongoing, and was well tolerated; hence, avelumab represents a new therapeutic option for advanced Merkel cell carcinoma.\n\nFunding: Merck KGaA, Darmstadt, Germany.\n\nIndexed on Europe PMC as PubMed record 27592805 (DOI 10.1016/s1470-2045(16)30364-3). Its abstract cites the registry id NCT02155647, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2016","url":"https://doi.org/10.1016/s1470-2045(16)30364-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27592805/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27592805"},{"label":"ClinicalTrials.gov NCT02155647","url":"https://clinicaltrials.gov/study/NCT02155647"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["javelin-merkel-200"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2016,"doi":"10.1016/s1470-2045(16)30364-3","pmid":"27592805","authors":"Kaufman HL, Russell J, Hamid O, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02155647 with the most citations, so it is the natural first reading for anyone following the JAVELIN Merkel 200 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-zuma-5-axi-cel-indolent-lymphoma-lancet-oncol-2022","kind":"paper","name":"Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma (ZUMA-5): a single-arm, multicentre, phase 2 trial","aka":["ZUMA-5","Jacobson 2022"],"tldr":"The first CAR-T trial in slow-growing lymphoma: more than nine in ten responded and three quarters went into complete remission, with severe neurological events in about one in five.","summary":"A single-arm phase 2 trial at 15 centres in the United States and two in France, in patients aged 18 or over with relapsed or refractory follicular lymphoma or marginal zone lymphoma who had received two or more previous lines including an anti-CD20 antibody with an alkylating agent. Patients had conditioning chemotherapy with cyclophosphamide 500 mg per square metre and fludarabine 30 mg per square metre on days minus 5, minus 4 and minus 3, then a single infusion of axicabtagene ciloleucel at 2 million chimeric antigen receptor T cells per kilogram.\n\nBetween 20 June 2017 and 16 July 2020, 153 patients were enrolled and axicabtagene ciloleucel was successfully manufactured for all of them; 148 were infused, 124 with follicular lymphoma and 24 with marginal zone lymphoma. Among the 104 patients eligible for the primary analysis, 96 (92 per cent, 95 per cent confidence interval 85 to 97) had an overall response and 77 (74 per cent) a complete response, at a median follow-up of 17.5 months.","asOf":"2026-10-01","links":[{"label":"Lancet Oncology 2022","url":"https://doi.org/10.1016/S1470-2045(21)00591-X"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34895487/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34895487"}],"tags":["lymphoma-evidence"],"related":["lymphoma-roadmap"],"cancers":["follicular-lymphoma","marginal-zone-lymphoma","non-hodgkin-lymphoma"],"sections":["cell-therapy"],"technologies":["car-t"],"targets":["cd19"],"drugs":["axicabtagene-ciloleucel","cyclophosphamide","fludarabine"],"companies":["gilead"],"institutions":[],"pathways":[],"terms":["crs","icans","lymphodepletion","lugano-classification"],"trials":["zuma-5","elara"],"people":["caron-jacobson","gilles-salles"],"bottlenecks":["b-manufacturing-cell-therapy","b-toxicity-qol"],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"Lancet Oncology","year":2022,"doi":"10.1016/S1470-2045(21)00591-X","pmid":"34895487","authors":"Jacobson CA, Chavez JC, Sehgal AR, et al.","paperType":"rct","findings":["Of 104 patients in the primary analysis, 96 (92 per cent, 95 per cent confidence interval 85 to 97) had an overall response and 77 (74 per cent) a complete response.","Axicabtagene ciloleucel was successfully manufactured for all 153 enrolled patients.","Grade 3 or worse cytokine release syndrome occurred in ten patients (7 per cent) and grade 3 or 4 neurological events in 28 (19 per cent).","The most common grade 3 or worse adverse events were cytopenias in 104 patients (70 per cent) and infections in 26 (18 per cent).","Deaths due to adverse events occurred in four patients (3 per cent), one deemed treatment-related."],"whatItMeans":"Axicabtagene ciloleucel as an option in relapsed follicular and marginal zone lymphoma. Compared with tisagenlecleucel in ELARA, the response rates are higher and the neurological toxicity substantially greater, which is the trade-off a patient and centre weigh.","caveats":["Single-arm, so the comparison with ELARA is cross-trial, with different eligibility and different follow-up.","Only 24 patients had marginal zone lymphoma, so the result in that disease rests on very small numbers.","Grade 3 or 4 neurological events in 19 per cent require a centre equipped to manage them.","Median follow-up of 17.5 months in a disease measured in decades."],"changedPractice":true,"participants":148},{"id":"paper-aza-001-fenaux-lancet-oncol-2009","kind":"paper","name":"AZA-001: azacitidine versus conventional care in higher-risk myelodysplastic syndromes","aka":[],"tldr":"Azacitidine was the first drug shown to lengthen survival in higher-risk myelodysplastic syndromes, adding about nine months of median survival compared with the usual supportive care or chemotherapy.","summary":"Phase 3 trial of 358 patients with higher-risk MDS randomised to azacitidine or a pre-selected conventional care regimen (best supportive care, low-dose cytarabine or intensive chemotherapy).\n\nMedian overall survival was 24.5 months with azacitidine against 15.0 months with conventional care (hazard ratio 0.58), with two-year survival roughly doubled and fewer transfusions and infections.","asOf":"2026-09-17","links":[{"label":"Lancet Oncol 2009","url":"https://doi.org/10.1016/S1470-2045(09)70003-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19230772/"}],"tags":[],"related":[],"cancers":["mds-higher-risk"],"sections":[],"technologies":[],"targets":[],"drugs":["azacitidine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["aza-001"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2009,"doi":"10.1016/S1470-2045(09)70003-8","pmid":"19230772","authors":"Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al.","paperType":"rct","findings":["Median overall survival 24.5 vs 15.0 months; hazard ratio 0.58.","Two-year survival 50.8 percent vs 26.2 percent."],"whatItMeans":"Azacitidine (and decitabine) became the standard for higher-risk MDS in patients not going straight to transplant, and the backbone for combination trials that have so far failed to beat it.","caveats":["Median time to response is several cycles, so treatment must continue for at least four to six cycles before judging failure.","Responses are not durable; outcomes after hypomethylating failure are poor."],"changedPractice":true,"participants":358},{"id":"paper-aza-aml-001-dombret-blood-2015","kind":"paper","name":"AZA-AML-001: azacitidine versus conventional care in older patients with acute myeloid leukaemia and more than 30 percent blasts","aka":[],"tldr":"In older people with acute myeloid leukaemia who were not good candidates for intensive chemotherapy, azacitidine lengthened median survival by about four months compared with the usual options and became the backbone that venetoclax was later added to.","summary":"Phase 3 trial of 488 patients aged 65 or over with newly diagnosed AML and over 30 percent marrow blasts, randomised to azacitidine or a pre-selected conventional care regimen (intensive chemotherapy, low-dose cytarabine or supportive care).\n\nMedian overall survival was 10.4 months with azacitidine against 6.5 months with conventional care, a difference that was clinically meaningful but not statistically significant in the primary analysis. One-year survival was 46.5 versus 34.2 percent.","asOf":"2026-09-17","links":[{"label":"Blood 2015","url":"https://doi.org/10.1182/blood-2015-01-621664"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25987659/"}],"tags":[],"related":[],"cancers":["aml-older-unfit"],"sections":[],"technologies":[],"targets":[],"drugs":["azacitidine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["herve-dombret"],"bottlenecks":[],"keyPapers":[],"journals":["blood"],"dependsOn":[],"notes":[],"journal":"Blood","year":2015,"doi":"10.1182/blood-2015-01-621664","pmid":"25987659","authors":"Dombret H, Seymour JF, Butrym A, et al.","paperType":"rct","findings":["Median overall survival 10.4 vs 6.5 months (hazard ratio 0.85, not significant in the primary analysis).","One-year survival 46.5 percent vs 34.2 percent."],"whatItMeans":"Azacitidine became the standard low-intensity treatment for older or unfit patients with AML and the control arm for later trials; venetoclax plus azacitidine (VIALE-A) now supersedes azacitidine alone where available.","caveats":["The primary endpoint was not formally met.","The comparator was heterogeneous and chosen by the investigator before randomisation."],"changedPractice":true,"participants":488},{"id":"paper-azacitidine-aml-j-clin-oncol-2010","kind":"paper","name":"Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia","aka":[],"tldr":"Phase 2 or 3 results paper on Azacitidine in Acute myeloid leukaemia, in Journal of Clinical Oncology (2010), one of the most cited Europe PMC records with Azacitidine in its title.","summary":"Purpose: In a phase III randomized trial, azacitidine significantly prolonged overall survival (OS) compared with conventional care regimens (CCRs) in patients with intermediate-2- and high-risk myelodysplastic syndromes. Approximately one third of these patients were classified as having acute myeloid leukemia (AML) under current WHO criteria. This analysis compared the effects of azacitidine versus CCR on OS in this subgroup.\n\nPatients and methods: Patients were randomly assigned to receive subcutaneous azacitidine 75 mg/m(2)/d or CCR (best supportive care [BSC] only, low-dose cytarabine (LDAC), or intensive chemotherapy [IC]).\n\nResults: Of the 113 elderly patients (median age, 70 years) randomly assigned to receive azacitidine (n = 55) or CCR (n = 58; 47% BSC, 34% LDAC, 19% IC), 86% were considered unfit for IC. At a median follow-up of 20.1 months, median OS for azacitidine-treated patients was 24.5 months compared with 16.0 months for CCR-treated patients (hazard ratio = 0.47; 95% CI, 0.28 to 0.79; P =.005), and 2-year OS rates were 50% and 16%, respectively (P =.001). Two-year OS rates were higher with azacitidine versus CCR in patients considered unfit for IC (P =.0003). Azacitidine was associated with fewer total days in hospital (P <.0001) than CCR.\n\nConclusion: In older adult patients with low marrow blast count (20% to 30%) WHO-defined AML, azacitidine significantly prolongs OS and significantly improves several patient morbidity measures compared with CCR.\n\nIndexed on Europe PMC as PubMed record 20026804 (DOI 10.1200/jco.2009.23.8329). Its title names Azacitidine and its text names Acute myeloid leukaemia; PubMed types it as a clinical trial report (Clinical Trial, Phase III, Comparative Study, Research Support, Non-U.S. Gov't, Multicenter Study, Randomized Controlled Trial). It was matched automatically to the idea \"Shorter venetoclax courses in unfit AML\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2010","url":"https://doi.org/10.1200/jco.2009.23.8329"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20026804/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/20026804"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2010,"doi":"10.1200/jco.2009.23.8329","pmid":"20026804","authors":"Fenaux P, Mufti GJ, Hellström-Lindberg E, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Azacitidine in Acute myeloid leukaemia, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Azacitidine in the title and Acute myeloid leukaemia in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-antoine-italiano-nature-2020","kind":"paper","name":"B cells are associated with survival and immunotherapy response in sarcoma","aka":[],"tldr":"Paper by Antoine Italiano indexed on Europe PMC as PubMed record 31942077, in Nature (2020), one of the most cited records naming an author with this name at Institut Bergonié.","summary":"Soft-tissue sarcomas represent a heterogeneous group of cancer, with more than 50 histological subtypes 1,2. The clinical presentation of patients with different subtypes is often atypical, and responses to therapies such as immune checkpoint blockade vary widely 3,4. To explain this clinical variability, here we study gene expression profiles in 608 tumours across subtypes of soft-tissue sarcoma. We establish an immune-based classification on the basis of the composition of the tumour microenvironment and identify five distinct phenotypes: immune-low (A and B), immune-high (D and E), and highly vascularized (C) groups. In situ analysis of an independent validation cohort shows that class E was characterized by the presence of tertiary lymphoid structures that contain T cells and follicular dendritic cells and are particularly rich in B cells. B cells are the strongest prognostic factor even in the context of high or low CD8 + T cells and cytotoxic contents. The class-E group demonstrated improved survival and a high response rate to PD1 blockade with pembrolizumab in a phase 2 clinical trial. Together, this work confirms the immune subtypes in patients with soft-tissue sarcoma, and unravels the potential of B-cell-rich tertiary lymphoid structures to guide clinical decision-making and treatments, which could have broader applications in other diseases.\n\nIndexed on Europe PMC as PubMed record 31942077 (DOI 10.1038/s41586-019-1906-8). Its author list gives \"Italiano A\" with the affiliation \"Institut Bergonié, Bordeaux, France\", which names Institut Bergonié; that is how the record was matched to Antoine Italiano, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2020","url":"https://doi.org/10.1038/s41586-019-1906-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31942077/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31942077"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["antoine-italiano"],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2020,"doi":"10.1038/s41586-019-1906-8","pmid":"31942077","authors":"Petitprez F, de Reyniès A, Keung EZ, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Antoine Italiano at Institut Bergonié, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-bcma-multiple-myeloma-leukemia-2020","kind":"paper","name":"B-cell maturation antigen (BCMA) in multiple myeloma: rationale for targeting and current therapeutic approaches","aka":[],"tldr":"Review on BCMA in Multiple myeloma, in Leukemia (2020), one of the most cited Europe PMC records with BCMA in its title.","summary":"Despite considerable advances in the treatment of multiple myeloma (MM) in the last decade, a substantial proportion of patients do not respond to current therapies or have a short duration of response. Furthermore, these treatments can have notable morbidity and are not uniformly tolerated in all patients. As there is no cure for MM, patients eventually become resistant to therapies, leading to development of relapsed/refractory MM. Therefore, an unmet need exists for MM treatments with novel mechanisms of action that can provide durable responses, evade resistance to prior therapies, and/or are better tolerated. B-cell maturation antigen (BCMA) is preferentially expressed by mature B lymphocytes, and its overexpression and activation are associated with MM in preclinical models and humans, supporting its potential utility as a therapeutic target for MM. Moreover, the use of BCMA as a biomarker for MM is supported by its prognostic value, correlation with clinical status, and its ability to be used in traditionally difficult-to-monitor patient populations. Here, we review three common treatment modalities used to target BCMA in the treatment of MM: bispecific antibody constructs, antibody-drug conjugates, and chimeric antigen receptor (CAR)-modified T-cell therapy. We provide an overview of preliminary clinical data from trials using these therapies, including the BiTE® (bispecific T-cell engager) immuno-oncology therapy AMG 420, the antibody-drug conjugate GSK2857916, and several CAR T-cell therapeutic agents including bb2121, NIH CAR-BCMA, and LCAR-B38M. Notable antimyeloma activity and high minimal residual disease negativity rates have been observed with several of these treatments. These clinical data outline the potential for BCMA-targeted therapies to improve the treatment landscape for MM. Importantly, clinical results to date suggest that these therapies may hold promise for deep and durable responses and support further investigation in earlier lines of treatment, including newly diagnosed MM.\n\nIndexed on Europe PMC as PubMed record 32055000 (DOI 10.1038/s41375-020-0734-z). Its title names BCMA and its text names Multiple myeloma; PubMed types it as a review (Research Support, Non-U.S. Gov't, review-article, Review). It was matched automatically to the idea \"In vivo CAR-T manufactured and priced like a generic biologic\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Leukemia 2020","url":"https://doi.org/10.1038/s41375-020-0734-z"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32055000/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32055000"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["leukemia"],"dependsOn":[],"notes":[],"journal":"Leukemia","year":2020,"doi":"10.1038/s41375-020-0734-z","pmid":"32055000","authors":"Shah N, Chari A, Scott E, et al.","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for BCMA in Multiple myeloma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by BCMA in the title and Multiple myeloma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-b7-h3-glioblastoma-int-j-biol-sci-2023","kind":"paper","name":"B7-H3 in Brain Malignancies: Immunology and Immunotherapy","aka":[],"tldr":"Review on B7-H3 in Glioma & glioblastoma, in International journal of biological sciences (2023), one of the most cited Europe PMC records with B7-H3 in its title.","summary":"The immune checkpoint B7-H3 (CD276), a member of the B7 family with immunoregulatory properties, has been identified recently as a novel target for immunotherapy for refractory blood cancers and solid malignant tumors. While research on B7-H3 in brain malignancies is limited, there is growing interest in exploring its therapeutic potential in this context. B7-H3 plays a crucial role in regulating the functions of immune cells, cancer-associated fibroblasts, and endothelial cells within the tumor microenvironment, contributing to the creation of a pro-tumorigenic milieu. This microenvironment promotes uncontrolled cancer cell proliferation, enhanced metabolism, increased cancer stemness, and resistance to standard treatments. Blocking B7-H3 and terminating its immunosuppressive function is expected to improve anti-tumor immune responses and, in turn, ameliorate the progression of tumors. Results from preclinical or observative studies and early-phase trials targeting B7-H3 have revealed promising anti-tumor efficacy and acceptable toxicity in glioblastoma (GBM), diffuse intrinsic pontine glioma (DIPG), medulloblastoma, neuroblastoma, craniopharyngioma, atypical teratoid/rhabdoid tumor, and brain metastases. Ongoing clinical trials are now investigating the use of CAR-T cell therapy and antibody-drug conjugate therapy, either alone or in combination with standard treatments or other therapeutic approaches, targeting B7-H3 in refractory or recurrent GBMs, DIPGs, neuroblastomas, medulloblastomas, ependymomas, and metastatic brain tumors. These trials hold promise for providing effective treatment options for these challenging intracranial malignancies in both adult and pediatric populations.\n\nIndexed on Europe PMC as PubMed record 37564196 (DOI 10.7150/ijbs.85813). Its title names B7-H3 and its text names Glioma & glioblastoma; PubMed types it as a review (Research Support, Non-U.S. Gov't, review-article, Review). It was matched automatically to the idea \"Focused-ultrasound BBB opening to deliver ADCs and radioligands to glioma\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Int J Biol Sci 2023","url":"https://doi.org/10.7150/ijbs.85813"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37564196/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37564196"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"International journal of biological sciences","year":2023,"doi":"10.7150/ijbs.85813","pmid":"37564196","authors":"Guo X, Chang M, Wang Y, et al.","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for B7-H3 in Glioma & glioblastoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by B7-H3 in the title and Glioma & glioblastoma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-balkwill-mantovani-inflammation-virchow-lancet-2001","kind":"paper","name":"Balkwill and Mantovani 2001: inflammation and cancer, back to Virchow?","aka":[],"tldr":"A short, widely cited essay reviving Virchow's 1863 observation that tumours are full of white blood cells, arguing that the inflammatory cells and cytokines in tumours help them grow rather than fight them.","summary":"Balkwill and Mantovani revisited Rudolf Virchow's observation of leukocytes in tumours and assembled the modern evidence: that chronic inflammatory conditions predispose to cancer, that tumours recruit macrophages and other inflammatory cells whose cytokines and chemokines promote growth, angiogenesis and invasion, and that inflammatory mediators such as TNF, IL-1 and IL-6 have tumour-promoting roles. They noted the reduced colorectal cancer risk in long-term users of non-steroidal anti-inflammatory drugs as clinical support and proposed anti-inflammatory strategies for prevention and treatment.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1016/S0140-6736(00)04046-0"}],"tags":[],"related":["paper-coussens-werb-inflammation-cancer-nature-2002","paper-grivennikov-immunity-inflammation-cancer-cell-2010"],"cancers":[],"sections":[],"technologies":["aspirin-cancer-prevention"],"targets":[],"drugs":[],"companies":[],"institutions":["humanitas"],"pathways":["inflammation-nfkb"],"terms":["inflammation","tumor-associated-macrophages","macrophage"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2001,"doi":"10.1016/S0140-6736(00)04046-0","authors":"Balkwill F, Mantovani A.","paperType":"review","findings":["Chronic inflammation predisposes to cancer and tumours themselves recruit inflammatory cells.","Cytokines and chemokines from tumour-associated leukocytes promote proliferation, angiogenesis and invasion.","Long-term NSAID use is associated with lower colorectal cancer risk, supporting the causal link."],"whatItMeans":"Together with the 2002 Nature review this essay put inflammation on the cancer research agenda; the tumour-associated macrophage and IL-6 work that followed, and the aspirin prevention trials, trace back to it.","caveats":["An essay rather than a systematic review.","Distinguishing tumour-promoting from tumour-fighting inflammation remains a central challenge."],"changedPractice":false},{"id":"paper-bao-glioma-stem-cells-radioresistance-nature-2006","kind":"paper","name":"Bao 2006: glioma stem cells resist radiotherapy by activating the DNA damage response","aka":[],"tldr":"The glioblastoma cells with stem-like features survive radiotherapy better than the rest of the tumour because they repair DNA damage more efficiently, which helps explain why the cancer returns after treatment and points to checkpoint inhibitors as a way to sensitise it.","summary":"Bao, Rich and colleagues showed that CD133-positive glioma cells, the fraction with stem cell properties, became enriched after ionising radiation both in mouse xenografts and in patient specimens. These cells activated the DNA damage checkpoint proteins ATM, Rad17, Chk1 and Chk2 more strongly and repaired radiation-induced DNA damage more effectively than CD133-negative cells. Blocking Chk1 and Chk2 with a small molecule reversed the radioresistance, suggesting a way to target the cells that survive standard treatment.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1038/nature05236"}],"tags":[],"related":["paper-reya-cancer-stem-cells-nature-2001"],"cancers":["glioblastoma"],"sections":[],"technologies":[],"targets":["atr"],"drugs":[],"companies":[],"institutions":["duke-cancer-institute"],"pathways":[],"terms":["stem-cell","radiotherapy","relapse-recurrence"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature","year":2006,"doi":"10.1038/nature05236","authors":"Bao S, Wu Q, McLendon RE, et al.","paperType":"basic","findings":["CD133-positive glioma cells were enriched after radiation in xenografts and in patient tumours.","These cells showed preferential activation of the DNA damage checkpoint (ATM, Rad17, Chk1, Chk2) and more effective DNA repair.","A Chk1 and Chk2 inhibitor reversed the radioresistance of the CD133-positive cells."],"whatItMeans":"This paper connected the cancer stem cell idea to a clinical problem, the near-universal recurrence of glioblastoma after radiotherapy, and gave a mechanism and a drug target. It is part of the rationale for combining radiotherapy with DNA damage response inhibitors now in trials.","caveats":["CD133 is an imperfect marker of glioma stem cells and CD133-negative cells can also initiate tumours.","Mouse xenograft and cell line work; the clinical benefit of checkpoint inhibition with radiotherapy is not yet proven."],"changedPractice":false},{"id":"paper-epstein-nat-rev-cancer","kind":"paper","name":"Basal cell carcinomas: attack of the hedgehog","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 18813320 and published in Nature Reviews Cancer; the citing page links this DOI, which is how the record was matched.","summary":"Basal cell carcinomas (BCCs) were essentially a molecular 'black box' until some 12 years ago, when identification of a genetic flaw in a rare subset of patients who have a great propensity to develop BCCs pointed to aberrant Hedgehog signalling as the pivotal defect leading to formation of these tumours. This discovery has facilitated a remarkable increase in our understanding of BCC carcinogenesis and has highlighted the carcinogenic role of this developmental pathway when aberrantly activated in adulthood. Importantly, a phase 1 first-in-human trial of a Hedgehog inhibitor has shown real progress in halting and even reversing the growth of these tumours.\n\nIndexed on Europe PMC as PubMed record 18813320 (DOI 10.1038/nrc2503). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Cancer 2008","url":"https://doi.org/10.1038/nrc2503"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/18813320/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/18813320"}],"tags":["europepmc-ingest"],"related":["basal-cell-carcinoma-signalling"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Cancer","year":2008,"doi":"10.1038/nrc2503","pmid":"18813320","authors":"Epstein EH","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-basch-epro-survival-jama-2017","kind":"paper","name":"Basch: asking patients to report symptoms online during chemotherapy improved survival","aka":[],"tldr":"Patients on chemotherapy for advanced cancer who reported 12 symptoms weekly through a web tool, with nurse alerts for severe symptoms, lived a median 5 months longer than those receiving usual care.","summary":"This single-centre trial at Memorial Sloan Kettering randomised 766 patients starting chemotherapy for metastatic solid tumours to weekly electronic self-reporting of 12 common symptoms (with email alerts to nurses when symptoms worsened or were severe) or to usual care, in which symptoms were discussed at visits.\n\nThe 2016 JCO report showed better health-related quality of life at 6 months (improved in 34% vs 18%), fewer emergency department visits (34% vs 41%), fewer hospitalisations and longer time on chemotherapy (8.2 vs 6.3 months). This 2017 research letter reported the overall survival analysis: median 31.2 months with self-reporting versus 26.0 months with usual care.\n\nThe survival result, replicated in a French lung cancer trial (Denis, JAMA 2019), turned symptom monitoring into a standard of care and drove the design of the multi-site PRO-TECT trial.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1001/jama.2017.7156"},{"label":"Primary report (JCO 2016)","url":"https://doi.org/10.1200/JCO.2015.63.0830"},{"label":"ClinicalTrials.gov NCT00578006","url":"https://clinicaltrials.gov/study/NCT00578006"}],"tags":[],"related":["idea-moon-pro-monitoring-standard","idea-acc-electronic-pro-monitoring-standard","idea-data-pro-as-structured-standard","idea-moon-pro-ctcae-in-every-pivotal-trial"],"cancers":[],"sections":["supportive-care"],"technologies":["epro-symptom-monitoring","remote-patient-monitoring"],"targets":[],"drugs":[],"companies":[],"institutions":["mskcc"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-patient-voice","b-toxicity-qol","b-care-fragmentation"],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2017,"doi":"10.1001/jama.2017.7156","pmid":"28586821","authors":"Basch E, Deal AM, Dueck AC, et al.","paperType":"rct","findings":["Median overall survival 31.2 vs 26.0 months (HR 0.83, 95% CI 0.70-0.99; p = 0.03)","Health-related quality of life improved in 34% vs 18% at 6 months (JCO 2016)","Emergency department visits 34% vs 41%; hospitalisations 45% vs 49%","Patients stayed on chemotherapy longer: median 8.2 vs 6.3 months"],"whatItMeans":"Routinely asking patients how they feel between visits, and acting on the answers, is a treatment in itself. It catches problems early, keeps people on effective therapy longer and appears to extend life. Cancer centres now build symptom monitoring into electronic records, though implementation is uneven.","caveats":["Single centre; survival was a secondary endpoint and the effect size is modest","The larger multi-site PRO-TECT trial (2022) improved physical function and symptom control but did not show a survival benefit","Requires nursing capacity to respond to alerts; the mechanism may be earlier intervention rather than the reporting itself","Patients unfamiliar with computers were given a bespoke system, a subgroup that showed the largest benefit"],"changedPractice":true,"participants":766},{"id":"paper-bclc-2022-reig-j-hepatol-2022","kind":"paper","name":"BCLC strategy for prognosis prediction and treatment recommendation: the 2022 update","aka":[],"tldr":"The 2022 Barcelona Clinic Liver Cancer update refines the staging system that links liver cancer stage to treatment, incorporating immunotherapy as first-line systemic therapy, treatment stage migration and a more nuanced view of intermediate-stage disease.","summary":"Update of the BCLC staging and treatment algorithm for hepatocellular carcinoma covering very early, early, intermediate, advanced and terminal stages, with revised recommendations for resection, ablation, transplantation, transarterial therapies, and systemic therapy led by atezolizumab-bevacizumab and durvalumab-tremelimumab, plus the concepts of treatment stage migration and untreatable progression.","asOf":"2026-09-17","links":[{"label":"J Hepatol 2022","url":"https://doi.org/10.1016/j.jhep.2021.11.018"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34801630/"}],"tags":[],"related":[],"cancers":["hcc-early","hcc-intermediate","hcc-advanced"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of Hepatology","year":2022,"doi":"10.1016/j.jhep.2021.11.018","pmid":"34801630","authors":"Reig M, Forner A, Rimola J, et al.","paperType":"guideline","findings":[],"whatItMeans":"The BCLC stages used on this site's hepatocellular carcinoma pages and their default treatments follow this update.","caveats":["Combination of locoregional and systemic therapy for intermediate disease (EMERALD-1, LEAP-012) postdates the update."],"changedPractice":true},{"id":"paper-beamion-lung-1-zongertinib-nejm-2025","kind":"paper","name":"Beamion LUNG-1: zongertinib in previously treated HER2-mutant non-small-cell lung cancer","aka":[],"tldr":"The oral HER2-selective kinase inhibitor zongertinib shrank tumours in about seven in ten patients with previously treated HER2-mutant lung cancer with little of the diarrhoea and rash that plagued earlier HER2 pills, becoming the first oral drug approved for this driver.","summary":"Phase 1a/1b study; the primary cohort treated 75 patients with previously treated HER2 tyrosine kinase domain-mutant advanced non-small-cell lung cancer with zongertinib 120 mg daily.\n\nObjective response was 71 percent with a median progression-free survival of 12.4 months, intracranial activity in patients with brain metastases, and mainly low-grade diarrhoea and rash; a separate cohort showed activity after prior trastuzumab deruxtecan.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2025","url":"https://doi.org/10.1056/NEJMoa2503704"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40293180/"}],"tags":[],"related":[],"cancers":["her2-mutant-nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":["zongertinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["beamion-lung-1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2025,"doi":"10.1056/NEJMoa2503704","pmid":"40293180","authors":"Heymach JV, Ruiter G, Ahn MJ, et al.","paperType":"observational","findings":["Objective response 71 percent.","Median progression-free survival 12.4 months."],"whatItMeans":"Zongertinib gives HER2-mutant lung cancer an oral targeted option with brain activity, used after platinum chemotherapy and increasingly before or after trastuzumab deruxtecan.","caveats":["Single-arm phase 1 data; first-line trials against chemo-immunotherapy are ongoing."],"changedPractice":true,"participants":75},{"id":"paper-rockstar-blood-2021","kind":"paper","name":"Belumosudil for chronic graft-versus-host disease after 2 or more prior lines of therapy: the ROCKstar Study","aka":[],"tldr":"The primary report of ROCKstar: about three in four patients with chronic graft-versus-host disease that had failed at least two treatments responded to belumosudil at either dose, and responses lasted about a year.","summary":"Phase 2 randomised multicentre registration study of belumosudil, an oral selective ROCK2 inhibitor that reduces type 17 and follicular T helper cells and enhances regulatory T cells, at 200 mg daily (66 patients) and 200 mg twice daily (66) in chronic graft-versus-host disease after 2 to 5 prior lines of therapy. The primary endpoint was best overall response rate; duration of response, Lee Symptom Scale change, failure-free survival, corticosteroid dose reduction and overall survival were also evaluated.\n\nAt a median follow-up of 14 months the best overall response rate was 74 percent (95% CI 62 to 84) with 200 mg daily and 77 percent (95% CI 65 to 87) with 200 mg twice daily, with high response rates in all subgroups and complete responses in all affected organs. Median duration of response was 54 weeks and 44 percent of patients remained on therapy for at least a year. Symptom reduction was reported in 59 and 62 percent. Sixteen patients (12 percent) discontinued because of possible drug-related adverse events.","asOf":"2026-09-24","links":[{"label":"Blood 2021","url":"https://doi.org/10.1182/blood.2021012021"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34265047/"},{"label":"ClinicalTrials.gov NCT03640481","url":"https://clinicaltrials.gov/study/NCT03640481"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["belumosudil"],"companies":["sanofi"],"institutions":[],"pathways":[],"terms":["gvhd","allogeneic-transplant"],"trials":["rockstar"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["blood"],"dependsOn":[],"notes":[],"journal":"Blood","year":2021,"doi":"10.1182/blood.2021012021","pmid":"34265047","authors":"Cutler C, Lee SJ, Arai S, et al.","paperType":"rct","findings":["Best overall response rate 74% (95% CI 62 to 84) with 200 mg daily and 77% (95% CI 65 to 87) with 200 mg twice daily.","Median duration of response 54 weeks; 44% of patients on therapy for at least 1 year.","Lee Symptom Scale reduction in 59% and 62%; 12% discontinued for possible drug-related adverse events."],"whatItMeans":"This is the trial behind belumosudil's July 2021 US approval for chronic graft-versus-host disease after two or more lines. For patients it means a once-daily pill with a high response rate in a condition where earlier treatments had failed; the FDA's own analysis, counting responses only through cycle 7 day 1, gave 75 percent.","caveats":["Both arms received belumosudil; there was no comparator, and response was assessed by site investigators.","The 74% and 77% are best response at any time; the FDA's stricter through-cycle-7 analysis and its 1.9-month median duration of response measure different things.","The registry records the study as terminated in 2023 because adolescents were hard to recruit, after the adult analysis and approval."],"changedPractice":true,"participants":132},{"id":"paper-belzutifan-vhl-jonasch-nejm-2021","kind":"paper","name":"Belzutifan for renal cell carcinoma and other tumours in von Hippel-Lindau disease","aka":[],"tldr":"The oral HIF-2 alpha inhibitor belzutifan shrank kidney cancers in about half of people with von Hippel-Lindau disease and also shrank their brain and spinal haemangioblastomas and pancreatic tumours, letting many avoid repeated operations.","summary":"Phase 2 study of 61 patients with von Hippel-Lindau disease and at least one measurable renal cell carcinoma not needing immediate surgery, treated with belzutifan 120 mg daily.\n\nObjective response in renal tumours was 49 percent, with responses in 30 percent of central nervous system haemangioblastomas and 77 percent of pancreatic neuroendocrine tumours; anaemia and hypoxia were the main side effects.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2021","url":"https://doi.org/10.1056/NEJMoa2103425"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34818478/"}],"tags":[],"related":[],"cancers":["spinal-cord-tumours"],"sections":[],"technologies":[],"targets":[],"drugs":["belzutifan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["eric-jonasch"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2021,"doi":"10.1056/NEJMoa2103425","pmid":"34818478","authors":"Jonasch E, Donskov F, Iliopoulos O, et al.","paperType":"observational","findings":["Renal cell carcinoma objective response 49 percent.","Central nervous system haemangioblastoma response 30 percent; pancreatic neuroendocrine tumour response 77 percent."],"whatItMeans":"Belzutifan is the first systemic therapy for von Hippel-Lindau disease, approved for renal, central nervous system and pancreatic tumours not needing immediate surgery, changing a lifetime of surveillance and surgery for many patients.","caveats":["Single-arm study; long-term durability and the effect on survival are unknown.","Anaemia in most patients, hypoxia in a minority; teratogenic."],"changedPractice":true,"participants":61},{"id":"paper-litespark-011-motzer-lancet-2026","kind":"paper","name":"Belzutifan plus lenvatinib versus cabozantinib in patients with previously treated advanced renal cell carcinoma (LITESPARK-011): an open-label, randomised, controlled, phase 3 trial","aka":[],"tldr":"In 747 people whose advanced clear-cell kidney cancer had grown after immunotherapy, belzutifan plus lenvatinib kept the cancer from progressing for a median of 14.8 months against 10.7 with cabozantinib, but at this interim look the survival difference was not statistically significant.","summary":"Primary publication of LITESPARK-011 (NCT04586231), an open-label, randomised, active-controlled phase 3 trial at 184 centres in 25 countries. Adults with advanced clear-cell renal cell carcinoma that had progressed after anti-PD-1 or anti-PD-L1 therapy, with or without a prior VEGFR tyrosine kinase inhibitor, were randomly assigned 1:1 to belzutifan 120 mg plus lenvatinib 20 mg or cabozantinib 60 mg, orally once daily, stratified by IMDC score, line of previous immunotherapy and region. The dual primary endpoints were progression-free survival by masked independent central review and overall survival in all randomised participants.\n\nBetween 5 March 2021 and 1 September 2023, 955 people were screened and 747 randomised (371 belzutifan plus lenvatinib, 376 cabozantinib); 76 percent were male and 87 percent White. At the second interim analysis (data cutoff 9 April 2025; median follow-up 29.0 months, IQR 23.7 to 34.9), progression-free survival was significantly longer with belzutifan plus lenvatinib (median 14.8 months, 95 percent CI 11.2 to 16.6, versus 10.7 months, 9.2 to 11.1; hazard ratio 0.70, 0.59 to 0.84; one-sided p less than 0.0001). Overall survival was not significantly different (median 34.9 months, 27.5 to not reached, versus 27.6 months, 24.0 to 31.4; hazard ratio 0.85, 0.68 to 1.05; one-sided p 0.061). Grade 3 or worse treatment-emergent adverse events occurred in 311 of 370 (84 percent) and 307 of 371 (83 percent) treated participants, most commonly hypertension (31 and 29 percent); treatment-related adverse events led to two deaths and one death respectively. The authors conclude that belzutifan plus lenvatinib is a novel and efficacious option that might become a new standard of care after immunotherapy, with a safety profile consistent with the individual drugs.","asOf":"2026-09-24","links":[{"label":"Lancet 2026","url":"https://doi.org/10.1016/S0140-6736(26)01089-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42586114/"},{"label":"ClinicalTrials.gov NCT04586231","url":"https://clinicaltrials.gov/study/NCT04586231"}],"tags":[],"related":[],"cancers":["rcc"],"sections":[],"technologies":[],"targets":[],"drugs":["belzutifan","lenvatinib","cabozantinib"],"companies":["merck","eisai"],"institutions":[],"pathways":[],"terms":[],"trials":["nct04586231"],"people":["robert-motzer"],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2026,"doi":"10.1016/S0140-6736(26)01089-5","pmid":"42586114","authors":"Motzer RJ, McDermott R, Park SH, et al.","paperType":"rct","findings":["Progression-free survival (final analysis): median 14.8 vs 10.7 months; hazard ratio 0.70 (95 percent CI 0.59 to 0.84); one-sided p<0.0001.","Overall survival (interim analysis): median 34.9 vs 27.6 months; hazard ratio 0.85 (0.68 to 1.05); one-sided p 0.061; not statistically significant.","Grade 3 or worse treatment-emergent adverse events in 84 percent vs 83 percent; hypertension the commonest; treatment-related deaths 2 vs 1."],"whatItMeans":"There has been no clear standard for clear-cell kidney cancer that progresses after immunotherapy; this is the first phase 3 to show a HIF-2 alpha inhibitor combination beating a standard tyrosine kinase inhibitor on progression-free survival in that setting. Whether it changes practice depends on the final overall survival analysis and on regulators, since the interim survival difference did not reach significance and the combination brings the toxicity of two drugs.","caveats":["Overall survival, a dual primary endpoint, was not statistically significant at this interim analysis; a survival benefit is not established.","Open-label design; progression-free survival was assessed by masked central review to limit bias.","87 percent of participants were White, and the comparator was cabozantinib alone rather than the newer sequences some centres use.","Funded by Merck Sharp & Dohme; the objective response and duration-of-response figures were presented at ASCO GU 2026 and are not in the abstract."],"changedPractice":false,"participants":747},{"id":"paper-rummel-lancet","kind":"paper","name":"Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial","aka":[],"tldr":"Paper cited by one treatment page, indexed on Europe PMC as PubMed record 23433739 and published in The Lancet; the citing page links this DOI, which is how the record was matched.","summary":"Background: Rituximab plus chemotherapy, most often CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), is the first-line standard of care for patients with advanced indolent lymphoma, and for elderly patients with mantle-cell lymphoma. Bendamustine plus rituximab is effective for relapsed or refractory disease. We compared bendamustine plus rituximab with CHOP plus rituximab (R-CHOP) as first-line treatment for patients with indolent and mantle-cell lymphomas.\n\nMethods: We did a prospective, multicentre, randomised, open-label, non-inferiority trial at 81 centres in Germany between Sept 1, 2003, and Aug 31, 2008. Patients aged 18 years or older with a WHO performance status of 2 or less were eligible if they had newly diagnosed stage III or IV indolent or mantle-cell lymphoma. Patients were stratified by histological lymphoma subtype, then randomly assigned according to a prespecified randomisation list to receive either intravenous bendamustine (90 mg/m(2) on days 1 and 2 of a 4-week cycle) or CHOP (cycles every 3 weeks of cyclophosphamide 750 mg/m(2), doxorubicin 50 mg/m(2), and vincristine 1.4 mg/m(2) on day 1, and prednisone 100 mg/day for 5 days) for a maximum of six cycles. Patients in both groups received rituximab 375 mg/m(2) on day 1 of each cycle. Patients and treating physicians were not masked to treatment allocation. The primary endpoint was progression-free survival, with a non-inferiority margin of 10%. Analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00991211, and the Federal Institute for Drugs and Medical Devices of Germany, BfArM 4021335.\n\nFindings: 274 patients were assigned to bendamustine plus rituximab (261 assessed) and 275 to R-CHOP (253 assessed). At median follow-up of 45 months (IQR 25-57), median progression-free survival was significantly longer in the bendamustine plus rituximab group than in the R-CHOP group (69.5 months [26.1 to not yet reached] vs 31.2 months [15.2-65.7]; hazard ratio 0.58, 95% CI 0.44-0.74; p<0.0001). Bendamustine plus rituximab was better tolerated than R-CHOP, with lower rates of alopecia (0 patients vs 245 (100%) of 245 patients who recieved ≥3 cycles; p<0.0001), haematological toxicity (77 [30%] vs 173 [68%]; p<0.0001), infections (96 [37%] vs 127 [50%]); p=0.0025), peripheral neuropathy (18 [7%] vs 73 [29%]; p<0.0001), and stomatitis (16 [6%] vs 47 [19%]; p<0.0001). Erythematous skin reactions were more common in patients in the bendamustine plus rituximab group than in those in the R-CHOP group (42 [16%] vs 23 [9%]; p=0.024).\n\nInterpretation: In patients with previously untreated indolent lymphoma, bendamustine plus rituximab can be considered as a preferred first-line treatment approach to R-CHOP because of increased progression-free survival and fewer toxic effects.\n\nFunding: Roche Pharma AG, Ribosepharm/Mundipharma GmbH.\n\nIndexed on Europe PMC as PubMed record 23433739 (DOI 10.1016/s0140-6736(12)61763-2). Matched by DOI alone: one treatment page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet 2013","url":"https://doi.org/10.1016/s0140-6736(12)61763-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23433739/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/23433739"}],"tags":["europepmc-ingest"],"related":["bendamustine"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2013,"doi":"10.1016/s0140-6736(12)61763-2","pmid":"23433739","authors":"Rummel MJ, Niederle N, Maschmeyer G, et al.","paperType":"rct","findings":[],"whatItMeans":"One treatment page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-sun-bmc-cancer","kind":"paper","name":"Benefits of hyperthermic intraperitoneal chemotherapy for patients with serosal invasion in gastric cancer: a meta-analysis of the randomized controlled trials","aka":[],"tldr":"Paper cited by one bottleneck page and eight idea pages, indexed on Europe PMC as PubMed record 23153379 and published in BMC cancer; the citing pages link this DOI, which is how the record was matched.","summary":"Background: In this meta-analysis we aimed to determine the effectiveness and safety of hyperthermic intraperitoneal chemotherapy (HIPC) for patients with advanced gastric cancer who underwent gastrectomy.\n\nMethods: In accordance with standard meta-analysis procedures, our study included patients who underwent resection for advanced gastric cancer and were randomly allocated to receive either hyperthermic intraperitoneal chemotherapy or control. We searched PubMed (up to November 2011), EMBASE (up to November 2011), Cochrane Database of Systematic Reviews (CDSR), and Cochrane Central Register of Controlled Trials (CCTR) (up to November 2011). Both published and unpublished trials were included in the analysis, and no search restrictions were imposed. There was no language restriction. The results were analyzed using RevMan 5.1 software, which was provided by Cochrane Collaboration.\n\nResults: There were ten randomized controlled trials included in the analysis. A total of 1062 patients with gastric cancer in these studies were divided into the HIPC group (n = 518) and control group (n = 544). A significant improvement in survival was observed in the HIPC groups compared to the control group in the mitomycin C (MMC) subgroup (RR = 0.75, 95%CI 0.65-0.86; P < 0.00001) and the 5-FU group (RR = 0.69, 95%CI 0.52-0.90; P < 0.00001); the total RR was 0.73 (95%CI 0.64-0.83; P < 0.00001). Our findings indicated that HIPC potentially exhibited a lower peritoneal recurrence rate in the HIPC group compared to the control group (RR = 0.45, 95%CI 0.28-0.72; P = 0.001).\n\nConclusions: Our meta-analysis demonstrated that HIPC may improve the overall survival rate for patients who receive resection for advance gastric cancer potentially, and help to prevent peritoneal local recurrence among patients with serosal invasion in gastric cancer.\n\nIndexed on Europe PMC as PubMed record 23153379 (DOI 10.1186/1471-2407-12-526). Matched by DOI alone: one bottleneck page and eight idea pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"BMC Cancer 2012","url":"https://doi.org/10.1186/1471-2407-12-526"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23153379/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/23153379"}],"tags":["europepmc-ingest"],"related":["b-funding-allocation","idea-fund-cachexia-programme","idea-fund-implementation-quota","idea-fund-non-drug-trial-quota","idea-fund-survivorship-endowment-levy","idea-fund-older-patients-trial-fund","idea-fund-lmic-burden-match","idea-fund-programme-officer-incentives","idea-fund-brain-metastases-programme"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["bmc-cancer"],"dependsOn":[],"notes":[],"journal":"BMC cancer","year":2012,"doi":"10.1186/1471-2407-12-526","pmid":"23153379","authors":"Sun J, Song Y, Wang Z, et al.","paperType":"meta-analysis","findings":[],"whatItMeans":"One bottleneck page and eight idea pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-olivier-chinot-cancer-treat-rev-2020","kind":"paper","name":"Bevacizumab (Avastin®) in cancer treatment: A review of 15 years of clinical experience and future outlook","aka":[],"tldr":"Paper by Olivier L. Chinot indexed on Europe PMC as PubMed record 32335505, in Cancer treatment reviews (2020), one of the most cited records naming an author with this name at Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille.","summary":"When the VEGF-A-targeting monoclonal antibody bevacizumab (Avastin®) entered clinical practice more than 15 years ago, it was one of the first targeted therapies and the first approved angiogenesis inhibitor. Marking the beginning for a new line of anti-cancer treatments, bevacizumab remains the most extensively characterized anti-angiogenetic treatment. Initially approved for treatment of metastatic colorectal cancer in combination with chemotherapy, its indications now include metastatic breast cancer, non-small-cell lung cancer, glioblastoma, renal cell carcinoma, ovarian cancer and cervical cancer. This review provides an overview of the clinical experience and lessons learned since bevacizumab's initial approval, and highlights how this knowledge has led to the investigation of novel combination therapies. In the past 15 years, our understanding of VEGF's role in the tumor microenvironment has evolved. We now know that VEGF not only plays a major role in controlling blood vessel formation, but also modulates tumor-induced immunosuppression. These immunomodulatory properties of bevacizumab have opened up new perspectives for combination therapy approaches, which are being investigated in clinical trials. Specifically, the combination of bevacizumab with cancer immunotherapy has recently been approved in non-small-cell lung cancer and clinical benefit was also demonstrated for treatment of hepatocellular carcinoma. However, despite intense investigation, reliable and validated biomarkers that would enable a more personalized use of bevacizumab remain elusive. Overall, bevacizumab is expected to remain a key agent in cancer therapy, both due to its established efficacy in approved indications and its promise as a partner in novel targeted combination treatments.\n\nIndexed on Europe PMC as PubMed record 32335505 (DOI 10.1016/j.ctrv.2020.102017). Its author list gives \"Chinot OL\" with the affiliation \"Aix-Marseille University, Assistance Publique-Hopitaux de Marseille, Centre Hospitalo-Universitaire Timone, Service de Neuro-Oncologie, Marseille, France\", which names Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille; that is how the record was matched to Olivier L. Chinot, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer Treat Rev 2020","url":"https://doi.org/10.1016/j.ctrv.2020.102017"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32335505/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32335505"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["olivier-chinot"],"bottlenecks":[],"keyPapers":[],"journals":["cancer-treatment-reviews"],"dependsOn":[],"notes":[],"journal":"Cancer treatment reviews","year":2020,"doi":"10.1016/j.ctrv.2020.102017","pmid":"32335505","authors":"Garcia J, Hurwitz HI, Sandler AB, et al.","paperType":"review","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Olivier L. Chinot at Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-olivier-chinot-n-engl-j-med-2014","kind":"paper","name":"Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma","aka":[],"tldr":"Paper by Olivier L. Chinot indexed on Europe PMC as PubMed record 24552318, in New England Journal of Medicine (2014), one of the most cited records naming an author with this name at Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille.","summary":"Background: Standard therapy for newly diagnosed glioblastoma is radiotherapy plus temozolomide. In this phase 3 study, we evaluated the effect of the addition of bevacizumab to radiotherapy-temozolomide for the treatment of newly diagnosed glioblastoma.\n\nMethods: We randomly assigned patients with supratentorial glioblastoma to receive intravenous bevacizumab (10 mg per kilogram of body weight every 2 weeks) or placebo, plus radiotherapy (2 Gy 5 days a week; maximum, 60 Gy) and oral temozolomide (75 mg per square meter of body-surface area per day) for 6 weeks. After a 28-day treatment break, maintenance bevacizumab (10 mg per kilogram intravenously every 2 weeks) or placebo, plus temozolomide (150 to 200 mg per square meter per day for 5 days), was continued for six 4-week cycles, followed by bevacizumab monotherapy (15 mg per kilogram intravenously every 3 weeks) or placebo until the disease progressed or unacceptable toxic effects developed. The coprimary end points were investigator-assessed progression-free survival and overall survival.\n\nResults: A total of 458 patients were assigned to the bevacizumab group, and 463 patients to the placebo group. The median progression-free survival was longer in the bevacizumab group than in the placebo group (10.6 months vs. 6.2 months; stratified hazard ratio for progression or death, 0.64; 95% confidence interval [CI], 0.55 to 0.74; P<0.001). The benefit with respect to progression-free survival was observed across subgroups. Overall survival did not differ significantly between groups (stratified hazard ratio for death, 0.88; 95% CI, 0.76 to 1.02; P=0.10). The respective overall survival rates with bevacizumab and placebo were 72.4% and 66.3% at 1 year (P=0.049) and 33.9% and 30.1% at 2 years (P=0.24). Baseline health-related quality of life and performance status were maintained longer in the bevacizumab group, and the glucocorticoid requirement was lower. More patients in the bevacizumab group than in the placebo group had grade 3 or higher adverse events (66.8% vs. 51.3%) and grade 3 or higher adverse events often associated with bevacizumab (32.5% vs. 15.8%).\n\nConclusions: The addition of bevacizumab to radiotherapy-temozolomide did not improve survival in patients with glioblastoma. Improved progression-free survival and maintenance of baseline quality of life and performance status were observed with bevacizumab; however, the rate of adverse events was higher with bevacizumab than with placebo. (Funded by F. Hoffmann-La Roche; ClinicalTrials.gov number, NCT00943826.).\n\nIndexed on Europe PMC as PubMed record 24552318 (DOI 10.1056/nejmoa1308345). Its author list gives \"Chinot OL\" with the affiliation \"From Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille, Service de Neuro-Oncologie, Centre Hospitaliere Universitaire Timone, Marseille (O.L.C.), UFR de Santé, Médecine et Biologie Humaine, Bobigny (A.F.C.), and Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Avicenne, Service de Neurologie, Université Paris 13 (A.F.C.), and AP-HP, Université Pierre-et-Marie-Curie, Group Hospitalier Pitié-Salpêtrière (K.H.-X.), Paris - all in France; University Hospital of Heidelberg, Department of Neurooncology, and German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany (W.W.); Princess Margaret Hospital, Toronto (W.M.), and McGill University, Montreal (P.K.) - both in Canada; Regional Cancer Center, Stockholm Gotland, Karolinska, Stockholm, and the Department of Radiation Sciences and Oncology, Umeå University, Umeå - both in Sweden (R.H.); the Royal Marsden National Health Service Foundation Trust, Sutton, Surrey, United Kingdom (F.S.); Saitama Medical University, Saitama, Japan (R.N.); Oncology Institute \"Ion Chiricuta,\" Cluj-Napoca, Romania (D.C.); Medical Oncology Department, Azienda Unità Sanitaria Locale, Bologna, Italy (A.A.B.); F. Hoffmann-La Roche, Basel, Switzerland (M.H., L.A.); and University of California, Los Angeles, Los Angeles (T.C.)\", which names Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille; that is how the record was matched to Olivier L. Chinot, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2014","url":"https://doi.org/10.1056/nejmoa1308345"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24552318/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/24552318"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["olivier-chinot"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2014,"doi":"10.1056/nejmoa1308345","pmid":"24552318","authors":"Chinot OL, Wick W, Mason W, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Olivier L. Chinot at Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-bien-pancreatoblastoma-expert-european-cooperative-ejc-2011","kind":"paper","name":"Bien 2011: pancreatoblastoma, a report from the European cooperative study group for paediatric rare tumours (EXPeRT)","aka":[],"tldr":"Pooling children treated across Europe over a decade, this study showed that complete surgical removal is what cures pancreatoblastoma, that cisplatin and doxorubicin chemotherapy can shrink tumours that cannot be removed at first, and that about four in five children survive.","summary":"Retrospective multinational series from the EXPeRT group of children with pancreatoblastoma treated in France, Germany, Italy, Poland and the United Kingdom between 2000 and 2009. Most tumours arose in young children and were large at diagnosis; alpha-fetoprotein was raised in the majority and served as a tumour marker.\n\nComplete resection, either upfront or after neoadjuvant chemotherapy, was the strongest determinant of outcome. Cisplatin and doxorubicin (PLADO) was the most active regimen, achieving responses that allowed delayed resection. Event-free survival was about 60 percent and overall survival close to 80 percent at five years, with relapses salvageable in some children.","asOf":"2026-09-21","links":[{"label":"Eur J Cancer 2011","url":"https://doi.org/10.1016/j.ejca.2011.05.022"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21696948/"}],"tags":[],"related":[],"cancers":["pancreatoblastoma","pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":["cisplatin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["european-journal-of-cancer"],"dependsOn":[],"notes":[],"journal":"European Journal of Cancer","year":2011,"doi":"10.1016/j.ejca.2011.05.022","pmid":"21696948","authors":"Bien E, Godzinski J, Dall'igna P, et al.","paperType":"observational","findings":["Complete resection was the strongest determinant of cure; neoadjuvant chemotherapy made delayed resection possible.","Cisplatin plus doxorubicin was the most active regimen.","Five-year event-free survival about 60 percent and overall survival close to 80 percent."],"whatItMeans":"The EXPeRT recommendations, surgery when feasible and PLADO chemotherapy for unresectable or metastatic disease, remain the treatment framework for childhood pancreatoblastoma.","caveats":["Retrospective series of a few dozen children with heterogeneous treatment.","Adult pancreatoblastoma was not included and behaves worse."],"changedPractice":true},{"id":"paper-bilcap-lancet-oncol-2019","kind":"paper","name":"BILCAP: capecitabine compared with observation in resected biliary tract cancer","aka":[],"tldr":"Six months of capecitabine tablets after surgery for bile duct or gallbladder cancer lengthened survival by about a year in the per-protocol analysis, and became the standard adjuvant treatment despite narrowly missing its primary endpoint.","summary":"Phase 3 trial of 447 patients with completely resected cholangiocarcinoma (intrahepatic, perihilar or distal) or gallbladder cancer randomised to eight cycles of capecitabine or observation.\n\nIn the intention-to-treat analysis median overall survival was 51.1 versus 36.4 months (hazard ratio 0.81, not significant); in the prespecified per-protocol analysis it was 53 versus 36 months (hazard ratio 0.75, significant), and the adjusted analysis and long-term follow-up supported benefit.","asOf":"2026-09-17","links":[{"label":"Lancet Oncol 2019","url":"https://doi.org/10.1016/S1470-2045(18)30915-X"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30922733/"}],"tags":[],"related":[],"cancers":["extrahepatic-cholangiocarcinoma","intrahepatic-cholangiocarcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":["capecitabine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["bilcap"],"people":["john-primrose"],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2019,"doi":"10.1016/S1470-2045(18)30915-X","pmid":"30922733","authors":"Primrose JN, Fox RP, Palmer DH, et al.","paperType":"rct","findings":["Intention to treat: median overall survival 51.1 vs 36.4 months; hazard ratio 0.81 (not significant).","Per protocol: 53 vs 36 months; hazard ratio 0.75."],"whatItMeans":"Adjuvant capecitabine is the standard after resection of intrahepatic and extrahepatic cholangiocarcinoma and gallbladder cancer, endorsed by ASCO and ESMO guidelines.","caveats":["Primary endpoint not met in the intention-to-treat population.","Whether gemcitabine-cisplatin or chemo-immunotherapy adjuvant regimens are better is under study."],"changedPractice":true,"participants":447},{"id":"paper-javle-biliary-ngs-cancer-2016","kind":"paper","name":"Biliary cancer: utility of next-generation sequencing for clinical management","aka":[],"tldr":"A large commercial sequencing series of 554 biliary cancers, including 85 gallbladder tumours, showed that gallbladder cancer has HER2 changes in about one in six and almost no IDH or FGFR changes, the mirror image of intrahepatic bile duct cancer.","summary":"Hybrid capture-based comprehensive genomic profiling was performed for 412 intrahepatic cholangiocarcinomas, 57 extrahepatic cholangiocarcinomas and 85 gallbladder carcinomas, and the mutational profile was correlated with outcomes of standard and experimental therapies for 321 patients. In gallbladder carcinoma the most frequent alterations were TP53 (59%), CDKN2A/B (19%), ARID1A (13%) and ERBB2 (16%); in intrahepatic tumours TP53 (27%), CDKN2A/B (27%), KRAS (22%), ARID1A (18%) and IDH1 (16%); in extrahepatic tumours KRAS (42%), TP53 (40%), CDKN2A/B (17%) and SMAD4 (21%).\n\nFGFR (11%) and IDH mutations (20%) were mostly limited to intrahepatic tumours and appeared mutually exclusive. TP53 and KRAS mutations predicted shorter survival in intrahepatic disease, FGFR2 alterations better survival, and patients with FGFR alterations had superior survival on FGFR-targeted therapy than on standard regimens (P = 0.006).","asOf":"2026-09-24","links":[{"label":"Javle et al., Cancer 2016: comprehensive genomic profiling of 554 biliary cancers including 85 gallbladder carcinomas","url":"https://doi.org/10.1002/cncr.30254"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27622582/"}],"tags":[],"related":[],"cancers":["gallbladder","cholangiocarcinoma","intrahepatic-cholangiocarcinoma","extrahepatic-cholangiocarcinoma"],"sections":[],"technologies":[],"targets":["tp53","cdkn2a","arid1a","her2","idh","fgfr2","kras","smad4"],"drugs":[],"companies":["foundation-medicine"],"institutions":["md-anderson"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-wiley"],"dependsOn":[],"notes":[],"journal":"Cancer","year":2016,"doi":"10.1002/cncr.30254","pmid":"27622582","authors":"Javle M, Bekaii-Saab T, Jain A, et al.","paperType":"translational","findings":["Gallbladder carcinoma (n = 85): TP53 59%, CDKN2A/B 19%, ARID1A 13%, ERBB2 16%.","FGFR alterations (11%) and IDH mutations (20%) were largely confined to intrahepatic cholangiocarcinoma and were mutually exclusive.","FGFR-altered patients lived longer on FGFR-targeted therapy than on standard regimens (P = 0.006)."],"whatItMeans":"The clearest early head-to-head of the three biliary sites on one platform: for gallbladder cancer it made HER2 the target to test for and showed that IDH and FGFR inhibitors would rarely apply.","caveats":["Commercial referral cohort (FoundationOne), not population based.","Outcome correlations were retrospective across mixed therapies."],"changedPractice":false,"participants":554},{"id":"paper-esmo-biliary-tract-cancer-guideline-ann-oncol-2023","kind":"paper","name":"Biliary tract cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","aka":[],"tldr":"The European oncology society's 2023 guideline for bile duct and gallbladder cancer, covering how the diseases are diagnosed, staged, operated on, treated with drugs and followed up.","summary":"ESMO Clinical Practice Guideline for biliary tract cancer, published in Annals of Oncology in 2023 by Vogel, Bridgewater, Edeline and colleagues for the ESMO Guidelines Committee. Europe PMC indexes no abstract for this article, so OnCo carries no figures from it; the guideline itself is open on the ESMO website and covers diagnosis, molecular testing, resection and adjuvant capecitabine, first-line gemcitabine-cisplatin with durvalumab, and later-line targeted options.","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2023","url":"https://doi.org/10.1016/j.annonc.2022.10.506"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36372281/"},{"label":"ESMO guidelines: gastrointestinal cancers","url":"https://www.esmo.org/guidelines/esmo-clinical-practice-guidelines-gastrointestinal-cancers"}],"tags":["gallbladder-evidence"],"related":["esmo-guidelines"],"cancers":["gallbladder","cholangiocarcinoma","biliary-tract-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["esmo"],"pathways":[],"terms":[],"trials":[],"people":["john-primrose","juan-valle"],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2023,"doi":"10.1016/j.annonc.2022.10.506","pmid":"36372281","authors":"Vogel A, Bridgewater J, Edeline J, et al.","paperType":"guideline","findings":["No abstract is indexed on Europe PMC; recommendations are read from the guideline itself."],"whatItMeans":"This is the reference European standard against which UK and NHS practice for gallbladder cancer is compared; it treats gallbladder cancer within biliary tract cancer rather than as its own disease.","caveats":["Gallbladder cancer recommendations are largely extrapolated from mixed biliary trials.","Published before the zanidatamab approvals of 2024 and 2025."],"changedPractice":true},{"id":"paper-nccn-biliary-tract-cancers-v2-2025-jnccn-2025","kind":"paper","name":"Biliary Tract Cancers, Version 2.2025, NCCN Clinical Practice Guidelines In Oncology","aka":[],"tldr":"The 2025 summary of the US NCCN guideline for gallbladder and bile duct cancers, focused on what to give after surgery.","summary":"Journal summary of the NCCN Guidelines for Biliary Tract Cancers, version 2.2025, which cover gallbladder cancer, intrahepatic and extrahepatic cholangiocarcinoma. The panel meets at least yearly to review requests and new data; this manuscript focuses on the adjuvant chemotherapy and chemoradiation recommendations. The 2023 Insights paper (Benson et al., JNCCN 2023, PMID 37433432) recorded the split of the former Hepatobiliary Cancers guideline into separate Hepatocellular Carcinoma and Biliary Tract Cancers guidelines.","asOf":"2026-09-24","links":[{"label":"JNCCN 2025","url":"https://doi.org/10.6004/jnccn.2025.0042"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40930144/"},{"label":"NCCN Guidelines: Biliary Tract Cancers","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1517"}],"tags":["gallbladder-evidence"],"related":["nccn"],"cancers":["gallbladder","cholangiocarcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["bilcap","swog-s0809"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jnccn"],"dependsOn":[],"notes":[],"journal":"Journal of the National Comprehensive Cancer Network","year":2025,"doi":"10.6004/jnccn.2025.0042","pmid":"40930144","authors":"Benson AB, D'Angelica MI, Abrams T, et al.","paperType":"guideline","findings":["Covers gallbladder cancer, intrahepatic and extrahepatic cholangiocarcinoma; this version's text concentrates on adjuvant chemotherapy and chemoradiation."],"whatItMeans":"NCCN is the source of the category grades quoted on the gallbladder cancer page; the adjuvant section leans on BILCAP for capecitabine and on SWOG S0809 for chemoradiation after margin-positive or node-positive resection.","caveats":["The full guideline requires free registration on nccn.org; the JNCCN article is a summary.","Adjuvant recommendations for gallbladder cancer rest on subgroup and single-arm data."],"changedPractice":true},{"id":"paper-binnewies-tumor-immune-microenvironment-natmed-2018","kind":"paper","name":"Binnewies 2018: understanding the tumour immune microenvironment for effective therapy","aka":[],"tldr":"A review that sorted tumours by where their immune cells sit, inflamed and infiltrated, infiltrated but excluded, or immune-poor, and argued that this classification should guide which immunotherapy a patient receives.","summary":"Binnewies, Krummel and colleagues proposed classifying the tumour immune microenvironment (TIME) by the density and position of immune cells: infiltrated-excluded tumours with T cells confined to the margins and stroma, infiltrated-inflamed tumours with T cells among the cancer cells and high PD-L1, and a subclass with tertiary lymphoid structures. They reviewed how these states arise from tumour genetics, the microbiome and host factors, how they predict response to checkpoint blockade, and how therapies including chemotherapy, radiotherapy and myeloid-targeting agents might convert excluded or cold tumours into inflamed ones.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1038/s41591-018-0014-x"}],"tags":[],"related":["paper-thorsson-immune-landscape-of-cancer-immunity-2018","paper-tumeh-pd1-adaptive-immune-resistance-nature-2014"],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["pdl1"],"drugs":[],"companies":[],"institutions":["ucsf"],"pathways":[],"terms":["cold-vs-hot","tils","immune-system"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2018,"doi":"10.1038/s41591-018-0014-x","authors":"Binnewies M, Roberts EW, Kersten K, et al.","paperType":"review","findings":["Tumour immune microenvironments fall into infiltrated-excluded, infiltrated-inflamed and tertiary lymphoid structure classes.","Inflamed tumours with intratumoural T cells and PD-L1 are the most likely to respond to checkpoint blockade.","Proposed therapeutic strategies to convert excluded or immune-poor tumours into inflamed ones."],"whatItMeans":"This framework is behind the everyday language of hot and cold tumours and the design of combination trials that pair checkpoint inhibitors with treatments meant to draw T cells into the tumour.","caveats":["Classes are descriptive and the boundaries between them are not sharp.","A review; prospective use of TIME classification to choose therapy is still being tested."],"changedPractice":false},{"id":"paper-villani-lancet-oncol","kind":"paper","name":"Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: 11 year follow-up of a prospective observational study","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 27501770 and published in The Lancet Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background: Carriers of a germline TP53 pathogenic variant have a substantial lifetime risk of developing cancer. In 2011, we did a prospective observational study of members of families who chose to either undergo a comprehensive surveillance protocol for individuals with Li-Fraumeni syndrome or not. We sought to update our assessment of and modify the surveillance protocol, so in this study we report both longer follow-up of these patients and additional patients who underwent surveillance, as well as update the originally presented surveillance protocol.\n\nMethods: A clinical surveillance protocol using physical examination and frequent biochemical and imaging studies (consisting of whole-body MRI, brain MRI, breast MRI, mammography, abdominal and pelvic ultrasound, and colonoscopy) was introduced at three tertiary care centres in Canada and the USA on Jan 1, 2004, for carriers of TP53 pathogenic variants. After confirmation of TP53 mutation, participants either chose to undergo surveillance or chose not to undergo surveillance. Patients could cross over between groups at any time. The primary outcome measure was detection of asymptomatic tumours by surveillance investigations. The secondary outcome measure was 5 year overall survival established from a tumour diagnosed symptomatically (in the non-surveillance group) versus one diagnosed by surveillance. We completed survival analyses using an as-treated approach.\n\nFindings: Between Jan 1, 2004, and July 1, 2015, we identified 89 carriers of TP53 pathogenic variants in 39 unrelated families, of whom 40 (45%) agreed to surveillance and 49 (55%) declined surveillance. 19 (21%) patients crossed over from the non-surveillance to the surveillance group, giving a total of 59 (66%) individuals undergoing surveillance for a median of 32 months (IQR 12-87). 40 asymptomatic tumours have been detected in 19 (32%) of 59 patients who underwent surveillance. Two additional cancers were diagnosed between surveillance assessments (false negatives) and two biopsied lesions were non-neoplastic entities on pathological review (false positives). Among the 49 individuals who initially declined surveillance, 61 symptomatic tumours were diagnosed in 43 (88%) patients. 21 (49%) of the 43 individuals not on surveillance who developed cancer were alive compared with 16 (84%) of the 19 individuals undergoing surveillance who developed cancer (p=0·012) after a median follow-up of 46 months (IQR 22-72) for those not on surveillance and 38 months (12-86) for those on surveillance. 5 year overall survival was 88·8% (95% CI 78·7-100) in the surveillance group and 59·6% (47·2-75·2) in the non-surveillance group (p=0·0132).\n\nInterpretation: Our findings show that long-term compliance with a comprehensive surveillance protocol for early tumour detection in individuals with pathogenic TP53 variants is feasible and that early tumour detection through surveillance is associated with improved long-term survival. Incorporation of this approach into clinical management of these patients should be considered.\n\nFunding: Canadian Institutes for Heath Research, Canadian Cancer Society, Terry Fox Research Institute, SickKids Foundation, and Soccer for Hope Foundation.\n\nIndexed on Europe PMC as PubMed record 27501770 (DOI 10.1016/s1470-2045(16)30249-2). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2016","url":"https://doi.org/10.1016/s1470-2045(16)30249-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27501770/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27501770"}],"tags":["europepmc-ingest"],"related":["li-fraumeni"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2016,"doi":"10.1016/s1470-2045(16)30249-2","pmid":"27501770","authors":"Villani A, Shore A, Wasserman JD, et al.","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-pandit-taskar-j-nucl-med","kind":"paper","name":"Biodistribution and Dosimetry of 18 F-Meta-Fluorobenzylguanidine: A First-in-Human PET/CT Imaging Study of Patients with Neuroendocrine Malignancies","aka":[],"tldr":"Paper cited by one idea page, indexed on Europe PMC as PubMed record 28705916 and published in Journal of Nuclear Medicine; the citing page links this DOI, which is how the record was matched.","summary":"123 I-meta-iodobenzylguanidine ( 123 I-MIBG) imaging is currently a mainstay in the evaluation of many neuroendocrine tumors, especially neuroblastoma. 123 I-MIBG imaging has several limitations that can be overcome by the use of a PET agent. 18 F-meta-fluorobenzylguanidine ( 18 F-MFBG) is a PET analog of MIBG that may allow for single-day, high-resolution quantitative imaging. We conducted a first-in-human study of 18 F-MFBG PET imaging to evaluate the safety, feasibility, pharmacokinetics, and dosimetry of 18 F-MFBG in neuroendocrine tumors (NETs). Methods: Ten patients (5 with neuroblastoma and 5 with paraganglioma/pheochromocytoma) received 148-444 MBq (4-12mCi) of 18 F-MFBG intravenously followed by serial whole-body imaging at 0.5-1, 1-2, and 3-4 after injection. Serial blood samples (a total of 6) were also obtained starting at 5 min after injection to as late as 4 h after injection; whole-body distribution and blood clearance data, lesion uptake, and normal-tissue uptake were determined, and radiation-absorbed doses to normal organs were calculated using OLINDA. Results: No side effects were seen in any patient after 18 F-MFBG injection. Tracer distribution showed prominent activity in the blood pool, liver, and salivary glands that decreased with time. Mild uptake was seen in the kidneys and spleen, which also decreased with time. Urinary excretion was prominent, with an average of 45% of the administered activity in the bladder by 1 h after injection; whole-body clearance was monoexponential, with a mean biologic half-life of 1.95 h, whereas blood clearance was biexponential, with a mean biologic half-life of 0.3 h (58%) for the rapid α phase and 6.1 h (42%) for the slower β phase. The urinary bladder received the highest radiation dose with a mean absorbed dose of 0.186 ± 0.195 mGy/MBq. The mean total-body dose was 0.011 ± 0.011 mGy/MBq, and the effective dose was 0.023 ± 0.012 mSv/MBq. Both skeletal and soft-tissue lesions were visualized with high contrast. The SUVmax (mean ± SD) of lesions at 1-2 h after injection was 8.6 ± 9.6. Conclusion: Preliminary data show that 18 F-MFBG imaging is safe and has favorable biodistribution and kinetics with good targeting of lesions. PET imaging with 18 F-MFBG allows for same-day imaging of NETs. 18 F-MFBG appears highly promising for imaging of patients with NETs, especially children with neuroblastoma.\n\nIndexed on Europe PMC as PubMed record 28705916 (DOI 10.2967/jnumed.117.193169). Matched by DOI alone: one idea page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Nucl Med 2018","url":"https://doi.org/10.2967/jnumed.117.193169"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28705916/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28705916"}],"tags":["europepmc-ingest"],"related":["idea-mfbg-pet-replaces-mibg"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-nuclear-medicine"],"dependsOn":[],"notes":[],"journal":"Journal of Nuclear Medicine","year":2018,"doi":"10.2967/jnumed.117.193169","pmid":"28705916","authors":"Pandit-Taskar N, Zanzonico P, Staton KD, et al.","paperType":"observational","findings":[],"whatItMeans":"One idea page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-levin-cell","kind":"paper","name":"Bioelectric signaling: Reprogrammable circuits underlying embryogenesis, regeneration, and cancer","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 33826908 and published in Cell; the citing page links this DOI, which is how the record was matched.","summary":"How are individual cell behaviors coordinated toward invariant large-scale anatomical outcomes in development and regeneration despite unpredictable perturbations? Endogenous distributions of membrane potentials, produced by ion channels and gap junctions, are present across all tissues. These bioelectrical networks process morphogenetic information that controls gene expression, enabling cell collectives to make decisions about large-scale growth and form. Recent progress in the analysis and computational modeling of developmental bioelectric circuits and channelopathies reveals how cellular collectives cooperate toward organ-level structural order. These advances suggest a roadmap for exploiting bioelectric signaling for interventions addressing developmental disorders, regenerative medicine, cancer reprogramming, and synthetic bioengineering.\n\nIndexed on Europe PMC as PubMed record 33826908 (DOI 10.1016/j.cell.2021.02.034). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cell 2021","url":"https://doi.org/10.1016/j.cell.2021.02.034"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33826908/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33826908"}],"tags":["europepmc-ingest"],"related":["bioelectric-theory-of-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Cell","year":2021,"doi":"10.1016/j.cell.2021.02.034","pmid":"33826908","authors":"Levin M","paperType":"review","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-rossi-richter-syndrome-blood-2018","kind":"paper","name":"Biology and treatment of Richter syndrome","aka":[],"tldr":"This review lays out how chronic lymphocytic leukaemia transforms into aggressive lymphoma, which genetic changes drive it, and how the diffuse large B-cell type should be treated, including the role of transplant and new agents.","summary":"Comprehensive review of Richter syndrome covering incidence, clonal relationship to the underlying CLL, the roles of TP53, NOTCH1, MYC and CDKN2A lesions, the effect of BTK inhibitor exposure, diagnostic work-up with PET-directed biopsy, prognostic scores, chemoimmunotherapy outcomes, consolidation with stem cell transplantation, and emerging targeted and immune therapies.","asOf":"2026-09-17","links":[{"label":"Blood 2018","url":"https://doi.org/10.1182/blood-2018-01-791376"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29692342/"}],"tags":[],"related":[],"cancers":["richter-transformation-cll"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["blood"],"dependsOn":[],"notes":[],"journal":"Blood","year":2018,"doi":"10.1182/blood-2018-01-791376","pmid":"29692342","authors":"Rossi D, Spina V, Gaidano G.","paperType":"review","findings":[],"whatItMeans":"The page's approach to Richter transformation (biopsy the hottest node, R-CHOP-type therapy, consolidate with transplant if fit, trial enrolment otherwise) follows the framework in this review.","caveats":["Predates the bispecific antibody and pirtobrutinib data that now shape trials."],"changedPractice":false},{"id":"paper-bardia-ascent-trop2-biomarker-ann-oncol-2021","kind":"paper","name":"Biomarker analyses in the phase III ASCENT study of sacituzumab govitecan versus chemotherapy in patients with metastatic triple-negative breast cancer","aka":[],"tldr":"In ASCENT, sacituzumab govitecan beat chemotherapy in tumours with high and medium TROP2 protein, and worked whether or not the patient carried a germline BRCA mutation; the low-TROP2 group was too small to judge.","summary":"Prespecified exploratory analysis of ASCENT (metastatic TNBC after two or more chemotherapies) relating tumour Trop-2 expression by validated immunohistochemistry H-score and germline BRCA1/2 status to outcome. Of 468 assessable patients, 290 had Trop-2 data and 292 known BRCA status. Median progression-free survival with sacituzumab versus chemotherapy was 6.9, 5.6 and 2.7 months versus 2.5, 2.2 and 1.6 months for high, medium and low Trop-2; overall survival 14.2, 14.9 and 9.3 versus 6.9, 6.9 and 7.6 months; response 44%, 38% and 22% versus 1%, 11% and 6%. Outcomes favoured sacituzumab with and without germline BRCA1/2 mutation.","asOf":"2026-09-24","links":[{"label":"Bardia et al., Ann Oncol 2021: Trop-2 and germline BRCA biomarker analyses in ASCENT","url":"https://doi.org/10.1016/j.annonc.2021.06.002"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34116144/"}],"tags":[],"related":["trop2-expression"],"cancers":["tnbc","tnbc-metastatic"],"sections":[],"technologies":[],"targets":["trop2","brca"],"drugs":["sacituzumab-govitecan"],"companies":["gilead"],"institutions":[],"pathways":[],"terms":["ihc","gbrca-mutation"],"trials":["ascent"],"people":["aditya-bardia","sara-tolaney","kevin-kalinsky","priyanka-sharma"],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2021,"doi":"10.1016/j.annonc.2021.06.002","pmid":"34116144","authors":"Bardia A, Tolaney SM, Punie K, et al.","paperType":"rct","findings":["High and medium Trop-2: PFS 6.9 and 5.6 versus 2.5 and 2.2 months; response 44% and 38% versus 1% and 11%.","Low Trop-2 group small (PFS 2.7 versus 1.6 months); no conclusion.","Benefit regardless of germline BRCA1/2 status."],"whatItMeans":"TROP2 IHC does not gate sacituzumab govitecan: the label requires no test, and the corpus records TROP2 as an expression readout without a threshold.","caveats":["Trop-2 data in 62% of patients; exploratory.","H-score bands were defined by the sponsor's assay."],"changedPractice":false,"participants":468},{"id":"paper-nct03334617-nat-med-2024","kind":"paper","name":"Biomarker-directed targeted therapy plus durvalumab in advanced non-small-cell lung cancer: a phase 2 umbrella trial","aka":[],"tldr":"Published report from the PD-L1 Containing Therapy trial registered as NCT03334617, in Nature Medicine (2024), chosen as the most cited paper whose own text cites the registry id.","summary":"For patients with non-small-cell lung cancer (NSCLC) tumors without currently targetable molecular alterations, standard-of-care treatment is immunotherapy with anti-PD-(L)1 checkpoint inhibitors, alone or with platinum-doublet therapy. However, not all patients derive durable benefit and resistance to immune checkpoint blockade is common. Understanding mechanisms of resistance-which can include defects in DNA damage response and repair pathways, alterations or functional mutations in STK11/LKB1, alterations in antigen-presentation pathways, and immunosuppressive cellular subsets within the tumor microenvironment-and developing effective therapies to overcome them, remains an unmet need. Here the phase 2 umbrella HUDSON study evaluated rational combination regimens for advanced NSCLC following failure of anti-PD-(L)1-containing immunotherapy and platinum-doublet therapy. A total of 268 patients received durvalumab (anti-PD-L1 monoclonal antibody)-ceralasertib (ATR kinase inhibitor), durvalumab-olaparib (PARP inhibitor), durvalumab-danvatirsen (STAT3 antisense oligonucleotide) or durvalumab-oleclumab (anti-CD73 monoclonal antibody). Greatest clinical benefit was observed with durvalumab-ceralasertib; objective response rate (primary outcome) was 13.9% (11/79) versus 2.6% (5/189) with other regimens, pooled, median progression-free survival (secondary outcome) was 5.8 (80% confidence interval 4.6-7.4) versus 2.7 (1.8-2.8) months, and median overall survival (secondary outcome) was 17.4 (14.1-20.3) versus 9.4 (7.5-10.6) months. Benefit with durvalumab-ceralasertib was consistent across known immunotherapy-refractory subgroups. In ATM-altered patients hypothesized to harbor vulnerability to ATR inhibition, objective response rate was 26.1% (6/23) and median progression-free survival/median overall survival were 8.4/22.8 months. Durvalumab-ceralasertib safety/tolerability profile was manageable. Biomarker analyses suggested that anti-PD-L1/ATR inhibition induced immune changes that reinvigorated antitumor immunity. Durvalumab-ceralasertib is under further investigation in immunotherapy-refractory NSCLC.ClinicalTrials.gov identifier: NCT03334617.\n\nIndexed on Europe PMC as PubMed record 38351187 (DOI 10.1038/s41591-024-02808-y). Its abstract cites the registry id NCT03334617, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Nat Med 2024","url":"https://doi.org/10.1038/s41591-024-02808-y"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38351187/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38351187"},{"label":"ClinicalTrials.gov NCT03334617","url":"https://clinicaltrials.gov/study/NCT03334617"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct03334617"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2024,"doi":"10.1038/s41591-024-02808-y","pmid":"38351187","authors":"Besse B, Pons-Tostivint E, Park K, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03334617 with the most citations, so it is the natural first reading for anyone following the PD-L1 Containing Therapy trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-redman-lancet-oncol","kind":"paper","name":"Biomarker-driven therapies for previously treated squamous non-small-cell lung cancer (Lung-MAP SWOG S1400): a biomarker-driven master protocol","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 33125909 and published in The Lancet Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background: The Lung Cancer Master Protocol (Lung-MAP; S1400) is a completed biomarker-driven master protocol designed to address an unmet need for better therapies for squamous non-small-cell lung cancer. Lung-MAP (S1400) was created to establish an infrastructure for biomarker screening and rapid regulatory intent evaluation of targeted therapies and was the first biomarker-driven master protocol initiated with the US National Cancer Institute (NCI).\n\nMethods: Lung-MAP (S1400) was done within the National Clinical Trials Network of the NCI using a public-private partnership. Eligible patients were aged 18 years or older, had stage IV or recurrent squamous non-small-cell lung cancer, had previously been treated with platinum-based chemotherapy, and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. The study included a screening component using the FoundationOne assay (Foundation Medicine, Cambridge, MA, USA) for next-generation sequencing, and a clinical trial component with biomarker-driven substudies and non-match substudies for patients who were ineligible for biomarker-driven substudies. Patients were pre-screened and received their substudy assignment upon progression, or they were screened at progression and received their substudy assignment upon completion of testing. Patients could enrol onto additional substudies after progression on a substudy. The study is registered with ClinicalTrials.gov, NCT02154490, and all research related to Lung-MAP (S1400) is completed.\n\nFindings: Between June 16, 2014, and Jan 28, 2019, 1864 patients enrolled and 1841 (98·9%) submitted tissue. 1674 (90·9%) of 1841 patients had biomarker results, and 1404 (83·9%) of 1674 patients received a substudy assignment. Of the assigned patients, 655 (46·7%) registered to a substudy. The biomarker-driven substudies evaluated taselisib (targeting PIK3CA alterations), palbociclib (cell cycle gene alterations), AZD4547 (FGFR alteration), rilotumumab plus erlotinib (MET), talazoparib (homologous recombination repair deficiency), and telisotuzumab vedotin (MET). The non-match substudies evaluated durvalumab, and nivolumab plus ipilimumab for anti-PD-1 or anti-PD-L1-naive disease, and durvalumab plus tremelimumab for anti-PD-1 or anti-PD-L1 relapsed disease. Combining data from the substudies, ten (7·0%) of 143 patients responded to targeted therapy, 53 (16·8%) of 315 patients responded to anti-PD-1 or anti-PD-L1 therapy for immunotherapy-naive disease, and three (5·4%) of 56 responded to docetaxel in the second line of therapy. Median overall survival was 5·9 months (95% CI 4·8-7·8) for the targeted therapy groups, 7·7 months (6·7-9·2) for the docetaxel groups, and 10·8 months (9·4-12·3) for the anti-PD-1 or anti-PD-L1-containing groups. Median progression-free survival was 2·5 months (95% CI 1·7-2·8) for the targeted therapy groups, 2·7 months (1·9-2·9) for the docetaxel groups, and 3·0 months (2·7-3·9) for the anti-PD-1 or anti-PD-L1-containing groups.\n\nInterpretation: Lung-MAP (S1400) met its goal to quickly address biomarker-driven therapy questions in squamous non-small-cell lung cancer. In early 2019, a new screening protocol was implemented expanding to all histological types of non-small-cell lung cancer and to add focus on immunotherapy combinations for anti-PD-1 and anti-PD-L1 therapy-relapsed disease. With these changes, Lung-MAP continues to meet its goal to focus on unmet needs in the treatment of advanced lung cancers.\n\nFunding: US National Institutes of Health, and AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Genentech, and Pfizer through the Foundation for the National Institutes of Health.\n\nIndexed on Europe PMC as PubMed record 33125909 (DOI 10.1016/s1470-2045(20)30475-7). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2020","url":"https://doi.org/10.1016/s1470-2045(20)30475-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33125909/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33125909"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["lung-map"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2020,"doi":"10.1016/s1470-2045(20)30475-7","pmid":"33125909","authors":"Redman MW, Papadimitrakopoulou VA, Minichiello K, et al.","paperType":"observational","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-andre-j-clin-oncol","kind":"paper","name":"Biomarkers for Adjuvant Endocrine and Chemotherapy in Early-Stage Breast Cancer: ASCO Guideline Update","aka":[],"tldr":"Paper cited by one treatment page, indexed on Europe PMC as PubMed record 35439025 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: To update recommendations on appropriate use of breast cancer biomarker assay results to guide adjuvant endocrine and chemotherapy decisions in early-stage breast cancer.\n\nMethods: An updated literature search identified randomized clinical trials and prospective-retrospective studies published from January 2016 to October 2021. Outcomes of interest included overall survival and disease-free or recurrence-free survival. Expert Panel members used informal consensus to develop evidence-based recommendations.\n\nResults: The search identified 24 studies informing the evidence base.\n\nRecommendations: Clinicians may use Onco type DX, MammaPrint, Breast Cancer Index (BCI), and EndoPredict to guide adjuvant endocrine and chemotherapy in patients who are postmenopausal or age > 50 years with early-stage estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative (ER+ and HER2-) breast cancer that is node-negative or with 1-3 positive nodes. Prosigna and BCI may be used in postmenopausal patients with node-negative ER+ and HER2- breast cancer. In premenopausal patients, clinicians may use Onco type in patients with node-negative ER+ and HER2- breast cancer. Current data suggest that premenopausal patients with 1-3 positive nodes benefit from chemotherapy regardless of genomic assay result. There are no data on use of genomic tests to guide adjuvant chemotherapy in patients with ≥ 4 positive nodes. Ki67 combined with other parameters or immunohistochemistry 4 score may be used in postmenopausal patients without access to genomic tests to guide adjuvant therapy decisions. BCI may be offered to patients with 0-3 positive nodes who received 5 years of endocrine therapy without evidence of recurrence to guide decisions about extended endocrine therapy. None of the assays are recommended for treatment guidance in individuals with HER2-positive or triple-negative breast cancer. Treatment decisions should also consider disease stage, comorbidities, and patient preferences.Additional information is available at www.asco.org/breast-cancer-guidelines.\n\nIndexed on Europe PMC as PubMed record 35439025 (DOI 10.1200/jco.22.00069). Matched by DOI alone: one treatment page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2022","url":"https://doi.org/10.1200/jco.22.00069"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35439025/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35439025"}],"tags":["europepmc-ingest"],"related":["breast-cancer-index"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2022,"doi":"10.1200/jco.22.00069","pmid":"35439025","authors":"Andre F, Ismaila N, Allison KH, et al.","paperType":"guideline","findings":[],"whatItMeans":"One treatment page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-asco-biomarkers-metastatic-breast-cancer-guideline-jco-2022","kind":"paper","name":"Biomarkers for Systemic Therapy in Metastatic Breast Cancer: ASCO Guideline Update","aka":[],"tldr":"The US oncology society's 2022 rules on which tests to run before choosing drugs for metastatic breast cancer: PD-L1 for pembrolizumab, germline BRCA for PARP inhibitors, and no routine test for TROP2 or for tumour DNA in blood.","summary":"ASCO guideline update by Henry, Somerfield, Dayao, Elias and colleagues, from a systematic review of 19 studies published January 2015 to January 2022. Candidates for a PI3K inhibitor regimen should be tested for PIK3CA mutations by next-generation sequencing of tissue or plasma ctDNA; candidates for PARP inhibitors should be tested for germline BRCA1 and BRCA2 pathogenic variants (evidence insufficient for PALB2); candidates for immune checkpoint inhibitors should be tested for PD-L1 expression in tumour and immune cells for pembrolizumab with chemotherapy, and for mismatch repair deficiency or microsatellite instability and tumour mutational burden; NTRK fusion testing may be used. Data were insufficient to recommend routine testing for ESR1 mutations, homologous recombination deficiency or TROP2 expression, or routine ctDNA or circulating tumour cell monitoring of response.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2022","url":"https://doi.org/10.1200/JCO.22.01063"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35759724/"}],"tags":["tnbc-evidence"],"related":[],"cancers":["tnbc","breast-hr-positive"],"sections":[],"technologies":[],"targets":["pdl1","brca","trop2"],"drugs":[],"companies":[],"institutions":["asco"],"pathways":[],"terms":["cps","ctdna","hrd","germline-testing"],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2022,"doi":"10.1200/JCO.22.01063","pmid":"35759724","authors":"Henry NL, Somerfield MR, Dayao Z, et al.","paperType":"guideline","findings":["Test PD-L1 in tumour and immune cells to select pembrolizumab with chemotherapy; test germline BRCA1/2 to select PARP inhibitors.","Insufficient data to recommend routine TROP2 expression testing, homologous recombination deficiency testing, or ctDNA monitoring of response."],"whatItMeans":"Confirms that the TROP2 antibody-drug conjugates are given without a TROP2 test and that PD-L1 remains the one selection assay in metastatic triple-negative disease, which is why assay harmonisation matters.","caveats":["Review closed January 2022, before the first-line antibody-drug conjugate trials.","US guideline; assay recommendations follow US approvals."],"changedPractice":true},{"id":"paper-nct05077449-nat-commun-2025","kind":"paper","name":"Bireociclib plus fulvestrant for HR+/HER2- advanced female breast cancer progressed on or after endocrine therapy: phase 3 BRIGHT-2 study interim analysis","aka":[],"tldr":"Published report from the trial registered as NCT05077449, in Nature Communications (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"The BRIGHT-2 study (NCT05077449) is a randomized, double-blind, placebo-controlled, phase 3 trial evaluating the efficacy and safety of bireociclib plus fulvestrant (BF) vs. placebo plus fulvestrant (F) in Chinese female patients with hormone receptor-positive (HR+)/HER2-negative (HER2-) advanced breast cancer (ABC) who had progressed on or after prior endocrine therapy (ET). Interim results were analyzed after 70% of progression-free survival (PFS) events across 64 centers in China between December 8, 2021, and March 28, 2023. Patients were randomized (2:1) to receive BF or F, with stratification based on visceral involvement (yes/no) and resistance to prior primary or secondary ET. As the primary outcome, PFS was significantly prolonged in the BF group (n = 204) (12.94 months; 95% CI: 11.07-not reached) compared to 7.29 months (95% CI: 5.45-11.04) in the F group (n = 101) (hazard ratio, 0.56; 95% CI: 0.39-0.80; p = 0.001). The objective response rate in the BF group was 39.7% in the intention-to-treat population. Grade ≥3 adverse events were more frequent in the BF group (64.7%) than in the F group (18.8%), with neutropenia, leukopenia, and anemia being the most common. These findings suggest that BF is a promising therapeutic option for patients with HR+/HER2- ABC following ET failure.\n\nIndexed on Europe PMC as PubMed record 40204778 (DOI 10.1038/s41467-025-58647-z). Its abstract cites the registry id NCT05077449, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Nat Commun 2025","url":"https://doi.org/10.1038/s41467-025-58647-z"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40204778/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40204778"},{"label":"ClinicalTrials.gov NCT05077449","url":"https://clinicaltrials.gov/study/NCT05077449"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05077449"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-communications"],"dependsOn":[],"notes":[],"journal":"Nature Communications","year":2025,"doi":"10.1038/s41467-025-58647-z","pmid":"40204778","authors":"Wang J, Zhang Q, Li H, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05077449 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-bischoff-onyx-015-science-1996","kind":"paper","name":"Bischoff 1996: the adenovirus that was said to replicate only where p53 was lost","aka":[],"tldr":"An adenovirus missing the gene that disables the cell's main tumour suppressor appeared to grow only in cancer cells that had already lost that suppressor, a claim that launched the field's first big clinical programme and was later shown to be the wrong explanation.","summary":"Adenovirus E1B encodes a 55-kilodalton protein that inactivates p53. Bischoff and colleagues showed that a mutant adenovirus lacking it replicated in and lysed p53-deficient human tumour cells but not cells with functional p53, and that putting the 55-kilodalton protein back into the latter made them susceptible. Injection into p53-deficient human cervical carcinomas in nude mice significantly reduced tumour size and completely regressed 60 per cent of tumours.\n\nThe virus became ONYX-015, the most heavily studied oncolytic virus of the 1990s, and later, with a nearly identical design, the Chinese product H101. The tidy mechanism did not survive: O'Shea and colleagues showed in 2004 that selectivity tracks late viral RNA export rather than p53 status, which is why ONYX-015 activity in trials never sorted by p53.","asOf":"2026-09-25","links":[{"label":"Science 1996","url":"https://doi.org/10.1126/science.274.5286.373"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/8832876/"},{"label":"O'Shea 2004, the correction to the mechanism (Cancer Cell)","url":"https://doi.org/10.1016/j.ccr.2004.11.012"}],"tags":[],"related":[],"cancers":[],"sections":["immunotherapy"],"technologies":["oncolytic-virus"],"targets":["tp53"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["frank-mccormick"],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":1996,"doi":"10.1126/science.274.5286.373","pmid":"8832876","authors":"Bischoff JR, Kirn DH, Williams A, et al.","paperType":"basic","findings":["An adenovirus not expressing the E1B 55-kilodalton protein replicated in and lysed p53-deficient human tumour cells but not cells with functional p53.","Ectopic expression of the 55-kilodalton E1B protein in p53-functional cells made them susceptible to the mutant virus.","Injection into p53-deficient human cervical carcinomas in nude mice reduced tumour size significantly and caused complete regression of 60 per cent of tumours."],"whatItMeans":"This is the paper that made oncolytic viruses look like precision medicine: a named genetic lesion, a virus built to exploit it, a biomarker to select patients. None of that held. It is the field's most useful cautionary tale, because the drug went into large trials on a mechanism that turned out to be wrong, and the selectivity that does exist has never been reducible to one gene.","caveats":["The p53 explanation was overturned. O'Shea and colleagues showed in Cancer Cell in 2004 that late viral RNA export, not p53 inactivation, determines the selectivity of this mutant.","Clinical response to ONYX-015 did not track p53 status in the trials that looked, so the biomarker never worked.","Nude-mouse xenografts of a cervical carcinoma line, with the virus injected directly into an accessible tumour."]},{"id":"paper-blinatumomab-infant-all-van-der-sluis-nejm-2023","kind":"paper","name":"Blinatumomab added to chemotherapy in infant KMT2A-rearranged acute lymphoblastic leukaemia","aka":[],"tldr":"Adding a single course of the bispecific antibody blinatumomab after induction chemotherapy in infants with KMT2A-rearranged leukaemia raised two-year disease-free survival from a historical 49 percent to 82 percent, the first major advance in infant leukaemia in decades.","summary":"Single-arm phase 2 study of 30 infants with newly diagnosed KMT2A-rearranged ALL treated on the Interfant-06 backbone with one 28-day course of blinatumomab after induction, compared with historical Interfant-06 controls.\n\nTwo-year disease-free survival was 81.6 percent against 49.4 percent historically, overall survival 93.3 versus 65.8 percent, and blinatumomab was well tolerated with no treatment discontinuations for toxicity; measurable residual disease became negative or low in almost all infants.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2023","url":"https://doi.org/10.1056/NEJMoa2214171"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37099340/"}],"tags":[],"related":[],"cancers":["all-infant"],"sections":[],"technologies":[],"targets":[],"drugs":["blinatumomab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["inge-van-der-sluis"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/NEJMoa2214171","pmid":"37099340","authors":"van der Sluis IM, de Lorenzo P, Kotecha RS, et al.","paperType":"observational","findings":["Two-year disease-free survival 81.6 percent vs 49.4 percent in historical controls.","Two-year overall survival 93.3 percent vs 65.8 percent."],"whatItMeans":"Blinatumomab after induction is now standard for KMT2A-rearranged infant ALL through the Interfant-21 protocol.","caveats":["Thirty patients with historical comparison; longer follow-up needed."],"changedPractice":true,"participants":30},{"id":"paper-blinatumomab-all-leukemia-n-engl-j-med-2017","kind":"paper","name":"Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia","aka":[],"tldr":"Phase 2 or 3 results paper on Blinatumomab in Acute lymphoblastic leukaemia, in New England Journal of Medicine (2017), one of the most cited Europe PMC records with Blinatumomab in its title.","summary":"Background: Blinatumomab, a bispecific monoclonal antibody construct that enables CD3-positive T cells to recognize and eliminate CD19-positive acute lymphoblastic leukemia (ALL) blasts, was approved for use in patients with relapsed or refractory B-cell precursor ALL on the basis of single-group trials that showed efficacy and manageable toxic effects.\n\nMethods: In this multi-institutional phase 3 trial, we randomly assigned adults with heavily pretreated B-cell precursor ALL, in a 2:1 ratio, to receive either blinatumomab or standard-of-care chemotherapy. The primary end point was overall survival.\n\nResults: Of the 405 patients who were randomly assigned to receive blinatumomab (271 patients) or chemotherapy (134 patients), 376 patients received at least one dose. Overall survival was significantly longer in the blinatumomab group than in the chemotherapy group. The median overall survival was 7.7 months in the blinatumomab group and 4.0 months in the chemotherapy group (hazard ratio for death with blinatumomab vs. chemotherapy, 0.71; 95% confidence interval [CI], 0.55 to 0.93; P=0.01). Remission rates within 12 weeks after treatment initiation were significantly higher in the blinatumomab group than in the chemotherapy group, both with respect to complete remission with full hematologic recovery (34% vs. 16%, P<0.001) and with respect to complete remission with full, partial, or incomplete hematologic recovery (44% vs. 25%, P<0.001). Treatment with blinatumomab resulted in a higher rate of event-free survival than that with chemotherapy (6-month estimates, 31% vs. 12%; hazard ratio for an event of relapse after achieving a complete remission with full, partial, or incomplete hematologic recovery, or death, 0.55; 95% CI, 0.43 to 0.71; P<0.001), as well as a longer median duration of remission (7.3 vs. 4.6 months). A total of 24% of the patients in each treatment group underwent allogeneic stem-cell transplantation. Adverse events of grade 3 or higher were reported in 87% of the patients in the blinatumomab group and in 92% of the patients in the chemotherapy group.\n\nConclusions: Treatment with blinatumomab resulted in significantly longer overall survival than chemotherapy among adult patients with relapsed or refractory B-cell precursor ALL. (Funded by Amgen; TOWER ClinicalTrials.gov number, NCT02013167.).\n\nIndexed on Europe PMC as PubMed record 28249141 (DOI 10.1056/nejmoa1609783). Its title names Blinatumomab and its text names Acute lymphoblastic leukaemia; PubMed types it as a clinical trial report (Clinical Trial, Phase III, Comparative Study, Research Support, Non-U.S. Gov't, research-article, Multicenter Study, Randomized Controlled Trial). It was matched automatically to the idea \"Menin inhibitors for infant KMT2A-rearranged ALL\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2017","url":"https://doi.org/10.1056/nejmoa1609783"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28249141/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28249141"},{"label":"ClinicalTrials.gov NCT02013167","url":"https://clinicaltrials.gov/study/NCT02013167"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["tower"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2017,"doi":"10.1056/nejmoa1609783","pmid":"28249141","authors":"Kantarjian H, Stein A, Gökbuget N, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Blinatumomab in Acute lymphoblastic leukaemia, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Blinatumomab in the title and Acute lymphoblastic leukaemia in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-gandara-blood-tmb-atezolizumab-nat-med-2018","kind":"paper","name":"Blood-based tumor mutational burden as a predictor of clinical benefit in non-small-cell lung cancer patients treated with atezolizumab","aka":[],"tldr":"Counting mutations in a blood sample rather than in a piece of tumour identified the patients who gained most from one immunotherapy drug, which matters because many patients with advanced lung cancer have no tissue left to test.","summary":"A blood-based assay to measure tumour mutational burden in plasma was developed and evaluated retrospectively in two large randomised trials used as test and validation studies. The assay is technically distinct from tissue-based approaches. High blood-based burden reproducibly identified patients who derived clinically significant improvements in progression-free survival from atezolizumab in second-line and later non-small-cell lung cancer.","asOf":"2026-09-25","links":[{"label":"Gandara et al., Nat Med 2018: blood-based tumour mutational burden as a predictor of atezolizumab benefit","url":"https://doi.org/10.1038/s41591-018-0134-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30082870/"}],"tags":[],"related":["tmb-high"],"cancers":["nsclc"],"sections":[],"technologies":["liquid-biopsy","tmb-testing","checkpoint-inhibitor"],"targets":["pdl1"],"drugs":["atezolizumab"],"companies":[],"institutions":[],"pathways":["pd1-checkpoint"],"terms":["tmb","ctdna","cfdna"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2018,"doi":"10.1038/s41591-018-0134-3","pmid":"30082870","authors":"Gandara DR, Paul SM, Kowanetz M, et al.","paperType":"translational","findings":["A plasma assay can estimate tumour mutational burden without tissue.","High blood-based burden identified atezolizumab benefit in test and validation trials.","Blood-based and tissue-based burden are distinct measurements with distinct thresholds."],"whatItMeans":"It answered the tissue-exhaustion problem for one biomarker, and in doing so added a third unit to a measurement that already had two, which is part of why the field never converged on a threshold.","caveats":["Retrospective analyses of trials not designed for the question.","Blood-based burden depends on tumour shedding, so low-shedding tumours are unclassifiable.","The prospective randomised test of a blood-based threshold did not confirm a treatment benefit."],"changedPractice":false},{"id":"paper-mainprize-sci-rep","kind":"paper","name":"Blood-Brain Barrier Opening in Primary Brain Tumors with Non-invasive MR-Guided Focused Ultrasound: A Clinical Safety and Feasibility Study","aka":[],"tldr":"Paper cited by two technology pages, indexed on Europe PMC as PubMed record 30674905 and published in Scientific reports; the citing pages link this DOI, which is how the record was matched.","summary":"The blood-brain barrier (BBB) has long limited therapeutic access to brain tumor and peritumoral tissue. In animals, MR-guided focused ultrasound (MRgFUS) with intravenously injected microbubbles can temporarily and repeatedly disrupt the BBB in a targeted fashion, without open surgery. Our objective is to demonstrate safety and feasibility of MRgFUS BBB opening with systemically administered chemotherapy in patients with glioma in a phase I, single-arm, open-label study. Five patients with previously confirmed or suspected high-grade glioma based on imaging underwent the MRgFUS in conjunction with administration of chemotherapy (n = 1 liposomal doxorubicin, n = 4 temozolomide) one day prior to their scheduled surgical resection. Samples of \"sonicated\" and \"unsonicated\" tissue were measured for the chemotherapy by liquid-chromatography-mass spectrometry. Complete follow-up was three months. The procedure was well-tolerated, with no adverse clinical or radiologic events related to the procedure. The BBB within the target volume showed radiographic evidence of opening with an immediate 15-50% increased contrast enhancement on T1-weighted MRI, and resolution approximately 20 hours after. Biochemical analysis of sonicated versus unsonicated tissue suggest chemotherapy delivery is feasible. In this study, we demonstrated transient BBB opening in tumor and peritumor tissue using non-invasive low-intensity MRgFUS with systemically administered chemotherapy was safe and feasible. The characterization of therapeutic delivery and clinical response to this treatment paradigm requires further investigation.\n\nIndexed on Europe PMC as PubMed record 30674905 (DOI 10.1038/s41598-018-36340-0). Matched by DOI alone: two technology pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Sci Rep 2019","url":"https://doi.org/10.1038/s41598-018-36340-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30674905/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30674905"}],"tags":["europepmc-ingest"],"related":["bbb-focused-ultrasound","transcranial-focused-ultrasound-systems"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Scientific reports","year":2019,"doi":"10.1038/s41598-018-36340-0","pmid":"30674905","authors":"Mainprize T, Lipsman N, Huang Y, et al.","paperType":"observational","findings":[],"whatItMeans":"Two technology pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-bmt-ctn-0803-autologous-transplant-hiv-lymphoma-alvarnas-blood-2016","kind":"paper","name":"BMT CTN 0803/AMC 071: autologous haematopoietic cell transplantation for HIV-related lymphoma","aka":[],"tldr":"People with HIV whose lymphoma had relapsed did as well after high-dose chemotherapy and a stem cell transplant as matched HIV-negative patients, with 87 percent alive at one year.","summary":"Single-arm phase 2 trial of the Blood and Marrow Transplant Clinical Trials Network and AIDS Malignancy Consortium: 43 HIV-infected patients with chemotherapy-sensitive relapsed or persistent aggressive B-cell or Hodgkin lymphoma were enrolled and 40 underwent autologous transplant after BEAM conditioning with consistent peri-transplant antiretroviral management.\n\nAt a median follow-up of 24.8 months one- and two-year overall survival were 87.3 and 82 percent, two-year progression-free survival 79.8 percent and one-year transplant-related mortality 5.2 percent; neutrophil and platelet recovery took 11 and 18 days; outcomes did not differ from 151 matched registry controls.","asOf":"2026-09-22","links":[{"label":"Blood 2016","url":"https://doi.org/10.1182/blood-2015-08-664706"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27297790/"}],"tags":[],"related":[],"cancers":["hiv-associated-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["bmt-ctn-0803"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["blood"],"dependsOn":[],"notes":[],"journal":"Blood","year":2016,"doi":"10.1182/blood-2015-08-664706","pmid":"27297790","authors":"Alvarnas JC, Le Rademacher J, Wang Y, et al.","paperType":"observational","findings":["One-year overall survival 87.3 percent (95% CI 72.1 to 94.5) and two-year 82 percent (65.9 to 91).","Two-year progression-free survival 79.8 percent; one-year transplant-related mortality 5.2 percent.","No significant difference from 151 matched HIV-negative controls."],"whatItMeans":"HIV infection is not a reason to withhold autologous transplant from patients with relapsed lymphoma who meet standard transplant criteria.","caveats":["Small single-arm study in patients with controlled HIV and chemotherapy-sensitive disease."],"changedPractice":true,"participants":43},{"id":"paper-bmt-ctn-1102-transplant-older-mds-nakamura-jco-2021","kind":"paper","name":"BMT CTN 1102: biologic assignment trial of reduced-intensity transplant by donor availability in patients aged 50 to 75 with advanced myelodysplastic syndrome","aka":[],"tldr":"Older people with higher-risk myelodysplastic syndrome who had a matched donor and went on to a reduced-intensity stem-cell transplant were much more likely to be alive three years later than those without a donor treated with drugs, which makes transplant part of standard planning for fit patients up to 75.","summary":"Multicentre biologic assignment trial of the Blood and Marrow Transplant Clinical Trials Network: 384 patients aged 50 to 75 with intermediate-2 or high-risk de novo myelodysplastic syndrome enrolled at 34 centres between 2014 and 2018 were assigned to the donor arm (reduced-intensity allogeneic transplant) or the no-donor arm (hypomethylating therapy or best supportive care) according to whether a matched donor was identified within 90 days.\n\nIn the intention-to-treat analysis, adjusted three-year overall survival was 47.9 percent in the donor arm against 26.6 percent in the no-donor arm (absolute difference 21.3 percentage points), and leukaemia-free survival 35.8 against 20.6 percent. The benefit was seen across all subgroups examined.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2021","url":"https://doi.org/10.1200/JCO.20.03380"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34106753/"}],"tags":[],"related":[],"cancers":["mds-higher-risk","mds"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["bmt-ctn-1102"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2021,"doi":"10.1200/JCO.20.03380","pmid":"34106753","authors":"Nakamura R, Saber W, Martens MJ, et al.","paperType":"rct","findings":["Adjusted three-year overall survival 47.9 percent (95% CI 41.3 to 54.1) with a donor versus 26.6 percent (18.4 to 35.6) without (p 0.0001).","Three-year leukaemia-free survival 35.8 versus 20.6 percent (p 0.003).","Survival benefit consistent across all subgroups."],"whatItMeans":"Allogeneic transplant should be included in the management plan of fit older adults with higher-risk myelodysplastic syndrome; donor search should start at diagnosis.","caveats":["Assignment by donor availability rather than randomisation; not every donor-arm patient was transplanted and the analysis is by intention to treat.","Reduced-intensity conditioning only."],"changedPractice":true,"participants":384},{"id":"paper-bolt-sonidegib-migden-lancet-oncol-2015","kind":"paper","name":"BOLT: two doses of sonidegib in locally advanced or metastatic basal cell carcinoma","aka":[],"tldr":"Sonidegib, a second hedgehog inhibitor, shrank tumours in about 40 percent of patients with locally advanced basal cell carcinoma at the lower 200 mg dose with fewer side effects than the higher dose, and was approved as an alternative to vismodegib.","summary":"Randomised phase 2 trial of 230 patients with locally advanced or metastatic basal cell carcinoma randomised to sonidegib 200 mg or 800 mg daily.\n\nObjective response by central review was 36 percent (200 mg) and 34 percent (800 mg) in locally advanced disease, with lower toxicity and discontinuation at 200 mg; the metastatic cohort response was lower, and later analyses reported higher responses with longer follow-up.","asOf":"2026-09-17","links":[{"label":"Lancet Oncol 2015","url":"https://doi.org/10.1016/S1470-2045(15)70100-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25981810/"}],"tags":[],"related":[],"cancers":["locally-advanced-bcc"],"sections":[],"technologies":[],"targets":[],"drugs":["sonidegib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["bolt"],"people":["michael-migden"],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2015,"doi":"10.1016/S1470-2045(15)70100-2","pmid":"25981810","authors":"Migden MR, Guminski A, Gutzmer R, et al.","paperType":"rct","findings":["Objective response 36 percent (200 mg) vs 34 percent (800 mg) in locally advanced disease.","Fewer grade 3 to 4 adverse events at 200 mg."],"whatItMeans":"Sonidegib 200 mg is an approved option for locally advanced basal cell carcinoma with a side-effect profile similar to vismodegib.","caveats":["Randomised between doses only; no comparison with vismodegib or placebo."],"changedPractice":true,"participants":230},{"id":"paper-esmo-bone-sarcoma-guideline-strauss-ann-oncol-2021","kind":"paper","name":"Bone sarcomas: ESMO-EURACAN-GENTURIS-ERN PaedCan clinical practice guideline","aka":[],"tldr":"The European guideline for bone sarcomas covers referral to specialist centres, biopsy, surgery, chemotherapy for osteosarcoma and Ewing sarcoma, and the surgery-based management of chondrosarcoma and chordoma including proton and carbon-ion radiotherapy.","summary":"Joint European guideline on the diagnosis, treatment and follow-up of bone sarcomas in adults and children, with sections on osteosarcoma, Ewing sarcoma, chondrosarcoma (including atypical cartilaginous tumour, dedifferentiated and mesenchymal subtypes), chordoma and giant cell tumour of bone.","asOf":"2026-09-17","links":[{"label":"Ann Oncol 2021","url":"https://doi.org/10.1016/j.annonc.2021.08.1995"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34500044/"}],"tags":[],"related":[],"cancers":["chondrosarcoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2021,"doi":"10.1016/j.annonc.2021.08.1995","pmid":"34500044","authors":"Strauss SJ, Frezza AM, Abecassis N, et al.","paperType":"guideline","findings":[],"whatItMeans":"The chondrosarcoma page's recommendations for curettage of low-grade limb lesions, wide resection for higher grades and particle therapy for skull base tumours follow this guideline.","caveats":["Evidence for chemotherapy in dedifferentiated and mesenchymal chondrosarcoma remains weak."],"changedPractice":true},{"id":"paper-hirose-radiother-oncol","kind":"paper","name":"Boron neutron capture therapy using cyclotron-based epithermal neutron source and borofalan ( 10 B) for recurrent or locally advanced head and neck cancer (JHN002): An open-label phase II trial","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 33186684 and published in Radiotherapy and Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background and purpose: Boron neutron capture therapy (BNCT) can be performed without reactors due to development of cyclotron-based epithermal neutron source (C-BENS), which is optimized for treatment for deeper-seated tumors. The purpose of this study was to evaluate efficacy and safety of cyclotron-based BNCT with borofalan ( 10 B) for recurrent or locally advanced head and neck cancer.\n\nMaterials and methods: In this open-label, phase II JHN002 trial of BNCT using C-BENS with borofalan ( 10 B), patients with recurrent squamous cell carcinoma (R-SCC) or with recurrent/locally advanced non-squamous cell carcinoma (R/LA-nSCC) of the head and neck were intravenously administered 400 mg/kg borofalan ( 10 B), followed by neutron irradiation. The tumor dose was determined passively as the mucosal maximum dose of 12 Gy-Eq. The primary endpoint was the objective response rate (ORR). Post-trial observational JHN002 Look Up study was planned for evaluating locoregional progression-free survival (LRPFS).\n\nResults: Eight R-SCC and 13 R/LA-nSCC patients were enrolled. All R-SCC patients had prior radiotherapy with a median dose of 65.5 Gy (range, 59.4-76.0 Gy). The ORR for all patients was 71%, and complete response/partial response were 50%/25% in R-SCC and 8%/62% in R/LA-nSCC. The 2-year overall survival for R-SCC and R/LA-nSCC were 58% and 100%, respectively. The median LRPFS was 11.5 months for R-SCC. Frequently observed adverse events included alopecia (95%), hyperamylasemia (86%), and nausea (81%).\n\nConclusion: These data suggest that BNCT using C-BENS with borofalan ( 10 B) is a promising treatment option for patients with R-SCC or R/LA-nSCC of the head and neck.\n\nIndexed on Europe PMC as PubMed record 33186684 (DOI 10.1016/j.radonc.2020.11.001). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Radiother Oncol 2021","url":"https://doi.org/10.1016/j.radonc.2020.11.001"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33186684/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33186684"}],"tags":["europepmc-ingest"],"related":["bnct-accelerator-systems"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["radiotherapy-and-oncology"],"dependsOn":[],"notes":[],"journal":"Radiotherapy and Oncology","year":2021,"doi":"10.1016/j.radonc.2020.11.001","pmid":"33186684","authors":"Hirose K, Konno A, Hiratsuka J, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-bullock-botensilimab-balstilimab-mss-colorectal-nat-med-2024","kind":"paper","name":"Botensilimab plus balstilimab in relapsed/refractory microsatellite stable metastatic colorectal cancer: a phase 1 trial","aka":[],"tldr":"The first immunotherapy signal in the 95 percent of bowel cancers that have always ignored it: an engineered CTLA-4 antibody plus a PD-1 antibody shrank tumours in 17 percent of 101 heavily treated patients.","summary":"Bullock, Schlechter, Fakih and colleagues report outcomes in 148 heavily pre-treated patients with microsatellite stable metastatic colorectal cancer (six from dose escalation, 142 from dose expansion) treated with botensilimab, an Fc-enhanced multifunctional anti-CTLA-4 antibody designed to extend therapy to poorly immunogenic tumours, plus balstilimab, an anti-PD-1 antibody. The primary endpoint was safety and tolerability; secondary endpoints included investigator-assessed objective response, disease control, duration of response and progression-free survival. One hundred and one patients were response evaluable with at least six months of follow-up.\n\nTreatment-related adverse events occurred in 131 of 148 patients (89 percent), most commonly fatigue (35 percent), diarrhoea (32 percent) and pyrexia (24 percent), with no grade 5 treatment-related events and a 12 percent discontinuation rate.","asOf":"2026-09-24","links":[{"label":"Nat Med 2024","url":"https://doi.org/10.1038/s41591-024-03083-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38871975/"},{"label":"Europe PMC full text (PMC11405281)","url":"https://europepmc.org/article/MED/38871975"}],"tags":["colorectal-evidence"],"related":["idea-immunotherapy-mss-crc","paper-le-mmr-deficiency-pd1-nejm-2015"],"cancers":["colorectal"],"sections":["immunotherapy"],"technologies":["checkpoint-inhibitor"],"targets":["ctla4","pd1"],"drugs":["botensilimab","balstilimab"],"companies":["agenus"],"institutions":[],"pathways":["pd1-checkpoint","cancer-immunity-cycle"],"terms":["msi","cold-vs-hot","mss-pmmr"],"trials":[],"people":["heinz-josef-lenz"],"bottlenecks":["b-immunotherapy-response","b-tme-immunosuppression"],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2024,"doi":"10.1038/s41591-024-03083-7","pmid":"38871975","authors":"Bullock AJ, Schlechter BL, Fakih MG, et al.","paperType":"rct","findings":["Objective response 17 percent (17 of 101; 95 percent CI 10 to 26) and disease control 61 percent (62 of 101; 51 to 71) in the response-evaluable population.","Median duration of response not reached (95 percent CI 5.7 months to not reached); median progression-free survival 3.5 months (2.7 to 4.1) at a median 10.3 months of follow-up.","Treatment-related adverse events in 89 percent (131 of 148); no grade 5 events; 12 percent discontinued for toxicity."],"whatItMeans":"The first credible response signal in microsatellite stable colorectal cancer, and the reason the field's attention has moved to Fc engineering and to excluding patients with active liver metastases, in whom responses are rare.","caveats":["Phase 1 expansion, single-arm, investigator-assessed: the response rate is not a randomised estimate.","Responses concentrate in patients without active liver metastases, so the population is narrower than the headline figure implies.","Immune-mediated toxicity is substantial and a randomised phase 3 has not yet reported."],"participants":148},{"id":"paper-bourgeois-daigneault-neoadjuvant-ovt-tnbc-scitranslmed-2018","kind":"paper","name":"Bourgeois-Daigneault 2018: giving the virus before surgery, not after everything else has failed","aka":[],"tldr":"In mice with triple-negative breast cancer, treating with a cancer-killing virus before the tumour was removed made checkpoint immunotherapy work afterwards, which it otherwise did not.","summary":"Triple-negative breast cancer has few treatment options and immune checkpoint inhibitors have had limited success in it. Because checkpoint inhibitors work best where anticancer immunity already exists, and oncolytic viruses induce anticancer immunity, Bourgeois-Daigneault and colleagues tested the virus as a way of creating the conditions for the checkpoint inhibitor.\n\nIn a model designed to mimic the course of treatment for a woman newly diagnosed with triple-negative breast cancer, early oncolytic virus treatment combined with surgical resection produced long-term benefit, and sensitised otherwise refractory tumours to checkpoint blockade, preventing relapse in most treated animals. The authors proposed testing this in the window between diagnosis and surgery.\n\nThis is the published rationale for the neoadjuvant use of oncolytic virotherapy, and it is the argument the 2024 self-experiment case report cites for its own design.","asOf":"2026-09-25","links":[{"label":"Sci Transl Med 2018","url":"https://doi.org/10.1126/scitranslmed.aao1641"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29298865/"}],"tags":[],"related":[],"cancers":["tnbc"],"sections":["immunotherapy"],"technologies":["oncolytic-virus"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["science-translational-medicine"],"dependsOn":[],"notes":[],"journal":"Science Translational Medicine","year":2018,"doi":"10.1126/scitranslmed.aao1641","pmid":"29298865","authors":"Bourgeois-Daigneault MC, Roy DG, Aitken AS, et al.","paperType":"basic","findings":["Oncolytic virus treatment given early, with surgical resection, produced long-term benefit in a model mimicking the treatment course of newly diagnosed triple-negative breast cancer.","The virus sensitised tumours otherwise refractory to immune checkpoint blockade, preventing relapse in most treated animals.","The proposed clinical translation is the window of opportunity between diagnosis and surgery, rather than the late metastatic setting where oncolytic viruses are usually tested."],"whatItMeans":"The field's standing explanation for its own poor clinical record is that it has been tested in the wrong patients: people with widely metastatic, heavily pretreated disease and exhausted immune systems. This paper is the preclinical case for testing it in the opposite situation, in early disease before surgery, where an immune response can still be built.","caveats":["Mouse models of triple-negative breast cancer, which have repeatedly predicted immunotherapy benefits that did not appear in patients.","The neoadjuvant hypothesis remains untested in a randomised trial in breast cancer.","Sensitising to checkpoint blockade in mice has a poor track record of translating; the randomised combination trial in melanoma was negative."]},{"id":"paper-braf-thyroid-endocr-rev-2007","kind":"paper","name":"BRAF mutation in papillary thyroid cancer: pathogenic role, molecular bases, and clinical implications","aka":[],"tldr":"Review on BRAF in Thyroid cancer, in Endocrine reviews (2007), one of the most cited Europe PMC records with BRAF in its title.","summary":"In recent years, the T1799A B-type Raf kinase (BRAF) mutation in thyroid cancer has received enthusiastic investigation, and significant progress has been made toward understanding its tumorigenic role and clinical significance. Among various thyroid tumors, this mutation occurs uniquely in papillary thyroid cancer (PTC), the most common endocrine malignancy, and some apparently PTC-derived anaplastic thyroid cancers. Many studies have found this mutation to be associated with those clinicopathological characteristics of PTC that are conventionally known to predict tumor progression and recurrence, including, for example, old patient age, extrathyroidal invasion, lymph node metastasis, and advanced tumor stages. Direct association of BRAF mutation with the clinical progression, recurrence, and treatment failure of PTC has also been demonstrated. The BRAF mutation has even been correlated with PTC recurrence in patients with conventionally low-risk clinicopathological factors. Some molecular mechanisms determining BRAF mutation-promoted progression and the aggressiveness of PTC have recently been uncovered. These include the down-regulation of major tumor suppressor genes and thyroid iodide-metabolizing genes and the up-regulation of cancer-promoting molecules, such as vascular endothelial growth factor, matrix metalloproteinases, nuclear transcription factor kappaB, and c-Met. Thus, BRAF mutation represents a novel indicator of the progression and aggressiveness of PTC. Significant advances have also occurred in the preclinical testing of new therapeutic strategies targeting the MAPK pathway aberrantly activated by BRAF mutation and other related mutations. New mitogen extracellular kinase (MEK) inhibitors developed recently are particularly promising therapeutic agents for thyroid cancer. With these advances, it has become clearer that BRAF mutation will likely have significant impact on the clinical management of PTC.\n\nIndexed on Europe PMC as PubMed record 17940185 (DOI 10.1210/er.2007-0007). Its title names BRAF and its text names Thyroid cancer; PubMed types it as a review (Research Support, Non-U.S. Gov't, Review, Research Support, N.I.H., Extramural). It was matched automatically to the idea \"BRAF/MEK plus PD-1 blockade as standard for BRAF-mutant anaplastic thyroid cancer\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Endocr Rev 2007","url":"https://doi.org/10.1210/er.2007-0007"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/17940185/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/17940185"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Endocrine reviews","year":2007,"doi":"10.1210/er.2007-0007","pmid":"17940185","authors":"Xing M","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for BRAF in Thyroid cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by BRAF in the title and Thyroid cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-braf-thyroid-endocr-relat-cancer-2005","kind":"paper","name":"BRAF mutation in thyroid cancer","aka":[],"tldr":"Review on BRAF in Thyroid cancer, in Endocrine-related cancer (2005), one of the most cited Europe PMC records with BRAF in its title.","summary":"Genetic alteration is the driving force for thyroid tumorigenesis and progression, based upon which novel approaches to the management of thyroid cancer can be developed. A recent important genetic finding in thyroid cancer is the oncogenic T1799A transversion mutation of BRAF (the gene for the B-type Raf kinase, BRAF). Since the initial report of this mutation in thyroid cancer 2 years ago, rapid advancements have been made. BRAF mutation is the most common genetic alteration in thyroid cancer, occurring in about 45% of sporadic papillary thyroid cancers (PTCs), particularly in the relatively aggressive subtypes, such as the tall-cell PTC. This mutation is mutually exclusive with other common genetic alterations, supporting its independent oncogenic role, as demonstrated by transgenic mouse studies that showed BRAF mutation-initiated development of PTC and its transition to anaplastic thyroid cancer. BRAF mutation is mutually exclusive with RET/PTC rearrangement, and also displays a reciprocal age association with this common genetic alteration in thyroid cancer. The T1799A BRAF mutation occurs exclusively in PTC and PTC-derived anaplastic thyroid cancer and is a specific diagnostic marker for this cancer when identified in cytological and histological specimens. This mutation is associated with a poorer clinicopathological outcome and is a novel independent molecular prognostic marker in the risk evaluation of thyroid cancer. Moreover, preclinical and clinical evaluations of the therapeutic value of novel specific mitogen-activated protein kinase pathway inhibitors in thyroid cancer are anticipated. This newly discovered BRAF mutation may prove to have an important impact on thyroid cancer in the clinic.\n\nIndexed on Europe PMC as PubMed record 15947100 (DOI 10.1677/erc.1.0978). Its title names BRAF and its text names Thyroid cancer; PubMed types it as a review (Research Support, Non-U.S. Gov't, Review). It was matched automatically to the idea \"BRAF/MEK plus PD-1 blockade as standard for BRAF-mutant anaplastic thyroid cancer\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Endocr Relat Cancer 2005","url":"https://doi.org/10.1677/erc.1.0978"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/15947100/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/15947100"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["endocrine-related-cancer"],"dependsOn":[],"notes":[],"journal":"Endocrine-related cancer","year":2005,"doi":"10.1677/erc.1.0978","pmid":"15947100","authors":"Xing M","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for BRAF in Thyroid cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by BRAF in the title and Thyroid cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-tiacci-n-engl-j-med","kind":"paper","name":"BRAF mutations in hairy-cell leukemia","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 21663470 and published in New England Journal of Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Background: Hairy-cell leukemia (HCL) is a well-defined clinicopathological entity whose underlying genetic lesion is still obscure.\n\nMethods: We searched for HCL-associated mutations by performing massively parallel sequencing of the whole exome of leukemic and matched normal cells purified from the peripheral blood of an index patient with HCL. Findings were validated by Sanger sequencing in 47 additional patients with HCL.\n\nResults: Whole-exome sequencing identified five missense somatic clonal mutations that were confirmed on Sanger sequencing, including a heterozygous mutation in BRAF that results in the BRAF V600E variant protein. Since BRAF V600E is oncogenic in other tumors, further analyses were focused on this genetic lesion. The same BRAF mutation was noted in all the other 47 patients with HCL who were evaluated by means of Sanger sequencing. None of the 195 patients with other peripheral B-cell lymphomas or leukemias who were evaluated carried the BRAF V600E variant, including 38 patients with splenic marginal-zone lymphomas or unclassifiable splenic lymphomas or leukemias. In immunohistologic and Western blot studies, HCL cells expressed phosphorylated MEK and ERK (the downstream targets of the BRAF kinase), indicating a constitutive activation of the RAF-MEK-ERK mitogen-activated protein kinase pathway in HCL. In vitro incubation of BRAF-mutated primary leukemic hairy cells from 5 patients with PLX-4720, a specific inhibitor of active BRAF, led to a marked decrease in phosphorylated ERK and MEK. CONCLUSIONS; The BRAF V600E mutation was present in all patients with HCL who were evaluated. This finding may have implications for the pathogenesis, diagnosis, and targeted therapy of HCL. (Funded by Associazione Italiana per la Ricerca sul Cancro and others.).\n\nIndexed on Europe PMC as PubMed record 21663470 (DOI 10.1056/nejmoa1014209). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2011","url":"https://doi.org/10.1056/nejmoa1014209"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21663470/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/21663470"}],"tags":["europepmc-ingest"],"related":["hairy-cell-leukemia"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2011,"doi":"10.1056/nejmoa1014209","pmid":"21663470","authors":"Tiacci E, Trifonov V, Schiavoni G, et al.","paperType":"basic","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-achrol-nat-rev-dis-primers","kind":"paper","name":"Brain metastases","aka":[],"tldr":"Paper cited by one bottleneck page, indexed on Europe PMC as PubMed record 30655533 and published in Nature reviews. Disease primers; the citing page links this DOI, which is how the record was matched.","summary":"An estimated 20% of all patients with cancer will develop brain metastases, with the majority of brain metastases occurring in those with lung, breast and colorectal cancers, melanoma or renal cell carcinoma. Brain metastases are thought to occur via seeding of circulating tumour cells into the brain microvasculature; within this unique microenvironment, tumour growth is promoted and the penetration of systemic medical therapies is limited. Development of brain metastases remains a substantial contributor to overall cancer mortality in patients with advanced-stage cancer because prognosis remains poor despite multimodal treatments and advances in systemic therapies, which include a combination of surgery, radiotherapy, chemotherapy, immunotherapy and targeted therapies. Thus, interest abounds in understanding the mechanisms that drive brain metastases so that they can be targeted with preventive therapeutic strategies and in understanding the molecular characteristics of brain metastases relative to the primary tumour so that they can inform targeted therapy selection. Increased molecular understanding of the disease will also drive continued development of novel immunotherapies and targeted therapies that have higher bioavailability beyond the blood-tumour barrier and drive advances in radiotherapies and minimally invasive surgical techniques. As these discoveries and innovations move from the realm of basic science to preclinical and clinical applications, future outcomes for patients with brain metastases are almost certain to improve.\n\nIndexed on Europe PMC as PubMed record 30655533 (DOI 10.1038/s41572-018-0055-y). Matched by DOI alone: one bottleneck page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Dis Primers 2019","url":"https://doi.org/10.1038/s41572-018-0055-y"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30655533/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30655533"}],"tags":["europepmc-ingest"],"related":["b-brain-delivery"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature reviews. Disease primers","year":2019,"doi":"10.1038/s41572-018-0055-y","pmid":"30655533","authors":"Achrol AS, Rennert RC, Anders C, et al.","paperType":"review","findings":[],"whatItMeans":"One bottleneck page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-bray-globocan-2018-cacancer-2018","kind":"paper","name":"Bray 2018: GLOBOCAN 2018, worldwide incidence and mortality for 36 cancers","aka":[],"tldr":"The IARC count for 2018: about 18.1 million new cancer cases worldwide, with lung cancer the most commonly diagnosed and most lethal, and about one in five men and one in six women developing cancer during their lifetime.","summary":"GLOBOCAN 2018 estimated cancer incidence and mortality for 36 cancers in 185 countries from national and regional registries and modelling. It counted 18.1 million new cases in 2018. Lung cancer was the most commonly diagnosed cancer and the leading cause of cancer death, followed for incidence by female breast, colorectal and prostate cancers. The report described how cancer patterns differ with a country's level of development, with infection-related cancers of the cervix, liver and stomach concentrated in transitioning economies.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.3322/caac.21492"},{"label":"IARC Global Cancer Observatory","url":"https://gco.iarc.who.int/today"}],"tags":[],"related":["paper-sung-globocan-2020-cacancer-2021","paper-bray-globocan-2022-cacancer-2024"],"cancers":["nsclc","breast-hr-positive","colorectal","prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["iarc"],"pathways":[],"terms":["incidence-vs-prevalence","mortality"],"trials":[],"people":["bray-freddie"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"CA: A Cancer Journal for Clinicians","year":2018,"doi":"10.3322/caac.21492","authors":"Bray F, Ferlay J, Soerjomataram I, et al.","paperType":"observational","findings":["About 18.1 million new cancer cases and 9.6 million cancer deaths worldwide in 2018.","Lung cancer the most commonly diagnosed (11.6% of cases) and the leading cause of cancer death (18.4% of deaths); female breast cancer also 11.6% of cases; colorectal 10.2%; prostate 7.1%.","About one in five men and one in six women develop cancer during their lifetime; one in eight men and one in eleven women die from it."],"whatItMeans":"This was the most cited description of the global cancer burden until the 2020 release and is the reference behind many national cancer plans of the late 2010s. Its country-level comparisons showed where prevention, such as HPV and hepatitis B vaccination and tobacco control, would have the largest effect.","caveats":["Registry coverage is incomplete in much of Africa and Asia, so those estimates depend on modelling.","Superseded by the 2020 and 2022 releases."],"changedPractice":false},{"id":"paper-bray-globocan-2022-cacancer-2024","kind":"paper","name":"Bray 2024: GLOBOCAN 2022, the world's cancer count for 36 cancers in 185 countries","aka":[],"tldr":"The IARC estimate that about 20 million people were diagnosed with cancer in 2022 and 9.7 million died of it, with lung cancer the most common and most lethal, breast cancer second, and the total expected to rise by about three quarters by 2050 as populations grow and age.","summary":"GLOBOCAN 2022, produced by the International Agency for Research on Cancer, estimates new cases and deaths for 36 cancer types in 185 countries from national registries and modelling. It counted close to 20 million new cases (including non-melanoma skin cancer) and 9.7 million deaths in 2022. Lung cancer was the most frequently diagnosed cancer and the leading cause of cancer death, followed by female breast cancer for incidence and colorectal cancer for both. About one in five people develop cancer in their lifetime. The report projects around 35 million new cases a year by 2050, an increase of roughly 77% driven mostly by demographic change, and it is the reference that country pages, prevalence charts and policy papers cite.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.3322/caac.21834"},{"label":"IARC Global Cancer Observatory","url":"https://gco.iarc.who.int/today"}],"tags":[],"related":[],"cancers":["nsclc","breast-hr-positive","colorectal"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["iarc"],"pathways":[],"terms":[],"trials":[],"people":["bray-freddie"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"CA: A Cancer Journal for Clinicians","year":2024,"doi":"10.3322/caac.21834","authors":"Bray F, Laversanne M, Sung H, et al.","paperType":"observational","findings":["Close to 20 million new cancer cases and 9.7 million cancer deaths worldwide in 2022.","Lung cancer: about 2.5 million cases (12.4% of the total) and 1.8 million deaths (18.7%), the leading cause of cancer death.","Female breast cancer second most common (about 2.3 million cases); colorectal cancer third for incidence and second for deaths.","Roughly one in five people develop cancer in their lifetime; about one in nine men and one in twelve women die from it.","Projection of about 35 million new cases in 2050, a 77% increase over 2022."],"whatItMeans":"This is the number behind almost every statement about how much cancer there is. It shows the burden shifting towards low- and middle-income countries and towards older populations, which is why prevention, screening and affordable treatment in those settings decide the global trend. OnCo's country and prevalence pages draw on the same GLOBOCAN release.","caveats":["Many countries lack population-based registries, so estimates there rest on modelling from neighbours and mortality data.","Non-melanoma skin cancer is counted inconsistently across registries and is often excluded from headline totals.","Estimates are for 2022 and are revised as registries report."],"changedPractice":false},{"id":"paper-breakwater-nejm-2025","kind":"paper","name":"BREAKWATER: encorafenib plus cetuximab with chemotherapy as first treatment for BRAF V600E-mutated colorectal cancer","aka":[],"tldr":"Adding a BRAF inhibitor and an EGFR antibody to first-line chemotherapy roughly doubled survival in BRAF V600E-mutated metastatic bowel cancer, one of the worst-prognosis subtypes.","summary":"Open-label phase 3 trial of patients with untreated BRAF V600E-mutated metastatic colorectal cancer randomised to encorafenib plus cetuximab plus mFOLFOX6, encorafenib plus cetuximab alone (arm later closed), or standard chemotherapy with or without bevacizumab. Primary endpoints were PFS and objective response rate.\n\nThe first report (Nature Medicine 2025) showed a response rate of about 61% vs 40%, supporting accelerated FDA approval in December 2024. The 2025 NEJM report showed median PFS 12.8 vs 7.1 months (HR 0.53) and median OS 30.3 vs 15.1 months (HR 0.49). It moved BRAF-targeted therapy from second line (BEACON) to first line and is the largest survival gain ever seen in this subgroup.","asOf":"2026-09-08","links":[{"label":"PubMed search: BREAKWATER encorafenib NEJM 2025","url":"https://pubmed.ncbi.nlm.nih.gov/?term=BREAKWATER+encorafenib+cetuximab+mFOLFOX6+colorectal"},{"label":"ClinicalTrials.gov NCT04607421","url":"https://clinicaltrials.gov/study/NCT04607421"}],"tags":[],"related":["braf-v600e"],"cancers":["colorectal"],"sections":[],"technologies":["kinase-inhibitors","monoclonal-antibody","cytotoxic-chemotherapy","cgp"],"targets":["braf","egfr"],"drugs":["encorafenib"],"companies":["pfizer"],"institutions":["vall-dhebron","md-anderson"],"pathways":["ras-mapk"],"terms":["orr","pfs","os","first-line","accelerated-approval"],"trials":[],"people":["elena-elez","yoshino-takayuki","shen-lin","kim-tae-won","josep-tabernero"],"bottlenecks":["b-resistance","b-combination-space","b-drug-pricing"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2025,"doi":"10.1056/NEJMoa2501912","pmid":"40444708","authors":"Elez E, Yoshino T, Shen L, et al.","paperType":"rct","findings":["Objective response about 61% vs 40% in the first analysis (Nature Medicine 2025), with longer duration of response.","Median PFS 12.8 vs 7.1 months; HR 0.53.","Median overall survival 30.3 vs 15.1 months; HR 0.49.","Grade 3 or higher adverse events were more frequent with the triplet plus chemotherapy, driven by skin toxicity, gastrointestinal events and neutropenia.","The chemotherapy-free encorafenib plus cetuximab arm was stopped early after emerging data from other studies."],"whatItMeans":"Patients with newly diagnosed metastatic colorectal cancer whose tumour carries a BRAF V600E mutation, which is about 8-12% of cases, should now be offered encorafenib and cetuximab together with FOLFOX from the start rather than after chemotherapy fails; median survival has roughly doubled to about two and a half years. BRAF testing at diagnosis is therefore essential, alongside RAS and mismatch repair testing. The regimen is more toxic than chemotherapy alone.","caveats":["Open-label; some figures come from conference presentations and interim analyses, and long-term follow-up is short.","Most patients had microsatellite-stable tumours; dMMR BRAF-mutated tumours should still receive immunotherapy first.","Combination toxicity and cost are considerable; treatment requires three targeted or antibody agents plus chemotherapy.","Resistance to BRAF/EGFR blockade remains universal; the trial does not address what follows."],"changedPractice":true},{"id":"paper-harbeck-nat-rev-dis-primers","kind":"paper","name":"Breast cancer","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 31548545 and published in Nature reviews. Disease primers; the citing page links this DOI, which is how the record was matched.","summary":"Breast cancer is the most frequent malignancy in women worldwide and is curable in ~70-80% of patients with early-stage, non-metastatic disease. Advanced breast cancer with distant organ metastases is considered incurable with currently available therapies. On the molecular level, breast cancer is a heterogeneous disease; molecular features include activation of human epidermal growth factor receptor 2 (HER2, encoded by ERBB2), activation of hormone receptors (oestrogen receptor and progesterone receptor) and/or BRCA mutations. Treatment strategies differ according to molecular subtype. Management of breast cancer is multidisciplinary; it includes locoregional (surgery and radiation therapy) and systemic therapy approaches. Systemic therapies include endocrine therapy for hormone receptor-positive disease, chemotherapy, anti-HER2 therapy for HER2-positive disease, bone stabilizing agents, poly(ADP-ribose) polymerase inhibitors for BRCA mutation carriers and, quite recently, immunotherapy. Future therapeutic concepts in breast cancer aim at individualization of therapy as well as at treatment de-escalation and escalation based on tumour biology and early therapy response. Next to further treatment innovations, equal worldwide access to therapeutic advances remains the global challenge in breast cancer care for the future.\n\nIndexed on Europe PMC as PubMed record 31548545 (DOI 10.1038/s41572-019-0111-2). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Dis Primers 2019","url":"https://doi.org/10.1038/s41572-019-0111-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31548545/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31548545"}],"tags":["europepmc-ingest"],"related":["breast-cancer-signalling"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature reviews. Disease primers","year":2019,"doi":"10.1038/s41572-019-0111-2","pmid":"31548545","authors":"Harbeck N, Penault-Llorca F, Cortes J, et al.","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-travis-breast-cancer-after-hodgkin-radiotherapy-jama-2003","kind":"paper","name":"Breast cancer following radiotherapy and chemotherapy among young women with Hodgkin disease","aka":["Travis 2003","Radiation dose and breast cancer risk after Hodgkin lymphoma"],"tldr":"In young women treated for Hodgkin lymphoma, breast cancer risk rose with the radiation dose to the breast, and fell when chemotherapy or radiation had stopped the ovaries working.","summary":"This international case-control study inside a cohort quantified the two things that decide breast cancer risk after Hodgkin lymphoma: how much radiation the breast received, and whether the ovaries kept working afterwards. 105 women who developed breast cancer were matched to 266 women with Hodgkin lymphoma who did not, all drawn from a cohort of 3,817 one-year survivors diagnosed at age 30 or younger between 1965 and 1994 across six population-based cancer registries.\n\nA radiation dose of 4 Gy or more to the site of the breast cancer was associated with a 3.2-fold increased risk (95 per cent confidence interval 1.4 to 8.2) compared with women who received lower doses and no alkylating agents. Risk rose to eightfold (2.6 to 26.4) with a dose above 40 Gy. The risk did not diminish at the highest doses or with the longest follow-up.\n\nThe protective finding is the mechanistic one. Ovarian damage from alkylating agents or from radiation to the ovaries reduced risk, which indicates that hormonal stimulation is required for radiation-induced breast cancer to develop. That is a biologically coherent and clinically unwelcome result: the treatment that lowers one risk raises others and causes infertility.","asOf":"2026-10-01","links":[{"label":"JAMA 2003","url":"https://doi.org/10.1001/jama.290.4.465"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/12876089/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/12876089"}],"tags":["lymphoma-evidence"],"related":["paper-schaapveld-second-cancer-risk-40-years-hodgkin-nejm-2015","paper-van-nimwegen-cardiovascular-disease-after-hodgkin-jama-intern-med-2015","lymphoma-roadmap"],"cancers":["hodgkin-lymphoma","early-stage-classical-hodgkin-lymphoma"],"sections":["radiation","early-detection","supportive-care"],"technologies":["radiotherapy","mammography"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol","b-early-detection"],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2003,"doi":"10.1001/jama.290.4.465","pmid":"12876089","authors":"Travis LB, Hill DA, Dores GM, et al.","paperType":"observational","findings":["A radiation dose of 4 Gy or more to the breast was associated with a 3.2-fold increased breast cancer risk (95 per cent confidence interval 1.4 to 8.2) compared with lower doses and no alkylating agents.","Risk rose to eightfold (2.6 to 26.4) with a dose above 40 Gy.","The radiation-related risk did not diminish at the highest doses or with the longest follow-up.","Ovarian damage from alkylating agents or from radiation to the ovaries was associated with reduced breast cancer risk, indicating that hormonal stimulation is important for radiation-induced breast cancer.","105 breast cancer cases were matched to 266 controls within a cohort of 3,817 women diagnosed with Hodgkin lymphoma at age 30 or younger."],"whatItMeans":"The dose-response curve behind breast surveillance programmes for women irradiated for Hodgkin lymphoma as teenagers or young adults, which in several countries start at 25 or eight years after radiotherapy and use magnetic resonance imaging as well as mammography.","caveats":["A case-control study within a cohort, with radiation doses reconstructed from treatment records rather than measured.","Treatment eras up to 1994, with mantle fields far larger than modern involved-site radiotherapy.","105 cases gives wide confidence intervals, particularly in the highest dose stratum.","The protective effect of ovarian failure is not a treatment recommendation: premature menopause carries its own substantial harms."],"changedPractice":true,"participants":371},{"id":"paper-nccn-breast-cancer-v4-2026-jnccn-2026","kind":"paper","name":"Breast Cancer, Version 4.2026, NCCN Clinical Practice Guidelines In Oncology","aka":[],"tldr":"The 2026 journal summary of the US NCCN breast cancer guideline, this version focused on recurrent and metastatic disease and how treatment is chosen by receptor status, prior therapy and time since treatment.","summary":"Journal summary of the NCCN Clinical Practice Guidelines for Breast Cancer, version 4.2026, by Gradishar, Moran, Abraham, Abramson and colleagues. The guidelines cover carcinoma in situ, invasive breast cancer, Paget's disease, phyllodes tumour, inflammatory breast cancer and breast cancer in pregnancy; the panel convenes annually. This selection concentrates on recurrent or stage IV (M1) disease and summarises treatment stratified by hormone receptor status and HER2 expression, prior therapy and disease-free interval, with supportive care, quality of life, toxicity minimisation and trial participation emphasised throughout. The NCCN category grades quoted on the triple-negative page (category 1, preferred for the KEYNOTE-522 regimen and for first-line sacituzumab govitecan with pembrolizumab) come from the full guideline.","asOf":"2026-09-24","links":[{"label":"JNCCN 2026","url":"https://doi.org/10.6004/jnccn.2026.0033"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42425164/"},{"label":"NCCN Guidelines: Breast Cancer","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1419"}],"tags":["tnbc-evidence"],"related":["nccn"],"cancers":["tnbc","breast-hr-positive","breast-her2-positive"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-522","ascent-04","ascent-03","tropion-breast02"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jnccn"],"dependsOn":[],"notes":[],"journal":"Journal of the National Comprehensive Cancer Network","year":2026,"doi":"10.6004/jnccn.2026.0033","pmid":"42425164","authors":"Gradishar WJ, Moran MS, Abraham J, et al.","paperType":"guideline","findings":["This version's text concentrates on recurrent or stage IV (M1) disease stratified by hormone receptor and HER2 status, prior therapy and disease-free interval.","Supportive care, quality of life, toxicity minimisation and trial participation are emphasised across all treatment lines."],"whatItMeans":"NCCN is the source of the category grades on the triple-negative breast cancer page and the first major guideline to place an antibody-drug conjugate first line for the disease.","caveats":["The full guideline requires free registration on nccn.org; the JNCCN article is a summary.","US practice and payer context; not all listed options are funded in the UK."],"changedPractice":true},{"id":"paper-kunkler-n-engl-j-med","kind":"paper","name":"Breast-Conserving Surgery with or without Irradiation in Early Breast Cancer","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 36791159 and published in New England Journal of Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Background: Limited level 1 evidence is available on the omission of radiotherapy after breast-conserving surgery in older women with hormone receptor-positive early breast cancer receiving adjuvant endocrine therapy.\n\nMethods: We performed a phase 3 randomized trial of the omission of irradiation; the trial population included women 65 years of age or older who had hormone receptor-positive, node-negative, T1 or T2 primary breast cancer (with tumors ≤3 cm in the largest dimension) treated with breast-conserving surgery with clear excision margins and adjuvant endocrine therapy. Patients were randomly assigned to receive whole-breast irradiation (40 to 50 Gy) or no irradiation. The primary end point was local breast cancer recurrence. Regional recurrence, breast cancer-specific survival, distant recurrence as the first event, and overall survival were also assessed.\n\nResults: A total of 1326 women were enrolled; 658 were randomly assigned to receive whole-breast irradiation and 668 to receive no irradiation. The median follow-up was 9.1 years. The cumulative incidence of local breast cancer recurrence within 10 years was 9.5% (95% confidence interval [CI], 6.8 to 12.3) in the no-radiotherapy group and 0.9% (95% CI, 0.1 to 1.7) in the radiotherapy group (hazard ratio, 10.4; 95% CI, 4.1 to 26.1; P<0.001). Although local recurrence was more common in the group that did not receive radiotherapy, the 10-year incidence of distant recurrence as the first event was not higher in the no-radiotherapy group than in the radiotherapy group, at 1.6% (95% CI, 0.4 to 2.8) and 3.0% (95% CI, 1.4 to 4.5), respectively. Overall survival at 10 years was almost identical in the two groups, at 80.8% (95% CI, 77.2 to 84.3) with no radiotherapy and 80.7% (95% CI, 76.9 to 84.3) with radiotherapy. The incidence of regional recurrence and breast cancer-specific survival also did not differ substantially between the two groups.\n\nConclusions: Omission of radiotherapy was associated with an increased incidence of local recurrence but had no detrimental effect on distant recurrence as the first event or overall survival among women 65 years of age or older with low-risk, hormone receptor-positive early breast cancer. (Funded by the Chief Scientist Office of the Scottish Government and the Breast Cancer Institute, Western General Hospital, Edinburgh; ISRCTN number, ISRCTN95889329.).\n\nIndexed on Europe PMC as PubMed record 36791159 (DOI 10.1056/nejmoa2207586). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2023","url":"https://doi.org/10.1056/nejmoa2207586"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36791159/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36791159"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["prime-ii"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/nejmoa2207586","pmid":"36791159","authors":"Kunkler IH, Williams LJ, Jack WJL, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-echelon-3-brentuximab-lenalidomide-rituximab-dlbcl-jco-2025","kind":"paper","name":"Brentuximab vedotin combination for relapsed diffuse large B-cell lymphoma","aka":["ECHELON-3","Bartlett 2025"],"tldr":"Adding a CD30-directed antibody-drug conjugate to a tablet-and-antibody pairing added about five months of median survival for heavily pretreated people with relapsed aggressive lymphoma.","summary":"A randomised, double-blind, placebo-controlled, multicentre phase 3 trial comparing brentuximab vedotin with lenalidomide and rituximab against placebo with lenalidomide and rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma. 230 patients were randomised, 112 to brentuximab vedotin and 118 to placebo; two in the placebo arm did not receive treatment. Brentuximab vedotin or placebo was given every three weeks, lenalidomide daily and rituximab every three weeks. Overall survival was the primary endpoint, with a prespecified interim analysis after 134 deaths against an efficacy boundary of two-sided p = 0.0232.\n\nAt a median follow-up of 16.4 months, median overall survival was 13.8 months with brentuximab vedotin against 8.5 months with placebo (hazard ratio 0.63, 95 per cent confidence interval 0.45 to 0.89, two-sided p = 0.009). Median progression-free survival was 4.2 months against 2.6 (hazard ratio 0.53, 0.38 to 0.73).","asOf":"2026-10-01","links":[{"label":"Journal of Clinical Oncology 2025","url":"https://doi.org/10.1200/JCO-24-02242"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39772655/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39772655"}],"tags":["lymphoma-evidence"],"related":["lymphoma-roadmap"],"cancers":["dlbcl","non-hodgkin-lymphoma"],"sections":["adcs","immunotherapy"],"technologies":["adc"],"targets":["cd30","cd20"],"drugs":["brentuximab-vedotin","lenalidomide","rituximab"],"companies":["pfizer"],"institutions":[],"pathways":[],"terms":[],"trials":["nct04404283"],"people":[],"bottlenecks":["b-toxicity-qol","b-aging-comorbidity"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2025,"doi":"10.1200/JCO-24-02242","pmid":"39772655","authors":"Bartlett NL, Hahn U, Kim WS, et al.","paperType":"rct","findings":["Median overall survival was 13.8 months with brentuximab vedotin, lenalidomide and rituximab against 8.5 months with placebo, lenalidomide and rituximab (hazard ratio 0.63, 95 per cent confidence interval 0.45 to 0.89, two-sided p = 0.009).","Median progression-free survival was 4.2 months against 2.6 months (hazard ratio 0.53, 0.38 to 0.73).","The result comes from a prespecified interim analysis after 134 overall survival events, against an efficacy boundary of two-sided p = 0.0232.","The trial was double-blind and placebo-controlled, which is unusual in this heavily pretreated setting."],"whatItMeans":"The evidence behind the United States approval of brentuximab vedotin with lenalidomide and a rituximab product for relapsed or refractory diffuse large B-cell lymphoma after two or more lines in patients not eligible for an autologous transplant or CAR-T. It is also the first demonstration that a CD30-directed conjugate helps in a disease where CD30 expression is variable.","caveats":["An interim analysis at a median follow-up of 16.4 months; the final overall survival estimate may move.","The comparator, lenalidomide with rituximab, is not a universal standard in this setting, so the size of the benefit against other options is unknown.","Medians of 13.8 and 8.5 months describe a population in which few are cured."],"changedPractice":true,"participants":230},{"id":"paper-horwitz-lancet","kind":"paper","name":"Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 30522922 and published in The Lancet; the citing page links this DOI, which is how the record was matched.","summary":"Background: Based on the encouraging activity and manageable safety profile observed in a phase 1 study, the ECHELON-2 trial was initiated to compare the efficacy and safety of brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone (A+CHP) versus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) for the treatment of CD30-positive peripheral T-cell lymphomas.\n\nMethods: ECHELON-2 is a double-blind, double-dummy, randomised, placebo-controlled, active-comparator phase 3 study. Eligible adults from 132 sites in 17 countries with previously untreated CD30-positive peripheral T-cell lymphomas (targeting 75% with systemic anaplastic large cell lymphoma) were randomly assigned 1:1 to receive either A+CHP or CHOP for six or eight 21-day cycles. Randomisation was stratified by histological subtype according to local pathology assessment and by international prognostic index score. All patients received cyclophosphamide 750 mg/m 2 and doxorubicin 50 mg/m 2 on day 1 of each cycle intravenously and prednisone 100 mg once daily on days 1 to 5 of each cycle orally, followed by either brentuximab vedotin 1·8 mg/kg and a placebo form of vincristine intravenously (A+CHP group) or vincristine 1·4 mg/m 2 and a placebo form of brentuximab vedotin intravenously (CHOP group) on day 1 of each cycle. The primary endpoint, progression-free survival according to blinded independent central review, was analysed by intent-to-treat. This trial is registered with ClinicalTrials.gov, number NCT01777152.\n\nFindings: Between Jan 24, 2013, and Nov 7, 2016, 601 patients assessed for eligibility, of whom 452 patients were enrolled and 226 were randomly assigned to both the A+CHP group and the CHOP group. Median progression-free survival was 48·2 months (95% CI 35·2-not evaluable) in the A+CHP group and 20·8 months (12·7-47·6) in the CHOP group (hazard ratio 0·71 [95% CI 0·54-0·93], p=0·0110). Adverse events, including incidence and severity of febrile neutropenia (41 [18%] patients in the A+CHP group and 33 [15%] in the CHOP group) and peripheral neuropathy (117 [52%] in the A+CHP group and 124 [55%] in the CHOP group), were similar between groups. Fatal adverse events occurred in seven (3%) patients in the A+CHP group and nine (4%) in the CHOP group.\n\nInterpretation: Front-line treatment with A+CHP is superior to CHOP for patients with CD30-positive peripheral T-cell lymphomas as shown by a significant improvement in progression-free survival and overall survival with a manageable safety profile.\n\nFunding: Seattle Genetics Inc, Millennium Pharmaceuticals Inc, a wholly owned subsidiary of Takeda Pharmacuetical Company Limited, and National Institutes of Health National Cancer Institute Cancer Center.\n\nIndexed on Europe PMC as PubMed record 30522922 (DOI 10.1016/s0140-6736(18)32984-2). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet 2019","url":"https://doi.org/10.1016/s0140-6736(18)32984-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30522922/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30522922"}],"tags":["europepmc-ingest"],"related":["peripheral-t-cell-lymphoma","lymphoma-roadmap","lymphoma-ev-randomised-evidence-for-the-t-cell-lymphomas"],"cancers":["peripheral-t-cell-lymphoma","non-hodgkin-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2019,"doi":"10.1016/s0140-6736(18)32984-2","pmid":"30522922","authors":"Horwitz S, O'Connor OA, Pro B, et al.","paperType":"rct","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-alta-jco-2017","kind":"paper","name":"Brigatinib in patients with crizotinib-refractory ALK-positive non-small-cell lung cancer: a randomized, multicenter phase II trial (ALTA)","aka":[],"tldr":"The primary report of ALTA: after crizotinib, brigatinib shrank tumours in about half of patients, more so at the 180 mg dose after a week at 90 mg, and held the disease for around a year.","summary":"Randomised phase 2 trial of two brigatinib regimens in 222 patients with ALK-positive non-small-cell lung cancer that had progressed on crizotinib, stratified by brain metastases and best response to crizotinib: 90 mg once daily (arm A) or 180 mg once daily after a 7-day 90 mg lead-in (arm B). The primary endpoint was investigator-assessed confirmed objective response rate.\n\nAt 8.0 months median follow-up the confirmed response rate was 45 percent in arm A and 54 percent in arm B; median progression-free survival was 9.2 and 12.9 months. Intracranial response by independent review in patients with measurable brain metastases was 42 percent (11 of 26) and 67 percent (12 of 18). Early-onset pulmonary adverse events occurred in 14 of 219 treated patients, none after escalation to 180 mg in arm B.","asOf":"2026-09-24","links":[{"label":"Journal of Clinical Oncology 2017","url":"https://doi.org/10.1200/JCO.2016.71.5904"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28475456/"},{"label":"ClinicalTrials.gov NCT02094573","url":"https://clinicaltrials.gov/study/NCT02094573"}],"tags":[],"related":[],"cancers":["nsclc","alk-positive-nsclc"],"sections":[],"technologies":[],"targets":["alk"],"drugs":["brigatinib"],"companies":["takeda"],"institutions":[],"pathways":[],"terms":[],"trials":["alta"],"people":["kim-dong-wan","ross-camidge"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2017,"doi":"10.1200/JCO.2016.71.5904","pmid":"28475456","authors":"Kim DW, Tiseo M, Ahn MJ, et al.","paperType":"rct","findings":["Confirmed objective response rate 45% (97.5% CI 34 to 56) with 90 mg and 54% (97.5% CI 43 to 65) with 180 mg after lead-in.","Median progression-free survival 9.2 months (95% CI 7.4 to 15.6) and 12.9 months (95% CI 11.1 to not reached).","Intracranial response 11 of 26 (42%) and 12 of 18 (67%) among patients with measurable brain metastases; early pulmonary events in 6% of treated patients, grade 3 or higher in 3%."],"whatItMeans":"This is the trial behind brigatinib's first approval, after crizotinib, and it set the 180 mg dose with a 90 mg lead-in that the label uses. For a patient it shows a drug with strong activity in the brain and an unusual early lung side effect that the lead-in week was designed to soften.","caveats":["No control arm: both arms received brigatinib, so the trial compares doses, not brigatinib against another treatment.","Median follow-up was only 8.0 months at the primary report.","The 97.5% confidence intervals reflect the two-arm design and are wider than the usual 95%."],"changedPractice":true,"participants":222},{"id":"paper-camidge-j-thorac-oncol","kind":"paper","name":"Brigatinib Versus Crizotinib in ALK Inhibitor-Naive Advanced ALK-Positive NSCLC: Final Results of Phase 3 ALTA-1L Trial","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 34537440 and published in Journal of Thoracic Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Introduction: In the phase 3 study entitled ALK in Lung cancer Trial of brigAtinib in 1st Line (ALTA-1L), which is a study of brigatinib in ALK inhibitor-naive advanced ALK-positive NSCLC, brigatinib exhibited superior progression-free survival (PFS) versus crizotinib in the two planned interim analyses. Here, we report the final efficacy, safety, and exploratory results.\n\nMethods: Patients were randomized to brigatinib 180 mg once daily (7-d lead-in at 90 mg once daily) or crizotinib 250 mg twice daily. The primary end point was a blinded independent review committee-assessed PFS. Genetic alterations in plasma cell-free DNA were assessed in relation to clinical efficacy.\n\nResults: A total of 275 patients were enrolled (brigatinib, n = 137; crizotinib, n = 138). At study end, (brigatinib median follow-up = 40.4 mo), the 3-year PFS by blinded independent review committee was 43% (brigatinib) versus 19% (crizotinib; median = 24.0 versus 11.1 mo, hazard ratio [HR] = 0.48, 95% confidence interval [CI]: 0.35-0.66). The median overall survival was not reached in either group (HR = 0.81, 95% CI: 0.53-1.22). Posthoc analyses suggested an overall survival benefit for brigatinib in patients with baseline brain metastases (HR = 0.43, 95% CI: 0.21-0.89). Detectable baseline EML4-ALK fusion variant 3 and TP53 mutation in plasma were associated with poor PFS. Brigatinib exhibited superior efficacy compared with crizotinib regardless of EML4-ALK variant and TP53 mutation. Emerging secondary ALK mutations were rare in patients progressing on brigatinib. No new safety signals were observed.\n\nConclusions: In the ALTA-1L final analysis, with longer follow-up, brigatinib continued to exhibit superior efficacy and tolerability versus crizotinib in patients with or without poor prognostic biomarkers. The suggested survival benefit with brigatinib in patients with brain metastases warrants future study.\n\nIndexed on Europe PMC as PubMed record 34537440 (DOI 10.1016/j.jtho.2021.07.035). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Thorac Oncol 2021","url":"https://doi.org/10.1016/j.jtho.2021.07.035"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34537440/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34537440"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["alta-1l"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-thoracic-oncology"],"dependsOn":[],"notes":[],"journal":"Journal of Thoracic Oncology","year":2021,"doi":"10.1016/j.jtho.2021.07.035","pmid":"34537440","authors":"Camidge DR, Kim HR, Ahn MJ, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-alta-1l-n-engl-j-med-2018","kind":"paper","name":"Brigatinib versus Crizotinib in ALK-Positive Non-Small-Cell Lung Cancer","aka":[],"tldr":"Published report from the ALTA-1L trial registered as NCT02737501, in New England Journal of Medicine (2018), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor, has robust efficacy in patients with ALK-positive non-small-cell lung cancer (NSCLC) that is refractory to crizotinib. The efficacy of brigatinib, as compared with crizotinib, in patients with advanced ALK-positive NSCLC who have not previously received an ALK inhibitor is unclear.\n\nMethods: In an open-label, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with advanced ALK-positive NSCLC who had not previously received ALK inhibitors to receive brigatinib at a dose of 180 mg once daily (with a 7-day lead-in period at 90 mg) or crizotinib at a dose of 250 mg twice daily. The primary end point was progression-free survival as assessed by blinded independent central review. Secondary end points included the objective response rate and intracranial response. The first interim analysis was planned when approximately 50% of 198 expected events of disease progression or death had occurred.\n\nResults: A total of 275 patients underwent randomization; 137 were assigned to brigatinib and 138 to crizotinib. At the first interim analysis (99 events), the median follow-up was 11.0 months in the brigatinib group and 9.3 months in the crizotinib group. The rate of progression-free survival was higher with brigatinib than with crizotinib (estimated 12-month progression-free survival, 67% [95% confidence interval {CI}, 56 to 75] vs. 43% [95% CI, 32 to 53]; hazard ratio for disease progression or death, 0.49 [95% CI, 0.33 to 0.74]; P<0.001 by the log-rank test). The confirmed objective response rate was 71% (95% CI, 62 to 78) with brigatinib and 60% (95% CI, 51 to 68) with crizotinib; the confirmed rate of intracranial response among patients with measurable lesions was 78% (95% CI, 52 to 94) and 29% (95% CI, 11 to 52), respectively. No new safety concerns were noted.\n\nConclusions: Among patients with ALK-positive NSCLC who had not previously received an ALK inhibitor, progression-free survival was significantly longer among patients who received brigatinib than among those who received crizotinib. (Funded by Ariad Pharmaceuticals; ALTA-1L ClinicalTrials.gov number, NCT02737501.).\n\nIndexed on Europe PMC as PubMed record 30280657 (DOI 10.1056/nejmoa1810171). Its abstract cites the registry id NCT02737501, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2018","url":"https://doi.org/10.1056/nejmoa1810171"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30280657/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30280657"},{"label":"ClinicalTrials.gov NCT02737501","url":"https://clinicaltrials.gov/study/NCT02737501"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["alta-1l"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2018,"doi":"10.1056/nejmoa1810171","pmid":"30280657","authors":"Camidge DR, Kim HR, Ahn MJ, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02737501 with the most citations, so it is the natural first reading for anyone following the ALTA-1L trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-chapman-vemurafenib-nejm-2011","kind":"paper","name":"BRIM-3: improved survival with vemurafenib in melanoma with BRAF V600E mutation","aka":[],"tldr":"Vemurafenib, the first drug targeting the BRAF V600E mutation, reduced deaths by 63 percent compared with dacarbazine chemotherapy in metastatic melanoma, launching targeted therapy in the disease.","summary":"Phase 3 trial of 675 patients with previously untreated BRAF V600E-mutant metastatic melanoma randomised to vemurafenib or dacarbazine.\n\nAt interim analysis, the hazard ratio for death was 0.37 and for progression 0.26, with response of 48 versus 5 percent; cutaneous squamous cell carcinomas, arthralgia and photosensitivity were the characteristic toxicities, and the data monitoring board recommended crossover.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2011","url":"https://doi.org/10.1056/NEJMoa1103782"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21639808/"}],"tags":[],"related":[],"cancers":["braf-v600-melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":["vemurafenib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["paul-chapman"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2011,"doi":"10.1056/NEJMoa1103782","pmid":"21639808","authors":"Chapman PB, Hauschild A, Robert C, et al.","paperType":"rct","findings":["Hazard ratio for death 0.37; for progression 0.26 at interim analysis.","Objective response 48 percent vs 5 percent."],"whatItMeans":"BRAF testing became mandatory in advanced melanoma and vemurafenib the first approved BRAF inhibitor; combination with MEK inhibitors soon replaced monotherapy.","caveats":["Early analysis; responses were often short because of acquired resistance.","Keratoacanthomas and squamous cell carcinomas in about 18 percent."],"changedPractice":true,"participants":675},{"id":"paper-bsg-cholangiocarcinoma-guideline-gut-2023","kind":"paper","name":"British Society of Gastroenterology guidelines for the diagnosis and management of cholangiocarcinoma","aka":[],"tldr":"The UK gastroenterology society's 2023 guideline for bile duct cancer, written with patient charities; there is no equivalent UK guideline written for gallbladder cancer.","summary":"Guideline commissioned by the British Society of Gastroenterology liver section, written by a multidisciplinary committee with patient and public representatives from AMMF (the Cholangiocarcinoma Charity) and PSC Support, with evidence graded in the AGREE II format. The recommendations are framed as guidance rather than protocol. Its scope is cholangiocarcinoma; a Europe PMC search on 24 September 2026 found no UK society guideline specific to gallbladder cancer, so UK gallbladder practice draws on this document, the ESMO guideline and NCCN.","asOf":"2026-09-24","links":[{"label":"Gut 2023","url":"https://doi.org/10.1136/gutjnl-2023-330029"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37770126/"}],"tags":["gallbladder-evidence"],"related":["paper-esmo-biliary-tract-cancer-guideline-ann-oncol-2023"],"cancers":["cholangiocarcinoma","gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["juan-valle"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Gut","year":2023,"doi":"10.1136/gutjnl-2023-330029","pmid":"37770126","authors":"Rushbrook SM, Kendall TJ, Zen Y, et al.","paperType":"guideline","findings":["Multidisciplinary UK guideline for cholangiocarcinoma with patient representation and AGREE II grading; gallbladder cancer is outside its stated scope."],"whatItMeans":"For a UK patient with gallbladder cancer the nearest national guideline is about a neighbouring disease; the UK and NHS page for gallbladder cancer names the gap.","caveats":["Scope is cholangiocarcinoma, not gallbladder cancer.","Guidance rather than protocol, by the authors' own framing."],"changedPractice":true},{"id":"paper-kim-j-clin-oncol","kind":"paper","name":"Broadening Eligibility Criteria to Make Clinical Trials More Representative: American Society of Clinical Oncology and Friends of Cancer Research Joint Research Statement","aka":[],"tldr":"Paper cited by one bottleneck page, indexed on Europe PMC as PubMed record 28968170 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose The primary purposes of eligibility criteria are to protect the safety of trial participants and define the trial population. Excessive or overly restrictive eligibility criteria can slow trial accrual, jeopardize the generalizability of results, and limit understanding of the intervention's benefit-risk profile. Methods ASCO, Friends of Cancer Research, and the US Food and Drug Administration examined specific eligibility criteria (ie, brain metastases, minimum age, HIV infection, and organ dysfunction and prior and concurrent malignancies) to determine whether to modify definitions to extend trials to a broader population. Working groups developed consensus recommendations based on review of evidence, consideration of the patient population, and consultation with the research community. Results Patients with treated or clinically stable brain metastases should be routinely included in trials and only excluded if there is compelling rationale. In initial dose-finding trials, pediatric-specific cohorts should be included based on strong scientific rationale for benefit. Later phase trials in diseases that span adult and pediatric populations should include patients older than age 12 years. HIV-infected patients who are healthy and have low risk of AIDS-related outcomes should be included absent specific rationale for exclusion. Renal function criteria should enable liberal creatinine clearance, unless the investigational agent involves renal excretion. Patients with prior or concurrent malignancies should be included, especially when the risk of the malignancy interfering with either safety or efficacy endpoints is very low. Conclusion To maximize generalizability of results, trial enrollment criteria should strive for inclusiveness. Rationale for excluding patients should be clearly articulated and reflect expected toxicities associated with the therapy under investigation.\n\nIndexed on Europe PMC as PubMed record 28968170 (DOI 10.1200/jco.2017.73.7916). Matched by DOI alone: one bottleneck page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2017","url":"https://doi.org/10.1200/jco.2017.73.7916"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28968170/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28968170"}],"tags":["europepmc-ingest"],"related":["b-trial-enrolment"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2017,"doi":"10.1200/jco.2017.73.7916","pmid":"28968170","authors":"Kim ES, Bruinooge SS, Roberts S, et al.","paperType":"observational","findings":[],"whatItMeans":"One bottleneck page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-stacchiotti-lancet-oncol","kind":"paper","name":"Building a global consensus approach to chordoma: a position paper from the medical and patient community","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 25638683 and published in The Lancet Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Chordomas are very rare bone malignant tumours that have had a shortage of effective treatments for a long time. New treatments are now available for both the local and the metastatic phase of the disease, but the degree of uncertainty in selecting the most appropriate treatment remains high and their adoption remains inconsistent across the world, resulting in suboptimum outcomes for many patients. In December, 2013, the European Society for Medical Oncology (ESMO) convened a consensus meeting to update its clinical practice guidelines on sarcomas. ESMO also hosted a parallel consensus meeting on chordoma that included more than 40 chordoma experts from several disciplines and from both sides of the Atlantic, with the contribution and sponsorship of the Chordoma Foundation, a global patient advocacy group. The consensus reached at that meeting is shown in this position paper.\n\nIndexed on Europe PMC as PubMed record 25638683 (DOI 10.1016/s1470-2045(14)71190-8). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2015","url":"https://doi.org/10.1016/s1470-2045(14)71190-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25638683/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25638683"}],"tags":["europepmc-ingest"],"related":["chordoma"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2015,"doi":"10.1016/s1470-2045(14)71190-8","pmid":"25638683","authors":"Stacchiotti S, Sommer J, Chordoma Global Consensus Group","paperType":"observational","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-ux023t-cl201-jan-de-beur-jbmr-2021","kind":"paper","name":"Burosumab for the treatment of tumor-induced osteomalacia (UX023T-CL201)","aka":[],"tldr":"In 14 adults whose bones had softened because a hidden tumour was making them lose phosphate, blocking the hormone responsible brought blood phosphate back to normal for nearly three years and let a third of their fractures heal fully.","summary":"Report of UX023T-CL201 (NCT02304367), an open-label phase 2 study of burosumab, a fully human monoclonal antibody that inhibits FGF23, in adults with tumour-induced osteomalacia or cutaneous skeletal hypophosphataemia syndrome. The analysis covers 14 patients with tumour-induced osteomalacia after excluding two found to have X-linked hypophosphataemia after enrolment and one with cutaneous skeletal hypophosphataemia syndrome. Key endpoints were changes in serum phosphorus and osteomalacia assessed on transiliac bone biopsies at week 48.\n\nSerum phosphorus increased from a baseline of 0.52 mmol/L and was maintained after dose titration from week 22 (0.91 mmol/L) to week 144 (0.82 mmol/L, p less than 0.0001). Most measures of osteomalacia improved at week 48: osteoid volume per bone volume, osteoid thickness and mineralisation lag time decreased, while osteoid surface per bone surface did not change. Of 249 fractures or pseudofractures detected at baseline across the 14 patients, 33 percent were fully healed and 13 percent partially healed at week 144. Patients reported less pain and fatigue and better physical health. Two patients discontinued; 16 serious adverse events occurred in seven patients and there was one death, all considered unrelated to treatment; nine patients had 16 treatment-related adverse events, all mild to moderate.","asOf":"2026-09-24","links":[{"label":"Journal of Bone and Mineral Research 2021","url":"https://doi.org/10.1002/jbmr.4233"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33338281/"},{"label":"ClinicalTrials.gov NCT02304367","url":"https://clinicaltrials.gov/study/NCT02304367"}],"tags":[],"related":[],"cancers":[],"sections":["supportive-care"],"technologies":[],"targets":[],"drugs":["burosumab"],"companies":["kyowa-kirin"],"institutions":[],"pathways":[],"terms":[],"trials":["ux023t-cl201"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of Bone and Mineral Research","year":2021,"doi":"10.1002/jbmr.4233","pmid":"33338281","authors":"Jan de Beur SM, Miller PD, Weber TJ, et al.","paperType":"observational","findings":["Serum phosphorus rose from 0.52 mmol/L at baseline to 0.91 mmol/L at week 22 and 0.82 mmol/L at week 144 (p<0.0001).","Of 249 baseline fractures or pseudofractures, 33 percent were fully healed and 13 percent partially healed at week 144.","All 16 serious adverse events and the one death were judged unrelated to burosumab; treatment-related events were mild to moderate."],"whatItMeans":"This is the main evidence behind the tumour-induced osteomalacia indication for burosumab in the EU and the US. For the rare patient whose phosphate-wasting tumour cannot be found or resected, it offers a way to treat the metabolic disease directly instead of relying on oral phosphate and active vitamin D.","caveats":["Single-arm open-label study of 14 analysed patients; no control group.","Three enrolled patients were excluded from the analysis after enrolment, so the registry's 17 differs from the 14 reported.","Sponsor-run study with sponsor employees among the authors."],"changedPractice":true,"participants":14},{"id":"paper-burris-gemcitabine-pancreatic-jco-1997","kind":"paper","name":"Burris 1997: gemcitabine becomes the first standard treatment for advanced pancreatic cancer","aka":[],"tldr":"A small trial that made gemcitabine the standard chemotherapy for pancreatic cancer for the next fifteen years, on the strength of more patients feeling better on treatment and a modest gain in survival over fluorouracil.","summary":"Burris and colleagues randomised 126 patients with advanced, symptomatic pancreatic cancer to weekly gemcitabine or weekly bolus fluorouracil. The primary endpoint was clinical benefit response, a composite of pain, performance status and weight, which gemcitabine improved in about a quarter of patients compared with a few percent on fluorouracil. Median survival was modestly longer and more patients were alive at one year. The trial led to gemcitabine's approval and defined the comparator arm for every pancreatic cancer trial until FOLFIRINOX and nab-paclitaxel.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1200/JCO.1997.15.6.2403"}],"tags":[],"related":["paper-conroy-folfirinox-pancreatic-nejm-2011","paper-mpact-nab-paclitaxel-gemcitabine-nejm-2013"],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":["gemcitabine","fluorouracil"],"companies":[],"institutions":[],"pathways":[],"terms":["os","quality-of-life"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":1997,"doi":"10.1200/JCO.1997.15.6.2403","authors":"Burris HA 3rd, Moore MJ, Andersen J, et al.","paperType":"rct","findings":["126 patients with advanced pancreatic cancer; gemcitabine vs fluorouracil.","Clinical benefit response 23.8% vs 4.8%.","Median survival 5.65 vs 4.41 months; survival at 12 months 18% vs 2%."],"whatItMeans":"This trial introduced a patient-centred composite endpoint and a drug that remained the backbone of pancreatic cancer treatment for a generation. Its small survival gain also shows how low the bar was, which is the context for the FOLFIRINOX and MPACT trials that followed.","caveats":["Small trial with a novel primary endpoint that regulators accepted once and rarely since.","The survival advantage was modest and the comparator, bolus fluorouracil, is no longer used this way."],"changedPractice":true,"participants":126},{"id":"paper-ogitani-cancer-sci","kind":"paper","name":"Bystander killing effect of DS-8201a, a novel anti-human epidermal growth factor receptor 2 antibody-drug conjugate, in tumors with human epidermal growth factor receptor 2 heterogeneity","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 27166974 and published in Cancer science; the citing page links this DOI, which is how the record was matched.","summary":"Antibody-drug conjugates deliver anticancer agents selectively and efficiently to tumor tissue and have significant antitumor efficacy with a wide therapeutic window. DS-8201a is a human epidermal growth factor receptor 2 (HER2)-targeting antibody-drug conjugate prepared using a novel linker-payload system with a potent topoisomerase I inhibitor, exatecan derivative (DX-8951 derivative, DXd). It was effective against trastuzumab emtansine (T-DM1)-insensitive patient-derived xenograft models with both high and low HER2 expression. In this study, the bystander killing effect of DS-8201a was evaluated and compared with that of T-DM1. We confirmed that the payload of DS-8201a, DXd (1), was highly membrane-permeable whereas that of T-DM1, Lys-SMCC-DM1, had a low level of permeability. Under a coculture condition of HER2-positive KPL-4 cells and negative MDA-MB-468 cells in vitro, DS-8201a killed both cells, whereas T-DM1 and an antibody-drug conjugate with a low permeable payload, anti-HER2-DXd (2), did not. In vivo evaluation was carried out using mice inoculated with a mixture of HER2-positive NCI-N87 cells and HER2-negative MDA-MB-468-Luc cells by using an in vivo imaging system. In vivo, DS-8201a reduced the luciferase signal of the mice, indicating suppression of the MDA-MB-468-Luc population; however, T-DM1 and anti-HER2-DXd (2) did not. Furthermore, it was confirmed that DS-8201a was not effective against MDA-MB-468-Luc tumors inoculated at the opposite side of the NCI-N87 tumor, suggesting that the bystander killing effect of DS-8201a is observed only in cells neighboring HER2-positive cells, indicating low concern in terms of systemic toxicity. These results indicated that DS-8201a has a potent bystander effect due to a highly membrane-permeable payload and is beneficial in treating tumors with HER2 heterogeneity that are unresponsive to T-DM1.\n\nIndexed on Europe PMC as PubMed record 27166974 (DOI 10.1111/cas.12966). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer Sci 2016","url":"https://doi.org/10.1111/cas.12966"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27166974/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27166974"}],"tags":["europepmc-ingest"],"related":["bystander-effect"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-science"],"dependsOn":[],"notes":[],"journal":"Cancer science","year":2016,"doi":"10.1111/cas.12966","pmid":"27166974","authors":"Ogitani Y, Hagihara K, Oitate M, et al.","paperType":"basic","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-c-144-01-lifileucel-melanoma-jco-2021","kind":"paper","name":"C-144-01: lifileucel, tumour-infiltrating lymphocytes grown from a patient's own tumour, in melanoma after checkpoint inhibitors have failed","aka":[],"tldr":"Immune cells harvested from a patient's tumour, expanded in the lab and reinfused shrank melanoma in 36% of patients whose disease had progressed on PD-1 blockade, with responses that mostly lasted.","summary":"Cohort 2 of the C-144-01 phase 2 trial treated 66 patients with advanced melanoma that had progressed after anti-PD-1 therapy (and BRAF/MEK inhibitors where indicated; median 3.3 prior lines) with a single infusion of lifileucel, autologous tumour-infiltrating lymphocytes expanded centrally over about 22 days, after non-myeloablative lymphodepletion and followed by up to six doses of high-dose interleukin-2. The objective response rate was 36% (2 complete, 22 partial) with disease control in 80%; median duration of response was not reached at 18.7 months of follow-up. Adverse events were largely attributable to lymphodepletion and IL-2 and resolved within two weeks, with two treatment-related deaths. Pooled analysis of 153 patients from cohorts 2 and 4 showed a 31% response rate and supported FDA accelerated approval in February 2024, the first TIL therapy and first cell therapy for a solid tumour.","asOf":"2026-09-08","links":[{"label":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=C-144-01%20lifileucel%20tumor-infiltrating%20lymphocyte%20melanoma%20Sarnaik%20JCO%202021"},{"label":"ClinicalTrials.gov NCT02360579","url":"https://clinicaltrials.gov/study/NCT02360579"}],"tags":[],"related":["paper-rohaas-til-vs-ipilimumab-nejm-2022"],"cancers":["melanoma"],"sections":[],"technologies":["til-therapy"],"targets":[],"drugs":["lifileucel","aldesleukin","cyclophosphamide"],"companies":["iovance"],"institutions":["moffitt","nci"],"pathways":[],"terms":["tils","orr"],"trials":["c-144-01"],"people":["amod-sarnaik","steven-rosenberg"],"bottlenecks":["b-manufacturing-cell-therapy","b-immunotherapy-response"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2021,"doi":"10.1200/JCO.21.00612","pmid":"33979178","authors":"Sarnaik AA, Hamid O, Khushalani NI, et al.","paperType":"translational","findings":["66 patients with anti-PD-1-refractory advanced melanoma; median 3.3 prior therapies; single lifileucel infusion after cyclophosphamide-fludarabine lymphodepletion, then up to 6 doses of high-dose IL-2.","Objective response 36% (3% complete); disease control 80%.","Median duration of response not reached at 18.7 months; responses deepened over time in some patients.","Grade 3-4 adverse events mostly cytopenias, febrile neutropenia and IL-2-related hypotension, resolving within 2 weeks; 2 treatment-related deaths.","Pooled cohorts 2 and 4 (153 patients): objective response 31.4%, supporting accelerated approval in 2024."],"whatItMeans":"Lifileucel proved that Steven Rosenberg's decades-old TIL concept could be industrialised into a licensed product and gave patients with checkpoint-refractory melanoma, who otherwise have few options, a chance of durable remission. It is the first cell therapy approved for any solid tumour. The treatment requires surgery to harvest tumour, hospitalisation for lymphodepletion and IL-2, and specialised centres, so its reach is limited.","caveats":["Single-arm trial; approval rested on response rate rather than survival.","Toxic conditioning and high-dose IL-2 make the regimen unsuitable for frail patients.","Manufacturing takes about three weeks and needs a resectable lesion; not all patients yield a product.","Cost (list price above 500,000 US dollars) and centre requirements restrict access."],"changedPractice":true,"participants":66},{"id":"paper-c-post-adjuvant-cemiplimab-nejm-2025","kind":"paper","name":"C-POST: adjuvant cemiplimab versus placebo in high-risk cutaneous squamous cell carcinoma","aka":[],"tldr":"A year of cemiplimab after surgery and radiotherapy for high-risk cutaneous squamous cell carcinoma cut the risk of recurrence or death by more than two thirds, the first adjuvant therapy to work in this skin cancer.","summary":"Phase 3 placebo-controlled trial of 415 patients with cutaneous squamous cell carcinoma at high risk of recurrence after surgery and postoperative radiotherapy (nodal disease with extracapsular extension, in-transit metastases, perineural invasion or recurrent tumours) randomised to cemiplimab or placebo for up to 48 weeks.\n\nDisease-free survival at 24 months was 87.1 versus 64.1 percent (hazard ratio 0.32), with reductions in both locoregional and distant recurrence; grade 3 or higher adverse events were 23.9 versus 14.2 percent.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2025","url":"https://doi.org/10.1056/NEJMoa2502449"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40454639/"}],"tags":[],"related":[],"cancers":["advanced-cutaneous-scc"],"sections":[],"technologies":[],"targets":[],"drugs":["cemiplimab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["danny-rischin"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2025,"doi":"10.1056/NEJMoa2502449","pmid":"40454639","authors":"Rischin D, Porceddu S, Day F, et al.","paperType":"rct","findings":["24-month disease-free survival 87.1 percent vs 64.1 percent; hazard ratio 0.32.","Freedom from locoregional recurrence hazard ratio 0.20; from distant recurrence 0.35."],"whatItMeans":"Adjuvant cemiplimab is a new standard for high-risk cutaneous squamous cell carcinoma after surgery and radiotherapy, particularly in patients with extracapsular nodal extension.","caveats":["Overall survival data immature.","Immunosuppressed and transplant patients, who bear much of the disease burden, were excluded."],"changedPractice":true,"participants":415},{"id":"paper-ctrak-tn-tissue-free-mrd-jamaoncol-2026","kind":"paper","name":"c-TRAK TN analysis: tissue-free versus tumour-informed ctDNA assays for residual disease in early triple-negative breast cancer","aka":[],"tldr":"A blood test that needs no tumour sample found leftover cancer DNA in a third of women after treatment for triple-negative breast cancer, and those women were far more likely to relapse; it agreed closely with the tests that first sequence the tumour.","summary":"Prognostic and exploratory analysis of the ctDNA surveillance period of c-TRAK TN, a multicentre phase 2 study in triple-negative breast cancer at moderate to high risk of recurrence. Plasma was collected every three months for up to two years after adjuvant therapy. A tissue-free methylation assay was compared with digital PCR and whole-exome-powered tumour-informed assays across 1,026 samples from 159 patients.","asOf":"2026-09-21","links":[{"label":"JAMA Oncology 2026","url":"https://doi.org/10.1001/jamaoncol.2026.2833"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42593771/"}],"tags":[],"related":[],"cancers":["tnbc"],"sections":[],"technologies":["liquid-biopsy","mrd-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tumour-informed-assay","mrd","ctdna"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2026,"doi":"10.1001/jamaoncol.2026.2833","pmid":"42593771","authors":"Cunningham N, Cutts RJ, Swift C, et al.","paperType":"translational","findings":["The tissue-free assay detected ctDNA in 54 of 159 patients (34 percent).","Detection was strongly associated with recurrence: hazard ratio 27.2 (95 percent CI 13.7 to 54.2) for recurrence-free survival."],"whatItMeans":"Residual-disease testing may not need the tumour to be sequenced first, which would remove the slowest step of tumour-informed assays; the comparison with tumour-informed results in the same patients is the evidence that matters.","caveats":["Exploratory analysis of a phase 2 study, not a randomised comparison of assays.","Single cancer type and a moderate to high-risk population; performance in other settings is untested.","Follow-up through January 2023 with analysis in 2025 to 2026."],"changedPractice":false,"participants":159},{"id":"paper-hess-ca19-9-response-chemotherapy-lancet-oncol-2008","kind":"paper","name":"CA 19-9 tumour-marker response to chemotherapy in patients with advanced pancreatic cancer enrolled in a randomised controlled trial","aka":[],"tldr":"In a randomised trial, a high CA 19-9 before treatment predicted shorter survival, but a 50% fall during chemotherapy did not mean living longer once the analysis was corrected, so a falling marker is not a valid substitute for survival.","summary":"CA 19-9 was measured at baseline and every 3 weeks in patients with histologically proven advanced pancreatic carcinoma in a randomised trial of gemcitabine versus gemcitabine plus capecitabine; those with normal or missing baseline values were excluded. Of 319 randomised patients, 247 were assessable for baseline and 175 for marker response, with comparisons corrected for guarantee-time bias by the landmark method. Median overall survival was 5.8 months for baseline at or above the median (59 times the upper limit of normal) against 10.3 months below it (P < 0.0001). An early decrease of at least 50% after two cycles was not associated with longer survival (10.1 versus 8.6 months; hazard ratio 1.11), nor was a 50% decrease at nadir (7.8 versus 6.7 months; hazard ratio 0.95). CA 19-9 response is therefore not a valid surrogate endpoint for survival.","asOf":"2026-09-24","links":[{"label":"Hess et al., Lancet Oncol 2008: CA 19-9 response to chemotherapy in a randomised trial","url":"https://doi.org/10.1016/s1470-2045(08)70001-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/18249033/"}],"tags":[],"related":[],"cancers":["pancreatic","metastatic-pdac"],"sections":[],"technologies":[],"targets":[],"drugs":["gemcitabine","capecitabine"],"companies":[],"institutions":[],"pathways":[],"terms":["ca19-9"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2008,"doi":"10.1016/s1470-2045(08)70001-9","pmid":"18249033","authors":"Hess V, Glimelius B, Grawe P, et al.","paperType":"rct","findings":["Baseline CA 19-9 above the median: overall survival 5.8 versus 10.3 months.","A 50% fall after two cycles or at nadir did not predict longer survival after correction for guarantee-time bias."],"whatItMeans":"It stops CA 19-9 response being used as a trial endpoint or as the reason to change treatment, while leaving baseline level as a prognostic factor.","caveats":["Gemcitabine-era chemotherapy.","Patients with normal baseline values, including non-producers, were excluded."],"changedPractice":false,"participants":319},{"id":"paper-cabinet-cabozantinib-nejm-2024","kind":"paper","name":"CABINET (Alliance A021602): cabozantinib for advanced neuroendocrine tumours","aka":[],"tldr":"Cabozantinib delayed progression in previously treated advanced neuroendocrine tumours of both pancreatic and extra-pancreatic origin compared with placebo, adding a new option after somatostatin analogues, everolimus or radioligand therapy.","summary":"Two parallel phase 3 placebo-controlled trials of cabozantinib in 298 patients with progressive advanced neuroendocrine tumours: 203 with extra-pancreatic (including lung and small bowel) and 95 with pancreatic tumours, all previously treated.\n\nMedian progression-free survival was 8.4 versus 3.9 months in extra-pancreatic tumours (hazard ratio 0.38) and 13.8 versus 4.4 months in pancreatic tumours (hazard ratio 0.23); hypertension, fatigue and diarrhoea were common.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2025","url":"https://doi.org/10.1056/NEJMoa2403991"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39282913/"}],"tags":[],"related":[],"cancers":["lung-net","pancreatic-net","small-intestinal-net"],"sections":[],"technologies":[],"targets":[],"drugs":["cabozantinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["cabinet"],"people":["jennifer-chan"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2025,"doi":"10.1056/NEJMoa2403991","pmid":"39282913","authors":"Chan JA, Geyer S, Zemla T, et al.","paperType":"rct","findings":["Extra-pancreatic: median progression-free survival 8.4 vs 3.9 months; hazard ratio 0.38.","Pancreatic: 13.8 vs 4.4 months; hazard ratio 0.23."],"whatItMeans":"Cabozantinib is approved for previously treated neuroendocrine tumours of any origin and is a standard later-line choice, including for lung carcinoids.","caveats":["Trials stopped early at interim analysis; overall survival not powered.","Dose reductions needed in most patients."],"changedPractice":true,"participants":298},{"id":"paper-florence-duffaud-lancet-oncol-2020","kind":"paper","name":"Cabozantinib in patients with advanced Ewing sarcoma or osteosarcoma (CABONE): a multicentre, single-arm, phase 2 trial","aka":[],"tldr":"Paper by Florence Duffaud indexed on Europe PMC as PubMed record 32078813, in The Lancet Oncology (2020), one of the most cited records naming an author with this name at Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille.","summary":"Background: Patients with Ewing sarcoma or osteosarcoma have a median overall survival of less than 12 months after diagnosis, and a standard treatment strategy has not yet been established. Pharmacological inhibition of MET signalling and aberrant angiogenesis has shown promising results in several preclinical models of Ewing sarcoma and osteosarcoma. We aimed to investigate the activity of cabozantinib, an inhibitor of MET and VEGFR2, in patients with advanced Ewing sarcoma and osteosarcoma.\n\nMethods: We did a multicentre, single-arm, two-stage, phase 2 trial in patients with advanced Ewing sarcoma or osteosarcoma recruited from ten centres in the French Sarcoma Group. Key eligibility criteria were aged 12 years or older, Eastern Cooperative Oncology Group performance status of 0-1, and documented disease progression (according to Response Evaluation Criteria in Solid Tumors version 1.1) before study entry. The number of previous lines of treatment was not limited. Patients received cabozantinib (adults 60 mg, children [<16 years] 40 mg/m 2) orally once daily in 28-day cycles until disease progression, unacceptable toxicity, the investigator's decision to discontinue, or participant withdrawal. The primary endpoint for Ewing sarcoma was best objective response within 6 months of treatment onset; for osteosarcoma, a dual primary endpoint of 6-month objective response and 6-month non-progression was assessed. All enrolled patients who received at least one dose of cabozantinib were included in the safety analysis, and all participants who received at least one complete or two incomplete treatment cycles were included in the efficacy population. This study was registered with ClinicalTrials.gov, number NCT02243605.\n\nFindings: Between April 16, 2015, and July 12, 2018, 90 patients (45 with Ewing sarcoma 45 with osteosarcoma) were recruited to the study. Median follow-up was 31·3 months (95% CI 12·4-35·4) for patients with Ewing sarcoma and 31·1 months (24·4-31·7) for patients with osteosarcoma. 39 (87%) patients with Ewing sarcoma and 42 (93%) patients with osteosarcoma were assessable for efficacy after histological and radiological review. In patients with Ewing sarcoma, ten (26%; 95% CI 13-42) of 39 patients had an objective response (all partial responses) by 6 months; in patients with osteosarcoma, five (12%; 4-26) of 42 patients had an objective response (all partial responses) and 14 (33%; 20-50) had 6-month non-progression. The most common grade 3 or 4 adverse events were hypophosphataemia (five [11%] for Ewing sarcoma, three [7%] for osteosarcoma), aspartate aminotransferase increase (two [4%] for Ewing sarcoma, three [7%] for osteosarcoma), palmar-plantar syndrome (three [7%] for Ewing sarcoma, two [4%] for osteosarcoma), pneumothorax (one [2%] for Ewing sarcoma, four [9%] for osteosarcoma), and neutropenia (two [4%] for Ewing sarcoma, four [9%] for osteosarcoma). At least one serious adverse event was reported in 61 (68%) of 90 patients. No patients died from drug-related toxic effects.\n\nInterpretation: Cabozantinib has antitumor activity in patients with advanced Ewing sarcoma and osteosarcoma and was generally well tolerated. Cabozantinib could represent a new therapeutic option in this setting, and deserves further investigation.\n\nFunding: Institut Bergonié; French National Cancer Institute; Association pour la Recherche contre le Cancer.\n\nIndexed on Europe PMC as PubMed record 32078813 (DOI 10.1016/s1470-2045(19)30825-3). Its author list gives \"Duffaud F\" with the affiliation \"Department of Medical Oncology, Assistance Publique des Hôpitaux de Marseille, Hôpital La Timone, Marseille, France\", which names Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille; that is how the record was matched to Florence Duffaud, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2020","url":"https://doi.org/10.1016/s1470-2045(19)30825-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32078813/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32078813"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["florence-duffaud"],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2020,"doi":"10.1016/s1470-2045(19)30825-3","pmid":"32078813","authors":"Italiano A, Mir O, Mathoulin-Pelissier S, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Florence Duffaud at Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-nct04446117-lancet-oncol-2025","kind":"paper","name":"Cabozantinib plus atezolizumab in metastatic prostate cancer (CONTACT-02): final analyses from a phase 3, open-label, randomised trial","aka":[],"tldr":"Published report from the CONTACT-02 trial registered as NCT04446117, in The Lancet Oncology (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Patients with metastatic castration-resistant prostate cancer (mCRPC) with extrapelvic soft-tissue metastases that has progressed on an androgen receptor pathway inhibitor (ARPI) have a poor prognosis with few treatment options. We aimed to assess efficacy and safety of cabozantinib, a tyrosine kinase inhibitor with immunomodulatory properties, plus the PD-L1 inhibitor atezolizumab in these patients.\n\nMethods: CONTACT-02 is an open-label, randomised, phase 3 study that enrolled patients at 184 sites across 24 countries (in Europe, North America, Asia-Pacific, and Latin America). Men aged 18 years and older, with an Eastern Cooperative Oncology Group performance status score of 0 or 1, and who had mCRPC and measurable extrapelvic soft-tissue metastases (lymph node or visceral) that had progressed on one previous ARPI were eligible. Patients were randomly assigned 1:1 to cabozantinib (40 mg orally once daily) plus atezolizumab (1200 mg intravenously once every 3 weeks) or ARPI switch (abiraterone 1000 mg orally once-daily plus prednisone 5 mg orally twice-daily, or enzalutamide 160 mg orally once-daily) using a web-based interactive response technology system and stratified by the presence of liver metastasis, previous docetaxel therapy, and disease status at first ARPI initiation. Dual primary endpoints were progression-free survival in the first 400 randomly assigned patients (progression-free survival intention-to treat [ITT] population) and overall survival in all randomly assigned patients (ITT population). Safety was assessed in all patients who received at least one dose of study treatment. Although the study is ongoing, with some patients remaining in follow-up, this analysis represents the protocol-specified final analysis. This trial is registered with ClinicalTrials.gov, NCT04446117.\n\nFindings: Between Aug 20, 2020 and June 7, 2023, 575 patients were randomly assigned to cabozantinib plus atezolizumab (n=289) or ARPI switch (n=286). Most patients were White (440 [77%]) or Asian (78 [14%]). After a median follow-up of 11·8 months (IQR 9·9-19·3), cabozantinib plus atezolizumab significantly improved progression-free survival versus ARPI switch (median 6·3 months [95% CI 6·2-8·8] vs 4·2 months [3·7-5·7]; hazard ratio [HR] 0·65 [95% CI 0·50-0·84], p=0·0007). After a median follow-up of 23·1 months (IQR 17·4-30·5), overall survival was not significantly different between the cabozantinib plus atezolizumab and ARPI switch groups (median 14·8 months [95% CI 13·4-16·7] vs 15·0 months [13·0-18·5]; HR 0·89 [95% CI 0·72-1·10], p=0·30). Any-cause grade 3-4 adverse events occurred in 158 (56%) of 284 patients given cabozantinib plus atezolizumab and 74 (26%) of 284 patients given ARPI switch; the most common in the cabozantinib plus atezolizumab group were hypertension (24 [8%] of 284 patients) and anaemia (23 [8%]) and the most common in the ARPI switch group was anaemia (18 [6%] of 284 patients). Serious adverse events deemed related to treatment occurred in 45 (16%) of 284 patients in the cabozantinib plus atezolizumab group and in 11 (4%) of 284 patients in the ARPI switch group; the most common with cabozantinib plus atezolizumab was diarrhoea (five [2%] of 284 patients) and the most common with ARPI switch was increase in alanine aminotransferase (two [1%] of 284 patients). Adverse events of any cause led to discontinuation of all components of study treatment in 49 (17%) of 284 patients in the cabozantinib plus atezolizumab group and in 42 (15%) of 284 patients in the ARPI switch group. No treatment-related deaths occurred.\n\nInterpretation: Cabozantinib plus atezolizumab, a novel drug combination that does not directly target androgen receptor signalling, could be a useful treatment option for patients with mCRPC and soft-tissue metastases who have progressed on an ARPI.\n\nFunding: Exelixis in partnership with Ipsen, Takeda, and Roche.\n\nIndexed on Europe PMC as PubMed record 40523369 (DOI 10.1016/s1470-2045(25)00209-8). Its abstract cites the registry id NCT04446117, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2025","url":"https://doi.org/10.1016/s1470-2045(25)00209-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40523369/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40523369"},{"label":"ClinicalTrials.gov NCT04446117","url":"https://clinicaltrials.gov/study/NCT04446117"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04446117"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2025,"doi":"10.1016/s1470-2045(25)00209-8","pmid":"40523369","authors":"Agarwal N, Azad AA, Carles J, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04446117 with the most citations, so it is the natural first reading for anyone following the CONTACT-02 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-calle-obesity-cancer-mortality-nejm-2003","kind":"paper","name":"Calle 2003: overweight, obesity and death from cancer in 900,000 US adults","aka":[],"tldr":"Following more than 900,000 American adults for 16 years, this study linked higher body weight to death from a wide range of cancers and estimated that excess weight could account for roughly one in seven cancer deaths in men and one in five in women in the United States.","summary":"Using the American Cancer Society's Cancer Prevention Study II, Calle and colleagues followed more than 900,000 adults who were cancer-free at enrolment in 1982 through 1998 and recorded 57,145 cancer deaths. Death rates from cancer rose with body mass index across most cancer sites, including cancers of the oesophagus, colon and rectum, liver, gallbladder, pancreas, kidney, stomach and prostate in men and breast, uterus, cervix and ovary in women. The heaviest participants had cancer death rates about half again higher than people of normal weight, and the authors estimated the share of US cancer deaths attributable to overweight and obesity.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa021423"}],"tags":[],"related":[],"cancers":["colorectal","hcc","pancreatic","endometrial","rcc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["obesity-related-cancers","risk-factor","mortality"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2003,"doi":"10.1056/NEJMoa021423","authors":"Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ.","paperType":"observational","findings":["Prospective cohort of more than 900,000 US adults followed for 16 years, with 57,145 cancer deaths.","Body mass index of 40 or more was associated with cancer death rates 52% higher in men and 62% higher in women than normal weight.","Overweight and obesity were estimated to account for about 14% of cancer deaths in men and 20% in women in the United States."],"whatItMeans":"This is the study most often cited for the size of the obesity and cancer link, and it broadened the list of weight-related cancers well beyond the few known before. It underlies weight management advice in cancer prevention guidance and the current interest in whether GLP-1 drugs change cancer risk.","caveats":["Observational, so confounding by diet, activity and other factors cannot be excluded.","Body weight was self-reported at enrolment only.","A US cohort in the 1980s and 1990s; patterns may differ elsewhere."],"changedPractice":false},{"id":"paper-nct04214288-lancet-oncol-2024","kind":"paper","name":"Camizestrant, a next-generation oral SERD, versus fulvestrant in post-menopausal women with oestrogen receptor-positive, HER2-negative advanced breast cancer (SERENA-2): a multi-dose, open-label, randomised, phase 2 trial","aka":[],"tldr":"Published report from the SERENA-2 trial registered as NCT04214288, in The Lancet Oncology (2024), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Resistance to endocrine therapies in hormone receptor-positive breast cancer is challenging. We aimed to assess the next-generation oral selective oestrogen receptor degrader (SERD) and complete oestrogen receptor antagonist, camizestrant, versus the first-approved SERD, fulvestrant, in post-menopausal women with oestrogen receptor-positive, HER2-negative, advanced breast cancer.\n\nMethods: SERENA-2 is an open-label, randomised, phase 2 trial that is being conducted at 74 study centres across Asia, Europe, the Middle East, and North America. Female patients aged 18 years or older who were post-menopausal with histologically or cytologically confirmed metastastic or locoregional oestrogen receptor-positive, HER2-negative breast cancer, an Eastern Cooperative Oncology Group or WHO performance status of 0 or 1, and disease recurrence or progression on at least one line of endocrine therapy, and no more than one previous endocrine therapy in the advanced setting. Patients were initially randomly assigned (1:1:1:1) to receive oral camizestrant once daily at 75 mg, 150 mg, or 300 mg (until the 300 mg group was closed), or fulvestrant intramuscularly at 500 mg (per label). Randomisation was managed through an interactive web-based system and stratified by previous treatment with CDK4/6 inhibitors and presence of liver and/or lung metastases. The primary objective was to determine clinical efficacy of camizestrant versus fulvestrant at each dose level using the primary endpoint of investigator-assessed progression-free survival, per Response Evaluation Criteria in Solid Tumours (version 1.1), assessed by intention to treat in all randomly assigned patients (full analysis set). No formal statistical comparison for the efficacy analysis of the camizestrant 300 mg dose versus fulvestrant was to be performed. Safety analyses included all randomly assigned patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT04214288, and is ongoing.\n\nFindings: Between May 11, 2020, and Aug 10, 2021, 240 patients were randomly assigned to receive camizestrant 75 mg (n=74), 150 mg (n=73), 300 mg (n=20), or fulvestrant (n=73), and were included in the full analysis set. All patients received at least one dose of study drug. Median follow-up was 16·6 months (IQR 12·9-19·4) for the camizestrant 75 mg group, 16·3 months (12·9-18·3) for the camizestrant 150 mg group, and 14·7 months (12·7-20·1) for the fulvestrant 500 mg group. Median progression-free survival was 7·2 months (90% CI 3·7-10·9) with camizestrant 75 mg, 7·7 months (5·5-12·9) with camizestrant 150 mg, and 3·7 months (2·0-6·0) with fulvestrant. The hazard ratio for camizestrant 75 mg versus fulvestrant was 0·59 (90% CI 0·42-0·82; p=0·017), and the hazard ratio for camizestrant 150 mg versus fulvestrant was 0·64 (0·46-0·89; p=0·0090). Treatment-related adverse events occurred in 39 (53%) of 74 patients in the camizestrant 75 mg group, 49 (67%) of 73 patients in the camizestrant 150 mg group, 14 (70%) of 20 patients in the camizestrant 300 mg group, and 13 (18%) of 73 patients in the fulvestrant group. No single grade 3 or worse treatment-emergent adverse event occurred in more than two (3%) patients in any group. Serious treatment-emergent adverse events occurred in six (8%) patients in the camizestrant 75 mg group, seven (10%) patients in the camizestrant 150 mg group, two (10%) patients in the camizestrant 300 mg group, and four (5%) patients in the fulvestrant group. No treatment-related deaths occurred.\n\nInterpretation: Camizestrant at 75 and 150 mg showed a significant benefit in progression-free survival versus fulvestrant. These results support further development of camizestrant for the treatment of oestrogen receptor-positive, HER2-negative breast cancer.\n\nFunding: AstraZeneca.\n\nIndexed on Europe PMC as PubMed record 39481395 (DOI 10.1016/s1470-2045(24)00387-5). Its abstract cites the registry id NCT04214288, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2024","url":"https://doi.org/10.1016/s1470-2045(24)00387-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39481395/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39481395"},{"label":"ClinicalTrials.gov NCT04214288","url":"https://clinicaltrials.gov/study/NCT04214288"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04214288"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2024,"doi":"10.1016/s1470-2045(24)00387-5","pmid":"39481395","authors":"Oliveira M, Pominchuk D, Nowecki Z, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04214288 with the most citations, so it is the natural first reading for anyone following the SERENA-2 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-camel-j-thorac-oncol-2023-update","kind":"paper","name":"Camrelizumab Plus Carboplatin and Pemetrexed as First-Line Treatment for Advanced Nonsquamous NSCLC: Extended Follow-Up of CameL Phase 3 Trial","aka":[],"tldr":"Later report from the CameL trial registered as NCT03134872, in Journal of Thoracic Oncology (2023); its title describes an updated or longer-term analysis.","summary":"Introduction: In CameL phase 3 study (ClinicalTrials.gov: NCT03134872), addition of camrelizumab to first-line chemotherapy significantly improved the progression-free survival in patients with stages IIIB to IV nonsquamous NSCLC. Here, we present outcomes after a minimum follow-up of 43.9 months since last patient randomization.\n\nMethods: Eligible patients were randomized 1:1 to 4 to 6 cycles of camrelizumab plus carboplatin and pemetrexed or chemotherapy alone every 3 weeks, followed by maintenance camrelizumab plus pemetrexed or pemetrexed only (n = 205 and 207, respectively). Total camrelizumab exposure was up to 2 years.\n\nResults: at January 31, 2022, camrelizumab plus chemotherapy exhibited substantially improved overall survival over chemotherapy alone (median, 27.1 versus 19.8 mo; hazard ratio = 0.72 [95% confidence interval: 0.57-0.92]). In the chemotherapy-alone group, 95 patients (45.9%) crossed over to camrelizumab monotherapy. After adjustment for crossover, the survival benefit with camrelizumab plus chemotherapy was more pronounced (adjusted hazard ratio = 0.55 [95% confidence interval: 0.42-0.71]). In camrelizumab plus chemotherapy group, 33 patients completed 2 years of camrelizumab. Objective response rate was 97.0%, with ongoing responses in 17 of the 32 responses (53.1%), and 93.9% (31 of 33) of the patients were alive at data cutoff. Safety profiles were consistent with the previous report, and no obvious evidence of cumulative toxicity was found with long exposure to camrelizumab.\n\nConclusions: Camrelizumab plus carboplatin and pemetrexed provides long-term survival benefit over chemotherapy, with manageable toxicity and remarkable and durable response in patients receiving 2 years of camrelizumab, further supporting camrelizumab combination as first-line treatment for advanced nonsquamous NSCLC.\n\nIndexed on Europe PMC as PubMed record 36646210 (DOI 10.1016/j.jtho.2022.12.017). Its abstract cites the registry id NCT03134872, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Thorac Oncol 2023","url":"https://doi.org/10.1016/j.jtho.2022.12.017"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36646210/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36646210"},{"label":"ClinicalTrials.gov NCT03134872","url":"https://clinicaltrials.gov/study/NCT03134872"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["camel"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-thoracic-oncology"],"dependsOn":[],"notes":[],"journal":"Journal of Thoracic Oncology","year":2023,"doi":"10.1016/j.jtho.2022.12.017","pmid":"36646210","authors":"Zhou C, Chen G, Huang Y, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the CameL trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-camel-lancet-respir-med-2021","kind":"paper","name":"Camrelizumab plus carboplatin and pemetrexed versus chemotherapy alone in chemotherapy-naive patients with advanced non-squamous non-small-cell lung cancer (CameL): a randomised, open-label, multicentre, phase 3 trial","aka":[],"tldr":"Published report from the CameL trial registered as NCT03134872, in The Lancet. Respiratory medicine (2021), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Immunotherapy combined with chemotherapy has been shown to be efficacious as treatment for advanced non-squamous non-small-cell lung cancer (NSCLC) without targetable genetic aberrations; however, there is scarce evidence of the effectiveness of the combinations in the Asian population. We evaluated camrelizumab plus chemotherapy against non-squamous NSCLC in China.\n\nMethods: We did a randomised, open-label, multicentre, phase 3 trial (CameL) in 52 hospitals in China for patients with non-squamous NSCLC without EGFR and ALK alteration. Eligible patients were aged 18-70 years and had no previous systemic chemotherapy, Eastern Cooperative Oncology Group performance status of 0 or 1, and at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (version 1.1). Patients were randomly assigned (1:1) to receive 4-6 cycles of carboplatin (area under curve 5 mg/mL per min) plus pemetrexed (500 mg/m 2) with or without camrelizumab (200 mg) every 3 weeks, followed by maintenance therapy with camrelizumab plus pemetrexed or pemetrexed alone. Medication was administered intravenously on day 1 of each 3-week treatment cycle. Randomisation was done using a centralised interactive web-response system with the block size randomly generated as four or six and stratified by sex and smoking history. The two primary endpoints were progression-free survival per blinded independent central review, in all patients and in patients who were PD-L1 positive. Primary analysis was done in the full analysis set that included all randomly assigned patients who received at least one dose of the study treatment. Herein, due to the primary endpoint being met at the interim analysis, we reported the findings of prespecified interim analysis, which only included confirmatory statistical testing for progression-free survival in all patients. Safety was assessed in the as-treated population. This study is registered with ClinicalTrials.gov, NCT03134872 (follow-up is ongoing).\n\nFindings: Between May 12, 2017, and June 6, 2018, of the 419 patients who were randomly assigned, seven did not receive assigned treatment and 412 received either camrelizumab plus chemotherapy (n=205) or chemotherapy alone (n=207). At interim analysis, median follow-up duration was 11·9 months (IQR 9·0-14·9). Progression-free survival in this interim analysis was significantly prolonged with camrelizumab plus chemotherapy than with chemotherapy alone (median 11·3 months [95% CI 9·6-15·4] vs 8·3 months [6·0-9·7]; hazard ratio 0·60 [0·45-0·79]; one-sided p=0·0001). Most common grade 3 or worse treatment-related adverse events were decreased neutrophil count (78 [38%] patients in the camrelizumab plus chemotherapy group vs 63 [30%] patients in the chemotherapy alone group), decreased white blood cell count (40 [20%] vs 30 [14%]), anaemia (38 [19%] vs 23 [11%]), and decreased platelet count (34 [17%] vs 24 [12%]). Serious treatment-related adverse events occurred in 74 (36%) patients in the camrelizumab plus chemotherapy group and 27 (13%) patients in the chemotherapy alone group.\n\nInterpretation: The primary endpoint was met at the interim analysis, showing a statistically significant and clinically meaningful improvement in progression-free survival with camrelizumab plus carboplatin and pemetrexed versus chemotherapy alone in all patients, supporting camrelizumab plus carboplatin and pemetrexed as a first-line treatment option for Chinese patients with advanced non-squamous NSCLC without EGFR and ALK alterations. The trial is being continued to collect long-term outcomes in all patients and carry out confirmatory statistical testing for progression-free survival in the PD-L1-positive population.\n\nFunding: Jiangsu Hengrui Medicine.\n\nIndexed on Europe PMC as PubMed record 33347829 (DOI 10.1016/s2213-2600(20)30365-9). Its abstract cites the registry id NCT03134872, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Respir Med 2021","url":"https://doi.org/10.1016/s2213-2600(20)30365-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33347829/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33347829"},{"label":"ClinicalTrials.gov NCT03134872","url":"https://clinicaltrials.gov/study/NCT03134872"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["camel"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Lancet. Respiratory medicine","year":2021,"doi":"10.1016/s2213-2600(20)30365-9","pmid":"33347829","authors":"Zhou C, Chen G, Huang Y, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03134872 with the most citations, so it is the natural first reading for anyone following the CameL trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-qin-lancet","kind":"paper","name":"Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma (CARES-310): a randomised, open-label, international phase 3 study","aka":[],"tldr":"Paper cited by one treatment page, indexed on Europe PMC as PubMed record 37499670 and published in The Lancet; the citing page links this DOI, which is how the record was matched.","summary":"Background: Immunotherapy with immune checkpoint inhibitors combined with an anti-angiogenic tyrosine-kinase inhibitor (TKI) has been shown to improve overall survival versus anti-angiogenic therapy alone in advanced solid tumours, but not in hepatocellular carcinoma. Therefore, a clinical study was conducted to compare the efficacy and safety of the anti-PD-1 antibody camrelizumab plus the VEGFR2-targeted TKI rivoceranib (also known as apatinib) versus sorafenib as first-line treatment for unresectable hepatocellular carcinoma.\n\nMethods: This randomised, open-label, international phase 3 trial (CARES-310) was done at 95 study sites across 13 countries and regions worldwide. Patients with unresectable or metastatic hepatocellular carcinoma who had not previously received any systemic treatment were randomly assigned (1:1) to receive either camrelizumab 200 mg intravenously every 2 weeks plus rivoceranib 250 mg orally once daily or sorafenib 400 mg orally twice daily. Randomisation was done via a centralised interactive response system. The primary endpoints were progression-free survival, as assessed by the blinded independent review committee per Response Evaluation Criteria in Solid Tumours version 1.1, and overall survival in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of the study drugs. We report the findings from the prespecified primary analysis for progression-free survival and interim analysis for overall survival. This study is registered with ClinicalTrials.gov (NCT03764293).\n\nFindings: Between June 28, 2019, and March 24, 2021, 543 patients were randomly assigned to the camrelizumab-rivoceranib (n=272) or sorafenib (n=271) group. At the primary analysis for progression-free survival (May 10, 2021), median follow-up was 7·8 months (IQR 4·1-10·6). Median progression-free survival was significantly improved with camrelizumab-rivoceranib versus sorafenib (5·6 months [95% CI 5·5-6·3] vs 3·7 months [2·8-3·7]; hazard ratio [HR] 0·52 [95% CI 0·41-0·65]; one-sided p<0·0001). At the interim analysis for overall survival (Feb 8, 2022), median follow-up was 14·5 months (IQR 9·1-18·7). Median overall survival was significantly extended with camrelizumab-rivoceranib versus sorafenib (22·1 months [95% CI 19·1-27·2] vs 15·2 months [13·0-18·5]; HR 0·62 [95% CI 0·49-0·80]; one-sided p<0·0001). The most common grade 3 or 4 treatment-related adverse events were hypertension (102 [38%] of 272 patients in the camrelizumab-rivoceranib group vs 40 [15%] of 269 patients in the sorafenib group), palmar-plantar erythrodysaesthesia syndrome (33 [12%] vs 41 [15%]), increased aspartate aminotransferase (45 [17%] vs 14 [5%]), and increased alanine aminotransferase (35 [13%] vs eight [3%]). Treatment-related serious adverse events were reported in 66 (24%) patients in the camrelizumab-rivoceranib group and 16 (6%) in the sorafenib group. Treatment-related death occurred in two patients: one patient in the camrelizumab-rivoceranib group (ie, multiple organ dysfunction syndrome) and one patient in the sorafenib group (ie, respiratory failure and circulatory collapse).\n\nInterpretation: Camrelizumab plus rivoceranib showed a statistically significant and clinically meaningful benefit in progression-free survival and overall survival compared with sorafenib for patients with unresectable hepatocellular carcinoma, presenting as a new and effective first-line treatment option for this population.\n\nFunding: Jiangsu Hengrui Pharmaceuticals and Elevar Therapeutics.\n\nIndexed on Europe PMC as PubMed record 37499670 (DOI 10.1016/s0140-6736(23)00961-3). Matched by DOI alone: one treatment page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet 2023","url":"https://doi.org/10.1016/s0140-6736(23)00961-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37499670/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37499670"}],"tags":["europepmc-ingest"],"related":["rivoceranib"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2023,"doi":"10.1016/s0140-6736(23)00961-3","pmid":"37499670","authors":"Qin S, Chan SL, Gu S, et al.","paperType":"rct","findings":[],"whatItMeans":"One treatment page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-aktipis-philos-trans-r-soc-lond-b-biol-sci","kind":"paper","name":"Cancer across the tree of life: cooperation and cheating in multicellularity","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 26056363 and published in Philosophical transactions of the Royal Society of London. Series B, Biological sciences; the citing page links this DOI, which is how the record was matched.","summary":"Multicellularity is characterized by cooperation among cells for the development, maintenance and reproduction of the multicellular organism. Cancer can be viewed as cheating within this cooperative multicellular system. Complex multicellularity, and the cooperation underlying it, has evolved independently multiple times. We review the existing literature on cancer and cancer-like phenomena across life, not only focusing on complex multicellularity but also reviewing cancer-like phenomena across the tree of life more broadly. We find that cancer is characterized by a breakdown of the central features of cooperation that characterize multicellularity, including cheating in proliferation inhibition, cell death, division of labour, resource allocation and extracellular environment maintenance (which we term the five foundations of multicellularity). Cheating on division of labour, exhibited by a lack of differentiation and disorganized cell masses, has been observed in all forms of multicellularity. This suggests that deregulation of differentiation is a fundamental and universal aspect of carcinogenesis that may be underappreciated in cancer biology. Understanding cancer as a breakdown of multicellular cooperation provides novel insights into cancer hallmarks and suggests a set of assays and biomarkers that can be applied across species and characterize the fundamental requirements for generating a cancer.\n\nIndexed on Europe PMC as PubMed record 26056363 (DOI 10.1098/rstb.2014.0219). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Philos Trans R Soc Lond B Biol Sci 2015","url":"https://doi.org/10.1098/rstb.2014.0219"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26056363/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26056363"}],"tags":["europepmc-ingest"],"related":["atavistic-theory-of-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Philosophical transactions of the Royal Society of London. Series B, Biological sciences","year":2015,"doi":"10.1098/rstb.2014.0219","pmid":"26056363","authors":"Aktipis CA, Boddy AM, Jansen G, et al.","paperType":"review","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-laconi-br-j-cancer","kind":"paper","name":"Cancer as a disease of old age: changing mutational and microenvironmental landscapes","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 32042067 and published in British Journal of Cancer; the citing page links this DOI, which is how the record was matched.","summary":"Why do we get cancer mostly when we are old? According to current paradigms, the answer is simple: mutations accumulate in our tissues throughout life, and some of these mutations contribute to cancers. Although mutations are necessary for cancer development, a number of studies shed light on roles for ageing and exposure-dependent changes in tissue landscapes that determine the impact of oncogenic mutations on cellular fitness, placing carcinogenesis into an evolutionary framework. Natural selection has invested in somatic maintenance to maximise reproductive success. Tissue maintenance not only ensures functional robustness but also prevents the occurrence of cancer through periods of likely reproduction by limiting selection for oncogenic events in our cells. Indeed, studies in organisms ranging from flies to humans are revealing conserved mechanisms to eliminate damaged or oncogenically initiated cells from tissues. Reports of the existence of striking numbers of oncogenically initiated clones in normal tissues and of how this clonal architecture changes with age or external exposure to noxious substances provide critical insight into the early stages of cancer development. A major challenge for cancer biology will be the integration of these studies with epidemiology data into an evolutionary theory of carcinogenesis, which could have a large impact on addressing cancer risk and treatment.\n\nIndexed on Europe PMC as PubMed record 32042067 (DOI 10.1038/s41416-019-0721-1). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Br J Cancer 2020","url":"https://doi.org/10.1038/s41416-019-0721-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32042067/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32042067"}],"tags":["europepmc-ingest"],"related":["ageing-tissue-field-theory"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["british-journal-of-cancer"],"dependsOn":[],"notes":[],"journal":"British Journal of Cancer","year":2020,"doi":"10.1038/s41416-019-0721-1","pmid":"32042067","authors":"Laconi E, Marongiu F, DeGregori J","paperType":"review","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-seyfried-nutr-metab-lond","kind":"paper","name":"Cancer as a metabolic disease","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 20181022 and published in Nutrition & metabolism; the citing page links this DOI, which is how the record was matched.","summary":"Emerging evidence indicates that impaired cellular energy metabolism is the defining characteristic of nearly all cancers regardless of cellular or tissue origin. In contrast to normal cells, which derive most of their usable energy from oxidative phosphorylation, most cancer cells become heavily dependent on substrate level phosphorylation to meet energy demands. Evidence is reviewed supporting a general hypothesis that genomic instability and essentially all hallmarks of cancer, including aerobic glycolysis (Warburg effect), can be linked to impaired mitochondrial function and energy metabolism. A view of cancer as primarily a metabolic disease will impact approaches to cancer management and prevention.\n\nIndexed on Europe PMC as PubMed record 20181022 (DOI 10.1186/1743-7075-7-7). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nutr Metab (Lond) 2010","url":"https://doi.org/10.1186/1743-7075-7-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20181022/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/20181022"}],"tags":["europepmc-ingest"],"related":["metabolic-theory-of-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nutrition & metabolism","year":2010,"doi":"10.1186/1743-7075-7-7","pmid":"20181022","authors":"Seyfried TN, Shelton LM","paperType":"review","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-merlo-nat-rev-cancer","kind":"paper","name":"Cancer as an evolutionary and ecological process","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 17109012 and published in Nature Reviews Cancer; the citing page links this DOI, which is how the record was matched.","summary":"Neoplasms are microcosms of evolution. Within a neoplasm, a mosaic of mutant cells compete for space and resources, evade predation by the immune system and can even cooperate to disperse and colonize new organs. The evolution of neoplastic cells explains both why we get cancer and why it has been so difficult to cure. The tools of evolutionary biology and ecology are providing new insights into neoplastic progression and the clinical control of cancer.\n\nIndexed on Europe PMC as PubMed record 17109012 (DOI 10.1038/nrc2013). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Cancer 2006","url":"https://doi.org/10.1038/nrc2013"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/17109012/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/17109012"}],"tags":["europepmc-ingest"],"related":["clonal-evolution-theory"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Cancer","year":2006,"doi":"10.1038/nrc2013","pmid":"17109012","authors":"Merlo LM, Pepper JW, Reid BJ, et al.","paperType":"review","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-schafer-nat-rev-mol-cell-biol","kind":"paper","name":"Cancer as an overhealing wound: an old hypothesis revisited","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 18628784 and published in Nature reviews. Molecular cell biology; the citing page links this DOI, which is how the record was matched.","summary":"What is the relationship between the wound-healing process and the development of cancer? Malignant tumours often develop at sites of chronic injury, and tissue injury has an important role in the pathogenesis of malignant disease, with chronic inflammation being the most important risk factor. The development and functional characterization of genetically modified mice that lack or overexpress genes that are involved in repair, combined with gene-expression analysis in wounds and tumours, have highlighted remarkable similarities between wound repair and cancer. However, a few crucial differences were also observed, which could account for the altered metabolism, impaired differentiation capacity and invasive growth of malignant tumours.\n\nIndexed on Europe PMC as PubMed record 18628784 (DOI 10.1038/nrm2455). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Mol Cell Biol 2008","url":"https://doi.org/10.1038/nrm2455"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/18628784/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/18628784"}],"tags":["europepmc-ingest"],"related":["microenvironment-inflammation-theory"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature reviews. Molecular cell biology","year":2008,"doi":"10.1038/nrm2455","pmid":"18628784","authors":"Schäfer M, Werner S","paperType":"review","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-solheim-bmj-support-palliat-care","kind":"paper","name":"Cancer cachexia: rationale for the MENAC (Multimodal-Exercise, Nutrition and Anti-inflammatory medication for Cachexia) trial","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 29440149 and published in BMJ supportive & palliative care; the citing page links this DOI, which is how the record was matched.","summary":"Cancer cachexia is a multifactorial syndrome characterised by an ongoing loss of skeletal muscle mass that cannot be fully reversed by conventional nutritional support alone. Cachexia has a high prevalence in cancer and a major impact on patient physical function, morbidity and mortality. Despite the consequences of cachexia, there is no licensed treatment for cachexia and no accepted standard of care. It has been argued that the multifactorial genesis of cachexia lends itself to therapeutic targeting through a multimodal treatment. Following a successful phase II trial, a phase III randomised controlled trial of a multimodal cachexia intervention is under way. Termed the MENAC trial (Multimodal-Exercise, Nutrition and Anti-inflammatory medication for Cachexia), this intervention is based on evidence to date and consists of non-steroidal anti-inflammatory drugs and eicosapentaenoic acid to reduce inflammation, a physical exercise programme using resistance and aerobic training to increase anabolism, as well as dietary counselling and oral nutritional supplements to promote energy and protein balance. Herein we describe the development of this trial.\n\nTrial registration number: NCT02330926.\n\nIndexed on Europe PMC as PubMed record 29440149 (DOI 10.1136/bmjspcare-2017-001440). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"BMJ Support Palliat Care 2018","url":"https://doi.org/10.1136/bmjspcare-2017-001440"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29440149/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29440149"}],"tags":["europepmc-ingest"],"related":["resistance-training-cachexia"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"BMJ supportive & palliative care","year":2018,"doi":"10.1136/bmjspcare-2017-001440","pmid":"29440149","authors":"Solheim TS, Laird BJA, Balstad TR, et al.","paperType":"review","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-mitsunaga-nat-med","kind":"paper","name":"Cancer cell-selective in vivo near infrared photoimmunotherapy targeting specific membrane molecules","aka":[],"tldr":"Paper cited by one idea page, indexed on Europe PMC as PubMed record 22057348 and published in Nature Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Three major modes of cancer therapy (surgery, radiation and chemotherapy) are the mainstay of modern oncologic therapy. To minimize the side effects of these therapies, molecular-targeted cancer therapies, including armed antibody therapy, have been developed with limited success. In this study, we have developed a new type of molecular-targeted cancer therapy, photoimmunotherapy (PIT), that uses a target-specific photosensitizer based on a near-infrared (NIR) phthalocyanine dye, IR700, conjugated to monoclonal antibodies (mAbs) targeting epidermal growth factor receptors. Cell death was induced immediately after irradiating mAb-IR700-bound target cells with NIR light. We observed in vivo tumor shrinkage after irradiation with NIR light in target cells expressing the epidermal growth factor receptor. The mAb-IR700 conjugates were most effective when bound to the cell membrane and produced no phototoxicity when not bound, suggesting a different mechanism for PIT as compared to conventional photodynamic therapies. Target-selective PIT enables treatment of cancer based on mAb binding to the cell membrane.\n\nIndexed on Europe PMC as PubMed record 22057348 (DOI 10.1038/nm.2554). Matched by DOI alone: one idea page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Med 2011","url":"https://doi.org/10.1038/nm.2554"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22057348/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/22057348"}],"tags":["europepmc-ingest"],"related":["idea-photoimmunotherapy-plus-pd1"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2011,"doi":"10.1038/nm.2554","pmid":"22057348","authors":"Mitsunaga M, Ogawa M, Kosaka N, et al.","paperType":"basic","findings":[],"whatItMeans":"One idea page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-tomasetti-science","kind":"paper","name":"Cancer etiology. Variation in cancer risk among tissues can be explained by the number of stem cell divisions","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 25554788 and published in Science; the citing page links this DOI, which is how the record was matched.","summary":"Some tissue types give rise to human cancers millions of times more often than other tissue types. Although this has been recognized for more than a century, it has never been explained. Here, we show that the lifetime risk of cancers of many different types is strongly correlated (0.81) with the total number of divisions of the normal self-renewing cells maintaining that tissue's homeostasis. These results suggest that only a third of the variation in cancer risk among tissues is attributable to environmental factors or inherited predispositions. The majority is due to \"bad luck,\" that is, random mutations arising during DNA replication in normal, noncancerous stem cells. This is important not only for understanding the disease but also for designing strategies to limit the mortality it causes.\n\nIndexed on Europe PMC as PubMed record 25554788 (DOI 10.1126/science.1260825). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Science 2015","url":"https://doi.org/10.1126/science.1260825"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25554788/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25554788"}],"tags":["europepmc-ingest"],"related":["somatic-mutation-theory"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2015,"doi":"10.1126/science.1260825","pmid":"25554788","authors":"Tomasetti C, Vogelstein B","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-vogelstein-cancer-genome-landscapes-science-2013","kind":"paper","name":"Cancer genome landscapes: about 140 driver genes, and each tumour needs only a handful","aka":[],"tldr":"Synthesising the first generation of cancer genome sequencing, Vogelstein and colleagues concluded that about 140 genes can drive cancer when mutated, that a typical solid tumour has 2 to 8 driver mutations among tens of passengers, and that all drivers act through a dozen signalling pathways.","summary":"By 2013 hundreds of tumours had been exome- or genome-sequenced. This review organised the results. Common adult solid tumours carry an average of 33 to 66 non-synonymous somatic mutations, most of them passengers; paediatric tumours and leukaemias carry far fewer, and tumours caused by mutagens (lung, melanoma) or with mismatch-repair defects carry many more.\n\nThe authors listed about 138 driver genes (71 tumour suppressors, 54 oncogenes), described the mutational landscape as a few mountains (frequently mutated genes) and many hills, and grouped all drivers into 12 pathways governing cell fate, cell survival and genome maintenance. They emphasised that intratumoural heterogeneity, the relative paucity of new driver genes and the small number of drugs against tumour suppressor pathways set limits on precision oncology, and argued that early detection and prevention would be at least as important as new drugs.\n\nThe framework shaped how targeted-therapy panels, driver calling and basket trials were designed.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1126/science.1235122"}],"tags":[],"related":["paper-tcga-pancancer-atlas-cell-2018","paper-detect-a-science-2020"],"cancers":[],"sections":["drug-discovery","diagnostics"],"technologies":["wes-wgs","cgp"],"targets":["tp53","kras","pik3ca","braf"],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":[],"terms":["oncogene-addiction","tmb","mutational-signature"],"trials":[],"people":["bert-vogelstein","kenneth-kinzler"],"bottlenecks":["b-undruggable-targets","b-tumor-heterogeneity","b-early-detection"],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2013,"doi":"10.1126/science.1235122","pmid":"23539594","authors":"Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA Jr, Kinzler KW","paperType":"review","findings":["About 140 driver genes identified; a typical common solid tumour has 2-8 driver mutations","Average 33-66 non-synonymous mutations per common adult solid tumour, with mutagen-exposed tumours carrying 200 or more","Drivers converge on 12 pathways in three core processes: cell fate, cell survival, genome maintenance","Most drivers are tumour suppressors, which cannot be directly targeted by conventional drugs","Argued that early detection would deliver more than new drugs for most cancers, foreshadowing the authors' later ctDNA work"],"whatItMeans":"There are not thousands of cancer genes, and any one patient's tumour is driven by only a few of them. That makes targeted sequencing panels sensible, but because most drivers are lost tumour suppressors, drugs exist for only a minority, which is why the same group turned to early detection.","caveats":["Counts of driver genes depend on statistical thresholds and have since grown with larger cohorts (about 300 in TCGA 2018)","Focus on point mutations and small indels; structural variants, epigenetic drivers and non-coding drivers were under-counted","Based on primary tumours; metastatic and treated tumours have additional drivers","Pathway assignments are a simplification of overlapping networks"],"changedPractice":false},{"id":"paper-dunn-nat-immunol","kind":"paper","name":"Cancer immunoediting: from immunosurveillance to tumor escape","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 12407406 and published in Nature immunology; the citing page links this DOI, which is how the record was matched.","summary":"The concept that the immune system can recognize and destroy nascent transformed cells was originally embodied in the cancer immunosurveillance hypothesis of Burnet and Thomas. This hypothesis was abandoned shortly afterwards because of the absence of strong experimental evidence supporting the concept. New data, however, clearly show the existence of cancer immunosurveillance and also indicate that it may function as a component of a more general process of cancer immunoediting. This process is responsible for both eliminating tumors and sculpting the immunogenic phenotypes of tumors that eventually form in immunocompetent hosts. In this review, we will summarize the historical and experimental basis of cancer immunoediting and discuss its dual roles in promoting host protection against cancer and facilitating tumor escape from immune destruction.\n\nIndexed on Europe PMC as PubMed record 12407406 (DOI 10.1038/ni1102-991). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Immunol 2002","url":"https://doi.org/10.1038/ni1102-991"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/12407406/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/12407406"}],"tags":["europepmc-ingest"],"related":["immune-surveillance-immunoediting"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature immunology","year":2002,"doi":"10.1038/ni1102-991","pmid":"12407406","authors":"Dunn GP, Bruce AT, Ikeda H, et al.","paperType":"review","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-han-j-natl-cancer-cent","kind":"paper","name":"Cancer incidence and mortality in China, 2022","aka":[],"tldr":"Paper cited by one institution page, indexed on Europe PMC as PubMed record 39036382 and published in Journal of the National Cancer Center; the citing page links this DOI, which is how the record was matched.","summary":"Background: The National Cancer Center (NCC) of China regularly reports the nationwide statistics on cancer incidence and mortality in China. The International Agency for Research on Cancer (IARC) calculates and publishes the cancer burden of countries around the world every two years. To ensure consistency between the actual surveillance data in China and the data published by IARC, NCC has received approval from the National Health Commission and IARC to simultaneously release the cancer burden data for China in GLOBOCAN 2022.\n\nMethods: There were a total of 700 registries reporting high-quality data on cancer incidence and mortality across China in 2018, of which 106 registries with continuous monitoring from 2010 to 2018 were used to establish an age-period-cohort model to simulate the trend of cancer incidence and mortality and to estimate the incidence and mortality in China in 2022. In addition, we analyzed the temporal trends of age-standardized cancer incidence and mortality from 2000 to 2018 using data from 22 continuous cancer registries.\n\nResults: It was estimated about 4,824,700 new cancer cases and 2,574,200 new cancer deaths occurred in China in 2022. Cancers of the lung, colon-rectum, thyroid, liver and stomach were the top five cancer types, accounting for 57.42% of new cancer cases. Cancers of the lung, liver, stomach, colon-rectum and esophagus were the five leading causes of cancer deaths, accounting for 67.50% of total cancer deaths. The crude rate and age-standardized incidence rate (ASIR) were 341.75 per 100,000 and 201.61 per 100,000, respectively. The crude mortality rate was 182.34 per 100,000 and the age-standardized mortality rate (ASMR) was 96.47 per 100,000. The ASIR of all cancers combined increased by approximately 1.4% per year during 2000-2018, while the ASMR decreased by approximately 1.3% per year. We observed decreasing trends in ASIR and ASMR for cancers of the esophagus, stomach, and liver, whereas the ASIR increased significantly for cancers of the thyroid, prostate, and cervix.\n\nConclusions: Cancer remains a major public health concern in China, with a cancer profile that reflects the coexistence of developed and developing regions. Sustained implementation of prevention and control measures has resulted in significant reductions in the incidence and mortality rates of certain historically high incidence cancers, such as esophageal, stomach and liver cancers. Adherence to the guidelines of the Healthy China Action Plan and the Cancer Prevention and Control Action Plan, along with continued efforts in comprehensive risk factor control, cancer screening, early diagnosis and treatment, and standardization of diagnostic and therapeutic protocols, are key strategies to effectively mitigate the increasing cancer burden by 2030.\n\nIndexed on Europe PMC as PubMed record 39036382 (DOI 10.1016/j.jncc.2024.01.006). Matched by DOI alone: one institution page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Natl Cancer Cent 2024","url":"https://doi.org/10.1016/j.jncc.2024.01.006"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39036382/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39036382"}],"tags":["europepmc-ingest"],"related":["ncc-china"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of the National Cancer Center","year":2024,"doi":"10.1016/j.jncc.2024.01.006","pmid":"39036382","authors":"Han B, Zheng R, Zeng H, et al.","paperType":"observational","findings":[],"whatItMeans":"One institution page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-friedl-cell","kind":"paper","name":"Cancer invasion and the microenvironment: plasticity and reciprocity","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 22118458 and published in Cell; the citing page links this DOI, which is how the record was matched.","summary":"Cancer invasion is a cell- and tissue-driven process for which the physical, cellular, and molecular determinants adapt and react throughout the progression of the disease. Cancer invasion is initiated and maintained by signaling pathways that control cytoskeletal dynamics in tumor cells and the turnover of cell-matrix and cell-cell junctions, followed by cell migration into the adjacent tissue. Here, we describe the cell-matrix and cell-cell adhesion, protease, and cytokine systems that underlie tissue invasion by cancer cells. We explain how the reciprocal reprogramming of both the tumor cells and the surrounding tissue structures not only guides invasion, but also generates diverse modes of dissemination. The resulting \"plasticity\" contributes to the generation of diverse cancer invasion routes and programs, enhanced tumor heterogeneity, and ultimately sustained metastatic dissemination.\n\nIndexed on Europe PMC as PubMed record 22118458 (DOI 10.1016/j.cell.2011.11.016). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cell 2011","url":"https://doi.org/10.1016/j.cell.2011.11.016"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22118458/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/22118458"}],"tags":["europepmc-ingest"],"related":["invasion-ecm-degradation"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Cell","year":2011,"doi":"10.1016/j.cell.2011.11.016","pmid":"22118458","authors":"Friedl P, Alexander S","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-johnson-j-natl-cancer-inst","kind":"paper","name":"Cancer Misinformation and Harmful Information on Facebook and Other Social Media: A Brief Report","aka":[],"tldr":"Paper cited by one bottleneck page and 15 idea pages, indexed on Europe PMC as PubMed record 34291289 and published in JNCI: Journal of the National Cancer Institute; the citing pages link this DOI, which is how the record was matched.","summary":"There are few data on the quality of cancer treatment information available on social media. Here, we quantify the accuracy of cancer treatment information on social media and its potential for harm. Two cancer experts reviewed 50 of the most popular social media articles on each of the 4 most common cancers. The proportion of misinformation and potential for harm were reported for all 200 articles and their association with the number of social media engagements using a 2-sample Wilcoxon rank-sum test. All statistical tests were 2-sided. Of 200 total articles, 32.5% (n = 65) contained misinformation and 30.5% (n = 61) contained harmful information. Among articles containing misinformation, 76.9% (50 of 65) contained harmful information. The median number of engagements for articles with misinformation was greater than factual articles (median [interquartile range] = 2300 [1200-4700] vs 1600 [819-4700], P =.05). The median number of engagements for articles with harmful information was statistically significantly greater than safe articles (median [interquartile range] = 2300 [1400-4700] vs 1500 [810-4700], P =.007).\n\nIndexed on Europe PMC as PubMed record 34291289 (DOI 10.1093/jnci/djab141). Matched by DOI alone: one bottleneck page and 15 idea pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Natl Cancer Inst 2022","url":"https://doi.org/10.1093/jnci/djab141"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34291289/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34291289"}],"tags":["europepmc-ingest"],"related":["b-misinformation","idea-moon-ai-cancer-answer-audit","idea-moon-unproven-clinic-registry","idea-moon-treatment-refusal-pathway","idea-moon-hype-index","idea-moon-supplement-interaction-database","idea-nl-ask-about-diet-prebunking","idea-moon-ban-unproven-therapy-ads","idea-moon-hpv-vaccine-confidence","idea-nl-antioxidant-supplement-harm-confirmation","idea-moon-integrative-oncology-bridge","idea-moon-prebunking-at-diagnosis","idea-moon-living-plain-evidence-summaries","idea-nl-ketogenic-gbm-definitive-trial","idea-moon-clinician-creator-programme","idea-moon-patient-community-moderators"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jnci"],"dependsOn":[],"notes":[],"journal":"JNCI: Journal of the National Cancer Institute","year":2022,"doi":"10.1093/jnci/djab141","pmid":"34291289","authors":"Johnson SB, Parsons M, Dorff T, et al.","paperType":"observational","findings":[],"whatItMeans":"One bottleneck page and 15 idea pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-esmo-cancer-of-unknown-primary-guideline-ann-oncol-2023","kind":"paper","name":"Cancer of unknown primary: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","aka":[],"tldr":"The European guideline on cancer that has spread from a primary no one can find: how far to look, which favourable subsets to treat like a known cancer, and what chemotherapy or targeted therapy to give the rest.","summary":"ESMO guideline defining cancer of unknown primary, the recommended diagnostic work-up (histology, immunohistochemistry, CT, PET-CT in selected cases, and comprehensive genomic profiling), the favourable subsets (such as women with peritoneal serous carcinoma, isolated axillary adenocarcinoma, squamous carcinoma in cervical nodes, poorly differentiated carcinoma with midline distribution, and neuroendocrine carcinoma) that are treated as their presumed primary, and empirical platinum-based chemotherapy for unfavourable disease with molecularly guided therapy where an actionable alteration is found.","asOf":"2026-09-18","links":[{"label":"Ann Oncol 2023","url":"https://doi.org/10.1016/j.annonc.2022.11.013"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36563965/"}],"tags":[],"related":[],"cancers":["cup-favourable-subsets","cup-unfavourable"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2023,"doi":"10.1016/j.annonc.2022.11.013","pmid":"36563965","authors":"Krämer A, Bochtler T, Pauli C, et al.","paperType":"guideline","findings":[],"whatItMeans":"The split between favourable and unfavourable cancer of unknown primary on OnCo, and the treatment on each page, follow this guideline.","caveats":["Published shortly before the CUPISCO result; the place of molecularly guided therapy is still being defined.","Tissue-of-origin gene expression tests are not recommended for routine treatment selection."],"changedPractice":true},{"id":"paper-mathur-ncrp-cancer-statistics-2020","kind":"paper","name":"Cancer Statistics, 2020: Report from National Cancer Registry Programme, India","aka":[],"tldr":"India's official cancer count: about 1.39 million new cancers in 2020, led by breast, lung, mouth, cervix and tongue, with most breast, cervical and head and neck cancers found only once locally advanced.","summary":"Analysis of 28 population-based and 58 hospital-based registries of the ICMR National Cancer Registry Programme (667,666 cases, 2012-2016). The projected number of cancer patients in India for 2020 was 1,392,179. The five leading sites were breast, lung, mouth, cervix uteri and tongue. Most patients presented at a locally advanced stage (breast 57.0%, cervix 60.0%, head and neck 66.6%, stomach 50.8%), while lung cancer presented mainly with distant metastasis (44.0% of men, 47.6% of women). Incidence rose over time at all registries, fastest in Kamrup urban (3.8% annual change); the highest age-adjusted rates were in Aizawl (men, 269.4 per 100,000) and Papumpare (women, 219.8). A 2022 update estimated 1,461,427 cases and a 12.8% rise by 2025.","asOf":"2026-09-10","links":[{"label":"JCO Global Oncology 2020","url":"https://doi.org/10.1200/GO.20.00122"},{"label":"2022 estimates and 2025 projection (IJMR)","url":"https://doi.org/10.4103/ijmr.ijmr_1821_22"}],"tags":[],"related":[],"cancers":["head-and-neck","cervical","breast-hr-positive","nsclc","gastric"],"sections":[],"technologies":["cancer-registries-surveillance"],"targets":[],"drugs":[],"companies":[],"institutions":["icmr-ncrp","icmr","nha-pmjay"],"pathways":[],"terms":[],"trials":[],"people":["mathur-prashant"],"bottlenecks":["b-early-detection","b-data-silos"],"keyPapers":[],"journals":["jco-global-oncology"],"dependsOn":[],"notes":[],"journal":"JCO Global Oncology","year":2020,"doi":"10.1200/GO.20.00122","authors":"Mathur P, Sathishkumar K, Chaturvedi M, et al.","paperType":"observational","findings":["1,392,179 projected new cancers in India in 2020 (1,461,427 estimated for 2022; +12.8% by 2025).","Leading sites: breast, lung, mouth, cervix uteri, tongue; tobacco-related cancers dominate in men.","Locally advanced at diagnosis: breast 57.0%, cervix 60.0%, head and neck 66.6%, stomach 50.8%.","Highest incidence in the north-east (Aizawl and Papumpare districts)."],"whatItMeans":"India's cancer problem is a late-diagnosis problem as much as a treatment problem: the same cancers that dominate (oral, cervical, breast) are the ones screening and vaccination can prevent or catch early. The numbers set the priorities of the National Cancer Grid, PM-JAY oncology packages and the national screening programme.","caveats":["Registries cover about a tenth of the population and are urban-weighted; national figures are projections.","GLOBOCAN 2022 estimates for India (1,413,316 cases) use different methods and are not identical.","Stage data come from hospital registries and may not represent patients never reaching hospital."],"changedPractice":false,"participants":667666},{"id":"paper-batlle-nat-med","kind":"paper","name":"Cancer stem cells revisited","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 28985214 and published in Nature Medicine; the citing page links this DOI, which is how the record was matched.","summary":"The cancer stem cell (CSC) concept was proposed four decades ago, and states that tumor growth, analogous to the renewal of healthy tissues, is fueled by small numbers of dedicated stem cells. It has gradually become clear that many tumors harbor CSCs in dedicated niches, and yet their identification and eradication has not been as obvious as was initially hoped. Recently developed lineage-tracing and cell-ablation strategies have provided insights into CSC plasticity, quiescence, renewal, and therapeutic response. Here we discuss new developments in the CSC field in relationship to changing insights into how normal stem cells maintain healthy tissues. Expectations in the field have become more realistic, and now, the first successes of therapies based on the CSC concept are emerging.\n\nIndexed on Europe PMC as PubMed record 28985214 (DOI 10.1038/nm.4409). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Med 2017","url":"https://doi.org/10.1038/nm.4409"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28985214/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28985214"}],"tags":["europepmc-ingest"],"related":["cancer-stem-cell-theory"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2017,"doi":"10.1038/nm.4409","pmid":"28985214","authors":"Batlle E, Clevers H","paperType":"review","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-gupta-nat-med","kind":"paper","name":"Cancer stem cells: mirage or reality?","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 19734877 and published in Nature Medicine; the citing page links this DOI, which is how the record was matched.","summary":"The similarities and differences between normal tissue stem cells and cancer stem cells (CSCs) have been the source of much contention, with some recent studies calling into question the very existence of CSCs. An examination of the literature indicates, however, that the CSC model rests on firm experimental foundations and that differences in the observed frequencies of CSCs within tumors reflect the various cancer types and hosts used to assay these cells. Studies of stem cells and the differentiation program termed the epithelial-mesenchymal transition (EMT) point to the possible existence of plasticity between stem cells and their more differentiated derivatives. If present, such plasticity would have major implications for the CSC model and for future therapeutic approaches.\n\nIndexed on Europe PMC as PubMed record 19734877 (DOI 10.1038/nm0909-1010). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Med 2009","url":"https://doi.org/10.1038/nm0909-1010"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19734877/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/19734877"}],"tags":["europepmc-ingest"],"related":["cancer-stem-cell-theory"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2009,"doi":"10.1038/nm0909-1010","pmid":"19734877","authors":"Gupta PB, Chaffer CL, Weinberg RA","paperType":"review","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-bolton-nat-genet","kind":"paper","name":"Cancer therapy shapes the fitness landscape of clonal hematopoiesis","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 33106634 and published in Nature Genetics; the citing page links this DOI, which is how the record was matched.","summary":"Acquired mutations are pervasive across normal tissues. However, understanding of the processes that drive transformation of certain clones to cancer is limited. Here we study this phenomenon in the context of clonal hematopoiesis (CH) and the development of therapy-related myeloid neoplasms (tMNs). We find that mutations are selected differentially based on exposures. Mutations in ASXL1 are enriched in current or former smokers, whereas cancer therapy with radiation, platinum and topoisomerase II inhibitors preferentially selects for mutations in DNA damage response genes (TP53, PPM1D, CHEK2). Sequential sampling provides definitive evidence that DNA damage response clones outcompete other clones when exposed to certain therapies. Among cases in which CH was previously detected, the CH mutation was present at tMN diagnosis. We identify the molecular characteristics of CH that increase risk of tMN. The increasing implementation of clinical sequencing at diagnosis provides an opportunity to identify patients at risk of tMN for prevention strategies.\n\nIndexed on Europe PMC as PubMed record 33106634 (DOI 10.1038/s41588-020-00710-0). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Genet 2020","url":"https://doi.org/10.1038/s41588-020-00710-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33106634/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33106634"}],"tags":["europepmc-ingest"],"related":["clonal-haematopoiesis"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":2020,"doi":"10.1038/s41588-020-00710-0","pmid":"33106634","authors":"Bolton KL, Ptashkin RN, Gao T, et al.","paperType":"observational","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-guilford-antiparasitic-acupuncture-meridian-case-series-2026","kind":"paper","name":"Cancer therapy using antiparasitic medications guided by acupuncture meridian assessment: a case series of six patients","aka":[],"tldr":"Six patients with advanced cancers treated over a decade with antiparasitic drugs chosen by measuring electrical conductance at acupuncture points were reported to have lived longer than expected; the method has no established basis and the series has no controls.","summary":"Six patients with stage IV breast, lung, prostate, glioblastoma and multiple myeloma seen between 2011 and 2022 received combinations of ivermectin, mebendazole, praziquantel, niclosamide and antifungals selected by acupuncture meridian assessment, a modification of electroacupuncture according to Voll that measures skin conductance, with dental infections treated at the same time (Guilford case series 2026). The authors report survival beyond conventional expectation in all six and no serious adverse events, and call for further study (Guilford case series 2026).","asOf":"2026-09-24","links":[{"label":"Guilford case series 2026","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13377776/"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42491797/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["fenbendazole-ivermectin-repurposing-claims"],"targets":[],"drugs":["ivermectin","mebendazole"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-misinformation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo agent (Claude Fable 5.1)","editedOn":"2026-09-24","note":"Written from cached ClinicalTrials.gov v2, Europe PMC, DailyMed, Drugs@FDA and WHO eEML responses; no figure appears without its source link."},"journal":"Integrative Medicine (Encinitas)","year":2026,"pmid":"42491797","authors":"Guilford FT, Yu S.","paperType":"observational","findings":["Six selected patients over eleven years; drug choice by skin-conductance readings; no controls."],"whatItMeans":"A case series selected by its authors from a decade of practice cannot show that any drug worked, and the selection method has no scientific basis.","caveats":["Retrospective, uncontrolled, author-selected; several patients also had conventional treatment.","Acupuncture meridian assessment has no validated relation to drug choice."],"changedPractice":false,"participants":6},{"id":"paper-davies-phys-biol","kind":"paper","name":"Cancer tumors as Metazoa 1.0: tapping genes of ancient ancestors","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 21301065 and published in Physical biology; the citing page links this DOI, which is how the record was matched.","summary":"The genes of cellular cooperation that evolved with multicellularity about a billion years ago are the same genes that malfunction to cause cancer. We hypothesize that cancer is an atavistic condition that occurs when genetic or epigenetic malfunction unlocks an ancient 'toolkit' of pre-existing adaptations, re-establishing the dominance of an earlier layer of genes that controlled loose-knit colonies of only partially differentiated cells, similar to tumors. The existence of such a toolkit implies that the progress of the neoplasm in the host organism differs distinctively from normal Darwinian evolution. Comparative genomics and the phylogeny of basal metazoans, opisthokonta and basal multicellular eukaryotes should help identify the relevant genes and yield the order in which they evolved. This order will be a rough guide to the reverse order in which cancer develops, as mutations disrupt the genes of cellular cooperation. Our proposal is consistent with current understanding of cancer and explains the paradoxical rapidity with which cancer acquires a suite of mutually-supportive complex abilities. Finally we make several predictions and suggest ways to test this model.\n\nIndexed on Europe PMC as PubMed record 21301065 (DOI 10.1088/1478-3975/8/1/015001). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Phys Biol 2011","url":"https://doi.org/10.1088/1478-3975/8/1/015001"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21301065/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/21301065"}],"tags":["europepmc-ingest"],"related":["atavistic-theory-of-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Physical biology","year":2011,"doi":"10.1088/1478-3975/8/1/015001","pmid":"21301065","authors":"Davies PC, Lineweaver CH","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-kinzler-nature","kind":"paper","name":"Cancer-susceptibility genes. Gatekeepers and caretakers","aka":[],"tldr":"Paper cited by one pathway page and one term page, indexed on Europe PMC as PubMed record 9126728 and published in Nature; the citing pages link this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 9126728 (DOI 10.1038/386761a0). Matched by DOI alone: one pathway page and one term page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 1997","url":"https://doi.org/10.1038/386761a0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/9126728/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/9126728"}],"tags":["europepmc-ingest"],"related":["oncogene-activation-two-hit","driver-passenger-model"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":1997,"doi":"10.1038/386761a0","pmid":"9126728","authors":"Kinzler KW, Vogelstein B","paperType":"observational","findings":[],"whatItMeans":"One pathway page and one term page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-peccatori-ann-oncol","kind":"paper","name":"Cancer, pregnancy and fertility: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 23813932 and published in Annals of Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 23813932 (DOI 10.1093/annonc/mdt199). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Ann Oncol 2013","url":"https://doi.org/10.1093/annonc/mdt199"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23813932/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/23813932"}],"tags":["europepmc-ingest"],"related":["cancer-in-pregnancy"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2013,"doi":"10.1093/annonc/mdt199","pmid":"23813932","authors":"Peccatori FA, Azim HA, Orecchia R, et al.","paperType":"guideline","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-burnet-br-med-j","kind":"paper","name":"Cancer; a biological approach. I. The processes of control","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 13404306 and published in BMJ; the citing page links this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 13404306 (DOI 10.1136/bmj.1.5022.779). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Br Med J 1957","url":"https://doi.org/10.1136/bmj.1.5022.779"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/13404306/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/13404306"}],"tags":["europepmc-ingest"],"related":["immune-surveillance-immunoediting"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["bmj"],"dependsOn":[],"notes":[],"journal":"BMJ","year":1957,"doi":"10.1136/bmj.1.5022.779","pmid":"13404306","authors":"BURNET M","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-vincent-bioessays","kind":"paper","name":"Cancer: a de-repression of a default survival program common to all cells?: a life-history perspective on the nature of cancer","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 22105565 and published in BioEssays; the citing page links this DOI, which is how the record was matched.","summary":"Cancer viewed as a programmed, evolutionarily conserved life-form, rather than just a random series of disease-causing mutations, answers the rarely asked question of what the cancer cell is for, provides meaning for its otherwise mysterious suite of attributes, and encourages a different type of thinking about treatment. The broad but consistent spectrum of traits, well-recognized in all aggressive cancers, group naturally into three categories: taxonomy (\"phylogenation\"), atavism (\"re-primitivization\") and robustness (\"adaptive resilience\"). The parsimonious explanation is not convergent evolution, but the release of an highly conserved survival program, honed by the exigencies of the Pre-Cambrian, to which the cancer cell seems better adapted; and which is recreated within, and at great cost to, its host. Central to this program is the Warburg Effect, whose malign influence permeates well beyond aerobic glycolysis to include biomass interconversion and genomic heuristics. Warburg-type metabolism and genomic instability are targets whose therapeutic disablement is a major priority.\n\nIndexed on Europe PMC as PubMed record 22105565 (DOI 10.1002/bies.201100049). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Bioessays 2012","url":"https://doi.org/10.1002/bies.201100049"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22105565/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/22105565"}],"tags":["europepmc-ingest"],"related":["atavistic-theory-of-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"BioEssays","year":2012,"doi":"10.1002/bies.201100049","pmid":"22105565","authors":"Vincent M","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-braun-j-clin-oncol","kind":"paper","name":"Cannabis and Cannabinoids in Adults With Cancer: ASCO Guideline","aka":[],"tldr":"Paper cited by two technology pages, indexed on Europe PMC as PubMed record 38478773 and published in Journal of Clinical Oncology; the citing pages link this DOI, which is how the record was matched.","summary":"Purpose: To guide clinicians, adults with cancer, caregivers, researchers, and oncology institutions on the medical use of cannabis and cannabinoids, including synthetic cannabinoids and herbal cannabis derivatives; single, purified cannabinoids; combinations of cannabis ingredients; and full-spectrum cannabis.\n\nMethods: A systematic literature review identified systematic reviews, randomized controlled trials (RCTs), and cohort studies on the efficacy and safety of cannabis and cannabinoids when used by adults with cancer. Outcomes of interest included antineoplastic effects, cancer treatment toxicity, symptoms, and quality of life. PubMed and the Cochrane Library were searched from database inception to January 27, 2023. ASCO convened an Expert Panel to review the evidence and formulate recommendations.\n\nResults: The evidence base consisted of 13 systematic reviews and five additional primary studies (four RCTs and one cohort study). The certainty of evidence for most outcomes was low or very low.\n\nRecommendations: Cannabis and/or cannabinoid access and use by adults with cancer has outpaced the science supporting their clinical use. This guideline provides strategies for open, nonjudgmental communication between clinicians and adults with cancer about the use of cannabis and/or cannabinoids. Clinicians should recommend against using cannabis or cannabinoids as a cancer-directed treatment unless within the context of a clinical trial. Cannabis and/or cannabinoids may improve refractory, chemotherapy-induced nausea and vomiting when added to guideline-concordant antiemetic regimens. Whether cannabis and/or cannabinoids can improve other supportive care outcomes remains uncertain. This guideline also highlights the critical need for more cannabis and/or cannabinoid research.Additional information is available at www.asco.org/supportive-care-guidelines.\n\nIndexed on Europe PMC as PubMed record 38478773 (DOI 10.1200/jco.23.02596). Matched by DOI alone: two technology pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2024","url":"https://doi.org/10.1200/jco.23.02596"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38478773/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38478773"}],"tags":["europepmc-ingest"],"related":["cannabinoids-nausea","cannabinoids-pain-appetite"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2024,"doi":"10.1200/jco.23.02596","pmid":"38478773","authors":"Braun IM, Bohlke K, Abrams DI, et al.","paperType":"review","findings":[],"whatItMeans":"Two technology pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-taha-oncologist","kind":"paper","name":"Cannabis Impacts Tumor Response Rate to Nivolumab in Patients with Advanced Malignancies","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 30670598 and published in The oncologist; the citing page links this DOI, which is how the record was matched.","summary":"Background: There has been a significant increase in the use of immunotherapy and cannabis recently, two modalities that have immunomodulatory effects and may have possible interaction. We evaluated the influence of cannabis use during immunotherapy treatment on response rate (RR), progression-free survival (PFS), and overall survival (OS).\n\nSubjects, materials, and methods: In this retrospective, observational study, data were collected from the files of patients treated with nivolumab in the years 2015-2016 at our hospital, and cannabis from six cannabis-supplying companies. Included were 140 patients (89 nivolumab alone, 51 nivolumab plus cannabis) with advanced melanoma, non-small cell lung cancer, and renal clear cell carcinoma. The groups were homogenous regarding demographic and disease characteristics. A comparison between the two arms was made.\n\nResults: In a multivariate model, cannabis was the only significant factor that reduced RR to immunotherapy (37.5% RR in nivolumab alone compared with 15.9% in the nivolumab-cannabis group ( p =.016, odds ratio = 3.13, 95% confidence interval 1.24-8.1). Cannabis use was not a significant factor for PFS or OS. Factors affecting PFS and OS were smoking (adjusted hazard ratio [HR] = 2.41 and 2.41, respectively (and brain metastases (adjusted HR = 2.04 and 2.83, respectively). Low performance status (adjusted HR = 2.83) affected OS alone. Tetrahydrocannabinol and cannabidiol percentages did not affect RR in any group ( p =.393 and.116, respectively).\n\nConclusion: In this retrospective analysis, the use of cannabis during immunotherapy treatment decreased RR, without affecting PFS or OS and without relation to cannabis composition. Considering the limitations of the study, further prospective clinical study is needed to investigate possible interaction.\n\nImplications for practice: Although the data are retrospective and a relation to cannabis composition was not detected, this information can be critical for cannabis users and indicates that caution is required when starting immunotherapy.\n\nIndexed on Europe PMC as PubMed record 30670598 (DOI 10.1634/theoncologist.2018-0383). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Oncologist 2019","url":"https://doi.org/10.1634/theoncologist.2018-0383"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30670598/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30670598"}],"tags":["europepmc-ingest"],"related":["cannabinoids-pain-appetite"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["the-oncologist"],"dependsOn":[],"notes":[],"journal":"The oncologist","year":2019,"doi":"10.1634/theoncologist.2018-0383","pmid":"30670598","authors":"Taha T, Meiri D, Talhamy S, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-adams-j-clin-oncol","kind":"paper","name":"Capecitabine Versus Active Monitoring in Stable or Responding Metastatic Colorectal Cancer After 16 Weeks of First-Line Therapy: Results of the Randomized FOCUS4-N Trial","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 34516759 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: Despite extensive randomized evidence supporting the use of treatment breaks in metastatic colorectal cancer (mCRC), they are not universally offered to patients despite improvements in quality of life without detriment to overall survival (OS). FOCUS4-N was set up to explore the impact of oral maintenance therapy in patients who are responding to first-line therapy.\n\nMethods: FOCUS4 was a molecularly stratified trial program that registered patients with newly diagnosed mCRC. The FOCUS4-N trial was offered to patients in whom a targeted subtrial was unavailable or biomarker tests failed. Patients were randomly assigned using a 1:1 ratio between maintenance capecitabine and active monitoring (AM). The primary outcome was progression-free survival (PFS) with secondary outcomes including OS toxicity and tolerability.\n\nResults: Between March 2014 and March 2020, 254 patients were randomly assigned (127 to capecitabine and 127 to AM) across 88 UK sites. Baseline characteristics were balanced. There was strong evidence of efficacy for PFS (hazard ratio = 0.40; 95% CI, 0.21 to 0.75; P <.0001), but no significant improvement in OS (hazard ratio, 0.93; 95% CI, 0.69 to 1.27; P =.66) was observed. Compliance with treatment was good, and toxicity from capecitabine versus AM was as expected with grade ≥ 2 fatigue (25% v 12%), diarrhea (23% v 13%), and hand-foot syndrome (26% v 3%). Quality of life showed little difference between the groups.\n\nConclusion: Despite strong evidence of disease control with maintenance therapy, OS remains unaffected and FOCUS4-N provides additional evidence to support the use of treatment breaks as safe management alternatives for patients who are stable or responding to first-line treatment for mCRC. Capecitabine without bevacizumab may be used to extend PFS in the interval after 16 weeks of first-line therapy.\n\nIndexed on Europe PMC as PubMed record 34516759 (DOI 10.1200/jco.21.01436). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2021","url":"https://doi.org/10.1200/jco.21.01436"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34516759/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34516759"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["focus4"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2021,"doi":"10.1200/jco.21.01436","pmid":"34516759","authors":"Adams RA, Fisher DJ, Graham J, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-capitello-291-nejm-2023","kind":"paper","name":"CAPItello-291: capivasertib plus fulvestrant in hormone receptor-positive advanced breast cancer","aka":[],"tldr":"Adding the AKT inhibitor capivasertib to fulvestrant doubled the time to progression in advanced hormone receptor-positive breast cancer after aromatase inhibitor failure, with the largest gain in tumours with PIK3CA, AKT1 or PTEN alterations.","summary":"Phase 3 placebo-controlled trial of 708 patients with hormone receptor-positive, HER2-negative advanced breast cancer that had relapsed or progressed on an aromatase inhibitor, about 70 percent after a CDK4/6 inhibitor, randomised to capivasertib or placebo with fulvestrant.\n\nMedian progression-free survival was 7.2 versus 3.6 months overall (hazard ratio 0.60) and 7.3 versus 3.1 months in the AKT pathway-altered population (hazard ratio 0.50). Diarrhoea, rash and hyperglycaemia were the main toxicities.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2023","url":"https://doi.org/10.1056/NEJMoa2214131"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37256976/"}],"tags":[],"related":[],"cancers":["hr-positive-metastatic-post-cdk46"],"sections":[],"technologies":[],"targets":[],"drugs":["capivasertib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["capitello-291"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/NEJMoa2214131","pmid":"37256976","authors":"Turner NC, Oliveira M, Howell SJ, et al.","paperType":"rct","findings":["Median progression-free survival 7.2 vs 3.6 months overall; hazard ratio 0.60.","AKT pathway-altered: 7.3 vs 3.1 months; hazard ratio 0.50."],"whatItMeans":"Capivasertib-fulvestrant is a standard option for tumours with PIK3CA, AKT1 or PTEN alterations after a CDK4/6 inhibitor, adding a second targeted pathway to endocrine therapy.","caveats":["Approval was limited to pathway-altered tumours because benefit in non-altered disease was uncertain.","Overall survival data were immature."],"changedPractice":true,"participants":708},{"id":"paper-capitello-281-ann-oncol-2026","kind":"paper","name":"Capivasertib plus abiraterone in PTEN-deficient metastatic hormone-sensitive prostate cancer: CAPItello-281 phase III study","aka":[],"tldr":"Published report from the CAPItello-281 trial registered as NCT04493853, in Annals of Oncology (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: In metastatic hormone-sensitive prostate cancer (mHSPC), phosphatase and tensin homolog (PTEN) deficiency results in phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway activation, providing an independent proliferative drive, which cannot be suppressed by androgen receptor pathway inhibitors (ARPIs), resulting in worse outcomes. Dual inhibition of PI3K/AKT and AR pathways with capivasertib and abiraterone may delay progression and improve disease outcomes.\n\nPatients and methods: In CAPItello-281 (NCT04493853), patients with PTEN-deficient mHSPC (diagnostic cut-off: ≥90% viable malignant cells with no specific cytoplasmic PTEN immunohistochemistry staining) received capivasertib or placebo (1: 1) plus abiraterone, prednisone/prednisolone, and androgen deprivation therapy (ADT). The primary endpoint was investigator-assessed radiographic progression-free survival (rPFS); overall survival (OS) was a key secondary endpoint. Post hoc exploratory subgroups at increasing PTEN cut-off thresholds were also assessed.\n\nResults: 25.3% (1519/6003) of patients with valid tumor test results had PTEN-deficient tumors. In the randomized PTEN-deficient population, a statistically significant improvement in rPFS was observed with capivasertib plus abiraterone (n = 507, median 33.2 months) versus placebo plus abiraterone [n = 505, 25.7 months; hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.66-0.98, P = 0.034]. Post hoc rPFS analyses for loss of PTEN cut-offs of ≥95%, ≥99%, and 100% showed that the capivasertib plus abiraterone arm performed consistently across cut-offs, but the placebo plus abiraterone arm performed progressively worse as the cut-off for the degree of PTEN loss was increased, resulting in a numerically improved treatment effect. In the overall population studied, the HR for OS (26.4% maturity) was 0.90, 95% CI 0.71-1.15, P = 0.401. The most common adverse events (AEs) for capivasertib plus abiraterone were diarrhea (51.9%; 8.0% placebo plus abiraterone), hyperglycemia (38.0%; 12.9%), and rash (35.4%; 7.0%). Deaths associated with an AE were reported in 36 (7.2%) and 26 (5.2%) patients in the capivasertib plus abiraterone and placebo plus abiraterone arms, respectively.\n\nConclusions: Capivasertib plus abiraterone improves rPFS versus placebo plus abiraterone in PTEN-deficient mHSPC, on a background of ADT, with a 7.5-month improvement in median rPFS. AE profile was consistent with that of the individual agents. Patients with PTEN-deficient mHSPC benefit from dual blockade of the PI3K/AKT and AR pathways with capivasertib plus abiraterone.\n\nIndexed on Europe PMC as PubMed record 41120017 (DOI 10.1016/j.annonc.2025.10.004). Its abstract cites the registry id NCT04493853, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2026","url":"https://doi.org/10.1016/j.annonc.2025.10.004"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41120017/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41120017"},{"label":"ClinicalTrials.gov NCT04493853","url":"https://clinicaltrials.gov/study/NCT04493853"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["capitello-281"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2026,"doi":"10.1016/j.annonc.2025.10.004","pmid":"41120017","authors":"Fizazi K, Clarke NW, De Santis M, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04493853 with the most citations, so it is the natural first reading for anyone following the CAPItello-281 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-capitello-290-capivasertib-paclitaxel-ann-oncol-2026","kind":"paper","name":"Capivasertib plus paclitaxel as first-line treatment for metastatic triple-negative breast cancer: results from the randomised, global phase III CAPItello-290 trial","aka":[],"tldr":"The 812-patient trial in which adding the AKT inhibitor capivasertib to first-line paclitaxel did not lengthen life in metastatic triple-negative breast cancer (17.7 versus 18.0 months), even in the 31 percent of patients whose tumours carried the pathway alterations it targets.","summary":"CAPItello-290 (Schmid, McArthur, Cortés, Xu and colleagues) randomised 812 patients with previously untreated metastatic triple-negative breast cancer between July 2019 and February 2022 to paclitaxel 80 mg/m2 on days 1, 8 and 15 of a four-week cycle plus capivasertib 400 mg or placebo twice daily on days 2 to 5 of each treatment week, following the positive phase 2 PAKT trial; 30.7 percent had PIK3CA, AKT1 or PTEN alterations by retrospective central testing. Dual primary endpoints were overall survival overall and in the altered group. At final analysis (18 March 2024) median overall survival was 17.7 versus 18.0 months (hazard ratio 0.92, 95 percent confidence interval 0.78 to 1.08, p=0.3239) and 20.4 months in both arms of the altered group (1.05, 0.77 to 1.43). Median progression-free survival numerically favoured capivasertib (5.6 versus 5.1 months, 0.72, 0.61 to 0.84; altered group 7.5 versus 5.6, 0.70). Grade 3 or higher diarrhoea occurred in 12.7 versus 0.7 percent, capivasertib was stopped for adverse events in 8.5 percent, and adverse events led to death in 4.2 percent of all patients.","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2026","url":"https://doi.org/10.1016/j.annonc.2025.12.012"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41422862/"},{"label":"ClinicalTrials.gov NCT03997123","url":"https://clinicaltrials.gov/study/NCT03997123"}],"tags":["tnbc-evidence"],"related":[],"cancers":["tnbc"],"sections":[],"technologies":[],"targets":["akt"],"drugs":["capivasertib","paclitaxel"],"companies":["astrazeneca"],"institutions":[],"pathways":["pi3k-akt-mtor"],"terms":["os","pfs"],"trials":["nct03997123"],"people":["peter-schmid","javier-cortes"],"bottlenecks":["b-negative-results","b-tumor-heterogeneity"],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2026,"doi":"10.1016/j.annonc.2025.12.012","pmid":"41422862","authors":"Schmid P, McArthur HL, Cortés J, et al.","paperType":"rct","findings":["Median overall survival 17.7 vs 18.0 months; hazard ratio 0.92 (95 percent CI 0.78 to 1.08), p=0.3239; altered group 20.4 months in both arms (1.05).","Median progression-free survival 5.6 vs 5.1 months (hazard ratio 0.72); altered group 7.5 vs 5.6 (0.70).","Grade 3 or higher diarrhoea 12.7 vs 0.7 percent; adverse events led to death in 4.2 percent."],"whatItMeans":"The latest in a line of negative targeted-therapy trials in triple-negative disease (EGFR, VEGF, iniparib, now AKT): a modest delay in progression that did not translate into survival, in the same year that an antibody-drug conjugate did. It is why the roadmap treats pathway-targeted small molecules as the road not taken.","caveats":["Paclitaxel alone is no longer the first-line comparator; the result cannot be read against antibody-drug conjugates or pembrolizumab combinations.","Molecular testing was retrospective and the altered group was a third of patients."],"changedPractice":false,"participants":812},{"id":"paper-schmid-pakt-capivasertib-tnbc-jco-2020","kind":"paper","name":"Capivasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer: the PAKT trial","aka":[],"tldr":"Adding capivasertib to first-line paclitaxel improved survival in metastatic triple-negative cancer from 12.6 to 19.1 months, with the largest gain in the fifth of patients whose tumours carried a PIK3CA, AKT1 or PTEN alteration.","summary":"140 women with untreated metastatic TNBC were randomised to paclitaxel 90 mg/m2 with capivasertib 400 mg twice daily (days 2 to 5, 9 to 12, 16 to 19) or placebo. Median PFS was 5.9 versus 4.2 months (HR 0.74; one-sided P 0.06 against a 0.10 threshold) and median overall survival 19.1 versus 12.6 months (HR 0.61). In 28 patients with PIK3CA/AKT1/PTEN-altered tumours PFS was 9.3 versus 3.7 months (HR 0.30). Grade 3 or worse diarrhoea 13% versus 1%.","asOf":"2026-09-24","links":[{"label":"Schmid et al., J Clin Oncol 2020: PAKT, capivasertib plus paclitaxel in 140 metastatic TNBC patients","url":"https://doi.org/10.1200/JCO.19.00368"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31841354/"}],"tags":[],"related":["pik3ca-hotspot-mutation","akt1-e17k","pten-alteration"],"cancers":["tnbc","tnbc-metastatic"],"sections":[],"technologies":[],"targets":["akt","pik3ca","pten"],"drugs":["capivasertib","paclitaxel"],"companies":["astrazeneca"],"institutions":[],"pathways":["pi3k-akt-mtor"],"terms":[],"trials":[],"people":["peter-schmid"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/JCO.19.00368","pmid":"31841354","authors":"Schmid P, Abraham J, Chan S, et al.","paperType":"rct","findings":["PFS 5.9 versus 4.2 months (HR 0.74); overall survival 19.1 versus 12.6 months (HR 0.61).","PIK3CA/AKT1/PTEN-altered (28 of 140, 20%): PFS 9.3 versus 3.7 months (HR 0.30)."],"whatItMeans":"PAKT gives the trial-based prevalence of PI3K-pathway alteration in first-line metastatic TNBC (one in five) and the strongest signal for AKT inhibition in that subgroup; the phase 3 CAPItello-290 did not confirm it.","caveats":["Phase 2 with a lenient one-sided significance level.","Subgroup of 28 patients; CAPItello-290 was negative."],"changedPractice":false,"participants":140},{"id":"paper-capivasertib-breast-hr-positive-drugs-2024","kind":"paper","name":"Capivasertib: First Approval","aka":[],"tldr":"Review on Capivasertib in HR-positive / HER2-negative breast cancer, in Drugs (2024), one of the most cited Europe PMC records with Capivasertib in its title.","summary":"Capivasertib (Truqap™) is an orally available, small-molecule pan-AKT inhibitor being developed by AstraZeneca for the treatment of various cancers, including breast and prostate cancers. Capivasertib received its first approval, in the USA, in November 2023 for use in combination with fulvestrant for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor 2 (HER2)-negative, locally advanced or metastatic breast cancer with one or more PIK3CA/AKT1/PTEN-alterations following progression on at least one endocrine-based regimen in the metastatic setting or recurrence on or within 12 months of completing adjuvant therapy. Capivasertib is also under regulatory review for HR-positive, HER2-negative breast cancer in the EU and several other countries, and in phase III clinical development for use (in combination with other anti-cancer agents) in the treatment of triple-negative breast cancer, castration-resistant prostate cancer, and hormone-sensitive prostate cancer. This article summarizes the milestones in the development of capivasertib leading to this first approval for HR-positive, HER2-negative, locally advanced or metastatic breast cancer.\n\nIndexed on Europe PMC as PubMed record 38388873 (DOI 10.1007/s40265-024-01998-6). Its title names Capivasertib and its text names HR-positive / HER2-negative breast cancer; PubMed types it as a review (Review). It was matched automatically to the idea \"Molecular-progression switching beyond ESR1\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Drugs 2024","url":"https://doi.org/10.1007/s40265-024-01998-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38388873/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38388873"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Drugs","year":2024,"doi":"10.1007/s40265-024-01998-6","pmid":"38388873","authors":"Shirley M","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for Capivasertib in HR-positive / HER2-negative breast cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Capivasertib in the title and HR-positive / HER2-negative breast cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-geometry-mono-1-lancet-oncol-2024-update","kind":"paper","name":"Capmatinib in MET exon 14-mutated non-small-cell lung cancer: final results from the open-label, phase 2 GEOMETRY mono-1 trial","aka":[],"tldr":"Later report from the GEOMETRY mono-1 trial registered as NCT02414139, in The Lancet Oncology (2024); its title describes an updated or longer-term analysis.","summary":"Background: Capmatinib has previously shown activity in treatment-naive and previously treated patients with non-small-cell lung cancer (NSCLC) and a MET exon 14-skipping mutation (METex14). Here, we report the final outcomes from the phase 2 GEOMETRY mono-1 study with an aim to provide further evidence for the activity of capmatinib.\n\nMethods: In this non-randomised, multi-cohort, open-label, phase 2 trial conducted in 152 centres and hospitals in 25 countries, with patients treated in 95 centres in 20 countries, eligible patients (aged ≥18 years) with MET-dysregulated, EGFR wild-type, and ALK rearrangement-negative advanced NSCLC (stage IIIB/IV) and an Eastern Cooperative Oncology Group performance status of 0 or 1 were assigned to cohorts (1a, 1b, 2, 3, 4, 5a, 5b, 6 and 7) based on their MET status (METex14 or MET amplification) and previous therapy lines. Patients received capmatinib (400 mg orally twice daily) in 21-day treatment cycles. The primary endpoint was overall response rate by blinded independent central review per Response Evaluation Criteria in Solid Tumours version 1.1 and was performed on the full analysis set (all patients who received at least one dose of capmatinib). Previous reports of this study had published interim or primary data for cohorts 1-7. Here, we report the final clinical outcomes from all METex14 cohorts (4, 5b, 6, and 7) and safety from all study cohorts (1-7). The trial is registered with ClinicalTrials.gov, NCT02414139, and has been completed.\n\nFindings: Of 373 treated patients enrolled from June 11, 2015, to March 12, 2020, 160 (97 [61%] female) patients had METex14 NSCLC and were enrolled in four cohorts: 60 treatment-naive (cohorts 5b and 7) and 100 previously treated (cohorts 4 and 6). The overall median study follow-up was 46·4 months (IQR 41·8-65·4) for the treatment-naïve patients and 66·9 months (56·7-73·9) for previously treated patients, respectively. Overall responses were recorded in 41 (68%; 95% CI 55·0-79·7) of 60 treatment-naive patients and 44 (44%; 95% CI 34·1-54·3) of 100 previously treated patients. In all 373 treated patients, the most common treatment-related adverse events were peripheral oedema (n=174; 47%), nausea (n=130; 35%), increased blood creatinine (n=78; 21%), and vomiting (n=74; 20%). Grade 3-4 serious adverse events occurred in 164 (44%) patients, dyspnoea being the most common (18 patients [5%]). Treatment-related deaths occurred in four (1%) patients (one each of cardiac arrest, hepatitis, organising pneumonia, and pneumonitis). No new safety signals were reported.\n\nInterpretation: These long-term results support METex14 as a targetable oncogenic driver in NSCLC and add to the evidence supporting capmatinib as a targeted treatment option for treatment-naive and previously treated patients with METex14 NSCLC.\n\nFunding: Novartis Pharmaceuticals.\n\nIndexed on Europe PMC as PubMed record 39362249 (DOI 10.1016/s1470-2045(24)00441-8). Its abstract cites the registry id NCT02414139, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2024","url":"https://doi.org/10.1016/s1470-2045(24)00441-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39362249/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39362249"},{"label":"ClinicalTrials.gov NCT02414139","url":"https://clinicaltrials.gov/study/NCT02414139"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["geometry-mono-1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2024,"doi":"10.1016/s1470-2045(24)00441-8","pmid":"39362249","authors":"Wolf J, Hochmair M, Han JY, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the GEOMETRY mono-1 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-wolf-geometry-mono-1-capmatinib-nejm-2020","kind":"paper","name":"Capmatinib in MET exon 14-mutated or MET-amplified non-small-cell lung cancer","aka":[],"tldr":"MET exon 14 skipping is found in 3 to 4 percent of lung cancers. Untreated patients given capmatinib responded 68 percent of the time; those already treated, 41 percent. Order of treatment mattered more than usual.","summary":"The GEOMETRY mono-1 investigators, reported by Wolf, Seto, Han and colleagues, assigned 364 patients with MET-dysregulated advanced non-small-cell lung cancer to cohorts by previous lines of therapy and MET status (exon 14 skipping mutation, or amplification by gene copy number), all receiving capmatinib 400 mg twice daily. The primary endpoint was overall response by independent review.\n\nIt is the trial that separated the two ways MET goes wrong. Exon 14 skipping behaves like a classical driver; amplification only behaves like one above a gene copy number of 10, and below that threshold the drug has little effect. Few targets in lung cancer have so clear a dose-of-target effect.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2020","url":"https://doi.org/10.1056/NEJMoa2002787"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32877583/"},{"label":"ClinicalTrials.gov NCT02414139","url":"https://clinicaltrials.gov/study/NCT02414139"}],"tags":["lung-evidence"],"related":["paper-frampton-met-exon-14-cancer-discov-2015","paper-mariposa-nejm-2024"],"cancers":["lung-cancer","nsclc","met-altered-nsclc"],"sections":["targeted-therapy","diagnostics"],"technologies":["ngs","kinase-inhibitors"],"targets":["met"],"drugs":["capmatinib","tepotinib"],"companies":["novartis"],"institutions":[],"pathways":[],"terms":["driver-mutation"],"trials":["geometry-mono-1"],"people":[],"bottlenecks":["b-biomarker-validation","b-rare-cancers","b-dose-optimisation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2020,"doi":"10.1056/NEJMoa2002787","pmid":"32877583","authors":"Wolf J, Seto T, Han JY, et al.","paperType":"rct","findings":["In MET exon 14 skipping disease, overall response 68 percent (95 percent confidence interval 48 to 84) in 28 previously untreated patients and 41 percent (29 to 53) in 69 previously treated patients.","Median duration of response 12.6 months in the untreated group and 9.7 months (5.6 to 13.0) in the previously treated group.","In MET amplification with a gene copy number of 10 or higher, response was 40 percent (16 to 68) in untreated and 29 percent (19 to 41) in previously treated patients.","In previously treated patients with MET amplification and a gene copy number below 10, response was 7 to 12 percent.","MET exon 14 skipping mutations occur in 3 to 4 percent of non-small-cell lung cancer and MET amplifications in 1 to 6 percent.","The commonest adverse events were peripheral oedema (51 percent) and nausea (45 percent), mostly grade 1 or 2."],"whatItMeans":"A rare driver with a real drug, and a warning about biomarker thresholds: the same gene, tested the same way, predicts response or does not depending on a copy-number cut-off that has to be measured rather than assumed.","caveats":["Single-arm cohort study with response as the primary endpoint; no randomised comparison against chemotherapy or immunotherapy.","Heavily cohort-dependent results, and the untreated cohorts are small (28 patients for the headline 68 percent).","MET exon 14 skipping is detected differently by DNA and RNA assays, and the false-negative rate of DNA-only panels is a live problem."],"changedPractice":true,"participants":364},{"id":"paper-capp2-aspirin-lynch-lancet-2020","kind":"paper","name":"CAPP2: two years of aspirin cuts bowel cancer in Lynch syndrome by more than a third over 10 years","aka":[],"tldr":"In carriers of Lynch syndrome, 600 mg of aspirin a day for about two years reduced colorectal cancer over the following decade (HR 0.65 by intention to treat; 0.56 in those who took it for at least two years).","summary":"CAPP2 randomised 861 carriers of a mismatch-repair gene mutation (Lynch syndrome) to aspirin 600 mg daily or placebo for a mean of 25 months, in a factorial design with resistant starch. The pre-specified 10-year follow-up reported here used national registries and questionnaires.\n\nBy intention to treat, 40 aspirin-arm and 58 placebo-arm participants developed colorectal cancer (HR 0.65). Among those who completed at least two years of treatment, the hazard ratio was 0.56. The protective effect emerged only after about five years and persisted for at least a decade after stopping. Adverse events did not differ during the treatment period.\n\nThe result led NICE and other guidelines to recommend daily aspirin for people with Lynch syndrome; the CAPP3 dose-finding trial (100 vs 300 vs 600 mg) followed.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1016/S0140-6736(20)30366-4"},{"label":"CAPP3 ISRCTN16261285","url":"https://www.isrctn.com/ISRCTN16261285"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32534647/"},{"label":"Europe PMC full text (PMC7294238)","url":"https://europepmc.org/article/MED/32534647"}],"tags":[],"related":["idea-prev-lynch-aspirin-implementation","idea-reg-aspirin-pik3ca-implementation","paper-tcga-colorectal-comprehensive-characterization-nature-2012"],"cancers":["colorectal","endometrial","colon-cancer","msi-high-colorectal"],"sections":["prevention"],"technologies":["chemoprevention","germline-testing"],"targets":[],"drugs":["aspirin"],"companies":[],"institutions":[],"pathways":[],"terms":["lynch-syndrome","msi","germline-vs-somatic","mmr"],"trials":["capp2"],"people":[],"bottlenecks":["b-hereditary-risk","b-prevention-adoption","b-generic-repurposing"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2020,"doi":"10.1016/S0140-6736(20)30366-4","pmid":"32534647","authors":"Burn J, Sheth H, Elliott F, et al.","paperType":"rct","findings":["Colorectal cancer: 40 of 427 on aspirin vs 58 of 434 on placebo, HR 0.65 (95% CI 0.43-0.97) by intention to treat","Per-protocol (at least 2 years of treatment): HR 0.56 (95% CI 0.34-0.91)","Protection was delayed, appearing about 5 years after randomisation, and persisted after aspirin was stopped","No significant difference in serious adverse events during the intervention period"],"whatItMeans":"People with Lynch syndrome should be offered daily aspirin, which roughly halves bowel cancer risk with a delayed and durable effect. Whether a lower dose (as tested in CAPP3) is as effective, and whether the finding extends to the general population, are separate questions.","caveats":["Original primary endpoint at the 2008 analysis was null; the effect emerged only with long follow-up, which invites scepticism about post-hoc timing","600 mg is a high dose with bleeding risk in older people; CAPP3 addresses dose","Most participants were under 60 and from specialist registries","Resistant starch, the other factorial arm, showed a reduction in non-colorectal Lynch cancers, complicating interpretation"],"changedPractice":true,"participants":861},{"id":"paper-captain-1st-camrelizumab-chemotherapy-npc-lancet-oncol-2021","kind":"paper","name":"CAPTAIN-1st: camrelizumab versus placebo with gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma","aka":[],"tldr":"A second PD-1 antibody, camrelizumab, also lengthened progression-free survival when added to gemcitabine and cisplatin in metastatic nasopharyngeal cancer, confirming that chemo-immunotherapy is the new first-line standard.","summary":"Chinese multicentre randomised double-blind phase 3 trial of 263 patients with recurrent or metastatic nasopharyngeal carcinoma assigned to camrelizumab or placebo with gemcitabine and cisplatin, followed by maintenance.\n\nMedian progression-free survival was 9.7 months with camrelizumab against 6.9 months with placebo (hazard ratio 0.54), with a higher response rate; reactive cutaneous capillary endothelial proliferation, characteristic of camrelizumab, was common but mostly mild.","asOf":"2026-09-18","links":[{"label":"Lancet Oncol 2021","url":"https://doi.org/10.1016/S1470-2045(21)00302-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34174189/"}],"tags":[],"related":[],"cancers":["recurrent-metastatic-nasopharyngeal-carcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":["camrelizumab","gemcitabine-cisplatin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["captain-1st"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2021,"doi":"10.1016/S1470-2045(21)00302-8","pmid":"34174189","authors":"Yang Y, Qu S, Li J, et al.","paperType":"rct","findings":["Median progression-free survival 9.7 months with camrelizumab plus chemotherapy versus 6.9 months with chemotherapy alone; hazard ratio 0.54."],"whatItMeans":"Together with JUPITER-02 and RATIONALE-309, this trial made PD-1 blockade plus gemcitabine-cisplatin the first-line standard for metastatic nasopharyngeal carcinoma.","caveats":["Conducted entirely in China.","Overall survival data were immature at publication."],"changedPractice":true,"participants":263},{"id":"paper-malouff-front-oncol","kind":"paper","name":"Carbon Ion Therapy: A Modern Review of an Emerging Technology","aka":[],"tldr":"Paper cited by two technology pages, indexed on Europe PMC as PubMed record 32117737 and published in Frontiers in oncology; the citing pages link this DOI, which is how the record was matched.","summary":"Radiation therapy is one of the most widely used therapies for malignancies. The therapeutic use of heavy ions, such as carbon, has gained significant interest due to advantageous physical and radiobiologic properties compared to photon based therapy. By taking advantage of these unique properties, carbon ion radiotherapy may allow dose escalation to tumors while reducing radiation dose to adjacent normal tissues. There are currently 13 centers treating with carbon ion radiotherapy, with many of these centers publishing promising safety and efficacy data from the first cohorts of patients treated. To date, carbon ion radiotherapy has been studied for almost every type of malignancy, including intracranial malignancies, head and neck malignancies, primary and metastatic lung cancers, tumors of the gastrointestinal tract, prostate and genitourinary cancers, sarcomas, cutaneous malignancies, breast cancer, gynecologic malignancies, and pediatric cancers. Additionally, carbon ion radiotherapy has been studied extensively in the setting of recurrent disease. We aim to provide a comprehensive review of the studies of each of these disease sites, with a focus on the current trials using carbon ion radiotherapy.\n\nIndexed on Europe PMC as PubMed record 32117737 (DOI 10.3389/fonc.2020.00082). Matched by DOI alone: two technology pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Front Oncol 2020","url":"https://doi.org/10.3389/fonc.2020.00082"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32117737/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32117737"}],"tags":["europepmc-ingest"],"related":["carbon-ion-synchrotrons","carbon-ion"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Frontiers in oncology","year":2020,"doi":"10.3389/fonc.2020.00082","pmid":"32117737","authors":"Malouff TD, Mahajan A, Krishnan S, et al.","paperType":"review","findings":[],"whatItMeans":"Two technology pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-calvert-j-clin-oncol","kind":"paper","name":"Carboplatin dosage: prospective evaluation of a simple formula based on renal function","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 2681557 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"A dosage formula has been derived from a retrospective analysis of carboplatin pharmacokinetics in 18 patients with pretreatment glomerular filtration rates (GFR) in the range of 33 to 136 mL/min. Carboplatin plasma clearance was linearly related to GFR (r = 0.85, P less than.00001) and rearrangements of the equation describing the correlation gave the dosage formula dose (mg) = target area under the free carboplatin plasma concentration versus time curve (AUC) x (1.2 x GFR + 20). In a prospective clinical and pharmacokinetic study the formula was used to determine the dose required to treat 31 patients (GFR range, 33 to 135 mL/min) with 40 courses of carboplatin. The target AUC was escalated from 3 to 8 mg carboplatin/mL/min. Over this AUC range the formula accurately predicted the observed AUC (observed/predicted ratio 1.24 +/- 0.11, r = 0.886) and using these additional data, the formula was refined. Dose (mg) = target AUC x (GFR + 25) is now the recommended formula. AUC values of 4 to 6 and 6 to 8 mg/mL. min gave rise to manageable hematological toxicity in previously treated and untreated patients, respectively, and hence target AUC values of 5 and 7 mg/mL min are recommended for single-agent carboplatin in these patient groups. Pharmacokinetic modeling demonstrated that the formula was reasonably accurate regardless of whether a one- or two-compartment model most accurately described carboplatin pharmacokinetics, assuming that body size did not influence nonrenal clearance. The validity of this assumption was demonstrated in 13 patients where no correlation between surface area and nonrenal clearance was found (r =.31, P =.30). Therefore, the formula provides a simple and consistent method of determining carboplatin dose in adults. Since the measure of carboplatin exposure in the formula is AUC, and not toxicity, it will not be influenced by previous or concurrent myelosuppressive therapy or supportive measures. The formula is therefore applicable to combination and high-dose studies as well as conventional single-agent therapy, although the target AUC for carboplatin will need to be redefined for combination chemotherapy.\n\nIndexed on Europe PMC as PubMed record 2681557 (DOI 10.1200/jco.1989.7.11.1748). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 1989","url":"https://doi.org/10.1200/jco.1989.7.11.1748"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/2681557/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/2681557"}],"tags":["europepmc-ingest"],"related":["pkpd-modelling"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":1989,"doi":"10.1200/jco.1989.7.11.1748","pmid":"2681557","authors":"Calvert AH, Newell DR, Gumbrell LA, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-tutt-nat-med","kind":"paper","name":"Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial","aka":[],"tldr":"Paper cited by one pairing page, indexed on Europe PMC as PubMed record 29713086 and published in Nature Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Germline mutations in BRCA1/2 predispose individuals to breast cancer (termed germline-mutated BRCA1/2 breast cancer, gBRCA-BC) by impairing homologous recombination (HR) and causing genomic instability. HR also repairs DNA lesions caused by platinum agents and PARP inhibitors. Triple-negative breast cancers (TNBCs) harbor subpopulations with BRCA1/2 mutations, hypothesized to be especially platinum-sensitive. Cancers in putative 'BRCAness' subgroups-tumors with BRCA1 methylation; low levels of BRCA1 mRNA (BRCA1 mRNA-low); or mutational signatures for HR deficiency and those with basal phenotypes-may also be sensitive to platinum. We assessed the efficacy of carboplatin and another mechanistically distinct therapy, docetaxel, in a phase 3 trial in subjects with unselected advanced TNBC. A prespecified protocol enabled biomarker-treatment interaction analyses in gBRCA-BC and BRCAness subgroups. The primary endpoint was objective response rate (ORR). In the unselected population (376 subjects; 188 carboplatin, 188 docetaxel), carboplatin was not more active than docetaxel (ORR, 31.4% versus 34.0%, respectively; P = 0.66). In contrast, in subjects with gBRCA-BC, carboplatin had double the ORR of docetaxel (68% versus 33%, respectively; biomarker, treatment interaction P = 0.01). Such benefit was not observed for subjects with BRCA1 methylation, BRCA1 mRNA-low tumors or a high score in a Myriad HRD assay. Significant interaction between treatment and the basal-like subtype was driven by high docetaxel response in the nonbasal subgroup. We conclude that patients with advanced TNBC benefit from characterization of BRCA1/2 mutations, but not BRCA1 methylation or Myriad HRD analyses, to inform choices on platinum-based chemotherapy. Additionally, gene expression analysis of basal-like cancers may also influence treatment selection.\n\nIndexed on Europe PMC as PubMed record 29713086 (DOI 10.1038/s41591-018-0009-7). Matched by DOI alone: one pairing page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Med 2018","url":"https://doi.org/10.1038/s41591-018-0009-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29713086/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29713086"}],"tags":["europepmc-ingest"],"related":["platinum-plus-hrd","brca-germline","hrd-positive"],"cancers":["tnbc","tnbc-metastatic"],"sections":[],"technologies":[],"targets":["brca"],"drugs":["carboplatin","mychoice-cdx"],"companies":[],"institutions":[],"pathways":[],"terms":["gbrca-mutation","hrd"],"trials":[],"people":["andrew-tutt"],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2018,"doi":"10.1038/s41591-018-0009-7","pmid":"29713086","authors":"Tutt A, Tovey H, Cheang MCU, et al.","paperType":"rct","findings":[],"whatItMeans":"One pairing page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-fader-trastuzumab-uterine-serous-jco-2018","kind":"paper","name":"Carboplatin-paclitaxel with or without trastuzumab in HER2-positive advanced or recurrent uterine serous carcinoma","aka":[],"tldr":"Adding trastuzumab to chemotherapy for HER2-positive uterine serous carcinoma, an aggressive endometrial cancer, lengthened progression-free survival by about four months and later showed a survival benefit, making HER2 testing routine in this subtype.","summary":"Randomised phase 2 trial of 61 women with HER2-positive (immunohistochemistry 3+ or amplified) advanced or recurrent uterine serous carcinoma treated with carboplatin-paclitaxel with or without trastuzumab continued as maintenance.\n\nMedian progression-free survival was 12.6 versus 8.0 months (hazard ratio 0.44), with the largest gain in newly diagnosed stage III to IV disease (17.9 versus 9.3 months); an update showed improved overall survival in that group.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2018","url":"https://doi.org/10.1200/JCO.2017.76.5966"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29584549/"}],"tags":[],"related":[],"cancers":["endometrial-p53-abnormal"],"sections":[],"technologies":[],"targets":[],"drugs":["carboplatin","trastuzumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["amanda-fader"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2018,"doi":"10.1200/JCO.2017.76.5966","pmid":"29584549","authors":"Fader AN, Roque DM, Siegel E, et al.","paperType":"rct","findings":["Median progression-free survival 12.6 vs 8.0 months; hazard ratio 0.44.","Stage III to IV newly diagnosed: 17.9 vs 9.3 months, with an overall survival benefit on update."],"whatItMeans":"HER2 testing of every serous endometrial cancer and trastuzumab with first-line chemotherapy for HER2-positive advanced disease are now guideline recommendations; trastuzumab deruxtecan extends the option.","caveats":["Small phase 2 trial.","About 30 percent of uterine serous carcinomas are HER2-positive; benefit in lower expression is unknown."],"changedPractice":true,"participants":61},{"id":"paper-bouvard-lancet-oncol","kind":"paper","name":"Carcinogenicity of consumption of red and processed meat","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 26514947 and published in The Lancet Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 26514947 (DOI 10.1016/s1470-2045(15)00444-1). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2015","url":"https://doi.org/10.1016/s1470-2045(15)00444-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26514947/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26514947"}],"tags":["europepmc-ingest"],"related":["red-processed-meat-reduction"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2015,"doi":"10.1016/s1470-2045(15)00444-1","pmid":"26514947","authors":"Bouvard V, Loomis D, Guyton KZ, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-loomis-lancet-oncol","kind":"paper","name":"Carcinogenicity of drinking coffee, mate, and very hot beverages","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 27318851 and published in The Lancet Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 27318851 (DOI 10.1016/s1470-2045(16)30239-x). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2016","url":"https://doi.org/10.1016/s1470-2045(16)30239-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27318851/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27318851"}],"tags":["europepmc-ingest"],"related":["coffee-intake-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2016,"doi":"10.1016/s1470-2045(16)30239-x","pmid":"27318851","authors":"Loomis D, Guyton KZ, Grosse Y, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-iarc-monographs-vol-124-group-lancet-oncol","kind":"paper","name":"Carcinogenicity of night shift work","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 31281097 and published in The Lancet Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 31281097 (DOI 10.1016/s1470-2045(19)30455-3). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2019","url":"https://doi.org/10.1016/s1470-2045(19)30455-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31281097/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31281097"}],"tags":["europepmc-ingest"],"related":["sleep-circadian-interventions"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2019,"doi":"10.1016/s1470-2045(19)30455-3","pmid":"31281097","authors":"IARC Monographs Vol 124 group","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nevin-gallbladder-carcinoma-staging-cancer-1976","kind":"paper","name":"Carcinoma of the gallbladder: staging, treatment, and prognosis","aka":[],"tldr":"The 1976 paper that first staged gallbladder cancer by how deeply it had grown through the wall, noting that almost every case had been found by chance during gallstone surgery.","summary":"Sixty-six cases from two Virginia hospitals were staged by depth of invasion and spread and graded histologically, and survival was correlated with both; results agreed with 399 reported cases in the literature that could be staged by depth of invasion. The authors describe a simple method combining staging and histological grade applicable to every surgically removed gallbladder cancer. Essentially all carcinomas in the series were incidental findings at surgery for gallstones, which the authors suggest explains a relatively high proportion of superficial carcinomas cured by cholecystectomy.","asOf":"2026-09-24","links":[{"label":"Cancer 1976","url":"https://doi.org/10.1002/1097-0142(197601)37:1<141::AID-CNCR2820370121>3.0.CO;2-Y"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/1247951/"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tnm-staging","incidental-gallbladder-cancer"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Cancer","year":1976,"doi":"10.1002/1097-0142(197601)37:1<141::AID-CNCR2820370121>3.0.CO;2-Y","pmid":"1247951","authors":"Nevin JE, Moran TJ, Kay S, King R.","paperType":"observational","findings":["Depth of invasion correlated with survival in 66 cases and 399 literature cases.","Essentially all cases were incidental findings at surgery for gallstones."],"whatItMeans":"Depth of invasion has been the organising principle of gallbladder cancer staging ever since, through the TNM editions to the 2017 T2a/T2b split; and the observation that most cases are incidental was already true fifty years ago.","caveats":["Small historical series.","Pre-TNM staging scheme, superseded."],"changedPractice":true,"participants":66},{"id":"paper-figo-annual-report-carcinoma-of-the-vagina-ijgo-2006","kind":"paper","name":"Carcinoma of the vagina: FIGO 26th Annual Report on the results of treatment in gynecological cancer","aka":[],"tldr":"The international registry report that gives stage-by-stage survival figures for vaginal cancer, a cancer so rare that no trial has ever been large enough to do so.","summary":"Chapter of the FIGO 26th Annual Report presenting the staging, treatment and survival of women with primary carcinoma of the vagina reported to the FIGO registry, by stage, histology and treatment modality.\n\nFive-year survival fell steeply with stage, from most women with stage I disease to a minority with stage IV, and radiotherapy was the mainstay of treatment across stages. The report is the reference for vaginal cancer prognosis by FIGO stage.","asOf":"2026-09-18","links":[{"label":"Int J Gynaecol Obstet 2006","url":"https://doi.org/10.1016/S0020-7292(06)60029-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29644658/"}],"tags":[],"related":[],"cancers":["vaginal-squamous-cell-carcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"International Journal of Gynecology & Obstetrics","year":2006,"doi":"10.1016/S0020-7292(06)60029-5","pmid":"29644658","authors":"Beller U, Benedet JL, Creasman WT, et al.","paperType":"observational","findings":["Five-year survival declined from stage I to stage IV, with radiotherapy the dominant treatment at every stage."],"whatItMeans":"Because primary vaginal cancer is too rare for randomised trials, staging and prognosis rest on registry reports like this one, and treatment is extrapolated from cervical cancer.","caveats":["Registry data from participating centres, with incomplete reporting of treatment details.","Predates modern chemoradiotherapy and image-guided brachytherapy."],"changedPractice":false},{"id":"paper-chen-nature-2016","kind":"paper","name":"Carcinoma-astrocyte gap junctions promote brain metastasis by cGAMP transfer","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 27225120 and published in Nature; the citing page links this DOI, which is how the record was matched.","summary":"Brain metastasis represents a substantial source of morbidity and mortality in various cancers, and is characterized by high resistance to chemotherapy. Here we define the role of the most abundant cell type in the brain, the astrocyte, in promoting brain metastasis. We show that human and mouse breast and lung cancer cells express protocadherin 7 (PCDH7), which promotes the assembly of carcinoma-astrocyte gap junctions composed of connexin 43 (Cx43). Once engaged with the astrocyte gap-junctional network, brain metastatic cancer cells use these channels to transfer the second messenger cGAMP to astrocytes, activating the STING pathway and production of inflammatory cytokines such as interferon-α (IFNα) and tumour necrosis factor (TNF). As paracrine signals, these factors activate the STAT1 and NF-κB pathways in brain metastatic cells, thereby supporting tumour growth and chemoresistance. The orally bioavailable modulators of gap junctions meclofenamate and tonabersat break this paracrine loop, and we provide proof-of-principle that these drugs could be used to treat established brain metastasis.\n\nIndexed on Europe PMC as PubMed record 27225120 (DOI 10.1038/nature18268). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2016","url":"https://doi.org/10.1038/nature18268"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27225120/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27225120"}],"tags":["europepmc-ingest"],"related":["blood-brain-barrier-metastasis"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2016,"doi":"10.1038/nature18268","pmid":"27225120","authors":"Chen Q, Boire A, Jin X, et al.","paperType":"observational","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-van-nimwegen-cardiovascular-disease-after-hodgkin-jama-intern-med-2015","kind":"paper","name":"Cardiovascular disease after Hodgkin lymphoma treatment: 40-year disease risk","aka":["van Nimwegen 2015","Dutch Hodgkin cardiovascular cohort"],"tldr":"Half of 2,524 people treated for Hodgkin lymphoma developed heart or valve disease within forty years, and the risk was still four to six times the general population's after thirty-five years.","summary":"The companion to the second-cancer cohort, from the same Dutch group. 2,524 patients diagnosed with Hodgkin lymphoma before the age of 51 (median 27.3 years) between 1965 and 1995, who survived at least five years, were followed through medical records and general practitioners, with cardiovascular events graded by the Common Terminology Criteria for Adverse Events version 4.0.\n\nAfter a median follow-up of 20 years, 1,713 cardiovascular events occurred in 797 patients. At 35 years or more, the standardised incidence ratio for coronary heart disease or heart failure was still four to six times the general population rate, corresponding to 857 excess events per 10,000 person-years. The 40-year cumulative incidence of cardiovascular disease within the cohort was 50 per cent (95 per cent confidence interval 47 to 52), and 51 per cent of those affected had more than one event. For patients treated before the age of 25, cumulative incidences at 60 years or older were 20 per cent for coronary heart disease, 31 per cent for valvular heart disease and 11 per cent for heart failure as first events.\n\nMediastinal radiotherapy raised the risk of coronary heart disease (hazard ratio 2.7, 2.0 to 3.7), valvular heart disease (6.6, 4.0 to 10.8) and heart failure (2.7, 1.6 to 4.8). Anthracycline-containing chemotherapy raised valvular heart disease (1.5, 1.1 to 2.1) and heart failure (3.0, 1.9 to 4.7). The joint effects of mediastinal radiotherapy, anthracyclines and smoking appeared additive, which is the finding a survivor can act on.","asOf":"2026-10-01","links":[{"label":"JAMA Internal Medicine 2015","url":"https://doi.org/10.1001/jamainternmed.2015.1180"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25915855/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25915855"}],"tags":["lymphoma-evidence"],"related":["paper-schaapveld-second-cancer-risk-40-years-hodgkin-nejm-2015","lymphoma-roadmap"],"cancers":["hodgkin-lymphoma","early-stage-classical-hodgkin-lymphoma","advanced-stage-classical-hodgkin-lymphoma"],"sections":["radiation","supportive-care"],"technologies":["radiotherapy","proton-therapy","imrt-igrt"],"targets":[],"drugs":["doxorubicin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["hd10","hd16","radar-hodgkin"],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol","b-aging-comorbidity"],"keyPapers":[],"journals":["jama-internal-medicine"],"dependsOn":[],"notes":[],"journal":"JAMA Internal Medicine","year":2015,"doi":"10.1001/jamainternmed.2015.1180","pmid":"25915855","authors":"van Nimwegen FA, Schaapveld M, Janus CP, et al.","paperType":"observational","findings":["1,713 cardiovascular events occurred in 797 of 2,524 Hodgkin lymphoma survivors after a median follow-up of 20 years.","At 35 years or more after treatment, the standardised incidence ratio for coronary heart disease or heart failure remained four to six times the general population rate, or 857 excess events per 10,000 person-years.","The 40-year cumulative incidence of cardiovascular disease within the cohort was 50 per cent (95 per cent confidence interval 47 to 52), and 51 per cent of affected patients had multiple events.","Mediastinal radiotherapy raised the hazard of coronary heart disease to 2.7, valvular heart disease to 6.6 and heart failure to 2.7.","Anthracycline-containing chemotherapy raised the hazard of valvular heart disease to 1.5 and heart failure to 3.0.","The joint effects of mediastinal radiotherapy, anthracyclines and smoking appeared additive."],"whatItMeans":"The reason cardiac surveillance belongs in Hodgkin lymphoma survivorship care, the reason smoking cessation is a specific intervention for this group rather than general advice, and part of the reason modern protocols try to limit both mediastinal radiation and cumulative anthracycline dose.","caveats":["Patients treated between 1965 and 1995 with radiotherapy fields far larger than those used today; absolute risks for people treated now should be lower, though by how much is unknown.","Observational, with the confounding by smoking and other cardiovascular risk factors that implies, although smoking was examined explicitly.","Event ascertainment relied on medical records and general practitioners, so milder events may be undercounted."],"changedPractice":true,"participants":2524},{"id":"paper-lenalidomide-multiple-myeloma-n-engl-j-med-2015","kind":"paper","name":"Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma","aka":[],"tldr":"Phase 2 or 3 results paper on Lenalidomide in Multiple myeloma, in New England Journal of Medicine (2015), one of the most cited Europe PMC records with Lenalidomide in its title.","summary":"Background: Lenalidomide plus dexamethasone is a reference treatment for relapsed multiple myeloma. The combination of the proteasome inhibitor carfilzomib with lenalidomide and dexamethasone has shown efficacy in a phase 1 and 2 study in relapsed multiple myeloma.\n\nMethods: We randomly assigned 792 patients with relapsed multiple myeloma to carfilzomib with lenalidomide and dexamethasone (carfilzomib group) or lenalidomide and dexamethasone alone (control group). The primary end point was progression-free survival.\n\nResults: Progression-free survival was significantly improved with carfilzomib (median, 26.3 months, vs. 17.6 months in the control group; hazard ratio for progression or death, 0.69; 95% confidence interval [CI], 0.57 to 0.83; P=0.0001). The median overall survival was not reached in either group at the interim analysis. The Kaplan-Meier 24-month overall survival rates were 73.3% and 65.0% in the carfilzomib and control groups, respectively (hazard ratio for death, 0.79; 95% CI, 0.63 to 0.99; P=0.04). The rates of overall response (partial response or better) were 87.1% and 66.7% in the carfilzomib and control groups, respectively (P<0.001; 31.8% and 9.3% of patients in the respective groups had a complete response or better; 14.1% and 4.3% had a stringent complete response). Adverse events of grade 3 or higher were reported in 83.7% and 80.7% of patients in the carfilzomib and control groups, respectively; 15.3% and 17.7% of patients discontinued treatment owing to adverse events. Patients in the carfilzomib group reported superior health-related quality of life.\n\nConclusions: In patients with relapsed multiple myeloma, the addition of carfilzomib to lenalidomide and dexamethasone resulted in significantly improved progression-free survival at the interim analysis and had a favorable risk-benefit profile. (Funded by Onyx Pharmaceuticals; ClinicalTrials.gov number, NCT01080391.).\n\nIndexed on Europe PMC as PubMed record 25482145 (DOI 10.1056/nejmoa1411321). Its title names Lenalidomide and its text names Multiple myeloma; PubMed types it as a clinical trial report (Research Support, Non-U.S. Gov't, Randomized Controlled Trial). It was matched automatically to the idea \"MRD-guided treatment-free intervals in myeloma\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2015","url":"https://doi.org/10.1056/nejmoa1411321"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25482145/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25482145"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2015,"doi":"10.1056/nejmoa1411321","pmid":"25482145","authors":"Stewart AK, Rajkumar SV, Dimopoulos MA, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Lenalidomide in Multiple myeloma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Lenalidomide in the title and Multiple myeloma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-cartitude-1-cilta-cel-lancet-2021","kind":"paper","name":"CARTITUDE-1: cilta-cel, a BCMA CAR-T, in heavily pretreated myeloma","aka":[],"tldr":"A single infusion of BCMA-directed CAR-T cells produced responses in 97% of patients whose myeloma had failed a median of six prior lines, with two-thirds reaching stringent complete response.","summary":"CARTITUDE-1 was a phase 1b/2 single-arm study of ciltacabtagene autoleucel (cilta-cel), a CAR-T with two BCMA-binding domains, in 97 patients with relapsed or refractory multiple myeloma exposed to a proteasome inhibitor, an immunomodulatory drug and an anti-CD38 antibody (median six prior lines, 88% triple-class refractory). The overall response rate was 97%, with stringent complete response in 67%; 12-month PFS was 77% and OS 89%. Cytokine release syndrome occurred in 95% (grade 3-4 in about 4%) and neurotoxicity in about 21%, including a small number of delayed movement and neurocognitive events. Long-term follow-up showed roughly a third of patients progression-free at five years without further therapy, unprecedented in this population.","asOf":"2026-09-08","links":[{"label":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=CARTITUDE-1%20ciltacabtagene%20autoleucel%20Berdeja%20Lancet%202021"},{"label":"ClinicalTrials.gov NCT03548207","url":"https://clinicaltrials.gov/study/NCT03548207"}],"tags":[],"related":["paper-cartitude-4-cilta-cel-nejm-2023"],"cancers":["multiple-myeloma"],"sections":[],"technologies":["car-t"],"targets":["bcma"],"drugs":["ciltacabtagene-autoleucel"],"companies":["legend-biotech","johnson-johnson"],"institutions":[],"pathways":[],"terms":["crs","icans","orr"],"trials":["cartitude-1"],"people":["saad-usmani"],"bottlenecks":["b-manufacturing-cell-therapy","b-toxicity-qol"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2021,"doi":"10.1016/S0140-6736(21)00933-8","pmid":"34175021","authors":"Berdeja JG, Madduri D, Usmani SZ, et al.","paperType":"translational","findings":["97 patients infused; median 6 prior lines; 88% triple-class refractory.","Overall response 97%; stringent complete response 67%; MRD-negativity in most evaluable responders.","12-month PFS 77%, OS 89%; median PFS about 35 months in later follow-up; about a third progression-free at 5 years.","CRS in 95% (grade 3-4 about 4%); ICANS 17%; delayed movement/neurocognitive syndrome in a minority.","Median time to CRS onset was 7 days, later than with CD19 CAR-Ts, enabling outpatient monitoring strategies."],"whatItMeans":"CARTITUDE-1 showed that a single CAR-T infusion can put late-stage myeloma into deep, multi-year remission, leading to FDA approval of cilta-cel in 2022 for heavily pretreated disease. It set the efficacy bar for BCMA-directed therapy and motivated moving CAR-T earlier (CARTITUDE-4). Late neurological toxicity and secondary malignancies remain the safety questions.","caveats":["Single-arm trial in fit, selected patients; no randomised comparator.","Manufacturing failures and bridging deaths are not captured in infused-patient analyses.","Delayed parkinsonism-like neurotoxicity and rare second primary malignancies (including T-cell lymphoma) emerged with follow-up.","Access limited by manufacturing slots and cost."],"changedPractice":true,"participants":97},{"id":"paper-cartitude-4-cilta-cel-nejm-2023","kind":"paper","name":"CARTITUDE-4: cilta-cel CAR-T versus standard combinations after one to three prior lines of myeloma therapy","aka":[],"tldr":"Moving BCMA CAR-T to the second line cut the risk of progression or death by 74% compared with standard triplets, and later improved overall survival.","summary":"CARTITUDE-4 randomised 419 patients with lenalidomide-refractory multiple myeloma after one to three prior lines to a single infusion of ciltacabtagene autoleucel (after bridging therapy) or standard of care (pomalidomide-bortezomib-dexamethasone or daratumumab-pomalidomide-dexamethasone). The primary endpoint was PFS by intention to treat. At 12 months PFS was 75.9% versus 48.6% (hazard ratio 0.26); overall response was 84.6% versus 67.3%, complete response or better 73.1% versus 21.8%, and MRD-negativity 60.6% versus 15.6%. In later follow-up overall survival was significantly better with cilta-cel (hazard ratio about 0.55). Toxicity was manageable, with lower CRS and neurotoxicity rates than in CARTITUDE-1.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa2303379"},{"label":"ClinicalTrials.gov NCT04181827","url":"https://clinicaltrials.gov/study/NCT04181827"}],"tags":[],"related":["paper-karmma-3-ide-cel-nejm-2023"],"cancers":["multiple-myeloma"],"sections":[],"technologies":["car-t"],"targets":["bcma"],"drugs":["ciltacabtagene-autoleucel","daratumumab","pomalidomide","bortezomib"],"companies":["legend-biotech","johnson-johnson"],"institutions":[],"pathways":[],"terms":["pfs","os","mrd-negativity-myeloma","crs"],"trials":["cartitude-4","cartitude-5"],"people":[],"bottlenecks":["b-manufacturing-cell-therapy","b-global-access"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/NEJMoa2303379","authors":"San-Miguel J, Dhakal B, Yong K, et al.","paperType":"rct","findings":["419 lenalidomide-refractory patients after 1-3 prior lines; cilta-cel vs PVd or DPd.","12-month PFS 75.9% vs 48.6%; hazard ratio 0.26 (intention-to-treat).","Complete response or better 73.1% vs 21.8%; MRD-negativity 60.6% vs 15.6%.","Overall survival significantly improved at second analysis (HR about 0.55).","CRS in 76% of infused patients (grade 3-4 about 1%); ICANS about 5%; cranial nerve palsy and movement disorders in a small minority."],"whatItMeans":"CARTITUDE-4 is the first randomised trial to show that a CAR-T improves survival in myeloma, and it moved cilta-cel into second-line use (FDA approval 2024). For patients whose disease returns after first-line lenalidomide, a one-off cell therapy now competes with continuous drug combinations. Capacity, cost and the need for bridging therapy still limit who actually receives it.","caveats":["Open-label; standard-of-care arm was a mix of two regimens, neither of which is the strongest available.","Intention-to-treat analysis includes patients who progressed during bridging; per-protocol PFS is even more favourable.","Only about 15% of standard-arm patients later received CAR-T, so the comparison is partly CAR-T now versus never.","Secondary haematological malignancies and late neurotoxicity remain concerns."],"changedPractice":true,"participants":419},{"id":"paper-cassiopeia-lancet-2019","kind":"paper","name":"CASSIOPEIA: daratumumab added to bortezomib, thalidomide and dexamethasone before and after transplant in newly diagnosed myeloma","aka":[],"tldr":"Adding the antibody daratumumab to a standard three-drug induction and consolidation around autologous transplant deepened responses and delayed progression in newly diagnosed myeloma, establishing four-drug induction.","summary":"Phase 3 trial of 1,085 transplant-eligible patients with newly diagnosed multiple myeloma randomised to bortezomib, thalidomide and dexamethasone with or without daratumumab for induction and consolidation around autologous stem cell transplant.\n\nStringent complete response after consolidation was 29 percent with daratumumab against 20 percent without, measurable residual disease negativity 64 versus 44 percent, and progression-free survival was improved (hazard ratio 0.47 at the first analysis).","asOf":"2026-09-17","links":[{"label":"Lancet 2019","url":"https://doi.org/10.1016/S0140-6736(19)31240-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31171419/"}],"tags":[],"related":[],"cancers":["myeloma-transplant-eligible"],"sections":[],"technologies":[],"targets":[],"drugs":["bortezomib","daratumumab","dexamethasone","thalidomide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["cassiopeia"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2019,"doi":"10.1016/S0140-6736(19)31240-1","pmid":"31171419","authors":"Moreau P, Attal M, Hulin C, et al.","paperType":"rct","findings":["Stringent complete response 29 percent vs 20 percent after consolidation.","Measurable residual disease negativity 64 percent vs 44 percent; 18-month progression-free survival 93 percent vs 85 percent."],"whatItMeans":"Quadruplet induction with a CD38 antibody became the standard for transplant-eligible patients in Europe. PERSEUS later did the same with the lenalidomide-based backbone used elsewhere.","caveats":["Thalidomide-based backbone is used less in the United States.","The second randomisation to daratumumab maintenance showed benefit mainly in those who had not received daratumumab induction."],"changedPractice":true,"participants":1085},{"id":"paper-catnon-lancet-2017","kind":"paper","name":"CATNON: concurrent and adjuvant temozolomide in anaplastic glioma without 1p/19q codeletion","aka":[],"tldr":"Twelve cycles of temozolomide after radiotherapy lengthened survival in grade 3 glioma without 1p/19q codeletion, while giving temozolomide during radiotherapy added nothing in these tumours.","summary":"Phase 3 factorial trial of 745 adults with newly diagnosed anaplastic glioma without 1p/19q codeletion randomised to radiotherapy alone, with concurrent temozolomide, with 12 cycles of adjuvant temozolomide, or with both.\n\nAdjuvant temozolomide improved overall survival (hazard ratio 0.65; five-year survival 55.9 versus 44.1 percent); concurrent temozolomide did not, and later analysis showed benefit was confined to IDH-mutant tumours.","asOf":"2026-09-17","links":[{"label":"Lancet 2017","url":"https://doi.org/10.1016/S0140-6736(17)31442-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28801186/"}],"tags":[],"related":[],"cancers":["idh-mutant-astrocytoma"],"sections":[],"technologies":[],"targets":[],"drugs":["temozolomide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["catnon"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2017,"doi":"10.1016/S0140-6736(17)31442-3","pmid":"28801186","authors":"van den Bent MJ, Baumert B, Erridge SC, et al.","paperType":"rct","findings":["Adjuvant temozolomide: five-year overall survival 55.9 percent vs 44.1 percent; hazard ratio 0.65.","Concurrent temozolomide: no significant benefit."],"whatItMeans":"Radiotherapy followed by a year of temozolomide is the standard for grade 3 IDH-mutant astrocytoma; concurrent temozolomide is not needed, and IDH-wild-type tumours behave and are treated like glioblastoma.","caveats":["Interim analysis; final results confirmed the pattern.","Applies to the pre-2021 category of anaplastic astrocytoma, now IDH-mutant astrocytoma grade 3."],"changedPractice":true,"participants":745},{"id":"paper-stylianopoulos-proc-natl-acad-sci-u-s-a","kind":"paper","name":"Causes, consequences, and remedies for growth-induced solid stress in murine and human tumors","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 22932871 and published in Proceedings of the National Academy of Sciences; the citing page links this DOI, which is how the record was matched.","summary":"The presence of growth-induced solid stresses in tumors has been suspected for some time, but these stresses were largely estimated using mathematical models. Solid stresses can deform the surrounding tissues and compress intratumoral lymphatic and blood vessels. Compression of lymphatic vessels elevates interstitial fluid pressure, whereas compression of blood vessels reduces blood flow. Reduced blood flow, in turn, leads to hypoxia, which promotes tumor progression, immunosuppression, inflammation, invasion, and metastasis and lowers the efficacy of chemo-, radio-, and immunotherapies. Thus, strategies designed to alleviate solid stress have the potential to improve cancer treatment. However, a lack of methods for measuring solid stress has hindered the development of solid stress-alleviating drugs. Here, we present a simple technique to estimate the growth-induced solid stress accumulated within animal and human tumors, and we show that this stress can be reduced by depleting cancer cells, fibroblasts, collagen, and/or hyaluronan, resulting in improved tumor perfusion. Furthermore, we show that therapeutic depletion of carcinoma-associated fibroblasts with an inhibitor of the sonic hedgehog pathway reduces solid stress, decompresses blood and lymphatic vessels, and increases perfusion. In addition to providing insights into the mechanopathology of tumors, our approach can serve as a rapid screen for stress-reducing and perfusion-enhancing drugs.\n\nIndexed on Europe PMC as PubMed record 22932871 (DOI 10.1073/pnas.1213353109). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Proc Natl Acad Sci U S A 2012","url":"https://doi.org/10.1073/pnas.1213353109"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22932871/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/22932871"}],"tags":["europepmc-ingest"],"related":["tumour-mechanics-models"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["pnas"],"dependsOn":[],"notes":[],"journal":"Proceedings of the National Academy of Sciences","year":2012,"doi":"10.1073/pnas.1213353109","pmid":"22932871","authors":"Stylianopoulos T, Martin JD, Chauhan VP, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-cd19-all-leukemia-j-clin-invest-2016","kind":"paper","name":"CD19 CAR-T cells of defined CD4+:CD8+ composition in adult B cell ALL patients","aka":[],"tldr":"Phase 2 or 3 results paper on CD19 in Acute lymphoblastic leukaemia, in Journal of Clinical Investigation (2016), one of the most cited Europe PMC records with CD19 in its title.","summary":"Background: T cells that have been modified to express a CD19-specific chimeric antigen receptor (CAR) have antitumor activity in B cell malignancies; however, identification of the factors that determine toxicity and efficacy of these T cells has been challenging in prior studies in which phenotypically heterogeneous CAR-T cell products were prepared from unselected T cells.\n\nMethods: We conducted a clinical trial to evaluate CD19 CAR-T cells that were manufactured from defined CD4+ and CD8+ T cell subsets and administered in a defined CD4+:CD8+ composition to adults with B cell acute lymphoblastic leukemia after lymphodepletion chemotherapy.\n\nResults: The defined composition product was remarkably potent, as 27 of 29 patients (93%) achieved BM remission, as determined by flow cytometry. We established that high CAR-T cell doses and tumor burden increase the risks of severe cytokine release syndrome and neurotoxicity. Moreover, we identified serum biomarkers that allow testing of early intervention strategies in patients at the highest risk of toxicity. Risk-stratified CAR-T cell dosing based on BM disease burden decreased toxicity. CD8+ T cell-mediated anti-CAR transgene product immune responses developed after CAR-T cell infusion in some patients, limited CAR-T cell persistence, and increased relapse risk. Addition of fludarabine to the lymphodepletion regimen improved CAR-T cell persistence and disease-free survival.\n\nConclusion: Immunotherapy with a CAR-T cell product of defined composition enabled identification of factors that correlated with CAR-T cell expansion, persistence, and toxicity and facilitated design of lymphodepletion and CAR-T cell dosing strategies that mitigated toxicity and improved disease-free survival.\n\nTrial registration: ClinicalTrials.gov NCT01865617.\n\nFunding: R01-CA136551; Life Science Development Fund; Juno Therapeutics; Bezos Family Foundation.\n\nIndexed on Europe PMC as PubMed record 27111235 (DOI 10.1172/jci85309). Its title names CD19 and its text names Acute lymphoblastic leukaemia; PubMed types it as a clinical trial report (Clinical Trial, Phase II, Research Support, Non-U.S. Gov't, research-article, Clinical Trial, Phase I, Research Support, N.I.H., Extramural). It was matched automatically to the idea \"Hospital-based CAR-T manufacturing at cost through a public network\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Invest 2016","url":"https://doi.org/10.1172/jci85309"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27111235/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27111235"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jci"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Investigation","year":2016,"doi":"10.1172/jci85309","pmid":"27111235","authors":"Turtle CJ, Hanafi LA, Berger C, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for CD19 in Acute lymphoblastic leukaemia, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by CD19 in the title and Acute lymphoblastic leukaemia in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-cd19-all-leukemia-blood-2015","kind":"paper","name":"CD19-targeted chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia","aka":[],"tldr":"Review on CD19 in Acute lymphoblastic leukaemia, in Blood (2015), one of the most cited Europe PMC records with CD19 in its title.","summary":"Relapsed and refractory acute lymphoblastic leukemia (ALL) remains difficult to treat, with minimal improvement in outcomes seen in more than 2 decades despite advances in upfront therapy and improved survival for de novo ALL. Adoptive transfer of T cells engineered to express a chimeric antigen receptor (CAR) has emerged as a powerful targeted immunotherapy, showing striking responses in highly refractory populations. Complete remission (CR) rates as high as 90% have been reported in children and adults with relapsed and refractory ALL treated with CAR-modified T cells targeting the B-cell-specific antigen CD19. Distinct CAR designs across several studies have produced similar promising CR rates, an encouraging finding. Even more encouraging are durable remissions observed in some patients without additional therapy. Duration of remission and CAR-modified T-cell persistence require further study and more mature follow-up, but emerging data suggest these factors may distinguish CAR designs. Supraphysiologic T-cell proliferation, a hallmark of this therapy, contributes to both efficacy and the most notable toxicity, cytokine release syndrome (CRS), posing a unique challenge for toxicity management. This review will discuss the current landscape of CD19 CAR clinical trials, CRS pathophysiology and management, and remaining challenges.\n\nIndexed on Europe PMC as PubMed record 25999455 (DOI 10.1182/blood-2014-12-580068). Its title names CD19 and its text names Acute lymphoblastic leukaemia; PubMed types it as a review (Research Support, Non-U.S. Gov't, review-article, Review, Research Support, N.I.H., Extramural). It was matched automatically to the idea \"Hospital-based CAR-T manufacturing at cost through a public network\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Blood 2015","url":"https://doi.org/10.1182/blood-2014-12-580068"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25999455/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25999455"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["blood"],"dependsOn":[],"notes":[],"journal":"Blood","year":2015,"doi":"10.1182/blood-2014-12-580068","pmid":"25999455","authors":"Maude SL, Teachey DT, Porter DL, et al.","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for CD19 in Acute lymphoblastic leukaemia, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by CD19 in the title and Acute lymphoblastic leukaemia in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-nct03381274-j-thorac-oncol-2023","kind":"paper","name":"CD73 Inhibitor Oleclumab Plus Osimertinib in Previously Treated Patients With Advanced T790M-Negative EGFR-Mutated NSCLC: A Brief Report","aka":[],"tldr":"Published report from the trial registered as NCT03381274, in Journal of Thoracic Oncology (2023), chosen as the most cited paper whose own text cites the registry id.","summary":"Introduction: CD73 is overexpressed in EGFR-mutated NSCLC and may promote immune evasion, suggesting potential for combining CD73 blockers with EGFR tyrosine kinase inhibitors (TKIs). This phase 1b-2 study (NCT03381274) evaluated the anti-CD73 antibody oleclumab plus the third-generation EGFR TKI osimertinib in advanced EGFR-mutated NSCLC.\n\nMethods: Patients had tissue T790M-negative NSCLC with TKI-sensitive EGFR mutations after progression on a first- or second-generation EGFR TKI and were osimertinib naive. They received osimertinib 80 mg orally once daily plus oleclumab 1500 mg (dose level 1 [DL1]) or 3000 mg (DL2) intravenously every 2 weeks. Primary end points included safety and objective response rate by Response Evaluation Criteria in Solid Tumors version 1.1.\n\nResults: By July 9, 2021, five patients received DL1 and 21 received DL2. Of these patients, 60.0% and 85.7% had any-grade treatment-related adverse events (TRAEs) and 20.0% and 14.3% had grade 3 TRAEs, respectively. No dose-limiting toxicities, serious TRAEs, or deaths occurred. Four patients were T790M positive on retrospective circulating tumor DNA (ctDNA) testing; three had objective partial responses. In patients who were T790M negative in tumor and ctDNA, objective response rate was 25.0% at DL1 and 11.8% at DL2 (all partial responses); response durations at DL2 were 14.8 and 16.6 months. In patients receiving DL2, excluding those who were T790M positive by ctDNA, median progression-free survival was 7.4 months, and median overall survival was 24.8 months. DL2 was the recommended phase 2 dose.\n\nConclusions: Oleclumab plus osimertinib was found to have moderate activity with acceptable tolerability in previously treated patients with advanced EGFR-mutated NSCLC.\n\nIndexed on Europe PMC as PubMed record 36641093 (DOI 10.1016/j.jtho.2022.12.021). Its abstract cites the registry id NCT03381274, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Thorac Oncol 2023","url":"https://doi.org/10.1016/j.jtho.2022.12.021"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36641093/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36641093"},{"label":"ClinicalTrials.gov NCT03381274","url":"https://clinicaltrials.gov/study/NCT03381274"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct03381274"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-thoracic-oncology"],"dependsOn":[],"notes":[],"journal":"Journal of Thoracic Oncology","year":2023,"doi":"10.1016/j.jtho.2022.12.021","pmid":"36641093","authors":"Kim DW, Kim SW, Camidge DR, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03381274 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-fernandez-cuesta-cd74-nrg1-fusion-lung-cancer-discov-2014","kind":"paper","name":"CD74-NRG1 fusions in lung adenocarcinoma","aka":[],"tldr":"Reading the active genes of 25 lung cancers from people who had never smoked turned up a fusion that does something unusual: instead of switching on a receptor directly, it hangs the receptor's own trigger on the outside of the cell.","summary":"A novel somatic gene fusion, CD74-NRG1, was discovered by transcriptome sequencing of 25 lung adenocarcinomas from never smokers. Screening 102 lung adenocarcinomas negative for known oncogenic alterations found four additional fusion-positive tumours, all of the invasive mucinous subtype. Mechanistically, CD74-NRG1 leads to extracellular expression of the EGF-like domain of NRG1 III-beta3, providing the ligand for ERBB2-ERBB3 receptor complexes. ERBB2 and ERBB3 expression was high in the index case, phospho-ERBB3 expression was specific to fusion-positive tumours, and ectopic expression of the fusion in lung cancer cells expressing both receptors activated ERBB3 and the PI3K-AKT pathway and increased colony formation in soft agar.","asOf":"2026-09-25","links":[{"label":"Fernandez-Cuesta et al., Cancer Discov 2014: CD74-NRG1 fusions in invasive mucinous lung adenocarcinoma","url":"https://doi.org/10.1158/2159-8290.CD-13-0633"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24469108/"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":["rna-seq"],"targets":["nrg1","her2"],"drugs":[],"companies":[],"institutions":[],"pathways":["rtk-activation","pi3k-akt-mtor"],"terms":["gene-fusion","driver-mutation"],"trials":[],"people":["roman-thomas"],"bottlenecks":[],"keyPapers":[],"journals":["cancer-discovery"],"dependsOn":[],"notes":[],"journal":"Cancer Discovery","year":2014,"doi":"10.1158/2159-8290.CD-13-0633","pmid":"24469108","authors":"Fernandez-Cuesta L, Plenker D, Osada H, et al.","paperType":"basic","findings":["CD74-NRG1 fusions discovered in never-smoker lung adenocarcinoma.","All additional cases were of the invasive mucinous subtype, a histology with no effective treatment.","The fusion supplies a ligand for HER2-HER3 dimers rather than activating a kinase directly.","Fusion-positive tumours show specific phospho-ERBB3 expression."],"whatItMeans":"It identified a driver in the one lung histology that had none, and it defined a mechanism, ligand presentation, that requires an antibody against the receptor pair rather than a kinase inhibitor.","caveats":["Very small numbers: one index case and four confirmations.","Requires RNA sequencing to detect, so prevalence from DNA panels is an undercount.","No approved therapy in this class at the time of publication."],"changedPractice":false},{"id":"paper-farwell-j-nucl-med","kind":"paper","name":"CD8-Targeted PET Imaging of Tumor-Infiltrating T Cells in Patients with Cancer: A Phase I First-in-Humans Study of 89 Zr-Df-IAB22M2C, a Radiolabeled Anti-CD8 Minibody","aka":[],"tldr":"Paper cited by one idea page, indexed on Europe PMC as PubMed record 34413145 and published in Journal of Nuclear Medicine; the citing page links this DOI, which is how the record was matched.","summary":"There is a need for in vivo diagnostic imaging probes that can noninvasively measure tumor-infiltrating CD8+ leukocytes. Such imaging probes could be used to predict early response to cancer immunotherapy, help select effective single or combination immunotherapies, and facilitate the development of new immunotherapies or immunotherapy combinations. This study was designed to optimize conditions for performing CD8 PET imaging with 89 Zr-Df-IAB22M2C and determine whether CD8 PET imaging could provide a safe and effective noninvasive method of visualizing the whole-body biodistribution of CD8+ leukocytes. Methods: We conducted a phase 1 first-in-humans PET imaging study using an anti-CD8 radiolabeled minibody, 89 Zr-Df-IAB22M2C, to detect whole-body and tumor CD8+ leukocyte distribution in patients with metastatic solid tumors. Patients received 111 MBq of 89 Zr-Df-IAB22M2C followed by serial PET scanning over 5-7 d. A 2-stage design included a dose-escalation phase and a dose-expansion phase. Biodistribution, radiation dosimetry, and semiquantitative evaluation of 89 Zr-Df-IAB22M2C uptake were performed in all patients. Results: Fifteen subjects with metastatic melanoma, non-small cell lung cancer, and hepatocellular carcinoma were enrolled. No drug-related adverse events or abnormal laboratory results were noted except for a transient increase in antidrug antibodies in 1 subject. 89 Zr-Df-IAB22M2C accumulated in tumors and CD8-rich tissues (e.g., spleen, bone marrow, nodes), with maximum uptake at 24-48 h after injection and low background activity in CD8-poor tissues (e.g., muscle and lung). Radiotracer uptake in tumors was noted in 10 of 15 subjects, including 7 of 8 subjects on immunotherapy, 1 of 2 subjects on targeted therapy, and 2 of 5 treatment-naïve subjects. In 3 patients with advanced melanoma or hepatocellular carcinoma on immunotherapy, posttreatment CD8 PET/CT scans demonstrated increased 89 Zr-Df-IAB22M2C uptake in tumor lesions, which correlated with response. Conclusion: CD8 PET imaging with 89 Zr-Df-IAB22M2C is safe and has the potential to visualize the whole-body biodistribution of CD8+ leukocytes in tumors and reference tissues, and may predict early response to immunotherapy.\n\nIndexed on Europe PMC as PubMed record 34413145 (DOI 10.2967/jnumed.121.262485). Matched by DOI alone: one idea page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Nucl Med 2022","url":"https://doi.org/10.2967/jnumed.121.262485"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34413145/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34413145"}],"tags":["europepmc-ingest"],"related":["idea-cd8-pet-io"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-nuclear-medicine"],"dependsOn":[],"notes":[],"journal":"Journal of Nuclear Medicine","year":2022,"doi":"10.2967/jnumed.121.262485","pmid":"34413145","authors":"Farwell MD, Gamache RF, Babazada H, et al.","paperType":"observational","findings":[],"whatItMeans":"One idea page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-malumbres-nat-rev-cancer","kind":"paper","name":"Cell cycle, CDKs and cancer: a changing paradigm","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 19238148 and published in Nature Reviews Cancer; the citing page links this DOI, which is how the record was matched.","summary":"Tumour-associated cell cycle defects are often mediated by alterations in cyclin-dependent kinase (CDK) activity. Misregulated CDKs induce unscheduled proliferation as well as genomic and chromosomal instability. According to current models, mammalian CDKs are essential for driving each cell cycle phase, so therapeutic strategies that block CDK activity are unlikely to selectively target tumour cells. However, recent genetic evidence has revealed that, whereas CDK1 is required for the cell cycle, interphase CDKs are only essential for proliferation of specialized cells. Emerging evidence suggests that tumour cells may also require specific interphase CDKs for proliferation. Thus, selective CDK inhibition may provide therapeutic benefit against certain human neoplasias.\n\nIndexed on Europe PMC as PubMed record 19238148 (DOI 10.1038/nrc2602). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Cancer 2009","url":"https://doi.org/10.1038/nrc2602"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19238148/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/19238148"}],"tags":["europepmc-ingest"],"related":["cell-cycle-engine-cdks"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Cancer","year":2009,"doi":"10.1038/nrc2602","pmid":"19238148","authors":"Malumbres M, Barbacid M","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-cella-fact-g-jco-1993","kind":"paper","name":"Cella 1993: the Functional Assessment of Cancer Therapy (FACT-G) quality of life scale","aka":[],"tldr":"The other widely used cancer quality of life questionnaire, developed in the United States alongside the EORTC QLQ-C30, covering physical, social and family, emotional and functional wellbeing and extended by cancer-specific modules.","summary":"Cella and colleagues developed and validated the Functional Assessment of Cancer Therapy general scale (FACT-G), a self-administered questionnaire for patients receiving cancer treatment, through item generation with patients and clinicians, item reduction and testing in patients with a range of cancers. The scale covers physical wellbeing, social and family wellbeing, emotional wellbeing and functional wellbeing, showed good reliability and validity, distinguished patients by performance status and stage, and was sensitive to change over time. Disease-, treatment- and symptom-specific subscales were built on top of the core.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1200/JCO.1993.11.3.570"},{"label":"FACIT measurement system","url":"https://www.facit.org/"}],"tags":[],"related":["paper-aaronson-eortc-qlq-c30-jnci-1993"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["northwestern-lurie"],"pathways":[],"terms":["quality-of-life","qol-pro"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":1993,"doi":"10.1200/JCO.1993.11.3.570","authors":"Cella DF, Tulsky DS, Gray G, et al.","paperType":"methods","findings":["A brief, self-administered general quality of life measure for patients on cancer treatment, with physical, social and family, emotional and functional wellbeing domains.","Demonstrated internal consistency, test-retest reliability and validity against performance status and stage.","Designed as a core to which cancer-specific subscales are added, now the FACIT measurement system."],"whatItMeans":"FACT-G and the EORTC QLQ-C30 are the two instruments behind most patient-reported quality of life results in cancer trials and regulatory submissions. Knowing which was used matters when comparing quality of life claims between trials.","caveats":["Developed and validated mainly in US patients.","Quality of life data in trials are often incomplete because the sickest patients stop completing questionnaires."],"changedPractice":true},{"id":"paper-demaria-cancer-discov","kind":"paper","name":"Cellular Senescence Promotes Adverse Effects of Chemotherapy and Cancer Relapse","aka":[],"tldr":"Paper cited by one idea page, indexed on Europe PMC as PubMed record 27979832 and published in Cancer Discovery; the citing page links this DOI, which is how the record was matched.","summary":"Cellular senescence suppresses cancer by irreversibly arresting cell proliferation. Senescent cells acquire a proinflammatory senescence-associated secretory phenotype. Many genotoxic chemotherapies target proliferating cells nonspecifically, often with adverse reactions. In accord with prior work, we show that several chemotherapeutic drugs induce senescence of primary murine and human cells. Using a transgenic mouse that permits tracking and eliminating senescent cells, we show that therapy-induced senescent (TIS) cells persist and contribute to local and systemic inflammation. Eliminating TIS cells reduced several short- and long-term effects of the drugs, including bone marrow suppression, cardiac dysfunction, cancer recurrence, and physical activity and strength. Consistent with our findings in mice, the risk of chemotherapy-induced fatigue was significantly greater in humans with increased expression of a senescence marker in T cells prior to chemotherapy. These findings suggest that senescent cells can cause certain chemotherapy side effects, providing a new target to reduce the toxicity of anticancer treatments.\n\nSignificance: Many genotoxic chemotherapies have debilitating side effects and also induce cellular senescence in normal tissues. The senescent cells remain chronically present where they can promote local and systemic inflammation that causes or exacerbates many side effects of the chemotherapy. Cancer Discov; 7(2); 165-76. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 115.\n\nIndexed on Europe PMC as PubMed record 27979832 (DOI 10.1158/2159-8290.cd-16-0241). Matched by DOI alone: one idea page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer Discov 2017","url":"https://doi.org/10.1158/2159-8290.cd-16-0241"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27979832/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27979832"}],"tags":["europepmc-ingest"],"related":["idea-senolytics-after-chemo"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-discovery"],"dependsOn":[],"notes":[],"journal":"Cancer Discovery","year":2017,"doi":"10.1158/2159-8290.cd-16-0241","pmid":"27979832","authors":"Demaria M, O'Leary MN, Chang J, et al.","paperType":"basic","findings":[],"whatItMeans":"One idea page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-cemiplimab-bcc-stratigos-lancet-oncol-2021","kind":"paper","name":"Cemiplimab in locally advanced basal cell carcinoma after hedgehog inhibitor therapy","aka":[],"tldr":"In patients whose locally advanced basal cell carcinoma had progressed on or could not tolerate a hedgehog inhibitor, cemiplimab shrank tumours in about three in ten, giving a second-line option where none existed.","summary":"Phase 2 study of 84 patients with locally advanced basal cell carcinoma after progression on or intolerance of hedgehog pathway inhibitors treated with cemiplimab.\n\nObjective response was 31 percent (6 percent complete), with an estimated 85 percent of responses lasting at least a year and toxicity typical of PD-1 blockade; the metastatic cohort responded in about a fifth.","asOf":"2026-09-17","links":[{"label":"Lancet Oncol 2021","url":"https://doi.org/10.1016/S1470-2045(21)00126-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34000246/"}],"tags":[],"related":[],"cancers":["locally-advanced-bcc"],"sections":[],"technologies":[],"targets":[],"drugs":["cemiplimab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["alexander-stratigos"],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2021,"doi":"10.1016/S1470-2045(21)00126-1","pmid":"34000246","authors":"Stratigos AJ, Sekulic A, Peris K, et al.","paperType":"observational","findings":["Objective response 31 percent; complete response 6 percent.","Estimated duration of response of at least 12 months in 85 percent of responders."],"whatItMeans":"Cemiplimab is approved for advanced basal cell carcinoma after hedgehog inhibitor therapy, adding immunotherapy to the pathway for this common but rarely advanced skin cancer.","caveats":["Single-arm; responses can take many months to become apparent."],"changedPractice":true,"participants":84},{"id":"paper-empower-cscc-1-lancet-oncol-2020","kind":"paper","name":"Cemiplimab in locally advanced cutaneous squamous cell carcinoma: results from an open-label, phase 2, single-arm trial","aka":[],"tldr":"Published report from the EMPOWER-CSCC-1 trial registered as NCT02760498, in The Lancet Oncology (2020), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Cemiplimab has shown substantial antitumour activity in patients with metastatic cutaneous squamous cell carcinoma. Patients with locally advanced cutaneous squamous cell carcinoma have poor prognosis with conventional systemic therapy. We present a primary analysis of the safety and antitumour activity of cemiplimab in patients with locally advanced cutaneous squamous cell carcinoma.\n\nMethods: This pivotal open-label, phase 2, single-arm trial was done across 25 outpatient clinics, primarily at academic medical centres, in Australia, Germany, and the USA. Eligible patients (aged ≥18 years with histologically confirmed locally advanced cutaneous squamous cell carcinoma and an Eastern Cooperative Oncology Group performance status of 0-1) received cemiplimab 3 mg/kg intravenously over 30 min every 2 weeks for up to 96 weeks. Tumour measurements were done every 8 weeks. The primary endpoint was objective response, defined as the proportion of patients with complete or partial response, according to independent central review as per Response Evaluation Criteria in Solid Tumors version 1.1 for radiological scans and WHO criteria for medical photography. Data cutoff was Oct 10, 2018, when the fully enrolled cohort reached the prespecified timepoint for the primary analysis. Analyses were done as per the intention-to-treat principle. The safety analysis comprised all patients who received at least one dose of cemiplimab. This study is registered with ClinicalTrials.gov, number NCT02760498.\n\nFindings: Between June 14, 2016, and April 25, 2018, 78 patients were enrolled and treated with cemiplimab. The median duration of study follow-up was 9·3 months (IQR 5·1-15·7) at the time of data cutoff. An objective response was observed in 34 (44%; 95% CI 32-55) of 78 patients. The best overall response was ten (13%) patients with a complete response and 24 (31%) with a partial response. Grade 3-4 treatment-emergent adverse events occurred in 34 (44%) of 78 patients; the most common were hypertension in six (8%) patients and pneumonia in four (5%). Serious treatment-emergent adverse events occurred in 23 (29%) of 78 patients. One treatment-related death was reported that occurred after onset of aspiration pneumonia.\n\nInterpretation: Cemiplimab showed antitumour activity and an acceptable safety profile in patients with locally advanced cutaneous squamous cell carcinoma for whom there was no widely accepted standard of care.\n\nFunding: Regeneron Pharmaceuticals and Sanofi.\n\nIndexed on Europe PMC as PubMed record 31952975 (DOI 10.1016/s1470-2045(19)30728-4). Its abstract cites the registry id NCT02760498, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2020","url":"https://doi.org/10.1016/s1470-2045(19)30728-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31952975/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31952975"},{"label":"ClinicalTrials.gov NCT02760498","url":"https://clinicaltrials.gov/study/NCT02760498"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["empower-cscc-1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2020,"doi":"10.1016/s1470-2045(19)30728-4","pmid":"31952975","authors":"Migden MR, Khushalani NI, Chang ALS, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02760498 with the most citations, so it is the natural first reading for anyone following the EMPOWER-CSCC-1 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-empower-lung-1-lancet-2021","kind":"paper","name":"Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial","aka":[],"tldr":"Published report from the EMPOWER-Lung 1 trial registered as NCT03088540, in The Lancet (2021), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: We aimed to examine cemiplimab, a programmed cell death 1 inhibitor, in the first-line treatment of advanced non-small-cell lung cancer with programmed cell death ligand 1 (PD-L1) of at least 50%.\n\nMethods: In EMPOWER-Lung 1, a multicentre, open-label, global, phase 3 study, eligible patients recruited in 138 clinics from 24 countries (aged ≥18 years with histologically or cytologically confirmed advanced non-small-cell lung cancer, an Eastern Cooperative Oncology Group performance status of 0-1; never-smokers were ineligible) were randomly assigned (1:1) to cemiplimab 350 mg every 3 weeks or platinum-doublet chemotherapy. Crossover from chemotherapy to cemiplimab was allowed following disease progression. Primary endpoints were overall survival and progression-free survival per masked independent review committee. Primary endpoints were assessed in the intention-to-treat population and in a prespecified PD-L1 of at least 50% population (per US Food and Drug Administration request to the sponsor), which consisted of patients with PD-L1 of at least 50% per 22C3 assay done according to instructions for use. Adverse events were assessed in all patients who received at least one dose of the assigned treatment. This study is registered with ClinicalTrials.gov, NCT03088540 and is ongoing.\n\nFindings: Between June 27, 2017 and Feb 27, 2020, 710 patients were randomly assigned (intention-to-treat population). In the PD-L1 of at least 50% population, which consisted of 563 patients, median overall survival was not reached (95% CI 17·9-not evaluable) with cemiplimab (n=283) versus 14·2 months (11·2-17·5) with chemotherapy (n=280; hazard ratio [HR] 0·57 [0·42-0·77]; p=0·0002). Median progression-free survival was 8·2 months (6·1-8·8) with cemiplimab versus 5·7 months (4·5-6·2) with chemotherapy (HR 0·54 [0·43-0·68]; p<0·0001). Significant improvements in overall survival and progression-free survival were also observed with cemiplimab in the intention-to-treat population despite a high crossover rate (74%). Grade 3-4 treatment-emergent adverse events occurred in 98 (28%) of 355 patients treated with cemiplimab and 135 (39%) of 342 patients treated with chemotherapy.\n\nInterpretation: Cemiplimab monotherapy significantly improved overall survival and progression-free survival compared with chemotherapy in patients with advanced non-small-cell lung cancer with PD-L1 of at least 50%, providing a potential new treatment option for this patient population.\n\nFunding: Regeneron Pharmaceuticals and Sanofi.\n\nIndexed on Europe PMC as PubMed record 33581821 (DOI 10.1016/s0140-6736(21)00228-2). Its abstract cites the registry id NCT03088540, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet 2021","url":"https://doi.org/10.1016/s0140-6736(21)00228-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33581821/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33581821"},{"label":"ClinicalTrials.gov NCT03088540","url":"https://clinicaltrials.gov/study/NCT03088540"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["empower-lung-1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2021,"doi":"10.1016/s0140-6736(21)00228-2","pmid":"33581821","authors":"Sezer A, Kilickap S, Gümüş M, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03088540 with the most citations, so it is the natural first reading for anyone following the EMPOWER-Lung 1 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-cepheus-dara-vrd-natmed-2025","kind":"paper","name":"CEPHEUS: daratumumab quadruplet for newly diagnosed myeloma patients not having a transplant, with MRD-negativity as the main endpoint","aka":[],"tldr":"In patients who were transplant-ineligible or deferred transplant, the daratumumab quadruplet raised deep-remission rates from about 39% to 61% and cut progression risk by 43%.","summary":"CEPHEUS randomised 395 patients with newly diagnosed multiple myeloma who were transplant-ineligible or for whom transplant was deferred to daratumumab plus bortezomib, lenalidomide and dexamethasone (D-VRd) or VRd. Unusually, the primary endpoint was the overall MRD-negativity rate at 10^-5 sensitivity, reflecting the FDA advisory committee's 2024 acceptance of MRD as an endpoint supporting accelerated approval. MRD-negativity was 60.9% versus 39.4%, complete response or better 81.2% versus 61.6%, and PFS favoured D-VRd (hazard ratio 0.57). Toxicity was in line with other daratumumab quadruplets.","asOf":"2026-09-08","links":[{"label":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=CEPHEUS%20daratumumab%20bortezomib%20lenalidomide%20transplant-ineligible%20Usmani%20Nature%20Medicine%202025"},{"label":"ClinicalTrials.gov NCT03652064","url":"https://clinicaltrials.gov/study/NCT03652064"}],"tags":[],"related":["paper-maia-daratumumab-rd-nejm-2019"],"cancers":["multiple-myeloma"],"sections":[],"technologies":["mrd-testing"],"targets":["cd38"],"drugs":["daratumumab","bortezomib","lenalidomide"],"companies":["johnson-johnson"],"institutions":[],"pathways":[],"terms":["mrd-negativity-myeloma","pfs"],"trials":["cepheus","imroz"],"people":["saad-usmani"],"bottlenecks":["b-trial-design","b-dormancy-mrd"],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2025,"doi":"10.1038/s41591-024-03485-7","pmid":"39910273","authors":"Usmani SZ, Facon T, Hungria V, et al.","paperType":"rct","findings":["395 transplant-ineligible or transplant-deferred patients; D-VRd vs VRd.","Primary endpoint, overall MRD-negativity at 10^-5: 60.9% vs 39.4%.","Complete response or better 81.2% vs 61.6%.","PFS hazard ratio 0.57 in favour of D-VRd.","Infection and cytopenia rates were higher with the quadruplet, consistent with PERSEUS."],"whatItMeans":"CEPHEUS extends the quadruplet standard to patients who are not going to transplant, closing the gap between transplant-eligible and ineligible populations. It is also one of the first phase 3 trials to be designed around MRD-negativity as the primary endpoint, which could shorten future myeloma trials by years. Frailer patients still need dose-adapted approaches.","caveats":["MRD-negativity is a surrogate; PFS and OS benefits need longer follow-up to confirm.","Included relatively fit transplant-deferred patients as well as truly ineligible ones.","Bortezomib-based induction is not ideal for very frail patients; the parallel IMROZ trial used a different quadruplet.","Cross-trial comparison with MAIA is indirect."],"changedPractice":true,"participants":395},{"id":"paper-cercek-dostarlimab-rectal-nejm-2022","kind":"paper","name":"Cercek 2022: six months of dostarlimab alone made rectal cancer disappear in every patient with mismatch-repair deficiency","aka":[],"tldr":"All 12 patients with locally advanced dMMR rectal cancer had a complete clinical response to a PD-1 antibody alone, avoiding chemotherapy, radiotherapy and surgery.","summary":"This single-centre phase 2 study at Memorial Sloan Kettering treated patients with stage II or III mismatch-repair-deficient rectal adenocarcinoma with dostarlimab 500 mg every three weeks for six months, with the plan to proceed to chemoradiotherapy and surgery only if disease persisted. In the first 12 patients who completed treatment and had at least six months of follow-up, all had a clinical complete response on MRI, endoscopy, digital examination and biopsy, and none required chemoradiotherapy or surgery; no grade 3 or higher adverse events occurred. The follow-up report (NEJM 2025) extended the approach to more than 100 patients with dMMR cancers of several organs, with rectal cancer patients continuing to show near-universal complete responses and most avoiding surgery at two years.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa2201445"},{"label":"ClinicalTrials.gov NCT04165772","url":"https://clinicaltrials.gov/study/NCT04165772"}],"tags":[],"related":["paper-niche-2-nejm-2024","paper-le-mmr-deficiency-pd1-nejm-2015","msi-high","dmmr-ihc","colorectal-roadmap","paper-cercek-nonoperative-management-mismatch-repair-deficient-tumours-nejm-2025"],"cancers":["colorectal"],"sections":[],"technologies":["checkpoint-inhibitor","msi-mmr-testing","mri"],"targets":["pd1","mmr"],"drugs":["dostarlimab","pembrolizumab"],"companies":["gsk"],"institutions":["mskcc"],"pathways":["mismatch-repair-msi","pd1-checkpoint"],"terms":["msi","pcr","neoadjuvant-adjuvant","breakthrough-designation"],"trials":[],"people":["andrea-cercek","luis-diaz"],"bottlenecks":["b-surgery-radiation-innovation","b-toxicity-qol","b-immunotherapy-response"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/NEJMoa2201445","authors":"Cercek A, Lumish M, Sinopoli J, et al.","paperType":"translational","findings":["12 patients with stage II-III dMMR rectal adenocarcinoma; dostarlimab 500 mg every 3 weeks for 6 months.","Clinical complete response in 12 of 12 (100%) at 6 months or more of follow-up.","No patient needed chemoradiotherapy or surgery; no recurrence at 6-25 months follow-up in the initial report.","No grade 3 or higher adverse events.","Larger follow-up (2025): sustained complete responses in the great majority of dMMR rectal cancer patients, and high rates of organ preservation across other dMMR tumour types."],"whatItMeans":"Cercek's dostarlimab study is the clearest demonstration that immunotherapy can replace surgery in a solid tumour: patients with dMMR rectal cancer can keep their rectum and avoid the permanent effects of pelvic radiotherapy and surgery. Non-operative management after PD-1 blockade is now in guidelines for this group, and MMR testing before treatment of rectal cancer is essential. The approach applies only to the 5-10% of rectal cancers that are dMMR.","caveats":["Small, single-centre, single-arm study; the 2022 report had only 12 patients and short follow-up.","Clinical complete response requires expert surveillance with MRI and endoscopy; salvage surgery must remain available.","Applies only to dMMR disease, a minority of rectal cancers.","Long-term durability beyond five years and late relapse risk are not yet known."],"changedPractice":true,"participants":12},{"id":"paper-tamrakar-cancer","kind":"paper","name":"Cervical cancer elimination in India: Repurposing diagnostics, vaccination, and accelerating policy for the 2030 target","aka":[],"tldr":"Paper cited by one treatment page, indexed on Europe PMC as PubMed record 41645272 and published in Cancer; the citing page links this DOI, which is how the record was matched.","summary":"Cervical cancer remains one of the most significant yet preventable causes of cancer-related mortality among women in India. Current estimates indicate that the country reports approximately 127,000 new cases and nearly 80,000 deaths annually, accounting for about one fifth of the global burden. Despite advances in vaccination, screening, and molecular diagnostics, coverage remains critically low: fewer than 2% of women undergo screening, and less than 1% have received a human papillomavirus (HPV) vaccine. The introduction of the indigenous quadrivalent vaccine Cervavac in 2023 has provided renewed momentum; however, limitations in infrastructure, public awareness, and stratic barrier to implementation continue to hinder progress toward achieving the World Health Organization's 2030 elimination targets. This opinion article highlights the epidemiological landscape, diagnostic and programmatic barriers, and emphasis to repurpose India's vast coronavirus disease-era reverse transcriptase-polymerase chain reaction network for HPV molecular testing. Integrating HPV vaccination into the Universal Immunization Program and incorporating the HPV Nucleic Acid Amplification Test (NAAT) into the National Essential Diagnostics List (NEDL) are critical steps for accelerating India's pathway to cervical cancer elimination by 2030.\n\nIndexed on Europe PMC as PubMed record 41645272 (DOI 10.1002/cncr.70292). Matched by DOI alone: one treatment page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer 2026","url":"https://doi.org/10.1002/cncr.70292"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41645272/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41645272"}],"tags":["europepmc-ingest"],"related":["cervavac"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-wiley"],"dependsOn":[],"notes":[],"journal":"Cancer","year":2026,"doi":"10.1002/cncr.70292","pmid":"41645272","authors":"Tamrakar VK, Sharma K, Singh P, et al.","paperType":"observational","findings":[],"whatItMeans":"One treatment page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-van-cutsem-crystal-cetuximab-folfiri-nejm-2009","kind":"paper","name":"Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer (CRYSTAL)","aka":[],"tldr":"The trial that added an EGFR antibody to first-line chemotherapy and, in the same paper, showed the benefit belongs only to patients whose KRAS gene is normal. It is the first negative predictive biomarker in bowel cancer.","summary":"Van Cutsem, Köhne, Hitre and colleagues randomly assigned patients with EGFR-positive colorectal cancer and unresectable metastases to FOLFIRI alone or with cetuximab, with progression-free survival as the primary end point, and sought associations between tumour KRAS mutation status and response. A total of 599 patients received cetuximab plus FOLFIRI and 599 received FOLFIRI alone.\n\nGrade 3 or 4 skin reactions occurred in 19.7 percent of the cetuximab group against 0.2 percent, infusion-related reactions in 2.5 against 0 percent and diarrhoea in 15.7 against 10.5 percent.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2009","url":"https://doi.org/10.1056/NEJMoa0805019"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19339720/"}],"tags":["colorectal-evidence"],"related":["paper-kras-colorectal-j-clin-oncol-2011","paper-kras-colorectal-j-clin-oncol-2008","paper-douillard-prime-panitumumab-ras-nejm-2013"],"cancers":["colorectal"],"sections":["targeted-therapy"],"technologies":["monoclonal-antibody"],"targets":["egfr","kras"],"drugs":["cetuximab","folfiri","irinotecan","fluorouracil"],"companies":[],"institutions":[],"pathways":["ras-mapk"],"terms":["sidedness"],"trials":["crystal-fire3"],"people":["eric-van-cutsem"],"bottlenecks":["b-biomarker-validation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2009,"doi":"10.1056/NEJMoa0805019","pmid":"19339720","authors":"Van Cutsem E, Köhne CH, Hitre E, et al.","paperType":"rct","findings":["Progression-free survival hazard ratio 0.85 (95 percent CI 0.72 to 0.99, p=0.048) overall.","No significant difference in overall survival overall (hazard ratio 0.93, 0.81 to 1.07, p=0.31).","Significant interaction between treatment and KRAS status for tumour response (p=0.03) but not for progression-free survival (p=0.07) or overall survival (p=0.44).","In KRAS wild-type tumours, progression-free survival hazard ratio 0.68 (0.50 to 0.94) in favour of cetuximab."],"whatItMeans":"Biomarker-directed treatment in colorectal cancer starts here: RAS testing became mandatory before an EGFR antibody, and the corpus's updated CRYSTAL analysis (paper-kras-colorectal-j-clin-oncol-2011) carries the mature survival figures in the wild-type group.","caveats":["The overall trial was positive only for progression-free survival, and narrowly; the important result is the subgroup defined by a biomarker tested retrospectively.","Only exon 2 KRAS was tested; the extended RAS analysis in PRIME four years later removed a further 17 percent of apparently eligible patients.","Sidedness, which turned out to matter more than the trial's own stratification factors, was not analysed."],"changedPractice":true,"participants":1198},{"id":"paper-kras-colorectal-j-clin-oncol-2011","kind":"paper","name":"Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status","aka":[],"tldr":"Phase 2 or 3 results paper on KRAS in Colorectal cancer, in Journal of Clinical Oncology (2011), one of the most cited Europe PMC records with KRAS in its title.","summary":"Purpose: The addition of cetuximab to irinotecan, fluorouracil, and leucovorin (FOLFIRI) as first-line treatment for metastatic colorectal cancer (mCRC) was shown to reduce the risk of disease progression and increase the chance of response in patients with KRAS wild-type disease. An updated survival analysis, including additional patients analyzed for tumor mutation status, was undertaken.\n\nPatients and methods: Patients were randomly assigned to receive FOLFIRI with or without cetuximab. DNA was extracted from additional slide-mounted tumor samples previously used to assess epidermal growth factor receptor expression. Clinical outcome according to the tumor mutation status of KRAS and BRAF was assessed in the expanded patient series.\n\nResults: The ascertainment rate of patients analyzed for tumor KRAS status was increased from 45% to 89%, with mutations detected in 37% of tumors. The addition of cetuximab to FOLFIRI in patients with KRAS wild-type disease resulted in significant improvements in overall survival (median, 23.5 v 20.0 months; hazard ratio [HR], 0.796; P =.0093), progression-free survival (median, 9.9 v 8.4 months; HR, 0.696; P =.0012), and response (rate 57.3% v 39.7%; odds ratio, 2.069; P <.001) compared with FOLFIRI alone. Significant interactions between KRAS status and treatment effect were noted for all key efficacy end points. KRAS mutation status was confirmed as a powerful predictive biomarker for the efficacy of cetuximab plus FOLFIRI. BRAF tumor mutation was a strong indicator of poor prognosis.\n\nConclusion: The addition of cetuximab to FOLFIRI as first-line therapy improves survival in patients with KRAS wild-type mCRC. BRAF tumor mutation is an indicator of poor prognosis.\n\nIndexed on Europe PMC as PubMed record 21502544 (DOI 10.1200/jco.2010.33.5091). Its title names KRAS and its text names Colorectal cancer; PubMed types it as a clinical trial report (Clinical Trial, Phase III, Research Support, Non-U.S. Gov't, Multicenter Study, Randomized Controlled Trial). It was matched automatically to the idea \"Covalent chemistry for the RAS mutations that still have no drug\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2011","url":"https://doi.org/10.1200/jco.2010.33.5091"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21502544/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/21502544"}],"tags":["europepmc-ingest"],"related":["paper-van-cutsem-crystal-cetuximab-folfiri-nejm-2009"],"cancers":["colorectal"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2011,"doi":"10.1200/jco.2010.33.5091","pmid":"21502544","authors":"Van Cutsem E, Köhne CH, Láng I, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for KRAS in Colorectal cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by KRAS in the title and Colorectal cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-chaarted-nejm-2015","kind":"paper","name":"CHAARTED: chemohormonal therapy in metastatic hormone-sensitive prostate cancer","aka":[],"tldr":"Giving six cycles of docetaxel at the start of hormone therapy for metastatic prostate cancer lengthened survival by over a year in men with high-volume disease, the first trial to show that early chemotherapy helps.","summary":"Phase 3 trial of 790 men with metastatic hormone-sensitive prostate cancer randomised to androgen deprivation alone or with six cycles of docetaxel.\n\nMedian overall survival was 57.6 versus 44.0 months (hazard ratio 0.61) overall, and 49.2 versus 32.2 months in high-volume disease; long-term follow-up showed no benefit in low-volume disease.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2015","url":"https://doi.org/10.1056/NEJMoa1503747"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26244877/"}],"tags":[],"related":["prostate-roadmap","paper-gravis-getug-afu-15-docetaxel-lancet-oncol-2013","paper-vale-stopcap-docetaxel-bisphosphonates-lancet-oncol-2016","paper-tannock-tax-327-docetaxel-prednisone-nejm-2004"],"cancers":["prostate-mhspc","prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["chaarted"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2015,"doi":"10.1056/NEJMoa1503747","pmid":"26244877","authors":"Sweeney CJ, Chen YH, Carducci M, et al.","paperType":"rct","findings":["Median overall survival 57.6 vs 44.0 months; hazard ratio 0.61.","High-volume disease: 49.2 vs 32.2 months; no benefit in low-volume disease on follow-up."],"whatItMeans":"Docetaxel with androgen deprivation is a standard for high-volume metastatic hormone-sensitive prostate cancer, now usually combined with an androgen receptor pathway inhibitor as triplet therapy.","caveats":["Open-label; defined the high-volume criteria (visceral metastases or four or more bone lesions with one beyond the pelvis and spine) used since."],"changedPractice":true,"participants":790},{"id":"paper-challenge-exercise-nejm-2025","kind":"paper","name":"CHALLENGE: a structured exercise programme after chemotherapy improves survival in colon cancer","aka":[],"tldr":"In CHALLENGE, three years of supervised, goal-based exercise after adjuvant chemotherapy for colon cancer reduced recurrence or death by 28% and deaths by 37%, the first randomised proof that exercise itself improves cancer survival.","summary":"CHALLENGE (CCTG CO.21) randomised 889 patients with resected stage III or high-risk stage II colon cancer who had completed adjuvant chemotherapy to a 3-year structured exercise programme (behavioural support and supervised sessions, targeting an increase of at least 10 MET-hours per week) or to health-education materials alone. The primary endpoint was disease-free survival.\n\nAfter a median follow-up of nearly 8 years, 5-year DFS was 80.3% with exercise versus 73.9% with education (HR 0.72). Eight-year overall survival was 90.3% versus 83.2% (HR 0.63). Physical functioning improved and musculoskeletal adverse events were more common in the exercise arm.\n\nThis is the first phase 3 trial to show that an exercise intervention, rather than exercise as a correlate, lengthens survival in cancer.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1056/NEJMoa2502760"},{"label":"ClinicalTrials.gov NCT00819208","url":"https://clinicaltrials.gov/study/NCT00819208"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40450658/"}],"tags":[],"related":["idea-exercise-as-adjuvant","idea-bio2-exercise-reimbursement","idea-bio2-gdf15-plus-exercise","survivorship-roadmap","paper-idea-duration-adjuvant-stage-iii-colon-nejm-2018"],"cancers":["colorectal","colon-cancer"],"sections":["nutrition-lifestyle","supportive-care"],"technologies":["exercise-oncology"],"targets":[],"drugs":[],"companies":["cctg"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["dancey-janet"],"bottlenecks":["b-survivorship","b-prevention-adoption","b-generic-repurposing","b-funding-allocation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2025,"doi":"10.1056/NEJMoa2502760","pmid":"40450658","authors":"Courneya KS, Vardy JL, O'Callaghan CJ, et al. (Canadian Cancer Trials Group CO.21)","paperType":"rct","findings":["Five-year disease-free survival 80.3% vs 73.9% (HR 0.72, 95% CI 0.55-0.94)","Eight-year overall survival 90.3% vs 83.2% (HR 0.63, 95% CI 0.43-0.94)","Median follow-up 7.9 years across 55 centres in Canada, Australia, the UK, France, Israel and the US","Musculoskeletal adverse events 18.5% vs 11.5%; the programme was delivered by physical activity consultants over 3 years"],"whatItMeans":"For colon cancer survivors, a prescribed, supported exercise programme is now an evidence-based treatment with a survival benefit comparable to many drugs. Health systems will need to fund exercise consultants as they fund chemotherapy. The trial does not tell us whether unsupervised advice achieves the same.","caveats":["The intervention was intensive (behavioural support for 3 years); uptake and cost in routine care are untested","Participants were fit enough to enrol and motivated; benefit in frail or sedentary populations is unproven","Open-label; DFS assessment could be influenced by differential surveillance","Recruitment took 15 years, so adjuvant regimens evolved during the trial"],"changedPractice":true,"participants":889},{"id":"paper-bear-pancreatic-immunotherapy-review-cancer-cell-2020","kind":"paper","name":"Challenges and opportunities for pancreatic cancer immunotherapy","aka":[],"tldr":"A review of why immune drugs fail in pancreatic cancer: the tumour's own driver genes build immune suppression from the start, single agents do nothing, and the proposed answer is to combine antigen delivery, T-cell support and stromal reprogramming.","summary":"Pancreatic ductal adenocarcinoma is among the most immune-resistant tumour types; its genomic landscape shaped by oncogenic drivers promotes immune suppression from the earliest stages of tumour inception and subverts adaptive T-cell immunity. Single-agent immune modulators have been clinically ineffective and multi-modal therapies targeting mechanisms of resistance are likely needed. The review covers strategies to confer antigen specificity, enhance T-cell effector function and neutralise immunosuppressive elements of the tumour microenvironment.","asOf":"2026-09-24","links":[{"label":"Bear, Vonderheide and O'Hara, Cancer Cell 2020: challenges and opportunities for pancreatic cancer immunotherapy","url":"https://doi.org/10.1016/j.ccell.2020.08.004"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32946773/"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["penn-abramson"],"pathways":["pd1-checkpoint","cancer-immunity-cycle","immune-desert-exclusion"],"terms":["cold-vs-hot","immune-exclusion"],"trials":[],"people":["robert-vonderheide"],"bottlenecks":[],"keyPapers":[],"journals":["cancer-cell"],"dependsOn":[],"notes":[],"journal":"Cancer Cell","year":2020,"doi":"10.1016/j.ccell.2020.08.004","pmid":"32946773","authors":"Bear AS, Vonderheide RH, O'Hara MH.","paperType":"review","findings":["Immune suppression in pancreatic cancer is driven by the oncogenic drivers from tumour inception.","Single-agent immune modulators are ineffective; three-part combinations are proposed."],"whatItMeans":"The clearest statement of why the corpus records so many negative immunotherapy trials here, and of the design logic behind the vaccine and agonist combinations now in trials.","caveats":["Narrative review, not a systematic analysis.","Predates the current vaccine readouts."],"changedPractice":false},{"id":"paper-upadhaya-nat-rev-drug-discov","kind":"paper","name":"Challenges and opportunities in the PD1/PDL1 inhibitor clinical trial landscape","aka":[],"tldr":"Paper cited by two bottleneck pages and eleven idea pages, indexed on Europe PMC as PubMed record 35145263 and published in Nature Reviews Drug Discovery; the citing pages link this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 35145263 (DOI 10.1038/d41573-022-00030-4). Matched by DOI alone: two bottleneck pages and eleven idea pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Drug Discov 2022","url":"https://doi.org/10.1038/d41573-022-00030-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35145263/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35145263"}],"tags":["europepmc-ingest"],"related":["b-incentive-misalignment","b-combination-space","idea-fund-repurposing-indication-exclusivity","idea-fund-abbreviated-pathway-me-too-biologics","idea-fund-duration-trial-exclusivity","idea-fund-phase-two-failure-reinsurance","idea-fund-public-car-t-manufacturing","idea-fund-first-in-class-prize","idea-fund-pay-for-cure-annuities","idea-fund-value-based-patent-extension","idea-fund-head-to-head-mandate","idea-fund-benefit-indexed-exclusivity","idea-fund-social-impact-bonds-prevention"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-drug-discovery"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Drug Discovery","year":2022,"doi":"10.1038/d41573-022-00030-4","pmid":"35145263","authors":"Upadhaya S, Neftelinov ST, Hodge J, et al.","paperType":"observational","findings":[],"whatItMeans":"Two bottleneck pages and eleven idea pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-mardones-frenz-chile-ges-mortality-rev-med-chile-2019","kind":"paper","name":"Changes in gallbladder cancer mortality and hospital discharges due to preventive cholecystectomy in Chile","aka":[],"tldr":"In the first years of Chile's preventive gallbladder surgery guarantee, deaths from gallbladder cancer among 35 to 49 year olds fell twice as fast as before, but the national trend did not visibly change.","summary":"Analysis of Chilean Ministry of Health mortality and hospital discharge databases for 2002 to 2014, standardised to the 2002 Chilean population, with Poisson regression for trends by region, sex and age, comparing the periods before and after the GES guarantee. Nationally there was a 4.5 percent decreasing mortality trend compared with before GES. Among people aged 35 to 49, mortality fell by 4 percent per period before GES and 8 percent after. Hospital discharges for biliary disease moved from a 1 percent decrease before GES to a 2 percent increase after, and in the 35 to 49 group from 0.1 to 2.9 percent. The authors conclude the rise in operations had not yet produced a break in the national mortality trend but did benefit the targeted age group.","asOf":"2026-09-24","links":[{"label":"Rev Med Chile 2019","url":"https://doi.org/10.4067/s0034-98872019000700860"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31859984/"}],"tags":["gallbladder-evidence"],"related":["paper-samaniego-chile-ges-programme-evaluation-rev-med-chile-2024"],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["prophylactic-cholecystectomy"],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Revista Medica de Chile","year":2019,"doi":"10.4067/s0034-98872019000700860","pmid":"31859984","authors":"Mardones ML, Frenz P.","paperType":"observational","findings":["National gallbladder cancer mortality trend 4.5 percent lower than before GES.","Mortality at ages 35 to 49 fell 4 percent before GES and 8 percent after; discharges in that group rose from 0.1 to 2.9 percent."],"whatItMeans":"Together with the 2024 evaluation and the American Journal of Epidemiology analysis, this is the evidence base for whether a prophylactic cholecystectomy policy prevents gallbladder cancer deaths: suggestive in the target age band, not yet convincing nationally.","caveats":["Ecological before-and-after design; secular trends and improved treatment are alternative explanations.","Follow-up to 2014 is short for a cancer with a long induction period."],"changedPractice":false},{"id":"paper-guckenberger-lancet-oncol","kind":"paper","name":"Characterisation and classification of oligometastatic disease: a European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer consensus recommendation","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 31908301 and published in The Lancet Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Oligometastatic disease has been proposed as an intermediate state between localised and systemically metastasised disease. In the absence of randomised phase 3 trials, early clinical studies show improved survival when radical local therapy is added to standard systemic therapy for oligometastatic disease. However, since no biomarker for the identification of patients with true oligometastatic disease is clinically available, the diagnosis of oligometastatic disease is based solely on imaging findings. A small number of metastases on imaging could represent different clinical scenarios, which are associated with different prognoses and might require different treatment strategies. 20 international experts including 19 members of the European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer OligoCare project developed a comprehensive system for characterisation and classification of oligometastatic disease. We first did a systematic review of the literature to identify inclusion and exclusion criteria of prospective interventional oligometastatic disease clinical trials. Next, we used a Delphi consensus process to select a total of 17 oligometastatic disease characterisation factors that should be assessed in all patients treated with radical local therapy for oligometastatic disease, both within and outside of clinical trials. Using a second round of the Delphi method, we established a decision tree for oligometastatic disease classification together with a nomenclature. We agreed oligometastatic disease as the overall umbrella term. A history of polymetastatic disease before diagnosis of oligometastatic disease was used as the criterion to differentiate between induced oligometastatic disease (previous history of polymetastatic disease) and genuine oligometastatic disease (no history of polymetastatic disease). We further subclassified genuine oligometastatic disease into repeat oligometastatic disease (previous history of oligometastatic disease) and de-novo oligometastatic disease (first time diagnosis of oligometastatic disease). In de-novo oligometastatic disease, we differentiated between synchronous and metachronous oligometastatic disease. We did a final subclassification into oligorecurrence, oligoprogression, and oligopersistence, considering whether oligometastatic disease is diagnosed during a treatment-free interval or during active systemic therapy and whether or not an oligometastatic lesion is progressing on current imaging. This oligometastatic disease classification and nomenclature needs to be prospectively evaluated by the OligoCare study.\n\nIndexed on Europe PMC as PubMed record 31908301 (DOI 10.1016/s1470-2045(19)30718-1). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2020","url":"https://doi.org/10.1016/s1470-2045(19)30718-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31908301/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31908301"}],"tags":["europepmc-ingest"],"related":["oligoprogression"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2020,"doi":"10.1016/s1470-2045(19)30718-1","pmid":"31908301","authors":"Guckenberger M, Lievens Y, Bouma AB, et al.","paperType":"rct","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-heetfeld-grade-3-net-erc-2015","kind":"paper","name":"Characteristics and treatment of patients with G3 gastroenteropancreatic neuroendocrine neoplasms","aka":[],"tldr":"Studying 204 grade 3 neuroendocrine neoplasms showed that well-differentiated tumours with a Ki-67 in the 20 to 55 percent range respond poorly to platinum chemotherapy but survive far longer than poorly differentiated carcinomas, establishing grade 3 neuroendocrine tumour as a separate disease.","summary":"Retrospective multicentre study of 204 patients with gastroenteropancreatic neuroendocrine neoplasms with Ki-67 over 20 percent, divided into well-differentiated neuroendocrine tumours and poorly differentiated carcinomas.\n\nWell-differentiated grade 3 tumours had a median survival of 99 months against 17 months for carcinomas, lower response to platinum-etoposide, and better response to alkylating agents and other tumour-type treatments; Ki-67 of 55 percent separated the groups.","asOf":"2026-09-17","links":[{"label":"Endocr Relat Cancer 2015","url":"https://doi.org/10.1530/ERC-15-0119"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26113608/"}],"tags":[],"related":[],"cancers":["grade-3-net"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["endocrine-related-cancer"],"dependsOn":[],"notes":[],"journal":"Endocrine-related cancer","year":2015,"doi":"10.1530/ERC-15-0119","pmid":"26113608","authors":"Heetfeld M, Chougnet CN, Olsen IH, et al.","paperType":"observational","findings":["Median overall survival 99 months for grade 3 neuroendocrine tumour vs 17 months for neuroendocrine carcinoma.","Platinum response 33 percent in tumours vs higher in carcinomas."],"whatItMeans":"Grade 3 neuroendocrine tumours are treated like aggressive grade 2 tumours (somatostatin analogues, capecitabine-temozolomide, radioligand therapy) rather than with small-cell regimens.","caveats":["Retrospective and treatment was heterogeneous."],"changedPractice":true,"participants":204},{"id":"paper-hoang-ivermectin-toxicity-clin-toxicol-2022","kind":"paper","name":"Characteristics of ivermectin toxicity in patients taking veterinary and human formulations for the prevention and treatment of COVID-19","aka":[],"tldr":"An Oregon poison centre saw 37 people poisoned by ivermectin in six months of the pandemic; 30 had nervous-system effects, 21 were admitted to hospital and one died, with veterinary products giving the largest doses and the most confusion.","summary":"The Oregon Poison Center reviewed 37 ivermectin exposures for COVID-19 prevention or treatment that led to a healthcare visit between 14 August 2021 and 31 January 2022; median age was 64, most were men, 21 were hospitalised, 13 treated in an emergency department and one died (Hoang poison centre series 2022). Neurotoxicity occurred in 30, gastrointestinal symptoms in 14 and musculoskeletal complaints in 7; the 17 who took veterinary formulations took higher doses and had more altered mental status than the 15 on prescription tablets, and chronic users on a median 13.5 mg a day for 3.8 weeks had milder toxicity (Hoang poison centre series 2022).","asOf":"2026-09-24","links":[{"label":"Hoang poison centre series 2022","url":"https://doi.org/10.1080/15563650.2022.2134788"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36374218/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["ivermectin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo agent (Claude Fable 5.1)","editedOn":"2026-09-24","note":"Written from cached ClinicalTrials.gov v2, Europe PMC, DailyMed, Drugs@FDA and WHO eEML responses; no figure appears without its source link."},"journal":"Clinical Toxicology","year":2022,"doi":"10.1080/15563650.2022.2134788","pmid":"36374218","authors":"Hoang R, Temple C, Correia MS, Clemons J, Hendrickson RG.","paperType":"observational","findings":["37 cases: neurotoxicity 30, hospitalised 21, one death.","Veterinary formulations were associated with higher doses and more altered mental status than prescription tablets."],"whatItMeans":"The pattern of harm that cancer self-dosing now repeats: mostly older men, veterinary products, and neurological effects that need hospital care.","caveats":["Retrospective single-centre series limited to cases that reached a poison centre; COVID-19 use rather than cancer use."],"changedPractice":false,"participants":37},{"id":"paper-cardoso-ann-oncol","kind":"paper","name":"Characterization of male breast cancer: results of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 29092024 and published in Annals of Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background: Male breast cancer (BC) is rare, managed by extrapolation from female BC. The International Male BC Program aims to better characterize and manage this disease. We report the results of part I, a retrospective joint analysis of cases diagnosed during a 20-year period.\n\nMethods: Patients with follow-up and tumor samples, treated between 1990 and 2010, in 93 centers/9 countries. Samples were centrally analyzed in three laboratories (the United Kingdom, the Netherlands and the United States).\n\nResults: Of 1822 patients enrolled, 1483 were analyzed; 63.5% were diagnosed between 2001 and 2010, 57 (5.1%) had metastatic disease (M1). Median age at diagnosis: 68.4 years. Of 1054 M0 cases, 56.2% were node-negative (N0) and 48.5% had T1 tumors; 4% had breast conserving surgery (BCS), 18% sentinel lymph-node biopsy; half received adjuvant radiotherapy; 29.8% (neo)adjuvant chemotherapy and 76.8% adjuvant endocrine therapy (ET), mostly tamoxifen (88.4%). Per central pathology, for M0 tumors: 84.8% ductal invasive carcinomas, 51.5% grade 2; 99.3% estrogen receptor (ER)-positive; 81.9% progesterone receptor (PR)-positive; 96.9% androgen receptor (AR)-positive [ER, PR or AR Allred score ≥3]; 61.1% Ki67 expression low (<14% positive cells); using immunohistochemistry (IHC) surrogates, 41.9% were Luminal-A-like, 48.6% Luminal-B-like/HER-2-negative, 8.7% HER-2-positive, 0.3% triple negative. Median follow-up: 8.2 years (0.0-23.8) for all, 7.2 years (0.0-23.2), for M0, 2.6 years (0.0-12.7) for M1 patients. A significant improvement over time was observed in age-corrected BC mortality. BC-specific-mortality was higher for men younger than 50 years. Better overall (OS) and recurrence-free survival (RFS) were observed for highly ER+ (P = 0.001), highly PR+ (P = 0.002), highly AR+ disease (P = 0.019). There was no association between OS/RFS and HER-2 status, Ki67, IHC subtypes nor grade.\n\nConclusions: Male BC is usually ER, PR and AR-positive, Luminal B-like/HER2-negative. Of note, 56% patients had T1 tumors but only 4% had BCS. ER was highly positive in >90% of cases but only 77% received adjuvant ET. ER, PR and AR were associated with OS and RFS, whereas grade, Ki67 and IHC surrogates were not. Significant improvement in survival over time was observed.\n\nIndexed on Europe PMC as PubMed record 29092024 (DOI 10.1093/annonc/mdx651). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Ann Oncol 2018","url":"https://doi.org/10.1093/annonc/mdx651"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29092024/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29092024"}],"tags":["europepmc-ingest"],"related":["male-breast-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2018,"doi":"10.1093/annonc/mdx651","pmid":"29092024","authors":"Cardoso F, Bartlett JMS, Slaets L, et al.","paperType":"observational","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-checkmate-017-nejm-2015","kind":"paper","name":"CheckMate 017: nivolumab beats docetaxel in squamous lung cancer after chemotherapy","aka":[],"tldr":"In squamous non-small-cell lung cancer that had progressed after platinum chemotherapy, the PD-1 antibody nivolumab prolonged life compared with docetaxel with far fewer severe side effects, regardless of PD-L1 status.","summary":"CheckMate 017 randomised 272 patients with advanced squamous non-small-cell lung cancer that had progressed during or after first-line platinum chemotherapy to nivolumab or docetaxel. Nivolumab improved overall survival, the primary endpoint, as well as response rate and progression-free survival, with a fraction of the grade 3 or 4 toxicity of docetaxel. Unlike its non-squamous companion trial CheckMate 057, the benefit did not depend on PD-L1 expression, which led to nivolumab's approval in squamous disease without a biomarker requirement.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa1504627"},{"label":"ClinicalTrials.gov NCT01642004","url":"https://clinicaltrials.gov/study/NCT01642004"}],"tags":[],"related":["paper-checkmate-057-nejm-2015"],"cancers":["nsclc"],"sections":[],"technologies":[],"targets":["pd1","pdl1"],"drugs":["nivolumab","docetaxel"],"companies":["bms"],"institutions":[],"pathways":[],"terms":["os","orr"],"trials":[],"people":["julie-brahmer"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2015,"doi":"10.1056/NEJMoa1504627","authors":"Brahmer J, Reckamp KL, Baas P, et al.","paperType":"rct","findings":["272 patients with previously treated squamous NSCLC; nivolumab vs docetaxel.","Median overall survival 9.2 vs 6.0 months, hazard ratio 0.59; one-year survival 42% vs 24%.","Response rate 20% vs 9%; median progression-free survival 3.5 vs 2.8 months, hazard ratio 0.62.","Grade 3 or 4 treatment-related adverse events 7% vs 55%; benefit was independent of PD-L1 expression."],"whatItMeans":"With CheckMate 057 this trial ended docetaxel's role as the default second-line treatment in lung cancer and gave the first phase 3 proof that PD-1 blockade extends life in a common carcinoma. Its PD-L1-independent benefit in squamous disease still shapes how the biomarker is used.","caveats":["Open-label design.","Second-line setting; first-line immunotherapy has since changed who reaches this point.","Squamous histology only."],"changedPractice":true,"participants":272},{"id":"paper-checkmate-026-first-line-nivolumab-nejm-2017","kind":"paper","name":"CheckMate 026: first-line nivolumab in stage IV or recurrent non-small-cell lung cancer","aka":[],"tldr":"Giving an immunotherapy drug instead of chemotherapy as the first treatment did not help patients selected only by a moderate level of the PD-L1 protein. It is the trial that showed the threshold, not the drug, was the problem.","summary":"Patients with untreated stage IV or recurrent non-small-cell lung cancer and a PD-L1 tumour-expression level of 1% or more were randomly assigned to nivolumab or platinum-based chemotherapy. Among the 423 patients with a PD-L1 expression level of 5% or more, median progression-free survival was 4.2 months with nivolumab against 5.9 months with chemotherapy (hazard ratio 1.15) and median overall survival was 14.4 against 13.2 months (hazard ratio 1.02); 60% of the chemotherapy group crossed over to nivolumab. Treatment-related adverse events of grade 3 or 4 occurred in 18% with nivolumab and 51% with chemotherapy.","asOf":"2026-09-25","links":[{"label":"Carbone et al., N Engl J Med 2017: CheckMate 026, first-line nivolumab in PD-L1-positive non-small-cell lung cancer","url":"https://doi.org/10.1056/NEJMoa1613493"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28636851/"}],"tags":[],"related":["pd-l1-tc-score","tmb-high"],"cancers":["nsclc"],"sections":[],"technologies":["checkpoint-inhibitor","histopathology-ihc"],"targets":["pdl1","pd1"],"drugs":["nivolumab"],"companies":[],"institutions":[],"pathways":["pd1-checkpoint"],"terms":["tmb","ihc"],"trials":[],"people":["martin-reck"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2017,"doi":"10.1056/NEJMoa1613493","pmid":"28636851","authors":"Carbone DP, Reck M, Paz-Ares L, et al.","paperType":"rct","findings":["No progression-free survival benefit at a PD-L1 threshold of 5% or more, hazard ratio 1.15.","Overall survival similar, hazard ratio 1.02, with 60% crossover.","Far fewer grade 3 or 4 adverse events with nivolumab.","An exploratory high mutation burden subgroup did better, which did not rescue the trial."],"whatItMeans":"Read beside the pembrolizumab trial that succeeded at a 50% threshold in the same setting, it is the cleanest demonstration that a PD-L1 threshold is not a property of the protein but of the trial that drew the line.","caveats":["The comparison with the successful pembrolizumab trial is across trials, with different assays and populations.","Extensive crossover obscures the survival comparison.","The high burden subgroup analysis was exploratory and not powered."],"changedPractice":true,"participants":541},{"id":"paper-checkmate-057-nejm-2015","kind":"paper","name":"CheckMate 057: nivolumab beats docetaxel after chemotherapy in non-squamous lung cancer","aka":[],"tldr":"After platinum chemotherapy had failed, the PD-1 antibody nivolumab prolonged life compared with docetaxel in non-squamous lung cancer with far fewer severe side effects, and the benefit was largest in tumours expressing PD-L1.","summary":"CheckMate 057 randomised 582 patients with non-squamous non-small-cell lung cancer that had progressed during or after platinum-based chemotherapy to nivolumab or docetaxel. Nivolumab improved overall survival, the primary endpoint, with a higher response rate, longer duration of response and a fraction of the severe toxicity of docetaxel. Unlike its squamous counterpart CheckMate 017, the benefit depended on PD-L1 expression, with little difference in PD-L1-negative tumours, which fuelled the debate about PD-L1 as a biomarker.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa1507643"},{"label":"ClinicalTrials.gov NCT01673867","url":"https://clinicaltrials.gov/study/NCT01673867"}],"tags":[],"related":["paper-keynote-024-nejm-2016"],"cancers":["nsclc"],"sections":[],"technologies":[],"targets":["pd1","pdl1"],"drugs":["nivolumab","docetaxel"],"companies":["bms"],"institutions":[],"pathways":[],"terms":["os","orr"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2015,"doi":"10.1056/NEJMoa1507643","authors":"Borghaei H, Paz-Ares L, Horn L, et al.","paperType":"rct","findings":["582 patients with previously treated non-squamous NSCLC; nivolumab vs docetaxel.","Median overall survival 12.2 vs 9.4 months, hazard ratio 0.73.","Response rate 19% vs 12%; median duration of response 17.2 vs 5.6 months.","Grade 3 or 4 treatment-related adverse events 10% vs 54%.","Survival benefit increased with PD-L1 expression and was not evident in PD-L1-negative tumours."],"whatItMeans":"With CheckMate 017 in squamous disease, this trial ended docetaxel's reign as the default second-line treatment for lung cancer and established PD-1 blockade as standard after chemotherapy. Its PD-L1 finding shaped how later first-line trials were designed and how the biomarker is used in the clinic.","caveats":["Open-label design.","Early crossing of the survival curves suggested some patients fared worse on nivolumab in the first months.","PD-L1 was assessed retrospectively on archival tissue."],"changedPractice":true,"participants":582},{"id":"paper-checkmate-067-10-year-nejm-2025","kind":"paper","name":"CheckMate 067 at ten years: nivolumab plus ipilimumab produces long-term survival in half of patients with advanced melanoma","aka":[],"tldr":"Ten years after starting treatment, about half of patients with advanced melanoma treated with nivolumab plus ipilimumab were still alive, most without any further treatment, showing that immunotherapy can cure a disease that once killed most patients within a year.","summary":"Final ten-year analysis of the double-blind phase 3 trial of 945 patients with untreated advanced melanoma randomised to nivolumab plus ipilimumab, nivolumab alone, or ipilimumab alone.\n\nMedian overall survival was 71.9 months with the combination, 36.9 months with nivolumab and 19.9 months with ipilimumab; 10-year OS was 43%, 37% and 19%. Median melanoma-specific survival was not reached for the combination, with 10-year melanoma-specific survival of 52%. The survival curves plateaued after about three years, and most surviving patients had been off treatment for years. It is the longest follow-up of any checkpoint inhibitor trial and the definitive evidence that immunotherapy can be curative.","asOf":"2026-09-08","links":[{"label":"NEJM 2025","url":"https://doi.org/10.1056/NEJMoa2407417"},{"label":"ClinicalTrials.gov NCT01844505","url":"https://clinicaltrials.gov/study/NCT01844505"},{"label":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=CheckMate%20067%2010-year%20nivolumab%20ipilimumab%20melanoma%20Wolchok%20NEJM%202025"},{"label":"Original report (Larkin 2015)","url":"https://doi.org/10.1056/NEJMoa1504030"}],"tags":[],"related":["paper-hodi-ipilimumab-melanoma-nejm-2010","paper-asco-irae-guideline-jco-2021"],"cancers":["melanoma"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["pd1","ctla4","lag3"],"drugs":["nivolumab","ipilimumab","relatlimab-nivolumab"],"companies":["bms"],"institutions":["mskcc"],"pathways":[],"terms":["os","irae","hazard-ratio"],"trials":["checkmate-067","relativity-047"],"people":["john-haanen","mcarthur-grant","f-stephen-hodi","james-larkin"],"bottlenecks":["b-immunotherapy-response","b-toxicity-qol","b-biomarker-validation","b-survivorship"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2025,"doi":"10.1056/NEJMoa2407417","pmid":"39282897","authors":"Wolchok JD, Chiarion-Sileni V, Rutkowski P, et al.","paperType":"rct","findings":["Median overall survival 71.9 months (nivolumab plus ipilimumab) vs 36.9 months (nivolumab) vs 19.9 months (ipilimumab).","10-year overall survival 43% vs 37% vs 19%; 10-year melanoma-specific survival 52% vs 44% vs 23%.","Median melanoma-specific survival not reached for the combination (over 120 months) vs 49.4 months for nivolumab.","Among patients alive at three years, subsequent melanoma deaths were rare, and most survivors had received no further systemic therapy.","The combination versus nivolumab alone was not formally powered for comparison; grade 3-4 treatment-related adverse events were 59% vs 24% vs 28% in the original report."],"whatItMeans":"For patients with advanced melanoma, immunotherapy offers a realistic chance of long-term survival and probably cure, and the ten-year data show that patients who are alive and progression-free at three years rarely die of melanoma afterwards. Nivolumab plus ipilimumab gives the best long-term results but at a high price in serious side effects; nivolumab alone or nivolumab plus relatlimab are alternatives for patients at lower risk or with autoimmune concerns. The trial is also a caution about surrogate endpoints: the survival plateau took years to become visible.","caveats":["The trial was not designed to compare the combination with nivolumab alone, and that difference is not statistically established.","Toxicity of the combination is substantial, with roughly one in three patients stopping for adverse events.","Patients were treated before BRAF/MEK inhibitors and relatlimab were standard, so sequencing questions are not answered.","Predicting who is cured versus who relapses late is still not possible from baseline biomarkers."],"changedPractice":true,"participants":945},{"id":"paper-checkmate-141-ferris-nejm-2016","kind":"paper","name":"CheckMate 141: nivolumab for recurrent head and neck squamous cell carcinoma after platinum","aka":[],"tldr":"Nivolumab lengthened survival compared with standard single-agent chemotherapy in head and neck cancer that had progressed within six months of platinum treatment, the first immunotherapy to improve survival in the disease.","summary":"Phase 3 trial of 361 patients with recurrent or metastatic head and neck squamous cell carcinoma progressing within six months of platinum-based therapy, randomised 2:1 to nivolumab or investigator's choice of methotrexate, docetaxel or cetuximab.\n\nMedian overall survival was 7.5 versus 5.1 months (hazard ratio 0.70) and one-year survival 36.0 versus 16.6 percent, with fewer grade 3 to 4 adverse events (13.1 versus 35.1 percent) and better quality of life.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2016","url":"https://doi.org/10.1056/NEJMoa1602252"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27718784/"}],"tags":[],"related":[],"cancers":["recurrent-metastatic-hnscc","oropharyngeal-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["nivolumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-141"],"people":["robert-ferris"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2016,"doi":"10.1056/NEJMoa1602252","pmid":"27718784","authors":"Ferris RL, Blumenschein G, Fayette J, et al.","paperType":"rct","findings":["Median overall survival 7.5 vs 5.1 months; hazard ratio 0.70.","One-year overall survival 36.0 percent vs 16.6 percent."],"whatItMeans":"PD-1 blockade after platinum became standard, and the trial opened the way for first-line pembrolizumab in KEYNOTE-048.","caveats":["Response rate was low (13.3 percent); benefit accrues to a minority of durable responders."],"changedPractice":true,"participants":361},{"id":"paper-checkmate-205-nivolumab-rr-hodgkin-extended-follow-up-jco-2018","kind":"paper","name":"CheckMate 205: nivolumab for relapsed or refractory classical Hodgkin lymphoma after autologous transplant failure, extended follow-up","aka":[],"tldr":"The PD-1 antibody nivolumab produced responses in about seven in ten patients whose Hodgkin lymphoma had returned after a stem cell transplant, with responses lasting well over a year, confirming the exquisite sensitivity of this lymphoma to checkpoint blockade.","summary":"Multicohort single-arm phase 2 study of 243 patients with classical Hodgkin lymphoma relapsed or refractory after autologous stem cell transplantation, treated with nivolumab; cohorts were brentuximab-naive, brentuximab after transplant, and brentuximab before and/or after transplant.\n\nWith extended follow-up the objective response rate was 69 percent, median duration of response 16.6 months and median progression-free survival 14.7 months; responses were independent of PD-L1 expression level, and the safety profile matched other nivolumab studies. The data underpinned regulatory approval of nivolumab in this setting.","asOf":"2026-09-18","links":[{"label":"J Clin Oncol 2018","url":"https://doi.org/10.1200/JCO.2017.76.0793"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29584546/"}],"tags":[],"related":[],"cancers":["relapsed-refractory-hodgkin-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["nivolumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-205"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2018,"doi":"10.1200/JCO.2017.76.0793","pmid":"29584546","authors":"Armand P, Engert A, Younes A, et al.","paperType":"observational","findings":["Objective response 69 percent; median duration of response 16.6 months; median progression-free survival 14.7 months."],"whatItMeans":"Nivolumab, like pembrolizumab, is a standard for relapsed Hodgkin lymphoma after transplant, and the activity seen here led to its testing in first-line therapy (S1826).","caveats":["Single-arm; no randomised comparison with brentuximab vedotin.","Complete responses were a minority and most patients eventually progressed."],"changedPractice":true,"participants":243},{"id":"paper-checkmate-214-nejm-2018","kind":"paper","name":"CheckMate 214: nivolumab plus ipilimumab versus sunitinib in advanced renal cell carcinoma","aka":[],"tldr":"Dual immunotherapy with nivolumab and ipilimumab lengthened survival compared with sunitinib in intermediate- and poor-risk advanced kidney cancer, with about one in ten patients achieving a complete response that has proved durable over years.","summary":"Phase 3 trial of 1,096 patients with untreated advanced clear cell renal cell carcinoma randomised to nivolumab plus ipilimumab (four doses) followed by nivolumab, or sunitinib, with co-primary endpoints in intermediate- and poor-risk patients.\n\nIn intermediate and poor risk, 18-month overall survival was 75 versus 60 percent (hazard ratio 0.63), response 42 versus 27 percent and complete response 9 versus 1 percent; favourable-risk patients had higher response to sunitinib at first analysis. Long-term follow-up shows sustained survival benefit.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2018","url":"https://doi.org/10.1056/NEJMoa1712126"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29562145/"}],"tags":[],"related":[],"cancers":["clear-cell-rcc"],"sections":[],"technologies":[],"targets":[],"drugs":["ipilimumab","nivolumab","sunitinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-214"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2018,"doi":"10.1056/NEJMoa1712126","pmid":"29562145","authors":"Motzer RJ, Tannir NM, McDermott DF, et al.","paperType":"rct","findings":["Intermediate and poor risk: 18-month overall survival 75 percent vs 60 percent; hazard ratio 0.63.","Complete response 9 percent vs 1 percent."],"whatItMeans":"Nivolumab-ipilimumab is a first-line standard for intermediate- and poor-risk clear cell kidney cancer, notable for durable complete responses and treatment-free intervals.","caveats":["Favourable-risk patients showed no clear benefit.","Immune-related adverse events requiring high-dose steroids in about a third."],"changedPractice":true,"participants":1096},{"id":"paper-checkmate-238-nejm-2017","kind":"paper","name":"CheckMate 238: adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma","aka":[],"tldr":"A year of adjuvant nivolumab after surgery for high-risk melanoma reduced recurrences more than the previous standard, high-dose ipilimumab, with a quarter of the severe toxicity, making PD-1 blockade the adjuvant standard.","summary":"Phase 3 trial of 906 patients with resected stage IIIB, IIIC or IV melanoma randomised to nivolumab or ipilimumab 10 mg/kg for one year.\n\nTwelve-month recurrence-free survival was 70.5 versus 60.8 percent (hazard ratio 0.65), with grade 3 to 4 treatment-related adverse events in 14.4 versus 45.9 percent; four-year recurrence-free survival was 51.7 versus 41.2 percent, with no overall survival difference.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2017","url":"https://doi.org/10.1056/NEJMoa1709030"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28891423/"}],"tags":[],"related":[],"cancers":["stage-iii-melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":["ipilimumab","nivolumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-238"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2017,"doi":"10.1056/NEJMoa1709030","pmid":"28891423","authors":"Weber J, Mandala M, Del Vecchio M, et al.","paperType":"rct","findings":["Twelve-month recurrence-free survival 70.5 percent vs 60.8 percent; hazard ratio 0.65.","Grade 3 to 4 adverse events 14.4 percent vs 45.9 percent."],"whatItMeans":"Adjuvant nivolumab (or pembrolizumab) is standard for resected stage III and IV melanoma; ipilimumab is no longer used in the adjuvant setting.","caveats":["No placebo arm; the comparison is against an active but toxic agent.","Overall survival did not differ, probably because of effective therapy at relapse."],"changedPractice":true,"participants":906},{"id":"paper-checkmate-577-nejm-2021","kind":"paper","name":"CheckMate 577: adjuvant nivolumab in resected oesophageal or gastro-oesophageal junction cancer","aka":[],"tldr":"A year of nivolumab after chemoradiotherapy and surgery doubled disease-free survival in patients with oesophageal or junctional cancer who still had residual tumour at surgery, the first adjuvant therapy to work in this setting.","summary":"Phase 3 placebo-controlled trial of 794 patients with resected stage II to III oesophageal or gastro-oesophageal junction cancer (both histologies) and residual pathological disease after neoadjuvant chemoradiotherapy, randomised 2:1 to nivolumab or placebo for up to one year.\n\nMedian disease-free survival was 22.4 versus 11.0 months (hazard ratio 0.69), with benefit in both squamous and adenocarcinoma and regardless of PD-L1 expression; grade 3 to 4 treatment-related adverse events were 13 versus 6 percent.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2021","url":"https://doi.org/10.1056/NEJMoa2032125"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33789008/"}],"tags":[],"related":[],"cancers":["oesophageal-squamous-cell-carcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":["nivolumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-577"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2021,"doi":"10.1056/NEJMoa2032125","pmid":"33789008","authors":"Kelly RJ, Ajani JA, Kuzdzal J, et al.","paperType":"rct","findings":["Median disease-free survival 22.4 vs 11.0 months; hazard ratio 0.69.","Benefit in squamous (hazard ratio 0.61) and adenocarcinoma (0.75)."],"whatItMeans":"Adjuvant nivolumab is standard for patients with residual disease after trimodality therapy for oesophageal cancer.","caveats":["Overall survival data pending.","Applies only after neoadjuvant chemoradiotherapy, not after perioperative chemotherapy."],"changedPractice":true,"participants":794},{"id":"paper-checkmate-648-nejm-2022","kind":"paper","name":"CheckMate 648: nivolumab combination therapy in advanced oesophageal squamous cell carcinoma","aka":[],"tldr":"Adding nivolumab to chemotherapy, or combining nivolumab with ipilimumab without chemotherapy, lengthened survival compared with chemotherapy alone in advanced oesophageal squamous cell carcinoma, with the largest gains in PD-L1-positive tumours.","summary":"Phase 3 trial of 970 patients with previously untreated advanced oesophageal squamous cell carcinoma randomised to nivolumab plus fluorouracil-cisplatin, nivolumab plus ipilimumab, or chemotherapy alone.\n\nIn tumours with PD-L1 expression of 1 percent or more, median overall survival was 15.4 months with nivolumab-chemotherapy and 13.7 months with nivolumab-ipilimumab against 9.1 months with chemotherapy (hazard ratios 0.54 and 0.64); benefit was also seen in the overall population.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2022","url":"https://doi.org/10.1056/NEJMoa2111380"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35108470/"}],"tags":[],"related":[],"cancers":["oesophageal-squamous-cell-carcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":["nivolumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-648"],"people":["yuichiro-doki"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/NEJMoa2111380","pmid":"35108470","authors":"Doki Y, Ajani JA, Kato K, et al.","paperType":"rct","findings":["PD-L1 1 percent or more: median overall survival 15.4 (nivolumab-chemotherapy) and 13.7 (nivolumab-ipilimumab) vs 9.1 months (chemotherapy).","All randomised: 13.2 and 12.7 vs 10.7 months."],"whatItMeans":"Nivolumab plus chemotherapy or nivolumab plus ipilimumab are first-line standards for advanced oesophageal squamous cell carcinoma, joining pembrolizumab-chemotherapy from KEYNOTE-590.","caveats":["Early progression was more frequent with chemotherapy-free nivolumab-ipilimumab.","Benefit in PD-L1-negative tumours was uncertain."],"changedPractice":true,"participants":970},{"id":"paper-checkmate-649-lancet-2021","kind":"paper","name":"CheckMate 649: nivolumab plus chemotherapy as first treatment for advanced gastric, gastro-oesophageal junction and oesophageal adenocarcinoma","aka":[],"tldr":"Adding the immunotherapy nivolumab to first-line chemotherapy helped patients with advanced stomach and oesophageal adenocarcinoma live longer, especially when the tumour showed PD-L1, making chemo-immunotherapy the new standard.","summary":"Open-label phase 3 trial of 1,581 patients with untreated, HER2-negative advanced gastric, gastro-oesophageal junction or oesophageal adenocarcinoma randomised to nivolumab plus chemotherapy (XELOX or FOLFOX) or chemotherapy alone (a third arm tested nivolumab plus ipilimumab). Primary endpoints were OS and PFS in patients with PD-L1 combined positive score (CPS) of 5 or more.\n\nIn CPS 5 or more, median OS was 14.4 vs 11.1 months (HR 0.71) and PFS 7.7 vs 6.0 months (HR 0.68); in all randomised patients OS was 13.8 vs 11.6 months (HR 0.80). It was the first immunotherapy to improve first-line survival in gastric cancer and it made PD-L1 CPS testing standard, though regulators disagreed about the CPS threshold for use.","asOf":"2026-09-08","links":[{"label":"PubMed search: CheckMate 649 Lancet 2021","url":"https://pubmed.ncbi.nlm.nih.gov/?term=CheckMate+649+nivolumab+chemotherapy+gastric+Janjigian+Lancet+2021"},{"label":"ClinicalTrials.gov NCT02872116","url":"https://clinicaltrials.gov/study/NCT02872116"}],"tags":[],"related":[],"cancers":["gastric","esophageal"],"sections":[],"technologies":["checkpoint-inhibitor","cytotoxic-chemotherapy","platinum"],"targets":["pd1","pdl1"],"drugs":["nivolumab","ipilimumab"],"companies":["bms"],"institutions":["mskcc"],"pathways":[],"terms":["cps","os","pfs","first-line","msi"],"trials":[],"people":["yelena-janjigian","shitara-kohei","shen-lin"],"bottlenecks":["b-biomarker-validation","b-immunotherapy-response","b-regulatory-fragmentation"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2021,"doi":"10.1016/S0140-6736(21)00797-2","pmid":"34102137","authors":"Janjigian YY, Shitara K, Moehler M, et al.","paperType":"rct","findings":["CPS 5 or more: median OS 14.4 vs 11.1 months, HR 0.71 (98.4% CI 0.59-0.86); median PFS 7.7 vs 6.0 months, HR 0.68.","All randomised patients: median OS 13.8 vs 11.6 months, HR 0.80 (99.3% CI 0.68-0.94).","Objective response in CPS 5 or more: 60% vs 45%.","Exploratory analysis showed little benefit in CPS below 5, and the EMA restricted the label to CPS 5 or more while the FDA initially approved it regardless of PD-L1 (later narrowed to CPS 1 or more).","Grade 3-4 treatment-related adverse events 59% vs 44%."],"whatItMeans":"Patients with newly diagnosed advanced stomach or oesophageal adenocarcinoma whose tumour is HER2-negative and PD-L1 positive (CPS 5 or more, or at least 1 in some regions) should receive chemotherapy with nivolumab (or pembrolizumab, from KEYNOTE-859), which adds about three months of median survival and doubles the chance of being alive at three years. The benefit in PD-L1-negative tumours is doubtful, and these patients may be better served by chemotherapy alone or by trials.","caveats":["Benefit is concentrated in PD-L1-positive tumours; the ITT result is driven by the CPS 5 or more subgroup.","Open-label design; CPS scoring reproducibility is imperfect.","Microsatellite-instability-high tumours (about 3%) derived very large benefit and inflate pooled estimates.","The nivolumab plus ipilimumab chemotherapy-free arm failed to improve OS."],"changedPractice":true,"participants":1581},{"id":"paper-checkmate-743-lancet-2021","kind":"paper","name":"CheckMate 743: first-line nivolumab plus ipilimumab in unresectable pleural mesothelioma","aka":[],"tldr":"Dual immunotherapy with nivolumab and ipilimumab lengthened survival compared with platinum-pemetrexed chemotherapy in pleural mesothelioma, the first improvement in first-line treatment in almost twenty years, with the largest gain in non-epithelioid tumours.","summary":"Phase 3 trial of 605 patients with untreated unresectable malignant pleural mesothelioma randomised to nivolumab plus ipilimumab or platinum plus pemetrexed.\n\nMedian overall survival was 18.1 versus 14.1 months (hazard ratio 0.74); in non-epithelioid histology it was 18.1 versus 8.8 months (hazard ratio 0.46), while the difference in epithelioid disease was small. Three-year survival was 23 versus 15 percent.","asOf":"2026-09-17","links":[{"label":"Lancet 2021","url":"https://doi.org/10.1016/S0140-6736(20)32714-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33485464/"}],"tags":[],"related":[],"cancers":["pleural-mesothelioma","peritoneal-mesothelioma"],"sections":[],"technologies":[],"targets":[],"drugs":["ipilimumab","nivolumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-743"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2021,"doi":"10.1016/S0140-6736(20)32714-8","pmid":"33485464","authors":"Baas P, Scherpereel A, Nowak AK, et al.","paperType":"rct","findings":["Median overall survival 18.1 vs 14.1 months; hazard ratio 0.74.","Non-epithelioid: 18.1 vs 8.8 months; hazard ratio 0.46."],"whatItMeans":"Nivolumab-ipilimumab is the preferred first-line treatment for non-epithelioid pleural mesothelioma and an option in epithelioid disease alongside chemo-immunotherapy.","caveats":["Open-label; early crossing of survival curves indicates some patients do worse without chemotherapy.","Epithelioid benefit was modest."],"changedPractice":true,"participants":605},{"id":"paper-checkmate-76k-nat-med-2023","kind":"paper","name":"CheckMate 76K: adjuvant nivolumab in resected stage IIB or IIC melanoma","aka":[],"tldr":"Adjuvant nivolumab for a year after surgery cut the risk of recurrence by more than half in stage IIB and IIC melanoma, confirming the benefit seen with pembrolizumab in the same setting.","summary":"Phase 3 placebo-controlled trial of 790 patients with completely resected stage IIB or IIC melanoma randomised 2:1 to nivolumab or placebo for 12 months.\n\nTwelve-month recurrence-free survival was 89.0 versus 79.4 percent (hazard ratio 0.42), with benefit across subgroups and a distant metastasis-free survival hazard ratio of 0.47; treatment-related grade 3 to 4 adverse events occurred in 10.3 percent.","asOf":"2026-09-17","links":[{"label":"Nat Med 2023","url":"https://doi.org/10.1038/s41591-023-02583-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37845511/"}],"tags":[],"related":[],"cancers":["stage-ii-melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":["nivolumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04099251"],"people":["john-kirkwood"],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2023,"doi":"10.1038/s41591-023-02583-2","pmid":"37845511","authors":"Kirkwood JM, Del Vecchio M, Weber J, et al.","paperType":"rct","findings":["Twelve-month recurrence-free survival 89.0 percent vs 79.4 percent; hazard ratio 0.42.","Distant metastasis-free survival hazard ratio 0.47."],"whatItMeans":"Nivolumab is a second approved adjuvant option for stage IIB and IIC melanoma with the same trade-offs as pembrolizumab.","caveats":["Short follow-up at primary analysis; no survival data."],"changedPractice":true,"participants":790},{"id":"paper-checkmate-816-nejm-2022","kind":"paper","name":"CheckMate 816: three cycles of nivolumab plus chemotherapy before lung cancer surgery","aka":[],"tldr":"Just three cycles of chemotherapy with the immunotherapy nivolumab before surgery wiped out all viable tumour in a quarter of patients and reduced relapse or death by about a third, without making surgery harder.","summary":"Open-label phase 3 trial of 358 patients with resectable stage IB-IIIA NSCLC randomised to three cycles of neoadjuvant nivolumab plus platinum-doublet chemotherapy or chemotherapy alone, followed by surgery. Primary endpoints were pathological complete response (pCR) and event-free survival (EFS).\n\npCR was 24.0% vs 2.2% and median EFS 31.6 vs 20.8 months (HR 0.63). Surgery rates and complications were not worse with nivolumab. A 2025 report confirmed an overall survival benefit (HR about 0.72). It was the first neoadjuvant immunotherapy approval in lung cancer and, together with the perioperative trials (KEYNOTE-671, AEGEAN, CheckMate 77T), moved immunotherapy before surgery.","asOf":"2026-09-08","links":[{"label":"NEJM 2022","url":"https://doi.org/10.1056/NEJMoa2202170"},{"label":"ClinicalTrials.gov NCT02998528","url":"https://clinicaltrials.gov/study/NCT02998528"}],"tags":[],"related":["lung-cancer-evidence-roadmap","paper-heymach-aegean-perioperative-durvalumab-nejm-2023"],"cancers":["nsclc","lung-cancer"],"sections":[],"technologies":["checkpoint-inhibitor","cytotoxic-chemotherapy"],"targets":["pd1"],"drugs":["nivolumab","carboplatin","paclitaxel"],"companies":["bms"],"institutions":["johns-hopkins"],"pathways":[],"terms":["pcr","efs","neoadjuvant-adjuvant"],"trials":[],"people":["patrick-forde","lu-shun","enriqueta-felip","julie-brahmer","everett-vokes"],"bottlenecks":["b-immunotherapy-response","b-trial-design","b-dormancy-mrd"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/NEJMoa2202170","authors":"Forde PM, Spicer J, Lu S, et al.","paperType":"rct","findings":["Pathological complete response 24.0% vs 2.2% (odds ratio 13.9).","Median event-free survival 31.6 vs 20.8 months; HR 0.63 (97.38% CI 0.43-0.91).","Definitive surgery was performed in 83% vs 75% of patients; grade 3-4 surgery-related adverse events 11% in both arms.","Patients achieving pCR had markedly better EFS (HR about 0.13 within the nivolumab arm).","Overall survival (2025 update): HR about 0.72, with 5-year OS of roughly 65% vs 55%."],"whatItMeans":"Patients with operable stage II-III lung cancer without EGFR or ALK alterations should have chemo-immunotherapy discussed before surgery rather than only afterwards. Three pre-operative cycles do not compromise the operation and improve cure rates. Whether to continue immunotherapy after surgery, as the perioperative trials do, and whether patients with pCR need any further treatment, remain open questions.","caveats":["Open-label; EFS by blinded review.","About one in six patients did not proceed to surgery in either arm, an under-appreciated risk of any neoadjuvant strategy.","Benefit was smaller in stage IB-II and in PD-L1-negative tumours.","No adjuvant immunotherapy was given, so the trial cannot say whether the perioperative approach adds value over neoadjuvant alone."],"changedPractice":true,"participants":358},{"id":"paper-checkmate-8hw-lancet-2025","kind":"paper","name":"CheckMate 8HW: nivolumab plus ipilimumab versus nivolumab alone in MSI-high metastatic colorectal cancer","aka":[],"tldr":"Dual immunotherapy with nivolumab and ipilimumab delayed progression more than nivolumab alone across all lines of treatment in microsatellite-unstable colorectal cancer, with about seven in ten patients progression-free at three years.","summary":"Phase 3 trial of 707 patients with microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer randomised to nivolumab plus ipilimumab, nivolumab alone or chemotherapy; this report compares the two immunotherapy arms across all lines.\n\nProgression-free survival favoured the combination (hazard ratio 0.62; three-year rate about 68 versus 51 percent) with a higher response rate (71 versus 58 percent); grade 3 to 4 treatment-related adverse events were 22 versus 14 percent.","asOf":"2026-09-17","links":[{"label":"Lancet 2025","url":"https://doi.org/10.1016/S0140-6736(24)02848-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39874977/"}],"tags":[],"related":[],"cancers":["msi-high-colorectal"],"sections":[],"technologies":[],"targets":[],"drugs":["ipilimumab","nivolumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-8hw"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2025,"doi":"10.1016/S0140-6736(24)02848-4","pmid":"39874977","authors":"André T, Elez E, Lenz HJ, et al.","paperType":"rct","findings":["Progression-free survival hazard ratio 0.62 for the combination vs nivolumab alone.","Objective response 71 percent vs 58 percent."],"whatItMeans":"Nivolumab-ipilimumab is a first-line standard for microsatellite-unstable metastatic colorectal cancer alongside pembrolizumab, with the trade-off of more immune toxicity for deeper and more durable control.","caveats":["Overall survival data immature at this report.","The earlier comparison with chemotherapy was first line only."],"changedPractice":true,"participants":707},{"id":"paper-macdonald-n-engl-j-med","kind":"paper","name":"Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 11547741 and published in New England Journal of Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Background: Surgical resection of adenocarcinoma of the stomach is curative in less than 40 percent of cases. We investigated the effect of surgery plus postoperative (adjuvant) chemoradiotherapy on the survival of patients with resectable adenocarcinoma of the stomach or gastroesophageal junction.\n\nMethods: A total of 556 patients with resected adenocarcinoma of the stomach or gastroesophageal junction were randomly assigned to surgery plus postoperative chemoradiotherapy or surgery alone. The adjuvant treatment consisted of 425 mg of fluorouracil per square meter of body-surface area per day, plus 20 mg of leucovorin per square meter per day, for five days, followed by 4500 cGy of radiation at 180 cGy per day, given five days per week for five weeks, with modified doses of fluorouracil and leucovorin on the first four and the last three days of radiotherapy. One month after the completion of radiotherapy, two five-day cycles of fluorouracil (425 mg per square meter per day) plus leucovorin (20 mg per square meter per day) were given one month apart.\n\nResults: The median overall survival in the surgery-only group was 27 months, as compared with 36 months in the chemoradiotherapy group; the hazard ratio for death was 1.35 (95 percent confidence interval, 1.09 to 1.66; P=0.005). The hazard ratio for relapse was 1.52 (95 percent confidence interval, 1.23 to 1.86; P<0.001). Three patients (1 percent) died from toxic effects of the chemoradiotherapy; grade 3 toxic effects occurred in 41 percent of the patients in the chemoradiotherapy group, and grade 4 toxic effects occurred in 32 percent.\n\nConclusions: Postoperative chemoradiotherapy should be considered for all patients at high risk for recurrence of adenocarcinoma of the stomach or gastroesophageal junction who have undergone curative resection.\n\nIndexed on Europe PMC as PubMed record 11547741 (DOI 10.1056/nejmoa010187). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2001","url":"https://doi.org/10.1056/nejmoa010187"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/11547741/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/11547741"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["int-0116"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2001,"doi":"10.1056/nejmoa010187","pmid":"11547741","authors":"Macdonald JS, Smalley SR, Benedetti J, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-lu-j-natl-cancer-inst","kind":"paper","name":"Chemoradiotherapy with or without AE-941 in stage III non-small cell lung cancer: a randomized phase III trial","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 20505152 and published in JNCI: Journal of the National Cancer Institute; the citing page links this DOI, which is how the record was matched.","summary":"BACKGROUND AE-941 is a standardized aqueous shark cartilage extract with antiangiogenic properties that has previously been evaluated in phase I and II clinical trials. Our objective was to determine the effect of adding AE-941 to chemoradiotherapy on overall survival of patients with unresectable stage III non-small cell lung cancer (NSCLC). METHODS A randomized, double-blinded, placebo-controlled, phase III clinical trial was designed to test the efficacy of AE-941 in unresectable stage III NSCLC patients who were treated with chemoradiotherapy. Between June 5, 2000, and February 6, 2006, 379 eligible patients were enrolled in community and academic oncology centers across the United States and Canada. In February 2006, the trial was closed to new patient entry before meeting the target sample size because of insufficient accrual. All subjects received induction chemotherapy followed by concurrent chemotherapy with chest radiotherapy. Each participating center administered one of the two chemotherapy regimens, either carboplatin and paclitaxel, or cisplatin and vinorelbine. The primary endpoint was overall survival, and secondary endpoints were time to progression, progression-free survival, tumor response rate, and toxic effects. Event-time distributions were estimated by the Kaplan-Meier method. All statistical tests were two-sided. RESULTS There was no statistically significant difference in overall survival between the chemoradiotherapy plus AE-941 group (n = 188; median survival = 14.4 months, 95% confidence interval = 12.6 to 17.9 months) and the chemoradiotherapy plus placebo group (n = 191; median survival = 15.6 months, 95% confidence interval = 13.8 to 18.1 months) (P =.73). Time to progression, progression-free survival, and tumor response rates were not statistically significantly different between the AE-941 and the placebo groups. No differences between the two groups were observed in common grade 3 or higher toxic effects attributable to chemoradiotherapy. CONCLUSIONS The addition of AE-941 to chemoradiotherapy did not improve overall survival in patients with unresectable stage III NSCLC. This study does not support the use of shark cartilage-derived products as therapy for lung cancer.\n\nIndexed on Europe PMC as PubMed record 20505152 (DOI 10.1093/jnci/djq179). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Natl Cancer Inst 2010","url":"https://doi.org/10.1093/jnci/djq179"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20505152/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/20505152"}],"tags":["europepmc-ingest"],"related":["shark-cartilage"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jnci"],"dependsOn":[],"notes":[],"journal":"JNCI: Journal of the National Cancer Institute","year":2010,"doi":"10.1093/jnci/djq179","pmid":"20505152","authors":"Lu C, Lee JJ, Komaki R, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-phergain-lancet-oncol-2021","kind":"paper","name":"Chemotherapy de-escalation using an 18 F-FDG-PET-based pathological response-adapted strategy in patients with HER2-positive early breast cancer (PHERGain): a multicentre, randomised, open-label, non-comparative, phase 2 trial","aka":[],"tldr":"Published report from the PHERGain trial registered as NCT03161353, in The Lancet Oncology (2021), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Several de-escalation approaches are under investigation in patients with HER2-positive, early-stage breast cancer. We assessed early metabolic responses to neoadjuvant trastuzumab and pertuzumab using 18 F-fluorodeoxyglucose ( 18 F-FDG)-PET ( 18 F-FDG-PET) and the possibility of chemotherapy de-escalation using a pathological response-adapted strategy.\n\nMethods: We did a multicentre, randomised, open-label, non-comparative, phase 2 trial in 45 hospitals in Spain, France, Belgium, Germany, the UK, Italy, and Portugal. Eligible participants were women aged 18 years or older with centrally confirmed, HER2-positive, stage I-IIIA, invasive, operable breast cancer (≥1·5 cm tumour size) with at least one breast lesion evaluable by 18 F-FDG-PET, an Eastern Cooperative Oncology Group performance status of 0 or 1, and a baseline left ventricular ejection fraction of at least 55%. We randomly assigned participants (1:4), via an interactive response system using central block randomisation with block sizes of five, stratified by hormone receptor status, to either docetaxel (75 mg/m 2 intravenous), carboplatin (area under the concentration-time curve 6 mg/mL per min intravenous), trastuzumab (subcutaneous 600 mg fixed dose), and pertuzumab (intravenous 840 mg loading dose, 420 mg maintenance doses; group A); or trastuzumab and pertuzumab (group B). Hormone receptor-positive patients allocated to group B were additionally given letrozole if postmenopausal (2·5 mg/day orally) or tamoxifen if premenopausal (20 mg/day orally). Centrally reviewed 18 F-FDG-PET scans were done before randomisation and after two treatment cycles. Patients assigned to group A completed six cycles of treatment (every 3 weeks) regardless of 18 F-FDG-PET results. All patients assigned to group B initially received two cycles of trastuzumab and pertuzumab. 18 F-FDG-PET responders in group B continued this treatment for six further cycles; 18 F-FDG-PET non-responders in this group were switched to six cycles of docetaxel, carboplatin, trastuzumab, and pertuzumab. Surgery was done 2-6 weeks after the last dose of study treatment. Adjuvant treatment was selected according to the neoadjuvant treatment administered, pathological response, hormone receptor status, and clinical stage at diagnosis. The coprimary endpoints were the proportion of 18 F-FDG-PET responders in group B with a pathological complete response in the breast and axilla (ypT0/is ypN0) as determined by a local pathologist after surgery after eight cycles of treatment, and 3-year invasive disease-free survival of patients in group B, both assessed by intention to treat. The definitive assessment of pathological complete response was done at this primary analysis; follow-up to assess invasive disease-free survival is continuing, hence these data are not included in this Article. Safety was assessed in all participants who received at least one dose of study drug. Health-related quality-of-life was assessed with EORTC QLQ-C30 and QLQ-BR23 questionnaires at baseline, after two cycles of treatment, and before surgery. This trial is registered with EudraCT (2016-002676-27) and ClinicalTrials.gov (NCT03161353), and is ongoing.\n\nFindings: Between June 26, 2017, and April 24, 2019, we randomly assigned 71 patients to group A and 285 to group B. Median follow-up was 5·7 months (IQR 5·3-6·0). 227 (80%) of 285 patients in group B were 18 F-FDG-PET responders, of whom 86 (37·9%, 95% CI 31·6-44·5; p<0·0001 compared with the historical rate) of 227 had a pathological complete response. The most common haematological grade 3-4 adverse events were anaemia (six [9%] of 68 patients in group A vs four [1%] of 283 patients in group B), neutropenia (16 [24%] vs ten [4%]), and febrile neutropenia (14 [21%] vs 11 [4%]). Serious adverse events occurred in 20 (29%) of 68 patients in group A versus 13 (5%) of 283 patients in group B. No deaths were reported during neoadjuvant treatment. Global health status declined by at least 10% in 65·0% (95% CI 46·5-72·4) and 35·5% (29·7-41·7) of patients in groups A and B, respectively INTERPRETATION: 18 F-FDG-PET identified patients with HER2-positive, early-stage breast cancer who were likely to benefit from chemotherapy-free dual HER2 blockade with trastuzumab and pertuzumab, and a reduced impact on global health status. Depending on the forthcoming results for the 3-year invasive disease-free survival endpoint, this strategy might be a valid approach to select patients not requiring chemotherapy.\n\nFunding: F Hoffmann-La Roche.\n\nIndexed on Europe PMC as PubMed record 34019819 (DOI 10.1016/s1470-2045(21)00122-4). Its abstract cites the registry id NCT03161353, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2021","url":"https://doi.org/10.1016/s1470-2045(21)00122-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34019819/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34019819"},{"label":"ClinicalTrials.gov NCT03161353","url":"https://clinicaltrials.gov/study/NCT03161353"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["phergain"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2021,"doi":"10.1016/s1470-2045(21)00122-4","pmid":"34019819","authors":"Pérez-García JM, Gebhart G, Ruiz Borrego M, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03161353 with the most citations, so it is the natural first reading for anyone following the PHERGain trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-nsclc-collaborative-group-chemotherapy-meta-analysis-bmj-1995","kind":"paper","name":"Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials","aka":[],"tldr":"Before 1995 many doctors thought chemotherapy did nothing for lung cancer. Pooling 9,387 patients from 52 trials showed it did something: a 27 percent reduction in the risk of death when added to supportive care, worth about 10 percent more people alive at one year.","summary":"The Non-small Cell Lung Cancer Collaborative Group's individual-patient-data meta-analysis of all available randomised trials, published and unpublished: 9,387 patients and 7,151 deaths from 52 trials.\n\nIts importance is as much methodological as clinical. It is an early demonstration that individual patient data, collected from investigators rather than read off published tables, can settle a question that a decade of separate underpowered trials had left open, and it is the paper that made cisplatin-based chemotherapy a standard rather than an option in non-small-cell lung cancer.","asOf":"2026-09-25","links":[{"label":"BMJ 1995","url":"https://europepmc.org/article/MED/7580546"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/7580546/"}],"tags":["lung-evidence"],"related":["chemotherapy-roadmap","paper-lace-adjuvant-cisplatin-pooled-analysis-jco-2008","paper-schiller-ecog-1594-four-chemotherapy-regimens-nejm-2002"],"cancers":["lung-cancer","nsclc"],"sections":["drug-discovery"],"technologies":["radiotherapy"],"targets":[],"drugs":["cisplatin"],"companies":[],"institutions":[],"pathways":[],"terms":["neoadjuvant-adjuvant"],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-negative-results","b-real-world-evidence"],"keyPapers":[],"journals":["bmj"],"dependsOn":[],"notes":[],"journal":"BMJ","year":1995,"pmid":"7580546","authors":"Non-small Cell Lung Cancer Collaborative Group.","paperType":"meta-analysis","findings":["Surgery plus chemotherapy against surgery alone: hazard ratio 0.87, a 13 percent reduction in the risk of death, an absolute benefit of 5 percent at five years.","Radical radiotherapy plus chemotherapy against radiotherapy alone: hazard ratio 0.87, an absolute benefit of 4 percent at two years.","Supportive care plus chemotherapy against supportive care alone: hazard ratio 0.73, a 27 percent reduction in the risk of death and a 10 percent improvement in survival at one year.","The essential drugs needed to achieve these effects were not identified.","No difference in the size of effect was seen in any subgroup of patients.","Older trials using long-term alkylating agents tended to show a detrimental effect, reaching conventional significance in the adjuvant surgical comparison."],"whatItMeans":"The paper that ended therapeutic nihilism in lung cancer. The effect was small, and saying so honestly is what made it credible; every later trial in advanced disease is measured against the platinum doublet this analysis justified.","caveats":["Trials from the 1960s to the early 1990s, with staging, supportive care and radiotherapy of that era.","It could not identify which drugs produced the benefit, and the regimens tested are not the ones used now.","An absolute five-year benefit of about 5 percent after surgery is real but modest, and comes with the toxicity of cisplatin."],"changedPractice":true,"participants":9387},{"id":"paper-chen-cancer-statistics-china-2015-cacancer-2016","kind":"paper","name":"Chen 2016: Cancer statistics in China, 2015","aka":[],"tldr":"The first national cancer estimate for China built from population registries, projecting about 4.3 million new cancer cases in 2015, with lung cancer the most common cancer and leading cause of cancer death, and stomach, oesophageal and liver cancers far more prominent than in Western countries.","summary":"Chen and colleagues at China's National Cancer Center used data from 72 local population-based cancer registries covering 2009 to 2011, about 6.5% of the population, to project cancer incidence and mortality in China for 2015. They estimated about 4.3 million new cases and 2.8 million deaths. Lung cancer was the most common cancer and the leading cause of death, followed by stomach, oesophageal, liver and colorectal cancers, and the report documented rising incidence in cities alongside higher mortality in rural areas, as well as a large burden of infection-related cancers.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.3322/caac.21338"}],"tags":[],"related":["paper-bray-globocan-2018-cacancer-2018"],"cancers":["nsclc","gastric","hcc","colorectal"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["ncc-china"],"pathways":[],"terms":["incidence-vs-prevalence","mortality"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"CA: A Cancer Journal for Clinicians","year":2016,"doi":"10.3322/caac.21338","authors":"Chen W, Zheng R, Baade PD, et al.","paperType":"observational","findings":["About 4,292,000 new cancer cases and 2,814,000 cancer deaths projected for China in 2015.","Lung cancer the most common cancer and leading cause of cancer death; stomach, oesophageal, liver and colorectal cancers next.","Based on 72 population-based registries covering about 6.5% of the population; rural areas had higher mortality than cities."],"whatItMeans":"China accounts for roughly a quarter of the world's cancer cases, and this paper is the reference that made its burden legible internationally. It explains why Chinese trial programmes and drug pipelines concentrate on lung, stomach, oesophageal and liver cancers.","caveats":["Registries covered a small, mainly urban share of the population, so estimates involve substantial extrapolation.","Later National Cancer Center reports have updated the figures."],"changedPractice":false},{"id":"paper-chen-mellman-cancer-immunity-cycle-immunity-2013","kind":"paper","name":"Chen and Mellman 2013: the cancer-immunity cycle","aka":[],"tldr":"The seven-step diagram of how the immune system should destroy a cancer, from releasing tumour antigens to killing tumour cells, and the idea that each patient's cancer breaks the cycle at a different step, which tells you which immunotherapies to combine.","summary":"Chen and Mellman at Genentech laid out the cancer-immunity cycle: release of cancer cell antigens, antigen presentation by dendritic cells, priming and activation of T cells, trafficking to the tumour, infiltration, recognition of cancer cells and killing, which releases more antigens. They argued that effective immunity requires every step to work, that tumours block different steps in different patients, and that therapies should be matched to the rate-limiting step, with PD-L1 and PD-1 blockade acting at the final killing step. They introduced the term immunostat for the factors that set the balance.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1016/j.immuni.2013.07.012"}],"tags":[],"related":["paper-pardoll-immune-checkpoint-blockade-nrc-2012","paper-binnewies-tumor-immune-microenvironment-natmed-2018"],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["pd1","pdl1"],"drugs":[],"companies":["roche-genentech"],"institutions":[],"pathways":[],"terms":["immune-system","neoantigen","cold-vs-hot"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Immunity","year":2013,"doi":"10.1016/j.immuni.2013.07.012","authors":"Chen DS, Mellman I.","paperType":"review","findings":["Anti-cancer immunity proceeds through seven steps from antigen release to tumour cell killing, each of which can fail.","Different tumours and patients are limited at different steps, so no single immunotherapy will work for all.","Checkpoint blockade acts at the recognition and killing step; other therapies target priming, trafficking or infiltration."],"whatItMeans":"The cycle is the most used framework for designing immunotherapy combinations, from vaccines and radiotherapy that release antigens to drugs that recruit T cells into cold tumours. Most trial rationales in immuno-oncology cite it.","caveats":["A conceptual review; the steps are idealised and the rate-limiting step is hard to measure in practice.","Written by authors at a company developing a PD-L1 antibody."],"changedPractice":false},{"id":"paper-chhip-lancet-oncol-2016","kind":"paper","name":"CHHiP: conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer","aka":[],"tldr":"Delivering prostate radiotherapy in 20 larger daily doses over four weeks was as effective as 37 smaller doses over seven and a half weeks, with no more side effects, and became the standard schedule in many countries.","summary":"Phase 3 non-inferiority trial of 3,216 men with localised prostate cancer (mostly intermediate risk) randomised to 74 Gy in 37 fractions, 60 Gy in 20 fractions or 57 Gy in 19 fractions of intensity-modulated radiotherapy with short-course androgen deprivation.\n\nFive-year biochemical or clinical failure-free rates were 88.3 percent (74 Gy), 90.6 percent (60 Gy) and 85.9 percent (57 Gy); 60 Gy in 20 fractions was non-inferior and toxicity was similar.","asOf":"2026-09-17","links":[{"label":"Lancet Oncol 2016","url":"https://doi.org/10.1016/S1470-2045(16)30102-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27339115/"}],"tags":[],"related":[],"cancers":["prostate-intermediate-risk"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["chhip"],"people":["david-dearnaley"],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2016,"doi":"10.1016/S1470-2045(16)30102-4","pmid":"27339115","authors":"Dearnaley D, Syndikus I, Mossop H, et al.","paperType":"rct","findings":["Five-year failure-free rate 90.6 percent (60 Gy/20) vs 88.3 percent (74 Gy/37); non-inferior.","57 Gy in 19 fractions did not meet non-inferiority."],"whatItMeans":"Moderate hypofractionation (60 Gy in 20 fractions) is a standard of care for localised prostate cancer, halving the number of hospital visits.","caveats":["Most men received short-course androgen deprivation.","Ultra-hypofractionation (five fractions) was tested separately in PACE-B."],"changedPractice":true,"participants":3216},{"id":"paper-aall1731-blinatumomab-children-nejm-2025","kind":"paper","name":"Children's Oncology Group AALL1731: blinatumomab added to chemotherapy for children with standard-risk B-cell ALL","aka":[],"tldr":"Two courses of blinatumomab added to standard chemotherapy cut relapses in children with average- or higher-risk standard-risk leukaemia, raising three-year disease-free survival from 88% to 96%.","summary":"AALL1731 was a phase 3 Children's Oncology Group trial in children aged 1 to under 10 with newly diagnosed National Cancer Institute standard-risk B-cell ALL. Those with average- or high-risk features after induction (1440 patients) were randomised to standard chemotherapy or the same chemotherapy with two 28-day cycles of blinatumomab. The primary endpoint was disease-free survival. At the first interim analysis three-year DFS was 96.0% with blinatumomab versus 87.9% (hazard ratio 0.39), and randomisation was stopped early for efficacy. Sepsis and catheter-related infections were more frequent with blinatumomab, but there were few grade 3 or higher CRS or neurological events.","asOf":"2026-09-08","links":[{"label":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=AALL1731%20blinatumomab%20standard-risk%20B-ALL%20children%20Gupta%20NEJM%202025"},{"label":"ClinicalTrials.gov NCT03914625","url":"https://clinicaltrials.gov/study/NCT03914625"}],"tags":[],"related":["blinatumomab-frontline-consolidation","paper-e1910-blinatumomab-mrd-negative-all-nejm-2024"],"cancers":["all-leukemia","all-paediatric-standard-risk"],"sections":[],"technologies":["bispecific-antibody","t-cell-engager"],"targets":["cd19","cd3"],"drugs":["blinatumomab"],"companies":["amgen","childrens-oncology-group"],"institutions":[],"pathways":[],"terms":["efs","mrd"],"trials":["aall1731"],"people":["rachel-rau"],"bottlenecks":["b-trial-design","b-survivorship"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2025,"doi":"10.1056/NEJMoa2411680","pmid":"39651791","authors":"Gupta S, Rau RE, Kairalla JA, et al.","paperType":"rct","findings":["1440 children with NCI standard-risk B-ALL (average- or high-risk subgroups) randomised; chemotherapy with or without 2 cycles of blinatumomab.","3-year disease-free survival 96.0% vs 87.9%; hazard ratio 0.39.","Benefit in both the average-risk and high-risk standard-risk subgroups.","Randomisation halted early at interim analysis for efficacy.","Higher rates of sepsis and catheter-related infections with blinatumomab; CRS and neurotoxicity rare and mostly low grade."],"whatItMeans":"AALL1731 brings immunotherapy into the front-line treatment of the commonest childhood cancer, in the group of children where most relapses were occurring despite good initial risk. Blinatumomab was approved for this use in 2024 and paediatric protocols worldwide are being amended. Whether it can allow less chemotherapy, and its effect on very low-risk children, are the next questions.","caveats":["Early stopping at interim analysis may overestimate the effect size.","Follow-up is short for a disease where late relapses occur; overall survival not yet different.","Infection-related toxicity and central-line management are practical concerns in small children.","Very favourable-risk children (not randomised) were not tested."],"changedPractice":true,"participants":1440},{"id":"paper-taixiang-cochrane-database-syst-rev","kind":"paper","name":"Chinese medical herbs for chemotherapy side effects in colorectal cancer patients","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 15674951 and published in The Cochrane database of systematic reviews; the citing page links this DOI, which is how the record was matched.","summary":"Background: Side effects, including nausea and vomiting, sore mouth, diarrhoea, hepatotoxicity, myelosuppression, and immunosuppression, are commonly encountered in patients with colorectal cancer who are treated with chemotherapy. A variety of Chinese herbal medicines have been used for managing these adverse effects.\n\nObjectives: To assess the effect of herbal medicines plus chemotherapy, compared with chemotherapy alone, on the side effects of chemotherapy on the quality of life, and on adverse events in patients with colorectal cancer.\n\nSearch strategy: We searched the Cochrane Library, MEDLINE, EMBASE, CBM, and handsearched the relevant Chinese journals.\n\nSelection criteria: Randomised trials comparing either chemotherapy only or chemotherapy plus anti-emetics (tropisetron, sulpiride etc) with chemotherapy plus Chinese herbs.\n\nData collection and analysis: Trial quality was assessed independently by two reviewers. Data were extracted by one reviewer and checked by the second reviewer. Since the four included studies differed significantly in design, we could only perform limited meta-analyses. We have therefore presented the majority of the data in narrative form.\n\nMain results: We included four relevant trials. All of them were of low quality. All of studies used a decoction containing Huangqi compounds as the intervention with chemotherapy. The intervention groups of three studies were compared to a chemotherapy alone control group, the fourth study compared the decoction of Huangqi compounds with two other Chinese herbal interventions. None of the studies reported on primary outcome using Common Toxicity Criteria (CTC). There was a significant reduction in the proportion of patients who experienced nausea & vomiting when decoctions of Huangqi compounds were given in addition to chemotherapy. There was also a decrease in the rate of leucopenia (WBC <3 x 10(9) per L). Huangqi compounds were also associated with increases in the proportions of T-lymphocyte subsets: CD3; CD4 and CD8. Huangqi decoctions had no significant effects on Immunoglobulins G, A or M.\n\nAuthors' conclusions: Despite the included studies being of low quality, the results suggest that decoctions of Huangqi compounds may stimulate immunocompetent cells and decrease side effects in patients treated with chemotherapy. Due to the methodological limitations of the studies, there is no robust demonstration of benefit. We found no evidence of harm arising from the use of Chinese herbs. We need high quality randomised controlled studies investigating the effects of decoctions of Chinese herbs, particularly Astragalus spp.(as in Huangqi), upon chemotherapy-related side effects.\n\nIndexed on Europe PMC as PubMed record 15674951 (DOI 10.1002/14651858.cd004540.pub2). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cochrane Database Syst Rev 2005","url":"https://doi.org/10.1002/14651858.cd004540.pub2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/15674951/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/15674951"}],"tags":["europepmc-ingest"],"related":["traditional-chinese-herbal-medicine"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Cochrane database of systematic reviews","year":2005,"doi":"10.1002/14651858.cd004540.pub2","pmid":"15674951","authors":"Taixiang W, Munro AJ, Guanjian L","paperType":"meta-analysis","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-chmielecki-acinar-cell-carcinoma-raf-fusions-dna-repair-cancer-discov-2014","kind":"paper","name":"Chmielecki 2014: comprehensive genomic profiling of pancreatic acinar cell carcinomas identifies recurrent RAF fusions and frequent inactivation of DNA repair genes","aka":[],"tldr":"Sequencing of acinar cell carcinomas found that they do not carry the KRAS mutation that drives ordinary pancreatic cancer; instead about a quarter have fusions activating BRAF or RAF1, which MEK-blocking drugs can shut down in the laboratory, and almost half have broken DNA repair genes that may make them sensitive to platinum and PARP inhibitors.","summary":"Targeted sequencing of 44 pancreatic acinar cell carcinomas. Recurrent gene fusions involving BRAF or RAF1 (including SND1-BRAF and HERPUD1-BRAF) were found in about 23 percent of tumours, with mutual exclusivity from other MAPK alterations, and cell lines expressing the fusions were sensitive to MEK inhibition.\n\nAbout 45 percent of tumours carried inactivating alterations in DNA repair genes such as BRCA2, PALB2, ATM and MSH2, and KRAS mutations were rare. The genomic landscape was distinct from ductal adenocarcinoma, with high mutational heterogeneity and few recurrent point mutations.","asOf":"2026-09-21","links":[{"label":"Cancer Discov 2014","url":"https://doi.org/10.1158/2159-8290.CD-14-0617"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25266736/"}],"tags":[],"related":[],"cancers":["pancreatic-acinar-cell-carcinoma","pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-discovery"],"dependsOn":[],"notes":[],"journal":"Cancer Discovery","year":2014,"doi":"10.1158/2159-8290.CD-14-0617","pmid":"25266736","authors":"Chmielecki J, Hutchinson KE, Frampton GM, et al.","paperType":"translational","findings":["RAF fusions (BRAF or RAF1) in about 23 percent of acinar cell carcinomas, sensitive to MEK inhibitors in models.","DNA repair gene inactivation in about 45 percent; KRAS mutations rare."],"whatItMeans":"Acinar cell carcinoma should be sequenced: RAF fusions and DNA repair defects offer targeted and platinum or PARP inhibitor options that ductal adenocarcinoma rarely has.","caveats":["Therapeutic sensitivity was shown in cell models and case reports, not trials.","Fusion detection depends on assay design; RNA-based testing finds more."],"participants":44},{"id":"paper-glunde-nat-rev-cancer","kind":"paper","name":"Choline metabolism in malignant transformation","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 22089420 and published in Nature Reviews Cancer; the citing page links this DOI, which is how the record was matched.","summary":"Abnormal choline metabolism is emerging as a metabolic hallmark that is associated with oncogenesis and tumour progression. Following transformation, the modulation of enzymes that control anabolic and catabolic pathways causes increased levels of choline-containing precursors and breakdown products of membrane phospholipids. These increased levels are associated with proliferation, and recent studies emphasize the complex reciprocal interactions between oncogenic signalling and choline metabolism. Because choline-containing compounds are detected by non-invasive magnetic resonance spectroscopy (MRS), increased levels of these compounds provide a non-invasive biomarker of transformation, staging and response to therapy. Furthermore, enzymes of choline metabolism, such as choline kinase, present novel targets for image-guided cancer therapy.\n\nIndexed on Europe PMC as PubMed record 22089420 (DOI 10.1038/nrc3162). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Cancer 2011","url":"https://doi.org/10.1038/nrc3162"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22089420/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/22089420"}],"tags":["europepmc-ingest"],"related":["choline-metabolism-in-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Cancer","year":2011,"doi":"10.1038/nrc3162","pmid":"22089420","authors":"Glunde K, Bhujwalla ZM, Ronen SM","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-bakhoum-nature","kind":"paper","name":"Chromosomal instability drives metastasis through a cytosolic DNA response","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 29342134 and published in Nature; the citing page links this DOI, which is how the record was matched.","summary":"Chromosomal instability is a hallmark of cancer that results from ongoing errors in chromosome segregation during mitosis. Although chromosomal instability is a major driver of tumour evolution, its role in metastasis has not been established. Here we show that chromosomal instability promotes metastasis by sustaining a tumour cell-autonomous response to cytosolic DNA. Errors in chromosome segregation create a preponderance of micronuclei whose rupture spills genomic DNA into the cytosol. This leads to the activation of the cGAS-STING (cyclic GMP-AMP synthase-stimulator of interferon genes) cytosolic DNA-sensing pathway and downstream noncanonical NF-κB signalling. Genetic suppression of chromosomal instability markedly delays metastasis even in highly aneuploid tumour models, whereas continuous chromosome segregation errors promote cellular invasion and metastasis in a STING-dependent manner. By subverting lethal epithelial responses to cytosolic DNA, chromosomally unstable tumour cells co-opt chronic activation of innate immune pathways to spread to distant organs.\n\nIndexed on Europe PMC as PubMed record 29342134 (DOI 10.1038/nature25432). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2018","url":"https://doi.org/10.1038/nature25432"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29342134/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29342134"}],"tags":["europepmc-ingest"],"related":["chromosomal-instability"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2018,"doi":"10.1038/nature25432","pmid":"29342134","authors":"Bakhoum SF, Ngo B, Laughney AM, et al.","paperType":"observational","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-oeffinger-n-engl-j-med","kind":"paper","name":"Chronic health conditions in adult survivors of childhood cancer","aka":[],"tldr":"Paper cited by one bottleneck page, indexed on Europe PMC as PubMed record 17035650 and published in New England Journal of Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Background: Only a few small studies have assessed the long-term morbidity that follows the treatment of childhood cancer. We determined the incidence and severity of chronic health conditions in adult survivors.\n\nMethods: The Childhood Cancer Survivor Study is a retrospective cohort study that tracks the health status of adults who received a diagnosis of childhood cancer between 1970 and 1986 and compares the results with those of siblings. We calculated the frequencies of chronic conditions in 10,397 survivors and 3034 siblings. A severity score (grades 1 through 4, ranging from mild to life-threatening or disabling) was assigned to each condition. Cox proportional-hazards models were used to estimate hazard ratios, reported as relative risks and 95% confidence intervals (CIs), for a chronic condition.\n\nResults: Survivors and siblings had mean ages of 26.6 years (range, 18.0 to 48.0) and 29.2 years (range, 18.0 to 56.0), respectively, at the time of the study. Among 10,397 survivors, 62.3% had at least one chronic condition; 27.5% had a severe or life-threatening condition (grade 3 or 4). The adjusted relative risk of a chronic condition in a survivor, as compared with siblings, was 3.3 (95% CI, 3.0 to 3.5); for a severe or life-threatening condition, the risk was 8.2 (95% CI, 6.9 to 9.7). Among survivors, the cumulative incidence of a chronic health condition reached 73.4% (95% CI, 69.0 to 77.9) 30 years after the cancer diagnosis, with a cumulative incidence of 42.4% (95% CI, 33.7 to 51.2) for severe, disabling, or life-threatening conditions or death due to a chronic condition.\n\nConclusions: Survivors of childhood cancer have a high rate of illness owing to chronic health conditions.\n\nIndexed on Europe PMC as PubMed record 17035650 (DOI 10.1056/nejmsa060185). Matched by DOI alone: one bottleneck page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2006","url":"https://doi.org/10.1056/nejmsa060185"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/17035650/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/17035650"}],"tags":["europepmc-ingest"],"related":["b-survivorship"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2006,"doi":"10.1056/nejmsa060185","pmid":"17035650","authors":"Oeffinger KC, Mertens AC, Sklar CA, et al.","paperType":"observational","findings":[],"whatItMeans":"One bottleneck page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-ciltacabtagene-autoleucel-multiple-myeloma-front-immunol-2022","kind":"paper","name":"Ciltacabtagene autoleucel: The second anti-BCMA CAR T-cell therapeutic armamentarium of relapsed or refractory multiple myeloma","aka":[],"tldr":"Review on Ciltacabtagene autoleucel in Multiple myeloma, in Frontiers in immunology (2022), one of the most cited Europe PMC records with Ciltacabtagene autoleucel in its title.","summary":"Ciltacabtagene autoleucel (also known as cilta-cel) is a chimeric antigen receptor (CAR) T-cell therapy that targets B-cell maturation antigen (BCMA) on the surface of cancer cells in B cell malignancies, such as multiple myeloma (MM). It is a second-generation CAR that is outfitted with an ectodomain comprising two BCMA-binding single chain variable fragment (ScFv) domains, a transmembrane domain, and an endodomain possessing CD3ζ and 4-1BB. Cilta-cel is an autologous, gene-edited CAR T-cell that is prepared by collecting and modifying the recipient's T-cells to create a patient personalized treatment in the laboratory to be infused back. This CAR T-cell product exceptionally entails CARs with two BCMA-targeting single-domain antibodies that detect two epitopes of BCMA expressed on the malignant cells of MM. Cilta-cel is the current addition to the treatment armamentarium of relapsed or refractory (r/r) MM after its approval by the FDA on February 28, 2022, based on the results of the Phase 1b/2 CARTITUDE-1 study. It was the second approved anti-BCMA CAR T-cell product after idecabtagene vicleucel (ide-cel) to treat myeloma patients. It induces early, deep, and long-lasting responses with a tolerable safety profile in r/r MM. Cilta-cel-treated myeloma patients may potentially experience adverse effects ranging from mild to life-threatening, but they are mostly manageable toxicities. Besides, it has a consistent safety profile upon a longer follow-up of patients. Cilta-cel generally outperforms ide cel in terms of efficacy in MM, but shows comparable adverse events. This review highlights the current updates on cilta-cel efficacy, adverse events, comparison with ide-cel, and its future direction in the treatment of MM.\n\nIndexed on Europe PMC as PubMed record 36119032 (DOI 10.3389/fimmu.2022.991092). Its title names Ciltacabtagene autoleucel and its text names Multiple myeloma; PubMed types it as a review (review-article, Review). It was matched automatically to the idea \"One CAR-T infusion instead of autologous transplant\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Front Immunol 2022","url":"https://doi.org/10.3389/fimmu.2022.991092"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36119032/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36119032"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Frontiers in immunology","year":2022,"doi":"10.3389/fimmu.2022.991092","pmid":"36119032","authors":"Chekol Abebe E, Yibeltal Shiferaw M, Tadele Admasu F, et al.","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for Ciltacabtagene autoleucel in Multiple myeloma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Ciltacabtagene autoleucel in the title and Multiple myeloma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-bernard-ctdna-exodna-pancreatic-gastroenterology-2019","kind":"paper","name":"Circulating nucleic acids are associated with outcomes of patients with pancreatic cancer","aka":[],"tldr":"Tracking tumour DNA both free in the blood and packaged in exosomes across 194 patients showed each carries prognostic information, and together they identified patients with a nearly eightfold risk of death.","summary":"Liquid biopsies from 194 patients treated for localised or metastatic pancreatic adenocarcinoma (425 samples before and during therapy) and 37 disease controls were analysed by droplet digital PCR for KRAS mutant allele fraction in circulating tumour DNA and exosome DNA, with 123 serial samples from 34 patients. In 34 patients with potentially resectable tumours, a rise in exosome DNA after neoadjuvant therapy was associated with disease progression (P = .003), while ctDNA was not. Concordance of KRAS mutations between resected tissue and liquid biopsy exceeded 95%. In metastatic disease, detectable baseline ctDNA gave a progression-free survival hazard ratio of 1.8 and overall survival hazard ratio of 2.8; exosome DNA allele fraction of 5% or more predicted progression-free (2.28) and overall survival (3.46), and detecting both at 5% or more gave an overall survival hazard ratio of 7.73.","asOf":"2026-09-24","links":[{"label":"Bernard et al., Gastroenterology 2019: ctDNA and exosome DNA in 194 patients","url":"https://doi.org/10.1053/j.gastro.2018.09.022"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30240661/"}],"tags":[],"related":["ctdna-mrd-positive"],"cancers":["pancreatic","metastatic-pdac","borderline-resectable-pdac"],"sections":[],"technologies":["liquid-biopsy"],"targets":["kras"],"drugs":[],"companies":[],"institutions":["md-anderson"],"pathways":[],"terms":["ctdna","cfdna"],"trials":[],"people":["anirban-maitra"],"bottlenecks":[],"keyPapers":[],"journals":["gastroenterology"],"dependsOn":[],"notes":[],"journal":"Gastroenterology","year":2019,"doi":"10.1053/j.gastro.2018.09.022","pmid":"30240661","authors":"Bernard V, Kim DU, San Lucas FA, et al.","paperType":"observational","findings":["Plasma and tissue KRAS concordance above 95%.","Baseline ctDNA in metastatic disease: death hazard ratio 2.8.","Exosome DNA plus ctDNA at 5% or more: overall survival hazard ratio 7.73."],"whatItMeans":"Exosome DNA adds signal where free DNA is scarce, particularly after neoadjuvant treatment, and the two together give the strongest published blood-based prognosis in this disease.","caveats":["KRAS-targeted droplet PCR only, so wild-type tumours are invisible.","Single-centre prospective cohort."],"changedPractice":false,"participants":194},{"id":"paper-aceto-cell","kind":"paper","name":"Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 25171411 and published in Cell; the citing page links this DOI, which is how the record was matched.","summary":"Circulating tumor cell clusters (CTC clusters) are present in the blood of patients with cancer but their contribution to metastasis is not well defined. Using mouse models with tagged mammary tumors, we demonstrate that CTC clusters arise from oligoclonal tumor cell groupings and not from intravascular aggregation events. Although rare in the circulation compared with single CTCs, CTC clusters have 23- to 50-fold increased metastatic potential. In patients with breast cancer, single-cell resolution RNA sequencing of CTC clusters and single CTCs, matched within individual blood samples, identifies the cell junction component plakoglobin as highly differentially expressed. In mouse models, knockdown of plakoglobin abrogates CTC cluster formation and suppresses lung metastases. In breast cancer patients, both abundance of CTC clusters and high tumor plakoglobin levels denote adverse outcomes. Thus, CTC clusters are derived from multicellular groupings of primary tumor cells held together through plakoglobin-dependent intercellular adhesion, and though rare, they greatly contribute to the metastatic spread of cancer.\n\nIndexed on Europe PMC as PubMed record 25171411 (DOI 10.1016/j.cell.2014.07.013). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cell 2014","url":"https://doi.org/10.1016/j.cell.2014.07.013"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25171411/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25171411"}],"tags":["europepmc-ingest"],"related":["intravasation-ctc-survival"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Cell","year":2014,"doi":"10.1016/j.cell.2014.07.013","pmid":"25171411","authors":"Aceto N, Bardia A, Miyamoto DT, et al.","paperType":"observational","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-cristofanilli-n-engl-j-med","kind":"paper","name":"Circulating tumor cells, disease progression, and survival in metastatic breast cancer","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 15317891 and published in New England Journal of Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Background: We tested the hypothesis that the level of circulating tumor cells can predict survival in metastatic breast cancer.\n\nMethods: In a prospective, multicenter study, we tested 177 patients with measurable metastatic breast cancer for levels of circulating tumor cells both before the patients were to start a new line of treatment and at the first follow-up visit. The progression of the disease or the response to treatment was determined with the use of standard imaging studies at the participating centers.\n\nResults: Outcomes were assessed according to levels of circulating tumor cells at baseline, before the patients started a new treatment for metastatic disease. Patients in a training set with levels of circulating tumor cells equal to or higher than 5 per 7.5 ml of whole blood, as compared with the group with fewer than 5 circulating tumor cells per 7.5 ml, had a shorter median progression-free survival (2.7 months vs. 7.0 months, P<0.001) and shorter overall survival (10.1 months vs. >18 months, P<0.001). At the first follow-up visit after the initiation of therapy, this difference between the groups persisted (progression-free survival, 2.1 months vs. 7.0 months; P<0.001; overall survival, 8.2 months vs. >18 months; P<0.001), and the reduced proportion of patients (from 49 percent to 30 percent) in the group with an unfavorable prognosis suggested that there was a benefit from therapy. The multivariate Cox proportional-hazards regression showed that, of all the variables in the statistical model, the levels of circulating tumor cells at baseline and at the first follow-up visit were the most significant predictors of progression-free and overall survival.\n\nConclusions: The number of circulating tumor cells before treatment is an independent predictor of progression-free survival and overall survival in patients with metastatic breast cancer.\n\nIndexed on Europe PMC as PubMed record 15317891 (DOI 10.1056/nejmoa040766). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2004","url":"https://doi.org/10.1056/nejmoa040766"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/15317891/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/15317891"}],"tags":["europepmc-ingest"],"related":["cellsearch-ctc-count"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2004,"doi":"10.1056/nejmoa040766","pmid":"15317891","authors":"Cristofanilli M, Budd GT, Ellis MJ, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-tie-ctdna-minimal-residual-disease-stage-ii-colon-sci-transl-med-2016","kind":"paper","name":"Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer","aka":[],"tldr":"Traces of tumour DNA in blood after a colon cancer operation identified the patients who would relapse with a hazard ratio of 18. It is the observation the whole ctDNA field is built on.","summary":"Tie, Wang, Tomasetti and colleagues used massively parallel sequencing-based assays to evaluate the ability of circulating tumour DNA to detect minimal residual disease in 1,046 plasma samples from a prospective cohort of 230 patients with resected stage II colon cancer.\n\nIn patients who were not given adjuvant chemotherapy, postoperative circulating tumour DNA identified a group whose recurrence risk was an order of magnitude higher than everyone else's; in patients who were treated, detectable circulating tumour DNA after chemotherapy carried the same meaning.","asOf":"2026-09-24","links":[{"label":"Sci Transl Med 2016","url":"https://doi.org/10.1126/scitranslmed.aaf6219"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27384348/"},{"label":"Europe PMC full text (PMC5346159)","url":"https://europepmc.org/article/MED/27384348"}],"tags":["colorectal-evidence"],"related":["ctdna-tests","paper-dynamic-nejm-2022","ctdna-mrd-positive"],"cancers":["colorectal","colon-cancer"],"sections":["diagnostics"],"technologies":["mrd-testing","liquid-biopsy","ngs","signatera"],"targets":[],"drugs":[],"companies":[],"institutions":["wehi","peter-mac","johns-hopkins"],"pathways":[],"terms":["ctdna","mrd","cfdna","tumour-informed-assay"],"trials":["dynamic"],"people":["jeanne-tie","bert-vogelstein","kenneth-kinzler"],"bottlenecks":["b-dormancy-mrd","b-biomarker-validation"],"keyPapers":[],"journals":["science-translational-medicine"],"dependsOn":[],"notes":[],"journal":"Science Translational Medicine","year":2016,"doi":"10.1126/scitranslmed.aaf6219","pmid":"27384348","authors":"Tie J, Wang Y, Tomasetti C, et al.","paperType":"translational","findings":["Circulating tumour DNA was detected postoperatively in 14 of 178 (7.9 percent) untreated patients, 11 (79 percent) of whom had recurred at a median 27 months.","Recurrence occurred in 16 of 164 (9.8 percent) patients with negative circulating tumour DNA: hazard ratio 18 (95 percent CI 7.9 to 40, p<0.001).","In chemotherapy-treated patients, circulating tumour DNA after completion of chemotherapy also predicted inferior recurrence-free survival (hazard ratio 11, 1.8 to 68, p=0.001)."],"whatItMeans":"Minimal residual disease became measurable in solid tumours, and the DYNAMIC and CIRCULATE trials that followed turned the measurement into a treatment decision.","caveats":["Observational: it shows prognosis, not that acting on the result helps.","Tumour-informed assay requiring tissue sequencing first, with a turnaround that constrains how soon after surgery it can be used.","Only 14 patients were positive, so the positive predictive estimate rests on a small number."],"changedPractice":true,"participants":230},{"id":"paper-dynamic-nat-med-2025-update","kind":"paper","name":"Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer: 5-year outcomes of the randomized DYNAMIC trial","aka":[],"tldr":"Later report from the DYNAMIC trial registered as ACTRN12615000381583, in Nature Medicine (2025); its title describes an updated or longer-term analysis.","summary":"Early data from the DYNAMIC study of circulating tumor DNA (ctDNA)-guided adjuvant chemotherapy (ACT) versus standard approach met its primary outcome demonstrating reduced ACT use without compromising 2-year recurrence-free survival (RFS) for stage II colon cancer. We report here other prespecified analyses of overall survival, ctDNA clearance and ctDNA level. At a median follow-up of 59.7 months, 5-year RFS was 88% and 87% with ctDNA-guided and standard management, respectively (difference 1.1%, 95% confidence interval -5.8% to 8.0%), and 5-year overall survival is similar (93.8% versus 93.3%, hazard ratio (HR) 1.05; P = 0.887). For treated ctDNA-positive patients, ctDNA clearance was observed at the end of ACT (EOT) in 35 out of 40 patients (87.5%). A higher than median postoperative tumor-derived mutant molecules per milliliter plasma was associated with worse 5-year RFS (HR 10.62; P = 0.005). For treated ctDNA-positive patients, post hoc analysis of ctDNA clearance at EOT assessed by a new assay that evaluated an average of 29 tumor-derived mutations per patient predicted for a favorable 5-year recurrence-free probability of 97% versus 0% for ctDNA persistence (P < 0.001). Mature DYNAMIC outcome data support a ctDNA-guided approach to ACT for stage II colon cancer, with potential to further risk stratify ctDNA-positive patients based on ctDNA burden and EOT results. Australian New Zealand Clinical Trials Registry Identifier: ACTRN12615000381583.\n\nIndexed on Europe PMC as PubMed record 40055522 (DOI 10.1038/s41591-025-03579-w). Its abstract cites the registry id ACTRN12615000381583, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Nat Med 2025","url":"https://doi.org/10.1038/s41591-025-03579-w"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40055522/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40055522"},{"label":"ClinicalTrials.gov ACTRN12615000381583","url":"https://clinicaltrials.gov/study/ACTRN12615000381583"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["dynamic"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2025,"doi":"10.1038/s41591-025-03579-w","pmid":"40055522","authors":"Tie J, Wang Y, Lo SN, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the DYNAMIC trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-groot-kras-ctdna-clinical-test-resected-pancreatic-ccr-2019","kind":"paper","name":"Circulating tumor DNA as a clinical test in resected pancreatic cancer","aka":[],"tldr":"A clinically accredited blood test for the four common KRAS mutations found tumour DNA in half of 59 patients before surgery and predicted recurrence afterwards with 90% sensitivity, about three months before the scan.","summary":"Digital droplet PCR was used in a CLIA and CAP-certified laboratory to detect the major pancreatic KRAS mutations (G12D, G12V, G12R, Q61H) in liquid biopsies, with 290 preoperative and longitudinal postoperative plasma samples from 59 patients. ctDNA was detected preoperatively in 29 (49%) and independently predicted decreased recurrence-free and overall survival. Patients who had neoadjuvant chemotherapy were less likely to have preoperative ctDNA (21% versus 69%). Levels dropped after resection; persistence immediately afterwards went with a high recurrence rate and median recurrence-free survival of 5 months. ctDNA during follow-up predicted recurrence with 90% sensitivity and 88% specificity at a median lead time of 84 days; detection during follow-up gave median overall survival 17 months against not reached at 30 months.","asOf":"2026-09-24","links":[{"label":"Groot et al., Clin Cancer Res 2019: KRAS ctDNA as a clinical laboratory test in 59 resected patients","url":"https://doi.org/10.1158/1078-0432.CCR-19-0197"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31142500/"}],"tags":[],"related":["ctdna-mrd-positive"],"cancers":["pancreatic","resectable-pdac"],"sections":[],"technologies":["liquid-biopsy","mrd-testing"],"targets":["kras"],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":[],"terms":["ctdna","mrd"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2019,"doi":"10.1158/1078-0432.CCR-19-0197","pmid":"31142500","authors":"Groot VP, Mosier S, Javed AA, et al.","paperType":"observational","findings":["Preoperative ctDNA in 49%; neoadjuvant chemotherapy lowers it to 21% from 69%.","Follow-up ctDNA predicted recurrence with 90% sensitivity and 88% specificity, lead time 84 days.","Detection during follow-up: overall survival 17 months versus not reached."],"whatItMeans":"It shows a KRAS ctDNA test can be run to clinical laboratory standards in this disease, and it quantifies the lead time a surveillance programme would gain.","caveats":["Four KRAS mutations only; 59 patients.","No trial has shown that earlier detection of recurrence changes outcome."],"changedPractice":false,"participants":59},{"id":"paper-lee-ctdna-adjuvant-benefit-localized-pancreatic-ann-oncol-2019","kind":"paper","name":"Circulating tumor DNA as a potential marker of adjuvant chemotherapy benefit following surgery for localized pancreatic cancer","aka":[],"tldr":"In an Australian study of patients having surgery for pancreatic cancer, everyone whose blood still held tumour DNA afterwards relapsed, including those who went on to have chemotherapy, which argues for testing whether such patients need more treatment.","summary":"Patients considered resectable were enrolled, with pre- and post-operative samples analysed by PCR-based SafeSeqS assays for KRAS codon 12, 13 and 61 mutations in the primary tumour and in plasma; management followed standard care blinded to results. Of 112 consented, 81 (72%) were resected; KRAS mutations were identified in 38 of 42 available tumours (91%). ctDNA was detected in 23 of 37 preoperative (62%) and 13 of 35 postoperative (37%) plasma samples. At a median 38.4 months, preoperative ctDNA predicted inferior recurrence-free (hazard ratio 4.1) and overall survival (4.1); postoperative detection predicted inferior recurrence-free (5.4) and overall survival (4.0). Recurrence occurred in 13 of 13 patients with detectable postoperative ctDNA, including 7 who received gemcitabine-based adjuvant chemotherapy.","asOf":"2026-09-24","links":[{"label":"Lee et al., Ann Oncol 2019: ctDNA before and after resection in 42 patients (Australian cohort)","url":"https://doi.org/10.1093/annonc/mdz200"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31250894/"}],"tags":[],"related":["ctdna-mrd-positive"],"cancers":["pancreatic","resectable-pdac"],"sections":[],"technologies":["liquid-biopsy","mrd-testing"],"targets":["kras"],"drugs":["gemcitabine"],"companies":[],"institutions":[],"pathways":[],"terms":["ctdna","mrd"],"trials":[],"people":["jeanne-tie"],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2019,"doi":"10.1093/annonc/mdz200","pmid":"31250894","authors":"Lee B, Lipton L, Cohen J, et al.","paperType":"observational","findings":["Preoperative ctDNA in 62%, postoperative in 37%.","All 13 patients with postoperative ctDNA recurred, including 7 given adjuvant gemcitabine.","Hazard ratios 4.1 preoperative and 5.4 postoperative for recurrence."],"whatItMeans":"Postoperative ctDNA marks a group that current adjuvant chemotherapy does not cure, the rationale for ctDNA-guided intensification trials.","caveats":["Feasibility was poor: many patients did not proceed to resection or complete sampling.","KRAS codon-restricted assay and gemcitabine-era adjuvant therapy."],"changedPractice":false,"participants":112},{"id":"paper-magbanua-ispy2-ctdna-neoadjuvant-ann-oncol-2021","kind":"paper","name":"Circulating tumor DNA in neoadjuvant-treated breast cancer reflects response and survival","aka":[],"tldr":"Tracking sixteen patient-specific mutations in blood during chemotherapy before surgery showed that every woman whose tumour vanished had cleared her ctDNA, and that women whose tumour did not vanish but whose ctDNA had cleared did just as well as those it did.","summary":"Cell-free DNA from 291 plasma samples of 84 high-risk early breast cancer patients (I-SPY 2, standard neoadjuvant chemotherapy with or without the AKT inhibitor MK-2206) was tested with a personalised 16-mutation assay at pretreatment, three weeks, between regimens and before surgery. ctDNA positivity fell from 73% to 35%, 14% and 9%. Patients still positive at three weeks were more likely to have residual disease (83% versus 52% non-pCR; OR 4.33). All 17 pCR patients were ctDNA-negative after chemotherapy; among 43 non-pCR patients the 14% who were ctDNA-positive had a metastatic recurrence HR of 10.4, whereas ctDNA-negative non-pCR patients did as well as pCR patients (HR 1.4). Median follow-up 4.8 years.","asOf":"2026-09-24","links":[{"label":"Magbanua et al., Ann Oncol 2021: ctDNA during neoadjuvant therapy in 84 I-SPY 2 patients","url":"https://doi.org/10.1016/j.annonc.2020.11.007"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33232761/"}],"tags":[],"related":["ctdna-mrd-positive"],"cancers":["tnbc","tnbc-early","breast-cancer"],"sections":[],"technologies":["mrd-testing"],"targets":[],"drugs":["signatera"],"companies":["natera"],"institutions":["ucsf"],"pathways":[],"terms":["ctdna","pcr","tumour-informed-assay"],"trials":["i-spy-2"],"people":["laura-esserman"],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2021,"doi":"10.1016/j.annonc.2020.11.007","pmid":"33232761","authors":"Magbanua MJM, Swigart LB, Wu HT, et al.","paperType":"translational","findings":["ctDNA positive 73% at baseline, 9% before surgery.","All pCR patients ctDNA-negative; ctDNA-positive non-pCR: recurrence HR 10.4; ctDNA-negative non-pCR: HR 1.4."],"whatItMeans":"ctDNA clearance may refine pCR as a surrogate: a patient with residual disease but no ctDNA may not need escalation, the hypothesis behind ctDNA-guided post-neoadjuvant trials.","caveats":["84 patients mixing HR-positive/HER2-negative and TNBC.","Tumour-informed assay requires exome sequencing of the pretreatment tumour."],"changedPractice":false,"participants":84},{"id":"paper-henriksen-ctdna-stage-iii-colorectal-improve-it-ccr-2022","kind":"paper","name":"Circulating tumor DNA in stage III colorectal cancer, beyond minimal residual disease detection, toward assessment of adjuvant therapy efficacy and clinical behavior of recurrences","aka":[],"tldr":"Following 168 patients with node-positive bowel cancer through and after chemotherapy showed not only who would relapse but how fast: tumour DNA in the blood grew slowly in some and five times faster in others, and the speed predicted survival.","summary":"168 patients with stage III colorectal cancer treated with curative intent at Danish and Spanish hospitals between 2014 and 2019 were recruited, and 1,204 plasma samples were profiled for 16 patient-specific somatic single-nucleotide variants by multiplex PCR next-generation sequencing. Detection of ctDNA was a strong recurrence predictor postoperatively (hazard ratio 7.0) and directly after adjuvant chemotherapy (hazard ratio 50.8). The recurrence rate among postoperatively ctDNA-positive patients treated with adjuvant chemotherapy was 80% (16 of 20), and only patients who cleared ctDNA permanently during chemotherapy did not relapse. Serial assessment after treatment was similarly predictive (hazard ratio 50.8) and revealed two distinct exponential growth rates, slow at 25% increase a month and fast at 143% a month, with the growth rate itself prognostic for survival (hazard ratio 2.7). Analysis every three months detected recurrence a median of 9.8 months before standard computed tomography.","asOf":"2026-09-24","links":[{"label":"Henriksen et al., Clin Cancer Res 2022: IMPROVE-IT, serial ctDNA in 168 stage III colorectal cancers","url":"https://doi.org/10.1158/1078-0432.CCR-21-2404"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34625408/"}],"tags":[],"related":["ctdna-mrd-positive"],"cancers":["colorectal"],"sections":[],"technologies":["mrd-testing","liquid-biopsy","continuous-ctdna-monitoring","mrd-kinetics-models"],"targets":[],"drugs":[],"companies":[],"institutions":["aarhus-university-hospital","incliva-valencia"],"pathways":[],"terms":["mrd","ctdna","cfdna","tumour-informed-assay","vaf"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2022,"doi":"10.1158/1078-0432.CCR-21-2404","pmid":"34625408","authors":"Henriksen TV, Tarazona N, Frydendahl A, et al.","paperType":"observational","findings":["Recurrence hazard ratio 7.0 postoperatively and 50.8 after adjuvant chemotherapy.","80% of postoperatively ctDNA-positive patients relapsed despite chemotherapy; only permanent clearers did not.","Two growth rates, 25% and 143% increase a month, with the rate prognostic (hazard ratio 2.7)."],"whatItMeans":"It reframes the blood test from a yes-or-no residual disease result into a measure of how well chemotherapy is working and how fast a relapse is coming, which is what an escalation trial would need.","caveats":["Observational; chemotherapy was not randomised by ctDNA result.","168 patients across two countries with differing adjuvant practice.","The growth-rate analysis rests on small numbers of serial positives."],"changedPractice":false,"participants":168},{"id":"paper-kurtz-j-clin-oncol","kind":"paper","name":"Circulating Tumor DNA Measurements As Early Outcome Predictors in Diffuse Large B-Cell Lymphoma","aka":[],"tldr":"Paper cited by one technology page and one idea page, indexed on Europe PMC as PubMed record 30125215 and published in Journal of Clinical Oncology; the citing pages link this DOI, which is how the record was matched.","summary":"Purpose: Outcomes for patients with diffuse large B-cell lymphoma remain heterogeneous, with existing methods failing to consistently predict treatment failure. We examined the additional prognostic value of circulating tumor DNA (ctDNA) before and during therapy for predicting patient outcomes.\n\nPatients and methods: We studied the dynamics of ctDNA from 217 patients treated at six centers, using a training and validation framework. We densely characterized early ctDNA dynamics during therapy using cancer personalized profiling by deep sequencing to define response-associated thresholds within a discovery set. These thresholds were assessed in two independent validation sets. Finally, we assessed the prognostic value of ctDNA in the context of established risk factors, including the International Prognostic Index and interim positron emission tomography/computed tomography scans.\n\nResults: Before therapy, ctDNA was detectable in 98% of patients; pretreatment levels were prognostic in both front-line and salvage settings. In the discovery set, ctDNA levels changed rapidly, with a 2-log decrease after one cycle (early molecular response [EMR]) and a 2.5-log decrease after two cycles (major molecular response [MMR]) stratifying outcomes. In the first validation set, patients receiving front-line therapy achieving EMR or MMR had superior outcomes at 24 months (EMR: EFS, 83% v 50%; P =.0015; MMR: EFS, 82% v 46%; P <.001). EMR also predicted superior 24-month outcomes in patients receiving salvage therapy in the first validation set (EFS, 100% v 13%; P =.011). The prognostic value of EMR and MMR was further confirmed in the second validation set. In multivariable analyses including International Prognostic Index and interim positron emission tomography/computed tomography scans across both cohorts, molecular response was independently prognostic of outcomes, including event-free and overall survival.\n\nConclusion: Pretreatment ctDNA levels and molecular responses are independently prognostic of outcomes in aggressive lymphomas. These risk factors could potentially guide future personalized risk-directed approaches.\n\nIndexed on Europe PMC as PubMed record 30125215 (DOI 10.1200/jco.2018.78.5246). Matched by DOI alone: one technology page and one idea page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2018","url":"https://doi.org/10.1200/jco.2018.78.5246"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30125215/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30125215"}],"tags":["europepmc-ingest"],"related":["ctdna-lymphoma-monitoring","idea-ctdna-guided-dlbcl-frontline","lymphoma-roadmap","paper-scherer-ctdna-lymphoma-subtypes-genome-evolution-sci-transl-med-2016","lymphoma-ev-ctdna-instead-of-the-interim-scan"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2018,"doi":"10.1200/jco.2018.78.5246","pmid":"30125215","authors":"Kurtz DM, Scherer F, Jin MC, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page and one idea page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-mody-biliary-ctdna-profiling-jco-po-2019","kind":"paper","name":"Circulating tumor DNA profiling of advanced biliary tract cancers","aka":[],"tldr":"Blood tests for tumour DNA found a mutation in three quarters of 124 patients with advanced bile duct or gallbladder cancer and a drug-relevant change in about half, showing the approach is feasible when tissue is hard to get.","summary":"From January 2015 to February 2018, 124 patients with locally advanced or metastatic biliary tract cancer at the Mayo Clinic underwent circulating tumour DNA testing with a clinically available assay, most (n = 122) on a 73-gene panel; about 70% had intrahepatic disease. 138 samples were included.\n\nExcluding variants of unknown significance, 105 samples (76%) had one or more alterations, with an average of three alterations per sample and a median allelic fraction of 0.52%. Therapeutically relevant alterations were observed in 76 patients (55%), including BRAF mutations, ERBB2 amplifications, FGFR2 fusions, FGFR2 mutations and IDH1 mutations seen in 21% of patients. A different spectrum was observed in patients under 50.","asOf":"2026-09-24","links":[{"label":"Mody et al., JCO Precis Oncol 2019: circulating tumour DNA profiling of 124 biliary tract cancers","url":"https://doi.org/10.1200/po.18.00324"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35100741/"}],"tags":[],"related":[],"cancers":["gallbladder","cholangiocarcinoma","biliary-tract-cancer"],"sections":[],"technologies":["liquid-biopsy"],"targets":["her2","braf","fgfr2","idh"],"drugs":["guardant360-cdx"],"companies":["guardant-health"],"institutions":["mayo-clinic"],"pathways":[],"terms":["ctdna"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco-precision-oncology"],"dependsOn":[],"notes":[],"journal":"JCO Precision Oncology","year":2019,"doi":"10.1200/po.18.00324","pmid":"35100741","authors":"Mody K, Kasi PM, Yang J, et al.","paperType":"observational","findings":["76% of 138 plasma samples carried at least one alteration; median allelic fraction 0.52%.","Therapeutically relevant alterations in 55% of patients, including ERBB2 amplification, BRAF, FGFR2 and IDH1.","Different alteration spectrum in patients under 50."],"whatItMeans":"Biliary tumours are often diagnosed on tiny biopsies or brushings, so a blood-based panel that detects HER2 amplification and other targets in half of patients is a practical route to testing, with tissue confirmation where the blood is uninformative.","caveats":["Single centre, predominantly intrahepatic; gallbladder cancers were a minority.","Plasma panel (Guardant360) of 73 genes; low allelic fractions mean negatives do not exclude a tissue alteration."],"changedPractice":false,"participants":124},{"id":"paper-nakamura-triumph-ctdna-pertuzumab-trastuzumab-her2-colorectal-nat-med-2021","kind":"paper","name":"Circulating tumor DNA-guided treatment with pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer: a phase 2 trial (TRIUMPH)","aka":[],"tldr":"The first trial to let a blood test decide who joins: patients whose plasma showed extra HER2 responded to dual HER2 antibodies just as often as those selected on tissue, while a matched group on standard salvage therapy had no responses at all.","summary":"TRIUMPH was a phase 2 trial of pertuzumab plus trastuzumab in metastatic colorectal cancer with HER2 amplification confirmed prospectively by tumour tissue or ctDNA analysis. HER2 amplification was confirmed in tissue or ctDNA in 30 patients. The study met its primary endpoint with a confirmed objective response rate of 30% in 27 tissue-positive patients and 28% in 25 ctDNA-positive patients, against 0% in a matched real-world reference population treated with standard-of-care salvage therapy. Post hoc analyses showed that baseline ctDNA genotyping of HER2 copy number and concurrent oncogenic alterations, adjusted for tumour fraction, stratified patients by efficacy with accuracy similar to tissue genotyping, and that a decrease in ctDNA fraction three weeks after starting treatment was associated with response.","asOf":"2026-09-24","links":[{"label":"Nakamura et al., Nat Med 2021: TRIUMPH, ctDNA-guided pertuzumab plus trastuzumab in HER2-amplified metastatic colorectal cancer","url":"https://doi.org/10.1038/s41591-021-01553-w"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34764486/"}],"tags":[],"related":["her2-ish-amplified","ctdna-mrd-positive"],"cancers":["colorectal"],"sections":[],"technologies":["liquid-biopsy","cgp"],"targets":["her2"],"drugs":["pertuzumab","trastuzumab"],"companies":[],"institutions":[],"pathways":["rtk-activation"],"terms":["ctdna","cfdna","gene-amplification"],"trials":["circulate-japan"],"people":["yoshino-takayuki"],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2021,"doi":"10.1038/s41591-021-01553-w","pmid":"34764486","authors":"Nakamura Y, Okamoto W, Kato T, et al.","paperType":"rct","findings":["Confirmed objective response 30% in 27 tissue-positive and 28% in 25 ctDNA-positive patients, against 0% in matched real-world salvage therapy.","Plasma HER2 copy number adjusted for tumour fraction stratified efficacy as well as tissue did.","Falling ctDNA fraction at three weeks tracked response."],"whatItMeans":"It is the proof that plasma genotyping can enrol patients for a targeted colorectal trial, which matters most for a 2 to 3% alteration where archival tissue is often exhausted or out of date.","caveats":["30 patients, single arm, with a real-world rather than randomised comparator.","Concurrent RAS alterations in plasma predicted poor response, so a HER2 call alone is not enough.","Plasma sensitivity depends on tumour fraction, so negative plasma does not exclude amplification."],"changedPractice":false,"participants":30},{"id":"paper-plasmamatch-lancet-oncol-2020","kind":"paper","name":"Circulating tumour DNA analysis to direct therapy in advanced breast cancer (plasmaMATCH): a multicentre, multicohort, phase 2a, platform trial","aka":[],"tldr":"Published report from the plasmaMATCH trial registered as NCT03182634, in The Lancet Oncology (2020), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Circulating tumour DNA (ctDNA) testing might provide a current assessment of the genomic profile of advanced cancer, without the need to repeat tumour biopsy. We aimed to assess the accuracy of ctDNA testing in advanced breast cancer and the ability of ctDNA testing to select patients for mutation-directed therapy.\n\nMethods: We did an open-label, multicohort, phase 2a, platform trial of ctDNA testing in 18 UK hospitals. Participants were women (aged ≥18 years) with histologically confirmed advanced breast cancer and an Eastern Cooperative Oncology Group performance status 0-2. Patients had completed at least one previous line of treatment for advanced breast cancer or relapsed within 12 months of neoadjuvant or adjuvant chemotherapy. Patients were recruited into four parallel treatment cohorts matched to mutations identified in ctDNA: cohort A comprised patients with ESR1 mutations (treated with intramuscular extended-dose fulvestrant 500 mg); cohort B comprised patients with HER2 mutations (treated with oral neratinib 240 mg, and if oestrogen receptor-positive with intramuscular standard-dose fulvestrant); cohort C comprised patients with AKT1 mutations and oestrogen receptor-positive cancer (treated with oral capivasertib 400 mg plus intramuscular standard-dose fulvestrant); and cohort D comprised patients with AKT1 mutations and oestrogen receptor-negative cancer or PTEN mutation (treated with oral capivasertib 480 mg). Each cohort had a primary endpoint of confirmed objective response rate. For cohort A, 13 or more responses among 78 evaluable patients were required to infer activity and three or more among 16 were required for cohorts B, C, and D. Recruitment to all cohorts is complete and long-term follow-up is ongoing. This trial is registered with ClinicalTrials.gov, NCT03182634; the European Clinical Trials database, EudraCT2015-003735-36; and the ISRCTN registry, ISRCTN16945804.\n\nFindings: Between Dec 21, 2016, and April 26, 2019, 1051 patients registered for the study, with ctDNA results available for 1034 patients. Agreement between ctDNA digital PCR and targeted sequencing was 96-99% (n=800, kappa 0·89-0·93). Sensitivity of digital PCR ctDNA testing for mutations identified in tissue sequencing was 93% (95% CI 83-98) overall and 98% (87-100) with contemporaneous biopsies. In all cohorts, combined median follow-up was 14·4 months (IQR 7·0-23·7). Cohorts B and C met or exceeded the target number of responses, with five (25% [95% CI 9-49]) of 20 patients in cohort B and four (22% [6-48]) of 18 patients in cohort C having a response. Cohorts A and D did not reach the target number of responses, with six (8% [95% CI 3-17]) of 74 in cohort A and two (11% [1-33]) of 19 patients in cohort D having a response. The most common grade 3-4 adverse events were raised gamma-glutamyltransferase (13 [16%] of 80 patients; cohort A); diarrhoea (four [25%] of 20; cohort B); fatigue (four [22%] of 18; cohort C); and rash (five [26%] of 19; cohort D). 17 serious adverse reactions occurred in 11 patients, and there was one treatment-related death caused by grade 4 dyspnoea (in cohort C).\n\nInterpretation: ctDNA testing offers accurate, rapid genotyping that enables the selection of mutation-directed therapies for patients with breast cancer, with sufficient clinical validity for adoption into routine clinical practice. Our results demonstrate clinically relevant activity of targeted therapies against rare HER2 and AKT1 mutations, confirming these mutations could be targetable for breast cancer treatment.\n\nFunding: Cancer Research UK, AstraZeneca, and Puma Biotechnology.\n\nIndexed on Europe PMC as PubMed record 32919527 (DOI 10.1016/s1470-2045(20)30444-7). Its abstract cites the registry id NCT03182634, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2020","url":"https://doi.org/10.1016/s1470-2045(20)30444-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32919527/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32919527"},{"label":"ClinicalTrials.gov NCT03182634","url":"https://clinicaltrials.gov/study/NCT03182634"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["plasmamatch"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2020,"doi":"10.1016/s1470-2045(20)30444-7","pmid":"32919527","authors":"Turner NC, Kingston B, Kilburn LS, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03182634 with the most citations, so it is the natural first reading for anyone following the plasmaMATCH trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-annala-ctdna-resistance-abiraterone-enzalutamide-cancer-discov-2018","kind":"paper","name":"Circulating tumour DNA genomics correlate with resistance to abiraterone and enzalutamide in prostate cancer","aka":[],"tldr":"A blood test taken before the first tablet identified the men whose disease would resist both standard hormone drugs, which the clinical variables could not do.","summary":"Two hundred and two men with treatment-naive metastatic castration-resistant prostate cancer were randomised to abiraterone or enzalutamide and had whole-exome and deep targeted 72-gene sequencing of plasma cell-free DNA before therapy. Time to progression was similar for the two agents, which had never been directly compared. Defects in BRCA2 and ATM were strongly associated with poor clinical outcomes independently of clinical prognostic factors and of circulating tumour DNA abundance. Somatic alterations in TP53, previously linked to reduced tumour dependency on androgen receptor signalling, were also independently associated with rapid resistance. Detection of AR amplification did not outperform standard prognostic biomarkers, but AR gene structural rearrangements truncating the ligand-binding domain were identified in several men with primary resistance.","asOf":"2026-09-25","links":[{"label":"Annala et al., Cancer Discov 2018: circulating tumour DNA genomics and resistance to abiraterone or enzalutamide in 202 randomised men with treatment-naive mCRPC","url":"https://doi.org/10.1158/2159-8290.CD-17-0937"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29367197/"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["liquid-biopsy","wes-wgs"],"targets":["brca","atm","tp53","androgen-receptor"],"drugs":["abiraterone","enzalutamide"],"companies":[],"institutions":[],"pathways":["ar-signaling","homologous-recombination-repair","p53-cell-cycle","resistance-routes-map"],"terms":["ctdna","cfdna","liquid-biopsy","resistance","castration-resistance"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-discovery"],"dependsOn":[],"notes":[],"journal":"Cancer Discovery","year":2018,"doi":"10.1158/2159-8290.CD-17-0937","pmid":"29367197","authors":"Annala M, Vandekerkhove G, Khalaf D, et al.","paperType":"rct","findings":["BRCA2 and ATM defects independently associated with poor outcome on either hormonal agent.","TP53 alterations independently associated with rapid resistance.","AR amplification detection did not outperform standard prognostic biomarkers.","AR structural rearrangements truncating the ligand-binding domain found in men with primary resistance.","Time to progression was similar for abiraterone and enzalutamide."],"whatItMeans":"It shows that the useful information in a castration-resistant plasma sample is in the repair genes and TP53 rather than in the androgen receptor finding that dominates the report, and it is the closest thing the field has to a head-to-head comparison of abiraterone against enzalutamide.","caveats":["A randomised phase 2 trial, so the drug comparison is not definitive.","Two hundred and two men at Canadian centres.","The prognostic associations have not been used prospectively to assign treatment."],"changedPractice":false,"participants":202},{"id":"paper-griffith-nat-genet","kind":"paper","name":"CIViC is a community knowledgebase for expert crowdsourcing the clinical interpretation of variants in cancer","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 28138153 and published in Nature Genetics; the citing page links this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 28138153 (DOI 10.1038/ng.3774). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Genet 2017","url":"https://doi.org/10.1038/ng.3774"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28138153/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28138153"}],"tags":["europepmc-ingest"],"related":["variant-knowledgebases"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":2017,"doi":"10.1038/ng.3774","pmid":"28138153","authors":"Griffith M, Spies NC, Krysiak K, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-clarinet-lanreotide-nejm-2014","kind":"paper","name":"CLARINET: lanreotide in metastatic enteropancreatic neuroendocrine tumours","aka":[],"tldr":"The long-acting somatostatin analogue lanreotide roughly halved the risk of progression in non-functioning gut and pancreatic neuroendocrine tumours, extending the use of these drugs from symptom control to slowing tumour growth.","summary":"Phase 3 placebo-controlled trial of 204 patients with advanced, well- or moderately differentiated, non-functioning, somatostatin receptor-positive enteropancreatic neuroendocrine tumours (Ki-67 under 10 percent) randomised to lanreotide autogel 120 mg monthly or placebo.\n\nMedian progression-free survival was not reached with lanreotide against 18.0 months with placebo (hazard ratio 0.47), with benefit in pancreatic and midgut tumours and in patients with high hepatic tumour load.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2014","url":"https://doi.org/10.1056/NEJMoa1316158"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25014687/"}],"tags":[],"related":[],"cancers":["pancreatic-net","small-intestinal-net"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["clarinet"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2014,"doi":"10.1056/NEJMoa1316158","pmid":"25014687","authors":"Caplin ME, Pavel M, Ćwikła JB, et al.","paperType":"rct","findings":["Progression-free survival hazard ratio 0.47.","24-month progression-free survival 65.1 percent vs 33.0 percent."],"whatItMeans":"Somatostatin analogues are the standard first-line antiproliferative treatment for grade 1 to 2 gastroenteropancreatic neuroendocrine tumours whether or not they cause a hormone syndrome.","caveats":["Most patients had stable disease at entry, so the natural history was slow.","No overall survival benefit shown."],"changedPractice":true,"participants":204},{"id":"paper-classic-5-year-follow-up-noh-lancet-oncol-2014","kind":"paper","name":"CLASSIC 5-year follow-up: adjuvant capecitabine plus oxaliplatin for gastric cancer after D2 gastrectomy","aka":[],"tldr":"Five years on, the benefit of adjuvant capecitabine and oxaliplatin held and translated into longer survival: 78 percent alive against 69 percent with surgery alone.","summary":"Five-year follow-up of the CLASSIC trial (1,035 patients) at a median of 62.4 months: disease-free survival events in 27 percent of chemotherapy patients against 39 percent of observation patients (hazard ratio 0.58); estimated five-year disease-free survival 68 against 53 percent and overall survival 78 against 69 percent (hazard ratio 0.66).","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2014","url":"https://doi.org/10.1016/S1470-2045(14)70473-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25439693/"}],"tags":[],"related":[],"cancers":["gastric"],"sections":[],"technologies":[],"targets":[],"drugs":["capecitabine","oxaliplatin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["classic"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2014,"doi":"10.1016/S1470-2045(14)70473-5","pmid":"25439693","authors":"Noh SH, Park SR, Yang HK, et al.","paperType":"rct","findings":["Five-year disease-free survival 68 percent (95% CI 63 to 73) versus 53 percent (47 to 58); hazard ratio 0.58 (0.47 to 0.72).","Five-year overall survival 78 percent (74 to 82) versus 69 percent (64 to 73); hazard ratio 0.66 (0.51 to 0.85), p 0.0015."],"whatItMeans":"Confirms a survival benefit for adjuvant CAPOX after D2 gastrectomy.","caveats":["Adverse event data were not collected after the primary analysis."],"changedPractice":true,"participants":1035},{"id":"paper-classic-adjuvant-capox-gastric-bang-lancet-2012","kind":"paper","name":"CLASSIC: adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy","aka":[],"tldr":"Six months of capecitabine and oxaliplatin after a D2 gastrectomy raised three-year disease-free survival from 59 to 74 percent in East Asian patients with stage II to III stomach cancer.","summary":"Open-label phase 3 trial at 37 centres in South Korea, China and Taiwan: 1,035 patients with stage II to IIIB gastric cancer after curative D2 gastrectomy were randomised to eight cycles of capecitabine and oxaliplatin (520) or observation (515).\n\nThree-year disease-free survival was 74 percent with chemotherapy against 59 percent with surgery alone (hazard ratio 0.56). Grade 3 or 4 adverse events occurred in 56 percent of chemotherapy patients against 6 percent of surgery-only patients, most commonly nausea, neutropenia and decreased appetite.","asOf":"2026-09-22","links":[{"label":"Lancet 2012","url":"https://doi.org/10.1016/S0140-6736(11)61873-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22226517/"}],"tags":[],"related":[],"cancers":["gastric"],"sections":[],"technologies":[],"targets":[],"drugs":["capecitabine","oxaliplatin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["classic"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2012,"doi":"10.1016/S0140-6736(11)61873-4","pmid":"22226517","authors":"Bang YJ, Kim YW, Yang HK, et al.","paperType":"rct","findings":["Three-year disease-free survival 74 percent (95% CI 69 to 79) versus 59 percent (53 to 64); hazard ratio 0.56 (0.44 to 0.72), p < 0.0001.","Grade 3 or 4 adverse events 56 percent versus 6 percent."],"whatItMeans":"Adjuvant CAPOX after D2 gastrectomy is a standard option for operable stage II to III gastric cancer, alongside S-1 in Japan.","caveats":["East Asian population with D2 surgery; Western practice relies on perioperative chemotherapy (FLOT) instead.","Open-label design."],"changedPractice":true,"participants":1035},{"id":"paper-loree-tumour-location-continuum-colorectal-ccr-2018","kind":"paper","name":"Classifying colorectal cancer by tumor location rather than sidedness highlights a continuum in mutation profiles and consensus molecular subtypes","aka":[],"tldr":"The left-right split is a convenient line but the bowel is a gradient. Mutation rates change continuously from caecum to rectum, and the sigmoid-rectal region and the transverse colon do not fit the convention.","summary":"Mutation prevalence and overall survival were compared by side and by precise tumour location in 1,876 patients with colorectal cancer, with consensus molecular subtype compared in a separate cohort of 608. Mutation prevalence differed by side and location for TP53, KRAS, BRAF V600, PIK3CA, SMAD4, CTNNB1, GNAS and PTEN, and substantial variation remained within each side. Within right-sided tumours, RAS mutations fell from 70% in the caecum to 43% at the hepatic flexure, while BRAF V600 mutations rose from 10% to 22% between the same locations. Within left-sided tumours, the sigmoid and rectal region had more TP53 mutations and less PIK3CA, BRAF and CTNNB1 mutation and less microsatellite instability than other left-sided locations. Despite this, a left-right division preceding the transverse colon maximised prognostic differences, and transverse colon tumours clustered with left-sided tumours by mutation profile. Consensus molecular subtype profiles showed a decline in CMS1 and CMS3 and a rise in CMS2 moving distally.","asOf":"2026-09-24","links":[{"label":"Loree et al., Clin Cancer Res 2018: tumour location rather than sidedness, a continuum of mutation profiles in 1,876 patients","url":"https://doi.org/10.1158/1078-0432.CCR-17-2484"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29180604/"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":[],"targets":["kras","braf","tp53","pik3ca","smad4","ctnnb1","gnas","pten"],"drugs":[],"companies":[],"institutions":["md-anderson"],"pathways":[],"terms":["sidedness","cms-subtypes"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2018,"doi":"10.1158/1078-0432.CCR-17-2484","pmid":"29180604","authors":"Loree JM, Pereira AAL, Lam M, et al.","paperType":"observational","findings":["RAS mutation falls from 70% at the caecum to 43% at the hepatic flexure; BRAF V600 rises from 10% to 22%.","The sigmoid-rectal region is molecularly distinct from the rest of the left colon.","CMS1 and CMS3 decline and CMS2 rises moving distally."],"whatItMeans":"It is the caution attached to the sidedness rule: a tumour at the hepatic flexure and one at the caecum are both called right-sided and are not the same disease.","caveats":["Retrospective single-centre sequencing cohort with a separate expression cohort.","Subsite recording in routine records is imprecise.","Did not change the left-right convention, which still gave the best prognostic separation."],"changedPractice":false,"participants":1876},{"id":"paper-ct041-st-01-lancet-2025","kind":"paper","name":"Claudin-18 isoform 2-specific CAR T-cell therapy (satri-cel) versus treatment of physician's choice for previously treated advanced gastric or gastro-oesophageal junction cancer (CT041-ST-01): a randomised, open-label, phase 2 trial","aka":[],"tldr":"The first randomised trial of CAR-T cells in a solid tumour: in heavily pretreated Claudin 18.2-positive stomach cancer, satri-cel held the disease for a median of 3.25 months against 1.77 months on the doctor's choice of drug, with almost universal cytokine release syndrome.","summary":"Open-label, multicentre, randomised controlled phase 2 trial in China in patients with CLDN18.2-positive (immunohistochemistry intensity at least 2+ and at least 40 percent positive tumour cells) advanced gastric or gastro-oesophageal junction cancer refractory to at least two previous lines. Patients were randomly allocated 2:1 to satri-cel (up to three infusions of 250 million cells) or treatment of physician's choice (nivolumab, paclitaxel, docetaxel, irinotecan or rivoceranib), with crossover to satri-cel allowed after progression or intolerance. The primary endpoint was progression-free survival by independent review committee in the intention-to-treat population.\n\nBetween March 2022 and July 2024, 266 patients were screened and 156 randomised (104 satri-cel, 52 physician's choice); 88 (85 percent) and 48 (92 percent) received study drug. Median progression-free survival was 3.25 months (95% CI 2.86 to 4.53) with satri-cel and 1.77 months (95% CI 1.61 to 2.04) with physician's choice (hazard ratio 0.37, 95% CI 0.24 to 0.56; one-sided log-rank p<0.0001). Grade 3 or higher treatment-emergent adverse events occurred in 87 of 88 (99 percent) treated satri-cel patients and 30 of 48 (63 percent) on physician's choice; cytokine release syndrome occurred in 84 of 88 (95 percent). Funded by CARsgen Therapeutics.","asOf":"2026-09-24","links":[{"label":"The Lancet 2025","url":"https://doi.org/10.1016/S0140-6736(25)00860-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40460847/"},{"label":"ClinicalTrials.gov NCT04581473","url":"https://clinicaltrials.gov/study/NCT04581473"}],"tags":["china"],"related":[],"cancers":["gastric","gastric-cldn18-2-positive"],"sections":[],"technologies":["car-t"],"targets":["cldn18-2"],"drugs":["satricabtagene-autoleucel"],"companies":["carsgen"],"institutions":["pku-cancer-hospital"],"pathways":[],"terms":[],"trials":["nct04581473"],"people":["qi-changsong","shen-lin"],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2025,"doi":"10.1016/S0140-6736(25)00860-8","pmid":"40460847","authors":"Qi C, Liu C, Peng Z, et al.","paperType":"rct","findings":["Median progression-free survival 3.25 vs 1.77 months; hazard ratio 0.37 (95% CI 0.24 to 0.56), one-sided log-rank p<0.0001.","156 randomised of 266 screened; 85% of the satri-cel arm and 92% of the physician's choice arm received study drug.","Grade 3 or higher treatment-emergent adverse events in 99% vs 63% of treated patients; cytokine release syndrome in 95% of treated satri-cel patients."],"whatItMeans":"This is the trial behind the first approval of a CAR-T therapy for a solid tumour, in China. The gain in progression-free survival is real but measured in weeks, 15 percent of patients randomised to satri-cel never received it, and nearly every treated patient had cytokine release syndrome, so the trade-off is very different from CAR-T in blood cancers. Overall survival is not reported in the abstract.","caveats":["Open-label, 2:1 randomisation, and crossover from physician's choice to satri-cel was allowed, which complicates any later survival comparison.","The abstract reports no overall survival figures.","Requires Claudin 18.2 testing by immunohistochemistry and manufacturing time; 16 of 104 randomised patients did not receive satri-cel."],"changedPractice":true,"participants":156},{"id":"paper-mackensen-nat-med","kind":"paper","name":"CLDN6-specific CAR-T cells plus amplifying RNA vaccine in relapsed or refractory solid tumors: the phase 1 BNT211-01 trial","aka":[],"tldr":"Paper cited by one target page, indexed on Europe PMC as PubMed record 37872225 and published in Nature Medicine; the citing page links this DOI, which is how the record was matched.","summary":"The oncofetal antigen Claudin 6 (CLDN6) is highly and specifically expressed in many solid tumors, and could be a promising treatment target. We report dose escalation results from the ongoing phase 1/2 BNT211-01 trial evaluating the safety and feasibility of chimeric antigen receptor (CAR) T cells targeting the CLDN6 with or without a CAR-T cell-amplifying RNA vaccine (CARVac) at two dose levels (DLs) in relapsed/refractory CLDN6-positive solid tumors. The primary endpoints were safety and tolerability, maximum tolerated dose and recommended phase 2 dose (RP2D). Secondary endpoints included objective response rate (ORR) and disease control rate. We observed manageable toxicity, with 10 out of 22 patients (46%) experiencing cytokine release syndrome including one grade 3 event and 1 out of 22 (5%) with grade 1 immune effector cell-associated neurotoxicity syndrome. Dose-limiting toxicities occurred in two patients at the higher DL, resolving without sequelae. CAR-T cell engraftment was robust, and the addition of CARVac was well tolerated. The unconfirmed ORR in 21 evaluable patients was 33% (7 of 21), including one complete response. The disease control rate was 67% (14 of 21), with stable disease in seven patients. Patients with germ cell tumors treated at the higher DL exhibited the highest response rate (ORR 57% (4 of 7)). The maximum tolerated dose and RP2D were not established as the trial has been amended to utilize an automated manufacturing process. A repeat of the dose escalation is ongoing and will identify a RP2D for pivotal trials. ClinicalTrials.gov Identifier: NCT04503278.\n\nIndexed on Europe PMC as PubMed record 37872225 (DOI 10.1038/s41591-023-02612-0). Matched by DOI alone: one target page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Med 2023","url":"https://doi.org/10.1038/s41591-023-02612-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37872225/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37872225"}],"tags":["europepmc-ingest"],"related":["cldn6"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2023,"doi":"10.1038/s41591-023-02612-0","pmid":"37872225","authors":"Mackensen A, Haanen JBAG, Koenecke C, et al.","paperType":"observational","findings":[],"whatItMeans":"One target page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-clear-nejm-2021","kind":"paper","name":"CLEAR: lenvatinib plus pembrolizumab versus sunitinib as first treatment for advanced kidney cancer","aka":[],"tldr":"Combining the multi-kinase inhibitor lenvatinib with pembrolizumab more than doubled the time to progression compared with sunitinib in advanced clear-cell kidney cancer and improved survival, with 71% of patients responding.","summary":"Open-label phase 3 trial of 1,069 patients with untreated advanced clear-cell renal cell carcinoma randomised to lenvatinib plus pembrolizumab, lenvatinib plus everolimus, or sunitinib. Primary endpoint was PFS by independent review.\n\nMedian PFS was 23.9 vs 9.2 months (HR 0.39) for lenvatinib plus pembrolizumab, with OS HR 0.66 and an objective response rate of 71.0% vs 36.1%. Alongside KEYNOTE-426 (axitinib plus pembrolizumab), CheckMate 9ER (cabozantinib plus nivolumab) and CheckMate 214 (nivolumab plus ipilimumab), it established immunotherapy-based combinations as universal first-line therapy for advanced kidney cancer.","asOf":"2026-09-08","links":[{"label":"NEJM 2021","url":"https://doi.org/10.1056/NEJMoa2035716"},{"label":"ClinicalTrials.gov NCT02811861","url":"https://clinicaltrials.gov/study/NCT02811861"}],"tags":[],"related":[],"cancers":["rcc"],"sections":[],"technologies":["checkpoint-inhibitor","kinase-inhibitors","antiangiogenic"],"targets":["pd1","vegf"],"drugs":["pembrolizumab"],"companies":["merck","eli-lilly"],"institutions":[],"pathways":[],"terms":["pfs","os","orr","first-line"],"trials":[],"people":["rha-sun-young","toni-choueiri"],"bottlenecks":["b-combination-space","b-toxicity-qol","b-dose-optimisation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2021,"doi":"10.1056/NEJMoa2035716","authors":"Motzer R, Alekseev B, Rha SY, et al.","paperType":"rct","findings":["Median PFS 23.9 vs 9.2 months; HR 0.39 (95% CI 0.32-0.49).","Overall survival HR 0.66 (95% CI 0.49-0.88) at the primary analysis; subsequent follow-up showed median OS about 53.7 vs 54.3 months with HR 0.79, as sunitinib patients received later immunotherapy.","Objective response 71.0% vs 36.1%; complete response 16.1% vs 4.2%.","Benefit across all IMDC risk groups, including favourable risk.","Grade 3 or higher adverse events 82.4% vs 71.8%; hypertension, diarrhoea and proteinuria led to frequent lenvatinib dose reductions."],"whatItMeans":"Patients with newly diagnosed advanced clear-cell kidney cancer should receive an immunotherapy-based combination; lenvatinib plus pembrolizumab gives the highest response rate and longest PFS of the available options, at the cost of more side effects requiring dose adjustment. Sunitinib alone is no longer an appropriate standard. Choosing among the combinations depends on risk group, symptoms, comorbidity and the value placed on treatment-free survival, which favours nivolumab plus ipilimumab in intermediate and poor risk.","caveats":["Open-label; no head-to-head comparison among the immunotherapy combinations.","The OS advantage narrowed with longer follow-up because of subsequent immunotherapy in the sunitinib arm.","High rates of dose reduction and discontinuation of lenvatinib; the 20 mg starting dose is debated.","Non-clear-cell histologies were excluded."],"changedPractice":true,"participants":1069},{"id":"paper-durvalumab-endometrial-j-immunother-cancer-2021","kind":"paper","name":"Clinical activity of durvalumab for patients with advanced mismatch repair-deficient and repair-proficient endometrial cancer. A nonrandomized phase 2 clinical trial","aka":[],"tldr":"Phase 2 or 3 results paper on Durvalumab in Endometrial cancer, in Journal for ImmunoTherapy of Cancer (2021), one of the most cited Europe PMC records with Durvalumab in its title.","summary":"Background: In this study, we assessed the activity of durvalumab, an antibody to programmed death ligand-1, in two cohorts of women with advanced endometrial cancers (AEC)-mismatch repair proficient (pMMR) and mismatch repair deficient (dMMR).\n\nMethods: A multicenter phase two study was performed in women with AEC with pMMR tumor progressing after one to three lines of chemotherapy and women with AEC with dMMR tumor progressing after zero to three lines of chemotherapy. Mismatch repair status was based on immunohistochemistry expression. All women received durvalumab 1500 mg given every 4 weeks until progression or unacceptable toxicity. The primary endpoint was objective tumor response by RECIST V.1.1 modified for immune-based therapeutics.\n\nResults: Seventy-one women were recruited: 35 dMMR and 36 pMMR. Median follow-up was 19 vs 21 months in dMMR versus pMMR, respectively. Median age was 67 years. Histology in dMMR versus pMMR included endometrioid (94% vs 57%) and serous (0% vs 31%) and was high grade in 26% vs 74%. The objective tumor response rate (OTRR) in the dMMR cohort was 47% (17/36, 95% CI 32 to 63), including 6 complete responses and 11 partial responses (PRs)) vs 3% in the pMMR cohort (1/35, 95% CI 1 to 15, PR). In the dMMR cohort, durvalumab was the first-line therapy in 58% (OTRR 57%) and the second-line therapy in 39% (OTRR 38%). Median progression-free survival was 8.3 months in the dMMR cohort vs 1.8 months in the pMMR cohort. The 12-month overall survival (OS) rate was 71% in dMMR vs 51% in pMMR, with median OS not reached for dMMR vs 12 months for pMMR. Immune-related adverse events occurred in 14 women, mostly grades 1-2.\n\nConclusion: Durvalumab monotherapy showed promising activity and acceptable safety in AEC with dMMR regardless of prior lines of chemotherapy, but activity was limited in AEC with pMMR.\n\nTrial registration numbers: ANZGOG1601, ACTRN12617000106336, and NCT03015129.\n\nIndexed on Europe PMC as PubMed record 34103352 (DOI 10.1136/jitc-2020-002255). Its title names Durvalumab and its text names Endometrial cancer; PubMed types it as a clinical trial report (Clinical Trial, Phase II, Research Support, Non-U.S. Gov't, research-article, Multicenter Study). It was matched automatically to the idea \"Molecular-class-directed adjuvant therapy in endometrial cancer\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Immunother Cancer 2021","url":"https://doi.org/10.1136/jitc-2020-002255"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34103352/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34103352"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jitc"],"dependsOn":[],"notes":[],"journal":"Journal for ImmunoTherapy of Cancer","year":2021,"doi":"10.1136/jitc-2020-002255","pmid":"34103352","authors":"Antill Y, Kok PS, Robledo K, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Durvalumab in Endometrial cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Durvalumab in the title and Endometrial cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-wagner-sirolimus-pecoma-jco-2010","kind":"paper","name":"Clinical activity of mTOR inhibition with sirolimus in malignant perivascular epithelioid cell tumours","aka":[],"tldr":"This report of three patients with malignant PEComa responding to oral sirolimus was the first evidence that these tumours, which share TSC1/TSC2 loss with tuberous sclerosis, depend on the mTOR pathway.","summary":"Case series of three patients with metastatic malignant PEComa treated with sirolimus, all showing radiological responses, with molecular analysis of tumour tissue demonstrating loss of TSC2 and activation of mTORC1 signalling.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2010","url":"https://doi.org/10.1200/JCO.2009.25.2981"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20048174/"}],"tags":[],"related":[],"cancers":["pecoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["andrew-wagner"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2010,"doi":"10.1200/JCO.2009.25.2981","pmid":"20048174","authors":"Wagner AJ, Malinowska-Kolodziej I, Morgan JA, et al.","paperType":"observational","findings":["Radiological responses in all three patients treated with sirolimus.","TSC2 loss and mTORC1 activation in tumour tissue."],"whatItMeans":"mTOR inhibition became the therapeutic strategy for PEComa, culminating in the AMPECT trial and approval of nab-sirolimus.","caveats":["Three patients; hypothesis-generating."],"changedPractice":true,"participants":3},{"id":"paper-aggarwal-t-sccpc-jco-2018","kind":"paper","name":"Clinical and genomic characterisation of treatment-emergent small-cell neuroendocrine prostate cancer","aka":[],"tldr":"Biopsying metastases in men progressing on modern hormone therapy found small-cell neuroendocrine prostate cancer in 17 percent, with a median survival under three years, showing how commonly the lineage switch occurs and why biopsy at progression matters.","summary":"Prospective multi-institutional study of 202 men with metastatic castration-resistant prostate cancer who underwent metastatic biopsy, with histological and transcriptomic classification of treatment-emergent small-cell neuroendocrine prostate cancer.\n\nSmall-cell neuroendocrine histology was found in 17 percent, associated with worse overall survival (36.6 versus 44.5 months), a distinct expression signature and low androgen receptor signalling; serum markers such as chromogranin were unreliable.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2018","url":"https://doi.org/10.1200/JCO.2017.77.6880"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29985747/"}],"tags":[],"related":["prostate-roadmap","paper-mu-sox2-lineage-plasticity-science-2017","idea-prostate-plasticity-surveillance-before-it-is-neuroendocrine"],"cancers":["prostate-nepc","prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["neuroendocrine-differentiation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2018,"doi":"10.1200/JCO.2017.77.6880","pmid":"29985747","authors":"Aggarwal R, Huang J, Alumkal JJ, et al.","paperType":"observational","findings":["Treatment-emergent small-cell neuroendocrine prostate cancer in 17 percent of biopsied patients.","Median overall survival 36.6 vs 44.5 months for adenocarcinoma."],"whatItMeans":"Biopsy of progressing lesions, especially with low PSA or visceral spread, is recommended to detect neuroendocrine transformation and switch to platinum-based therapy or trials.","caveats":["Selected patients undergoing biopsy at academic centres."],"changedPractice":true,"participants":202},{"id":"paper-mondaca-erbb2-gallbladder-us-chile-jco-go-2024","kind":"paper","name":"Clinical and genomic characterization of ERBB2-altered gallbladder cancer: exploring differences between an American and a Chilean cohort","aka":[],"tldr":"In 260 gallbladder cancer patients from New York and Santiago, HER2 gene changes were found in about one in seven at both centres, split between extra copies and point mutations, and patients with them lived longer.","summary":"260 patients with gallbladder cancer, 237 from Memorial Sloan Kettering and 23 from the Pontificia Universidad Catolica de Chile, were profiled with MSK-IMPACT. Clinical characteristics did not differ except gallstone prevalence, which was higher in Chile (85% versus 44%; P = 0.0003). The prevalence of ERBB2 alterations was comparable (15% versus 9%; P = 0.42).\n\nOverall, ERBB2 alterations were present in 14% of patients: 8% amplification, 4% mutation, 1.5% concurrent amplification and mutation, and 0.4% fusion. Patients whose tumours harboured ERBB2 alterations had better overall survival than ERBB2 wild-type patients (22.3 versus 11.8 months; P = 0.024).","asOf":"2026-09-24","links":[{"label":"Mondaca et al., JCO Glob Oncol 2024: ERBB2-altered gallbladder cancer in an American and a Chilean cohort","url":"https://doi.org/10.1200/go.24.00090"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39388662/"}],"tags":[],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":["her2"],"drugs":["zanidatamab","trastuzumab-deruxtecan"],"companies":[],"institutions":["mskcc"],"pathways":[],"terms":[],"trials":[],"people":["ghassan-abou-alfa"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"JCO Global Oncology","year":2024,"doi":"10.1200/go.24.00090","pmid":"39388662","authors":"Mondaca S, Walch H, Sepulveda S, et al.","paperType":"observational","findings":["ERBB2 altered in 14% overall: 8% amplification, 4% mutation, 1.5% both, 0.4% fusion.","15% (United States) versus 9% (Chile), not significantly different; gallstones 44% versus 85%.","Overall survival 22.3 versus 11.8 months with and without an ERBB2 alteration (P = 0.024)."],"whatItMeans":"The cleanest split of HER2 alterations in gallbladder cancer into amplification and mutation, which matters because IHC and ISH only see the amplified tumours. It also shows the high-incidence Chilean population has not been sequenced at scale.","caveats":["Only 23 Chilean patients.","Survival advantage may reflect access to HER2-directed therapy at MSK rather than biology."],"changedPractice":false,"participants":260},{"id":"paper-denkert-her2-low-pooled-neoadjuvant-lancet-oncol-2021","kind":"paper","name":"Clinical and molecular characteristics of HER2-low-positive breast cancer: pooled analysis of individual patient data from four prospective, neoadjuvant clinical trials","aka":[],"tldr":"Among 2,310 patients in four German neoadjuvant trials, 34% of hormone receptor-negative tumours were HER2-low; they responded to chemotherapy as often as HER2-zero tumours but had better three-year survival.","summary":"2,310 patients with HER2-non-amplified primary breast cancer treated in GeparSepto, GeparOcto, GeparX and GAIN-2 with prospective central HER2 testing were pooled. 1,098 (47.5%) were HER2-low-positive (IHC 1+ or 2+/ISH-negative) and 1,212 HER2-zero; 703 (64.0%) of HER2-low versus 445 (36.7%) of HER2-zero tumours were hormone receptor-positive, so 395 of 1,162 hormone receptor-negative tumours (34.0%) were HER2-low. pCR was lower in HER2-low tumours overall (29.2% versus 39.0%) and in the HR-positive subgroup but not in the HR-negative subgroup (50.1% versus 48.0%). HER2-low patients had longer three-year disease-free (83.4% versus 76.1%) and overall survival (91.6% versus 85.8%), with the differences seen in HR-negative tumours (DFS 84.5% versus 74.4%; OS 90.2% versus 84.3%).","asOf":"2026-09-24","links":[{"label":"Denkert et al., Lancet Oncol 2021: HER2-low-positive disease in 2,310 patients from four neoadjuvant trials","url":"https://doi.org/10.1016/S1470-2045(21)00301-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34252375/"}],"tags":[],"related":["her2-low-ihc"],"cancers":["tnbc","tnbc-early","her2-low-metastatic-breast-cancer"],"sections":[],"technologies":[],"targets":["her2"],"drugs":[],"companies":["gbg"],"institutions":[],"pathways":[],"terms":["her2-low","pcr"],"trials":[],"people":["carsten-denkert","sibylle-loibl"],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2021,"doi":"10.1016/S1470-2045(21)00301-6","pmid":"34252375","authors":"Denkert C, Seither F, Schneeweiss A, et al.","paperType":"observational","findings":["HER2-low in 395 of 1,162 hormone receptor-negative tumours, 34.0%.","pCR in HR-negative disease 50.1% HER2-low versus 48.0% HER2-zero.","HR-negative HER2-low: three-year DFS 84.5% versus 74.4%, OS 90.2% versus 84.3%."],"whatItMeans":"The trial-grade HER2-low share for TNBC is about a third, and the survival difference hints that HER2-zero triple-negative disease is the more aggressive group.","caveats":["Pooled trial populations with different regimens.","Survival data available for 1,694 patients."],"changedPractice":false,"participants":2310},{"id":"paper-atchley-brca-status-triple-negative-jco-2008","kind":"paper","name":"Clinical and pathologic characteristics of patients with BRCA-positive and BRCA-negative breast cancer","aka":[],"tldr":"A 2008 MD Anderson series showing that 57 percent of breast cancers in BRCA1 carriers were triple-negative against 14 percent in women without a BRCA fault, the clinical number behind the rule that triple-negative diagnosis should prompt a genetic test.","summary":"Atchley, Albarracin, Lopez, Valero and colleagues examined tumour pathology and clinical characteristics in 491 women with breast cancer who had genetic testing for BRCA mutations between 1997 and 2006; 391 were BRCA-negative and 86 BRCA-positive. Triple-negative breast cancer was diagnosed in 57.1 percent of BRCA1-positive patients, 23.3 percent of BRCA2-positive patients and 13.8 percent of BRCA-negative patients. BRCA1 carriers had higher nuclear grade tumours (p<0.001), and among triple-negative patients BRCA2 carriers were older at diagnosis than BRCA1 carriers and non-carriers (p<0.01). The authors suggest BRCA1-associated tumours divide into triple-negative and non-triple-negative groups.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2008","url":"https://doi.org/10.1200/JCO.2008.16.6231"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/18779615/"}],"tags":["tnbc-evidence"],"related":[],"cancers":["tnbc"],"sections":[],"technologies":["germline-testing"],"targets":["brca"],"drugs":[],"companies":[],"institutions":["md-anderson"],"pathways":[],"terms":["germline-testing"],"trials":[],"people":[],"bottlenecks":["b-hereditary-risk"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2008,"doi":"10.1200/JCO.2008.16.6231","pmid":"18779615","authors":"Atchley DP, Albarracin CT, Lopez A, et al.","paperType":"observational","findings":["Triple-negative disease in 57.1 percent of BRCA1 carriers, 23.3 percent of BRCA2 carriers and 13.8 percent of non-carriers.","BRCA1 carriers had higher nuclear grade tumours (p<0.001)."],"whatItMeans":"Turned the laboratory link between BRCA1 and basal-like biology into a clinical rule: a triple-negative diagnosis is itself a reason to offer germline testing, now embedded in NICE, NCCN and ESMO criteria.","caveats":["Single-centre series of women referred for genetic testing, so enrichment for hereditary disease is expected.","Retrospective record review."],"changedPractice":true,"participants":491},{"id":"paper-sausen-ctdna-pancreatic-resection-nat-commun-2015","kind":"paper","name":"Clinical implications of genomic alterations in the tumour and circulation of pancreatic cancer patients","aka":[],"tldr":"Sequencing tumours and blood from 101 patients found that mutations in chromatin genes go with better survival and that tumour DNA can be found in the blood of 43% of patients with localised cancer, flagging relapse six and a half months before a scan.","summary":"Whole-exome analyses of 24 tumours and targeted genomic analyses of 77 were combined with non-invasive examination of tumour-specific mutations in the circulation. Somatic mutations in the chromatin-regulating genes MLL, MLL2, MLL3 and ARID1A were found in 20% of patients and associated with improved survival; alterations in genes with potential therapeutic utility were found in over a third of cases. Liquid biopsy showed detectable circulating tumour DNA at diagnosis in 43% of patients with localised disease, and detection after resection predicted clinical relapse and poor outcome, with recurrence detected by ctDNA 6.5 months earlier than by computed tomography.","asOf":"2026-09-24","links":[{"label":"Sausen et al., Nat Commun 2015: tumour and circulating alterations in 101 patients","url":"https://doi.org/10.1038/ncomms8686"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26154128/"}],"tags":[],"related":["ctdna-mrd-positive"],"cancers":["pancreatic","resectable-pdac"],"sections":[],"technologies":["liquid-biopsy","mrd-testing"],"targets":["arid1a","kmt2c","kmt2d"],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":[],"terms":["ctdna","mrd","cfdna"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-communications"],"dependsOn":[],"notes":[],"journal":"Nature Communications","year":2015,"doi":"10.1038/ncomms8686","pmid":"26154128","authors":"Sausen M, Phallen J, Adleff V, et al.","paperType":"translational","findings":["Chromatin gene mutations in 20%, associated with improved survival.","ctDNA detectable in 43% of localised disease at diagnosis.","Post-resection ctDNA predicted relapse 6.5 months before imaging."],"whatItMeans":"The first demonstration that molecular residual disease can be read in pancreatic cancer and that it moves months ahead of the scan.","caveats":["Small cohort; detection depends on assay sensitivity.","No trial has yet shown that acting on the result helps."],"changedPractice":false,"participants":101},{"id":"paper-aggarwal-plasma-genotyping-personalised-therapy-jama-oncol-2019","kind":"paper","name":"Clinical implications of plasma-based genotyping with the delivery of personalized therapy in metastatic non-small cell lung cancer","aka":[],"tldr":"Adding a blood test to routine practice nearly doubled the number of patients found to have a treatable mutation, and a third of those tested by blood alone were spared a biopsy.","summary":"A prospective cohort of 323 patients with metastatic non-small-cell lung cancer had plasma next-generation sequencing on a 73-gene platform ordered as part of routine clinical management. Therapeutically targetable mutations in EGFR, ALK, MET, BRCA1, ROS1, RET, ERBB2 or BRAF were detected in 113 patients overall, 35.0%. Ninety-four patients had plasma testing only, and a targetable mutation was found in 31 of them, 33.0%, sparing an invasive biopsy. Among the remaining 229 patients who had concurrent plasma and tissue testing or could not have tissue testing, a targetable mutation was detected in tissue alone for 47 patients, 20.5%, and the addition of plasma raised this to 82, 35.8%. Thirty-six of 42 patients treated on the basis of a plasma result achieved a complete or partial response or stable disease.","asOf":"2026-09-25","links":[{"label":"Aggarwal et al., JAMA Oncol 2019: plasma-based genotyping and the delivery of matched treatment in 323 metastatic lung cancers","url":"https://doi.org/10.1001/jamaoncol.2018.4305"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30325992/"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":["liquid-biopsy","cgp"],"targets":["egfr","alk","met","ros1","ret","her2","braf"],"drugs":[],"companies":[],"institutions":[],"pathways":["rtk-activation"],"terms":["ctdna","cfdna","ngs","biopsy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2019,"doi":"10.1001/jamaoncol.2018.4305","pmid":"30325992","authors":"Aggarwal C, Thompson JC, Black TA, et al.","paperType":"observational","findings":["Targetable mutations in 35.0% of patients overall with plasma sequencing in routine use.","Plasma-only testing found a targetable mutation in 33% of those patients, avoiding a biopsy.","Adding plasma to tissue raised detection from 20.5% to 35.8%.","Thirty-six of 42 patients treated on a plasma result responded or remained stable."],"whatItMeans":"It showed the benefit of plasma testing is not only analytical but logistical: it reaches patients who are too unwell, or whose disease is too inaccessible, for a repeat biopsy.","caveats":["Single centre, not randomised, and testing was at physician discretion.","Allele fraction did not correlate with depth of response.","Median follow-up was seven months."],"changedPractice":true,"participants":323},{"id":"paper-larson-jco-precis-oncol","kind":"paper","name":"Clinical Outcomes of Molecular Tumor Boards: A Systematic Review","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 34632252 and published in JCO Precision Oncology; the citing page links this DOI, which is how the record was matched.","summary":"We conducted this systematic review to evaluate the clinical outcomes associated with molecular tumor board (MTB) review in patients with cancer.\n\nMethods: A systematic search of PubMed was performed to identify studies reporting clinical outcomes in patients with cancer who were reviewed by an MTB. To be included, studies had to report clinical outcomes, including clinical benefit, response, progression-free survival, or overall survival. Two reviewers independently selected studies and assessed quality with the Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group or the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies depending on the type of study being reviewed.\n\nResults: Fourteen studies were included with a total of 3,328 patients with cancer. All studies included patients without standard-of-care treatment options and usually with multiple prior lines of therapy. In studies reporting response rates, patients receiving MTB-recommended therapy had overall response rates ranging from 0% to 67%. In the only trial powered on clinical outcome and including a control group, the group receiving MTB-recommended therapy had significantly improved rate of progression-free survival compared with those receiving conventional therapy.\n\nConclusion: Although data quality is limited by a lack of prospective randomized controlled trials, MTBs appear to improve clinical outcomes for patients with cancer. Future research should concentrate on prospective trials and standardization of approach and outcomes.\n\nIndexed on Europe PMC as PubMed record 34632252 (DOI 10.1200/po.20.00495). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JCO Precis Oncol 2021","url":"https://doi.org/10.1200/po.20.00495"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34632252/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34632252"}],"tags":["europepmc-ingest"],"related":["multidisciplinary-tumour-board"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco-precision-oncology"],"dependsOn":[],"notes":[],"journal":"JCO Precision Oncology","year":2021,"doi":"10.1200/po.20.00495","pmid":"34632252","authors":"Larson KL, Huang B, Weiss HL, et al.","paperType":"review","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-thakker-j-clin-endocrinol-metab","kind":"paper","name":"Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1)","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 22723327 and published in The Journal of clinical endocrinology and metabolism; the citing page links this DOI, which is how the record was matched.","summary":"Objective: The aim was to provide guidelines for evaluation, treatment, and genetic testing for multiple endocrine neoplasia type 1 (MEN1).\n\nParticipants: The group, which comprised 10 experts, including physicians, surgeons, and geneticists from international centers, received no corporate funding or remuneration.\n\nProcess: Guidelines were developed by reviews of peer-reviewed publications; a draft was prepared, reviewed, and rigorously revised at several stages; and agreed-upon revisions were incorporated.\n\nConclusions: MEN1 is an autosomal dominant disorder that is due to mutations in the tumor suppressor gene MEN1, which encodes a 610-amino acid protein, menin. Thus, the finding of MEN1 in a patient has important implications for family members because first-degree relatives have a 50% risk of developing the disease and can often be identified by MEN1 mutational analysis. MEN1 is characterized by the occurrence of parathyroid, pancreatic islet, and anterior pituitary tumors. Some patients may also develop carcinoid tumors, adrenocortical tumors, meningiomas, facial angiofibromas, collagenomas, and lipomas. Patients with MEN1 have a decreased life expectancy, and the outcomes of current treatments, which are generally similar to those for the respective tumors occurring in non-MEN1 patients, are not as successful because of multiple tumors, which may be larger, more aggressive, and resistant to treatment, and the concurrence of metastases. The prognosis for MEN1 patients might be improved by presymptomatic tumor detection and undertaking treatment specific for MEN1 tumors. Thus, it is recommended that MEN1 patients and their families should be cared for by multidisciplinary teams comprising relevant specialists with experience in the diagnosis and treatment of patients with endocrine tumors.\n\nIndexed on Europe PMC as PubMed record 22723327 (DOI 10.1210/jc.2012-1230). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Endocrinol Metab 2012","url":"https://doi.org/10.1210/jc.2012-1230"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22723327/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/22723327"}],"tags":["europepmc-ingest"],"related":["multiple-endocrine-neoplasia"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Journal of clinical endocrinology and metabolism","year":2012,"doi":"10.1210/jc.2012-1230","pmid":"22723327","authors":"Thakker RV, Newey PJ, Walls GV, et al.","paperType":"review","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-jshbps-biliary-tract-cancer-guidelines-2019-jhbps-2021","kind":"paper","name":"Clinical practice guidelines for the management of biliary tract cancers 2019: The 3rd English edition","aka":[],"tldr":"Japan's surgical society guideline for bile duct, gallbladder and ampullary cancer, the only major guideline with a section on preventive treatment.","summary":"Third English edition of the Japanese Society of Hepato-Biliary-Pancreatic Surgery guidelines, first issued in 2007 and revised in 2014. Thirty-one clinical questions cover six topics: prophylactic treatment, diagnosis, biliary drainage, surgical treatment, chemotherapy and radiation therapy, graded with GRADE as strong (14 recommendations) or weak (14), with three questions left without a recommendation.","asOf":"2026-09-24","links":[{"label":"J Hepatobiliary Pancreat Sci 2021","url":"https://doi.org/10.1002/jhbp.870"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33259690/"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder","cholangiocarcinoma","ampullary"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["radical-cholecystectomy","prophylactic-cholecystectomy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of Hepato-Biliary-Pancreatic Sciences","year":2021,"doi":"10.1002/jhbp.870","pmid":"33259690","authors":"Nagino M, Hirano S, Yoshitomi H, et al.","paperType":"guideline","findings":["31 clinical questions across six topics including prophylactic treatment.","14 strong and 14 weak recommendations; three questions with no recommendation."],"whatItMeans":"Japanese surgeons operate on gallbladder cancer far more often than UK surgeons and their guideline addresses prevention (pancreaticobiliary maljunction, polyps) as a clinical topic, which Western guidelines do not.","caveats":["Surgical-society guideline; systemic therapy sections predate the immunotherapy trials.","Evidence for many surgical questions is retrospective."],"changedPractice":true},{"id":"paper-greenlee-ca-cancer-j-clin","kind":"paper","name":"Clinical practice guidelines on the evidence-based use of integrative therapies during and after breast cancer treatment","aka":[],"tldr":"Paper cited by four technology pages, indexed on Europe PMC as PubMed record 28436999 and published in CA: A Cancer Journal for Clinicians; the citing pages link this DOI, which is how the record was matched.","summary":"Answer questions and earn CME/CNE Patients with breast cancer commonly use complementary and integrative therapies as supportive care during cancer treatment and to manage treatment-related side effects. However, evidence supporting the use of such therapies in the oncology setting is limited. This report provides updated clinical practice guidelines from the Society for Integrative Oncology on the use of integrative therapies for specific clinical indications during and after breast cancer treatment, including anxiety/stress, depression/mood disorders, fatigue, quality of life/physical functioning, chemotherapy-induced nausea and vomiting, lymphedema, chemotherapy-induced peripheral neuropathy, pain, and sleep disturbance. Clinical practice guidelines are based on a systematic literature review from 1990 through 2015. Music therapy, meditation, stress management, and yoga are recommended for anxiety/stress reduction. Meditation, relaxation, yoga, massage, and music therapy are recommended for depression/mood disorders. Meditation and yoga are recommended to improve quality of life. Acupressure and acupuncture are recommended for reducing chemotherapy-induced nausea and vomiting. Acetyl-L-carnitine is not recommended to prevent chemotherapy-induced peripheral neuropathy due to a possibility of harm. No strong evidence supports the use of ingested dietary supplements to manage breast cancer treatment-related side effects. In summary, there is a growing body of evidence supporting the use of integrative therapies, especially mind-body therapies, as effective supportive care strategies during breast cancer treatment. Many integrative practices, however, remain understudied, with insufficient evidence to be definitively recommended or avoided. CA Cancer J Clin 2017;67:194-232. © 2017 American Cancer Society.\n\nIndexed on Europe PMC as PubMed record 28436999 (DOI 10.3322/caac.21397). Matched by DOI alone: four technology pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"CA Cancer J Clin 2017","url":"https://doi.org/10.3322/caac.21397"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28436999/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28436999"}],"tags":["europepmc-ingest"],"related":["acupuncture-nausea","acupuncture-hot-flushes","reflexology-cancer","reiki-energy-therapies"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["ca-cancer-journal"],"dependsOn":[],"notes":[],"journal":"CA: A Cancer Journal for Clinicians","year":2017,"doi":"10.3322/caac.21397","pmid":"28436999","authors":"Greenlee H, DuPont-Reyes MJ, Balneaves LG, et al.","paperType":"review","findings":[],"whatItMeans":"Four technology pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-neyaz-pdl1-gallbladder-histopathology-2018","kind":"paper","name":"Clinical relevance of PD-L1 expression in gallbladder cancer: a potential target for therapy","aka":[],"tldr":"In 174 Indian gallbladder cancers, about a quarter had PD-L1 on tumour cells and a quarter on immune cells, more so in higher-grade tumours, but PD-L1 did not predict survival.","summary":"174 cases of gallbladder carcinoma were evaluated for PD-L1 expression with the SP263 clone on tissue microarrays, at cut-offs of 1%, 10% and 50% in tumour cells and in tumour-infiltrating lymphocytes, and correlated with clinicopathological characteristics and survival. Mean age was 49.9 years, the male to female ratio 1 to 2.9, and 73.6% presented with stage 3 or 4 disease.\n\nTumour cells expressed PD-L1 in 23.0% of cases and tumour-infiltrating lymphocytes in 24.1%; at cut-offs of 10% and 50%, 14.9% and 7.5% of cases were positive. Tumour proportion score was associated with histological type, histological and nuclear grade, nodal metastasis, higher stage and tumour-infiltrating lymphocytes. Paired lymph node metastases showed discordantly higher PD-L1 than primaries. Overall survival was not associated with PD-L1 expression (P = 0.546).","asOf":"2026-09-24","links":[{"label":"Neyaz et al., Histopathology 2018: PD-L1 (SP263) in 174 Indian gallbladder cancers","url":"https://doi.org/10.1111/his.13669"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29882997/"}],"tags":[],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":["pdl1"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ihc","tils"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Histopathology","year":2018,"doi":"10.1111/his.13669","pmid":"29882997","authors":"Neyaz A, Husain N, Kumari S, et al.","paperType":"observational","findings":["PD-L1 on tumour cells in 23.0% at 1%, 14.9% at 10% and 7.5% at 50%; on immune cells in 24.1% (SP263).","Associated with histological type and grade, nuclear grade and nodal metastasis; higher in nodal metastases than primaries.","No association with overall survival (P = 0.546)."],"whatItMeans":"The largest PD-L1 series from a high-incidence country; the one-in-four figure is the number quoted for gallbladder cancer, though the Western series with a different clone found fewer. No biliary approval uses PD-L1 to select patients.","caveats":["Tissue microarrays sample a small core of heterogeneous tumours.","SP263 clone and tumour-cell scoring are not interchangeable with 22C3 CPS."],"changedPractice":false,"participants":174},{"id":"paper-yaeger-metastatic-colorectal-genomic-landscape-cancer-cell-2018","kind":"paper","name":"Clinical sequencing defines the genomic landscape of metastatic colorectal cancer","aka":[],"tldr":"Sequencing 1,134 bowel cancers in the clinic rather than in a research study showed that essentially every one of them has the WNT growth signal switched on, and that right-sided and left-sided tumours reach that state by different routes.","summary":"Prospective targeted sequencing of 1,134 colorectal cancers identified splice alterations in intronic regions of APC and large in-frame deletions in CTNNB1, taking oncogenic WNT pathway alterations to 96% of colorectal cancers. Right-sided primary site in microsatellite-stable metastatic disease was associated with shorter survival, older age at diagnosis, more mutations and enrichment of oncogenic alterations in KRAS, BRAF, PIK3CA, AKT1, RNF43 and SMAD4 compared with left-sided primaries. Left-sided tumours frequently had no identifiable genetic alteration in mitogenic signalling but exhibited higher mitogenic ligand expression. The authors concluded that right- and left-sided microsatellite-stable colorectal cancers follow different routes to tumourigenesis.\n\nDeposited as crc_msk_2017 on cBioPortal (1,134 MSK-IMPACT samples; 601 primaries and 533 metastases; 1,120 with a recorded side, 341 right and 779 left).","asOf":"2026-09-24","links":[{"label":"Yaeger et al., Cancer Cell 2018: prospective targeted sequencing of 1,134 colorectal cancers (MSK)","url":"https://doi.org/10.1016/j.ccell.2017.12.004"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29316426/"},{"label":"cBioPortal study crc_msk_2017 (MSK, Cancer Cell 2018; 1,134 MSK-IMPACT samples from patients with metastatic disease, 601 primaries and 533 metastases)","url":"https://www.cbioportal.org/study/summary?id=crc_msk_2017"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["cgp","ngs-bioinformatics-software"],"targets":["apc","ctnnb1","kras","braf","pik3ca","rnf43","smad4"],"drugs":[],"companies":[],"institutions":["mskcc"],"pathways":["wnt","ras-mapk","colorectal-cancer-signalling"],"terms":["sidedness","wild-type","ngs"],"trials":[],"people":["rona-yaeger","andrea-cercek"],"bottlenecks":[],"keyPapers":[],"journals":["cancer-cell"],"dependsOn":[],"notes":[],"journal":"Cancer Cell","year":2018,"doi":"10.1016/j.ccell.2017.12.004","pmid":"29316426","authors":"Yaeger R, Chatila WK, Lipsyc MD, et al.","paperType":"observational","findings":["Oncogenic WNT alterations in 96% of cancers once intronic APC splice events and large in-frame CTNNB1 deletions are counted.","Right-sided microsatellite-stable tumours enriched for KRAS, BRAF, PIK3CA, AKT1, RNF43 and SMAD4 alterations and shorter survival.","Left-sided tumours often lack a mitogenic driver but express more mitogenic ligand."],"whatItMeans":"It turned sidedness from an epidemiological curiosity into a mechanistic statement, and it is the reason a wild-type mitogenic report on a left-sided tumour is read as ligand dependence rather than as an absence.","caveats":["A targeted panel, so genes off MSK-IMPACT read zero.","A referral population enriched for metastatic disease, which lowers the measured microsatellite instability rate.","Ligand expression was measured in a subset."],"changedPractice":false,"participants":1134},{"id":"paper-bar-j-pers-med","kind":"paper","name":"Clinical Utility of an Ex Vivo Functional Test in Personalized Cancer Treatment","aka":[],"tldr":"Paper cited by one company page, indexed on Europe PMC as PubMed record 42346609 and published in Journal of personalized medicine; the citing page links this DOI, which is how the record was matched.","summary":"Background/Objectives: Providing optimized and accurate treatment to cancer patients remains a major challenge in oncology care. The emergence of precision medicine tools to match the correct therapy to the patient has significantly advanced treatment modalities in the last few years. While genomics has been shown to be critical in selecting targeted therapies for a specific somatic mutation, the overall clinical benefit of broad genomic sequencing has been found lacking. Here, we evaluate the utility of our previously clinically validated ex vivo functional assay across different treatment scenarios, demonstrating its ability to transform predicted non-responders into predicted responders, rule out ineffective treatments, provide multiple treatment options, and validate physician choices. Methods: The evaluation was performed on a post-market surveillance study analyzing 312 patients, from which 278 patients had successful test reports (an 89.1% test success rate), with clinical outcomes available from 45 of those patients. Results: We show that in the group of patients with clinical response data, the tests yield a PPV of 91.18% and NPV of 90.91% with clinical utility impacting physician decision in 51.1% of cases. Further analysis of the entire cohort showed the potential of clinical utility to reach up to 59.3% on a large group of patients. Conclusions: The accurate prediction of patient response using the test suggests the potential for the platform to improve patient treatment in clinical practice by reducing ineffective drug use and optimizing personalized patient drug regiments.\n\nIndexed on Europe PMC as PubMed record 42346609 (DOI 10.3390/jpm16060298). Matched by DOI alone: one company page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Pers Med 2026","url":"https://doi.org/10.3390/jpm16060298"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42346609/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42346609"}],"tags":["europepmc-ingest"],"related":["curesponse"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of personalized medicine","year":2026,"doi":"10.3390/jpm16060298","pmid":"42346609","authors":"Bar V, Zundelevich A, Gavert N, et al.","paperType":"observational","findings":[],"whatItMeans":"One company page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-preempt-crc-shaukat-jama-2025","kind":"paper","name":"Clinical validation of a circulating tumor DNA-based blood test to screen for colorectal cancer (PREEMPT CRC)","aka":[],"tldr":"In more than 27,000 average-risk adults who then had a colonoscopy, Freenome's blood test picked up 79 percent of bowel cancers with few false alarms, but found only one in eight advanced precancerous polyps.","summary":"Primary publication of PREEMPT CRC (NCT04369053), a prospective, multicentre, cross-sectional observational study at 201 centres across 49 US states and the United Arab Emirates. Asymptomatic adults aged 45 to 85 at average risk of colorectal cancer gave blood before a standard-of-care screening colonoscopy; participants, staff, pathologists and the laboratory were blinded. Primary endpoints were sensitivity for colorectal cancer and specificity, negative predictive value and positive predictive value for advanced colorectal neoplasia; the secondary endpoint was sensitivity for advanced precancerous lesions.\n\nIn the evaluable cohort of 27,010 (median age 57.0 years, 55.8 percent women), sensitivity for colorectal cancer was 79.2 percent (57 of 72; 95 percent CI 68.4 to 86.9) and specificity for advanced colorectal neoplasia 91.5 percent (22,306 of 24,371; 91.2 to 91.9). Negative predictive value was 90.8 percent (22,306 of 24,567) and positive predictive value 15.5 percent (378 of 2,443). All primary endpoints met prespecified acceptance criteria. Sensitivity for advanced precancerous lesions was 12.5 percent (321 of 2,567; 11.3 to 13.8), which did not meet its criterion.","asOf":"2026-09-24","links":[{"label":"JAMA 2025","url":"https://doi.org/10.1001/jama.2025.7515"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40455622/"},{"label":"ClinicalTrials.gov NCT04369053","url":"https://clinicaltrials.gov/study/NCT04369053"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["colorectal-screening","liquid-biopsy"],"targets":[],"drugs":["simplescreen-crc"],"companies":["freenome"],"institutions":[],"pathways":[],"terms":[],"trials":["preempt-crc"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2025,"doi":"10.1001/jama.2025.7515","pmid":"40455622","authors":"Shaukat A, Burke CA, Chan AT, et al.","paperType":"observational","findings":["Sensitivity for colorectal cancer 79.2 percent (57 of 72; 95 percent CI 68.4 to 86.9).","Specificity for advanced colorectal neoplasia 91.5 percent; negative predictive value 90.8 percent; positive predictive value 15.5 percent.","Sensitivity for advanced precancerous lesions 12.5 percent, below the prespecified acceptance criterion."],"whatItMeans":"This is the validation study behind the July 2026 FDA approval of SimpleScreen CRC. For someone who will not take a stool test or colonoscopy it offers a real option for catching cancer, but because it misses most advanced polyps it prevents fewer cancers than the established tests, and a positive result still needs a colonoscopy.","caveats":["Cross-sectional accuracy study; it does not measure whether screening with the test reduces colorectal cancer deaths.","The evaluable cohort of 27,010 is a subset of the 48,995 enrolled on the registry.","Funded by Freenome; several authors are employees or consultants."],"changedPractice":true,"participants":27010},{"id":"paper-klein-ccga3-mced-validation-ann-oncol-2021","kind":"paper","name":"Clinical validation of a targeted methylation-based multi-cancer early detection test using an independent validation set","aka":[],"tldr":"The methylation blood test now sold as Galleri detected half of all cancers and one in six stage I cancers in 4,077 people, while wrongly flagging one healthy person in 200, and named the organ correctly in 89% of positives.","summary":"The third and final substudy of the Circulating Cell-free Genome Atlas validated a multi-cancer early detection test using cell-free DNA methylation sequencing with machine learning in 4,077 participants (2,823 cancer, 1,254 non-cancer confirmed at one year). Specificity for cancer signal detection was 99.5%; overall sensitivity was 51.5%, rising by stage (I 16.8%, II 40.4%, III 77.0%, IV 90.1%). Stage I to III sensitivity was 67.6% in 12 pre-specified cancers accounting for about two-thirds of US cancer deaths and 40.7% across all cancers. Cancer signals were detected across more than 50 cancer types and accuracy of cancer signal origin prediction was 88.7%.","asOf":"2026-09-24","links":[{"label":"Klein et al., Ann Oncol 2021: CCGA3 validation of the Galleri methylation test in 4,077 participants","url":"https://doi.org/10.1016/j.annonc.2021.05.806"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34176681/"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":["mced","cfdna-methylation-testing","methylation-profiling","liquid-biopsy"],"targets":[],"drugs":["galleri"],"companies":["grail"],"institutions":[],"pathways":[],"terms":["cfdna","ctdna"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2021,"doi":"10.1016/j.annonc.2021.05.806","pmid":"34176681","authors":"Klein EA, Richards D, Cohn A, et al.","paperType":"observational","findings":["Specificity 99.5%; overall sensitivity 51.5%.","Stage I sensitivity 16.8%; stage IV 90.1%.","Cancer signal origin correct in 88.7% of true positives."],"whatItMeans":"Methylation-based screening is real but weakest exactly where pancreatic cancer needs it, at stage I, which is why high-risk surveillance rather than population screening carries the field here.","caveats":["Case-control validation, not a screening population.","Pancreas-specific stage I sensitivity is not given in the abstract."],"changedPractice":false,"participants":4077},{"id":"paper-schettini-her2-low-features-npj-breast-cancer-2021","kind":"paper","name":"Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer","aka":[],"tldr":"A 3,689-patient study showing that 36.6 percent of triple-negative tumours are HER2-low, that in triple-negative disease HER2-low tumours are biologically no different from HER2-zero ones, and that pathologists agree poorly on the score; the label matters only because a drug now depends on it.","summary":"Schettini, Chic, Brasó-Maristany, Paré and colleagues collected retrospective clinicopathological and PAM50 data from 3,689 patients with HER2-negative breast cancer. HER2-low (immunohistochemistry 1+ or 2+ without ERBB2 amplification) was more common in hormone receptor-positive disease (65.4 percent) than triple-negative disease (36.6 percent). Within hormone receptor-positive disease ERBB2 and luminal genes were more expressed in HER2-low than HER2 0 tumours, whereas in triple-negative disease no gene was differentially expressed by HER2 level; within HER2-low, ERBB2 levels were higher in hormone receptor-positive than triple-negative tumours; HER2-low was not associated with overall survival in either group; and reproducibility of the HER2-low call among pathologists was suboptimal.","asOf":"2026-09-24","links":[{"label":"NPJ Breast Cancer 2021","url":"https://doi.org/10.1038/s41523-020-00208-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33397968/"}],"tags":["tnbc-evidence"],"related":["paper-destiny-breast04-nejm-2022","her2-low-ihc"],"cancers":["tnbc","breast-hr-positive","her2-low-metastatic-breast-cancer"],"sections":[],"technologies":["digital-pathology-ai"],"targets":["her2"],"drugs":["trastuzumab-deruxtecan"],"companies":[],"institutions":[],"pathways":[],"terms":["her2-low","her2-ultralow","ihc","pam50"],"trials":["destiny-breast04"],"people":["aleix-prat"],"bottlenecks":["b-biomarker-validation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"NPJ Breast Cancer","year":2021,"doi":"10.1038/s41523-020-00208-2","pmid":"33397968","authors":"Schettini F, Chic N, Brasó-Maristany F, et al.","paperType":"observational","findings":["HER2-low in 36.6 percent of triple-negative vs 65.4 percent of hormone receptor-positive HER2-negative tumours.","No gene differentially expressed between HER2-low and HER2 0 triple-negative tumours; HER2-low not associated with overall survival.","Suboptimal inter-pathologist reproducibility of the HER2-low score."],"whatItMeans":"HER2-low is a drug eligibility label, not a biological subtype, in triple-negative disease; because a third of patients qualify for trastuzumab deruxtecan on a score pathologists disagree about, re-scoring and digital assistance for HER2 0 versus 1+ is a practical gap.","caveats":["Retrospective, multiple cohorts and scoring eras.","Predates the HER2-ultralow category and the DESTINY-Breast06 result in hormone receptor-positive disease."],"changedPractice":false,"participants":3689},{"id":"paper-cll12-ibrutinib-early-stage-langerbeins-jco-2025","kind":"paper","name":"CLL12: ibrutinib in early-stage chronic lymphocytic leukaemia, a randomised placebo-controlled phase 3 trial","aka":[],"tldr":"Giving the pill ibrutinib to people with early, symptom-free chronic lymphocytic leukaemia delayed the disease but, after almost six years, did not help them live longer than placebo, so doctors should keep watching and waiting rather than treating early.","summary":"Final analysis of the German CLL Study Group's randomised, double-blind, placebo-controlled phase 3 CLL12 trial: 363 patients with asymptomatic, treatment-naive Binet stage A chronic lymphocytic leukaemia at increased risk of progression received ibrutinib 420 mg daily (n 182) or placebo (n 181); 152 low-risk patients were followed on watch and wait.\n\nIbrutinib significantly delayed progression to symptomatic disease, but at a median observation of 69.3 months five-year survival was 93.3 percent with ibrutinib, 93.6 percent with placebo and 97.9 percent on watch and wait. Adverse events occurred in almost every patient in both groups, with more cardiovascular toxicity on ibrutinib.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2025","url":"https://doi.org/10.1200/JCO.24.00975"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39602678/"}],"tags":[],"related":[],"cancers":["cll","cll-treatment-naive"],"sections":[],"technologies":[],"targets":[],"drugs":["ibrutinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["cll12"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2025,"doi":"10.1200/JCO.24.00975","pmid":"39602678","authors":"Langerbeins P, Robrecht S, Nieper P, et al.","paperType":"rct","findings":["Ibrutinib significantly delayed progression to symptomatic disease compared with placebo.","Five-year overall survival 93.3 percent (ibrutinib), 93.6 percent (placebo) and 97.9 percent (watch and wait).","Estimated ten-year survival from diagnosis 89.8, 86.5 and 95.3 percent respectively; increased cardiovascular toxicity with ibrutinib."],"whatItMeans":"Watch and wait remains the standard of care for early-stage chronic lymphocytic leukaemia irrespective of risk factors, even with a targeted drug available.","caveats":["Few deaths and long survival mean the trial could not exclude a small survival effect.","Ibrutinib was given as continuous single-agent therapy; time-limited combinations were not tested."],"changedPractice":false,"participants":515},{"id":"paper-cll14-venetoclax-obinutuzumab-nejm-2019","kind":"paper","name":"CLL14: one year of venetoclax plus obinutuzumab instead of chemo-immunotherapy in older, less fit CLL patients","aka":[],"tldr":"A fixed one-year course of two targeted drugs kept CLL under control far longer than chemo-immunotherapy, and most patients had no detectable disease when treatment stopped.","summary":"CLL14 randomised 432 previously untreated patients with CLL and coexisting conditions (CIRS score above 6 or creatinine clearance under 70 mL/min) to 12 cycles of venetoclax plus obinutuzumab or chlorambucil plus obinutuzumab. The primary endpoint was investigator-assessed progression-free survival. At 24 months PFS was 88.2% versus 64.1% (hazard ratio 0.35), and undetectable MRD in peripheral blood three months after treatment ended was 75.5% versus 35.2%. Grade 3-4 neutropenia and infections were similar between arms. With six years of follow-up more than half of venetoclax-obinutuzumab patients remained progression-free against roughly a fifth on chemo-immunotherapy, though overall survival was not significantly different.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa1815281"},{"label":"ClinicalTrials.gov NCT02242942","url":"https://clinicaltrials.gov/study/NCT02242942"}],"tags":[],"related":["venetoclax-plus-obinutuzumab"],"cancers":["cll"],"sections":[],"technologies":[],"targets":["bcl2","cd20"],"drugs":["venetoclax","obinutuzumab"],"companies":["abbvie","roche-genentech"],"institutions":[],"pathways":[],"terms":["mrd","pfs","ighv-status","del17p-tp53"],"trials":["cll14","cll13-gaia"],"people":["michael-hallek"],"bottlenecks":["b-dormancy-mrd","b-aging-comorbidity"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2019,"doi":"10.1056/NEJMoa1815281","authors":"Fischer K, Al-Sawaf O, Bahlo J, et al.","paperType":"rct","findings":["432 patients with untreated CLL and comorbidities; 12 cycles of venetoclax-obinutuzumab vs chlorambucil-obinutuzumab.","24-month PFS 88.2% vs 64.1%; hazard ratio 0.35.","Undetectable MRD (below 10^-4) in blood 3 months after treatment end: 75.5% vs 35.2%.","Grade 3-4 neutropenia 52.8% vs 48.1%; grade 3-4 infections 17.5% vs 15.0%.","Benefit held across IGHV-unmutated and TP53-aberrant subgroups, though del(17p)/TP53 patients relapsed earlier."],"whatItMeans":"CLL14 established the first chemotherapy-free, fixed-duration regimen for front-line CLL and made MRD-guided thinking mainstream in the disease. Patients get a year of treatment and then a treatment-free period rather than indefinite therapy. The choice today is between fixed-duration venetoclax combinations and continuous BTK inhibitors, with no proven survival difference.","caveats":["Overall survival has not differed significantly, partly because effective salvage therapies exist.","Patients were older and less fit; CLL13/GAIA later confirmed benefit in fit patients.","Venetoclax requires a 5-week ramp-up and tumour-lysis monitoring, which is a practical burden.","Retreatment strategy after relapse was not defined by the trial."],"changedPractice":true,"participants":432},{"id":"paper-greaves-nature","kind":"paper","name":"Clonal evolution in cancer","aka":[],"tldr":"Paper cited by one pathway page and one term page, indexed on Europe PMC as PubMed record 22258609 and published in Nature; the citing pages link this DOI, which is how the record was matched.","summary":"Cancers evolve by a reiterative process of clonal expansion, genetic diversification and clonal selection within the adaptive landscapes of tissue ecosystems. The dynamics are complex, with highly variable patterns of genetic diversity and resulting clonal architecture. Therapeutic intervention may destroy cancer clones and erode their habitats, but it can also inadvertently provide a potent selective pressure for the expansion of resistant variants. The inherently Darwinian character of cancer is the primary reason for this therapeutic failure, but it may also hold the key to more effective control.\n\nIndexed on Europe PMC as PubMed record 22258609 (DOI 10.1038/nature10762). Matched by DOI alone: one pathway page and one term page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2012","url":"https://doi.org/10.1038/nature10762"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22258609/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/22258609"}],"tags":["europepmc-ingest"],"related":["theories-of-cancer","clonal-evolution-theory"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2012,"doi":"10.1038/nature10762","pmid":"22258609","authors":"Greaves M, Maley CC","paperType":"review","findings":[],"whatItMeans":"One pathway page and one term page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-kakiuchi-nat-rev-cancer","kind":"paper","name":"Clonal expansion in non-cancer tissues","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 33627798 and published in Nature Reviews Cancer; the citing page links this DOI, which is how the record was matched.","summary":"Cancer is a clonal disorder derived from a single ancestor cell and its progenies that are positively selected by acquisition of 'driver mutations'. However, the evolution of positively selected clones does not necessarily imply the presence of cancer. On the contrary, it has become clear that expansion of these clones in phenotypically normal or non-cancer tissues is commonly seen in association with ageing and/or in response to environmental insults and chronic inflammation. Recent studies have reported expansion of clones harbouring mutations in cancer driver genes in the blood, skin, oesophagus, bronchus, liver, endometrium and bladder, where the expansion could be so extensive that tissues undergo remodelling of an almost entire tissue. The presence of common cancer driver mutations in normal tissues suggests a strong link to cancer development, providing an opportunity to understand early carcinogenic processes. Nevertheless, some driver mutations are unique to normal tissues or have a mutation frequency that is much higher in normal tissue than in cancer, indicating that the respective clones may not necessarily be destined for evolution to cancer but even negatively selected for carcinogenesis depending on the mutated gene. Moreover, tissues that are remodelled by genetically altered clones might define functionalities of aged tissues or modified inflammatory processes. In this Review, we provide an overview of major findings on clonal expansion in phenotypically normal or non-cancer tissues and discuss their biological significance not only in cancer development but also in ageing and inflammatory diseases.\n\nIndexed on Europe PMC as PubMed record 33627798 (DOI 10.1038/s41568-021-00335-3). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Cancer 2021","url":"https://doi.org/10.1038/s41568-021-00335-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33627798/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33627798"}],"tags":["europepmc-ingest"],"related":["ageing-tissue-field-theory"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Cancer","year":2021,"doi":"10.1038/s41568-021-00335-3","pmid":"33627798","authors":"Kakiuchi N, Ogawa S","paperType":"review","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-jaiswal-science","kind":"paper","name":"Clonal hematopoiesis in human aging and disease","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 31672865 and published in Science; the citing page links this DOI, which is how the record was matched.","summary":"As people age, their tissues accumulate an increasing number of somatic mutations. Although most of these mutations are of little or no functional consequence, a mutation may arise that confers a fitness advantage on a cell. When this process happens in the hematopoietic system, a substantial proportion of circulating blood cells may derive from a single mutated stem cell. This outgrowth, called \"clonal hematopoiesis,\" is highly prevalent in the elderly population. Here we discuss recent advances in our knowledge of clonal hematopoiesis, its relationship to malignancies, its link to nonmalignant diseases of aging, and its potential impact on immune function. Clonal hematopoiesis provides a glimpse into the process of mutation and selection that likely occurs in all somatic tissues.\n\nIndexed on Europe PMC as PubMed record 31672865 (DOI 10.1126/science.aan4673). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Science 2019","url":"https://doi.org/10.1126/science.aan4673"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31672865/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31672865"}],"tags":["europepmc-ingest"],"related":["ageing-tissue-field-theory"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2019,"doi":"10.1126/science.aan4673","pmid":"31672865","authors":"Jaiswal S, Ebert BL","paperType":"review","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-mcgranahan-cell","kind":"paper","name":"Clonal Heterogeneity and Tumor Evolution: Past, Present, and the Future","aka":[],"tldr":"Paper cited by one bottleneck page, indexed on Europe PMC as PubMed record 28187284 and published in Cell; the citing page links this DOI, which is how the record was matched.","summary":"Intratumor heterogeneity, which fosters tumor evolution, is a key challenge in cancer medicine. Here, we review data and technologies that have revealed intra-tumor heterogeneity across cancer types and the dynamics, constraints, and contingencies inherent to tumor evolution. We emphasize the importance of macro-evolutionary leaps, often involving large-scale chromosomal alterations, in driving tumor evolution and metastasis and consider the role of the tumor microenvironment in engendering heterogeneity and drug resistance. We suggest that bold approaches to drug development, harnessing the adaptive properties of the immune-microenvironment while limiting those of the tumor, combined with advances in clinical trial-design, will improve patient outcome.\n\nIndexed on Europe PMC as PubMed record 28187284 (DOI 10.1016/j.cell.2017.01.018). Matched by DOI alone: one bottleneck page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cell 2017","url":"https://doi.org/10.1016/j.cell.2017.01.018"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28187284/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28187284"}],"tags":["europepmc-ingest"],"related":["b-tumor-heterogeneity"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Cell","year":2017,"doi":"10.1016/j.cell.2017.01.018","pmid":"28187284","authors":"McGranahan N, Swanton C","paperType":"review","findings":[],"whatItMeans":"One bottleneck page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-lee-clonal-history-small-cell-transformation-jco-2017","kind":"paper","name":"Clonal history and genetic predictors of transformation into small-cell carcinomas from lung adenocarcinomas","aka":[],"tldr":"Some lung cancers escape a targeted pill by changing into a different kind of cancer. Reading whole genomes from the same patients over time showed the change was set up from the beginning, in tumours that had already lost two particular genes.","summary":"Twenty-one patients with advanced EGFR-mutant lung adenocarcinoma that transformed into resistant small-cell lung cancer were investigated, with whole-genome sequencing of nine tumours from four patients at various time points to reconstruct clonal evolutionary history. The resistant adenocarcinomas and small-cell cancers shared a common clonal origin and followed branched evolutionary trajectories, with the small-cell ancestors diverging before the first treatment. Complete inactivation of both RB1 and TP53 was present from the early adenocarcinoma stage. Immunohistochemistry in early-stage tissue from 75 patients treated with EGFR inhibitors found inactivation of both Rb and p53 in 82% of the transformed group against 3% of the non-transformed group, odds ratio 131. Among 65 patients in a predefined cohort, an adenocarcinoma with both proteins inactivated carried a 43-fold higher risk of transformation. APOBEC-induced hypermutation was frequent in the branches leading to transformation.","asOf":"2026-09-25","links":[{"label":"Lee et al., J Clin Oncol 2017: clonal history and genetic predictors of small-cell transformation from lung adenocarcinoma","url":"https://doi.org/10.1200/JCO.2016.71.9096"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28498782/"}],"tags":[],"related":[],"cancers":["nsclc","sclc"],"sections":[],"technologies":["wes-wgs","histopathology-ihc"],"targets":["egfr","rb1","tp53"],"drugs":[],"companies":[],"institutions":[],"pathways":["lineage-plasticity-neuroendocrine","clonal-evolution","resistance-routes-map","mutagenesis-signatures"],"terms":["histologic-transformation","resistance","mutational-signature","ihc"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2017,"doi":"10.1200/JCO.2016.71.9096","pmid":"28498782","authors":"Lee JK, Lee J, Kim S, et al.","paperType":"translational","findings":["Transformed small-cell cancers branch from the adenocarcinoma clone before treatment begins.","Both RB1 and TP53 are completely inactivated from the early adenocarcinoma stage.","Inactivation of both proteins was present in 82% of transformed against 3% of non-transformed cases.","APOBEC hypermutation marks the branches that transform."],"whatItMeans":"It made transformation predictable from the first biopsy, using two stains that most pathology laboratories can already run, which is the practical way to know which patients need close watching and early rebiopsy.","caveats":["Twenty-one transformed patients and four with serial whole genomes.","The immunohistochemistry validation is retrospective.","Predicting risk does not yet change treatment, since no intervention has been shown to prevent transformation."],"changedPractice":false,"participants":21},{"id":"paper-skoulidis-kras-co-mutation-subsets-cancer-discov-2015","kind":"paper","name":"Co-occurring genomic alterations define major subsets of KRAS-mutant lung adenocarcinoma with distinct biology, immune profiles, and therapeutic vulnerabilities","aka":[],"tldr":"Lung cancers driven by a mutated KRAS gene behave so differently from one another that they are better thought of as three diseases, and which of the three a patient has depends on the second gene that is broken.","summary":"An integrative analysis of genomic, transcriptomic and proteomic data from early-stage and chemorefractory lung adenocarcinoma identified three robust subsets of KRAS-mutant disease, dominated respectively by co-occurring events in STK11 or LKB1 (the KL subgroup), TP53 (KP) and CDKN2A or CDKN2B inactivation coupled with low expression of the NKX2-1 (TTF1) transcription factor (KC). KC tumours frequently showed mucinous histology and suppressed mTORC1 signalling. KL tumours had high rates of KEAP1 inactivation and expressed lower levels of immune markers including PD-L1. KP tumours had higher somatic mutation levels, inflammatory markers, immune checkpoint effector molecules and improved relapse-free survival. Drug sensitivity also differed, with KL cells showing increased vulnerability to HSP90 inhibition.","asOf":"2026-09-25","links":[{"label":"Skoulidis et al., Cancer Discov 2015: co-occurring alterations define the KL, KP and KC subsets of KRAS-mutant lung adenocarcinoma","url":"https://doi.org/10.1158/2159-8290.CD-14-1236"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26069186/"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":["rna-seq","cgp"],"targets":["kras","stk11","tp53","cdkn2a","nkx2-1","keap1","pdl1"],"drugs":[],"companies":[],"institutions":["md-anderson"],"pathways":["ras-mapk","t-cell-exhaustion","keap1-nrf2","pi3k-akt-mtor"],"terms":["kras-mutation-subtypes","stk11-keap1","cold-vs-hot"],"trials":[],"people":["ferdinandos-skoulidis"],"bottlenecks":[],"keyPapers":[],"journals":["cancer-discovery"],"dependsOn":[],"notes":[],"journal":"Cancer Discovery","year":2015,"doi":"10.1158/2159-8290.CD-14-1236","pmid":"26069186","authors":"Skoulidis F, Byers LA, Diao L, et al.","paperType":"translational","findings":["Three subgroups of KRAS-mutant lung adenocarcinoma: KL, KP and KC.","KL tumours are immune-poor with low PD-L1 and frequent KEAP1 loss.","KP tumours are inflamed, more mutated and have better relapse-free survival.","KC tumours are mucinous with suppressed mTORC1 signalling."],"whatItMeans":"It is the origin of the idea, now central to lung oncology, that the co-mutation and not the driver decides how a KRAS-mutant tumour behaves and whether immunotherapy will work.","caveats":["Derived from expression and proteomic clustering, so subgroup boundaries depend on the method.","Drug sensitivity findings are preclinical.","No prospective trial has randomised on these subgroups."],"changedPractice":false},{"id":"paper-herbst-j-clin-oncol","kind":"paper","name":"COAST: An Open-Label, Phase II, Multidrug Platform Study of Durvalumab Alone or in Combination With Oleclumab or Monalizumab in Patients With Unresectable, Stage III Non-Small-Cell Lung Cancer","aka":[],"tldr":"Paper cited by one target page, indexed on Europe PMC as PubMed record 35452273 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: Durvalumab significantly improves overall survival for patients with unresectable stage III non-small-cell lung cancer and no progression after concurrent chemoradiotherapy (cCRT). Building upon that standard of care, COAST is a phase II study of durvalumab alone or combined with the anti-CD73 monoclonal antibody oleclumab or anti-NKG2A monoclonal antibody monalizumab as consolidation therapy in this setting.\n\nMethods: Patients with unresectable stage III non-small-cell lung cancer, Eastern Cooperative Oncology Group performance status 0/1, and no progression after cCRT were randomly assigned 1:1:1, ≤ 42 days post-cCRT, to durvalumab alone or combined with oleclumab or monalizumab for up to 12 months, stratified by histology. The primary end point was investigator-assessed confirmed objective response rate (ORR; RECIST v1.1).\n\nResults: Between January 2019 and July 2020, 189 patients were randomly assigned. At this interim analysis (data cutoff, May 17, 2021), median follow-up was 11.5 months (range, 0.4-23.4 months; all patients). Confirmed ORR was numerically higher with durvalumab plus oleclumab (30.0%; 95% CI, 18.8 to 43.2) and durvalumab plus monalizumab (35.5%; 95% CI, 23.7 to 48.7) versus durvalumab (17.9%; 95% CI, 9.6 to 29.2). Progression-free survival (PFS) was prolonged with both combinations versus durvalumab (plus oleclumab: hazard ratio, 0.44; 95% CI, 0.26 to 0.75; and plus monalizumab: hazard ratio, 0.42; 95% CI, 0.24 to 0.72), with higher 12-month PFS rates (plus oleclumab: 62.6% [95% CI, 48.1 to 74.2] and plus monalizumab: 72.7% [95% CI, 58.8 to 82.6] v durvalumab alone: 33.9% [95% CI, 21.2 to 47.1]). All-cause grade ≥ 3 treatment-emergent adverse events occurred in 40.7%, 27.9%, and 39.4% with durvalumab plus oleclumab, durvalumab plus monalizumab, and durvalumab, respectively.\n\nConclusion: Both combinations increased ORR and prolonged PFS versus durvalumab alone. Safety was similar across arms with no new or significant safety signals identified with either combination. These data support their further evaluation in a phase III trial.\n\nIndexed on Europe PMC as PubMed record 35452273 (DOI 10.1200/jco.22.00227). Matched by DOI alone: one target page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2022","url":"https://doi.org/10.1200/jco.22.00227"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35452273/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35452273"}],"tags":["europepmc-ingest"],"related":["cd73-adenosine"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2022,"doi":"10.1200/jco.22.00227","pmid":"35452273","authors":"Herbst RS, Majem M, Barlesi F, et al.","paperType":"rct","findings":[],"whatItMeans":"One target page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-cobrim-lancet-oncol-2016-update","kind":"paper","name":"Cobimetinib combined with vemurafenib in advanced BRAF(V600)-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial","aka":[],"tldr":"Later report from the coBRIM trial registered as NCT01689519, in The Lancet Oncology (2016); its title describes an updated or longer-term analysis.","summary":"Background: The combination of cobimetinib with vemurafenib improves progression-free survival compared with placebo and vemurafenib in previously untreated patients with BRAF(V600)-mutant advanced melanoma, as previously reported in the coBRIM study. In this Article, we report updated efficacy results, including overall survival and safety after longer follow-up, and selected biomarker correlative studies.\n\nMethods: In this double-blind, randomised, placebo-controlled, multicentre study, adult patients (aged ≥18 years) with histologically confirmed BRAF(V600) mutation-positive unresectable stage IIIC or stage IV melanoma were randomly assigned (1:1) using an interactive response system to receive cobimetinib (60 mg once daily for 21 days followed by a 7-day rest period in each 28-day cycle) or placebo, in combination with oral vemurafenib (960 mg twice daily). Progression-free and overall survival were primary and secondary endpoints, respectively; all analyses were done on the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01689519, and is ongoing but no longer recruiting participants.\n\nFindings: Between Jan 8, 2013, and Jan 31, 2014, 495 eligible adult patients were enrolled and randomly assigned to the cobimetinib plus vemurafenib group (n=247) or placebo plus vemurafenib group (n=248). At a median follow-up of 14·2 months (IQR 8·5-17·3), the updated investigator-assessed median progression-free survival was 12·3 months (95% CI 9·5-13·4) for cobimetinib and vemurafenib versus 7·2 months (5·6-7·5) for placebo and vemurafenib (HR 0·58 [95% CI 0·46-0·72], p<0·0001). The final analysis for overall survival occurred when 255 (52%) patients had died (Aug 28, 2015). Median overall survival was 22·3 months (95% CI 20·3-not estimable) for cobimetinib and vemurafenib versus 17·4 months (95% CI 15·0-19·8) for placebo and vemurafenib (HR 0·70, 95% CI 0·55-0·90; p=0·005). The safety profile for cobimetinib and vemurafenib was tolerable and manageable, and no new safety signals were observed with longer follow-up. The most common grade 3-4 adverse events occurring at a higher frequency in patients in the cobimetinib and vemurafenib group compared with the vemurafenib group were γ-glutamyl transferase increase (36 [15%] in the cobimetinib and vemurafenib group vs 25 [10%] in the placebo and vemurafenib group), blood creatine phosphokinase increase (30 [12%] vs one [<1%]), and alanine transaminase increase (28 [11%] vs 15 [6%]). Serious adverse events occurred in 92 patients (37%) in the cobimetinib and vemurafenib group and 69 patients (28%) in the vemurafenib group. Pyrexia (six patients [2%]) and dehydration (five patients [2%]) were the most common serious adverse events reported in the cobimetinib and vemurafenib group. A total of 259 patients have died: 117 (47%) in the cobimetinib and vemurafenib group and 142 (58%) in the vemurafenib group. The primary cause of death was disease progression in most patients: 109 (93%) of 117 in the cobimetinib and vemurafenib group and 133 (94%) of 142 in the vemurafenib group.\n\nInterpretation: These data confirm the clinical benefit of cobimetinib combined with vemurafenib and support the use of the combination as a standard first-line approach to improve survival in patients with advanced BRAF(V600)-mutant melanoma.\n\nFunding: F Hoffmann-La Roche-Genentech.\n\nIndexed on Europe PMC as PubMed record 27480103 (DOI 10.1016/s1470-2045(16)30122-x). Its abstract cites the registry id NCT01689519, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2016","url":"https://doi.org/10.1016/s1470-2045(16)30122-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27480103/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27480103"},{"label":"ClinicalTrials.gov NCT01689519","url":"https://clinicaltrials.gov/study/NCT01689519"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["cobrim"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2016,"doi":"10.1016/s1470-2045(16)30122-x","pmid":"27480103","authors":"Ascierto PA, McArthur GA, Dréno B, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the coBRIM trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-codebreak-100-sotorasib-kras-g12c-pancreatic-nejm-2023","kind":"paper","name":"CodeBreaK 100: sotorasib in KRAS p.G12C-mutated advanced pancreatic cancer","aka":[],"tldr":"The first KRAS-blocking pill shrank tumours in about one in five patients with heavily pretreated pancreatic cancer carrying the G12C mutation and controlled the disease in most for a few months. Modest as that is, it was the first direct hit on the gene that drives nearly every pancreatic cancer.","summary":"Phase 1 and 2 single-arm cohorts of the CodeBreaK 100 trial in 38 patients with KRAS p.G12C-mutated metastatic pancreatic ductal adenocarcinoma who had received at least one prior systemic therapy (most had received two or more), treated with sotorasib 960 mg once daily.\n\nThe confirmed objective response rate was 21 percent and disease control about 84 percent; median progression-free survival was 4.0 months and median overall survival 6.9 months. Treatment-related grade 3 adverse events occurred in about one in six patients, mainly diarrhoea and fatigue, with no fatal events.","asOf":"2026-09-21","links":[{"label":"N Engl J Med 2023","url":"https://doi.org/10.1056/NEJMoa2208470"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36546651/"}],"tags":[],"related":["kras-g12c"],"cancers":["kras-g12c-pdac","pancreatic"],"sections":[],"technologies":["kras-inhibitors"],"targets":["kras"],"drugs":["sotorasib"],"companies":[],"institutions":[],"pathways":["ras-mapk"],"terms":["kras-mutation-subtypes"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/NEJMoa2208470","pmid":"36546651","authors":"Strickler JH, Satake H, George TJ, et al.","paperType":"observational","findings":["Objective response 21 percent; disease control about 84 percent.","Median progression-free survival 4.0 months and median overall survival 6.9 months."],"whatItMeans":"Sotorasib is a guideline-listed later-line option for the 1 to 2 percent of pancreatic cancers with KRAS G12C, and the proof that KRAS in pancreatic cancer is druggable; the larger opportunity lies with inhibitors of G12D and pan-RAS drugs.","caveats":["A small single-arm cohort with no comparator; the response rate is far below that seen in lung cancer.","Responses were short, and resistance mechanisms in pancreatic cancer are only partly described."],"changedPractice":true,"participants":38},{"id":"paper-codebreak-200-lancet-2023","kind":"paper","name":"CodeBreaK 200: sotorasib versus docetaxel in KRAS G12C-mutated lung cancer, a modest win for the first KRAS drug","aka":[],"tldr":"The first drug to directly block mutant KRAS beat docetaxel chemotherapy on delaying progression in KRAS G12C lung cancer, but only by about a month, and did not improve survival.","summary":"Open-label phase 3 trial of 345 patients with KRAS G12C-mutated advanced NSCLC previously treated with platinum chemotherapy and a PD-1 inhibitor, randomised to sotorasib 960 mg daily or docetaxel. Primary endpoint was PFS by blinded review.\n\nMedian PFS was 5.6 vs 4.5 months (HR 0.66) with a higher response rate (28.1% vs 13.2%) and less high-grade toxicity, but overall survival was not different (HR about 1.0), partly because a third of docetaxel patients crossed over. It confirmed that KRAS G12C is druggable, and also that first-generation inhibitors give short-lived benefit; the FDA's concerns about the trial's design and a later dose-comparison requirement shaped how KRAS inhibitors were subsequently developed.","asOf":"2026-09-08","links":[{"label":"PubMed search: CodeBreaK 200 Lancet 2023","url":"https://pubmed.ncbi.nlm.nih.gov/?term=CodeBreaK+200+sotorasib+docetaxel+de+Langen+Lancet"},{"label":"ClinicalTrials.gov NCT04303780","url":"https://clinicaltrials.gov/study/NCT04303780"},{"label":"Lancet 2023","url":"https://doi.org/10.1016/S0140-6736(23)00221-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36764316/"}],"tags":[],"related":["paper-ostrem-kras-g12c-nature-2013","paper-kras-nsclc-n-engl-j-med-2021","kras-roadmap"],"cancers":["nsclc","lung-cancer","kras-g12c-nsclc"],"sections":["targeted-therapy","drug-discovery"],"technologies":["kras-inhibitors","kinase-inhibitors"],"targets":["kras"],"drugs":["sotorasib","adagrasib","docetaxel"],"companies":["amgen"],"institutions":["nki"],"pathways":["ras-mapk"],"terms":["pfs","os","orr","resistance","accelerated-approval","driver-mutation"],"trials":["codebreak-300","codebreak-200","codebreak-100"],"people":["luis-paz-ares","solange-peters"],"bottlenecks":["b-undruggable-targets","b-resistance","b-trial-design","b-dose-optimisation","b-combination-space"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2023,"doi":"10.1016/S0140-6736(23)00221-0","pmid":"36764316","authors":"de Langen AJ, Johnson ML, Mazieres J, et al.","paperType":"rct","findings":["Median PFS 5.6 vs 4.5 months; HR 0.66 (95% CI 0.51-0.86); 12-month PFS 24.8% vs 10.1%.","Objective response 28.1% vs 13.2%; disease control 82.5% vs 60.3%.","Grade 3 or higher treatment-related adverse events 33% vs 40%; diarrhoea and liver enzyme elevation were the main sotorasib toxicities.","Overall survival not significantly different; the trial was not powered for OS and 34% of docetaxel patients crossed over to sotorasib.","The KRYSTAL-12 trial of adagrasib versus docetaxel later reported a similar PFS result (5.5 vs 3.8 months, HR 0.58)."],"whatItMeans":"Patients with KRAS G12C lung cancer that has progressed after chemo-immunotherapy can take an oral KRAS inhibitor instead of docetaxel and gain a somewhat longer time to progression with fewer severe side effects, but should understand that most tumours become resistant within a year and that survival is not improved. KRAS G12C testing is worthwhile, but first-generation inhibitors are a step rather than a cure; combinations and next-generation inhibitors are the active research fronts.","caveats":["Open-label with a modest absolute PFS gain of about one month and no OS benefit.","Crossover and the sample size reduction made during the trial (from 650 to 345) drew criticism from regulators.","Resistance develops through multiple mechanisms (secondary KRAS mutations, bypass pathways), limiting durability.","Response rates in KRAS G12C lung cancer (around 30-40%) are far lower than for EGFR or ALK inhibitors, reflecting KRAS biology."],"changedPractice":true,"participants":345},{"id":"paper-codebreak-300-nejm-2023","kind":"paper","name":"CodeBreaK 300: sotorasib plus panitumumab in chemotherapy-refractory KRAS G12C colorectal cancer","aka":[],"tldr":"Combining a KRAS G12C inhibitor with an EGFR antibody produced responses in about a quarter of patients with heavily pretreated KRAS G12C bowel cancer, versus none with standard chemotherapy, and more than doubled the time to progression.","summary":"Open-label phase 3 trial of 160 patients with KRAS G12C-mutated metastatic colorectal cancer that had progressed after fluoropyrimidine, oxaliplatin and irinotecan, randomised 1:1:1 to sotorasib 960 mg or 240 mg daily plus panitumumab, or investigator's choice of trifluridine-tipiracil or regorafenib. Primary endpoint was PFS by blinded review.\n\nMedian PFS was 5.6 months with sotorasib 960 mg (HR 0.49) and 3.9 months with 240 mg (HR 0.58) versus 2.2 months with standard care; response rates were 26.4%, 5.7% and 0%. It showed that KRAS G12C inhibition in colorectal cancer needs EGFR co-blockade to overcome adaptive feedback, and led to FDA approval of the combination in 2025.","asOf":"2026-09-08","links":[{"label":"NEJM 2023","url":"https://doi.org/10.1056/NEJMoa2308795"},{"label":"ClinicalTrials.gov NCT05198934","url":"https://clinicaltrials.gov/study/NCT05198934"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37870968/"}],"tags":[],"related":["kras-g12c","kras-roadmap","paper-ostrem-kras-g12c-nature-2013","paper-douillard-prime-panitumumab-ras-nejm-2013"],"cancers":["colorectal","kras-g12c-colorectal"],"sections":["targeted-therapy"],"technologies":["kras-inhibitors","monoclonal-antibody"],"targets":["kras","egfr"],"drugs":["sotorasib","panitumumab","trifluridine-tipiracil","regorafenib"],"companies":["amgen"],"institutions":[],"pathways":["ras-mapk"],"terms":["pfs","orr","resistance"],"trials":["codebreak-300"],"people":["kim-tae-won","david-cunningham"],"bottlenecks":["b-undruggable-targets","b-resistance","b-dose-optimisation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/NEJMoa2308795","pmid":"37870968","authors":"Fakih MG, Salvatore L, Esaki T, et al.","paperType":"rct","findings":["Median PFS 5.6 months (sotorasib 960 mg plus panitumumab) vs 2.2 months (standard care); HR 0.49 (95% CI 0.30-0.80).","Median PFS 3.9 months with sotorasib 240 mg plus panitumumab; HR 0.58.","Objective response 26.4% (960 mg), 5.7% (240 mg) and 0% (standard care).","Skin toxicity (from panitumumab) and hypomagnesaemia were the main adverse events; grade 3 or higher treatment-related events about 36% (960 mg), 30% (240 mg) and 43% (standard care).","Overall survival showed a trend favouring the 960 mg arm but was not powered to detect a difference."],"whatItMeans":"Patients with metastatic colorectal cancer carrying a KRAS G12C mutation (about 3-4% of cases) who have exhausted standard chemotherapy now have a targeted option that works far better than trifluridine-tipiracil or regorafenib. The higher sotorasib dose is clearly superior, and the EGFR antibody is essential because KRAS inhibition alone has little effect in bowel cancer. Responses are still modest and short-lived compared with EGFR or ALK inhibitors in lung cancer.","caveats":["Small trial with a PFS primary endpoint; OS benefit not established.","The comparator drugs are of very limited efficacy, so the bar was low.","Median PFS of 5.6 months underlines that resistance develops quickly.","Only KRAS G12C is covered; the far more common G12D and G12V mutations await other inhibitors."],"changedPractice":true,"participants":160},{"id":"paper-poole-bmj","kind":"paper","name":"Coffee consumption and health: umbrella review of meta-analyses of multiple health outcomes","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 29167102 and published in BMJ; the citing page links this DOI, which is how the record was matched.","summary":"Objectives To evaluate the existing evidence for associations between coffee consumption and multiple health outcomes. Design Umbrella review of the evidence across meta-analyses of observational and interventional studies of coffee consumption and any health outcome. Data sources PubMed, Embase, CINAHL, Cochrane Database of Systematic Reviews, and screening of references. Eligibility criteria for selecting studies Meta-analyses of both observational and interventional studies that examined the associations between coffee consumption and any health outcome in any adult population in all countries and all settings. Studies of genetic polymorphisms for coffee metabolism were excluded. Results The umbrella review identified 201 meta-analyses of observational research with 67 unique health outcomes and 17 meta-analyses of interventional research with nine unique outcomes. Coffee consumption was more often associated with benefit than harm for a range of health outcomes across exposures including high versus low, any versus none, and one extra cup a day. There was evidence of a non-linear association between consumption and some outcomes, with summary estimates indicating largest relative risk reduction at intakes of three to four cups a day versus none, including all cause mortality (relative risk 0.83 (95% confidence interval 0.79 to 0.88), cardiovascular mortality (0.81, 0.72 to 0.90), and cardiovascular disease (0.85, 0.80 to 0.90). High versus low consumption was associated with an 18% lower risk of incident cancer (0.82, 0.74 to 0.89). Consumption was also associated with a lower risk of several specific cancers and neurological, metabolic, and liver conditions. Harmful associations were largely nullified by adequate adjustment for smoking, except in pregnancy, where high versus low/no consumption was associated with low birth weight (odds ratio 1.31, 95% confidence interval 1.03 to 1.67), preterm birth in the first (1.22, 1.00 to 1.49) and second (1.12, 1.02 to 1.22) trimester, and pregnancy loss (1.46, 1.06 to 1.99). There was also an association between coffee drinking and risk of fracture in women but not in men. Conclusion Coffee consumption seems generally safe within usual levels of intake, with summary estimates indicating largest risk reduction for various health outcomes at three to four cups a day, and more likely to benefit health than harm. Robust randomised controlled trials are needed to understand whether the observed associations are causal. Importantly, outside of pregnancy, existing evidence suggests that coffee could be tested as an intervention without significant risk of causing harm. Women at increased risk of fracture should possibly be excluded.\n\nIndexed on Europe PMC as PubMed record 29167102 (DOI 10.1136/bmj.j5024). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"BMJ 2017","url":"https://doi.org/10.1136/bmj.j5024"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29167102/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29167102"}],"tags":["europepmc-ingest"],"related":["coffee-intake-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["bmj"],"dependsOn":[],"notes":[],"journal":"BMJ","year":2017,"doi":"10.1136/bmj.j5024","pmid":"29167102","authors":"Poole R, Kennedy OJ, Roderick P, et al.","paperType":"meta-analysis","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-coffey-reovirus-ras-science-1998","kind":"paper","name":"Coffey 1998: reovirus grows in cells with an activated Ras pathway, which describes a great many cancers","aka":[],"tldr":"A common gut virus that does almost nothing in healthy adults turned out to need a switched-on growth pathway to replicate, and that switch is stuck on in a large share of human cancers.","summary":"Human reovirus requires an activated Ras signalling pathway to infect cultured cells. Coffey and colleagues tested whether that dependence could be used against tumours. A single intratumoural injection caused regression in 65 to 80 per cent of severe combined immunodeficient mice bearing tumours from v-erbB-transformed murine NIH 3T3 cells or human U87 glioblastoma cells. In immunocompetent C3H mice bearing tumours from ras-transformed C3H-10T1/2 cells, regression also occurred but needed a series of injections.\n\nThis is the second of the two classic selectivity arguments, alongside the interferon defect: a naturally occurring, essentially harmless virus whose replication requirement happens to be a hallmark of transformed cells. It became the basis of pelareorep, the reovirus product that has been in clinical trials for more than two decades.","asOf":"2026-09-25","links":[{"label":"Science 1998","url":"https://doi.org/10.1126/science.282.5392.1332"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/9812900/"}],"tags":[],"related":[],"cancers":[],"sections":["immunotherapy"],"technologies":["oncolytic-virus"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":1998,"doi":"10.1126/science.282.5392.1332","pmid":"9812900","authors":"Coffey MC, Strong JE, Forsyth PA, Lee PW","paperType":"basic","findings":["Human reovirus requires an activated Ras signalling pathway to infect cultured cells.","A single intratumoural injection caused tumour regression in 65 to 80 per cent of severe combined immunodeficient mice bearing v-erbB-transformed murine or human U87 glioblastoma tumours.","In immunocompetent C3H mice with ras-transformed tumours regression also occurred, but only after a series of injections rather than one."],"whatItMeans":"Selectivity does not have to be engineered. A wild virus can already prefer cancer cells if its replication depends on something the cancer has turned on. The difference between one injection in an immunodeficient mouse and a series in an immunocompetent one is the first clear signal in the literature that the host immune response both helps and hinders, which is still the central tension of the field.","caveats":["Ras pathway activation is common but is not measured before treatment in the reovirus trials, so the selectivity argument has never been tested as a biomarker in patients.","Rodent tumour models greatly overstate what intratumoural virus achieves in human tumours, which are larger, older and more fibrous.","Pelareorep, the product built on this work, has run for more than twenty years without a positive randomised phase 3 result."]},{"id":"paper-p9641-low-risk-neuroblastoma-strother-jco-2012","kind":"paper","name":"COG P9641: surgery alone or with restricted chemotherapy for low-risk neuroblastoma","aka":[],"tldr":"In the largest low-risk neuroblastoma trial, surgery alone cured almost all children with stage 1 and most with stage 2 disease, with chemotherapy reserved for symptoms or unfavourable features, confirming that many children need no drug treatment.","summary":"Children's Oncology Group phase 3 study of 915 children with low-risk neuroblastoma (stage 1, asymptomatic stage 2 and 4S with favourable biology) treated with surgery alone, with chemotherapy only for symptomatic, unresectable or progressive disease.\n\nFive-year event-free survival was 89 percent and overall survival 97 percent; outcomes were excellent for stage 1 and for stage 2 with favourable biology, and lower in stage 2 with unfavourable histology or diploidy in children over 18 months.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2012","url":"https://doi.org/10.1200/JCO.2011.37.9990"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22529259/"}],"tags":[],"related":[],"cancers":["neuroblastoma-low-risk"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2012,"doi":"10.1200/JCO.2011.37.9990","pmid":"22529259","authors":"Strother DR, London WB, Schmidt ML, et al.","paperType":"observational","findings":["Five-year overall survival 97 percent; event-free survival 89 percent.","Stage 1: event-free survival 93 percent with surgery alone."],"whatItMeans":"Surgery alone, or observation, is standard for low-risk neuroblastoma, with chemotherapy limited to those with symptoms or unfavourable biology.","caveats":["Non-randomised risk-adapted design."],"changedPractice":true,"participants":915},{"id":"paper-zauber-national-polyp-study-colonoscopic-polypectomy-nejm-2012","kind":"paper","name":"Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths (National Polyp Study)","aka":[],"tldr":"Twenty-three years after having their adenomas removed at colonoscopy, 2,602 people in the National Polyp Study had half the bowel cancer deaths expected for the general population. This is the evidence that removing a polyp prevents a death.","summary":"Zauber, Winawer, O'Brien and colleagues followed everyone prospectively referred for initial colonoscopy at National Polyp Study centres between 1980 and 1990 who had polyps, using the National Death Index to identify deaths and their causes for as long as 23 years. Mortality from colorectal cancer among patients whose adenomas had been removed was compared with the expected incidence-based mortality in the general population, estimated from the SEER programme, and with the observed mortality among patients who had non-adenomatous polyps.\n\nMortality from colorectal cancer was similar in the two polyp groups during the first ten years after polypectomy, which is the interval in which the removal of adenomas would not yet be expected to show.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2012","url":"https://doi.org/10.1056/NEJMoa1100370"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22356322/"},{"label":"Europe PMC full text (PMC3322371)","url":"https://europepmc.org/article/MED/22356322"}],"tags":["colorectal-evidence"],"related":["paper-vogelstein-genetic-alterations-colorectal-tumor-development-nejm-1988","paper-nordicc-nejm-2022","paper-kaminski-adenoma-detection-rate-interval-cancer-nejm-2010","paper-capp2-aspirin-lynch-lancet-2020"],"cancers":["colorectal"],"sections":["early-detection","prevention"],"technologies":["colonoscopy","endoscopy","colorectal-screening"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-prevention-adoption"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2012,"doi":"10.1056/NEJMoa1100370","pmid":"22356322","authors":"Zauber AG, Winawer SJ, O'Brien MJ, et al.","paperType":"observational","findings":["After a median of 15.8 years, 1,246 of 2,602 patients with adenomas removed had died of any cause and 12 had died of colorectal cancer.","Against 25.4 expected deaths in the general population, the standardised incidence-based mortality ratio was 0.47 (95 percent CI 0.26 to 0.80): a 53 percent reduction.","Colorectal cancer mortality was similar in patients with adenomas and with non-adenomatous polyps during the first ten years (relative risk 1.2, 95 percent CI 0.1 to 10.6)."],"whatItMeans":"The clinical proof of Vogelstein's sequence: interrupting the adenoma-carcinoma pathway with a snare prevents the cancer, which is why colonoscopy is the only screening test that both detects and prevents.","caveats":["Not randomised; the comparator is SEER expected mortality, so differences in the screened population's baseline risk cannot be ruled out.","Colonoscopy technique, bowel preparation and adenoma detection rates in 1980 to 1990 differ from today's."],"changedPractice":true,"participants":2602},{"id":"paper-dekker-lancet","kind":"paper","name":"Colorectal cancer","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 31631858 and published in The Lancet; the citing page links this DOI, which is how the record was matched.","summary":"Several decades ago, colorectal cancer was infrequently diagnosed. Nowadays, it is the world's fourth most deadly cancer with almost 900 000 deaths annually. Besides an ageing population and dietary habits of high-income countries, unfavourable risk factors such as obesity, lack of physical exercise, and smoking increase the risk of colorectal cancer. Advancements in pathophysiological understanding have increased the array of treatment options for local and advanced disease leading to individual treatment plans. Treatments include endoscopic and surgical local excision, downstaging preoperative radiotherapy and systemic therapy, extensive surgery for locoregional and metastatic disease, local ablative therapies for metastases, and palliative chemotherapy, targeted therapy, and immunotherapy. Although these new treatment options have doubled overall survival for advanced disease to 3 years, survival is still best for those with non-metastasised disease. As the disease only becomes symptomatic at an advanced stage, worldwide organised screening programmes are being implemented, which aim to increase early detection and reduce morbidity and mortality from colorectal cancer.\n\nIndexed on Europe PMC as PubMed record 31631858 (DOI 10.1016/s0140-6736(19)32319-0). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet 2019","url":"https://doi.org/10.1016/s0140-6736(19)32319-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31631858/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31631858"}],"tags":["europepmc-ingest"],"related":["colorectal-cancer-signalling"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2019,"doi":"10.1016/s0140-6736(19)32319-0","pmid":"31631858","authors":"Dekker E, Tanis PJ, Vleugels JLA, et al.","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-siegel-colorectal-incidence-birth-cohort-jnci-2017","kind":"paper","name":"Colorectal cancer incidence patterns in the United States, 1974-2013","aka":[],"tldr":"The analysis that showed the rise in bowel cancer in young adults is a birth-cohort effect: someone born in 1990 has twice the colon cancer risk and four times the rectal cancer risk of someone born in 1950 at the same age.","summary":"Siegel, Fedewa, Anderson, Miller, Ma, Rosenberg and Jemal analysed colorectal cancer incidence trends in Surveillance, Epidemiology and End Results areas from 1974 to 2013, covering 490,305 cases, by five-year age group and birth cohort using incidence rate ratios and age-period-cohort modelling.\n\nAge-specific relative risk by birth cohort declined from around 1890 until 1950 and then rose continuously through 1990, so that risk for contemporary birth cohorts has returned to the level of those born around 1890. The authors concluded that screening initiation before age 50 should be considered, an argument the United States Preventive Services Task Force accepted in 2021.","asOf":"2026-09-24","links":[{"label":"J Natl Cancer Inst 2017","url":"https://doi.org/10.1093/jnci/djw322"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28376186/"},{"label":"Europe PMC full text (PMC6059239)","url":"https://europepmc.org/article/MED/28376186"}],"tags":["colorectal-evidence"],"related":["paper-vuik-early-onset-colorectal-europe-gut-2019","paper-siegel-colorectal-cancer-statistics-ca-2023","paper-diaz-gay-colibactin-geographic-age-mutational-processes-nature-2025"],"cancers":["colorectal","early-onset-colorectal","rectal-cancer"],"sections":["early-detection","prevention"],"technologies":["colorectal-screening"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-prevention-adoption"],"keyPapers":[],"journals":["jnci"],"dependsOn":[],"notes":[],"journal":"JNCI: Journal of the National Cancer Institute","year":2017,"doi":"10.1093/jnci/djw322","pmid":"28376186","authors":"Siegel RL, Fedewa SA, Anderson WF, et al.","paperType":"observational","findings":["Colon cancer incidence rose 1.0 to 2.4 percent annually since the mid-1980s in adults aged 20 to 39, and 0.5 to 1.3 percent since the mid-1990s in adults aged 40 to 54.","Rectal cancer incidence rose 3.2 percent annually from 1974 to 2013 in adults aged 20 to 29.","The proportion of rectal cancers diagnosed under 55 doubled from 14.6 percent to 29.2 percent between 1989-1990 and 2012-2013.","Compared with those born around 1950, people born around 1990 have double the colon cancer risk (incidence rate ratio 2.40, 95 percent CI 1.11 to 5.19) and quadruple the rectal cancer risk (4.32, 2.19 to 8.51)."],"whatItMeans":"The paper that turned early-onset colorectal cancer from an anecdote into a policy problem, and the direct evidence behind lowering the screening start age from 50 to 45 in the United States.","caveats":["Registry incidence cannot say why the cohort effect exists; obesity, diet, antibiotics and the microbiome are all candidates and none is established.","Age-period-cohort models cannot separate the three effects without assumptions, and the youngest cohorts rest on few cases, hence the wide confidence intervals.","United States data; the European picture (Vuik 2019) is similar but not identical."],"changedPractice":true,"participants":490305},{"id":"paper-siegel-colorectal-cancer-statistics-ca-2023","kind":"paper","name":"Colorectal cancer statistics, 2023","aka":[],"tldr":"The American Cancer Society's three-yearly stocktake: overall deaths are still falling, but one in five new cases is now in someone under 55, and more cancers are being found after they have spread than twenty years ago.","summary":"Siegel, Wagle, Cercek, Smith and Jemal's triennial update of United States colorectal cancer statistics, using incidence from population-based registries and mortality from the National Center for Health Statistics. The report projected roughly 153,020 diagnoses and 52,550 deaths in 2023, including 19,550 cases and 3,750 deaths in people younger than 50.\n\nThe headline is a shift rather than a reversal: total incidence and mortality continue to fall, but the disease is moving younger, later-stage and more left-sided, undoing part of the stage shift screening had produced.","asOf":"2026-09-24","links":[{"label":"CA Cancer J Clin 2023","url":"https://doi.org/10.3322/caac.21772"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36856579/"}],"tags":["colorectal-evidence"],"related":["paper-siegel-colorectal-incidence-birth-cohort-jnci-2017"],"cancers":["colorectal","early-onset-colorectal","rectal-cancer"],"sections":["early-detection","prevention"],"technologies":["colorectal-screening"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["andrea-cercek"],"bottlenecks":["b-early-detection","b-global-access"],"keyPapers":[],"journals":["ca-cancer-journal"],"dependsOn":[],"notes":[],"journal":"CA: A Cancer Journal for Clinicians","year":2023,"doi":"10.3322/caac.21772","pmid":"36856579","authors":"Siegel RL, Wagle NS, Cercek A, Smith RA, Jemal A.","paperType":"observational","findings":["Roughly 153,020 diagnoses and 52,550 deaths projected in the United States in 2023, including 19,550 cases and 3,750 deaths under 50.","The decline in incidence slowed from 3 to 4 percent annually in the 2000s to 1 percent annually during 2011 to 2019.","The proportion of cases in people under 55 rose from 11 percent in 1995 to 20 percent in 2019.","60 percent of new cases were advanced in 2019 against 52 percent in the mid-2000s and 57 percent in 1995.","Rectal cancer rose from 27 percent of cases in 1995 to 31 percent in 2019.","Mortality fell 2 percent annually from 2011 to 2020 overall but rose 0.5 to 3 percent annually in people under 50."],"whatItMeans":"The numbers behind the argument that the screening programme is working for the people it covers and failing everyone below its start age; the stage shift going into reverse is the most uncomfortable figure on this roadmap.","caveats":["United States registry data; the age structure, screening offer and insurance context are not the UK's.","Projected 2023 counts are modelled forward from observed data, not counted.","Descriptive statistics: they establish the pattern, not its cause."]},{"id":"paper-nct04068610-br-j-cancer-2024","kind":"paper","name":"COLUMBIA-1: a randomised study of durvalumab plus oleclumab in combination with chemotherapy and bevacizumab in metastatic microsatellite-stable colorectal cancer","aka":[],"tldr":"Published report from the COLUMBIA-1 trial registered as NCT04068610, in British Journal of Cancer (2024), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: To determine whether the addition of durvalumab (anti-PD-L1) and oleclumab (anti-CD73) to standard-of-care treatment (FOLFOX and bevacizumab) enhances the anti-tumour effect in patients with metastatic colorectal cancer (mCRC).\n\nMethods: COLUMBIA-1 (NCT04068610) was a Phase Ib (feasibility; Part 1)/Phase II (randomised; Part 2) trial in patients with treatment-naïve microsatellite stable mCRC. Patients in Part 2 were randomised to receive standard-of-care (control arm) or standard-of-care plus durvalumab and oleclumab (experimental arm). Primary objectives included safety and efficacy.\n\nResults: Seven patients were enrolled in Part 1 and 52 in Part 2 (n = 26 in each arm). Grade ≥3 treatment-emergent adverse events (TEAE) occurred in 80.8% and 65.4% of patients in the control and experimental arms of Part 2, respectively, with 26.9% and 46.3% experiencing serious TEAEs. The confirmed objective response rate (ORR) was numerically higher in the experimental arm compared with the control arm (61.5% [95% confidence interval (CI), 40.6-79.8] vs 46.2% [95% CI, 26.6-66.6]) but did not meet the statistically significant threshold in either arm.\n\nConclusion: The safety profile of FOLFOX and bevacizumab in combination with durvalumab and oleclumab was manageable; however, the efficacy results do not warrant further development of this combination in patients with microsatellite stable mCRC.\n\nRegistration: NCT04068610.\n\nIndexed on Europe PMC as PubMed record 39048638 (DOI 10.1038/s41416-024-02796-3). Its abstract cites the registry id NCT04068610, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Br J Cancer 2024","url":"https://doi.org/10.1038/s41416-024-02796-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39048638/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39048638"},{"label":"ClinicalTrials.gov NCT04068610","url":"https://clinicaltrials.gov/study/NCT04068610"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04068610"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["british-journal-of-cancer"],"dependsOn":[],"notes":[],"journal":"British Journal of Cancer","year":2024,"doi":"10.1038/s41416-024-02796-3","pmid":"39048638","authors":"Segal NH, Tie J, Kopetz S, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04068610 with the most citations, so it is the natural first reading for anyone following the COLUMBIA-1 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-columbus-lancet-oncol-2018","kind":"paper","name":"COLUMBUS: encorafenib plus binimetinib versus vemurafenib or encorafenib in BRAF-mutant melanoma","aka":[],"tldr":"The third BRAF-MEK combination, encorafenib plus binimetinib, delayed progression more than vemurafenib and produced the longest median survival of any targeted regimen in BRAF-mutant melanoma, with less fever than dabrafenib-trametinib.","summary":"Phase 3 trial of 577 patients with advanced BRAF V600-mutant melanoma randomised to encorafenib plus binimetinib, encorafenib alone or vemurafenib alone.\n\nMedian progression-free survival was 14.9 months with the combination against 7.3 months with vemurafenib (hazard ratio 0.54), and median overall survival 33.6 versus 16.9 months on later analysis; the combination had a distinct toxicity profile with less pyrexia and photosensitivity.","asOf":"2026-09-17","links":[{"label":"Lancet Oncol 2018","url":"https://doi.org/10.1016/S1470-2045(18)30142-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29573941/"}],"tags":[],"related":[],"cancers":["braf-v600-melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":["binimetinib","encorafenib","vemurafenib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["columbus"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2018,"doi":"10.1016/S1470-2045(18)30142-6","pmid":"29573941","authors":"Dummer R, Ascierto PA, Gogas HJ, et al.","paperType":"rct","findings":["Median progression-free survival 14.9 vs 7.3 months; hazard ratio 0.54.","Median overall survival 33.6 vs 16.9 months."],"whatItMeans":"Encorafenib-binimetinib is one of three standard BRAF-MEK doublets for advanced melanoma and is often chosen for its tolerability.","caveats":["Open-label; vemurafenib monotherapy is a dated comparator."],"changedPractice":true,"participants":577},{"id":"paper-combi-ad-nejm-2017","kind":"paper","name":"COMBI-AD: adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma","aka":[],"tldr":"A year of dabrafenib plus trametinib after surgery for stage III BRAF-mutant melanoma cut the risk of relapse by more than half, giving patients with BRAF mutations a targeted alternative to adjuvant immunotherapy.","summary":"Phase 3 placebo-controlled trial of 870 patients with completely resected stage III BRAF V600E or V600K melanoma randomised to 12 months of dabrafenib plus trametinib or placebo.\n\nThree-year relapse-free survival was 58 versus 39 percent (hazard ratio 0.47) with an early overall survival benefit (hazard ratio 0.57); five-year relapse-free survival was 52 versus 36 percent. Pyrexia and fatigue led to discontinuation in about a quarter.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2017","url":"https://doi.org/10.1056/NEJMoa1708539"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28891408/"}],"tags":[],"related":[],"cancers":["braf-v600-melanoma","stage-iii-melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":["dabrafenib","trametinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["combi-ad"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2017,"doi":"10.1056/NEJMoa1708539","pmid":"28891408","authors":"Long GV, Hauschild A, Santinami M, et al.","paperType":"rct","findings":["Three-year relapse-free survival 58 percent vs 39 percent; hazard ratio 0.47.","Five-year relapse-free survival 52 percent vs 36 percent."],"whatItMeans":"Adjuvant dabrafenib-trametinib is a standard for resected stage III BRAF-mutant melanoma alongside adjuvant PD-1 blockade; the choice weighs a finite year of oral therapy against immune side effects.","caveats":["Final overall survival analysis pending.","Discontinuation for adverse events in 26 percent."],"changedPractice":true,"participants":870},{"id":"paper-combi-d-long-lancet-2015","kind":"paper","name":"COMBI-d: dabrafenib and trametinib versus dabrafenib alone for BRAF V600-mutant melanoma","aka":[],"tldr":"Adding the MEK inhibitor trametinib to the BRAF inhibitor dabrafenib lengthened survival and reduced the skin cancers caused by BRAF inhibition alone in metastatic BRAF-mutant melanoma, establishing dual blockade as the standard for targeted therapy.","summary":"Phase 3 double-blind trial of 423 patients with untreated BRAF V600E or V600K metastatic melanoma randomised to dabrafenib plus trametinib or dabrafenib plus placebo.\n\nMedian overall survival was 25.1 versus 18.7 months (hazard ratio 0.71), median progression-free survival 11.0 versus 8.8 months and response 69 versus 53 percent; cutaneous squamous cell carcinomas were fewer with the combination, while pyrexia was more common.","asOf":"2026-09-17","links":[{"label":"Lancet 2015","url":"https://doi.org/10.1016/S0140-6736(15)60898-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26037941/"}],"tags":[],"related":[],"cancers":["braf-v600-melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":["dabrafenib","trametinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["combi-d"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2015,"doi":"10.1016/S0140-6736(15)60898-4","pmid":"26037941","authors":"Long GV, Stroyakovskiy D, Gogas H, et al.","paperType":"rct","findings":["Median overall survival 25.1 vs 18.7 months; hazard ratio 0.71.","Objective response 69 percent vs 53 percent."],"whatItMeans":"BRAF plus MEK inhibitor doublets replaced BRAF monotherapy, and dabrafenib-trametinib became the reference regimen for BRAF-mutant melanoma, later extended to adjuvant use in COMBI-AD.","caveats":["Pyrexia in over half of combination patients.","Long-term follow-up shows a plateau of about one third of patients alive at five years."],"changedPractice":true,"participants":423},{"id":"paper-palmer-cell","kind":"paper","name":"Combination Cancer Therapy Can Confer Benefit via Patient-to-Patient Variability without Drug Additivity or Synergy","aka":[],"tldr":"Paper cited by one bottleneck page and 18 idea pages, indexed on Europe PMC as PubMed record 29245013 and published in Cell; the citing pages link this DOI, which is how the record was matched.","summary":"Combination cancer therapies aim to improve the probability and magnitude of therapeutic responses and reduce the likelihood of acquired resistance in an individual patient. However, drugs are tested in clinical trials on genetically diverse patient populations. We show here that patient-to-patient variability and independent drug action are sufficient to explain the superiority of many FDA-approved drug combinations in the absence of drug synergy or additivity. This is also true for combinations tested in patient-derived tumor xenografts. In a combination exhibiting independent drug action, each patient benefits solely from the drug to which his or her tumor is most sensitive, with no added benefit from other drugs. Even when drug combinations exhibit additivity or synergy in pre-clinical models, patient-to-patient variability and low cross-resistance make independent action the dominant mechanism in clinical populations. This insight represents a different way to interpret trial data and a different way to design combination therapies.\n\nIndexed on Europe PMC as PubMed record 29245013 (DOI 10.1016/j.cell.2017.11.009). Matched by DOI alone: one bottleneck page and 18 idea pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cell 2017","url":"https://doi.org/10.1016/j.cell.2017.11.009"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29245013/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29245013"}],"tags":["europepmc-ingest"],"related":["b-combination-space","idea-tr2-combination-utility","idea-tr2-combination-patent-pool","idea-tr2-sequence-registry","idea-tr2-combination-forecast-tournament","idea-moon-automated-combination-discovery","idea-tr2-resistance-mechanism-baskets","idea-tr2-rwe-combination-emulation","idea-tr2-combo-readiness-dossier","idea-tr2-organoid-coclinical-arms","idea-tr2-ctdna-futility-gates","idea-tr2-bandit-allocation","idea-tr2-contribution-of-components-mandate","idea-tr2-payer-combo-cwe","idea-tr2-pragmatic-sequence-randomisation","idea-tr2-smart-sequencing-adc","idea-tr2-alternating-vs-concurrent","idea-tr2-window-of-opportunity-triplets","idea-tr2-antagonism-surveillance"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Cell","year":2017,"doi":"10.1016/j.cell.2017.11.009","pmid":"29245013","authors":"Palmer AC, Sorger PK","paperType":"basic","findings":[],"whatItMeans":"One bottleneck page and 18 idea pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-atlantis-lancet-respir-med-2023","kind":"paper","name":"Combination lurbinectedin and doxorubicin versus physician's choice of chemotherapy in patients with relapsed small-cell lung cancer (ATLANTIS): a multicentre, randomised, open-label, phase 3 trial","aka":[],"tldr":"Published report from the ATLANTIS trial registered as NCT02566993, in The Lancet. Respiratory medicine (2023), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Lurbinectedin is a synthetic marine-derived anticancer agent that acts as a selective inhibitor of oncogenic transcription. Lurbinectedin monotherapy (3·2 mg/m 2 every 3 weeks) received accelerated approval from the US Food and Drug Administration on the basis of efficacy in patients with small-cell lung cancer (SCLC) who relapsed after first-line platinum-based chemotherapy. The ATLANTIS trial assessed the efficacy and safety of combination lurbinectedin and the anthracycline doxorubicin as second-line treatment for SCLC.\n\nMethods: In this phase 3, open-label, randomised study, adult patients aged 18 years or older with SCLC who relapsed after platinum-based chemotherapy were recruited from 135 hospitals across North America, South America, Europe, and the Middle East. Patients were randomly assigned (1:1) centrally by dynamic allocation to intravenous lurbinectedin 2·0 mg/m 2 plus doxorubicin 40·0 mg/m 2 administered on day 1 of 21-day cycles or physician's choice of control therapy (intravenous topotecan 1·5 mg/m 2 on days 1-5 of 21-day cycles; or intravenous cyclophosphamide 1000 mg/m 2, doxorubicin 45·0 mg/m 2, and vincristine 2·0 mg on day 1 of 21-day cycles [CAV]) administered until disease progression or unacceptable toxicity. Primary granulocyte-colony stimulating factor prophylaxis was mandatory in both treatment groups. Neither patients nor clinicians were masked to treatment allocation, but the independent review committee, which assessed outcomes, was masked to patients' treatment allocation. The primary endpoint was overall survival in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02566993, and with EudraCT, 2015-001641-89, and is complete.\n\nFindings: Between Aug 30, 2016, and Aug 20, 2018, 613 patients were randomly assigned to lurbinectedin plus doxorubicin (n=307) or control (topotecan, n=127; CAV, n=179) and comprised the intention-to-treat population; safety endpoints were assessed in patients who had received any partial or complete study treatment infusions (lurbinectedin plus doxorubicin, n=303; control, n=289). After a median follow-up of 24·1 months (95% CI 21·7-26·3), 303 patients in the lurbinectedin plus doxorubicin group and 289 patients in the control group had discontinued study treatment; progressive disease was the most common reason for discontinuation (213 [70%] patients in the lurbinectedin plus doxorubicin group vs 152 [53%] in the control group). Median overall survival was 8·6 months (95% CI 7·1-9·4) in the lurbinectedin plus doxorubicin group versus 7·6 months (6·6-8·2) in the control group (stratified log-rank p=0·90; hazard ratio 0·97 [95% CI 0·82-1·15], p=0·70). 12 patients died because of treatment-related adverse events: two (<1%) of 303 in the lurbinectedin plus doxorubicin group and ten (3%) of 289 in the control group. 296 (98%) of 303 patients in the lurbinectedin plus doxorubicin group had treatment-emergent adverse events compared with 284 (98%) of 289 patients in the control group; treatment-related adverse events occurred in 268 (88%) patients in the lurbinectedin plus doxorubicin group and 266 (92%) patients in the control group. Grade 3 or worse haematological adverse events were less frequent in the lurbinectedin plus doxorubicin group than the control group (anaemia, 57 [19%] of 302 patients in the lurbinectedin plus doxorubicin group vs 110 [38%] of 288 in the control group; neutropenia, 112 [37%] vs 200 [69%]; thrombocytopenia, 42 [14%] vs 90 [31%]). The frequency of treatment-related adverse events leading to treatment discontinuation was lower in the lurbinectedin plus doxorubicin group than in the control group (26 [9%] of 303 patients in the lurbinectedin plus doxorubicin group vs 47 [16%] of 289 in the control group).\n\nInterpretation: Combination therapy with lurbinectedin plus doxorubicin did not improve overall survival versus control in patients with relapsed SCLC. However, lurbinectedin plus doxorubicin showed a favourable haematological safety profile compared with control.\n\nFunding: PharmaMar.\n\nIndexed on Europe PMC as PubMed record 36252599 (DOI 10.1016/s2213-2600(22)00309-5). Its abstract cites the registry id NCT02566993, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Respir Med 2023","url":"https://doi.org/10.1016/s2213-2600(22)00309-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36252599/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36252599"},{"label":"ClinicalTrials.gov NCT02566993","url":"https://clinicaltrials.gov/study/NCT02566993"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["atlantis"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Lancet. Respiratory medicine","year":2023,"doi":"10.1016/s2213-2600(22)00309-5","pmid":"36252599","authors":"Aix SP, Ciuleanu TE, Navarro A, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02566993 with the most citations, so it is the natural first reading for anyone following the ATLANTIS trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-ctla-4-colorectal-j-exp-clin-cancer-res-2019","kind":"paper","name":"Combination of CTLA-4 and PD-1 blockers for treatment of cancer","aka":[],"tldr":"Review on CTLA-4 in Colorectal cancer, in Journal of experimental & clinical cancer research (2019), one of the most cited Europe PMC records with CTLA-4 in its title.","summary":"Targeting checkpoints of immune cell activation has been demonstrated to be the most effective approach for activation of anti-tumor immune responses. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1), both inhibitory checkpoints commonly seen on activated T-cells have been found to be the most reliable targets for the treatment of cancer. Six drugs targeting PD-1 or its ligand PD-L1 and one drug targeting CTLA-4 have been approved for treatment of different types of cancers and several others are in advanced stages of development. The drugs when administered as monotherapy had dramatic increase in durable response rates and had manageable safety profile, but more than 50% of patients failed to respond to treatment. Combination of CTLA-4 and PD-1 blockers was then evaluated to increase the response rates in patients, and ipilimumab (anti-CTLA-4) plus nivolumab (anti-PD-1) combination was shown to significantly enhance efficacy in metastatic melanoma patients. Subsequently, ipilimumab plus nivolumab was approved for treatment of metastatic melanoma, advanced renal cell carcinoma and metastatic colorectal cancer with MMR/MSI-H aberrations. The success of combination encouraged multiple clinical studies in other cancer types. Efficacy of the combination has been shown in a number of published studies and is under evaluation in multiple ongoing studies. This review aims to support future research in combination immunotherapy by discussing the basic details of CTLA-4 and PD-1 pathways and the results from clinical studies that evaluated combination of CTLA-4 and PD-1/PD-L1 blockers.\n\nIndexed on Europe PMC as PubMed record 31196207 (DOI 10.1186/s13046-019-1259-z). Its title names CTLA-4 and its text names Colorectal cancer; PubMed types it as a review (review-article, Review). It was matched automatically to the idea \"Making microsatellite-stable colorectal cancer immunotherapy-responsive\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Exp Clin Cancer Res 2019","url":"https://doi.org/10.1186/s13046-019-1259-z"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31196207/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31196207"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-experimental-and-clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Journal of experimental & clinical cancer research","year":2019,"doi":"10.1186/s13046-019-1259-z","pmid":"31196207","authors":"Rotte A","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for CTLA-4 in Colorectal cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by CTLA-4 in the title and Colorectal cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-fushimi-androgen-deprivation-salivary-duct-ann-oncol-2018","kind":"paper","name":"Combined androgen blockade in androgen receptor-positive salivary gland carcinoma","aka":[],"tldr":"Hormone therapy of the kind used in prostate cancer shrank or controlled tumours in most patients with androgen receptor-positive salivary duct carcinoma, a treatment with far less toxicity than chemotherapy.","summary":"Prospective phase 2 study of 36 patients with androgen receptor-positive locally advanced or metastatic salivary gland carcinoma (predominantly salivary duct carcinoma) treated with leuprorelin and bicalutamide.\n\nObjective response was 41.7 percent with a clinical benefit rate of 75 percent, median progression-free survival 8.8 months and median overall survival 30.5 months, and toxicity was mild.","asOf":"2026-09-17","links":[{"label":"Ann Oncol 2018","url":"https://doi.org/10.1093/annonc/mdx771"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29211833/"}],"tags":[],"related":[],"cancers":["salivary-duct-carcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2018,"doi":"10.1093/annonc/mdx771","pmid":"29211833","authors":"Fushimi C, Tada Y, Takahashi H, et al.","paperType":"observational","findings":["Objective response 41.7 percent; clinical benefit 75 percent.","Median progression-free survival 8.8 months; median overall survival 30.5 months."],"whatItMeans":"Androgen receptor testing and androgen deprivation therapy are now standard options for salivary duct carcinoma, often before chemotherapy in slowly progressing disease.","caveats":["Small single-arm trial; a subsequent randomised comparison with chemotherapy showed similar efficacy with less toxicity."],"changedPractice":true,"participants":36},{"id":"paper-combi-d-n-engl-j-med-2014","kind":"paper","name":"Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma","aka":[],"tldr":"Published report from the COMBI-d trial registered as NCT01584648, in New England Journal of Medicine (2014), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Combined BRAF and MEK inhibition, as compared with BRAF inhibition alone, delays the emergence of resistance and reduces toxic effects in patients who have melanoma with BRAF V600E or V600K mutations.\n\nMethods: In this phase 3 trial, we randomly assigned 423 previously untreated patients who had unresectable stage IIIC or stage IV melanoma with a BRAF V600E or V600K mutation to receive a combination of dabrafenib (150 mg orally twice daily) and trametinib (2 mg orally once daily) or dabrafenib and placebo. The primary end point was progression-free survival. Secondary end points included overall survival, response rate, response duration, and safety. A preplanned interim overall survival analysis was conducted.\n\nResults: The median progression-free survival was 9.3 months in the dabrafenib-trametinib group and 8.8 months in the dabrafenib-only group (hazard ratio for progression or death in the dabrafenib-trametinib group, 0.75; 95% confidence interval [CI], 0.57 to 0.99; P=0.03). The overall response rate was 67% in the dabrafenib-trametinib group and 51% in the dabrafenib-only group (P=0.002). At 6 months, the interim overall survival rate was 93% with dabrafenib-trametinib and 85% with dabrafenib alone (hazard ratio for death, 0.63; 95% CI, 0.42 to 0.94; P=0.02). However, a specified efficacy-stopping boundary (two-sided P=0.00028) was not crossed. Rates of adverse events were similar in the two groups, although more dose modifications occurred in the dabrafenib-trametinib group. The rate of cutaneous squamous-cell carcinoma was lower in the dabrafenib-trametinib group than in the dabrafenib-only group (2% vs. 9%), whereas pyrexia occurred in more patients (51% vs. 28%) and was more often severe (grade 3, 6% vs. 2%) in the dabrafenib-trametinib group.\n\nConclusions: A combination of dabrafenib and trametinib, as compared with dabrafenib alone, improved the rate of progression-free survival in previously untreated patients who had metastatic melanoma with BRAF V600E or V600K mutations. (Funded by GlaxoSmithKline; Clinical Trials.gov number, NCT01584648.).\n\nIndexed on Europe PMC as PubMed record 25265492 (DOI 10.1056/nejmoa1406037). Its abstract cites the registry id NCT01584648, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2014","url":"https://doi.org/10.1056/nejmoa1406037"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25265492/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25265492"},{"label":"ClinicalTrials.gov NCT01584648","url":"https://clinicaltrials.gov/study/NCT01584648"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["combi-d"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2014,"doi":"10.1056/nejmoa1406037","pmid":"25265492","authors":"Long GV, Stroyakovskiy D, Gogas H, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT01584648 with the most citations, so it is the natural first reading for anyone following the COMBI-d trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-cohen-ctdna-protein-liquid-biopsy-pancreatic-pnas-2017","kind":"paper","name":"Combined circulating tumor DNA and protein biomarker-based liquid biopsy for the earlier detection of pancreatic cancers","aka":[],"tldr":"A blood test combining KRAS mutations with four proteins found 64% of 221 operable pancreatic cancers while wrongly flagging only one of 182 people without cancer.","summary":"Blood tests for KRAS gene mutations were combined with carefully thresholded protein biomarkers in 221 patients with resectable pancreatic ductal adenocarcinoma and 182 control patients without known cancer. KRAS mutations were detected in the plasma of 66 patients (30%), and every mutation found in plasma was identical to that subsequently found in the primary tumour (100% concordance). KRAS with four thresholded protein biomarkers increased sensitivity to 64%. Only one of the 182 control plasma samples was positive for any DNA or protein biomarker (99.5% specificity).","asOf":"2026-09-24","links":[{"label":"Cohen et al., PNAS 2017: KRAS ctDNA plus protein markers in 221 resectable cancers","url":"https://doi.org/10.1073/pnas.1704961114"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28874546/"}],"tags":[],"related":[],"cancers":["pancreatic","resectable-pdac"],"sections":[],"technologies":["liquid-biopsy","mced","proteomics"],"targets":["kras"],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":[],"terms":["ctdna","cfdna","ca19-9"],"trials":[],"people":["bert-vogelstein","nickolas-papadopoulos"],"bottlenecks":[],"keyPapers":[],"journals":["pnas"],"dependsOn":[],"notes":[],"journal":"PNAS","year":2017,"doi":"10.1073/pnas.1704961114","pmid":"28874546","authors":"Cohen JD, Javed AA, Thoburn C, et al.","paperType":"observational","findings":["Plasma KRAS in only 30% of resectable cancers, with 100% concordance with the tumour.","Adding four proteins raised sensitivity to 64% at 99.5% specificity."],"whatItMeans":"It quantifies how little DNA an operable pancreatic cancer sheds and why every serious early detection panel pairs DNA with proteins.","caveats":["Case-control design overstates performance against a screening population.","Resectable cancers are already symptomatic in most cases."],"changedPractice":false,"participants":403},{"id":"paper-checkmate-204-n-engl-j-med-2018","kind":"paper","name":"Combined Nivolumab and Ipilimumab in Melanoma Metastatic to the Brain","aka":[],"tldr":"Published report from the CheckMate 204 trial registered as NCT02320058, in New England Journal of Medicine (2018), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Brain metastases are a common cause of disabling neurologic complications and death in patients with metastatic melanoma. Previous studies of nivolumab combined with ipilimumab in metastatic melanoma have excluded patients with untreated brain metastases. We evaluated the efficacy and safety of nivolumab plus ipilimumab in patients with melanoma who had untreated brain metastases.\n\nMethods: In this open-label, multicenter, phase 2 study, patients with metastatic melanoma and at least one measurable, nonirradiated brain metastasis (tumor diameter, 0.5 to 3 cm) and no neurologic symptoms received nivolumab (1 mg per kilogram of body weight) plus ipilimumab (3 mg per kilogram) every 3 weeks for up to four doses, followed by nivolumab (3 mg per kilogram) every 2 weeks until progression or unacceptable toxic effects. The primary end point was the rate of intracranial clinical benefit, defined as the percentage of patients who had stable disease for at least 6 months, complete response, or partial response.\n\nResults: Among 94 patients with a median follow-up of 14.0 months, the rate of intracranial clinical benefit was 57% (95% confidence interval [CI], 47 to 68); the rate of complete response was 26%, the rate of partial response was 30%, and the rate of stable disease for at least 6 months was 2%. The rate of extracranial clinical benefit was 56% (95% CI, 46 to 67). Treatment-related grade 3 or 4 adverse events were reported in 55% of patients, including events involving the central nervous system in 7%. One patient died from immune-related myocarditis. The safety profile of the regimen was similar to that reported in patients with melanoma who do not have brain metastases.\n\nConclusions: Nivolumab combined with ipilimumab had clinically meaningful intracranial efficacy, concordant with extracranial activity, in patients with melanoma who had untreated brain metastases. (Funded by Bristol-Myers Squibb and the National Cancer Institute; CheckMate 204 ClinicalTrials.gov number, NCT02320058.).\n\nIndexed on Europe PMC as PubMed record 30134131 (DOI 10.1056/nejmoa1805453). Its abstract cites the registry id NCT02320058, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2018","url":"https://doi.org/10.1056/nejmoa1805453"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30134131/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30134131"},{"label":"ClinicalTrials.gov NCT02320058","url":"https://clinicaltrials.gov/study/NCT02320058"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-204"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2018,"doi":"10.1056/nejmoa1805453","pmid":"30134131","authors":"Tawbi HA, Forsyth PA, Algazi A, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02320058 with the most citations, so it is the natural first reading for anyone following the CheckMate 204 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-nivolumab-melanoma-n-engl-j-med-2015","kind":"paper","name":"Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma","aka":[],"tldr":"Phase 2 or 3 results paper on Nivolumab in Melanoma, in New England Journal of Medicine (2015), one of the most cited Europe PMC records with Nivolumab in its title.","summary":"Background: Nivolumab (a programmed death 1 [PD-1] checkpoint inhibitor) and ipilimumab (a cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4] checkpoint inhibitor) have been shown to have complementary activity in metastatic melanoma. In this randomized, double-blind, phase 3 study, nivolumab alone or nivolumab plus ipilimumab was compared with ipilimumab alone in patients with metastatic melanoma.\n\nMethods: We assigned, in a 1:1:1 ratio, 945 previously untreated patients with unresectable stage III or IV melanoma to nivolumab alone, nivolumab plus ipilimumab, or ipilimumab alone. Progression-free survival and overall survival were coprimary end points. Results regarding progression-free survival are presented here.\n\nResults: The median progression-free survival was 11.5 months (95% confidence interval [CI], 8.9 to 16.7) with nivolumab plus ipilimumab, as compared with 2.9 months (95% CI, 2.8 to 3.4) with ipilimumab (hazard ratio for death or disease progression, 0.42; 99.5% CI, 0.31 to 0.57; P<0.001), and 6.9 months (95% CI, 4.3 to 9.5) with nivolumab (hazard ratio for the comparison with ipilimumab, 0.57; 99.5% CI, 0.43 to 0.76; P<0.001). In patients with tumors positive for the PD-1 ligand (PD-L1), the median progression-free survival was 14.0 months in the nivolumab-plus-ipilimumab group and in the nivolumab group, but in patients with PD-L1-negative tumors, progression-free survival was longer with the combination therapy than with nivolumab alone (11.2 months [95% CI, 8.0 to not reached] vs. 5.3 months [95% CI, 2.8 to 7.1]). Treatment-related adverse events of grade 3 or 4 occurred in 16.3% of the patients in the nivolumab group, 55.0% of those in the nivolumab-plus-ipilimumab group, and 27.3% of those in the ipilimumab group.\n\nConclusions: Among previously untreated patients with metastatic melanoma, nivolumab alone or combined with ipilimumab resulted in significantly longer progression-free survival than ipilimumab alone. In patients with PD-L1-negative tumors, the combination of PD-1 and CTLA-4 blockade was more effective than either agent alone. (Funded by Bristol-Myers Squibb; CheckMate 067 ClinicalTrials.gov number, NCT01844505.).\n\nIndexed on Europe PMC as PubMed record 26027431 (DOI 10.1056/nejmoa1504030). Its title names Nivolumab and its text names Melanoma; PubMed types it as a clinical trial report (Clinical Trial, Phase III, Comparative Study, Research Support, Non-U.S. Gov't, research-article, Randomized Controlled Trial). It was matched automatically to the idea \"Treat the draining lymph node before removing it\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2015","url":"https://doi.org/10.1056/nejmoa1504030"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26027431/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26027431"},{"label":"ClinicalTrials.gov NCT01844505","url":"https://clinicaltrials.gov/study/NCT01844505"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-067"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2015,"doi":"10.1056/nejmoa1504030","pmid":"26027431","authors":"Larkin J, Chiarion-Sileni V, Gonzalez R, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Nivolumab in Melanoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Nivolumab in the title and Melanoma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-aparicio-aggressive-variant-prostate-tumour-suppressors-ccr-2016","kind":"paper","name":"Combined tumour suppressor defects characterise clinically defined aggressive variant prostate cancers","aka":[],"tldr":"Prostate cancers that behave like small cell carcinoma without looking like it turn out to share the same broken genes, so the clinical description can be checked against the molecular one.","summary":"Morphologically heterogeneous prostate cancers that behave clinically like small cell prostate cancers share their chemotherapy responsiveness. Fifty-nine prostate cancer samples from 40 clinical trial participants meeting aggressive variant criteria, and 8 patient-derived xenografts from 6 of them, were stained for markers aberrantly expressed in small cell prostate cancer, and DNA from 36 samples and 8 xenografts was analysed for copy-number gains and losses. Irrespective of morphology, Ki67 and Tp53 stained in at least 10% of cells in 80% and 41% of samples; RB1 stained in fewer than 10% of cells in 61% and androgen receptor in 36%. MYC copy gain, a surrogate for 8q, and RB1 copy loss were each present in 54% of 44 samples and PTEN copy loss in 48%. All but 1 of 8 xenografts carried Tp53 missense mutations. RB1 copy loss was the strongest discriminator between unselected castration-resistant prostate cancer and the aggressive variant, and combined alterations in RB1, Tp53 and PTEN were more frequent in aggressive variant disease than in unselected castration-resistant disease or in TCGA samples.","asOf":"2026-09-25","links":[{"label":"Aparicio et al., Clin Cancer Res 2016: combined RB1, TP53 and PTEN defects characterise clinically defined aggressive variant prostate cancer (59 samples from 40 trial participants)","url":"https://doi.org/10.1158/1078-0432.CCR-15-1259"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26546118/"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc","prostate-nepc"],"sections":[],"technologies":["histopathology-ihc"],"targets":["rb1","tp53","pten","androgen-receptor","mki67"],"drugs":[],"companies":[],"institutions":[],"pathways":["lineage-plasticity-neuroendocrine","p53-cell-cycle","pi3k-akt-mtor","chromosomal-instability"],"terms":["histologic-transformation","ihc","copy-number-variation-term","castration-resistance"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2016,"doi":"10.1158/1078-0432.CCR-15-1259","pmid":"26546118","authors":"Aparicio AM, Shen L, Tapia ELN, et al.","paperType":"translational","findings":["RB1 loss the strongest single discriminator between unselected castration-resistant disease and the aggressive variant.","MYC copy gain and RB1 copy loss each in 54% of 44 samples, PTEN copy loss in 48%.","RB1 staining in under 10% of cells in 61% of samples and androgen receptor in 36%.","Combined RB1, TP53 and PTEN alterations enriched in aggressive variant disease."],"whatItMeans":"It validates a clinical definition against a molecular one, which is unusual and useful: a man whose disease behaves like small cell carcinoma can be treated as such even when his biopsy does not look like it, because the underlying genotype is the same.","caveats":["Fifty-nine samples from 40 trial participants, a selected population.","Copy-number analysis on archival material rather than sequencing.","The aggressive variant criteria are clinical and were defined by the same group."],"changedPractice":false,"participants":40},{"id":"paper-cobrim-n-engl-j-med-2014","kind":"paper","name":"Combined vemurafenib and cobimetinib in BRAF-mutated melanoma","aka":[],"tldr":"Published report from the coBRIM trial registered as NCT01689519, in New England Journal of Medicine (2014), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: The combined inhibition of BRAF and MEK is hypothesized to improve clinical outcomes in patients with melanoma by preventing or delaying the onset of resistance observed with BRAF inhibitors alone. This randomized phase 3 study evaluated the combination of the BRAF inhibitor vemurafenib and the MEK inhibitor cobimetinib.\n\nMethods: We randomly assigned 495 patients with previously untreated unresectable locally advanced or metastatic BRAF V600 mutation-positive melanoma to receive vemurafenib and cobimetinib (combination group) or vemurafenib and placebo (control group). The primary end point was investigator-assessed progression-free survival.\n\nResults: The median progression-free survival was 9.9 months in the combination group and 6.2 months in the control group (hazard ratio for death or disease progression, 0.51; 95% confidence interval [CI], 0.39 to 0.68; P<0.001). The rate of complete or partial response in the combination group was 68%, as compared with 45% in the control group (P<0.001), including rates of complete response of 10% in the combination group and 4% in the control group. Progression-free survival as assessed by independent review was similar to investigator-assessed progression-free survival. Interim analyses of overall survival showed 9-month survival rates of 81% (95% CI, 75 to 87) in the combination group and 73% (95% CI, 65 to 80) in the control group. Vemurafenib and cobimetinib was associated with a nonsignificantly higher incidence of adverse events of grade 3 or higher, as compared with vemurafenib and placebo (65% vs. 59%), and there was no significant difference in the rate of study-drug discontinuation. The number of secondary cutaneous cancers decreased with the combination therapy.\n\nConclusions: The addition of cobimetinib to vemurafenib was associated with a significant improvement in progression-free survival among patients with BRAF V600-mutated metastatic melanoma, at the cost of some increase in toxicity. (Funded by F. Hoffmann-La Roche/Genentech; coBRIM ClinicalTrials.gov number, NCT01689519.).\n\nIndexed on Europe PMC as PubMed record 25265494 (DOI 10.1056/nejmoa1408868). Its abstract cites the registry id NCT01689519, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2014","url":"https://doi.org/10.1056/nejmoa1408868"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25265494/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25265494"},{"label":"ClinicalTrials.gov NCT01689519","url":"https://clinicaltrials.gov/study/NCT01689519"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["cobrim"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2014,"doi":"10.1056/nejmoa1408868","pmid":"25265494","authors":"Larkin J, Ascierto PA, Dréno B, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT01689519 with the most citations, so it is the natural first reading for anyone following the coBRIM trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-comfort-1-ruxolitinib-myelofibrosis-nejm-2012","kind":"paper","name":"COMFORT-I: ruxolitinib, the first JAK inhibitor, versus placebo for myelofibrosis","aka":[],"tldr":"Ruxolitinib shrank the enlarged spleen by more than a third in 42% of myelofibrosis patients versus under 1% on placebo, and halved symptom scores in nearly half.","summary":"COMFORT-I was a double-blind phase 3 trial that randomised 309 patients with intermediate-2 or high-risk myelofibrosis to the JAK1/JAK2 inhibitor ruxolitinib or placebo. The primary endpoint was the proportion with at least a 35% reduction in spleen volume at 24 weeks by imaging. This was 41.9% versus 0.7%, and a 50% or greater improvement in total symptom score was seen in 45.9% versus 5.3%. Anaemia and thrombocytopenia were the main toxicities. A parallel trial, COMFORT-II, showed similar spleen responses against best available therapy. Later analyses suggested a survival advantage for ruxolitinib despite crossover. It was the first drug approved for myelofibrosis and the first approved JAK inhibitor for a malignancy.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa1110557"},{"label":"ClinicalTrials.gov NCT00952289","url":"https://clinicaltrials.gov/study/NCT00952289"}],"tags":[],"related":["paper-momentum-momelotinib-lancet-2023"],"cancers":["myeloproliferative-neoplasms"],"sections":[],"technologies":[],"targets":["jak2"],"drugs":["ruxolitinib","fedratinib","pacritinib","momelotinib"],"companies":["incyte","novartis"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-rare-cancers"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2012,"doi":"10.1056/NEJMoa1110557","authors":"Verstovsek S, Mesa RA, Gotlib J, et al.","paperType":"rct","findings":["309 patients with intermediate-2 or high-risk myelofibrosis; ruxolitinib vs placebo, double-blind.","Spleen volume reduction of at least 35% at week 24: 41.9% vs 0.7%.","Symptom score improvement of at least 50%: 45.9% vs 5.3%.","Grade 3-4 anaemia 45% and thrombocytopenia 13% with ruxolitinib; rarely led to discontinuation.","Pooled COMFORT analyses later showed an overall survival advantage (hazard ratio about 0.7) despite extensive crossover."],"whatItMeans":"COMFORT-I turned the 2005 discovery of the JAK2 V617F mutation into the first effective medicine for myelofibrosis, transforming symptom control for a disease with no prior standard. Ruxolitinib is still the reference first-line therapy, with fedratinib, pacritinib and momelotinib as alternatives for cytopenic patients. It does not eliminate the malignant clone or reverse fibrosis in most patients.","caveats":["Primary endpoint was spleen volume, a surrogate; survival gains were shown only in later, crossover-confounded analyses.","Ruxolitinib worsens anaemia, limiting use in already-anaemic patients.","Benefit is largely symptomatic; molecular responses are uncommon.","Discontinuation is followed by rapid symptom rebound."],"changedPractice":true,"participants":309},{"id":"paper-comfort-ii-ruxolitinib-best-available-therapy-harrison-nejm-2012","kind":"paper","name":"COMFORT-II: JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis","aka":[],"tldr":"In this European trial, ruxolitinib shrank the spleen by more than a third in 28 percent of people with myelofibrosis after 48 weeks while no patient on the best alternative treatment achieved that, and symptoms and quality of life improved.","summary":"Open-label phase 3 trial that randomised 219 patients with intermediate-2 or high-risk primary, post-polycythaemia vera or post-essential thrombocythaemia myelofibrosis two to one to oral ruxolitinib or best available therapy. The primary endpoint was a spleen volume reduction of at least 35 percent at week 48 on MRI or CT; the key secondary endpoint was the same reduction at week 24.\n\n28 percent of the ruxolitinib group met the primary endpoint against 0 percent on best available therapy; responses were durable and role functioning and quality of life improved, with modest toxic effects. An influence on overall survival had not been shown at the primary analysis.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2012","url":"https://doi.org/10.1056/NEJMoa1110556"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22375970/"}],"tags":[],"related":[],"cancers":["primary-myelofibrosis","myeloproliferative-neoplasms"],"sections":[],"technologies":[],"targets":[],"drugs":["ruxolitinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["comfort-ii"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2012,"doi":"10.1056/NEJMoa1110556","pmid":"22375970","authors":"Harrison C, Kiladjian JJ, Al-Ali HK, et al.","paperType":"rct","findings":["Spleen volume reduction of at least 35 percent at week 48 in 28 percent of patients on ruxolitinib versus 0 percent on best available therapy (p < 0.001).","Durable reductions in splenomegaly and disease-related symptoms, with improved role functioning and quality of life.","Modest toxic effects, mainly anaemia and thrombocytopenia."],"whatItMeans":"With COMFORT-I, the evidence for ruxolitinib as the first approved treatment for myelofibrosis and for JAK inhibition as the standard for spleen and symptom control.","caveats":["Open-label against a heterogeneous comparator, mostly hydroxycarbamide or no treatment.","No survival benefit was demonstrated at the primary analysis; pooled long-term follow-up later suggested one."],"changedPractice":true,"participants":219},{"id":"paper-commands-luspatercept-mds-lancet-2023","kind":"paper","name":"COMMANDS: luspatercept versus epoetin alfa as first treatment for anaemia in lower-risk MDS needing transfusions","aka":[],"tldr":"In COMMANDS, luspatercept, a drug that frees late-stage red cell production from TGF-beta-family braking, freed 59% of transfusion-dependent MDS patients from transfusions for at least 12 weeks, against 31% with the standard erythropoietin injection.","summary":"COMMANDS randomised patients with lower-risk MDS (the three lowest risk categories) who were red-cell transfusion dependent and had not received erythropoiesis-stimulating agents to subcutaneous luspatercept every three weeks or weekly epoetin alfa. The primary endpoint was red-cell transfusion independence for at least 12 weeks with a concurrent haemoglobin rise of at least 1.5 g/dL within the first 24 weeks. In the interim analysis of 301 patients this was achieved by 58.5% versus 31.2%, with benefit in both ring-sideroblast-positive and negative disease, although the difference was smaller in patients without ring sideroblasts. Adverse events were similar, with fatigue, diarrhoea and hypertension more common with luspatercept.","asOf":"2026-09-08","links":[{"label":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=COMMANDS%20luspatercept%20epoetin%20alfa%20lower-risk%20MDS%20Platzbecker%20Lancet%202023"},{"label":"ClinicalTrials.gov NCT03682536","url":"https://clinicaltrials.gov/study/NCT03682536"}],"tags":[],"related":["paper-imerge-imetelstat-mds-lancet-2024"],"cancers":["mds"],"sections":[],"technologies":[],"targets":["tgf-beta"],"drugs":["luspatercept","imetelstat"],"companies":["bms"],"institutions":[],"pathways":[],"terms":["orr"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-drug-pricing"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2023,"doi":"10.1016/S0140-6736(23)00874-7","pmid":"37311468","authors":"Platzbecker U, Della Porta MG, Santini V, et al.","paperType":"rct","findings":["Interim analysis of 301 ESA-naive, transfusion-dependent, lower-risk MDS patients; luspatercept vs epoetin alfa.","Primary endpoint (12-week transfusion independence plus haemoglobin rise of at least 1.5 g/dL in weeks 1-24): 58.5% vs 31.2%.","Benefit in ring-sideroblast-positive disease was largest; the effect in ring-sideroblast-negative disease was smaller and less certain.","Median duration of transfusion independence was longer with luspatercept.","Safety comparable; no increase in progression to AML."],"whatItMeans":"COMMANDS moved luspatercept from second line (after ESA failure, MEDALIST trial) to first line, offering transfusion-dependent lower-risk MDS patients a better chance of transfusion freedom from the start. It changed guidelines and labels in 2023. Erythropoietin remains a reasonable and cheaper option for patients without ring sideroblasts or with low transfusion burden.","caveats":["Interim analysis of an open-label trial; the composite primary endpoint is a surrogate for quality of life and survival.","Uncertain benefit in ring-sideroblast-negative and SF3B1-unmutated disease.","Excluded patients with del(5q) and those with high transfusion burden plus low erythropoietin only partially represented.","Cost is far higher than epoetin."],"changedPractice":true,"participants":301},{"id":"paper-menden-nat-commun","kind":"paper","name":"Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen","aka":[],"tldr":"Paper cited by one bottleneck page, indexed on Europe PMC as PubMed record 31209238 and published in Nature Communications; the citing page links this DOI, which is how the record was matched.","summary":"The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca's large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.\n\nIndexed on Europe PMC as PubMed record 31209238 (DOI 10.1038/s41467-019-09799-2). Matched by DOI alone: one bottleneck page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Commun 2019","url":"https://doi.org/10.1038/s41467-019-09799-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31209238/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31209238"}],"tags":["europepmc-ingest"],"related":["b-combination-space"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-communications"],"dependsOn":[],"notes":[],"journal":"Nature Communications","year":2019,"doi":"10.1038/s41467-019-09799-2","pmid":"31209238","authors":"Menden MP, Wang D, Mason MJ, et al.","paperType":"basic","findings":[],"whatItMeans":"One bottleneck page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-barchuk-registry-validity-acta-oncol-2021","kind":"paper","name":"Comparability and validity of cancer registry data in the north-west of Russia","aka":[],"tldr":"An audit of ten Russian regional cancer registries against international rules found four of the ten fit to compare with other countries, with morphological verification as low as 62 per cent in some regions and up to 23 per cent of Saint Petersburg cases known only from a death certificate.","summary":"Data from ten population-based cancer registries in the Northwestern Federal District, covering about 13 million people of whom about 5 million are in Saint Petersburg, were processed against IARC, IACR and European Network of Cancer Registries recommendations, focusing on cases diagnosed between 2008 and 2017.\n\nData collection followed international standards and the distribution of diagnosis dates was broadly uniform. The proportion of multiple primaries ranged from 6.7 per cent in Vologda oblast to 12.4 per cent in Saint Petersburg. Between 2013 and 2017 the proportion of morphologically verified cases ranged from 61.7 to 89 per cent across the regions, and death-certificate-only cases from 1 to 14 per cent, except Saint Petersburg where they reached 23 per cent. Cases with unknown primary site were 1 to 3 per cent. Validity was lowest for pancreatic, liver, haematological and central nervous system tumours and in older age groups.","asOf":"2026-09-25","links":[{"label":"Acta Oncologica 2021","url":"https://doi.org/10.1080/0284186X.2021.1967443"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34424113/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34424113"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["petrov-institute"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["acta-oncologica"],"dependsOn":[],"notes":[],"journal":"Acta oncologica","year":2021,"doi":"10.1080/0284186X.2021.1967443","pmid":"34424113","authors":"Barchuk A, Tursun-Zade R, Belayev A, et al.","paperType":"methods","findings":["Four of ten north-western regional registries met international standards for comparability and validity.","Morphological verification ranged from 61.7 to 89 per cent across regions in 2013 to 2017.","Death-certificate-only cases were 1 to 14 per cent in most regions and up to 23 per cent in Saint Petersburg.","Validity was lowest for pancreatic, liver, haematological and central nervous system tumours and in the oldest age groups."],"whatItMeans":"Russian national cancer figures are assembled from regional registries of very uneven quality, so a national average conceals both real differences in disease and differences in how carefully cases are recorded. It is the reason to read the Herzen institute's annual volumes alongside an independent audit rather than on their own.","caveats":["Covers ten regions of one federal district, not the whole country; the other seventy-odd regions have not been audited in the same way in English.","Local registration instructions differ between regions, which the authors say need updating and enforcing."]},{"id":"paper-comstock-jama","kind":"paper","name":"Comparison of Abbreviated Breast MRI vs Digital Breast Tomosynthesis for Breast Cancer Detection Among Women With Dense Breasts Undergoing Screening","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 32096852 and published in JAMA; the citing page links this DOI, which is how the record was matched.","summary":"Importance: Improved screening methods for women with dense breasts are needed because of their increased risk of breast cancer and of failed early diagnosis by screening mammography.\n\nObjective: To compare the screening performance of abbreviated breast magnetic resonance imaging (MRI) and digital breast tomosynthesis (DBT) in women with dense breasts.\n\nDesign, setting, and participants: Cross-sectional study with longitudinal follow-up at 48 academic, community hospital, and private practice sites in the United States and Germany, conducted between December 2016 and November 2017 among average-risk women aged 40 to 75 years with heterogeneously dense or extremely dense breasts undergoing routine screening. Follow-up ascertainment of cancer diagnoses was complete through September 12, 2019.\n\nExposures: All women underwent screening by both DBT and abbreviated breast MRI, performed in randomized order and read independently to avoid interpretation bias.\n\nMain outcomes and measures: The primary end point was the invasive cancer detection rate. Secondary outcomes included sensitivity, specificity, additional imaging recommendation rate, and positive predictive value (PPV) of biopsy, using invasive cancer and ductal carcinoma in situ (DCIS) to define a positive reference standard. All outcomes are reported at the participant level. Pathology of core or surgical biopsy was the reference standard for cancer detection rate and PPV; interval cancers reported until the next annual screen were included in the reference standard for sensitivity and specificity.\n\nResults: Among 1516 enrolled women, 1444 (median age, 54 [range, 40-75] years) completed both examinations and were included in the analysis. The reference standard was positive for invasive cancer with or without DCIS in 17 women and for DCIS alone in another 6. No interval cancers were observed during follow-up. Abbreviated breast MRI detected all 17 women with invasive cancer and 5 of 6 women with DCIS. Digital breast tomosynthesis detected 7 of 17 women with invasive cancer and 2 of 6 women with DCIS. The invasive cancer detection rate was 11.8 (95% CI, 7.4-18.8) per 1000 women for abbreviated breast MRI vs 4.8 (95% CI, 2.4-10.0) per 1000 women for DBT, a difference of 7 (95% CI, 2.2-11.6) per 1000 women (exact McNemar P =.002). For detection of invasive cancer and DCIS, sensitivity was 95.7% (95% CI, 79.0%-99.2%) with abbreviated breast MRI vs 39.1% (95% CI, 22.2%-59.2%) with DBT (P =.001) and specificity was 86.7% (95% CI, 84.8%-88.4%) vs 97.4% (95% CI, 96.5%-98.1%), respectively (P <.001). The additional imaging recommendation rate was 7.5% (95% CI, 6.2%-9.0%) with abbreviated breast MRI vs 10.1% (95% CI, 8.7%-11.8%) with DBT (P =.02) and the PPV was 19.6% (95% CI, 13.2%-28.2%) vs 31.0% (95% CI, 17.0%-49.7%), respectively (P =.15).\n\nConclusions and relevance: Among women with dense breasts undergoing screening, abbreviated breast MRI, compared with DBT, was associated with a significantly higher rate of invasive breast cancer detection. Further research is needed to better understand the relationship between screening methods and clinical outcome.\n\nTrial registration: ClinicalTrials.gov Identifier: NCT02933489.\n\nIndexed on Europe PMC as PubMed record 32096852 (DOI 10.1001/jama.2020.0572). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA 2020","url":"https://doi.org/10.1001/jama.2020.0572"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32096852/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32096852"}],"tags":["europepmc-ingest"],"related":["breast-mri-coils-abbreviated-mri"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2020,"doi":"10.1001/jama.2020.0572","pmid":"32096852","authors":"Comstock CE, Gatsonis C, Newstead GM, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-huo-tcga-ancestry-breast-jama-oncol-2017","kind":"paper","name":"Comparison of breast cancer molecular features and survival by African and European ancestry in The Cancer Genome Atlas","aka":[],"tldr":"Among 930 TCGA patients, those of African ancestry were nearly four times as likely to have basal-like cancer, had more TP53 and fewer PIK3CA mutations and relapsed sooner; about 44% of the subtype difference was explained by inherited variants.","summary":"Tumour and matched normal data for 930 TCGA breast cancer patients (154 black patients of African ancestry, 776 white of European ancestry) were compared. Black patients had a worse breast cancer-free interval (HR 1.67), higher odds of basal-like (OR 3.80) and HER2-enriched (OR 2.22) subtypes, more TP53 and fewer PIK3CA mutations. Most molecular differences disappeared after adjusting for intrinsic subtype, leaving 16 methylation probes, 4 copy-number segments, 1 protein and 142 genes differentially expressed. Heritability of basal versus non-basal subtype from germline genotypes was 0.436; the ER-negative polygenic risk score was much higher in black patients.","asOf":"2026-09-24","links":[{"label":"Huo et al., JAMA Oncol 2017: breast cancer molecular features by African and European ancestry in TCGA","url":"https://doi.org/10.1001/jamaoncol.2017.0595"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28472234/"}],"tags":[],"related":[],"cancers":["tnbc","breast-cancer"],"sections":[],"technologies":[],"targets":["tp53","pik3ca"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["pam50"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2017,"doi":"10.1001/jamaoncol.2017.0595","pmid":"28472234","authors":"Huo D, Hu H, Rhie SK, et al.","paperType":"observational","findings":["African ancestry: basal-like OR 3.80, HER2-enriched OR 2.22, breast cancer-free interval HR 1.67.","More TP53 and fewer PIK3CA mutations; most differences explained by subtype.","Heritability of basal versus non-basal subtype 0.436; higher ER-negative polygenic risk score."],"whatItMeans":"The excess of triple-negative disease in women of African ancestry is substantially genetic in origin rather than only social, which supports ancestry-aware risk models and trial enrolment.","caveats":["Convenience cohort with self-reported race refined by genotype; 154 black patients.","Survival follow-up in TCGA is short."],"changedPractice":false,"participants":930},{"id":"paper-schiller-ecog-1594-four-chemotherapy-regimens-nejm-2002","kind":"paper","name":"Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer","aka":[],"tldr":"1,207 patients were randomised between four platinum doublets. All four gave the same result: about one in five responded and median survival was just under eight months. Chemotherapy had reached a ceiling.","summary":"The Eastern Cooperative Oncology Group's E1594 trial, reported by Schiller, Harrington, Belani, Langer, Sandler, Krook, Zhu and Johnson. A reference regimen of cisplatin and paclitaxel was compared against cisplatin and gemcitabine, cisplatin and docetaxel, and carboplatin and paclitaxel in 1,207 patients with advanced non-small-cell lung cancer, of whom 1,155 were eligible.\n\nThe trial is remembered for a negative result that mattered: no regimen was better than any other, so the choice between them became a matter of toxicity, convenience and cost. It fixed the plateau that targeted therapy and immunotherapy were later measured against, and it is the reason a median survival of about eight months is the reference point for advanced lung cancer in 2002.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2002","url":"https://doi.org/10.1056/NEJMoa011954"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/11784875/"}],"tags":["lung-evidence"],"related":["chemotherapy-roadmap","paper-nsclc-collaborative-group-chemotherapy-meta-analysis-bmj-1995","paper-scagliotti-cisplatin-pemetrexed-histology-jco-2008"],"cancers":["lung-cancer","nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":["cisplatin","carboplatin","paclitaxel","docetaxel","gemcitabine"],"companies":["ecog-acrin"],"institutions":[],"pathways":[],"terms":["performance-status"],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-biomarker-validation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2002,"doi":"10.1056/NEJMoa011954","pmid":"11784875","authors":"Schiller JH, Harrington D, Belani CP, et al.","paperType":"rct","findings":["Response rate 19 percent across all 1,155 eligible patients; median survival 7.9 months (95 percent confidence interval 7.3 to 8.5).","One-year survival 33 percent (30 to 36) and two-year survival 11 percent (8 to 12).","Neither response rate nor survival differed significantly between the reference regimen and any of the three experimental regimens.","Cisplatin and gemcitabine gave a significantly longer time to progression than cisplatin and paclitaxel but caused more grade 3, 4 or 5 renal toxicity (9 percent against 3 percent).","Patients with a performance status of 2 had significantly lower survival than those with performance status 0 or 1."],"whatItMeans":"The ceiling of undirected cytotoxic chemotherapy, measured precisely. Everything that came afterwards, from histology-directed pemetrexed to EGFR inhibitors to checkpoint blockade, is an attempt to break a plateau this trial demonstrated could not be broken by changing the drugs.","caveats":["Four regimens, not a test of whether chemotherapy helps at all; that question was settled by the 1995 meta-analysis.","Molecular subgroups were unknown in 2002, so a trial of unselected patients averaged over populations now treated completely differently.","Performance status 2 patients did badly and remain under-represented in lung cancer trials."],"changedPractice":true,"participants":1207},{"id":"paper-marina-lancet-oncol","kind":"paper","name":"Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1): an open-label, international, randomised controlled trial","aka":[],"tldr":"Paper cited by one cancer page and one trial page, indexed on Europe PMC as PubMed record 27569442 and published in The Lancet Oncology; the citing pages link this DOI, which is how the record was matched.","summary":"Background: We designed the EURAMOS-1 trial to investigate whether intensified postoperative chemotherapy for patients whose tumour showed a poor response to preoperative chemotherapy (≥10% viable tumour) improved event-free survival in patients with high-grade osteosarcoma.\n\nMethods: EURAMOS-1 was an open-label, international, phase 3 randomised, controlled trial. Consenting patients with newly diagnosed, resectable, high-grade osteosarcoma aged 40 years or younger were eligible for randomisation. Patients were randomly assigned (1:1) to receive either postoperative cisplatin, doxorubicin, and methotrexate (MAP) or MAP plus ifosfamide and etoposide (MAPIE) using concealed permuted blocks with three stratification factors: trial group; location of tumour (proximal femur or proximal humerus vs other limb vs axial skeleton); and presence of metastases (no vs yes or possible). The MAP regimen consisted of cisplatin 120 mg/m 2, doxorubicin 37·5 mg/m 2 per day on days 1 and 2 (on weeks 1 and 6) followed 3 weeks later by high-dose methotrexate 12 g/m 2 over 4 h. The MAPIE regimen consisted of MAP as a base regimen, with the addition of high-dose ifosfamide (14 g/m 2) at 2·8 g/m 2 per day with equidose mesna uroprotection, followed by etoposide 100 mg/m 2 per day over 1 h on days 1-5. The primary outcome measure was event-free survival measured in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00134030.\n\nFindings: Between April 14, 2005, and June 30, 2011, 2260 patients were registered from 325 sites in 17 countries. 618 patients with poor response were randomly assigned; 310 to receive MAP and 308 to receive MAPIE. Median follow-up was 62·1 months (IQR 46·6-76·6); 62·3 months (IQR 46·9-77·1) for the MAP group and 61·1 months (IQR 46·5-75·3) for the MAPIE group. 307 event-free survival events were reported (153 in the MAP group vs 154 in the MAPIE group). 193 deaths were reported (101 in the MAP group vs 92 in the MAPIE group). Event-free survival did not differ between treatment groups (hazard ratio [HR] 0·98 [95% CI 0·78-1·23]); hazards were non-proportional (p=0·0003). The most common grade 3-4 adverse events were neutropenia (268 [89%] patients in MAP vs 268 [90%] in MAPIE), thrombocytopenia (231 [78% in MAP vs 248 [83%] in MAPIE), and febrile neutropenia without documented infection (149 [50%] in MAP vs 217 [73%] in MAPIE). MAPIE was associated with more frequent grade 4 non-haematological toxicity than MAP (35 [12%] of 301 in the MAP group vs 71 [24%] of 298 in the MAPIE group). Two patients died during postoperative therapy, one from infection (although their absolute neutrophil count was normal), which was definitely related to their MAP treatment (specifically doxorubicin and cisplatin), and one from left ventricular systolic dysfunction, which was probably related to MAPIE treatment (specifically doxorubicin). One suspected unexpected serious adverse reaction was reported in the MAP group: bone marrow infarction due to methotrexate.\n\nInterpretation: EURAMOS-1 results do not support the addition of ifosfamide and etoposide to postoperative chemotherapy in patients with poorly responding osteosarcoma because its administration was associated with increased toxicity without improving event-free survival. The results define standard of care for this population. New strategies are required to improve outcomes in this setting.\n\nFunding: UK Medical Research Council, National Cancer Institute, European Science Foundation, St Anna Kinderkrebsforschung, Fonds National de la Recherche Scientifique, Fonds voor Wetenschappelijk Onderzoek-Vlaanderen, Parents Organization, Danish Medical Research Council, Academy of Finland, Deutsche Forschungsgemeinschaft, Deutsche Krebshilfe, Federal Ministry of Education and Research, Semmelweis Foundation, ZonMw (Council for Medical Research), Research Council of Norway, Scandinavian Sarcoma Group, Swiss Paediatric Oncology Group, Cancer Research UK, National Institute for Health Research, University College London Hospitals, and Biomedical Research Centre.\n\nIndexed on Europe PMC as PubMed record 27569442 (DOI 10.1016/s1470-2045(16)30214-5). Matched by DOI alone: one cancer page and one trial page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2016","url":"https://doi.org/10.1016/s1470-2045(16)30214-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27569442/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27569442"}],"tags":["europepmc-ingest"],"related":["osteosarcoma"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["euramos-1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2016,"doi":"10.1016/s1470-2045(16)30214-5","pmid":"27569442","authors":"Marina NM, Smeland S, Bielack SS, et al.","paperType":"rct","findings":[],"whatItMeans":"One cancer page and one trial page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-van-der-zee-lancet","kind":"paper","name":"Comparison of radiotherapy alone with radiotherapy plus hyperthermia in locally advanced pelvic tumours: a prospective, randomised, multicentre trial. Dutch Deep Hyperthermia Group","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 10791373 and published in The Lancet; the citing page links this DOI, which is how the record was matched.","summary":"Background: Local-control rates after radiotherapy for locally advanced tumours of the bladder, cervix, and rectum are disappointing. We investigated the effect of adding hyperthermia to standard radiotherapy.\n\nMethods: The study was a prospective, randomised, multicentre trial. 358 patients were enrolled from 1990 to 1996, in cancer centres in the Netherlands, who had bladder cancer stages T2, T3, or T4, NO, MO, cervical cancer stages IIB, IIIB, or IV, or rectal cancer stage M0-1 were assessed. Patients were randomly assigned radiotherapy (median total dose 65 Gy) alone (n=176) or radiotherapy plus hyperthermia (n=182). Our primary endpoints were complete response and duration of local control. We did the analysis by intention to treat.\n\nFindings: Complete-response rates were 39% after radiotherapy and 55% after radiotherapy plus hyperthermia (p<0.001). The duration of local control was significantly longer with radiotherapy plus hyperthermia than with radiotherapy alone (p=0.04). Treatment effect did not differ significantly by tumour site, but the addition of hyperthermia seemed to be most important for cervical cancer, for which the complete-response rate with radiotherapy plus hyperthermia was 83% compared with 57% after radiotherapy alone (p=0.003). 3-year overall survival was 27% in the radiotherapy group and 51% in the radiotherapy plus hyperthermia group. For bladder cancer, an initial difference in local control disappeared during follow-up.\n\nInterpretation: Hyperthermia in addition to standard radiotherapy may be especially useful in locally advanced cervical tumours. Studies of larger numbers of patients are needed for other pelvic tumour sites before practical recommendations can be made.\n\nIndexed on Europe PMC as PubMed record 10791373 (DOI 10.1016/s0140-6736(00)02059-6). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet 2000","url":"https://doi.org/10.1016/s0140-6736(00)02059-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/10791373/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/10791373"}],"tags":["europepmc-ingest"],"related":["hyperthermia-systems"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2000,"doi":"10.1016/s0140-6736(00)02059-6","pmid":"10791373","authors":"van der Zee J, González González D, van Rhoon GC, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-sigurjonsdottir-sp142-22c3-tnbc-bcr-2023","kind":"paper","name":"Comparison of SP142 and 22C3 PD-L1 assays in a population-based cohort of triple-negative breast cancer patients in the context of their clinically established scoring algorithms","aka":[],"tldr":"In 232 Swedish early triple-negative cancers, half were PD-L1-positive by the atezolizumab test (SP142 IC 1%) but only 27% by the pembrolizumab threshold (22C3 CPS 10), and the two tests picked partly different patients.","summary":"PD-L1 by SP142 immune-cell score and 22C3 combined positive score was compared in 232 early-stage TNBC patients from the population-based SCAN-B cohort. Positivity was 50.9% for SP142 IC 1% or more, 27.2% for 22C3 CPS 10 or more, 53.9% for CPS 1 or more and 41.8% for 22C3 IC 1% or more. Concordance between SP142 IC-positive and the three 22C3 scores was 73.7% (kappa 0.48), 81.5% (0.63) and 86.6% (0.73). CD274 mRNA correlated with every scoring (Spearman 0.59 to 0.62). PD-L1 positivity and TILs were favourable prognostic factors in chemotherapy-treated patients, strongest for CPS 10 and distant relapse-free interval (HR 0.18), but PD-L1 was not independent of TILs.","asOf":"2026-09-24","links":[{"label":"Sigurjonsdottir et al., Breast Cancer Res 2023: SP142 versus 22C3 in 232 population-based early TNBCs (SCAN-B)","url":"https://doi.org/10.1186/s13058-023-01724-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37817263/"}],"tags":[],"related":["pd-l1-ic-score","pd-l1-cps"],"cancers":["tnbc","tnbc-early"],"sections":[],"technologies":[],"targets":["pdl1"],"drugs":["ventana-pd-l1-sp142","dako-pd-l1-22c3-pharmdx"],"companies":[],"institutions":["lund-skane"],"pathways":[],"terms":["cps","tils","ihc"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["breast-cancer-research"],"dependsOn":[],"notes":[],"journal":"Breast Cancer Research","year":2023,"doi":"10.1186/s13058-023-01724-2","pmid":"37817263","authors":"Sigurjonsdottir G, De Marchi T, Ehinger A, et al.","paperType":"observational","findings":["SP142 IC 1% or more 50.9%; 22C3 CPS 10 or more 27.2%; CPS 1 or more 53.9%.","SP142 versus CPS 10 agreement weak (kappa 0.48).","PD-L1 was prognostic but not independent of tumour-infiltrating lymphocytes."],"whatItMeans":"This is the population-based prevalence for the two label thresholds in early TNBC, and it shows the KEYNOTE-355 CPS 10 gate would admit only about a quarter of unselected patients.","caveats":["Early-stage surgical specimens; the trials scored metastatic biopsies.","Single Swedish region."],"changedPractice":false,"participants":232},{"id":"paper-ebctcg-polychemotherapy-regimens-meta-analysis-lancet-2012","kind":"paper","name":"Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials","aka":[],"tldr":"The Oxford overview of 123 trials and 100,000 women showing that anthracycline and taxane chemotherapy cuts breast cancer deaths by about a third, largely regardless of age, nodes, size, grade or hormone receptor status; it is the foundation triple-negative chemotherapy rests on.","summary":"The Early Breast Cancer Trialists' Collaborative Group performed individual patient data meta-analyses of trials comparing taxane-plus-anthracycline regimens with the same or more non-taxane chemotherapy (44,000 women), one anthracycline regimen with another (7,000) or with CMF (18,000), and polychemotherapy with none (32,000). Adding four separate taxane cycles to a fixed anthracycline regimen reduced breast cancer mortality (rate ratio 0.86, standard error 0.04, 2p=0.0005); when controls received extra non-taxane cycles instead there was no significant difference (0.94). Standard 4AC and standard CMF were equivalent (0.98), but higher-cumulative-dose anthracycline regimens (CAF, CEF) beat CMF (0.78, 2p=0.0004). Against no chemotherapy, CAF (0.64), standard 4AC (0.78) and CMF (0.76) all reduced mortality. Proportional reductions were little affected by age, nodal status, tumour diameter, differentiation, oestrogen receptor status or tamoxifen use; some taxane-plus-anthracycline or higher-dose anthracycline regimens reduced breast cancer mortality by about one third, and ten-year overall mortality differences paralleled this despite toxicity.","asOf":"2026-09-24","links":[{"label":"Lancet 2012","url":"https://doi.org/10.1016/S0140-6736(11)61625-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22152853/"}],"tags":["tnbc-evidence"],"related":[],"cancers":["tnbc","breast-hr-positive"],"sections":[],"technologies":[],"targets":[],"drugs":["doxorubicin","cyclophosphamide","paclitaxel"],"companies":[],"institutions":["cruk"],"pathways":[],"terms":["anthracycline","taxane","neoadjuvant-adjuvant"],"trials":["scarlet-s2212"],"people":["richard-peto"],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2012,"doi":"10.1016/S0140-6736(11)61625-5","pmid":"22152853","authors":"Early Breast Cancer Trialists' Collaborative Group (EBCTCG), Peto R, Davies C, et al.","paperType":"meta-analysis","findings":["Adding a taxane to a fixed anthracycline regimen: breast cancer mortality rate ratio 0.86 (SE 0.04, 2p=0.0005).","Higher-dose anthracycline regimens (CAF, CEF) vs CMF: 0.78 (2p=0.0004); CAF vs no chemotherapy 0.64.","About one-third reduction in breast cancer mortality, largely independent of age, nodes, size, grade or oestrogen receptor status."],"whatItMeans":"Chemotherapy works in receptor-negative disease at least as well as in receptor-positive disease in proportional terms, and because triple-negative absolute risk is high the absolute gain is large; this is why anthracycline and taxane backbone survived into KEYNOTE-522 and why SCARLET now asks whether the anthracycline can go.","caveats":["Trials predate receptor-defined subgroups; triple-negative status was not recorded.","The overview cannot say which patients need which regimen, a gap it names itself."],"changedPractice":true,"participants":100000},{"id":"paper-nct04765059-esmo-open-2025","kind":"paper","name":"COMPEL: osimertinib plus platinum-based chemotherapy in patients with EGFR-mutated advanced NSCLC and progression on first-line osimertinib","aka":[],"tldr":"Published report from the COMPEL trial registered as NCT04765059, in ESMO Open (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: COMPEL (NCT04765059) was a global, randomized, double-blind study that evaluated osimertinib plus chemotherapy versus placebo plus chemotherapy in patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) following non-central nervous system (CNS) progression on first-line osimertinib.\n\nPatients and methods: Patients were randomly assigned to receive osimertinib 80 mg, or placebo, once daily (o.d.) in combination with chemotherapy [cisplatin 75 mg/m 2 or carboplatin area under the curve 5 plus pemetrexed 500 mg/m 2 every 3 weeks (q3w) for four cycles], followed by osimertinib 80 mg, or placebo, o.d. in combination with maintenance pemetrexed (500 mg/m 2 q3w) until progression. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included CNS PFS according to CNS metastases status at baseline and overall survival (OS).\n\nResults: Ninety-eight patients were randomly assigned (49 per arm). Median PFS in all patients was 8.4 months [95% confidence interval (CI) 5.7-11.8 months] with osimertinib plus chemotherapy versus 4.4 months (95% CI 3.5-5.6 months) with placebo plus chemotherapy [hazard ratio (HR) 0.43, 95% CI 0.27-0.70]. CNS PFS was longer with osimertinib plus chemotherapy versus placebo plus chemotherapy (HR 0.56, 95% CI 0.27-1.13) in patients without baseline CNS metastases (n = 75). Median OS in all patients was 15.9 months (95% CI 12.4-20.8 months) with osimertinib plus chemotherapy versus 9.8 months (95% CI 8.4-17.2 months) with placebo plus chemotherapy (HR 0.71, 95% CI 0.42-1.23). Grade ≥3 adverse events occurred more frequently with osimertinib plus chemotherapy (63%) than placebo plus chemotherapy (46%).\n\nConclusions: In patients with non-CNS progression on first-line osimertinib, osimertinib plus chemotherapy was associated with improved PFS and longer OS compared with placebo plus chemotherapy. These findings support osimertinib as a backbone treatment for EGFR-mutated advanced NSCLC through lines of therapy.\n\nIndexed on Europe PMC as PubMed record 41139117 (DOI 10.1016/j.esmoop.2025.105807). Its abstract cites the registry id NCT04765059, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"ESMO Open 2025","url":"https://doi.org/10.1016/j.esmoop.2025.105807"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41139117/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41139117"},{"label":"ClinicalTrials.gov NCT04765059","url":"https://clinicaltrials.gov/study/NCT04765059"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04765059"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["esmo-open"],"dependsOn":[],"notes":[],"journal":"ESMO Open","year":2025,"doi":"10.1016/j.esmoop.2025.105807","pmid":"41139117","authors":"Peled N, Tufman A, Sequist LV, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04765059 with the most citations, so it is the natural first reading for anyone following the COMPEL trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-barchuk-registry-completeness-bmc-cancer-2023","kind":"paper","name":"Completeness of regional cancer registry data in north-west Russia, 2008 to 2017","aka":[],"tldr":"Eight of ten north-western Russian cancer registries were judged complete enough for research, but Saint Petersburg, the largest, fell below 90 per cent, and about a tenth of its cases never reached the national annual report.","summary":"The same ten population-based registries, covering 13 million people, were assessed for completeness and timeliness using historic-data methods against European reference rates, mortality-to-incidence ratios and death-certificate methods, with the Lincoln-Petersen estimator and the Ajiki formula used to estimate unregistered cases.\n\nIncidence trends were stable except in Leningrad oblast, with a slight fall in older age groups against European reference rates for several sites. Completeness was above 90 per cent in most regions, low or implausible in Leningrad oblast and below 90 per cent in Saint Petersburg. The national annual report for 2008 to 2017 omitted about 10 per cent of the cases later held in the Saint Petersburg registry database; the same gap was below 3 per cent for Arkhangelsk, Murmansk, Novgorod and Vologda oblasts and the Republic of Karelia.","asOf":"2026-09-25","links":[{"label":"BMC Cancer 2023","url":"https://doi.org/10.1186/s12885-023-11492-z"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37853404/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37853404"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["petrov-institute"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["bmc-cancer"],"dependsOn":[],"notes":[],"journal":"BMC cancer","year":2023,"doi":"10.1186/s12885-023-11492-z","pmid":"37853404","authors":"Barchuk A, Tursun-Zade R, Nazarova E, et al.","paperType":"methods","findings":["Eight of ten registries collected data with an acceptable degree of completeness.","Saint Petersburg, with about 5 million people, was below 90 per cent complete; Leningrad oblast produced low or implausible estimates.","The national annual report missed about 10 per cent of Saint Petersburg cases later held in the registry database, against under 3 per cent for five other regions."],"whatItMeans":"The national figures published each year are the sum of regional reporting forms, not of the registry databases, and the two differ. Anyone comparing Russian incidence with another country's should know which of the two they are reading.","caveats":["Confined to the Northwestern Federal District.","Completeness estimators rely on European reference rates that may not fit the Russian population."]},{"id":"paper-pritchard-complex-msh2-msh6-hypermutated-prostate-nat-commun-2014","kind":"paper","name":"Complex MSH2 and MSH6 mutations in hypermutated microsatellite unstable advanced prostate cancer","aka":[],"tldr":"The prostate cancers with a broken proofreading system usually break it by tearing the gene apart rather than by switching it off, which is the opposite of what happens in bowel cancer.","summary":"A hypermutated subtype of advanced prostate cancer had been described but its prevalence and mechanism were not characterised. Of 60 advanced prostate cancers examined, 7, 12%, were hypermutated, and all of the hypermutated cancers had mismatch repair gene mutations and microsatellite instability. The mutations were frequently complex MSH2 or MSH6 structural rearrangements rather than MLH1 epigenetic silencing, identifying both parallels and differences with the mechanisms of hypermutation in other microsatellite instability-associated cancers.","asOf":"2026-09-25","links":[{"label":"Pritchard et al., Nat Commun 2014: complex MSH2 and MSH6 rearrangements in hypermutated microsatellite-unstable advanced prostate cancer (60 cancers)","url":"https://doi.org/10.1038/ncomms5988"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25255306/"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["wes-wgs","cgp"],"targets":["msh2","msh6","mmr"],"drugs":[],"companies":[],"institutions":[],"pathways":["mismatch-repair-msi","ddr"],"terms":["msi","lynch-syndrome","tmb"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-communications"],"dependsOn":[],"notes":[],"journal":"Nature Communications","year":2014,"doi":"10.1038/ncomms5988","pmid":"25255306","authors":"Pritchard CC, Morrissey C, Kumar A, et al.","paperType":"basic","findings":["Seven of 60 advanced prostate cancers hypermutated, 12%.","All hypermutated cancers had mismatch repair gene mutations and microsatellite instability.","Complex MSH2 or MSH6 structural rearrangements rather than MLH1 promoter methylation."],"whatItMeans":"It matters for how the test is done. A mismatch repair assay designed around the colorectal mechanism, looking for MLH1 promoter methylation and simple mutations, can miss the prostate mechanism entirely, which is one reason microsatellite instability was under-recognised in this disease for so long.","caveats":["Sixty advanced cancers, so the 12% is imprecise and higher than the 3.1% found in a much larger prospectively sequenced series.","Rapid-autopsy and research material.","Structural rearrangements are hard to call on short-read panel data, so this mechanism is still under-detected."],"changedPractice":false,"participants":60},{"id":"paper-anderson-n-engl-j-med","kind":"paper","name":"Compliance with results reporting at ClinicalTrials.gov","aka":[],"tldr":"Paper cited by one bottleneck page and 14 idea pages, indexed on Europe PMC as PubMed record 25760355 and published in New England Journal of Medicine; the citing pages link this DOI, which is how the record was matched.","summary":"Background: The Food and Drug Administration Amendments Act (FDAAA) mandates timely reporting of results of applicable clinical trials to ClinicalTrials.gov. We characterized the proportion of applicable clinical trials with publicly available results and determined independent factors associated with the reporting of results.\n\nMethods: Using an algorithm based on input from the National Library of Medicine, we identified trials that were likely to be subject to FDAAA provisions (highly likely applicable clinical trials, or HLACTs) from 2008 through 2013. We determined the proportion of HLACTs that reported results within the 12-month interval mandated by the FDAAA or at any time during the 5-year study period. We used regression models to examine characteristics associated with reporting at 12 months and throughout the 5-year study period.\n\nResults: From all the trials at ClinicalTrials.gov, we identified 13,327 HLACTs that were terminated or completed from January 1, 2008, through August 31, 2012. Of these trials, 77.4% were classified as drug trials. A total of 36.9% of the trials were phase 2 studies, and 23.4% were phase 3 studies; 65.6% were funded by industry. Only 13.4% of trials reported summary results within 12 months after trial completion, whereas 38.3% reported results at any time up to September 27, 2013. Timely reporting was independently associated with factors such as FDA oversight, a later trial phase, and industry funding. A sample review suggested that 45% of industry-funded trials were not required to report results, as compared with 6% of trials funded by the National Institutes of Health (NIH) and 9% of trials that were funded by other government or academic institutions.\n\nConclusions: Despite ethical and legal obligations to disclose findings promptly, most HLACTs did not report results to ClinicalTrials.gov in a timely fashion during the study period. Industry-funded trials adhered to legal obligations more often than did trials funded by the NIH or other government or academic institutions. (Funded by the Clinical Trials Transformation Initiative and the NIH.).\n\nIndexed on Europe PMC as PubMed record 25760355 (DOI 10.1056/nejmsa1409364). Matched by DOI alone: one bottleneck page and 14 idea pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2015","url":"https://doi.org/10.1056/nejmsa1409364"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25760355/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25760355"}],"tags":["europepmc-ingest"],"related":["b-negative-results","idea-tr2-negative-results-journal","idea-moon-negative-results-ledger","idea-tr2-failure-taxonomy","idea-tr2-reversal-registry","idea-tr2-preclinical-negative-registry","idea-tr2-negative-plenaries","idea-tr2-null-result-reporting","idea-tr2-material-failure-disclosure","idea-tr2-irb-results-gate","idea-tr2-termination-reports","idea-tr2-off-label-outcome-registry","idea-tr2-failed-trial-biobank","idea-tr2-model-report-cards","idea-tr2-writeup-grants"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2015,"doi":"10.1056/nejmsa1409364","pmid":"25760355","authors":"Anderson ML, Chiswell K, Peterson ED, et al.","paperType":"observational","findings":[],"whatItMeans":"One bottleneck page and 14 idea pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-kahles-cancer-cell","kind":"paper","name":"Comprehensive Analysis of Alternative Splicing Across Tumors from 8,705 Patients","aka":[],"tldr":"Paper cited by one idea page, indexed on Europe PMC as PubMed record 30078747 and published in Cancer Cell; the citing page links this DOI, which is how the record was matched.","summary":"Our comprehensive analysis of alternative splicing across 32 The Cancer Genome Atlas cancer types from 8,705 patients detects alternative splicing events and tumor variants by reanalyzing RNA and whole-exome sequencing data. Tumors have up to 30% more alternative splicing events than normal samples. Association analysis of somatic variants with alternative splicing events confirmed known trans associations with variants in SF3B1 and U2AF1 and identified additional trans-acting variants (e.g., TADA1, PPP2R1A). Many tumors have thousands of alternative splicing events not detectable in normal samples; on average, we identified ≈930 exon-exon junctions (\"neojunctions\") in tumors not typically found in GTEx normals. From Clinical Proteomic Tumor Analysis Consortium data available for breast and ovarian tumor samples, we confirmed ≈1.7 neojunction- and ≈0.6 single nucleotide variant-derived peptides per tumor sample that are also predicted major histocompatibility complex-I binders (\"putative neoantigens\").\n\nIndexed on Europe PMC as PubMed record 30078747 (DOI 10.1016/j.ccell.2018.07.001). Matched by DOI alone: one idea page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer Cell 2018","url":"https://doi.org/10.1016/j.ccell.2018.07.001"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30078747/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30078747"}],"tags":["europepmc-ingest"],"related":["idea-splice-neoantigens"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-cell"],"dependsOn":[],"notes":[],"journal":"Cancer Cell","year":2018,"doi":"10.1016/j.ccell.2018.07.001","pmid":"30078747","authors":"Kahles A, Lehmann KV, Toussaint NC, et al.","paperType":"observational","findings":[],"whatItMeans":"One idea page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-cortes-ciriano-nat-genet","kind":"paper","name":"Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 32025003 and published in Nature Genetics; the citing page links this DOI, which is how the record was matched.","summary":"Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer.\n\nIndexed on Europe PMC as PubMed record 32025003 (DOI 10.1038/s41588-019-0576-7). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Genet 2020","url":"https://doi.org/10.1038/s41588-019-0576-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32025003/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32025003"}],"tags":["europepmc-ingest"],"related":["aneuploidy-theory-of-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":2020,"doi":"10.1038/s41588-019-0576-7","pmid":"32025003","authors":"Cortés-Ciriano I, Lee JJ, Xi R, et al.","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-luchini-msi-dmmr-pancreatic-systematic-review-gut-2021","kind":"paper","name":"Comprehensive characterisation of pancreatic ductal adenocarcinoma with microsatellite instability: histology, molecular pathology and clinical implications","aka":[],"tldr":"Pooling 34 studies and 8,323 patients, this review put mismatch repair deficient pancreatic cancer at about 1 to 2%, typically with medullary or colloid appearance and without the usual KRAS and TP53 mutations, and recommended testing those histologies.","summary":"PubMed, SCOPUS and Embase were searched to November 2019 for MSI or mismatch repair deficiency in pancreatic ductal adenocarcinoma; 34 studies with 8,323 patients were included and compared with SEER and TCGA references. MSI/dMMR had a very low prevalence, around 1 to 2%, and was strongly associated with medullary and mucinous/colloid histology and with a KRAS/TP53 wild-type background with commoner JAK gene mutations; survival data were unclear. The authors recommend routine testing of medullary or colloid tumours by immunohistochemistry followed by MSI PCR where doubtful, and next-generation sequencing where tissue is limited or profiling is being done anyway.","asOf":"2026-09-24","links":[{"label":"Luchini et al., Gut 2021: systematic review of mismatch repair deficient pancreatic cancer (34 studies, 8,323 patients)","url":"https://doi.org/10.1136/gutjnl-2020-320726"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32350089/"}],"tags":[],"related":["msi-high","dmmr-ihc"],"cancers":["pancreatic","msi-high-pdac"],"sections":[],"technologies":["msi-mmr-testing"],"targets":["mmr"],"drugs":[],"companies":[],"institutions":[],"pathways":["mismatch-repair-msi"],"terms":["msi"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["gut"],"dependsOn":[],"notes":[],"journal":"Gut","year":2021,"doi":"10.1136/gutjnl-2020-320726","pmid":"32350089","authors":"Luchini C, Brosens LAA, Wood LD, et al.","paperType":"meta-analysis","findings":["MSI/dMMR prevalence about 1 to 2%.","Associated with medullary and colloid histology and KRAS/TP53 wild-type tumours.","Test by immunohistochemistry, then PCR where doubtful, or on a sequencing panel."],"whatItMeans":"It tells the pathologist which pancreatic cancers to test for the one immunotherapy-responsive subgroup and how.","caveats":["Heterogeneous assays across 34 studies.","Survival of MSI pancreatic cancer remains unclear."],"changedPractice":false,"participants":8323},{"id":"paper-burstein-tnbc-genomic-subtypes-ccr-2015","kind":"paper","name":"Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer","aka":[],"tldr":"A 2015 Baylor study of 198 triple-negative tumours that found four stable subtypes, luminal androgen receptor, mesenchymal, basal-like immune-suppressed and basal-like immune-activated, with the immune-activated group faring best and the immune-suppressed worst.","summary":"Burstein, Tsimelzon, Poage, Covington and colleagues profiled RNA and DNA in 198 triple-negative tumours (oestrogen receptor negativity defined as Allred score 2 or less, more than 50 percent cellularity; discovery 84, validation 114) collected at Baylor College of Medicine, with an external set of seven public studies for confirmation. Four subtypes were identified and confirmed: luminal androgen receptor (LAR), mesenchymal (MES), basal-like immunosuppressed (BLIS) and basal-like immune-activated (BLIA). Prognosis was worst for BLIS and best for BLIA for both disease-free survival (p=0.042 and 0.041) and disease-specific survival (p=0.039 and 0.029). Copy number analysis separated LAR from the other three and suggested amplification drives expression in some cases (FGFR2 in BLIS). Candidate subtype-specific targets were androgen receptor and MUC1 (LAR), PDGF receptor A and c-Kit (MES), VTCN1 (BLIS) and Stat molecules and cytokines (BLIA).","asOf":"2026-09-24","links":[{"label":"Clin Cancer Res 2015","url":"https://doi.org/10.1158/1078-0432.CCR-14-0432"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25208879/"}],"tags":["tnbc-evidence"],"related":["paper-lehmann-tnbc-subtypes-jci-2011"],"cancers":["tnbc"],"sections":[],"technologies":["rna-seq"],"targets":["androgen-receptor","b7h4","fgfr2","pdgfrb"],"drugs":[],"companies":[],"institutions":["baylor-duncan"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity","b-immunotherapy-response"],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2015,"doi":"10.1158/1078-0432.CCR-14-0432","pmid":"25208879","authors":"Burstein MD, Tsimelzon A, Poage GM, et al.","paperType":"translational","findings":["Four subtypes confirmed in 198 tumours and seven external studies: LAR, MES, BLIS, BLIA.","Disease-free survival worst for BLIS (p=0.042) and best for BLIA (p=0.041); disease-specific survival likewise (p=0.039 and 0.029).","Candidate targets: androgen receptor and MUC1; PDGFRA and c-Kit; VTCN1; Stat signalling."],"whatItMeans":"Independently arrived at the same partition as the refined Lehmann scheme and added the insight that immune activation within basal-like tumours separates longer from shorter survival, the biology immunotherapy would exploit three years later.","caveats":["Single-institution discovery set.","Candidate targets are computational; VTCN1 (B7-H4) antibody-drug conjugates are only now in early trials."],"changedPractice":false,"participants":198},{"id":"paper-tcga-lung-squamous-nature-2012","kind":"paper","name":"Comprehensive genomic characterization of squamous cell lung cancers","aka":[],"tldr":"The first complete genomic reading of 178 squamous lung cancers found a chaotic genome with almost universal loss of the p53 gene, and identified a possible drug target in most tumours in a cancer that until then had none.","summary":"One hundred and seventy-eight lung squamous cell carcinomas were profiled across platforms. The tumour type is characterised by complex genomic alterations, with a mean of 360 exonic mutations, 165 genomic rearrangements and 323 segments of copy-number alteration per tumour. Recurrent mutations were found in 11 genes, including TP53 in nearly all specimens. Previously unreported loss-of-function mutations were seen in the class I gene HLA-A. Significantly altered pathways included NFE2L2 and KEAP1 in 34% of tumours, squamous differentiation genes in 44%, phosphatidylinositol-3-kinase pathway genes in 47%, and CDKN2A and RB1 in 72%. A potential therapeutic target was identified in most tumours.","asOf":"2026-09-25","links":[{"label":"Cancer Genome Atlas Research Network, Nature 2012: comprehensive genomic characterisation of 178 squamous cell lung cancers","url":"https://doi.org/10.1038/nature11404"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22960745/"},{"label":"cBioPortal study lusc_tcga_pub (TCGA, Nature 2012; the 178 squamous cell lung cancers of the landmark paper)","url":"https://www.cbioportal.org/study/summary?id=lusc_tcga_pub"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":["wes-wgs","rna-seq","methylation-profiling"],"targets":["tp53","cdkn2a","rb1","nfe2l2","keap1","cul3","pik3ca","pten","sox2","tp63","fgfr1","hla-a","notch1"],"drugs":[],"companies":[],"institutions":["broad-institute"],"pathways":["nsclc-signalling","keap1-nrf2","p53-cell-cycle","pi3k-akt-mtor","chromosomal-instability","antigen-presentation-immunoediting"],"terms":["gene-amplification","copy-number-variation-term","driver-mutation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2012,"doi":"10.1038/nature11404","pmid":"22960745","authors":"Cancer Genome Atlas Research Network.","paperType":"basic","findings":["TP53 mutated in nearly all specimens; a mean of 360 exonic mutations and 323 copy-number segments per tumour.","NFE2L2 and KEAP1 pathway altered in 34%, squamous differentiation genes in 44%, PI3K pathway in 47%, CDKN2A and RB1 in 72%.","Loss-of-function mutations in HLA-A, a route to immune escape.","A candidate therapeutic target present in most tumours."],"whatItMeans":"It explained why squamous lung cancer has no equivalent of an EGFR inhibitor: its commonest alterations are a transcription factor amplicon, a tumour suppressor deletion and an antioxidant switch, none of which is a drug target in the way a mutant kinase is.","caveats":["The candidate targets identified here, including FGFR1 and the PI3K pathway, have largely failed in trials since.","A resected cohort, so stage IV biology is not represented.","178 tumours, so rarer events are missed."],"changedPractice":false,"participants":178},{"id":"paper-george-sclc-genomic-profiles-nature-2015","kind":"paper","name":"Comprehensive genomic profiles of small cell lung cancer","aka":[],"tldr":"Sequencing 110 small-cell lung cancers found that losing both copies of TP53 and RB1 is obligatory. That is a loss of two brakes, not a gain of a target, which is why the disease has been so hard to drug.","summary":"George, Lim, Jang and colleagues, with Thomas as senior author, sequenced the genomes of 110 small-cell lung cancers. Bi-allelic inactivation of TP53 and RB1 was present in nearly all of them, sometimes through complex genomic rearrangements; two tumours with wild-type RB1 showed chromothripsis producing cyclin D1 overexpression, an alternative route to the same deregulation.\n\nThe paper explains the therapeutic history of the disease. Small-cell lung cancer is defined by the loss of two tumour suppressors, and a loss cannot be inhibited, so forty years of kinase inhibitor development passed it by. The NOTCH finding, inactivating mutations in a quarter of tumours with Notch activation suppressing tumour growth in mouse models, is the one actionable lead the study produced, and it led to DLL3.","asOf":"2026-09-25","links":[{"label":"Nature 2015","url":"https://doi.org/10.1038/nature14664"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26168399/"},{"label":"cBioPortal study sclc_ucologne_2015 (University of Cologne, Nature 2015; 120 small-cell lung cancers, no copy-number profile deposited)","url":"https://www.cbioportal.org/study/summary?id=sclc_ucologne_2015"}],"tags":["lung-evidence"],"related":["paper-rudin-sclc-molecular-subtypes-nat-rev-cancer-2019","paper-dll3-sclc-clin-cancer-res-2019","paper-dellphi-301-nejm-2023"],"cancers":["lung-cancer","sclc"],"sections":["drug-discovery","diagnostics"],"technologies":["wes-wgs","ngs"],"targets":["tp53","rb1","notch1","dll3","kmt2d","crebbp","ep300","pten","mycl","myc-gene"],"drugs":[],"companies":[],"institutions":[],"pathways":["notch","cell-cycle","sclc-signalling","p53-cell-cycle","lineage-plasticity-neuroendocrine","chromosomal-instability"],"terms":["driver-mutation","somatic-mutations-wxs-wgs","copy-number-variation-term"],"trials":[],"people":["roman-thomas"],"bottlenecks":["b-undruggable-targets","b-rare-cancers","b-preclinical-models"],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2015,"doi":"10.1038/nature14664","pmid":"26168399","authors":"George J, Lim JS, Jang SJ, et al.","paperType":"basic","findings":["Bi-allelic inactivation of TP53 and RB1 in nearly all 110 tumours, sometimes by complex genomic rearrangements; loss of both is obligatory in small-cell lung cancer.","Two tumours with wild-type RB1 showed chromothripsis leading to overexpression of cyclin D1, an alternative mechanism of Rb1 deregulation.","Somatic genomic rearrangements of TP73 creating an oncogenic TP73 delta exon 2/3 were discovered.","Inactivating mutations in NOTCH family genes in 25 percent of tumours; activating Notch signalling in a mouse model strikingly reduced tumour number and extended survival, and abrogated neuroendocrine gene expression.","Kinase gene mutations were present in rare cases, offering a possible therapeutic opportunity for individual patients."],"whatItMeans":"Why small-cell lung cancer has no targeted therapy in the conventional sense: it is built from the loss of TP53 and RB1, and the drugs that transformed non-small-cell disease inhibit gains rather than restore losses. The NOTCH result pointed at DLL3 and, eventually, at tarlatamab.","caveats":["110 tumours, largely surgical specimens from a disease that is rarely operated on, so the sample is not representative of the extensive-stage majority.","Genomic classification does not map cleanly onto the transcription-factor subtypes proposed four years later.","No treatment has yet been assigned on the basis of a small-cell genome in routine care."],"changedPractice":false,"participants":110},{"id":"paper-tcga-gastric-nature-2014","kind":"paper","name":"Comprehensive molecular characterisation of gastric adenocarcinoma (The Cancer Genome Atlas)","aka":[],"tldr":"Sequencing 295 stomach cancers divided them into four molecular groups, Epstein-Barr virus-positive, microsatellite unstable, genomically stable and chromosomally unstable, each with distinct drivers and potential therapies.","summary":"Integrated genomic analysis by The Cancer Genome Atlas of 295 primary gastric adenocarcinomas identifying four subtypes: Epstein-Barr virus-positive (PIK3CA mutations, PD-L1/2 amplification), microsatellite unstable (hypermutation), genomically stable (diffuse histology, RHOA and CLDN18-ARHGAP fusions) and chromosomal instability (TP53 mutation, receptor tyrosine kinase amplifications).","asOf":"2026-09-17","links":[{"label":"Nature 2014","url":"https://doi.org/10.1038/nature13480"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25079317/"}],"tags":[],"related":[],"cancers":["gastric-msi-high"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2014,"doi":"10.1038/nature13480","pmid":"25079317","authors":"Cancer Genome Atlas Research Network.","paperType":"translational","findings":["Four molecular subtypes with distinct genomic features.","Microsatellite-unstable tumours in about 22 percent and Epstein-Barr virus-positive in about 9 percent of the cohort."],"whatItMeans":"The immunotherapy sensitivity of microsatellite-unstable and Epstein-Barr virus-positive gastric cancer and the claudin 18.2 and HER2 targets map onto these subtypes.","caveats":["Subtypes are not yet used directly to choose treatment beyond microsatellite status and HER2."],"changedPractice":true,"participants":295},{"id":"paper-tcga-papillary-rcc-nejm-2016","kind":"paper","name":"Comprehensive molecular characterisation of papillary renal cell carcinoma (The Cancer Genome Atlas)","aka":[],"tldr":"Genomic analysis of 161 papillary kidney cancers showed that type 1 tumours are driven by MET alterations while type 2 tumours are a mixture of distinct diseases including CDKN2A-silenced, SETD2-mutated, fumarate hydratase-deficient and a CpG island methylator phenotype with very short survival.","summary":"Integrated genomic study by The Cancer Genome Atlas of 161 papillary renal cell carcinomas showing MET alterations in 81 percent of type 1 tumours, and in type 2 tumours CDKN2A loss, SETD2 and other chromatin modifier mutations, TFE3 fusions, NRF2-ARE pathway activation and a CpG island methylator phenotype associated with fumarate hydratase deficiency and the worst outcomes.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2016","url":"https://doi.org/10.1056/NEJMoa1505917"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26536169/"}],"tags":[],"related":[],"cancers":["papillary-rcc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2016,"doi":"10.1056/NEJMoa1505917","pmid":"26536169","authors":"Cancer Genome Atlas Research Network, Linehan WM, Spellman PT, et al.","paperType":"translational","findings":["MET alterations in 81 percent of type 1 tumours.","CpG island methylator phenotype subgroup with fumarate hydratase loss and short survival among type 2 tumours."],"whatItMeans":"Papillary renal cell carcinoma is several diseases; the finding of MET dependence in type 1 tumours underpins the use of cabozantinib and savolitinib, and the 2022 WHO classification dropped the type 1 and 2 split in favour of molecular entities.","caveats":["Treatment-naive primary tumours; metastatic disease may differ."],"changedPractice":true,"participants":161},{"id":"paper-giraldo-gallbladder-msk-impact-ccr-2022","kind":"paper","name":"Comprehensive molecular characterization of gallbladder carcinoma and potential targets for intervention","aka":[],"tldr":"The largest sequencing study of gallbladder cancer at one centre, 244 samples on a 505-gene panel, found TP53 in 63%, HER2 changes in 15% and something actionable in a third of patients; SMAD4 and STK11 marked shorter survival.","summary":"244 gallbladder carcinoma samples (57% primary tumours and 43% metastases) from 233 patients were analysed with the MSK-IMPACT targeted panel of 505 cancer-associated genes; 85% were adenocarcinomas, 10% carcinomas with squamous differentiation and 5% neuroendocrine carcinomas. The most common oncogenic alterations were in the cell cycle (TP53 63%, CDKN2A 21%) and RTK-RAS pathways (ERBB2 15%, KRAS 11%). No recurrent structural variants were identified and the molecular landscape of primaries and metastases did not differ.\n\nVariants in SMAD4 and STK11 were independently associated with reduced survival in metastatic disease. Alterations considered clinically actionable in gallbladder or other solid tumours (NTRK1 fusions, oncogenic variants in ERBB2, PIK3CA or BRCA1/2) were identified in 35% of patients, and 18% of patients with metastatic disease were treated off-label or enrolled in a trial on the basis of the findings.","asOf":"2026-09-24","links":[{"label":"Giraldo et al., Clin Cancer Res 2022: MSK-IMPACT profiling of 244 gallbladder carcinoma samples","url":"https://doi.org/10.1158/1078-0432.ccr-22-1954"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36228155/"},{"label":"cBioPortal study gbc_mskcc_2022 (Gallbladder Cancer, MSK 2022; 244 samples from 233 patients)","url":"https://www.cbioportal.org/study/summary?id=gbc_mskcc_2022"}],"tags":[],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":["tp53","cdkn2a","her2","kras","smad4","stk11","ntrk","pik3ca","brca"],"drugs":[],"companies":[],"institutions":["mskcc"],"pathways":[],"terms":[],"trials":[],"people":["ghassan-abou-alfa"],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2022,"doi":"10.1158/1078-0432.ccr-22-1954","pmid":"36228155","authors":"Giraldo NA, Drill E, Satravada BA, et al.","paperType":"translational","findings":["TP53 63%, CDKN2A 21%, ERBB2 15%, KRAS 11% among 244 samples.","Clinically actionable alterations in 35% of patients; 18% of metastatic patients treated on them.","SMAD4 and STK11 variants independently predicted shorter survival in metastatic disease; primaries and metastases did not differ."],"whatItMeans":"The reference Western cohort for gallbladder cancer frequencies, deposited on cBioPortal as gbc_mskcc_2022, where the per-gene sample counts on OnCo were read. It supports panel testing at diagnosis: one patient in three has a targetable finding.","caveats":["Tertiary referral centre; metastatic and pretreated patients are over-represented.","Actionability was graded with the OncoKB database, which OnCo does not reproduce."],"changedPractice":false,"participants":233},{"id":"paper-tcga-colorectal-comprehensive-characterization-nature-2012","kind":"paper","name":"Comprehensive molecular characterization of human colon and rectal cancer","aka":[],"tldr":"The Cancer Genome Atlas read the DNA, copy number, methylation and gene activity of 276 bowel cancers, found that one in six carries an enormous number of mutations, and showed that once those are set aside colon and rectal cancers look the same.","summary":"A genome-scale analysis of 276 samples combined exome sequence, DNA copy number, promoter methylation, messenger RNA and microRNA expression, with low-coverage whole-genome sequencing in 97. Sixteen per cent of colorectal carcinomas were hypermutated: three-quarters of those had the expected high microsatellite instability, usually with hypermethylation and MLH1 silencing, and one-quarter had somatic mismatch repair gene and polymerase epsilon (POLE) mutations. Excluding the hypermutated cancers, colon and rectum cancers had considerably similar patterns of genomic alteration. Twenty-four genes were significantly mutated: in addition to the expected APC, TP53, SMAD4, PIK3CA and KRAS, frequent mutations were found in ARID1A, SOX9 and FAM123B. Recurrent copy-number alterations included potentially drug-targetable amplification of ERBB2 and newly discovered amplification of IGF2; recurrent translocations included a fusion of NAV2 with the WNT pathway member TCF7L1. Integrative analysis suggested new markers of aggressive disease and an important role for MYC-directed transcriptional activation and repression.\n\nDeposited as coadread_tcga_pub (276 samples) and, re-analysed, as coadread_tcga_pan_can_atlas_2018 (594 samples) on cBioPortal.","asOf":"2026-09-24","links":[{"label":"Cancer Genome Atlas Network, Nature 2012: comprehensive molecular characterisation of 276 colon and rectal cancers","url":"https://doi.org/10.1038/nature11252"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22810696/"},{"label":"cBioPortal study coadread_tcga_pub (TCGA, Nature 2012; 276 samples, 224 sequenced, 257 with copy number)","url":"https://www.cbioportal.org/study/summary?id=coadread_tcga_pub"},{"label":"cBioPortal study coadread_tcga_pan_can_atlas_2018 (TCGA PanCancer Atlas colorectal; 594 samples, 534 sequenced, 592 with copy number)","url":"https://www.cbioportal.org/study/summary?id=coadread_tcga_pan_can_atlas_2018"},{"label":"Europe PMC full text (PMC3401966)","url":"https://europepmc.org/article/MED/22810696"}],"tags":[],"related":["paper-cms-guinney-nat-med-2015","paper-vogelstein-genetic-alterations-colorectal-tumor-development-nejm-1988"],"cancers":["colorectal","colon-cancer","rectal-cancer","msi-high-colorectal","her2-amplified-colorectal"],"sections":[],"technologies":["wes-wgs","rna-seq","methylation-profiling","ngs"],"targets":["apc","tp53","kras","smad4","pik3ca","arid1a","sox9","amer1","her2","myc-gene","myc"],"drugs":[],"companies":[],"institutions":["nci","broad-institute"],"pathways":["colorectal-cancer-signalling","wnt","chromosomal-instability","mismatch-repair-msi","myc","ras-mapk"],"terms":["msi","somatic-mutations-wxs-wgs","mmr"],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity"],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2012,"doi":"10.1038/nature11252","pmid":"22810696","authors":"Cancer Genome Atlas Network.","paperType":"translational","findings":["16% hypermutated: three-quarters MSI with MLH1 silencing, one-quarter somatic mismatch repair or POLE mutation.","24 significantly mutated genes, adding ARID1A, SOX9 and FAM123B to the known drivers.","ERBB2 and IGF2 amplification; WNT signalling altered in 93% of tumours."],"whatItMeans":"It is the reference description of the disease and the source of the hypermutated split that decides who gets immunotherapy; it also put HER2 on the colorectal map as a drug target.","caveats":["Surgical resections, so metastatic disease and its enrichment for microsatellite-stable tumours are under-represented.","The public deposit differs from the analysed set; the PanCancer Atlas re-analysis covers 594 samples.","Expression subtypes from this paper were superseded by the consensus molecular subtypes."],"changedPractice":false,"participants":276},{"id":"paper-tcga-breast-molecular-portraits-nature-2012","kind":"paper","name":"Comprehensive molecular portraits of human breast tumours","aka":[],"tldr":"The Cancer Genome Atlas profiled hundreds of breast cancers on six platforms and found four main classes; the basal-like class, which is 80% triple-negative, carries TP53 mutation in 80%, frequent PTEN and RB1 loss, MYC and EGFR gains and looks molecularly like high-grade serous ovarian cancer.","summary":"Primary breast cancers were analysed by copy-number arrays, DNA methylation, exome sequencing (510 with matched normals), mRNA arrays, microRNA sequencing and reverse-phase protein arrays. Only TP53, PIK3CA and GATA3 were mutated in more than 10% of all breast cancers. Basal-like tumours carried TP53 mutations in 80%, PIK3CA in 9%, PTEN mutation or loss in 35%, INPP4B loss in 30% and RB1 mutation or loss in 20%; PIK3CA (49%), KRAS (32%), BRAF (30%) and EGFR (23%) were amplified or gained but rarely mutated. Comparison with high-grade serous ovarian cancer showed many commonalities, indicating related aetiology and similar therapeutic opportunities. 80% of basal-like tumours were triple-negative.\n\nDeposited as brca_tcga_pub on cBioPortal, with the 2018 PanCancer Atlas re-analysis as brca_tcga_pan_can_atlas_2018.","asOf":"2026-09-24","links":[{"label":"Cancer Genome Atlas Network, Nature 2012: comprehensive molecular portraits of human breast tumours","url":"https://doi.org/10.1038/nature11412"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23000897/"},{"label":"cBioPortal study brca_tcga_pub (TCGA, Nature 2012; 825 samples, 123 recorded ER-, PR- and HER2-negative, 84 of them exome-sequenced)","url":"https://www.cbioportal.org/study/summary?id=brca_tcga_pub"},{"label":"cBioPortal study brca_tcga_pan_can_atlas_2018 (TCGA PanCancer Atlas; the same 123 triple-negative patients, all sequenced, 119 with copy number)","url":"https://www.cbioportal.org/study/summary?id=brca_tcga_pan_can_atlas_2018"}],"tags":[],"related":[],"cancers":["tnbc","breast-cancer","high-grade-serous-ovarian-cancer"],"sections":[],"technologies":[],"targets":["tp53","pik3ca","pten","rb1","egfr"],"drugs":[],"companies":[],"institutions":[],"pathways":["p53-cell-cycle","pi3k-akt-mtor","myc"],"terms":["pam50"],"trials":[],"people":["charles-perou"],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2012,"doi":"10.1038/nature11412","pmid":"23000897","authors":"Cancer Genome Atlas Network.","paperType":"translational","findings":["Basal-like: TP53 mutation 80%, PTEN mutation or loss 35%, INPP4B loss 30%, RB1 mutation or loss 20%, PIK3CA mutation 9%.","Amplification rather than mutation of PIK3CA (49%), KRAS (32%), BRAF (30%) and EGFR (23%) in basal-like tumours.","Basal-like breast and high-grade serous ovarian cancers share their molecular profile; 80% of basal-like tumours are triple-negative."],"whatItMeans":"This is the reference frequency table for basal-like disease: it explains why PARP inhibitors and platinum, borrowed from ovarian cancer, work in TNBC, and why the PI3K pathway is broken by copy number rather than the hotspot mutations that drugs were designed against.","caveats":["Basal-like is not identical to triple-negative: 10% of basal-like tumours are ER-positive and about a quarter of TNBCs are non-basal.","Frequencies are from 2012 pipelines; the 2018 PanCancer Atlas calls differ (PTEN deep deletion 21% and RB1 10.9% of 119 triple-negative samples on cBioPortal)."],"changedPractice":false,"participants":825},{"id":"paper-tcga-lung-adenocarcinoma-nature-2014","kind":"paper","name":"Comprehensive molecular profiling of lung adenocarcinoma","aka":[],"tldr":"Reading 230 surgically removed lung adenocarcinomas on every available platform produced the reference map of the disease, found three new driver genes, and showed that a tenth of tumours with no obvious oncogene were driven by alterations nobody had counted as drivers before.","summary":"Molecular profiling of 230 resected lung adenocarcinomas combined messenger RNA, microRNA and DNA sequencing with copy number, methylation and proteomic analyses. Somatic mutation rates were high, a mean of 8.9 mutations per megabase. Eighteen genes were significantly mutated, including activating RIT1 mutations and newly described loss-of-function MGA mutations that were mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in women and RBM10 mutations in men. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples that otherwise lacked an activated oncogene, arguing that they are drivers in those tumours. Matched DNA and messenger RNA revealed splicing alterations driven by somatic genomic change, including exon 14 skipping in MET messenger RNA in 4% of cases. MAPK and PI3K pathway activity measured at the protein level was explained by known mutations in only a fraction of cases.","asOf":"2026-09-25","links":[{"label":"Cancer Genome Atlas Research Network, Nature 2014: comprehensive molecular profiling of 230 resected lung adenocarcinomas","url":"https://doi.org/10.1038/nature13385"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25079552/"},{"label":"cBioPortal study luad_tcga_pub (TCGA, Nature 2014; the 230 resected lung adenocarcinomas of the landmark paper)","url":"https://www.cbioportal.org/study/summary?id=luad_tcga_pub"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":["wes-wgs","rna-seq","methylation-profiling"],"targets":["egfr","kras","tp53","stk11","keap1","met","nf1","rbm10","rit1","mga","her2","nkx2-1"],"drugs":[],"companies":[],"institutions":["broad-institute"],"pathways":["nsclc-signalling","ras-mapk","rtk-activation","pi3k-akt-mtor","keap1-nrf2"],"terms":["driver-mutation","met-exon-14-skipping","somatic-mutations-wxs-wgs"],"trials":[],"people":["matthew-meyerson"],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2014,"doi":"10.1038/nature13385","pmid":"25079552","authors":"Cancer Genome Atlas Research Network.","paperType":"basic","findings":["Mean somatic mutation rate 8.9 per megabase, among the highest of any cancer.","Eighteen significantly mutated genes, adding RIT1 and MGA to the driver list.","NF1, MET, ERBB2 and RIT1 aberrations in 13% of cases, enriched where no other oncogene was activated.","MET exon 14 skipping read directly in messenger RNA in 4% of tumours."],"whatItMeans":"It is the reference table the field still argues against, and it made two practical points that outlived it: a tumour with no driver on a standard panel usually has one that the panel did not look for, and pathway activity measured on protein does not follow from the mutation list.","caveats":["A surgical, mostly early-stage, mostly smoker cohort, so the driver frequencies do not match those of a metastatic clinic.","Fusion detection was limited by the sequencing used, so ALK, ROS1 and RET rates read low.","230 tumours is too few to find drivers below about 2%."],"changedPractice":false,"participants":230},{"id":"paper-boveri-j-cell-sci","kind":"paper","name":"Concerning the origin of malignant tumours by Theodor Boveri. Translated and annotated by Henry Harris","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 18089652 and published in Journal of cell science; the citing page links this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 18089652 (DOI 10.1242/jcs.025742). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Cell Sci 2008","url":"https://doi.org/10.1242/jcs.025742"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/18089652/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/18089652"}],"tags":["europepmc-ingest"],"related":["aneuploidy-theory-of-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of cell science","year":2008,"doi":"10.1242/jcs.025742","pmid":"18089652","authors":"Boveri T","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-perez-jco-precis-oncol","kind":"paper","name":"Concordance in Molecular Tumor Board Case Reviews in the ASCO TAPUR Study","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 38564684 and published in JCO Precision Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: With the advent of precision medicine, molecular tumor boards (MTBs) were established to interpret genomic results and guide decision making for targeted therapy in oncology patients. There are currently no universal guidelines for how MTBs should operate and thus variance can be seen depending on which MTB is reviewing the case. This study assesses the concordance of MTB recommendations when a participant case is reviewed by two different MTBs, establishes potential reasons for discordance, and advocates for the establishment of standard MTB operating guidelines.\n\nPatients and methods: Participants with advanced cancer, who had exhausted all standard treatment options were screened for the Targeted Agent and Profiling Utilization Registry (TAPUR) Study. Cases were submitted for MTB review if the treatment proposal was outside the protocol genomic matching rules, or if multiple treatment options were identified. Of the 306 cases submitted for review by the TAPUR MTB from 2016 to 2018, 107 were randomly selected for secondary review by a different MTB group. Recommendations from the original review were not disclosed. Concordance between MTB group recommendations was assessed. Concordance was defined as agreement between MTB reviews on the genomic alteration and study drug match proposed by the clinical site. Thematic qualitative analysis was conducted for the discordant cases to assess reasons for discordance.\n\nResults: Complete or partial concordance was observed in 79% of cases (95% CI, 70 to 86; one-sided P =.25). Most discordant analyses were due to disagreements on the strength of evidence regarding efficacy of the proposed treatment (32%).\n\nConclusion: When presented with identical participant cases, different MTB review groups make the same or similar treatment recommendations approximately 80% of the time.\n\nIndexed on Europe PMC as PubMed record 38564684 (DOI 10.1200/po.23.00615). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JCO Precis Oncol 2024","url":"https://doi.org/10.1200/po.23.00615"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38564684/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38564684"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["tapur"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco-precision-oncology"],"dependsOn":[],"notes":[],"journal":"JCO Precision Oncology","year":2024,"doi":"10.1200/po.23.00615","pmid":"38564684","authors":"Perez JK, Kleber J, Rothe M, et al.","paperType":"observational","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-wyatt-ctdna-tissue-concordance-mcrpc-jnci-2017","kind":"paper","name":"Concordance of circulating tumour DNA and matched metastatic tissue biopsy in prostate cancer","aka":[],"tldr":"Comparing a blood test with a needle biopsy taken the same day showed that when the blood carried enough tumour DNA, it found everything the biopsy found.","summary":"Targeted sequencing across 72 clinically relevant genes was performed on 45 plasma cell-free DNA samples collected at the time of a metastatic tissue biopsy in men with metastatic castration-resistant prostate cancer, and the alterations were compared with exome sequencing data from the matched tissue. Seventy-five point six per cent of the cell-free DNA samples had a circulating tumour DNA proportion greater than 2% of total cell-free DNA. In those men, all somatic mutations identified in the matched metastatic tissue biopsies were concurrently present in circulating tumour DNA, and the hierarchy of variant allele fractions for shared mutations was closely similar between the two. Copy-number profiles between matched liquid and solid biopsy were highly correlated and individual copy-number calls in clinically actionable genes were 88.9% concordant. Detected alterations included AR amplification in 22 samples, 64.7%, SPOP mutation in 3, 8.8%, and inactivating alterations in TP53, PTEN, RB1, APC, CDKN1B, BRCA2 and PIK3R1. In several men, circulating tumour DNA sequencing revealed changes not present in the paired solid biopsy, including alterations in the androgen receptor, WNT and PI3K pathways.","asOf":"2026-09-25","links":[{"label":"Wyatt et al., J Natl Cancer Inst 2017: concordance of circulating tumour DNA and matched metastatic tissue biopsy in 45 men with mCRPC","url":"https://doi.org/10.1093/jnci/djx118"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29206995/"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["liquid-biopsy","cgp"],"targets":["androgen-receptor","tp53","pten","rb1","brca","spop"],"drugs":[],"companies":[],"institutions":[],"pathways":["ar-signaling","wnt","pi3k-akt-mtor","clonal-evolution"],"terms":["ctdna","cfdna","liquid-biopsy","biopsy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jnci"],"dependsOn":[],"notes":[],"journal":"Journal of the National Cancer Institute","year":2017,"doi":"10.1093/jnci/djx118","pmid":"29206995","authors":"Wyatt AW, Annala M, Aggarwal R, et al.","paperType":"translational","findings":["Circulating tumour DNA above 2% of total cell-free DNA in 75.6% of samples.","In those samples, every somatic mutation found in matched tissue was also found in plasma.","Copy-number calls in actionable genes 88.9% concordant.","Plasma revealed AR, WNT and PI3K pathway changes absent from the paired tissue in several men."],"whatItMeans":"It is the study that justified using plasma instead of a bone biopsy in this disease, with the honest caveat attached: the concordance holds only above a tumour fraction threshold, and below it the test is uninformative rather than negative.","caveats":["Forty-five paired samples at academic centres.","Nearly a quarter of samples fell below the 2% tumour fraction threshold.","A 72-gene panel, so genes outside it were not compared."],"changedPractice":false,"participants":45},{"id":"paper-holderfield-ras-on-multi-selective-inhibitor-nature-2024","kind":"paper","name":"Concurrent inhibition of oncogenic and wild-type RAS-GTP for cancer therapy","aka":[],"tldr":"The 2024 Nature paper describing the chemistry behind daraxonrasib: a reversible drug that clamps the active form of every RAS protein, mutant or normal, and shrank tumours across RAS-driven models.","summary":"Holderfield and colleagues at Revolution Medicines describe RMC-7977, a reversible tri-complex RAS inhibitor with broad-spectrum activity for the active (GTP-bound) state of mutant and wild-type KRAS, NRAS and HRAS, a RAS(ON) multi-selective inhibitor. Preclinically it showed potent activity against RAS-addicted tumours of various genotypes, particularly models with KRAS codon 12 mutations, led to tumour regression, was well tolerated in diverse models and inhibited KRAS G12C models that had become resistant to G12C inhibitors through restored RAS pathway signalling. The paper notes that KRAS G12C accounts for only around 15 percent of KRAS-mutant cancers and that no inhibitor was approved for the rest, and that the related compound RMC-6236 (daraxonrasib) was in clinical evaluation (NCT05379985).","asOf":"2026-09-24","links":[{"label":"Nature 2024","url":"https://doi.org/10.1038/s41586-024-07205-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38589574/"}],"tags":["pancreatic-evidence"],"related":["kras-roadmap","paper-daraxonrasib-pancreatic-n-engl-j-med-2026"],"cancers":["pancreatic"],"sections":[],"technologies":["kras-inhibitors"],"targets":["kras"],"drugs":["daraxonrasib"],"companies":["revolution-medicines"],"institutions":[],"pathways":["ras-mapk"],"terms":[],"trials":["rasolute-302"],"people":[],"bottlenecks":["b-undruggable-targets","b-resistance"],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2024,"doi":"10.1038/s41586-024-07205-6","pmid":"38589574","authors":"Holderfield M, Lee BJ, Jiang J, et al.","paperType":"basic","findings":["RMC-7977 inhibits GTP-bound mutant and wild-type KRAS, NRAS and HRAS.","Regression in RAS-addicted models, strongest in KRAS codon 12 mutants, with tolerability.","Activity in G12C models resistant to G12C inhibitors.","KRAS G12C is around 15 percent of KRAS-mutant cancers; daraxonrasib (RMC-6236) was already in trials."],"whatItMeans":"The mechanism that let one drug address G12D, G12V and G12R together, which is why the RASolute 302 trial could enrol unselected pancreatic cancer and nearly double survival.","caveats":["Preclinical; the human data are in the RASolute 302 paper.","Inhibiting wild-type RAS raises the question of on-target toxicity (rash, stomatitis) that the trials measure."],"changedPractice":true},{"id":"paper-convert-lancet-oncol-2017","kind":"paper","name":"Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial","aka":[],"tldr":"Published report from the CONVERT trial registered as NCT00433563, in The Lancet Oncology (2017), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Concurrent chemoradiotherapy is the standard of care in limited-stage small-cell lung cancer, but the optimal radiotherapy schedule and dose remains controversial. The aim of this study was to establish a standard chemoradiotherapy treatment regimen in limited-stage small-cell lung cancer.\n\nMethods: The CONVERT trial was an open-label, phase 3, randomised superiority trial. We enrolled adult patients (aged ≥18 years) who had cytologically or histologically confirmed limited-stage small-cell lung cancer, Eastern Cooperative Oncology Group performance status of 0-2, and adequate pulmonary function. Patients were recruited from 73 centres in eight countries. Patients were randomly assigned to receive either 45 Gy radiotherapy in 30 twice-daily fractions of 1·5 Gy over 19 days, or 66 Gy in 33 once-daily fractions of 2 Gy over 45 days, starting on day 22 after commencing cisplatin-etoposide chemotherapy (given as four to six cycles every 3 weeks in both groups). The allocation method used was minimisation with a random element, stratified by institution, planned number of chemotherapy cycles, and performance status. Treatment group assignments were not masked. The primary endpoint was overall survival, defined as time from randomisation until death from any cause, analysed by modified intention-to-treat. A 12% higher overall survival at 2 years in the once-daily group versus the twice-daily group was considered to be clinically significant to show superiority of the once-daily regimen. The study is registered with ClinicalTrials.gov (NCT00433563) and is currently in follow-up.\n\nFindings: Between April 7, 2008, and Nov 29, 2013, 547 patients were enrolled and randomly assigned to receive twice-daily concurrent chemoradiotherapy (274 patients) or once-daily concurrent chemoradiotherapy (273 patients). Four patients (one in the twice-daily group and three in the once-daily group) did not return their case report forms and were lost to follow-up; these patients were not included in our analyses. At a median follow-up of 45 months (IQR 35-58), median overall survival was 30 months (95% CI 24-34) in the twice-daily group versus 25 months (21-31) in the once-daily group (hazard ratio for death in the once daily group 1·18 [95% CI 0·95-1·45]; p=0·14). 2-year overall survival was 56% (95% CI 50-62) in the twice-daily group and 51% (45-57) in the once-daily group (absolute difference between the treatment groups 5·3% [95% CI -3·2% to 13·7%]). The most common grade 3-4 adverse event in patients evaluated for chemotherapy toxicity was neutropenia (197 [74%] of 266 patients in the twice-daily group vs 170 [65%] of 263 in the once-daily group). Most toxicities were similar between the groups, except there was significantly more grade 4 neutropenia with twice-daily radiotherapy (129 [49%] vs 101 [38%]; p=0·05). In patients assessed for radiotherapy toxicity, was no difference in grade 3-4 oesophagitis between the groups (47 [19%] of 254 patients in the twice-daily group vs 47 [19%] of 246 in the once-daily group; p=0·85) and grade 3-4 radiation pneumonitis (4 [3%] of 254 vs 4 [2%] of 246; p=0·70). 11 patients died from treatment-related causes (three in the twice-daily group and eight in the once-daily group).\n\nInterpretation: Survival outcomes did not differ between twice-daily and once-daily concurrent chemoradiotherapy in patients with limited-stage small-cell lung cancer, and toxicity was similar and lower than expected with both regimens. Since the trial was designed to show superiority of once-daily radiotherapy and was not powered to show equivalence, the implication is that twice-daily radiotherapy should continue to be considered the standard of care in this setting.\n\nFunding: Cancer Research UK (Clinical Trials Awards and Advisory Committee), French Ministry of Health, Canadian Cancer Society Research Institute, European Organisation for Research and Treatment of Cancer (Cancer Research Fund, Lung Cancer, and Radiation Oncology Groups).\n\nIndexed on Europe PMC as PubMed record 28642008 (DOI 10.1016/s1470-2045(17)30318-2). Its abstract cites the registry id NCT00433563, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2017","url":"https://doi.org/10.1016/s1470-2045(17)30318-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28642008/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28642008"},{"label":"ClinicalTrials.gov NCT00433563","url":"https://clinicaltrials.gov/study/NCT00433563"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["convert"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2017,"doi":"10.1016/s1470-2045(17)30318-2","pmid":"28642008","authors":"Faivre-Finn C, Snee M, Ashcroft L, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT00433563 with the most citations, so it is the natural first reading for anyone following the CONVERT trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-offin-rb1-tp53-transformation-risk-jto-2019","kind":"paper","name":"Concurrent RB1 and TP53 alterations define a subset of EGFR-mutant lung cancers at risk for histologic transformation and inferior clinical outcomes","aka":[],"tldr":"Lung cancers with mutations in all three of the same genes make up only a twentieth of the targetable group, but they are the ones that turn into a different cancer, and they stop responding to treatment three times sooner than the rest.","summary":"Patients with EGFR, RB1 and TP53-mutant lung cancers identified by next-generation sequencing between 2014 and 2018 were compared with patients with untreated metastatic EGFR-mutant lung cancers lacking both RB1 and TP53 alterations. The triple-mutant group represented 43 of 863 EGFR-mutant lung cancers, 5%, but was uniquely at risk of transformation, 7 of 39, 18%, with no transformations among EGFR-mutant cancers without baseline TP53 and RB1 alterations. Irrespective of transformation, triple-mutant patients had a shorter time to EGFR inhibitor discontinuation than EGFR and TP53-mutant or EGFR-only cancers, 9.5 against 12.3 against 36.6 months. The triple-mutant population had a higher incidence of whole-genome doubling than non-small-cell lung cancer at large, 80% against 34%, further enriched in those that eventually became small-cell, and an APOBEC mutation signature was enriched in the cancers that transformed.","asOf":"2026-09-25","links":[{"label":"Offin et al., J Thorac Oncol 2019: concurrent RB1 and TP53 alterations and the risk of histological transformation in EGFR-mutant lung cancer","url":"https://doi.org/10.1016/j.jtho.2019.06.002"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31228622/"}],"tags":[],"related":[],"cancers":["nsclc","sclc"],"sections":[],"technologies":["cgp"],"targets":["egfr","rb1","tp53"],"drugs":[],"companies":[],"institutions":["mskcc"],"pathways":["lineage-plasticity-neuroendocrine","resistance-routes-map","clonal-evolution","mutagenesis-signatures"],"terms":["histologic-transformation","resistance","mutational-signature"],"trials":[],"people":["charles-rudin"],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-thoracic-oncology"],"dependsOn":[],"notes":[],"journal":"Journal of Thoracic Oncology","year":2019,"doi":"10.1016/j.jtho.2019.06.002","pmid":"31228622","authors":"Offin M, Chan JM, Tenet M, et al.","paperType":"observational","findings":["Triple-mutant EGFR, RB1 and TP53 cancers are 5% of EGFR-mutant disease and account for the transformations.","Transformation occurred in 18% of the triple-mutant group and in none without baseline RB1 and TP53 loss.","Time to EGFR inhibitor discontinuation 9.5 against 36.6 months for EGFR-only cancers.","Whole-genome doubling in 80% of the triple-mutant group."],"whatItMeans":"It gives the sequencing report a prognostic reading that does not depend on a repeat biopsy: an EGFR-mutant cancer that also carries RB1 and TP53 alterations will stop responding sooner and should be watched for a change of histology.","caveats":["Single centre and retrospective.","Transformation is diagnosed only where a rebiopsy was taken, so the rate may be underestimated in both groups.","Whole-genome doubling estimates come from panel data."],"changedPractice":false,"participants":863},{"id":"paper-promise-talhouk-cancer-2017","kind":"paper","name":"Confirmation of ProMisE: a genomics-based clinical classifier for endometrial cancer","aka":[],"tldr":"The ProMisE classifier uses three tests, mismatch repair and p53 immunohistochemistry plus POLE sequencing, to sort endometrial cancers into four molecular groups that reproduce the Cancer Genome Atlas subtypes and predict outcome.","summary":"Confirmation study in 319 endometrial cancers of the Proactive Molecular Risk Classifier for Endometrial Cancer, assigning tumours to POLE-mutated, mismatch repair-deficient, p53-abnormal or p53 wild-type (no specific molecular profile) groups using immunohistochemistry and targeted sequencing.\n\nThe classifier was reproducible, could be applied to biopsy material and stratified survival, with POLE tumours faring best and p53-abnormal worst, independent of traditional risk factors.","asOf":"2026-09-17","links":[{"label":"Cancer 2017","url":"https://doi.org/10.1002/cncr.30496"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28061006/"}],"tags":[],"related":[],"cancers":["endometrial-nsmp","endometrial-mmr-deficient","endometrial-p53-abnormal","endometrial-pole-ultramutated"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-wiley"],"dependsOn":[],"notes":[],"journal":"Cancer","year":2017,"doi":"10.1002/cncr.30496","pmid":"28061006","authors":"Talhouk A, McConechy MK, Leung S, et al.","paperType":"translational","findings":["Four molecular groups with distinct survival; p53-abnormal worst, POLE best.","Classifier reproducible on diagnostic biopsies with high concordance to hysterectomy specimens."],"whatItMeans":"Molecular classification of every endometrial cancer, now embedded in the WHO classification and the ESGO/ESTRO/ESP guideline, rests on ProMisE; it decides adjuvant therapy and identifies candidates for immunotherapy.","caveats":["Tumours with more than one classifying feature (multiple classifiers) need hierarchical assignment rules.","POLE sequencing is not yet universally available."],"changedPractice":true,"participants":319},{"id":"paper-hans-immunohistochemistry-cell-of-origin-dlbcl-blood-2004","kind":"paper","name":"Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray","aka":["Hans algorithm","Hans 2004","CD10, BCL6 and MUM1 classifier"],"tldr":"Three ordinary laboratory stains, available in any hospital, were shown to sort lymphoma into the same two prognostic groups that an expensive gene-expression machine had found.","summary":"The cell-of-origin classification was a research technique: it needed fresh-frozen tissue and a microarray. Hans and colleagues asked whether routine immunohistochemistry on paraffin-embedded tissue could reproduce it. They built tissue microarray blocks from 152 cases of diffuse large B-cell lymphoma, 142 of which had already been classified by complementary DNA microarray (75 germinal-centre, 41 activated B-cell, 26 type 3), and stained for CD10, BCL6, MUM1, FOXP1, cyclin D2 and BCL2.\n\nBCL6 (p < 0.001) and CD10 (p = 0.019) expression went with better overall survival, MUM1 (p = 0.009) and cyclin D2 (p < 0.001) with worse. Using CD10, BCL6 and MUM1, 64 cases (42 per cent) were classed germinal-centre and 88 (58 per cent) non-germinal-centre. Five-year overall survival was 76 per cent for the germinal-centre group against 34 per cent for the non-germinal-centre group (p < 0.001), similar to what the microarray gave. On multivariate analysis an International Prognostic Index of 3 to 5 and the non-germinal-centre phenotype were independent adverse predictors (p < 0.0001).\n\nThe algorithm is the reason the classification exists outside research centres. It is also the reason the classification is noisier than it looks on paper.","asOf":"2026-10-01","links":[{"label":"Blood 2004","url":"https://doi.org/10.1182/blood-2003-05-1545"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/14504078/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/14504078"}],"tags":["lymphoma-evidence"],"related":["paper-rosenwald-molecular-profiling-dlbcl-nejm-2002","paper-wright-lymphgen-genetic-subtypes-dlbcl-cancer-cell-2020","lymphoma-roadmap"],"cancers":["dlbcl","non-hodgkin-lymphoma"],"sections":["diagnostics"],"technologies":[],"targets":["bcl2","bcl6"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cell-of-origin","ipi-score"],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation","b-global-access"],"keyPapers":[],"journals":["blood"],"dependsOn":[],"notes":[],"journal":"Blood","year":2004,"doi":"10.1182/blood-2003-05-1545","pmid":"14504078","authors":"Hans CP, Weisenburger DD, Greiner TC, et al.","paperType":"translational","findings":["A three-antibody algorithm using CD10, BCL6 and MUM1 classified 42 per cent of 152 cases as germinal-centre and 58 per cent as non-germinal-centre.","Five-year overall survival was 76 per cent in the germinal-centre group against 34 per cent in the non-germinal-centre group (p < 0.001), similar to the complementary DNA microarray classification.","BCL6 and CD10 expression were associated with better overall survival; MUM1 and cyclin D2 with worse.","BCL2 and cyclin D2 were adverse predictors within the non-germinal-centre group.","On multivariate analysis, an International Prognostic Index of 3 to 5 and the non-germinal-centre phenotype were independent adverse predictors."],"whatItMeans":"The practical form of cell-of-origin classification, used in pathology laboratories worldwide. When a report says germinal-centre or non-germinal-centre, this is almost always the algorithm behind it.","caveats":["Concordance with gene-expression profiling is imperfect, and estimates of the disagreement rate vary widely between series; the algorithm misclassifies a meaningful minority of cases.","Scoring thresholds for the three stains are not fully standardised between laboratories, so the same tumour can be called differently in two hospitals.","The 152 cases came from the same consortium as the profiling study, so this is a confirmation within a cohort rather than an independent validation.","Trials that selected patients by this algorithm for activated B-cell-directed drugs, such as PHOENIX and ROBUST, were negative, which is part of the evidence that it is too blunt an instrument."],"changedPractice":true,"participants":152},{"id":"paper-swain-cancer","kind":"paper","name":"Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials","aka":[],"tldr":"Paper cited by one pairing page, indexed on Europe PMC as PubMed record 12767102 and published in Cancer; the citing page links this DOI, which is how the record was matched.","summary":"Background: Doxorubicin is a highly effective and widely used cytotoxic agent with application that is limited by cardiotoxicity related to the cumulative dose of the drug. A large-scale study that retrospectively evaluated the cardiotoxicity of doxorubicin reported that an estimated 7% of patients developed doxorubicin-related congestive heart failure (CHF) after a cumulative dose of 550 mg/m(2). To assess whether this estimate is reflective of the incidence in the broader clinical oncology setting, the authors evaluated data from three prospective studies to determine both the incidence of doxorubicin-related CHF and the accumulated dose of doxorubicin at which CHF occurs.\n\nMethods: A group of 630 patients who were randomized to a doxorubicin-plus-placebo arm of three Phase III studies, two studies in patients with breast carcinoma and one study in patients with small cell lung carcinoma, were included in the analysis.\n\nResults: Thirty-two of 630 patients had a diagnosis of CHF. Analysis indicated that an estimated cumulative 26% of patients would experience doxorubicin-related CHF at a cumulative dose of 550 mg/m(2). Age appeared to be an important risk factor for doxorubicin-related CHF after a cumulative dose of 400 mg/m(2), with older patients (age > 65 years) showing a greater incidence of CHF compared with younger patients (age < or = 65 years). In addition, > 50% of the patients who experienced doxorubicin-related CHF had a reduction < 30% in left ventricular ejection fraction (LVEF) while they were on study.\n\nConclusions: Doxorubicin-related CHF occurs with greater frequency and at a lower cumulative dose than previously reported. These findings further indicate that LVEF is not an accurate predictor of CHF in patients who receive doxorubicin.\n\nIndexed on Europe PMC as PubMed record 12767102 (DOI 10.1002/cncr.11407). Matched by DOI alone: one pairing page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer 2003","url":"https://doi.org/10.1002/cncr.11407"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/12767102/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/12767102"}],"tags":["europepmc-ingest"],"related":["doxorubicin-cardio-caution"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-wiley"],"dependsOn":[],"notes":[],"journal":"Cancer","year":2003,"doi":"10.1002/cncr.11407","pmid":"12767102","authors":"Swain SM, Whaley FS, Ewer MS","paperType":"rct","findings":[],"whatItMeans":"One pairing page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-conko-001-adjuvant-gemcitabine-long-term-oettle-jama-2013","kind":"paper","name":"CONKO-001: adjuvant gemcitabine and long-term outcomes after resected pancreatic cancer","aka":[],"tldr":"Six months of gemcitabine after complete removal of pancreatic cancer doubled the time to relapse and roughly doubled five-year survival, from 10 to 21 percent, in the trial that established adjuvant chemotherapy for the disease.","summary":"Long-term report of the German and Austrian open-label phase 3 CONKO-001 trial: 368 patients randomised between 1998 and 2004 to six months of adjuvant gemcitabine or observation, 354 analysed by intention to treat, median follow-up 136 months.\n\nMedian disease-free survival was 13.4 months with gemcitabine against 6.7 months with observation (hazard ratio 0.55); overall survival was improved (hazard ratio 0.76, p 0.01), with five-year survival 20.7 against 10.4 percent and ten-year survival 12.2 against 7.7 percent.","asOf":"2026-09-22","links":[{"label":"JAMA 2013","url":"https://doi.org/10.1001/jama.2013.279201"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24104372/"}],"tags":[],"related":["paper-conko-001-adjuvant-gemcitabine-observation-jama-2007"],"cancers":["resectable-pdac","pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":["gemcitabine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["conko-001"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2013,"doi":"10.1001/jama.2013.279201","pmid":"24104372","authors":"Oettle H, Neuhaus P, Hochhaus A, et al.","paperType":"rct","findings":["Median disease-free survival 13.4 months (95% CI 11.6 to 15.3) versus 6.7 months (6.0 to 7.5); hazard ratio 0.55 (0.44 to 0.69), p < 0.001.","Overall survival hazard ratio 0.76 (0.61 to 0.95), p 0.01; five-year survival 20.7 versus 10.4 percent; ten-year survival 12.2 versus 7.7 percent."],"whatItMeans":"Adjuvant chemotherapy is standard after pancreatic cancer resection; gemcitabine alone remains the option for patients who cannot tolerate combinations.","caveats":["Later methodological critiques raised concerns about randomisation and surgical standardisation.","Registered with ISRCTN only (ISRCTN34802808)."],"changedPractice":true,"participants":368},{"id":"paper-conroy-folfirinox-pancreatic-nejm-2011","kind":"paper","name":"Conroy 2011: FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer (PRODIGE 4/ACCORD 11)","aka":[],"tldr":"A four-drug chemotherapy combination gave fit patients with metastatic pancreatic cancer clearly longer survival than the standard gemcitabine, the first real improvement in the disease in over a decade, at the cost of more side effects.","summary":"This French phase 2-3 trial randomised 342 patients with metastatic pancreatic adenocarcinoma and good performance status to FOLFIRINOX (oxaliplatin, irinotecan, leucovorin and fluorouracil) or gemcitabine. FOLFIRINOX improved overall survival, progression-free survival and response rate, and delayed the decline in quality of life despite more grade 3 and 4 toxicity, particularly neutropenia, febrile neutropenia, diarrhoea and sensory neuropathy. It made FOLFIRINOX a first-line standard for fit patients and the backbone later moved into the adjuvant setting.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa1011923"},{"label":"ClinicalTrials.gov NCT00112658","url":"https://clinicaltrials.gov/study/NCT00112658"}],"tags":[],"related":["paper-napoli-1-nanoliposomal-irinotecan-lancet-2016"],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":["oxaliplatin","irinotecan","fluorouracil","gemcitabine"],"companies":[],"institutions":[],"pathways":[],"terms":["os","pfs","febrile-neutropenia"],"trials":["prodige-24"],"people":["thierry-conroy"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2011,"doi":"10.1056/NEJMoa1011923","pmid":"21561347","authors":"Conroy T, Desseigne F, Ychou M, et al.","paperType":"rct","findings":["342 patients with metastatic pancreatic cancer and ECOG performance status 0 or 1; FOLFIRINOX vs gemcitabine.","Median overall survival 11.1 vs 6.8 months, hazard ratio 0.57.","Median progression-free survival 6.4 vs 3.3 months, hazard ratio 0.47; response rate 31.6% vs 9.4%.","Grade 3 or 4 neutropenia 45.7% vs 21.0%, febrile neutropenia 5.4% vs 1.2%, sensory neuropathy 9.0% vs 0%."],"whatItMeans":"FOLFIRINOX and, soon after, gemcitabine plus nab-paclitaxel ended the era of single-agent gemcitabine for metastatic pancreatic cancer. The regimen's modified form later improved survival after surgery in PRODIGE 24, and its toxicity is why fitness, not just stage, decides which treatment a patient is offered.","caveats":["Restricted to fit patients under 76 with good performance status; most patients with pancreatic cancer are not eligible.","Toxicity is substantial and needs experienced supportive care.","Open-label design."],"changedPractice":true,"participants":342},{"id":"paper-rosai-dorfman-destombes-consensus-recommendations-blood-2018","kind":"paper","name":"Consensus recommendations for the diagnosis and clinical management of Rosai-Dorfman-Destombes disease","aka":[],"tldr":"The first expert guidance on Rosai-Dorfman disease: how to confirm the diagnosis, which patients can be watched, and which need surgery, steroids, chemotherapy or targeted treatment.","summary":"Consensus from the Histiocyte Society and international experts on Rosai-Dorfman-Destombes disease covering histopathology (S100 and CD68 positive, CD1a negative histiocytes with emperipolesis), the clinical spectrum from isolated lymph node disease to extranodal, cutaneous and IgG4-related forms, molecular findings (KRAS and MAP2K1 mutations in a subset), and management: observation for asymptomatic disease, surgery for isolated lesions, corticosteroids, sirolimus, cladribine or other chemotherapy, and MEK inhibitors for MAPK-mutant disease.","asOf":"2026-09-18","links":[{"label":"Blood 2018","url":"https://doi.org/10.1182/blood-2018-03-839753"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29720485/"}],"tags":[],"related":[],"cancers":["rosai-dorfman-disease"],"sections":[],"technologies":[],"targets":[],"drugs":["cobimetinib","cladribine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["blood"],"dependsOn":[],"notes":[],"journal":"Blood","year":2018,"doi":"10.1182/blood-2018-03-839753","pmid":"29720485","authors":"Abla O, Jacobsen E, Picarsic J, et al.","paperType":"guideline","findings":[],"whatItMeans":"The treatment rows on the Rosai-Dorfman page, from watchful waiting to cobimetinib, follow these recommendations.","caveats":["Consensus on case series; no prospective trial exists.","The proportion of cases that are clonal neoplasms versus reactive is still debated."],"changedPractice":true},{"id":"paper-fiolet-bmj","kind":"paper","name":"Consumption of ultra-processed foods and cancer risk: results from NutriNet-Santé prospective cohort","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 29444771 and published in BMJ; the citing page links this DOI, which is how the record was matched.","summary":"Objective: To assess the prospective associations between consumption of ultra-processed food and risk of cancer.\n\nDesign: Population based cohort study.\n\nSetting and participants: 104 980 participants aged at least 18 years (median age 42.8 years) from the French NutriNet-Santé cohort (2009-17). Dietary intakes were collected using repeated 24 hour dietary records, designed to register participants' usual consumption for 3300 different food items. These were categorised according to their degree of processing by the NOVA classification.\n\nMain outcome measures: Associations between ultra-processed food intake and risk of overall, breast, prostate, and colorectal cancer assessed by multivariable Cox proportional hazard models adjusted for known risk factors.\n\nResults: Ultra-processed food intake was associated with higher overall cancer risk (n=2228 cases; hazard ratio for a 10% increment in the proportion of ultra-processed food in the diet 1.12 (95% confidence interval 1.06 to 1.18); P for trend<0.001) and breast cancer risk (n=739 cases; hazard ratio 1.11 (1.02 to 1.22); P for trend=0.02). These results remained statistically significant after adjustment for several markers of the nutritional quality of the diet (lipid, sodium, and carbohydrate intakes and/or a Western pattern derived by principal component analysis).\n\nConclusions: In this large prospective study, a 10% increase in the proportion of ultra-processed foods in the diet was associated with a significant increase of greater than 10% in risks of overall and breast cancer. Further studies are needed to better understand the relative effect of the various dimensions of processing (nutritional composition, food additives, contact materials, and neoformed contaminants) in these associations.\n\nStudy registration: Clinicaltrials.gov NCT03335644.\n\nIndexed on Europe PMC as PubMed record 29444771 (DOI 10.1136/bmj.k322). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"BMJ 2018","url":"https://doi.org/10.1136/bmj.k322"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29444771/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29444771"}],"tags":["europepmc-ingest"],"related":["ultra-processed-food-ssb"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["bmj"],"dependsOn":[],"notes":[],"journal":"BMJ","year":2018,"doi":"10.1136/bmj.k322","pmid":"29444771","authors":"Fiolet T, Srour B, Sellem L, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-ben-david-nat-rev-genet","kind":"paper","name":"Context is everything: aneuploidy in cancer","aka":[],"tldr":"Paper cited by one idea page, indexed on Europe PMC as PubMed record 31548659 and published in Nature reviews. Genetics; the citing page links this DOI, which is how the record was matched.","summary":"Cancer is driven by multiple types of genetic alterations, which range in size from point mutations to whole-chromosome gains and losses, known as aneuploidy. Chromosome instability, the process that gives rise to aneuploidy, can promote tumorigenesis by increasing genetic heterogeneity and promoting tumour evolution. However, much less is known about how aneuploidy itself contributes to tumour formation and progression. Unlike some pan-cancer oncogenes and tumour suppressor genes that drive transformation in virtually all cell types and cellular contexts, aneuploidy is not a universal promoter of tumorigenesis. Instead, recent studies suggest that aneuploidy is a context-dependent, cancer-type-specific oncogenic event that may have clinical relevance as a prognostic marker and as a potential therapeutic target.\n\nIndexed on Europe PMC as PubMed record 31548659 (DOI 10.1038/s41576-019-0171-x). Matched by DOI alone: one idea page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Genet 2020","url":"https://doi.org/10.1038/s41576-019-0171-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31548659/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31548659"}],"tags":["europepmc-ingest"],"related":["idea-targeting-aneuploidy"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature reviews. Genetics","year":2020,"doi":"10.1038/s41576-019-0171-x","pmid":"31548659","authors":"Ben-David U, Amon A","paperType":"review","findings":[],"whatItMeans":"One idea page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-roumenina-nat-rev-cancer","kind":"paper","name":"Context-dependent roles of complement in cancer","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 31666715 and published in Nature Reviews Cancer; the citing page links this DOI, which is how the record was matched.","summary":"The tumour microenvironment (TME) highly influences the growth and spread of tumours, thus impacting the patient's clinical outcome. In this context, the complement system plays a major and complex role. It may either act to kill antibody-coated tumour cells, support local chronic inflammation or hamper antitumour T cell responses favouring tumour progression. Recent studies demonstrate that these opposing effects are dependent upon the sites of complement activation, the composition of the TME and the tumour cell sensitivity to complement attack. In this Review, we present the evidence that has so far accrued showing a role for complement activation and its effects on cancer control and clinical outcome under different TME contexts. We also include a new analysis of the publicly available transcriptomic data to provide an overview of the prognostic value of complement gene expression in 30 cancer types. We argue that the interplay of complement components within each cancer type is unique, governed by the properties of the tumour cells and the TME. This concept is of critical importance for the design of efficient therapeutic strategies aimed at targeting complement components and their signalling.\n\nIndexed on Europe PMC as PubMed record 31666715 (DOI 10.1038/s41568-019-0210-0). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Cancer 2019","url":"https://doi.org/10.1038/s41568-019-0210-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31666715/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31666715"}],"tags":["europepmc-ingest"],"related":["complement-in-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Cancer","year":2019,"doi":"10.1038/s41568-019-0210-0","pmid":"31666715","authors":"Roumenina LT, Daugan MV, Petitprez F, et al.","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-continuum-sintilimab-nasopharyngeal-liu-lancet-2024","kind":"paper","name":"CONTINUUM: induction-concurrent chemoradiotherapy with or without sintilimab in locoregionally advanced nasopharyngeal carcinoma","aka":[],"tldr":"Adding the PD-1 antibody sintilimab to chemotherapy and radiotherapy for advanced, non-metastatic nasopharyngeal cancer raised three-year event-free survival from 76 to 86 percent, with more but manageable side effects.","summary":"Multicentre open-label randomised phase 3 trial at nine hospitals in China: 425 adults with high-risk stage III to IVa nasopharyngeal carcinoma were randomised to gemcitabine-cisplatin induction and concurrent cisplatin radiotherapy with (210) or without (215) 12 cycles of sintilimab.\n\nAt a median follow-up of 41.9 months, three-year event-free survival was 86 percent with sintilimab against 76 percent without (stratified hazard ratio 0.59, p 0.019). Grade 3 to 4 adverse events occurred in 74 against 65 percent; grade 3 to 4 immune-related adverse events in 10 percent of the sintilimab group, with two immune-related deaths.","asOf":"2026-09-22","links":[{"label":"Lancet 2024","url":"https://doi.org/10.1016/S0140-6736(24)00594-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38824941/"}],"tags":[],"related":[],"cancers":["locoregionally-advanced-nasopharyngeal-carcinoma","nasopharyngeal"],"sections":[],"technologies":[],"targets":[],"drugs":["sintilimab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["continuum"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2024,"doi":"10.1016/S0140-6736(24)00594-4","pmid":"38824941","authors":"Liu X, Zhang Y, Yang KY, et al.","paperType":"rct","findings":["Three-year event-free survival 86 percent (95% CI 81 to 90) versus 76 percent (70 to 81); hazard ratio 0.59 (0.38 to 0.92), p 0.019.","Grade 3 to 4 adverse events 74 versus 65 percent; grade 3 to 4 immune-related events 10 percent with sintilimab."],"whatItMeans":"PD-1 blockade added to chemoradiotherapy is a new option for high-risk locoregionally advanced nasopharyngeal carcinoma; longer follow-up will show whether it lengthens survival.","caveats":["Chinese population with endemic EBV-related disease; open-label; overall survival immature."],"changedPractice":true,"participants":425},{"id":"paper-jochelson-radiology","kind":"paper","name":"Contrast-enhanced Mammography: State of the Art","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 33650905 and published in Radiology; the citing page links this DOI, which is how the record was matched.","summary":"Contrast-enhanced mammography (CEM) has emerged as a viable alternative to contrast-enhanced breast MRI, and it may increase access to vascular imaging while reducing examination cost. Intravenous iodinated contrast materials are used in CEM to enhance the visualization of tumor neovascularity. After injection, imaging is performed with dual-energy digital mammography, which helps provide a low-energy image and a recombined or iodine image that depict enhancing lesions in the breast. CEM has been demonstrated to help improve accuracy compared with digital mammography and US in women with abnormal screening mammographic findings or symptoms of breast cancer. It has also been demonstrated to approach the accuracy of breast MRI in preoperative staging of patients with breast cancer and in monitoring response after neoadjuvant chemotherapy. There are early encouraging results from trials evaluating CEM in the screening of women who are at an increased risk of breast cancer. Although CEM is a promising tool, it slightly increases radiation dose and carries a small risk of adverse reactions to contrast materials. This review details the CEM technique, diagnostic and screening uses, and future applications, including artificial intelligence and radiomics.\n\nIndexed on Europe PMC as PubMed record 33650905 (DOI 10.1148/radiol.2021201948). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Radiology 2021","url":"https://doi.org/10.1148/radiol.2021201948"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33650905/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33650905"}],"tags":["europepmc-ingest"],"related":["contrast-enhanced-mammography"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["radiology"],"dependsOn":[],"notes":[],"journal":"Radiology","year":2021,"doi":"10.1148/radiol.2021201948","pmid":"33650905","authors":"Jochelson MS, Lobbes MBI","paperType":"review","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-jones-pancreatic-core-pathways-science-2008","kind":"paper","name":"Core signaling pathways in human pancreatic cancers revealed by global genomic analyses","aka":[],"tldr":"The first complete reading of the protein-coding genes in 24 pancreatic cancers found an average of 63 changes per tumour that, however varied gene by gene, hit the same dozen cellular pathways in almost every case.","summary":"The sequences of 23,219 transcripts representing 20,661 protein-coding genes were determined in 24 pancreatic cancers, with SNP arrays for homozygous deletions and amplifications and next-generation transcriptome sequencing. Pancreatic cancers contained an average of 63 genetic alterations, mostly point mutations, defining a core set of 12 signalling pathways and processes each altered in 67 to 100% of tumours. The authors concluded that dysregulation of these core pathways can explain the major features of pancreatic tumorigenesis and that the pathways only become evident once coding regions are analysed in depth.","asOf":"2026-09-24","links":[{"label":"Jones et al., Science 2008: core signalling pathways in 24 pancreatic cancers","url":"https://doi.org/10.1126/science.1164368"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/18772397/"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":["kras","tp53","cdkn2a","smad4"],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":["pancreatic-cancer-signalling"],"terms":["driver-mutation"],"trials":[],"people":["bert-vogelstein","kenneth-kinzler","nickolas-papadopoulos","elizabeth-jaffee","anirban-maitra"],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2008,"doi":"10.1126/science.1164368","pmid":"18772397","authors":"Jones S, Zhang X, Parsons DW, et al.","paperType":"translational","findings":["Average of 63 genetic alterations per tumour, mostly point mutations.","Twelve core pathways and processes each altered in 67 to 100% of the 24 tumours."],"whatItMeans":"It set the frame that every later landscape paper filled in: pancreatic cancer is a disease of a few pathways broken by many different genes, so drugs must aim at pathways or their dependencies rather than one rare mutation.","caveats":["24 tumours, Sanger-era depth, no stromal correction.","Pathway membership was defined by the authors' curation."],"changedPractice":false,"participants":24},{"id":"paper-almogy-biorxiv","kind":"paper","name":"Cost-efficient whole genome-sequencing using novel mostly natural sequencing-by-synthesis chemistry and open fluidics platform","aka":[],"tldr":"Preprint cited by one technology page, indexed on Europe PMC as preprint record PPR499502 and posted on bioRxiv; the citing page links this DOI, which is how the record was matched.","summary":"We introduce a massively parallel novel sequencing platform that combines an open flow cell design on a circular wafer with a large surface area and mostly natural nucleotides that allow optical end-point detection without reversible terminators. This platform enables sequencing billions of reads with longer read length (∼300bp) and fast runs times (<20hrs) with high base accuracy (Q30 > 85%), at a low cost of $1/Gb. We establish system performance by whole-genome sequencing of the Genome-In-A-Bottle reference samples HG001-7, demonstrating high accuracy for SNPs (99.6%) and Indels in homopolymers up to length 10 (96.4%) across the vast majority (>98%) of the defined high-confidence regions of these samples. We demonstrate scalability of the whole-genome sequencing workflow by sequencing an additional 224 selected samples from the 1000 Genomes project achieving high concordance with reference data.\n\nIndexed on Europe PMC as preprint record PPR499502 (DOI 10.1101/2022.05.29.493900). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"bioRxiv 2022","url":"https://doi.org/10.1101/2022.05.29.493900"},{"label":"Europe PMC","url":"https://europepmc.org/article/PPR/PPR499502"}],"tags":["europepmc-ingest","preprint"],"related":["next-gen-short-read-platforms"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"bioRxiv (preprint)","year":2022,"doi":"10.1101/2022.05.29.493900","authors":"Almogy G, Pratt M, Oberstrass F, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this preprint by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper.","This is a preprint: it has not been peer reviewed, and Europe PMC links no journal version of it at the time of writing."]},{"id":"paper-cou-aa-301-abiraterone-de-bono-nejm-2011","kind":"paper","name":"COU-AA-301: abiraterone and increased survival in metastatic castration-resistant prostate cancer after docetaxel","aka":[],"tldr":"Abiraterone, a pill that blocks androgen synthesis throughout the body, lengthened survival in men with metastatic prostate cancer that had progressed after docetaxel, proving that the disease remains hormone-driven even when castration-resistant.","summary":"Phase 3 placebo-controlled trial of 1,195 men with metastatic castration-resistant prostate cancer previously treated with docetaxel randomised 2:1 to abiraterone plus prednisone or placebo plus prednisone.\n\nMedian overall survival was 14.8 versus 10.9 months (hazard ratio 0.65), with improvements in PSA response, radiographic progression and pain; mineralocorticoid excess (fluid retention, hypokalaemia, hypertension) was the characteristic toxicity.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2011","url":"https://doi.org/10.1056/NEJMoa1014618"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21612468/"}],"tags":[],"related":["prostate-roadmap","paper-attard-abiraterone-phase-1-cyp17-jco-2008","paper-scher-affirm-enzalutamide-nejm-2012"],"cancers":["prostate-mcrpc","prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2011,"doi":"10.1056/NEJMoa1014618","pmid":"21612468","authors":"de Bono JS, Logothetis CJ, Molina A, et al.","paperType":"rct","findings":["Median overall survival 14.8 vs 10.9 months; hazard ratio 0.65.","PSA response 29 percent vs 6 percent."],"whatItMeans":"Abiraterone became a standard treatment for metastatic castration-resistant prostate cancer and, after later trials, for hormone-sensitive and high-risk localised disease.","caveats":["Requires concurrent prednisone.","Cross-resistance with enzalutamide limits sequential use."],"changedPractice":true,"participants":1195},{"id":"paper-coussens-werb-inflammation-cancer-nature-2002","kind":"paper","name":"Coussens and Werb 2002: inflammation and cancer","aka":[],"tldr":"The review that made the immune cells inside a tumour part of the disease: long-running inflammation, whether from infection, irritation or the tumour's own signals, supplies growth factors, blood vessels and DNA damage that help cancers start and spread.","summary":"Coussens and Werb drew together epidemiology and mouse genetics to argue that chronic inflammation is a cause of cancer rather than a bystander. They reviewed the infections and inflammatory conditions tied to specific cancers, such as Helicobacter pylori and stomach cancer, hepatitis viruses and liver cancer, and inflammatory bowel disease and bowel cancer, and described how macrophages, neutrophils and mast cells in the tumour microenvironment release cytokines, proteases, reactive oxygen species and angiogenic factors that promote proliferation, invasion and new blood vessels. They cited estimates that about 15% of cancers worldwide are linked to infection and proposed that anti-inflammatory strategies could prevent or treat cancer.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1038/nature01322"}],"tags":[],"related":["paper-hallmarks-of-cancer-cell-2000"],"cancers":["gastric","hcc","colorectal"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["inflammation","immune-system"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature","year":2002,"doi":"10.1038/nature01322","authors":"Coussens LM, Werb Z.","paperType":"review","findings":["Chronic inflammation from infection or irritation precedes many cancers; the authors cite estimates that about 15% of cancers worldwide are attributable to infections.","Innate immune cells recruited to tumours supply cytokines, growth factors, proteases and reactive oxygen species that drive proliferation, angiogenesis, invasion and DNA damage.","Mouse models in which inflammatory cells or their mediators are removed develop fewer or slower tumours."],"whatItMeans":"This paper is why the tumour microenvironment is studied as intensely as the cancer cell itself. It underpins vaccination against HPV and hepatitis B as cancer prevention, aspirin and anti-inflammatory trials in bowel cancer, and the current work on macrophages and myeloid cells as immunotherapy targets.","caveats":["A review, so it synthesises rather than tests; several proposed mechanisms rested on mouse models.","Inflammation is also part of effective anti-tumour immunity, and the balance between the two is still being worked out."],"changedPractice":false},{"id":"paper-weisenberger-cimp-braf-mlh1-colorectal-nat-genet-2006","kind":"paper","name":"CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer","aka":[],"tldr":"Some bowel cancers switch off large numbers of genes by chemical tagging. This study settled a long argument by showing that those tumours are a genuinely distinct group, that they nearly all carry a BRAF mutation, and that they are where sporadic loss of the DNA spell-checker comes from.","summary":"A systematic, stepwise screen of 195 CpG island methylation markers using MethyLight technology was performed on 295 primary human colorectal tumours, involving 16,785 separate quantitative analyses. CIMP-positive tumours were shown to represent a distinct subset, encompassing almost all cases of tumours with BRAF mutation (odds ratio 203). Sporadic cases of mismatch repair deficiency occurred almost exclusively as a consequence of CIMP-associated methylation of MLH1. The authors proposed a five-marker panel to classify CIMP-positive tumours.","asOf":"2026-09-24","links":[{"label":"Weisenberger et al., Nat Genet 2006: CIMP underlies sporadic microsatellite instability and tracks BRAF mutation (295 tumours)","url":"https://doi.org/10.1038/ng1834"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/16804544/"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["methylation-profiling"],"targets":["braf","mlh1","mmr"],"drugs":[],"companies":[],"institutions":[],"pathways":["epigenetic-reprogramming","mismatch-repair-msi"],"terms":["msi","lynch-syndrome"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":2006,"doi":"10.1038/ng1834","pmid":"16804544","authors":"Weisenberger DJ, Siegmund KD, Campan M, et al.","paperType":"translational","findings":["CIMP-positive tumours are a distinct subset encompassing almost all BRAF-mutant cancers (odds ratio 203).","Sporadic mismatch repair deficiency arises almost exclusively through CIMP-associated MLH1 methylation.","A five-marker classification panel was proposed."],"whatItMeans":"It is the molecular definition of the serrated route and the reason BRAF V600E is used as a practical surrogate for sporadic rather than inherited MLH1 loss.","caveats":["Marker panels for CIMP still differ between laboratories, so reported CIMP rates vary.","CIMP is not itself a treatment decision anywhere."],"changedPractice":false,"participants":295},{"id":"paper-cpx-351-study-301-lancet-je-jco-2018","kind":"paper","name":"CPX-351 versus 7+3 chemotherapy in older adults with newly diagnosed secondary acute myeloid leukaemia","aka":[],"tldr":"A liposomal formulation locking cytarabine and daunorubicin in a fixed ratio lengthened survival compared with standard 7+3 chemotherapy in patients aged 60 to 75 with secondary or therapy-related acute myeloid leukaemia, and more of them reached transplant.","summary":"Phase 3 trial of 309 patients aged 60 to 75 with newly diagnosed high-risk or secondary AML randomised to CPX-351 or conventional cytarabine plus daunorubicin (7+3).\n\nMedian overall survival was 9.56 months with CPX-351 against 5.95 months with 7+3 (hazard ratio 0.69); remission rates were higher and outcomes after transplant were better, with a longer recovery of blood counts as the main cost.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2018","url":"https://doi.org/10.1200/JCO.2017.77.6112"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30024784/"}],"tags":[],"related":[],"cancers":["aml-secondary"],"sections":[],"technologies":[],"targets":[],"drugs":["cytarabine","daunorubicin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["jeffrey-lancet"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2018,"doi":"10.1200/JCO.2017.77.6112","pmid":"30024784","authors":"Lancet JE, Uy GL, Cortes JE, et al.","paperType":"rct","findings":["Median overall survival 9.56 vs 5.95 months; hazard ratio 0.69.","Complete remission (with or without incomplete recovery) 47.7 percent vs 33.3 percent."],"whatItMeans":"CPX-351 is the preferred intensive induction for fit older patients with secondary or therapy-related AML in many centres, mainly as a bridge to allogeneic transplant.","caveats":["Open-label; longer neutropenia and thrombocytopenia with CPX-351.","Benefit in patients under 60 and in de novo AML is not established."],"changedPractice":true,"participants":309},{"id":"paper-schoffski-lancet-respir-med","kind":"paper","name":"Crizotinib in patients with advanced, inoperable inflammatory myofibroblastic tumours with and without anaplastic lymphoma kinase gene alterations (European Organisation for Research and Treatment of Cancer 90101 CREATE): a multicentre, single-drug, prospective, non-randomised phase 2 trial","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 29669701 and published in The Lancet. Respiratory medicine; the citing page links this DOI, which is how the record was matched.","summary":"Background: An inflammatory myofibroblastic tumour (IMFT) is a rare mesenchymal neoplasm characterised by anaplastic lymphoma kinase (ALK) gene rearrangements. We assessed the activity and safety of crizotinib, a tyrosine kinase inhibitor, targeting ALK in patients with advanced IMFT either with or without ALK alterations.\n\nMethods: We did a multicentre, biomarker-driven, single-drug, non-randomised, open-label, two-stage phase 2 trial (European Organisation for Research and Treatment of Cancer 90101 CREATE) at 13 study sites (five university hospitals and eight specialty clinics) in eight European countries (Belgium, France, Germany, Italy, Netherlands, Poland, Slovakia, and the UK). Eligible participants were patients aged at least 15 years with a local diagnosis of advanced or metastatic IMFT deemed incurable with surgery, radiotherapy, or systemic therapy; measurable disease; an Eastern Cooperative Oncology Group performance status of 0-2; and adequate haematological, renal, and liver function. Central reference pathology was done for confirmation of the diagnosis, and ALK positivity or negativity was assessed centrally using immunohistochemistry and fluorescence in-situ hybridisation based on archival tumour tissue and defined as ALK immunopositivity or rearrangements in at least 15% of tumour cells. Eligible ALK-positive and ALK-negative patients received oral crizotinib 250 mg twice per day administered on a continuous daily dosing schedule (the duration of each treatment cycle was 21 days) until documented disease progression, unacceptable toxicity, or patient refusal. If at least two of the first 12 eligible and assessable ALK-positive patients achieved a confirmed complete or partial response according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, a maximum of 35 patients were to be enrolled. If at least six ALK-positive patients achieved a confirmed response, the trial would be deemed successful. The primary endpoint was the proportion of patients who achieved an objective response (ie, a complete or partial response) as per RECIST 1.1, with response confirmation assessed by the local investigator every other cycle. Activity and safety endpoints were analysed in the per-protocol population. This trial is registered with ClinicalTrials.gov, number NCT01524926.\n\nFindings: Between Oct 3, 2012, and April 12, 2017, we recruited and treated 20 eligible participants, 19 of whom were assessable for the primary endpoint. Median follow-up was 863 days (IQR 358-1304). Six of 12 ALK-positive patients (50%, 95% CI 21·1-78·9) and one of seven ALK-negative patients (14%, 0·0-57·9) achieved an objective response. The most common treatment-related adverse events in the 20 participants were nausea (11 [55%]), fatigue (9 [45%]), blurred vision (nine [45%]), vomiting (seven [35%]), and diarrhoea (seven [35%]). Eight serious adverse events occurred in five patients: pneumonia, fever of unknown cause, a heart attack with increased creatinine and possible sepsis, an abdominal abscess with acute renal insufficiency, and a QT prolongation.\n\nInterpretation: With 50% of participants with ALK-positive tumours achieving an objective response, crizotinib met the prespecified criteria for success in this trial. The results presented here support the rationale for inhibiting ALK in patients with IMFT. Crizotinib could be considered as the standard of care for patients with locally advanced or metastatic ALK-positive IMFT who do not qualify for curative surgery.\n\nFunding: The European Organisation for Research and Treatment of Cancer and Pfizer.\n\nIndexed on Europe PMC as PubMed record 29669701 (DOI 10.1016/s2213-2600(18)30116-4). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Respir Med 2018","url":"https://doi.org/10.1016/s2213-2600(18)30116-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29669701/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29669701"}],"tags":["europepmc-ingest"],"related":["inflammatory-myofibroblastic-tumour"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Lancet. Respiratory medicine","year":2018,"doi":"10.1016/s2213-2600(18)30116-4","pmid":"29669701","authors":"Schöffski P, Sufliarsky J, Gelderblom H, et al.","paperType":"rct","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-shaw-crizotinib-ros1-nejm-2014","kind":"paper","name":"Crizotinib in ROS1-rearranged non-small-cell lung cancer","aka":[],"tldr":"Crizotinib shrank tumours in almost three quarters of patients with ROS1-rearranged lung cancer and controlled the disease for a median of 19 months, establishing ROS1 as a targetable driver and leading to the first approval.","summary":"Expansion cohort of a phase 1 study treating 50 patients with advanced ROS1-rearranged non-small-cell lung cancer with crizotinib 250 mg twice daily.\n\nObjective response was 72 percent with median duration of response 17.6 months and median progression-free survival 19.2 months; the safety profile matched that seen in ALK-positive disease.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2014","url":"https://doi.org/10.1056/NEJMoa1406766"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25264305/"}],"tags":[],"related":[],"cancers":["ros1-positive-nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":["crizotinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["alice-shaw"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2014,"doi":"10.1056/NEJMoa1406766","pmid":"25264305","authors":"Shaw AT, Ou SH, Bang YJ, et al.","paperType":"observational","findings":["Objective response 72 percent.","Median progression-free survival 19.2 months."],"whatItMeans":"ROS1 testing became standard in lung adenocarcinoma; crizotinib was the first approved ROS1 inhibitor and remains an option, though entrectinib, repotrectinib and taletrectinib now offer brain penetration and resistance coverage.","caveats":["Single-arm study of 50 patients.","Poor brain penetration and the G2032R resistance mutation limit crizotinib."],"changedPractice":true,"participants":50},{"id":"paper-alk-nsclc-n-engl-j-med-2013","kind":"paper","name":"Crizotinib versus chemotherapy in advanced ALK-positive lung cancer","aka":[],"tldr":"Phase 2 or 3 results paper on ALK in Non-small-cell lung cancer, in New England Journal of Medicine (2013), one of the most cited Europe PMC records with ALK in its title.","summary":"Background: In single-group studies, chromosomal rearrangements of the anaplastic lymphoma kinase gene (ALK) have been associated with marked clinical responses to crizotinib, an oral tyrosine kinase inhibitor targeting ALK. Whether crizotinib is superior to standard chemotherapy with respect to efficacy is unknown.\n\nMethods: We conducted a phase 3, open-label trial comparing crizotinib with chemotherapy in 347 patients with locally advanced or metastatic ALK-positive lung cancer who had received one prior platinum-based regimen. Patients were randomly assigned to receive oral treatment with crizotinib (250 mg) twice daily or intravenous chemotherapy with either pemetrexed (500 mg per square meter of body-surface area) or docetaxel (75 mg per square meter) every 3 weeks. Patients in the chemotherapy group who had disease progression were permitted to cross over to crizotinib as part of a separate study. The primary end point was progression-free survival.\n\nResults: The median progression-free survival was 7.7 months in the crizotinib group and 3.0 months in the chemotherapy group (hazard ratio for progression or death with crizotinib, 0.49; 95% confidence interval [CI], 0.37 to 0.64; P<0.001). The response rates were 65% (95% CI, 58 to 72) with crizotinib, as compared with 20% (95% CI, 14 to 26) with chemotherapy (P<0.001). An interim analysis of overall survival showed no significant improvement with crizotinib as compared with chemotherapy (hazard ratio for death in the crizotinib group, 1.02; 95% CI, 0.68 to 1.54; P=0.54). Common adverse events associated with crizotinib were visual disorder, gastrointestinal side effects, and elevated liver aminotransferase levels, whereas common adverse events with chemotherapy were fatigue, alopecia, and dyspnea. Patients reported greater reductions in symptoms of lung cancer and greater improvement in global quality of life with crizotinib than with chemotherapy.\n\nConclusions: Crizotinib is superior to standard chemotherapy in patients with previously treated, advanced non-small-cell lung cancer with ALK rearrangement. (Funded by Pfizer; ClinicalTrials.gov number, NCT00932893.).\n\nIndexed on Europe PMC as PubMed record 23724913 (DOI 10.1056/nejmoa1214886). Its title names ALK and its text names Non-small-cell lung cancer; PubMed types it as a clinical trial report (Clinical Trial, Phase III, Comparative Study, Research Support, Non-U.S. Gov't, Multicenter Study, Randomized Controlled Trial). It was matched automatically to the idea \"Test intermittent dosing of targeted drugs to delay resistance, with honest priors\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2013","url":"https://doi.org/10.1056/nejmoa1214886"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23724913/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/23724913"}],"tags":["europepmc-ingest"],"related":["lung-cancer-evidence-roadmap","paper-kwak-crizotinib-alk-nsclc-nejm-2010","paper-soda-eml4-alk-fusion-nature-2007"],"cancers":["lung-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2013,"doi":"10.1056/nejmoa1214886","pmid":"23724913","authors":"Shaw AT, Kim DW, Nakagawa K, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for ALK in Non-small-cell lung cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by ALK in the title and Non-small-cell lung cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-elyada-antigen-presenting-cafs-single-cell-cancer-discov-2019","kind":"paper","name":"Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts","aka":[],"tldr":"Reading pancreatic tumours one cell at a time confirmed the two known fibroblast types and found a third that carries the molecules used to show antigens to immune cells and can switch on helper T cells.","summary":"Single-cell RNA sequencing characterised the neoplastic and microenvironment content of human and mouse pancreatic tumours. Myofibroblastic and inflammatory CAFs were corroborated and their in vivo gene signatures defined. A new CAF population expressing MHC class II and CD74 but not classic costimulatory molecules was described and termed antigen-presenting CAFs; they activated CD4-positive T cells in an antigen-specific fashion in a model system, confirming an immune-modulatory capacity.","asOf":"2026-09-24","links":[{"label":"Elyada et al., Cancer Discov 2019: antigen-presenting fibroblasts by single-cell sequencing","url":"https://doi.org/10.1158/2159-8290.CD-19-0094"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31197017/"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":["single-cell-spatial"],"targets":[],"drugs":[],"companies":[],"institutions":["cold-spring-harbor"],"pathways":["caf-activation-desmoplasia","antigen-presentation-immunoediting","tumor-microenvironment"],"terms":[],"trials":[],"people":["david-tuveson","elizabeth-jaffee"],"bottlenecks":[],"keyPapers":[],"journals":["cancer-discovery"],"dependsOn":[],"notes":[],"journal":"Cancer Discovery","year":2019,"doi":"10.1158/2159-8290.CD-19-0094","pmid":"31197017","authors":"Elyada E, Bolisetty M, Laise P, et al.","paperType":"basic","findings":["Three CAF states: myofibroblastic, inflammatory and antigen-presenting.","Antigen-presenting CAFs express MHC class II and CD74 and activate CD4 T cells in a model."],"whatItMeans":"Fibroblasts are part of the immune conversation, not just a physical barrier, which is why stromal and immune strategies are now designed together.","caveats":["Descriptive single-cell atlas; function shown in a model system.","Whether antigen-presenting CAFs help or suppress immunity in patients is unknown."],"changedPractice":false},{"id":"paper-cross-nejm-2012","kind":"paper","name":"CROSS: preoperative chemoradiotherapy for oesophageal or junctional cancer","aka":[],"tldr":"Five weeks of carboplatin-paclitaxel with radiotherapy before oesophagectomy lengthened median survival from 24 to 49 months in oesophageal cancer compared with surgery alone, with a complete pathological response in almost half of squamous cancers.","summary":"Phase 3 trial of 366 patients with resectable oesophageal or junctional cancer (75 percent adenocarcinoma) randomised to weekly carboplatin-paclitaxel with 41.4 Gy radiotherapy followed by surgery, or surgery alone.\n\nMedian overall survival was 49.4 versus 24.0 months (hazard ratio 0.657), complete resection 92 versus 69 percent and pathological complete response 29 percent overall (49 percent in squamous cell carcinoma); the ten-year update confirmed the benefit.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2012","url":"https://doi.org/10.1056/NEJMoa1112088"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22646630/"}],"tags":[],"related":[],"cancers":["oesophageal-adenocarcinoma","oesophageal-squamous-cell-carcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["cross"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2012,"doi":"10.1056/NEJMoa1112088","pmid":"22646630","authors":"van Hagen P, Hulshof MC, van Lanschot JJ, et al.","paperType":"rct","findings":["Median overall survival 49.4 vs 24.0 months; hazard ratio 0.657.","Pathological complete response 29 percent overall; 49 percent in squamous cell carcinoma."],"whatItMeans":"CROSS chemoradiotherapy is a standard for locally advanced oesophageal cancer, particularly squamous cell carcinoma; for adenocarcinoma, perioperative FLOT is now often preferred after ESOPEC.","caveats":["Adenocarcinoma benefit was smaller than in squamous cell carcinoma.","Postoperative morbidity was not increased but the regimen requires fitness for surgery."],"changedPractice":true,"participants":366},{"id":"paper-csco-asco-nasopharyngeal-carcinoma-guideline-jco-2021","kind":"paper","name":"CSCO and ASCO guideline: chemotherapy in combination with radiotherapy for definitive-intent treatment of stage II to IVA nasopharyngeal carcinoma","aka":[],"tldr":"The joint Chinese and American guideline on when to add chemotherapy to radiotherapy for nasopharyngeal cancer: concurrent cisplatin for most stage II to IVA disease, induction gemcitabine-cisplatin for higher-risk disease, and how to handle patients who cannot take cisplatin.","summary":"Evidence-based guideline from the Chinese Society of Clinical Oncology and the American Society of Clinical Oncology based on a systematic review of randomised trials in stage II to IVA nasopharyngeal carcinoma, recommending concurrent cisplatin chemoradiotherapy, induction chemotherapy (gemcitabine-cisplatin preferred) for stage III to IVA disease with high-risk features, adjuvant chemotherapy in selected patients, and alternatives for cisplatin-ineligible patients, with cumulative cisplatin dose targets.","asOf":"2026-09-18","links":[{"label":"J Clin Oncol 2021","url":"https://doi.org/10.1200/JCO.20.03237"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33405943/"}],"tags":[],"related":[],"cancers":["locoregionally-advanced-nasopharyngeal-carcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":["cisplatin","gemcitabine-cisplatin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2021,"doi":"10.1200/JCO.20.03237","pmid":"33405943","authors":"Chen YP, Ismaila N, Chua MLK, et al.","paperType":"guideline","findings":[],"whatItMeans":"The standard-of-care rows on the locoregionally advanced nasopharyngeal page follow this guideline.","caveats":["Predates trials adding PD-1 antibodies to chemoradiotherapy and metronomic capecitabine adjuvant therapy.","Most evidence comes from endemic regions."],"changedPractice":true},{"id":"paper-stecklein-ctdna-rcb-tnbc-residual-disease-npj-2023","kind":"paper","name":"ctDNA and residual cancer burden are prognostic in triple-negative breast cancer patients with residual disease","aka":[],"tldr":"Among 80 women with triple-negative cancer left at surgery after chemotherapy, a third had ctDNA in their blood; their three-year event-free survival was 48% against 82%, and the blood test added to the pathologist's residual cancer burden score.","summary":"End-of-treatment ctDNA was analysed in 80 TNBC patients with residual disease after neoadjuvant systemic therapy in a prospective multisite registry. 33% were ctDNA-positive; residual cancer burden was RCB-I 26%, RCB-II 49%, RCB-III 18%. ctDNA positivity rose with RCB class (14%, 31%, 57%; P 0.028) and was associated with inferior three-year event-free survival (48% versus 82%) and overall survival (50% versus 86%), including within RCB-II (65% versus 87%). RCB class (HR 5.16) and ctDNA status (HR 3.71) were independently prognostic after adjusting for T stage and nodes.","asOf":"2026-09-24","links":[{"label":"Stecklein et al., npj Breast Cancer 2023: ctDNA and residual cancer burden in 80 TNBC patients with residual disease","url":"https://doi.org/10.1038/s41523-023-00512-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36878909/"}],"tags":[],"related":["ctdna-mrd-positive"],"cancers":["tnbc","tnbc-early"],"sections":[],"technologies":["mrd-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ctdna","rcb","mrd"],"trials":[],"people":["priyanka-sharma"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"npj Breast Cancer","year":2023,"doi":"10.1038/s41523-023-00512-7","pmid":"36878909","authors":"Stecklein SR, Kimler BF, Yoder R, et al.","paperType":"observational","findings":["ctDNA positive in 33%; 14%, 31% and 57% of RCB-I, II and III.","Three-year EFS 48% versus 82%; OS 50% versus 86%.","RCB (HR 5.16) and ctDNA (HR 3.71) independently prognostic."],"whatItMeans":"ctDNA and RCB measure different things and both should stratify post-neoadjuvant TNBC trials; an RCB-II patient with negative ctDNA has an 87% three-year event-free survival.","caveats":["80 patients; registry rather than trial.","Assay details and lead times are not in the abstract."],"changedPractice":false,"participants":80},{"id":"paper-pd-1-nsclc-am-j-clin-oncol-2016","kind":"paper","name":"CTLA-4 and PD-1 Pathways: Similarities, Differences, and Implications of Their Inhibition","aka":[],"tldr":"Review on PD-1 in Non-small-cell lung cancer, in American journal of clinical oncology (2016), one of the most cited Europe PMC records with PD-1 in its title.","summary":"The cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1) immune checkpoints are negative regulators of T-cell immune function. Inhibition of these targets, resulting in increased activation of the immune system, has led to new immunotherapies for melanoma, non-small cell lung cancer, and other cancers. Ipilimumab, an inhibitor of CTLA-4, is approved for the treatment of advanced or unresectable melanoma. Nivolumab and pembrolizumab, both PD-1 inhibitors, are approved to treat patients with advanced or metastatic melanoma and patients with metastatic, refractory non-small cell lung cancer. In addition the combination of ipilimumab and nivolumab has been approved in patients with BRAF WT metastatic or unresectable melanoma. The roles of CTLA-4 and PD-1 in inhibiting immune responses, including antitumor responses, are largely distinct. CTLA-4 is thought to regulate T-cell proliferation early in an immune response, primarily in lymph nodes, whereas PD-1 suppresses T cells later in an immune response, primarily in peripheral tissues. The clinical profiles of immuno-oncology agents inhibiting these 2 checkpoints may vary based on their mechanistic differences. This article provides an overview of the CTLA-4 and PD-1 pathways and implications of their inhibition in cancer therapy.\n\nIndexed on Europe PMC as PubMed record 26558876 (DOI 10.1097/coc.0000000000000239). Its title names PD-1 and its text names Non-small-cell lung cancer; PubMed types it as a review (review-article, Review). It was matched automatically to the idea \"Give immunotherapy in the morning\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Am J Clin Oncol 2016","url":"https://doi.org/10.1097/coc.0000000000000239"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26558876/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26558876"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["american-journal-of-clinical-oncology"],"dependsOn":[],"notes":[],"journal":"American journal of clinical oncology","year":2016,"doi":"10.1097/coc.0000000000000239","pmid":"26558876","authors":"Buchbinder EI, Desai A","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for PD-1 in Non-small-cell lung cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by PD-1 in the title and Non-small-cell lung cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-cupisco-molecularly-guided-therapy-cup-lancet-2024","kind":"paper","name":"CUPISCO: molecularly guided therapy versus chemotherapy after disease control in unfavourable cancer of unknown primary","aka":[],"tldr":"In the first large randomised trial in cancer of unknown primary, choosing a targeted drug or immunotherapy from the tumour's genomic profile after three cycles of chemotherapy held the disease back for longer than simply continuing chemotherapy.","summary":"International open-label randomised phase 2 trial in which 636 patients with newly diagnosed unfavourable cancer of unknown primary received three cycles of platinum-based chemotherapy; the 436 with disease control were randomised 3:1 to molecularly guided therapy chosen by a tumour board from comprehensive genomic profiling or to three further cycles of the same chemotherapy.\n\nMedian progression-free survival was 6.1 months with molecularly guided therapy against 4.4 months with chemotherapy (hazard ratio 0.72). Overall survival data were immature.","asOf":"2026-09-18","links":[{"label":"Lancet 2024","url":"https://doi.org/10.1016/S0140-6736(24)00814-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39096924/"}],"tags":[],"related":[],"cancers":["cup-unfavourable"],"sections":[],"technologies":[],"targets":[],"drugs":["carboplatin","paclitaxel","gemcitabine-cisplatin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["cupisco"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2024,"doi":"10.1016/S0140-6736(24)00814-6","pmid":"39096924","authors":"Krämer A, Bochtler T, Pauli C, et al.","paperType":"rct","findings":["Median progression-free survival 6.1 months with molecularly guided therapy versus 4.4 months with continued chemotherapy; hazard ratio 0.72.","About one third of enrolled patients progressed during induction and were never randomised."],"whatItMeans":"Comprehensive genomic profiling at diagnosis is now justified for unfavourable cancer of unknown primary, with a switch to a matched drug after induction chemotherapy when an actionable target is found.","caveats":["Open-label, progression-free survival endpoint, and the benefit was modest in absolute terms.","Many patients had no actionable alteration and received drugs of uncertain value."],"changedPractice":true,"participants":436},{"id":"paper-falini-npm1-nejm-2005","kind":"paper","name":"Cytoplasmic nucleophosmin in acute myeloid leukaemia with a normal karyotype","aka":[],"tldr":"This study discovered that about a third of acute myeloid leukaemias, and most with normal chromosomes, carry a mutation in the NPM1 gene that displaces its protein into the cytoplasm, defining a distinct and relatively favourable form of the disease.","summary":"Immunohistochemical and sequencing study of 591 AML cases showing cytoplasmic nucleophosmin in 35 percent, almost always caused by mutations in exon 12 of NPM1, concentrated in normal-karyotype AML (about 50 to 60 percent), associated with monocytic features, CD34 negativity and a good response to induction chemotherapy in the absence of FLT3-ITD.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2005","url":"https://doi.org/10.1056/NEJMoa041974"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/15659725/"}],"tags":[],"related":[],"cancers":["aml-npm1-kmt2a"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2005,"doi":"10.1056/NEJMoa041974","pmid":"15659725","authors":"Falini B, Mecucci C, Tiacci E, et al.","paperType":"translational","findings":["Cytoplasmic NPM1 in 35.2 percent of primary AML and in the majority of normal-karyotype cases.","Associated with higher complete remission rates and mutual exclusivity with recurrent translocations."],"whatItMeans":"NPM1-mutated AML is now its own WHO category. The mutation is a stable target for measurable residual disease monitoring and the disease is one of the two indications for menin inhibitors.","caveats":["Prognostic benefit is lost when FLT3-ITD is co-mutated at high allelic ratio.","Discovery study; clinical management implications developed over the following decade."],"changedPractice":true,"participants":591},{"id":"paper-yan-peritoneal-mesothelioma-crs-hipec-jco-2009","kind":"paper","name":"Cytoreductive surgery and HIPEC for malignant peritoneal mesothelioma: multi-institutional registry","aka":[],"tldr":"Pooling eight centres, this registry showed that removing all visible peritoneal mesothelioma and washing the abdomen with heated chemotherapy gave a median survival of over four years, transforming the outlook for selected patients.","summary":"Retrospective multi-institutional registry of 405 patients with diffuse malignant peritoneal mesothelioma treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy at eight specialised centres.\n\nMedian overall survival was 53 months with three- and five-year survival of 60 and 47 percent; epithelioid histology, absence of nodal metastases, completeness of cytoreduction and use of HIPEC were independently associated with survival, while perioperative mortality was 2 percent.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2009","url":"https://doi.org/10.1200/JCO.2009.23.9640"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19917862/"}],"tags":[],"related":[],"cancers":["peritoneal-mesothelioma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2009,"doi":"10.1200/JCO.2009.23.9640","pmid":"19917862","authors":"Yan TD, Deraco M, Baratti D, et al.","paperType":"observational","findings":["Median overall survival 53 months; five-year survival 47 percent.","Completeness of cytoreduction and epithelioid subtype were the strongest prognostic factors."],"whatItMeans":"Cytoreductive surgery with HIPEC in an experienced centre is the standard for fit patients with resectable epithelioid peritoneal mesothelioma, a disease that had a median survival of about a year on chemotherapy alone.","caveats":["Retrospective registry with selection of fit patients with resectable disease.","No randomised comparison with systemic therapy exists."],"changedPractice":true,"participants":405},{"id":"paper-quenet-prodige-7-hipec-peritoneal-colorectal-lancet-oncol-2021","kind":"paper","name":"Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases (PRODIGE 7)","aka":[],"tldr":"The trial that took the heated chemotherapy away and found the survival was the same: 41.7 against 41.2 months. The benefit had always been in the surgery.","summary":"Quénet, Elias, Roca and colleagues ran a randomised open-label phase 3 trial at 17 cancer centres in France in patients aged 18 to 70 with histologically proven colorectal cancer and peritoneal metastases, WHO performance status 0 or 1, a Peritoneal Cancer Index of 25 or less, and eligibility for six months of systemic chemotherapy. Patients in whom complete macroscopic resection, or resection with less than 1 mm of residual tumour, was achieved were randomised 1:1 to cytoreductive surgery with or without oxaliplatin-based hyperthermic intraperitoneal chemotherapy. All patients received systemic chemotherapy with or without targeted therapy before or after surgery, or both. The primary endpoint was overall survival in the intention-to-treat population.\n\nBetween February 2008 and January 2014, 265 patients were randomised: 133 to surgery plus hyperthermic intraperitoneal chemotherapy and 132 to surgery alone.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2021","url":"https://doi.org/10.1016/S1470-2045(20)30599-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33476595/"}],"tags":["colorectal-evidence"],"related":["paper-verwaal-cytoreduction-hipec-peritoneal-colorectal-jco-2003"],"cancers":["colorectal"],"sections":["surgery","chemotherapy"],"technologies":["hipec"],"targets":[],"drugs":["oxaliplatin","fluorouracil","leucovorin"],"companies":["unicancer"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-negative-results","b-surgery-radiation-innovation"],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2021,"doi":"10.1016/S1470-2045(20)30599-4","pmid":"33476595","authors":"Quénet F, Elias D, Roca L, et al.","paperType":"rct","findings":["After a median 63.8 months, median overall survival 41.7 months (95 percent CI 36.2 to 53.8) with hyperthermic intraperitoneal chemotherapy against 41.2 months (35.1 to 49.7) without: hazard ratio 1.00 (95.37 percent CI 0.63 to 1.58), stratified log-rank p=0.99.","Two treatment-related deaths at 30 days in each group.","Grade 3 or worse adverse events at 30 days were similar (56 of 133, 42 percent, against 42 of 132, 32 percent; p=0.083) but more common at 60 days with hyperthermic intraperitoneal chemotherapy (34 of 131, 26 percent, against 20 of 130, 15 percent; p=0.035)."],"whatItMeans":"Complete cytoreductive surgery with modern systemic chemotherapy gives a median survival over 40 months in selected patients with peritoneal metastases, and the heated intraperitoneal oxaliplatin adds only late complications.","caveats":["The trial tests oxaliplatin-based hyperthermic chemotherapy specifically; mitomycin-based regimens and pressurised aerosol delivery are not addressed.","Highly selected patients: Peritoneal Cancer Index 25 or less, under 70, fit for six months of chemotherapy, and randomised only after complete cytoreduction was achieved.","A 41-month median survival in both arms is far better than historic series and reflects that selection, not a general result for peritoneal disease."],"changedPractice":true,"participants":265},{"id":"paper-fitzgerald-lancet","kind":"paper","name":"Cytosponge-trefoil factor 3 versus usual care to identify Barrett's oesophagus in a primary care setting: a multicentre, pragmatic, randomised controlled trial","aka":[],"tldr":"Paper cited by one idea page, indexed on Europe PMC as PubMed record 32738955 and published in The Lancet; the citing page links this DOI, which is how the record was matched.","summary":"Background: Treatment of dysplastic Barrett's oesophagus prevents progression to adenocarcinoma; however, the optimal diagnostic strategy for Barrett's oesophagus is unclear. The Cytosponge-trefoil factor 3 (TFF3) is a non-endoscopic test for Barrett's oesophagus. The aim of this study was to investigate whether offering this test to patients on medication for gastro-oesophageal reflux would increase the detection of Barrett's oesophagus compared with standard management.\n\nMethods: This multicentre, pragmatic, randomised controlled trial was done in 109 socio-demographically diverse general practice clinics in England. Randomisation was done both at the general practice clinic level (cluster randomisation) and at the individual patient level, and the results for each type of randomisation were analysed separately before being combined. Patients were eligible if they were aged 50 years or older, had been taking acid-suppressants for symptoms of gastro-oesophageal reflux for more than 6 months, and had not undergone an endoscopy procedure within the past 5 years. General practice clinics were selected by the local clinical research network and invited to participate in the trial. For cluster randomisation, clinics were randomly assigned (1:1) by the trial statistician using a computer-generated randomisation sequence; for individual patient-level randomisation, patients were randomly assigned (1:1) by the general practice clinics using a centrally prepared computer-generated randomisation sequence. After randomisation, participants received either standard management of gastro-oesophageal reflux (usual care group), in which participants only received an endoscopy if required by their general practitioner, or usual care plus an offer of the Cytosponge-TFF3 procedure, with a subsequent endoscopy if the procedure identified TFF3-positive cells (intervention group). The primary outcome was the diagnosis of Barrett's oesophagus at 12 months after enrolment, expressed as a rate per 1000 person-years, in all participants in the intervention group (regardless of whether they had accepted the offer of the Cytosponge-TFF3 procedure) compared with all participants in the usual care group. Analyses were intention-to-treat. The trial is registered with the ISRCTN registry, ISRCTN68382401, and is completed.\n\nFindings: Between March 20, 2017, and March 21, 2019, 113 general practice clinics were enrolled, but four clinics dropped out shortly after randomisation. Using an automated search of the electronic prescribing records of the remaining 109 clinics, we identified 13 657 eligible patients who were sent an introductory letter with 14 days to opt out. 13 514 of these patients were randomly assigned (per practice or at the individual patient level) to the usual care group (n=6531) or the intervention group (n=6983). Following randomisation, 149 (2%) of 6983 participants in the intervention group and 143 (2%) of 6531 participants in the usual care group, on further scrutiny, did not meet all eligibility criteria or withdrew from the study. Of the remaining 6834 participants in the intervention group, 2679 (39%) expressed an interest in undergoing the Cytosponge-TFF3 procedure. Of these, 1750 (65%) met all of the eligibility criteria on telephone screening and underwent the procedure. Most of these participants (1654 [95%]; median age 69 years) swallowed the Cytosponge successfully and produced a sample. 231 (3%) of 6834 participants had a positive Cytosponge-TFF3 result and were referred for an endoscopy. Patients who declined the offer of the Cytosponge-TFF3 procedure and all participants in the usual care group only had an endoscopy if deemed necessary by their general practitioner. During an average of 12 months of follow-up, 140 (2%) of 6834 participants in the intervention group and 13 (<1%) of 6388 participants in the usual care group were diagnosed with Barrett's oesophagus (absolute difference 18·3 per 1000 person-years [95% CI 14·8-21·8]; rate ratio adjusted for cluster randomisation 10·6 [95% CI 6·0-18·8], p<0·0001). Nine (<1%) of 6834 participants were diagnosed with dysplastic Barrett's oesophagus (n=4) or stage I oesophago-gastric cancer (n=5) in the intervention group, whereas no participants were diagnosed with dysplastic Barrett's oesophagus or stage I gastro-oesophageal junction cancer in the usual care group. Among 1654 participants in the intervention group who swallowed the Cytosponge device successfully, 221 (13%) underwent endoscopy after testing positive for TFF3 and 131 (8%, corresponding to 59% of those having an endoscopy) were diagnosed with Barrett's oesophagus or cancer. One patient had a detachment of the Cytosponge from the thread requiring endoscopic removal, and the most common side-effect was a sore throat in 63 (4%) of 1654 participants.\n\nInterpretation: In patients with gastro-oesophageal reflux, the offer of Cytosponge-TFF3 testing results in improved detection of Barrett's oesophagus. Cytosponge-TFF3 testing could also lead to the diagnosis of treatable dysplasia and early cancer. This strategy will lead to additional endoscopies with some false positive results.\n\nFunding: Cancer Research UK, National Institute for Health Research, the UK National Health Service, Medtronic, and the Medical Research Council.\n\nIndexed on Europe PMC as PubMed record 32738955 (DOI 10.1016/s0140-6736(20)31099-0). Matched by DOI alone: one idea page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet 2020","url":"https://doi.org/10.1016/s0140-6736(20)31099-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32738955/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32738955"}],"tags":["europepmc-ingest"],"related":["idea-non-endoscopic-barretts-screening"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2020,"doi":"10.1016/s0140-6736(20)31099-0","pmid":"32738955","authors":"Fitzgerald RC, di Pietro M, O'Donovan M, et al.","paperType":"rct","findings":[],"whatItMeans":"One idea page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-li-j-thorac-oncol","kind":"paper","name":"D-1553 (Garsorasib), a Potent and Selective Inhibitor of KRAS G12C in Patients With NSCLC: Phase 1 Study Results","aka":[],"tldr":"Paper cited by one treatment page, indexed on Europe PMC as PubMed record 36948246 and published in Journal of Thoracic Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Introduction: D-1553 (garsorasib) is a potent and selective oral KRAS G12C inhibitor. We report results from a phase I dose-escalation and dose-expansion study of D-1553 in patients with KRAS G12C-mutated NSCLC in multiple sites in the People's Republic of China.\n\nMethods: Patients with KRAS G12C-mutated NSCLC have administrated D-1553 600 mg orally once daily, 800 mg once daily, 1200 mg once daily, 400 mg twice a day, or 600 mg twice a day in dose escalation. In dose-expansion, all patients received 600 mg twice a day. The safety, pharmacokinetics, and efficacy of D-1553 were evaluated.\n\nResults: Among a total of 79 treated patients, 75 patients (94.9%) reported treatment-related adverse events with 30 patients experiencing grade 3 or 4 events (38.0%). Most of the adverse events were manageable and the patients tolerated the study treatment well. Among 74 patients assessable for efficacy analysis, 30 patients had a partial response and 38 had stable disease with a confirmed objective response rate (ORR) and disease control rate (DCR) of 40.5% and 91.9%, respectively. The median progression-free survival was 8.2 months, and the median duration of response was 7.1 months. Among 62 patients assessable for response at the recommended phase 2 dose, partial response occurred in 24 patients (ORR, 38.7%) and stable disease in 32 patients (DCR, 90.3%). The median progression-free survival and duration of response were 7.6 months and 6.9 months, respectively. In patients with brain metastasis, ORR and DCR were 17% and 100%, respectively.\n\nConclusions: D-1553 represents a promising therapeutic option for patients with KRAS G12C-mutated NSCLC with a well-tolerated safety profile and encouraging antitumor activity.\n\nIndexed on Europe PMC as PubMed record 36948246 (DOI 10.1016/j.jtho.2023.03.015). Matched by DOI alone: one treatment page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Thorac Oncol 2023","url":"https://doi.org/10.1016/j.jtho.2023.03.015"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36948246/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36948246"}],"tags":["europepmc-ingest"],"related":["garsorasib"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-thoracic-oncology"],"dependsOn":[],"notes":[],"journal":"Journal of Thoracic Oncology","year":2023,"doi":"10.1016/j.jtho.2023.03.015","pmid":"36948246","authors":"Li Z, Song Z, Zhao Y, et al.","paperType":"observational","findings":[],"whatItMeans":"One treatment page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-damico-risk-groups-jama-1998","kind":"paper","name":"D'Amico risk groups: biochemical outcome after radical prostatectomy, external beam radiotherapy or brachytherapy","aka":[],"tldr":"This analysis of nearly 1,900 men introduced the low, intermediate and high-risk groups for localised prostate cancer based on PSA, Gleason score and stage, a classification still used to choose between surveillance, surgery and radiotherapy.","summary":"Retrospective cohort study of 1,872 men treated with radical prostatectomy, external beam radiotherapy or brachytherapy, stratified into low (PSA 10 or less, Gleason 6 or less, T1c to T2a), intermediate and high (PSA over 20, Gleason 8 to 10, or T2c) risk groups by five-year PSA failure.\n\nLow-risk men had equivalent outcomes with all three treatments; intermediate- and high-risk men did worse with brachytherapy alone than with surgery or external beam radiotherapy.","asOf":"2026-09-17","links":[{"label":"JAMA 1998","url":"https://doi.org/10.1001/jama.280.11.969"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/9749478/"}],"tags":[],"related":["prostate-roadmap","paper-catalona-psa-screening-test-nejm-1991","paper-bill-axelson-spcg-4-29-year-nejm-2018"],"cancers":["prostate-high-risk","prostate-intermediate-risk","prostate-low-risk","prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":1998,"doi":"10.1001/jama.280.11.969","pmid":"9749478","authors":"D'Amico AV, Whittington R, Malkowicz SB, et al.","paperType":"observational","findings":["Three risk groups with distinct five-year PSA failure-free survival.","Brachytherapy alone inferior for intermediate- and high-risk disease."],"whatItMeans":"The D'Amico system, refined by the NCCN, remains the framework for the very-low to very-high-risk categories used on this site's prostate pages.","caveats":["Retrospective, PSA-based endpoint; modern imaging and genomics refine the groups."],"changedPractice":true,"participants":1872},{"id":"paper-subbiah-dabrafenib-trametinib-atc-jco-2018","kind":"paper","name":"Dabrafenib and trametinib in BRAF V600E-mutant anaplastic thyroid cancer (ROAR)","aka":[],"tldr":"In one of the most lethal cancers known, dabrafenib plus trametinib shrank BRAF-mutant anaplastic thyroid cancer in about two thirds of patients, leading to the first ever drug approval for the disease.","summary":"Anaplastic thyroid cancer cohort of the phase 2 ROAR basket trial: 16 patients with BRAF V600E-mutant locally advanced or metastatic anaplastic thyroid cancer treated with dabrafenib plus trametinib.\n\nObjective response was 69 percent with responses lasting more than a year in most, twelve-month overall survival of about 80 percent in an updated analysis, and manageable toxicity; the approval followed in 2018.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2018","url":"https://doi.org/10.1200/JCO.2017.73.6785"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29072975/"}],"tags":[],"related":[],"cancers":["anaplastic-thyroid-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["dabrafenib","trametinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["vivek-subbiah"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2018,"doi":"10.1200/JCO.2017.73.6785","pmid":"29072975","authors":"Subbiah V, Kreitman RJ, Wainberg ZA, et al.","paperType":"observational","findings":["Objective response 69 percent (11 of 16).","Median duration of response and survival substantially exceeding historical months."],"whatItMeans":"Rapid BRAF testing is mandatory at diagnosis of anaplastic thyroid cancer, and BRAF-MEK inhibition, increasingly with pembrolizumab and as neoadjuvant therapy, is the standard for BRAF-mutant disease.","caveats":["Very small cohort; only about 40 percent of anaplastic thyroid cancers carry BRAF V600E."],"changedPractice":true,"participants":16},{"id":"paper-salama-j-clin-oncol","kind":"paper","name":"Dabrafenib and Trametinib in Patients With Tumors With BRAF V600E Mutations: Results of the NCI-MATCH Trial Subprotocol H","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 32758030 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: BRAF V600 mutations are commonly found in melanoma and thyroid cancers and to a lesser degree in other tumor types. Subprotocol H (EAY131-H) of the NCI-MATCH platform trial sought to investigate the selective BRAF inhibitor dabrafenib and the MEK1/2 inhibitor trametinib in patients with solid tumors, lymphomas, or multiple myeloma whose tumors harbored a BRAF V600 mutation.\n\nPatients and methods: EAY131-H is an open-label, single-arm study. Patients with melanoma, thyroid, or colorectal cancer were excluded; patients with non-small-cell lung cancer were later excluded in an amendment. Patients received dabrafenib 150 mg twice per day and trametinib 2 mg per day continuously until disease progression or intolerable toxicity. The primary end point was centrally assessed objective response rate (ORR); secondary end points included progression-free survival (PFS), 6-month PFS, and overall survival.\n\nResults: Thirty-five patients were enrolled, and 29 were included in the primary efficacy analysis as prespecified in the protocol. Median age was 59 years, and 45% of the patients had received ≥ 3 lines of therapy. The confirmed ORR was 38% (90% CI, 22.9% to 54.9%) with P <.0001 against a null rate of 5%, and PFS was 11.4 months (90% CI, 8.4 to 16.3 months); responses were seen in 7 distinct tumor types. Seven patients had a duration of response of > 12 months, including 4 patients with a duration of response of > 24 months. An additional 8 patients had a PFS > 6 months. The median overall survival was 28.6 months. Reported adverse events were comparable to those noted in previously reported profiles of dabrafenib and trametinib.\n\nConclusion: This study met its primary end point, with an ORR of 38% ( P <.0001) in this mixed histology, pretreated cohort. This promising activity warrants additional investigations in BRAF V600 -mutated tumors outside of currently approved indications.\n\nIndexed on Europe PMC as PubMed record 32758030 (DOI 10.1200/jco.20.00762). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2020","url":"https://doi.org/10.1200/jco.20.00762"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32758030/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32758030"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nci-match"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/jco.20.00762","pmid":"32758030","authors":"Salama AKS, Li S, Macrae ER, et al.","paperType":"observational","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-roar-lancet-oncol-2020","kind":"paper","name":"Dabrafenib plus trametinib in patients with BRAF V600E -mutated biliary tract cancer (ROAR): a phase 2, open-label, single-arm, multicentre basket trial","aka":[],"tldr":"Published report from the ROAR trial registered as NCT02034110, in The Lancet Oncology (2020), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Effective treatments for patients with cholangiocarcinoma after progression on gemcitabine-based chemotherapy are urgently needed. Mutations in the BRAF gene have been found in 5% of biliary tract tumours. The combination of dabrafenib and trametinib has shown activity in several BRAF V600E -mutated cancers. We aimed to assess the activity and safety of dabrafenib and trametinib combination therapy in patients with BRAF V600E -mutated biliary tract cancer.\n\nMethods: This study is part of an ongoing, phase 2, open-label, single-arm, multicentre, Rare Oncology Agnostic Research (ROAR) basket trial in patients with BRAF V600E -mutated rare cancers. Patients were eligible for the biliary tract cancer cohort if they were aged 18 years or older, had BRAF V600E -mutated, unresectable, metastatic, locally advanced, or recurrent biliary tract cancer, an Eastern Cooperative Oncology Group performance status of 0-2, and had received previous systemic treatment. All patients were treated with oral dabrafenib 150 mg twice daily and oral trametinib 2 mg once daily until disease progression or intolerance of treatment. The primary endpoint was the overall response rate, which was determined by Response Evaluation Criteria in Solid Tumors version 1.1 in the intention-to-treat evaluable population, which comprised all enrolled patients regardless of receiving treatment who were evaluable (ie, had progression, began a new anticancer treatment, withdrew consent, died, had stable disease for 6 weeks or longer, or had two or more post-baseline assessments). The ROAR trial is registered with ClinicalTrials.gov, NCT02034110. These results are based on an interim analysis; the study is active but not recruiting.\n\nFindings: Between March 12, 2014, and July 18, 2018, 43 patients with BRAF V600E -mutated biliary tract cancer were enrolled to the study and were evaluable. Median follow-up was 10 months (IQR 6-15). An investigator-assessed overall response was achieved by 22 (51%, 95% CI 36-67) of 43 patients. An independent reviewer-assessed overall response was achieved by 20 (47%, 95% CI 31-62) of 43 patients. The most common grade 3 or worse adverse event was increased γ-glutamyltransferase in five (12%) patients. 17 (40%) patients had serious adverse events and nine (21%) had treatment-related serious adverse events, the most frequent of which was pyrexia (eight [19%]). No treatment-related deaths were reported.\n\nInterpretation: Dabrafenib plus trametinib combination treatment showed promising activity in patients with BRAF V600E -mutated biliary tract cancer, with a manageable safety profile. Routine testing for BRAF V600E mutations should be considered in patients with biliary tract cancer.\n\nFunding: GlaxoSmithKline and Novartis.\n\nIndexed on Europe PMC as PubMed record 32818466 (DOI 10.1016/s1470-2045(20)30321-1). Its abstract cites the registry id NCT02034110, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2020","url":"https://doi.org/10.1016/s1470-2045(20)30321-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32818466/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32818466"},{"label":"ClinicalTrials.gov NCT02034110","url":"https://clinicaltrials.gov/study/NCT02034110"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["roar"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2020,"doi":"10.1016/s1470-2045(20)30321-1","pmid":"32818466","authors":"Subbiah V, Lassen U, Élez E, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02034110 with the most citations, so it is the natural first reading for anyone following the ROAR trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-roar-ann-oncol-2022-update","kind":"paper","name":"Dabrafenib plus trametinib in patients with BRAF V600E-mutant anaplastic thyroid cancer: updated analysis from the phase II ROAR basket study","aka":[],"tldr":"Later report from the ROAR trial registered as NCT02034110, in Annals of Oncology (2022); its title describes an updated or longer-term analysis.","summary":"Background: Combined therapy with dabrafenib plus trametinib was approved in several countries for treatment of BRAF V600E-mutant anaplastic thyroid cancer (ATC) based on an earlier interim analysis of 23 response-assessable patients in the ATC cohort of the phase II Rare Oncology Agnostic Research (ROAR) basket study. We report an updated analysis describing the efficacy and safety of dabrafenib plus trametinib in the full ROAR ATC cohort of 36 patients with ∼4 years of additional study follow-up.\n\nPatients and methods: ROAR (NCT02034110) is an open-label, nonrandomized, phase II basket study evaluating dabrafenib plus trametinib in BRAF V600E-mutant rare cancers. The ATC cohort comprised 36 patients with unresectable or metastatic ATC who received dabrafenib 150 mg twice daily plus trametinib 2 mg once daily orally until disease progression, unacceptable toxicity, or death. The primary endpoint was investigator-assessed overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints were duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.\n\nResults: At data cutoff (14 September 2020), median follow-up was 11.1 months (range, 0.9-76.6 months). The investigator-assessed ORR was 56% (95% confidence interval, 38.1% to 72.1%), including three complete responses; the 12-month DOR rate was 50%. Median PFS and OS were 6.7 and 14.5 months, respectively. The respective 12-month PFS and OS rates were 43.2% and 51.7%, and the 24-month OS rate was 31.5%. No new safety signals were identified with additional follow-up, and adverse events were consistent with the established tolerability of dabrafenib plus trametinib.\n\nConclusions: These updated results confirm the substantial clinical benefit and manageable toxicity of dabrafenib plus trametinib in BRAF V600E-mutant ATC. Dabrafenib plus trametinib notably improved long-term survival and represents a meaningful treatment option for this rare, aggressive cancer.\n\nIndexed on Europe PMC as PubMed record 35026411 (DOI 10.1016/j.annonc.2021.12.014). Its abstract cites the registry id NCT02034110, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2022","url":"https://doi.org/10.1016/j.annonc.2021.12.014"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35026411/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35026411"},{"label":"ClinicalTrials.gov NCT02034110","url":"https://clinicaltrials.gov/study/NCT02034110"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["roar"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2022,"doi":"10.1016/j.annonc.2021.12.014","pmid":"35026411","authors":"Subbiah V, Kreitman RJ, Wainberg ZA, et al.","paperType":"observational","findings":[],"whatItMeans":"A second publication from the ROAR trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-bouffet-n-engl-j-med","kind":"paper","name":"Dabrafenib plus Trametinib in Pediatric Glioma with BRAF V600 Mutations","aka":[],"tldr":"Paper cited by one cancer page and one trial page, indexed on Europe PMC as PubMed record 37733309 and published in New England Journal of Medicine; the citing pages link this DOI, which is how the record was matched.","summary":"Background: Detection of the BRAF V600E mutation in pediatric low-grade glioma has been associated with a lower response to standard chemotherapy. In previous trials, dabrafenib (both as monotherapy and in combination with trametinib) has shown efficacy in recurrent pediatric low-grade glioma with BRAF V600 mutations, findings that warrant further evaluation of this combination as first-line therapy.\n\nMethods: In this phase 2 trial, patients with pediatric low-grade glioma with BRAF V600 mutations who were scheduled to receive first-line therapy were randomly assigned in a 2:1 ratio to receive dabrafenib plus trametinib or standard chemotherapy (carboplatin plus vincristine). The primary outcome was the independently assessed overall response (complete or partial response) according to the Response Assessment in Neuro-Oncology criteria. Also assessed were the clinical benefit (complete or partial response or stable disease for ≥24 weeks) and progression-free survival.\n\nResults: A total of 110 patients underwent randomization (73 to receive dabrafenib plus trametinib and 37 to receive standard chemotherapy). At a median follow-up of 18.9 months, an overall response occurred in 47% of the patients treated with dabrafenib plus trametinib and in 11% of those treated with chemotherapy (risk ratio, 4.31; 95% confidence interval [CI], 1.7 to 11.2; P<0.001). Clinical benefit was observed in 86% of the patients receiving dabrafenib plus trametinib and in 46% receiving chemotherapy (risk ratio, 1.88; 95% CI, 1.3 to 2.7). The median progression-free survival was significantly longer with dabrafenib plus trametinib than with chemotherapy (20.1 months vs. 7.4 months; hazard ratio, 0.31; 95% CI, 0.17 to 0.55; P<0.001). Grade 3 or higher adverse events occurred in 47% of the patients receiving dabrafenib plus trametinib and in 94% of those receiving chemotherapy.\n\nConclusions: Among pediatric patients with low-grade glioma with BRAF V600 mutations, dabrafenib plus trametinib resulted in significantly more responses, longer progression-free survival, and a better safety profile than standard chemotherapy as first-line therapy. (Funded by Novartis; ClinicalTrials.gov number, NCT02684058.).\n\nIndexed on Europe PMC as PubMed record 37733309 (DOI 10.1056/nejmoa2303815). Matched by DOI alone: one cancer page and one trial page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2023","url":"https://doi.org/10.1056/nejmoa2303815"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37733309/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37733309"}],"tags":["europepmc-ingest"],"related":["paediatric-low-grade-glioma"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["tadpole"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/nejmoa2303815","pmid":"37733309","authors":"Bouffet E, Hansford JR, Garrè ML, et al.","paperType":"rct","findings":[],"whatItMeans":"One cancer page and one trial page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-planchard-dabrafenib-trametinib-braf-nsclc-lancet-oncol-2016","kind":"paper","name":"Dabrafenib plus trametinib in previously treated BRAF V600E-mutant metastatic non-small-cell lung cancer","aka":[],"tldr":"Combining a BRAF inhibitor with a MEK inhibitor shrank tumours in about two thirds of previously treated patients with BRAF V600E-mutant lung cancer, far more than BRAF inhibition alone, leading to the first approval for this driver.","summary":"Phase 2 multicohort study; this cohort treated 57 patients with previously treated BRAF V600E-mutant metastatic non-small-cell lung cancer with dabrafenib plus trametinib.\n\nObjective response was 63.2 percent with a median progression-free survival of 9.7 months, compared with 33 percent for dabrafenib alone in an earlier cohort; pyrexia, nausea and fatigue were common.","asOf":"2026-09-17","links":[{"label":"Lancet Oncol 2016","url":"https://doi.org/10.1016/S1470-2045(16)30146-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27283860/"}],"tags":[],"related":[],"cancers":["braf-v600e-nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":["dabrafenib","trametinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2016,"doi":"10.1016/S1470-2045(16)30146-2","pmid":"27283860","authors":"Planchard D, Besse B, Groen HJM, et al.","paperType":"observational","findings":["Objective response 63.2 percent.","Median progression-free survival 9.7 months."],"whatItMeans":"BRAF V600E is a routinely tested lung cancer driver, and BRAF plus MEK inhibition is the standard targeted therapy for it.","caveats":["Single-arm study with 57 patients.","Non-V600 BRAF mutations do not respond."],"changedPractice":true,"participants":57},{"id":"paper-planchard-dabrafenib-trametinib-first-line-lancet-oncol-2017","kind":"paper","name":"Dabrafenib plus trametinib in previously untreated BRAF V600E-mutant metastatic non-small-cell lung cancer","aka":[],"tldr":"Used as first treatment, dabrafenib plus trametinib shrank tumours in almost two thirds of patients with BRAF V600E-mutant lung cancer and controlled the disease for over a year, supporting its use before chemotherapy.","summary":"First-line cohort of the phase 2 multicohort study: 36 patients with untreated BRAF V600E-mutant metastatic non-small-cell lung cancer received dabrafenib plus trametinib.\n\nObjective response was 64 percent with a median progression-free survival of 10.9 months and median overall survival of 24.6 months at the initial report; updated analyses showed durable benefit.","asOf":"2026-09-17","links":[{"label":"Lancet Oncol 2017","url":"https://doi.org/10.1016/S1470-2045(17)30679-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28919011/"}],"tags":[],"related":[],"cancers":["braf-v600e-nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":["dabrafenib","trametinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2017,"doi":"10.1016/S1470-2045(17)30679-4","pmid":"28919011","authors":"Planchard D, Smit EF, Groen HJM, et al.","paperType":"observational","findings":["Objective response 64 percent.","Median progression-free survival 10.9 months; median overall survival 24.6 months."],"whatItMeans":"BRAF plus MEK inhibition is a standard first-line option for BRAF V600E lung cancer, with chemo-immunotherapy as the alternative or subsequent line.","caveats":["Small single-arm cohort; no comparison with chemo-immunotherapy."],"changedPractice":true,"participants":36},{"id":"paper-hargrave-dabrafenib-trametinib-paediatric-hgg-jco-2023","kind":"paper","name":"Dabrafenib plus trametinib in relapsed or refractory BRAF V600-mutant paediatric high-grade glioma","aka":[],"tldr":"In children whose BRAF V600-mutant high-grade glioma had relapsed, the combination of dabrafenib and trametinib shrank tumours in more than half and gave responses lasting well over a year, far better than historical chemotherapy.","summary":"Phase 2 study of 41 children and adolescents with relapsed or refractory BRAF V600-mutant high-grade glioma treated with dabrafenib plus trametinib.\n\nObjective response by independent review was 56 percent with a median duration of response of 22.2 months and median progression-free survival of 9.0 months, compared with expected responses of under 20 percent with chemotherapy; toxicity was mostly fever, rash and gastrointestinal.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2023","url":"https://doi.org/10.1200/JCO.23.00558"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37643378/"}],"tags":[],"related":[],"cancers":["paediatric-high-grade-glioma"],"sections":[],"technologies":[],"targets":[],"drugs":["dabrafenib","trametinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["darren-hargrave"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2023,"doi":"10.1200/JCO.23.00558","pmid":"37643378","authors":"Hargrave DR, Terashima K, Hara J, et al.","paperType":"observational","findings":["Objective response 56 percent; median duration of response 22.2 months.","Median overall survival 32.8 months."],"whatItMeans":"BRAF V600E testing is mandatory in childhood high-grade glioma and the combination is a standard at relapse and, increasingly, alongside or before radiotherapy in newly diagnosed disease; it supported the tumour-agnostic approval in children.","caveats":["Small single-arm cohort.","Resistance eventually develops in most patients."],"changedPractice":true,"participants":41},{"id":"paper-archer-1050-lancet-oncol-2017","kind":"paper","name":"Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial","aka":[],"tldr":"The primary report of ARCHER 1050: dacomitinib held untreated EGFR-mutant lung cancer for a median of 14.7 months against 9.2 months on gefitinib, at the cost of more rash and diarrhoea.","summary":"International, multicentre, randomised, open-label phase 3 trial at 71 academic centres in seven countries or regions in adults with newly diagnosed advanced non-small-cell lung cancer and one EGFR mutation (exon 19 deletion or Leu858Arg). Patients were randomised 1:1 to oral dacomitinib 45 mg a day or gefitinib 250 mg a day, stratified by race and EGFR mutation type. The primary endpoint was progression-free survival by masked independent review in the intention-to-treat population.\n\nBetween May 2013 and March 2015, 452 patients were randomised (227 dacomitinib, 225 gefitinib). Median progression-free survival was 14.7 months (95% CI 11.1 to 16.6) with dacomitinib and 9.2 months (95% CI 9.1 to 11.0) with gefitinib (hazard ratio 0.59, 95% CI 0.47 to 0.74). The most common grade 3 to 4 adverse events on dacomitinib were dermatitis acneiform (14 percent) and diarrhoea (8 percent). Funded by SFJ Pharmaceuticals Group and Pfizer.","asOf":"2026-09-24","links":[{"label":"The Lancet Oncology 2017","url":"https://doi.org/10.1016/S1470-2045(17)30608-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28958502/"},{"label":"ClinicalTrials.gov NCT01774721","url":"https://clinicaltrials.gov/study/NCT01774721"}],"tags":[],"related":[],"cancers":["nsclc","egfr-mutant-nsclc"],"sections":[],"technologies":[],"targets":["egfr"],"drugs":["dacomitinib","gefitinib"],"companies":["pfizer"],"institutions":[],"pathways":[],"terms":[],"trials":["nct01774721"],"people":["wu-yi-long","tony-mok"],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2017,"doi":"10.1016/S1470-2045(17)30608-3","pmid":"28958502","authors":"Wu YL, Cheng Y, Zhou X, et al.","paperType":"rct","findings":["Median progression-free survival 14.7 vs 9.2 months by masked independent review; hazard ratio 0.59 (95% CI 0.47 to 0.74).","452 patients randomised between May 2013 and March 2015; median follow-up for progression-free survival 22.1 months.","Grade 3 to 4 dermatitis acneiform in 14% and diarrhoea in 8% on dacomitinib."],"whatItMeans":"ARCHER 1050 supported dacomitinib's 2018 US first-line approval and was the first head-to-head win of a second-generation EGFR inhibitor over a first-generation one on progression-free survival. FLAURA, reported the same year, made osimertinib the usual first choice, so dacomitinib is now rarely used.","caveats":["Open-label; patients with brain metastases were excluded, so the result does not speak to the commonest site of EGFR-mutant relapse.","Overall survival was reported separately (Mok 2018).","Dose reductions were needed in two thirds of dacomitinib patients according to the US label."],"changedPractice":true,"participants":452},{"id":"paper-dawna-1-nat-med-2021","kind":"paper","name":"Dalpiciclib or placebo plus fulvestrant in hormone receptor-positive and HER2-negative advanced breast cancer: a randomized, phase 3 trial","aka":[],"tldr":"Published report from the DAWNA-1 trial registered as NCT03927456, in Nature Medicine (2021), chosen as the most cited paper whose own text cites the registry id.","summary":"Blockade of the cyclin-dependent kinase 4 and 6 pathway has been shown to be effective in the treatment of hormone receptor-positive advanced breast cancer (ABC). We report the interim results of DAWNA-1 ( NCT03927456), a double-blind, randomized, phase 3 trial of dalpiciclib (a new cyclin-dependent kinase 4 and 6 inhibitor) plus fulvestrant in hormone receptor-positive, HER2-negative ABC with disease progression after endocrine therapy. A total of 361 patients were randomized 2:1 to receive dalpiciclib plus fulvestrant or placebo plus fulvestrant. The study met the primary end point, showing significantly prolonged investigator-assessed progression-free survival with dalpiciclib plus fulvestrant versus placebo plus fulvestrant (median = 15.7, 95% confidence interval (CI) = 11.1-not reached versus 7.2, 95% CI = 5.6-9.2 months; hazard ratio = 0.42, 95% CI = 0.31-0.58; one-sided P < 0.0001 (boundary was P ≤ 0.008)). The most common grade 3 or 4 adverse events with dalpiciclib plus fulvestrant were neutropenia (84.2%) and leukopenia (62.1%). The incidence of serious adverse events was 5.8% with dalpiciclib plus fulvestrant versus 6.7% with placebo plus fulvestrant. Our findings support dalpiciclib plus fulvestrant as a new treatment option for pretreated hormone receptor-positive, HER2-negative ABC.\n\nIndexed on Europe PMC as PubMed record 34737452 (DOI 10.1038/s41591-021-01562-9). Its abstract cites the registry id NCT03927456, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Nat Med 2021","url":"https://doi.org/10.1038/s41591-021-01562-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34737452/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34737452"},{"label":"ClinicalTrials.gov NCT03927456","url":"https://clinicaltrials.gov/study/NCT03927456"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["dawna-1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2021,"doi":"10.1038/s41591-021-01562-9","pmid":"34737452","authors":"Xu B, Zhang Q, Zhang P, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03927456 with the most citations, so it is the natural first reading for anyone following the DAWNA-1 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-bradt-cochrane-database-syst-rev","kind":"paper","name":"Dance/movement therapy for improving psychological and physical outcomes in cancer patients","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 25565627 and published in The Cochrane database of systematic reviews; the citing page links this DOI, which is how the record was matched.","summary":"Background: Current cancer care increasingly incorporates psychosocial interventions. Cancer patients use dance/movement therapy to learn to accept and reconnect with their bodies, build new self-confidence, enhance self-expression, address feelings of isolation, depression, anger and fear and to strengthen personal resources.\n\nObjectives: To update the previously published review that examined the effects of dance/movement therapy and standard care versus standard care alone or standard care and other interventions on psychological and physical outcomes in patients with cancer.\n\nSearch methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 6), MEDLINE (OvidSP, 1950 to June week 4, 2014), EMBASE (OvidSP, 1980 to 2014 week 26), CINAHL (EBSCOhost, 1982 to July 15 2014), PsycINFO (EBSCOhost, 1806 to July 15 2014), LILACS (Virual Health Library, 1982 to July 15 2014), Science Citation Index (ISI, 1974 to July 15 2014), CancerLit (1983 to 2003), International Bibliography of Theatre and Dance (1989 to July 15 2014), the National Research Register (2000 to September 2007), Proquest Digital Dissertations, ClinicalTrials.gov, and Current Controlled Trials (all to July 15 2014). We handsearched dance/movement therapy and related topics journals, reviewed reference lists and contacted experts. There was no language restriction.\n\nSelection criteria: We included all randomized and quasi-randomized controlled trials of dance/movement therapy interventions for improving psychological and physical outcomes in patients with cancer. We considered studies only if dance/movement therapy was provided by a formally trained dance/movement therapist or by trainees in a formal dance/movement therapy program.\n\nData collection and analysis: Two review authors independently extracted the data and assessed the methodological quality, seeking additional information from the trial researchers when necessary. Results were presented using standardized mean differences.\n\nMain results: We identified one new trial for inclusion in this update. In total, the evidence for this review rests on three studies with a total of 207 participants.We found no evidence for an effect of dance/movement therapy on depression (standardized mean difference (SMD) = 0.02, 95% confidence interval (CI) -0.28 to 0.32, P = 0.89, I2 = 0%) (two studies, N = 170), stress (SMD = -0.18, 95% CI -0.48 to 0.12, P = 0.24, I2 = 0%) (two studies, N = 170), anxiety (SMD = 0.21, 95% CI -0.09 to 0.51 P = 0.18, I2 = 0%) (two studies, N = 170), fatigue (SMD = -0.36, 95% -1.26 to 0.55, P = 0.44, I² = 80%) (two studies, N = 170) and body image (SMD = -0.13, 95% CI -0.61 to 0.34, P = 0.58, I2 = 0%) (two studies, N = 68) in women with breast cancer. The data of one study with moderate risk of bias suggested that dance/movement therapy had a large beneficial effect on 37 participants' quality of life (QoL) (SMD = 0.89, 95% CI 0.21 to 1.57). One study with a high risk of bias reported greater improvements in vigor and greater reduction in somatization in the dance/movement therapy group compared to a standard care control group (N = 31). The individual studies did not find support for an effect of dance/movement therapy on mood, mental health, and pain. It is unclear whether this was due to ineffectiveness of the treatment, inappropriate outcome measures or limited power of the trials. Finally, the results of one study did not find evidence for an effect of dance/movement therapy on shoulder range of motion (ROM) or arm circumference in 37 women who underwent a lumpectomy or breast surgery. However, this was likely due to large within-group variability for shoulder ROM and a limited number of participants with lymphedema.Two studies presented moderate risk of bias and one study high risk of bias. Therefore, overall, the quality of the evidence is very low.\n\nAuthors' conclusions: We did not find support for an effect of dance/movement therapy on depression, stress, anxiety, fatigue and body image. The findings of individual studies suggest that dance/movement therapy may have a beneficial effect on QoL, somatization, and vigor. However, the limited number of studies prevents us from drawing conclusions concerning the effects of dance/movement therapy on psychological and physical outcomes in cancer patients.\n\nIndexed on Europe PMC as PubMed record 25565627 (DOI 10.1002/14651858.cd007103.pub3). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cochrane Database Syst Rev 2015","url":"https://doi.org/10.1002/14651858.cd007103.pub3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25565627/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25565627"}],"tags":["europepmc-ingest"],"related":["dance-movement-therapy"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Cochrane database of systematic reviews","year":2015,"doi":"10.1002/14651858.cd007103.pub3","pmid":"25565627","authors":"Bradt J, Shim M, Goodill SW","paperType":"meta-analysis","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-lenalidomide-multiple-myeloma-n-engl-j-med-2016","kind":"paper","name":"Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma","aka":[],"tldr":"Phase 2 or 3 results paper on Lenalidomide in Multiple myeloma, in New England Journal of Medicine (2016), one of the most cited Europe PMC records with Lenalidomide in its title.","summary":"Background: Daratumumab showed promising efficacy alone and with lenalidomide and dexamethasone in a phase 1-2 study involving patients with relapsed or refractory multiple myeloma.\n\nMethods: In this phase 3 trial, we randomly assigned 569 patients with multiple myeloma who had received one or more previous lines of therapy to receive lenalidomide and dexamethasone either alone (control group) or in combination with daratumumab (daratumumab group). The primary end point was progression-free survival.\n\nResults: At a median follow-up of 13.5 months in a protocol-specified interim analysis, 169 events of disease progression or death were observed (in 53 of 286 patients [18.5%] in the daratumumab group vs. 116 of 283 [41.0%] in the control group; hazard ratio, 0.37; 95% confidence interval [CI], 0.27 to 0.52; P<0.001 by stratified log-rank test). The Kaplan-Meier rate of progression-free survival at 12 months was 83.2% (95% CI, 78.3 to 87.2) in the daratumumab group, as compared with 60.1% (95% CI, 54.0 to 65.7) in the control group. A significantly higher rate of overall response was observed in the daratumumab group than in the control group (92.9% vs. 76.4%, P<0.001), as was a higher rate of complete response or better (43.1% vs. 19.2%, P<0.001). In the daratumumab group, 22.4% of the patients had results below the threshold for minimal residual disease (1 tumor cell per 10 5 white cells), as compared with 4.6% of those in the control group (P<0.001); results below the threshold for minimal residual disease were associated with improved outcomes. The most common adverse events of grade 3 or 4 during treatment were neutropenia (in 51.9% of the patients in the daratumumab group vs. 37.0% of those in the control group), thrombocytopenia (in 12.7% vs. 13.5%), and anemia (in 12.4% vs. 19.6%). Daratumumab-associated infusion-related reactions occurred in 47.7% of the patients and were mostly of grade 1 or 2.\n\nConclusions: The addition of daratumumab to lenalidomide and dexamethasone significantly lengthened progression-free survival among patients with relapsed or refractory multiple myeloma. Daratumumab was associated with infusion-related reactions and a higher rate of neutropenia than the control therapy. (Funded by Janssen Research and Development; POLLUX ClinicalTrials.gov number, NCT02076009.).\n\nIndexed on Europe PMC as PubMed record 27705267 (DOI 10.1056/nejmoa1607751). Its title names Lenalidomide and its text names Multiple myeloma; PubMed types it as a clinical trial report (Clinical Trial, Phase III, Research Support, Non-U.S. Gov't, Multicenter Study, Randomized Controlled Trial). It was matched automatically to the idea \"MRD-guided treatment-free intervals in myeloma\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2016","url":"https://doi.org/10.1056/nejmoa1607751"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27705267/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27705267"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2016,"doi":"10.1056/nejmoa1607751","pmid":"27705267","authors":"Dimopoulos MA, Oriol A, Nahi H, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Lenalidomide in Multiple myeloma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Lenalidomide in the title and Multiple myeloma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-nct05379985-n-engl-j-med-2026","kind":"paper","name":"Daraxonrasib in Previously Treated Advanced RAS -Mutated Pancreatic Cancer","aka":[],"tldr":"Published report from the trial registered as NCT05379985, in New England Journal of Medicine (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Current therapies for patients with pancreatic ductal adenocarcinoma (PDAC) provide modest benefit. Activating RAS mutations occur in more than 90% of PDAC tumors. Daraxonrasib (RMC-6236) is an oral RAS(ON) multiselective inhibitor that targets guanosine triphosphate-bound mutant and wild-type RAS.\n\nMethods: In this phase 1-2 study, we evaluated daraxonrasib in patients with advanced solid tumors with activating RAS mutations. Patients received 10 to 400 mg of daraxonrasib orally once daily; 300 mg was selected as the phase 3 dose. The primary end point was safety. Pharmacokinetics and antitumor activity were secondary end points. This report focuses on the 168 study patients with previously treated RAS -mutated PDAC.\n\nResults: Among the 168 patients with PDAC who received daraxonrasib at a dose of 300 mg or less, treatment-related adverse events of any grade were reported in 96%; such events of grade 3 or higher were reported in 30%. Treatment-related adverse events that occurred in at least 10% of the patients included rash, diarrhea, nausea, stomatitis or mucositis, vomiting, and fatigue. In a subgroup of 26 patients with RAS G12 mutations who were treated with second-line daraxonrasib at a dose of 300 mg, an objective response to therapy was reported in 35% (95% confidence interval [CI], 17 to 56). The median duration of response was 8.2 months (95% CI, 3.8 to not evaluable), with median values of 8.5 months for progression-free survival and 13.1 months for overall survival. Among the 38 patients with RAS G12, G13, or Q61 mutations, 29% (95% CI, 15 to 46) had an objective response. The median duration of response was 8.2 months (95% CI, 3.8 to 8.8), with median values of 8.1 months for progression-free survival and 15.6 months for overall survival.\n\nConclusions: Daraxonrasib was associated with treatment-related adverse events of grade 3 or higher in one third of patients with previously treated RAS -mutated PDAC; antitumor activity was also reported. (Funded by Revolution Medicines; RMC-6236-001 ClinicalTrials.gov number, NCT05379985.).\n\nIndexed on Europe PMC as PubMed record 42090791 (DOI 10.1056/nejmoa2505783). Its abstract cites the registry id NCT05379985, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2026","url":"https://doi.org/10.1056/nejmoa2505783"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42090791/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42090791"},{"label":"ClinicalTrials.gov NCT05379985","url":"https://clinicaltrials.gov/study/NCT05379985"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05379985"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2026,"doi":"10.1056/nejmoa2505783","pmid":"42090791","authors":"Wolpin BM, Park W, Garrido-Laguna I, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05379985 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-daraxonrasib-pancreatic-n-engl-j-med-2026","kind":"paper","name":"Daraxonrasib or Chemotherapy in Previously Treated Metastatic Pancreatic Cancer","aka":[],"tldr":"Phase 2 or 3 results paper on Daraxonrasib in Pancreatic ductal adenocarcinoma, in New England Journal of Medicine (2026), one of the most cited Europe PMC records with Daraxonrasib in its title.","summary":"Background: Current therapies offer limited benefit for patients with previously treated metastatic pancreatic ductal adenocarcinoma (mPDAC). Aberrant activation of the RAS pathway is the key driver of PDAC, with oncogenic RAS mutations present in more than 90% of cases. Daraxonrasib is an oral RAS(ON) multiselective, tri-complex inhibitor of the active guanosine triphosphate-bound state of mutant and wild-type RAS.\n\nMethods: In this phase 3, international, open-label, randomized trial, we randomly assigned patients with previously treated mPDAC to receive daraxonrasib or chemotherapy of the investigator's choice. The dual primary end points were overall survival and progression-free survival in the subpopulation of patients with RAS G12 mutations (the RAS G12 population). Key secondary end points included overall survival and progression-free survival in the overall population (which included patients with RAS G12, G13, or Q61 mutations or with no RAS mutation identified) and objective response and patient-reported quality of life in the RAS G12 and overall populations. Safety was also assessed.\n\nResults: A total of 500 patients, including 91.8% with RAS G12 mutations, were randomly assigned to receive daraxonrasib (248 patients) or chemotherapy (252 patients). The median overall survival in the RAS G12 population was 13.2 months with daraxonrasib and 6.6 months with chemotherapy, and the median overall survival in the overall population was 13.2 months and 6.7 months, respectively; the hazard ratio was 0.40 in both populations (P<0.001). The median progression-free survival in the RAS G12 population was 7.3 months with daraxonrasib and 3.5 months with chemotherapy, and that in the overall population was 7.2 months and 3.6 months, respectively; the hazard ratios were 0.45 and 0.49, respectively (P<0.001 for both comparisons). Adverse events that occurred after the start of treatment were reported in all the patients in the daraxonrasib group and in 97.7% of those in the chemotherapy group; the incidence of adverse events of grade 3 or higher was 61.8% and 69.6%, respectively. Treatment-related adverse events that led to treatment discontinuation occurred in 1.2% of the patients in the daraxonrasib group and in 11.2% of those in the chemotherapy group.\n\nConclusions: Among patients with previously treated mPDAC, treatment with daraxonrasib led to significantly longer overall survival and progression-free survival than chemotherapy. (Funded by Revolution Medicines; RASolute 302 ClinicalTrials.gov number, NCT06625320.).\n\nIndexed on Europe PMC as PubMed record 42223072 (DOI 10.1056/nejmoa2605555). Its title names Daraxonrasib and its text names Pancreatic ductal adenocarcinoma; PubMed types it as a clinical trial report (Clinical Trial, Phase III, Comparative Study, Multicenter Study, Randomized Controlled Trial). It was matched automatically to the idea \"RAS(ON) inhibitors to convert unresectable pancreatic cancer to resectable\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2026","url":"https://doi.org/10.1056/nejmoa2605555"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42223072/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42223072"},{"label":"ClinicalTrials.gov NCT06625320","url":"https://clinicaltrials.gov/study/NCT06625320"}],"tags":["europepmc-ingest"],"related":["kras-g12d","kras-g12c"],"cancers":["pancreatic","metastatic-pdac"],"sections":[],"technologies":["kras-inhibitors"],"targets":["kras"],"drugs":["daraxonrasib"],"companies":[],"institutions":[],"pathways":["ras-mapk"],"terms":["kras-mutation-subtypes"],"trials":["rasolute-302"],"people":["eileen-oreilly","zev-wainberg"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2026,"doi":"10.1056/nejmoa2605555","pmid":"42223072","authors":"O'Reilly EM, Wainberg ZA, Hendifar AE, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Daraxonrasib in Pancreatic ductal adenocarcinoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Daraxonrasib in the title and Pancreatic ductal adenocarcinoma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-daraxonrasib-pancreatic-cureus-2026","kind":"paper","name":"Daraxonrasib: A Breakthrough in Pancreatic Ductal Adenocarcinoma","aka":[],"tldr":"Review on Daraxonrasib in Pancreatic ductal adenocarcinoma, in Cureus (2026), one of the most cited Europe PMC records with Daraxonrasib in its title.","summary":"Pancreatic cancer is one of the leading causes of cancer-related mortality. Diagnosis at an advanced stage, aggressive tumor biology, and chemoresistance all contribute to the overall dismal prognosis. Somatic, non-hereditary activating mutations involving the proto-oncogene Kirsten rat sarcoma viral oncogene (KRAS) are encountered in the vast majority of patients. KRAS mutations are involved in tumor initiation as well as the progression of pancreatic cancer and are key determinants of prognosis. Beyond pancreatic ductal adenocarcinoma (PDAC), KRAS mutations have been reported in multiple human solid-organ neoplasms. Over the past few decades, targeted molecular therapy has evolved into an indispensable part of oncology. Molecules targeting rat sarcoma viral oncogene (RAS) mutations have gained considerable interest in molecular oncology owing to their pivotal role in common cancers such as non-small cell lung, colon, and pancreatic cancer. One of the recent breakthroughs in PDAC treatment is the discovery of the multi-selective RAS inhibitor specific to its ON conformation: the first of its class, the RAS(ON) inhibitor daraxonrasib. Preclinical and early clinical data confirmed its utility in PDAC, leading to United States Food and Drug Administration permission to expand access treatment protocols for patients with previously treated metastatic PDAC in May 2026. This narrative review summarizes the published literature on the safety and efficacy of daraxonrasib in PDAC, based on a comprehensive PubMed literature search. at June 2026, the utility of daraxonrasib is limited to metastatic PDAC as a second-line agent in patients who failed or were intolerant of first-line chemotherapy. An ongoing trial is evaluating the efficacy of daraxonrasib as a first-line targeted therapy in metastatic PDAC. Further, large-scale, blinded, multicenter randomized trials are required to confirm the efficacy and safety of daraxonrasib in PDAC and other solid-organ neoplasms. The orally administered daraxonrasib could be a potential game changer in the treatment of PDAC, which is otherwise considered one of the least chemotherapy-amenable human cancers.\n\nIndexed on Europe PMC as PubMed record 42694779 (DOI 10.7759/cureus.113927). Its title names Daraxonrasib and its text names Pancreatic ductal adenocarcinoma; PubMed types it as a review (review-article, Review). It was matched automatically to the idea \"RAS(ON) inhibitors to convert unresectable pancreatic cancer to resectable\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cureus 2026","url":"https://doi.org/10.7759/cureus.113927"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42694779/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42694779"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Cureus","year":2026,"doi":"10.7759/cureus.113927","pmid":"42694779","authors":"Zacharia GS, Pandey U, Thartori O, et al.","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for Daraxonrasib in Pancreatic ductal adenocarcinoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Daraxonrasib in the title and Pancreatic ductal adenocarcinoma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-darnell-jak-stat-science-1994","kind":"paper","name":"Darnell, Kerr and Stark 1994: JAK-STAT pathways and transcriptional activation by interferons","aka":[],"tldr":"The review that defined the JAK-STAT pathway, the direct route by which interferons and many other cytokines tell a cell's genes to respond, and which is now the target of JAK inhibitors used in blood cancers.","summary":"Darnell, Kerr and Stark drew together the genetics and biochemistry that revealed how interferons signal: receptor binding activates Janus kinases (JAKs), which phosphorylate STAT proteins that dimerise, move to the nucleus and switch on genes within minutes. They showed that the same JAK-STAT logic is shared by many cytokines and growth factors, each using a particular combination of JAKs and STATs. The paper gave the pathway its name and set out the model that has held since.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1126/science.8197455"}],"tags":[],"related":["paper-grivennikov-immunity-inflammation-cancer-cell-2010"],"cancers":[],"sections":[],"technologies":[],"targets":["jak2","ifnar1"],"drugs":[],"companies":[],"institutions":[],"pathways":["jak-stat"],"terms":["cytokine","signalling-pathway"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Science","year":1994,"doi":"10.1126/science.8197455","authors":"Darnell JE Jr, Kerr IM, Stark GR.","paperType":"review","findings":["Interferon receptors activate JAK kinases, which phosphorylate STAT transcription factors that move directly to the nucleus.","Different cytokines use distinct combinations of the JAK and STAT family members.","The pathway provides a rapid, direct route from cell surface to gene activation."],"whatItMeans":"The JAK-STAT pathway explains how interferon and interleukin signals act in immunity and cancer. Its discovery underlies ruxolitinib and other JAK inhibitors in myeloproliferative neoplasms, the role of STAT3 in tumour-promoting inflammation, and the interferon-gamma signalling that determines whether tumours respond to checkpoint inhibitors.","caveats":["A review from the pathway's early days; negative regulators such as SOCS proteins were described later.","Focused on interferons; oncogenic JAK2 mutations were discovered in 2005."],"changedPractice":false},{"id":"paper-aranote-eur-urol-2026","kind":"paper","name":"Darolutamide Plus Androgen-deprivation Therapy in Metastatic Hormone-sensitive Prostate Cancer by Disease Volume and Risk Subgroups in the Phase 3 ARANOTE Trial","aka":[],"tldr":"Published report from the ARANOTE trial registered as NCT04736199, in European Urology (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"In ARANOTE (NCT04736199), darolutamide plus androgen-deprivation therapy (ADT) significantly reduced the risk of radiologic progression or death versus placebo plus ADT in patients with metastatic hormone-sensitive prostate cancer, with favorable safety. Here, we report on post hoc outcomes by disease volume/risk. Randomized patients received darolutamide plus ADT or placebo plus ADT (2:1). High-volume (HV) and high-risk (HR) disease were defined by the CHAARTED and LATITUDE criteria, respectively. End points included radiologic progression-free survival (primary; rPFS), time to initiation of subsequent systemic anticancer therapy, time to metastatic castration-resistant prostate cancer, time to prostate-specific antigen (PSA) progression, time to pain progression, PSA <0.2 ng/ml rates, overall survival, and safety. Of 669 patients, 472 had HV disease, 197 had low-volume (LV) disease, 400 had HR disease, and 269 had low-risk (LR) disease; baseline characteristics were generally balanced. Darolutamide consistently reduced the rPFS (HV: 40% [hazard ratio, 0.60; 95% confidence interval, 0.44 to 0.80]; LV: 70% [0.30; 0.15 to 0.60]; HR: 39% [0.61; 0.44 to 0.86]; LR: 60% [0.40; 0.25 to 0.62]), with similar trends for all secondary end points versus placebo. Treatment-emergent adverse events were similar between treatment arms across all subgroups. Darolutamide was well tolerated, and outcomes were improved versus placebo, regardless of disease volume/risk. Prior presentation: Presented at the American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, San Francisco, CA, February 13-15, 2025. Clinical trial registration: NCT04736199 (EudraCT 2020-003093-48).\n\nIndexed on Europe PMC as PubMed record 42586872 (DOI 10.1016/j.eururo.2026.07.026). Its abstract cites the registry id NCT04736199, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Eur Urol 2026","url":"https://doi.org/10.1016/j.eururo.2026.07.026"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42586872/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42586872"},{"label":"ClinicalTrials.gov NCT04736199","url":"https://clinicaltrials.gov/study/NCT04736199"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["aranote"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["european-urology"],"dependsOn":[],"notes":[],"journal":"European Urology","year":2026,"doi":"10.1016/j.eururo.2026.07.026","pmid":"42586872","authors":"Saad F, Shore N, Vjaters E, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04736199 with the most citations, so it is the natural first reading for anyone following the ARANOTE trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-dart-nivolumab-ipilimumab-nec-patel-ccr-2020","kind":"paper","name":"DART (SWOG 1609): nivolumab plus ipilimumab in rare tumours, non-pancreatic neuroendocrine neoplasms cohort","aka":[],"tldr":"In a basket trial of rare cancers, dual immunotherapy shrank tumours in about a quarter of patients with non-pancreatic neuroendocrine neoplasms, almost all of them high-grade carcinomas, giving an immunotherapy option for a disease with few treatments.","summary":"Neuroendocrine cohort of the phase 2 DART basket trial: 32 patients with non-pancreatic neuroendocrine neoplasms treated with nivolumab plus ipilimumab.\n\nObjective response was 25 percent overall and 44 percent in high-grade neuroendocrine carcinoma, with no responses in low- or intermediate-grade tumours; median progression-free survival was 4 months and overall survival 11 months.","asOf":"2026-09-17","links":[{"label":"Clin Cancer Res 2020","url":"https://doi.org/10.1158/1078-0432.CCR-19-3356"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31969335/"}],"tags":[],"related":[],"cancers":["extrapulmonary-nec"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2020,"doi":"10.1158/1078-0432.CCR-19-3356","pmid":"31969335","authors":"Patel SP, Othus M, Chae YK, et al.","paperType":"observational","findings":["Objective response 25 percent overall; 44 percent in high-grade neuroendocrine carcinoma.","No responses in grade 1 to 2 neuroendocrine tumours."],"whatItMeans":"Nivolumab plus ipilimumab is a guideline-listed option for extrapulmonary neuroendocrine carcinoma after platinum chemotherapy, whereas well-differentiated tumours do not respond.","caveats":["Very small cohort; responses were not always durable.","A subsequent expansion cohort reported lower response rates."],"changedPractice":true,"participants":32},{"id":"paper-dasatinib-vs-imatinib-ph-positive-all-shen-jama-oncol-2020","kind":"paper","name":"Dasatinib versus imatinib with chemotherapy for paediatric Philadelphia chromosome-positive acute lymphoblastic leukaemia (CCCG-ALL-2015)","aka":[],"tldr":"In Chinese children with Philadelphia-positive leukaemia, dasatinib given at a high dose with chemotherapy improved four-year event-free survival compared with imatinib and reduced central nervous system relapses, without cranial irradiation or routine transplant.","summary":"Phase 3 trial of 189 children with Ph-positive ALL randomised to dasatinib 80 mg per square metre or imatinib 300 mg per square metre daily with intensive chemotherapy, without prophylactic cranial irradiation.\n\nFour-year event-free survival was 71.0 percent with dasatinib against 48.9 percent with imatinib, overall survival 88.4 versus 69.2 percent, and the cumulative risk of isolated central nervous system relapse was 2.7 versus 8.4 percent.","asOf":"2026-09-17","links":[{"label":"JAMA Oncol 2020","url":"https://doi.org/10.1001/jamaoncol.2019.5868"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31944221/"}],"tags":[],"related":[],"cancers":["all-paediatric-ph-positive"],"sections":[],"technologies":[],"targets":[],"drugs":["dasatinib","imatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2020,"doi":"10.1001/jamaoncol.2019.5868","pmid":"31944221","authors":"Shen S, Chen X, Cai J, et al.","paperType":"rct","findings":["Four-year event-free survival 71.0 percent vs 48.9 percent.","Isolated central nervous system relapse 2.7 percent vs 8.4 percent."],"whatItMeans":"Dasatinib is preferred over imatinib for paediatric Ph-positive ALL in many protocols because of its central nervous system penetration and superior outcomes in this trial.","caveats":["Open-label single-country trial with a higher dasatinib dose than used elsewhere."],"changedPractice":true,"participants":189},{"id":"paper-nct03742102-ann-oncol-2026","kind":"paper","name":"Datopotamab deruxtecan (Dato-DXd) in combination with durvalumab as first-line treatment for unresectable locally advanced or metastatic triple-negative breast cancer: results from arms 7 and 8 of the phase Ib/II BEGONIA study","aka":[],"tldr":"Published report from the BEGONIA trial registered as NCT03742102, in Annals of Oncology (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: BEGONIA (NCT03742102) is a phase Ib/II, Simon's 2-stage, open-label, platform study evaluating the safety and efficacy of durvalumab, an anti-programmed death ligand-1 (PD-L1) antibody, combined with novel therapies, as first-line treatment for patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC). Arms 7 and 8 of BEGONIA assessed the combination of datopotamab deruxtecan (Dato-DXd), a TROP2-directed antibody-drug conjugate, with durvalumab.\n\nPatients and methods: Arm 7 included patients regardless of tumor PD-L1 expression level. Arm 8 then enrolled patients with PD-L1-high tumors, as determined by local immunohistochemistry-based testing. In Arms 7 and 8, patients received Dato-DXd 6 mg/kg intravenously plus durvalumab 1120 mg intravenously every 3 weeks. Primary endpoints were safety and tolerability, and investigator-assessed confirmed objective response rate (cORR). Secondary endpoints included cORR (Part 1), duration of response (DoR), progression-free survival (PFS) per RECIST 1.1 and overall survival (OS).\n\nResults: Overall, 62 and 33 patients had received Dato-DXd and durvalumab in Arms 7 and 8, respectively. At data cutoff (29 November 2024), median study follow-up was 35.0 and 10.7 months in Arms 7 and 8, respectively. In Arm 7, cORR was 79.0% [95% confidence interval (CI) 66.8-88.3], median DoR was 17.6 months (95% CI 10.5-27.3), median PFS was 14.0 months (11.0-21.1) and median OS was not reached. In Arm 8, cORR was 81.8% (95% CI 64.5-93.0). The median DoR and median PFS for Arm 8 were immature given the short median follow-up (8.3 months in censored patients). The safety profile of the combination was manageable, with no new safety signals versus prior studies.\n\nConclusions: First-line Dato-DXd plus durvalumab demonstrated substantial and durable antitumor activity in locally advanced unresectable or metastatic TNBC, regardless of PD-L1 status.\n\nIndexed on Europe PMC as PubMed record 42167437 (DOI 10.1016/j.annonc.2026.05.693). Its abstract cites the registry id NCT03742102, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2026","url":"https://doi.org/10.1016/j.annonc.2026.05.693"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42167437/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42167437"},{"label":"ClinicalTrials.gov NCT03742102","url":"https://clinicaltrials.gov/study/NCT03742102"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct03742102"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2026,"doi":"10.1016/j.annonc.2026.05.693","pmid":"42167437","authors":"Schmid P, Wang HC, Lynce F, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03742102 with the most citations, so it is the natural first reading for anyone following the BEGONIA trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-tropion-lung05-j-clin-oncol-2025","kind":"paper","name":"Datopotamab Deruxtecan in Advanced or Metastatic Non-Small Cell Lung Cancer With Actionable Genomic Alterations: Results From the Phase II TROPION-Lung05 Study","aka":[],"tldr":"Published report from the TROPION-Lung05 trial registered as NCT04484142, in Journal of Clinical Oncology (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Purpose: Datopotamab deruxtecan (Dato-DXd) is a trophoblast cell-surface antigen-2-directed antibody-drug conjugate with a highly potent topoisomerase I inhibitor payload. The TROPION-Lung05 phase II trial (ClinicalTrials.gov identifier: NCT04484142) evaluated the safety and clinical activity of Dato-DXd in patients with advanced/metastatic non-small cell lung cancer (NSCLC) with actionable genomic alterations progressing on or after targeted therapy and platinum-based chemotherapy.\n\nPatients and methods: Patients received Dato-DXd 6 mg/kg once every 3 weeks. The primary end point was objective response rate (ORR) by blinded independent central review. Secondary end points included duration of response (DOR), safety, tolerability, and survival.\n\nResults: Among 137 patients who received at least 1 dose of Dato-DXd, 71.5% received at least three lines of prior therapies for advanced/metastatic disease. Overall, 56.9% had EGFR mutations and 24.8% had ALK rearrangements. Median treatment duration was 4.4 months (range, 0.7-20.6). The confirmed ORR was 35.8% (95% CI, 27.8 to 44.4) overall, and 43.6% (95% CI, 32.4 to 55.3) and 23.5% (95% CI, 10.7 to 41.2) in those with EGFR mutations and ALK rearrangements, respectively. The median DOR was 7.0 months (95% CI, 4.2 to 9.8), and the overall disease control rate was 78.8% (95% CI, 71.0 to 85.3). Grade ≥3 treatment-related adverse events (TRAEs) occurred in 28.5% of patients. The most common TRAE was stomatitis (preferred term; any grade: 56.2%; grade ≥3: 9.5%). Five (3.6%) patients experienced adjudicated treatment-related interstitial lung disease/pneumonitis, with 1 (0.7%) grade 5 event.\n\nConclusion: Encouraging and durable antitumor activity was observed with Dato-DXd in this heavily pretreated advanced/metastatic NSCLC population with actionable genomic alterations. The rate of treatment-related grade ≥3 toxicities was comparable with previous observations, and no new safety signals were observed.\n\nIndexed on Europe PMC as PubMed record 39761483 (DOI 10.1200/jco-24-01349). Its abstract cites the registry id NCT04484142, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2025","url":"https://doi.org/10.1200/jco-24-01349"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39761483/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39761483"},{"label":"ClinicalTrials.gov NCT04484142","url":"https://clinicaltrials.gov/study/NCT04484142"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["tropion-lung05"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2025,"doi":"10.1200/jco-24-01349","pmid":"39761483","authors":"Sands J, Ahn MJ, Lisberg A, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04484142 with the most citations, so it is the natural first reading for anyone following the TROPION-Lung05 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-tropion-breast02-ann-oncol-2026","kind":"paper","name":"Datopotamab deruxtecan in patients with untreated, advanced triple-negative breast cancer (TROPION-Breast02): a randomised, open-label, international, phase III trial","aka":[],"tldr":"The trial of 644 women with newly metastatic triple-negative breast cancer who could not have immunotherapy, in which the antibody-drug conjugate datopotamab deruxtecan held the cancer still for 10.8 months against 5.6 with chemotherapy and lengthened life from 18.7 to 23.7 months.","summary":"TROPION-Breast02 (Dent, Shao, Schmid, Cortes and colleagues) randomised 644 patients with previously untreated, locally recurrent inoperable or metastatic triple-negative breast cancer for whom immunotherapy was not an option, between 16 May 2022 and 11 June 2024, to datopotamab deruxtecan 6 mg/kg every three weeks (323) or investigator's choice of chemotherapy (321), stratified by geography, disease-free interval and PD-L1 status; dual primary endpoints were progression-free survival by blinded independent central review and overall survival. Median progression-free survival was 10.8 months (95 percent confidence interval 8.6 to 13.0) versus 5.6 months (5.0 to 7.0), hazard ratio 0.57 (99 percent CI 0.44 to 0.73, p<0.0001); median overall survival 23.7 months (19.8 to 25.6) versus 18.7 months (16.0 to 21.8), hazard ratio 0.79 (95.01 percent CI 0.64 to 0.98, p=0.029). Grade 3 or higher treatment-related adverse events occurred in 33 versus 29 percent, led to discontinuation in 4 versus 7 percent, and there were no treatment-related deaths.","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2026","url":"https://doi.org/10.1016/j.annonc.2026.03.008"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41937088/"},{"label":"ClinicalTrials.gov NCT05374512","url":"https://clinicaltrials.gov/study/NCT05374512"}],"tags":["tnbc-evidence"],"related":["trop2-adc-roadmap"],"cancers":["tnbc"],"sections":[],"technologies":["adc","topoisomerase-inhibitors"],"targets":["trop2"],"drugs":["datopotamab-deruxtecan"],"companies":["astrazeneca","daiichi-sankyo"],"institutions":[],"pathways":[],"terms":["pfs","os","adc-sequencing"],"trials":["tropion-breast02","tropion-breast05","ascent-03"],"people":["rebecca-dent","peter-schmid","javier-cortes"],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2026,"doi":"10.1016/j.annonc.2026.03.008","pmid":"41937088","authors":"Dent R, Shao Z, Schmid P, et al.","paperType":"rct","findings":["Median progression-free survival 10.8 vs 5.6 months; hazard ratio 0.57 (99 percent CI 0.44 to 0.73), p<0.0001.","Median overall survival 23.7 vs 18.7 months; hazard ratio 0.79 (95.01 percent CI 0.64 to 0.98), p=0.029.","Grade 3 or higher treatment-related adverse events 33 vs 29 percent; discontinuation 4 vs 7 percent; no treatment-related deaths."],"whatItMeans":"The first-line overall survival result that made an antibody-drug conjugate the standard for PD-L1-negative or immunotherapy-ineligible metastatic triple-negative disease, and the reason the sequencing question (which TROP2 drug first, what after it) is now urgent.","caveats":["Open-label design; progression-free survival was centrally reviewed to compensate.","Excluded patients eligible for immunotherapy, so it does not compare with pembrolizumab-based first-line treatment; TROPION-Breast05 does.","Interstitial lung disease is a class risk and its rate is read from the full paper, not the abstract."],"changedPractice":true,"participants":644},{"id":"paper-watson-nature","kind":"paper","name":"De novo design of protein structure and function with RFdiffusion","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 37433327 and published in Nature; the citing page links this DOI, which is how the record was matched.","summary":"There has been considerable recent progress in designing new proteins using deep-learning methods 1-9. Despite this progress, a general deep-learning framework for protein design that enables solution of a wide range of design challenges, including de novo binder design and design of higher-order symmetric architectures, has yet to be described. Diffusion models 10,11 have had considerable success in image and language generative modelling but limited success when applied to protein modelling, probably due to the complexity of protein backbone geometry and sequence-structure relationships. Here we show that by fine-tuning the RoseTTAFold structure prediction network on protein structure denoising tasks, we obtain a generative model of protein backbones that achieves outstanding performance on unconditional and topology-constrained protein monomer design, protein binder design, symmetric oligomer design, enzyme active site scaffolding and symmetric motif scaffolding for therapeutic and metal-binding protein design. We demonstrate the power and generality of the method, called RoseTTAFold diffusion (RFdiffusion), by experimentally characterizing the structures and functions of hundreds of designed symmetric assemblies, metal-binding proteins and protein binders. The accuracy of RFdiffusion is confirmed by the cryogenic electron microscopy structure of a designed binder in complex with influenza haemagglutinin that is nearly identical to the design model. In a manner analogous to networks that produce images from user-specified inputs, RFdiffusion enables the design of diverse functional proteins from simple molecular specifications.\n\nIndexed on Europe PMC as PubMed record 37433327 (DOI 10.1038/s41586-023-06415-8). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2023","url":"https://doi.org/10.1038/s41586-023-06415-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37433327/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37433327"}],"tags":["europepmc-ingest"],"related":["rfdiffusion"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2023,"doi":"10.1038/s41586-023-06415-8","pmid":"37433327","authors":"Watson JL, Juergens D, Bennett NR, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-de-escalate-lancet-2019","kind":"paper","name":"De-ESCALaTE HPV: radiotherapy plus cisplatin or cetuximab in low-risk HPV-positive oropharyngeal cancer","aka":[],"tldr":"This European trial, like its American counterpart, found that replacing cisplatin with cetuximab in low-risk HPV-positive oropharyngeal cancer caused more recurrences and deaths without reducing severe toxicity.","summary":"Phase 3 trial of 334 patients with low-risk HPV-positive oropharyngeal cancer (non-smokers or light smokers) randomised to radiotherapy 70 Gy with cisplatin or with cetuximab, with severe toxicity as the primary endpoint.\n\nSevere toxicity did not differ, while two-year overall survival was 97.5 percent with cisplatin against 89.4 percent with cetuximab (hazard ratio 5.0) and recurrence was 6.0 versus 16.1 percent.","asOf":"2026-09-17","links":[{"label":"Lancet 2019","url":"https://doi.org/10.1016/S0140-6736(18)32752-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30449623/"}],"tags":[],"related":[],"cancers":["hpv-positive-oropharyngeal-cancer","oropharyngeal-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["cetuximab","cisplatin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["de-escalate"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2019,"doi":"10.1016/S0140-6736(18)32752-1","pmid":"30449623","authors":"Mehanna H, Robinson M, Hartley A, et al.","paperType":"rct","findings":["Two-year overall survival 97.5 percent (cisplatin) vs 89.4 percent (cetuximab).","Two-year recurrence 6.0 percent vs 16.1 percent."],"whatItMeans":"Cetuximab is not an acceptable substitute for cisplatin in HPV-positive disease; de-escalation must be tested through other routes such as dose reduction after response or surgery-based pathways.","caveats":["Small trial powered for toxicity rather than survival."],"changedPractice":true,"participants":334},{"id":"paper-gilligan-am-j-med","kind":"paper","name":"Death or Debt? National Estimates of Financial Toxicity in Persons with Newly-Diagnosed Cancer","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 29906429 and published in The American journal of medicine; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: The purpose of this study was to evaluate the impact of cancer upon a patient's net worth and debt in the US.\n\nMethods: This longitudinal study used the Health and Retirement Study from 1998-2014. Persons ≥50years with newly-diagnosed malignancies were included, excluding minor skin cancers. Multivariable generalized linear models assessed changes in net worth and debt (consumer, mortgage, home equity) at 2 and 4 years after diagnosis (year +2, year +4), controlling for demographic and clinically-related variables, cancer-specific attributes, economic factors, and mortality. A 2-year period before cancer diagnosis served as a historical control.\n\nResults: Across 9.5 million estimated new diagnoses of cancer from 2000-2012, individuals averaged 68.6±9.4 years with slight majorities being married (54.7%), not retired (51.1%), and Medicare beneficiaries (56.6%). At year +2, 42.4% depleted their entire life's assets, with higher adjusted odds associated with worsening cancer, requirement of continued treatment, demographic and socioeconomic factors (ie, female, Medicaid, uninsured, retired, increasing age, income, and household size), and clinical characteristics (ie, current smoker, worse self-reported health, hypertension, diabetes, lung disease) (P<.05); average losses were $92,098. At year +4, financial insolvency extended to 38.2%, with several consistent socioeconomic, cancer-related, and clinical characteristics remaining significant predictors of complete asset depletion.\n\nConclusions: This nationally-representative investigation of an initially-estimated 9.5 million newly-diagnosed persons with cancer who were ≥50 years of age found a substantial proportion incurring financial toxicity. As large financial burdens have been found to adversely affect access to care and outcomes among cancer patients, the active development of approaches to mitigate these effects among already vulnerable groups remains of key importance.\n\nIndexed on Europe PMC as PubMed record 29906429 (DOI 10.1016/j.amjmed.2018.05.020). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Am J Med 2018","url":"https://doi.org/10.1016/j.amjmed.2018.05.020"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29906429/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29906429"}],"tags":["europepmc-ingest"],"related":["financial-navigation"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The American journal of medicine","year":2018,"doi":"10.1016/j.amjmed.2018.05.020","pmid":"29906429","authors":"Gilligan AM, Alberts DS, Roe DJ, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-decision-sorafenib-lancet-2014","kind":"paper","name":"DECISION: sorafenib in radioactive iodine-refractory differentiated thyroid cancer","aka":[],"tldr":"Sorafenib was the first drug shown to delay progression in iodine-refractory differentiated thyroid cancer, adding about five months compared with placebo and opening the era of kinase inhibitors for the disease.","summary":"Phase 3 placebo-controlled trial of 417 patients with progressive radioactive iodine-refractory differentiated thyroid cancer randomised to sorafenib or placebo.\n\nMedian progression-free survival was 10.8 versus 5.8 months (hazard ratio 0.59) with response 12.2 versus 0.5 percent; hand-foot skin reaction, diarrhoea, alopecia and rash were common.","asOf":"2026-09-17","links":[{"label":"Lancet 2014","url":"https://doi.org/10.1016/S0140-6736(14)60421-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24768112/"}],"tags":[],"related":[],"cancers":["follicular-thyroid-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["sorafenib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["decision-sorafenib"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2014,"doi":"10.1016/S0140-6736(14)60421-9","pmid":"24768112","authors":"Brose MS, Nutting CM, Jarzab B, et al.","paperType":"rct","findings":["Median progression-free survival 10.8 vs 5.8 months; hazard ratio 0.59.","Objective response 12.2 percent vs 0.5 percent."],"whatItMeans":"Sorafenib is an approved option for iodine-refractory thyroid cancer, now usually used after or instead of lenvatinib depending on tolerability.","caveats":["No overall survival benefit; response rate low compared with lenvatinib."],"changedPractice":true,"participants":417},{"id":"paper-koopman-deficient-mismatch-repair-advanced-colorectal-bjc-2009","kind":"paper","name":"Deficient mismatch repair system in patients with sporadic advanced colorectal cancer","aka":[],"tldr":"Broken DNA repair is common in bowel cancers removed by surgery but rare once the disease has spread, which is evidence that those tumours are less able to metastasise in the first place.","summary":"Data were collected from a phase 3 study in 820 patients with advanced colorectal cancer. Mismatch repair protein expression was examined by immunohistochemistry, with microsatellite instability analysis and MLH1 promoter methylation status. Deficient mismatch repair was found in only 18 of 515 evaluable patients (3.5%), 13 of them caused by MLH1 promoter hypermethylation. Median overall survival was 17.9 months in proficient patients, 7.4 months in those deficient through MLH1 hypermethylation and 10.2 months in all deficient patients; disease control was 83% against 56%. The authors concluded that deficient mismatch repair is rare in sporadic advanced colorectal cancer, supporting the hypothesis that such tumours have reduced metastatic potential.","asOf":"2026-09-24","links":[{"label":"Koopman et al., Br J Cancer 2009: deficient mismatch repair in 515 patients with sporadic advanced colorectal cancer","url":"https://doi.org/10.1038/sj.bjc.6604867"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19165197/"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["msi-mmr-testing","histopathology-ihc"],"targets":["mmr","mlh1"],"drugs":[],"companies":[],"institutions":["radboudumc"],"pathways":["mismatch-repair-msi"],"terms":["msi","mss-pmmr","ihc"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["british-journal-of-cancer"],"dependsOn":[],"notes":[],"journal":"British Journal of Cancer","year":2009,"doi":"10.1038/sj.bjc.6604867","pmid":"19165197","authors":"Koopman M, Kortman GA, Mekenkamp L, et al.","paperType":"observational","findings":["Deficient mismatch repair in 18 of 515 evaluable advanced patients (3.5%), 13 from MLH1 hypermethylation.","Median overall survival 17.9 months proficient against 10.2 months deficient."],"whatItMeans":"It is the reason the immunotherapy-eligible fraction of metastatic colorectal cancer is about 5% rather than the 15% quoted for resected disease, and it frames microsatellite instability as a barrier to metastasis that becomes a liability once crossed.","caveats":["Small number of deficient patients, so the survival comparison is imprecise.","Predates checkpoint inhibitors, so the prognosis described no longer applies to treated patients."],"changedPractice":false,"participants":820},{"id":"paper-depmap-tsherniak-cell-2017","kind":"paper","name":"Defining a Cancer Dependency Map: which genes each cancer cell line cannot live without","aka":[],"tldr":"Genome-scale RNAi screens across 501 cancer cell lines, analysed with the DEMETER algorithm to remove off-target noise, identified 769 genes on which subsets of cancers depend and showed that most dependencies can be predicted from the cell's molecular features.","summary":"The Broad Institute's Project Achilles knocked down 17,098 genes in 501 cell lines drawn from a broad range of cancer types using pooled shRNA libraries. A new computational method, DEMETER, separated on-target from seed-sequence off-target effects, a longstanding problem of RNAi screens.\n\nThe analysis identified 769 genes with strong differential dependency across lines; more than 90% of lines depended on at least one such gene, and 426 of the 769 dependencies could be predicted from mutation, copy number or expression features. Predictive markers were often not the gene itself but paralog loss, lineage or pathway activity, pointing to synthetic-lethal and lineage-specific targets.\n\nThe paper defined the goal of the Cancer Dependency Map (DepMap), which has since moved to genome-wide CRISPR screens (Meyers 2017, Behan 2019) in over 1,000 lines with matched multi-omics, and is the most-used resource for target discovery and biomarker hypothesis generation.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1016/j.cell.2017.06.010"},{"label":"CRISPR-based DepMap (Meyers 2017)","url":"https://doi.org/10.1038/ng.3984"},{"label":"DepMap portal","url":"https://depmap.org"}],"tags":[],"related":["depmap","high-throughput-screening-libraries"],"cancers":[],"sections":["drug-discovery"],"technologies":["crispr-screens","synthetic-lethality-approaches","functional-drug-testing"],"targets":["wrn","prmt5-mtap"],"drugs":[],"companies":[],"institutions":["broad-institute","dana-farber"],"pathways":[],"terms":["synthetic-lethality"],"trials":[],"people":[],"bottlenecks":["b-preclinical-models","b-undruggable-targets","b-translational-valley"],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Cell","year":2017,"doi":"10.1016/j.cell.2017.06.010","pmid":"28753430","authors":"Tsherniak A, Vazquez F, Montgomery PG, et al.","paperType":"basic","findings":["501 cell lines screened with 17,098-gene shRNA library; DEMETER algorithm removed seed-based off-target effects","769 genes with differential dependency; over 90% of lines depended on at least one","426 dependencies (55%) predictable from genomic or expression features, often via paralogs or lineage factors","Dependencies on WRN in MSI-high lines and on paralogs (for example SMARCA2 in SMARCA4-mutant lines) emerged from these and follow-on screens"],"whatItMeans":"DepMap is the lookup table drug hunters use to ask: which cancers would die if we blocked this gene, and how would we recognise them? It generated targets such as WRN and PRMT5-MTAP now in clinical trials, and it is public.","caveats":["Cell lines lack microenvironment, immune context and drug pharmacology; many in vitro dependencies do not translate","RNAi knockdown is partial; CRISPR knockout can give different results for essential genes","Lineages and ancestries are unevenly represented; some cancers have few lines","Dependency does not equal druggability; most dependencies are transcription factors or lineage genes"],"changedPractice":false},{"id":"paper-lievens-radiother-oncol","kind":"paper","name":"Defining oligometastatic disease from a radiation oncology perspective: An ESTRO-ASTRO consensus document","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 32388150 and published in Radiotherapy and Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background: Recognizing the rapidly increasing interest and evidence in using metastasis-directed radiotherapy (MDRT) for oligometastatic disease (OMD), ESTRO and ASTRO convened a committee to establish consensus regarding definitions of OMD and define gaps in current evidence.\n\nMethods: A systematic literature review focused on curative intent MDRT was performed in Medline, Embase and Cochrane. Subsequent consensus opinion, using a Delphi process, highlighted the current state of evidence and the limitations in the available literature.\n\nResults: Available evidence regarding the use of MDRT for OMD mostly derives from retrospective, single-centre series, with significant heterogeneity in patient inclusion criteria, definition of OMD, and outcomes reported. Consensus was reached that OMD is largely independent of primary tumour, metastatic location and the presence or length of a disease-free interval, supporting both synchronous and metachronous OMD. In the absence of clinical data supporting a maximum number of metastases and organs to define OMD, and of validated molecular biomarkers, consensus supported the ability to deliver safe and clinically meaningful radiotherapy with curative intent to all metastatic sites as a minimum requirement for defining OMD in the context of radiotherapy. Systemic therapy induced OMD was identified as a distinct state of OMD. High-resolution imaging to assess and confirm OMD is crucial, including brain imaging when indicated. Minimum common endpoints such as progression-free and overall survival, local control, toxicity and quality-of-life should be reported; uncommon endpoints as deferral of systemic therapy and cost were endorsed.\n\nConclusion: While significant heterogeneity exists in the current OMD definitions in the literature, consensus was reached on multiple key questions. Based on available data, OMD can to date be defined as 1-5 metastatic lesions, a controlled primary tumor being optional, but where all metastatic sites must be safely treatable. Consistent definitions and reporting are warranted and encouraged in ongoing trials and reports generating further evidence to optimize patient benefits.\n\nIndexed on Europe PMC as PubMed record 32388150 (DOI 10.1016/j.radonc.2020.04.003). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Radiother Oncol 2020","url":"https://doi.org/10.1016/j.radonc.2020.04.003"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32388150/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32388150"}],"tags":["europepmc-ingest"],"related":["oligometastatic"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["radiotherapy-and-oncology"],"dependsOn":[],"notes":[],"journal":"Radiotherapy and Oncology","year":2020,"doi":"10.1016/j.radonc.2020.04.003","pmid":"32388150","authors":"Lievens Y, Guckenberger M, Gomez D, et al.","paperType":"review","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-fearon-lancet-oncol","kind":"paper","name":"Definition and classification of cancer cachexia: an international consensus","aka":[],"tldr":"Paper cited by one term page, one bottleneck page and eleven idea pages, indexed on Europe PMC as PubMed record 21296615 and published in The Lancet Oncology; the citing pages link this DOI, which is how the record was matched.","summary":"To develop a framework for the definition and classification of cancer cachexia a panel of experts participated in a formal consensus process, including focus groups and two Delphi rounds. Cancer cachexia was defined as a multifactorial syndrome defined by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment. Its pathophysiology is characterised by a negative protein and energy balance driven by a variable combination of reduced food intake and abnormal metabolism. The agreed diagnostic criterion for cachexia was weight loss greater than 5%, or weight loss greater than 2% in individuals already showing depletion according to current bodyweight and height (body-mass index [BMI] <20 kg/m(2)) or skeletal muscle mass (sarcopenia). An agreement was made that the cachexia syndrome can develop progressively through various stages--precachexia to cachexia to refractory cachexia. Severity can be classified according to degree of depletion of energy stores and body protein (BMI) in combination with degree of ongoing weight loss. Assessment for classification and clinical management should include the following domains: anorexia or reduced food intake, catabolic drive, muscle mass and strength, functional and psychosocial impairment. Consensus exists on a framework for the definition and classification of cancer cachexia. After validation, this should aid clinical trial design, development of practice guidelines, and, eventually, routine clinical management.\n\nIndexed on Europe PMC as PubMed record 21296615 (DOI 10.1016/s1470-2045(10)70218-7). Matched by DOI alone: one term page, one bottleneck page and eleven idea pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2011","url":"https://doi.org/10.1016/s1470-2045(10)70218-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21296615/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/21296615"}],"tags":["europepmc-ingest"],"related":["cachexia","b-cachexia-supportive","idea-bio2-low-dose-olanzapine-appetite","idea-nl-dietitian-in-every-mdt","idea-bio2-remote-weight-step-monitoring","idea-bio2-lean-mass-dosing","idea-bio2-prehabilitation-standard","idea-bio2-anamorelin-access","idea-bio2-exercise-reimbursement","idea-bio2-ai-sarcopenia-from-ct","idea-bio2-protein-plus-training-during-io","idea-moon-cachexia-as-treatable-disease","idea-bio2-cachexia-pathway-code"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2011,"doi":"10.1016/s1470-2045(10)70218-7","pmid":"21296615","authors":"Fearon K, Strasser F, Anker SD, et al.","paperType":"review","findings":[],"whatItMeans":"One term page, one bottleneck page and eleven idea pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-jak2-polycythaemia-vera-lancet-2005","kind":"paper","name":"Definition of subtypes of essential thrombocythaemia and relation to polycythaemia vera based on JAK2 V617F mutation status: a prospective study","aka":[],"tldr":"Phase 2 or 3 results paper on JAK2 in Polycythaemia vera, in The Lancet (2005), one of the most cited Europe PMC records with JAK2 in its title.","summary":"Background: An acquired V617F mutation in JAK2 occurs in most patients with polycythaemia vera, but is seen in only half those with essential thrombocythaemia and idiopathic myelofibrosis. We aimed to assess whether patients with the mutation are biologically distinct from those without, and why the same mutation is associated with different disease phenotypes.\n\nMethods: Two sensitive PCR-based methods were used to assess the JAK2 mutation status of 806 patients with essential thrombocythaemia, including 776 from the Medical Research Council's Primary Thrombocythaemia trial (MRC PT-1) and two other prospective studies. Laboratory and clinical features, response to treatment, and clinical events were compared for V617F-positive and V617F-negative patients with essential thrombocythaemia.\n\nFindings: Mutation-positive patients had multiple features resembling polycythaemia vera, with significantly increased haemoglobin (mean increase 9.6 g/L, 95% CI 7.6-11.6 g/L; p<0.0001), neutrophil counts (1.1x10(9)/L, 0.7-1.5x10(9)/L; p<0.0001), bone marrow erythropoiesis and granulopoiesis, more venous thromboses, and a higher rate of polycythaemic transformation than those without the mutation. Mutation-positive patients had lower serum erythropoietin (mean decrease 13.8 U/L; 95% CI, 10.8-16.9 U/L; p<0.0001) and ferritin (n=182; median 58 vs 91 mug/L; p=0.01) concentrations than did mutation-negative patients. Mutation-negative patients did, nonetheless, show many clinical and laboratory features that were characteristic of a myeloproliferative disorder. V617F-positive individuals were more sensitive to therapy with hydroxyurea, but not anagrelide, than those without the JAK2 mutation.\n\nInterpretation: Our results suggest that JAK2 V617F-positive essential thrombocythaemia and polycythaemia vera form a biological continuum, with the degree of erythrocytosis determined by physiological or genetic modifiers.\n\nIndexed on Europe PMC as PubMed record 16325696 (DOI 10.1016/s0140-6736(05)67785-9). Its title names JAK2 and its text names Polycythaemia vera; PubMed types it as a clinical trial report (Research Support, Non-U.S. Gov't, Multicenter Study, Randomized Controlled Trial). It was matched automatically to the idea \"Clearing the JAK2 clone in polycythaemia vera: interferon plus mutant-selective inhibitors as a route to treatment-free remission\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet 2005","url":"https://doi.org/10.1016/s0140-6736(05)67785-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/16325696/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/16325696"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2005,"doi":"10.1016/s0140-6736(05)67785-9","pmid":"16325696","authors":"Campbell PJ, Scott LM, Buck G, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for JAK2 in Polycythaemia vera, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by JAK2 in the title and Polycythaemia vera in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-shindo-germline-sporadic-pancreatic-jco-2017","kind":"paper","name":"Deleterious germline mutations in patients with apparently sporadic pancreatic adenocarcinoma","aka":[],"tldr":"Sequencing normal tissue from 854 people who had pancreatic cancer surgery at Johns Hopkins found an inherited cancer-gene mutation in 3.9%, and only three of those 33 patients had a family history of the disease.","summary":"Thirty-two genes were sequenced in normal tissue DNA from 854 patients with pancreatic ductal adenocarcinoma, 288 with other pancreatic and periampullary neoplasms and 51 with non-neoplastic disease resected at Johns Hopkins (2000 to 2015). Thirty-three (3.9%) pancreatic cancer patients had a deleterious germline mutation, 31 (3.5%) in known susceptibility genes: BRCA2 (12), ATM (10), BRCA1 (3), PALB2 (2), MLH1 (2), CDKN2A (1), TP53 (1), plus BUB1B and BUB3. Carriers were younger (60.8 versus 65.1 years). Only 3 of 33 reported a family history of pancreatic cancer. Five (1.7%) of 288 with other periampullary neoplasms also carried a mutation.","asOf":"2026-09-24","links":[{"label":"Shindo et al., J Clin Oncol 2017: germline mutations in 854 apparently sporadic pancreatic cancers (Johns Hopkins)","url":"https://doi.org/10.1200/JCO.2017.72.3502"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28767289/"}],"tags":[],"related":["brca-germline"],"cancers":["pancreatic","resectable-pdac","brca-palb2-pdac"],"sections":[],"technologies":["germline-testing"],"targets":["brca","atm","palb2","mlh1","cdkn2a"],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":[],"terms":["gbrca-mutation","germline-vs-somatic"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2017,"doi":"10.1200/JCO.2017.72.3502","pmid":"28767289","authors":"Shindo K, Yu J, Suenaga M, et al.","paperType":"observational","findings":["Germline mutation in 33 of 854, 3.9%: BRCA2 12, ATM 10, BRCA1 3, PALB2 2, MLH1 2, CDKN2A 1, TP53 1.","Only 3 of 33 carriers had a family history of pancreatic cancer."],"whatItMeans":"Family-history criteria miss nine in ten carriers, the finding that moved guidelines to offer germline testing to every patient.","caveats":["Resected patients at one centre.","Thirty-two genes only."],"changedPractice":true,"participants":854},{"id":"paper-mullighan-ikzf1-nejm-2009","kind":"paper","name":"Deletion of IKZF1 and prognosis in acute lymphoblastic leukaemia","aka":[],"tldr":"Deletion or mutation of the IKZF1 gene marked a subgroup of childhood B-cell acute lymphoblastic leukaemia with a threefold higher risk of relapse, and these cases shared a gene expression signature with Philadelphia-positive leukaemia.","summary":"Genomic study of 221 children with high-risk B-ALL identifying IKZF1 deletions or mutations in 28.6 percent, associated with a hazard ratio of about 3.5 for relapse, poor outcome independent of other factors, and a gene expression profile resembling BCR-ABL1-positive ALL; findings were validated in a second cohort.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2009","url":"https://doi.org/10.1056/NEJMoa0808253"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19129520/"}],"tags":[],"related":[],"cancers":["all-ph-like"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2009,"doi":"10.1056/NEJMoa0808253","pmid":"19129520","authors":"Mullighan CG, Su X, Zhang J, et al.","paperType":"translational","findings":["IKZF1 alterations in 28.6 percent of high-risk B-ALL.","Hazard ratio for relapse about 3.5 with IKZF1 alteration."],"whatItMeans":"IKZF1 status is part of risk stratification in several paediatric ALL protocols and is a hallmark of Ph-like ALL.","caveats":["Prognostic effect is attenuated by measurable residual disease-directed therapy and co-occurring favourable lesions."],"changedPractice":true,"participants":221},{"id":"paper-pramesh-lancet-oncol","kind":"paper","name":"Delivery of affordable and equitable cancer care in India","aka":[],"tldr":"Paper cited by one roadmap page, indexed on Europe PMC as PubMed record 24731888 and published in The Lancet Oncology; the citing page links this DOI, which is how the record was matched.","summary":"The delivery of affordable and equitable cancer care is one of India's greatest public health challenges. Public expenditure on cancer in India remains below US$10 per person (compared with more than US$100 per person in high-income countries), and overall public expenditure on health care is still only slightly above 1% of gross domestic product. Out-of-pocket payments, which account for more than three-quarters of cancer expenditures in India, are one of the greatest threats to patients and families, and a cancer diagnosis is increasingly responsible for catastrophic expenditures that negatively affect not only the patient but also the welfare and education of several generations of their family. We explore the complex nature of cancer care systems across India, from state to government levels, and address the crucial issues of infrastructure, manpower shortages, and the pressing need to develop cross-state solutions to prevention and early detection of cancer, in addition to governance of the largely unregulated private sector and the cost of new technologies and drugs. We discuss the role of public insurance schemes, the need to develop new political mandates and authority to set priorities, the necessity to greatly improve the quality of care, and the drive to understand and deliver cost-effective cancer care programmes.\n\nIndexed on Europe PMC as PubMed record 24731888 (DOI 10.1016/s1470-2045(14)70117-2). Matched by DOI alone: one roadmap page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2014","url":"https://doi.org/10.1016/s1470-2045(14)70117-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24731888/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/24731888"}],"tags":["europepmc-ingest"],"related":["global-access-roadmap"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2014,"doi":"10.1016/s1470-2045(14)70117-2","pmid":"24731888","authors":"Pramesh CS, Badwe RA, Borthakur BB, et al.","paperType":"observational","findings":[],"whatItMeans":"One roadmap page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-dellphi-301-nejm-2023","kind":"paper","name":"DeLLphi-301: tarlatamab, a DLL3-targeting T-cell engager, in previously treated small-cell lung cancer","aka":[],"tldr":"A bispecific antibody that pulls T cells onto small-cell lung cancer cells produced responses in 40% of patients whose cancer had come back after chemotherapy, lasting far longer than any previous drug in this setting.","summary":"Open-label phase 2 trial of 220 patients with small-cell lung cancer that had progressed after platinum-based chemotherapy (and usually immunotherapy), testing tarlatamab, a DLL3 x CD3 bispecific T-cell engager, at 10 mg or 100 mg every two weeks. Primary endpoint was objective response rate.\n\nAt 10 mg the response rate was 40%, median PFS 4.9 months and median OS 14.3 months, with cytokine release syndrome in about half of patients, mostly grade 1-2 and mainly during the first cycle. It led to accelerated FDA approval in 2024 and was confirmed by the phase 3 DeLLphi-304 trial, which showed a survival benefit over chemotherapy (median OS 13.6 vs 8.3 months, HR 0.60).","asOf":"2026-09-08","links":[{"label":"NEJM 2023","url":"https://doi.org/10.1056/NEJMoa2307980"},{"label":"ClinicalTrials.gov NCT05060016","url":"https://clinicaltrials.gov/study/NCT05060016"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37861218/"}],"tags":[],"related":["paper-tarlatamab-sclc-n-engl-j-med-2025","paper-dll3-sclc-clin-cancer-res-2019","paper-rudin-sclc-molecular-subtypes-nat-rev-cancer-2019"],"cancers":["sclc","lung-cancer","extensive-stage-sclc"],"sections":["immunotherapy","drug-discovery"],"technologies":["t-cell-engager","bispecific-antibody"],"targets":["dll3","cd3"],"drugs":["tarlatamab"],"companies":["amgen"],"institutions":["samsung-medical-center"],"pathways":[],"terms":["orr","crs","icans","accelerated-approval","resistance"],"trials":["dellphi-304"],"people":["ahn-myung-ju","cho-byoung-chul","enriqueta-felip","juergen-wolf","fiona-blackhall","luis-paz-ares"],"bottlenecks":["b-undruggable-targets","b-dose-optimisation","b-toxicity-qol","b-rare-cancers","b-manufacturing-cell-therapy","b-care-fragmentation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/NEJMoa2307980","pmid":"37861218","authors":"Ahn MJ, Cho BC, Felip E, et al.","paperType":"rct","findings":["Objective response 40% at 10 mg and 32% at 100 mg; median duration of response over 9 months.","At 10 mg: median PFS 4.9 months; median overall survival 14.3 months in a population with a historical OS of 6-8 months.","Cytokine release syndrome 51% (10 mg) and 61% (100 mg), mostly grade 1-2 in cycle 1; ICANS or associated neurological events in about 8% (10 mg).","Discontinuation for treatment-related adverse events 3% at the 10 mg dose, which was selected for further development.","DeLLphi-304 phase 3 (2025): OS 13.6 vs 8.3 months versus chemotherapy, HR 0.60."],"whatItMeans":"Patients with small-cell lung cancer that has relapsed after chemotherapy now have a drug that works far better than topotecan or lurbinectedin, and it is the first T-cell engager approved for a solid tumour. Treatment requires inpatient monitoring for the first doses because of cytokine release syndrome, which most centres now manage on a short-stay basis. It does not yet apply to first-line treatment, where trials are ongoing.","caveats":["Single-arm phase 2 with a randomised dose comparison, not a randomised comparison against chemotherapy (that came with DeLLphi-304).","Cytokine release syndrome and neurotoxicity require hospital-based step-up dosing and limit use in frail patients or centres without experience.","Every-two-week intravenous dosing is burdensome for patients with a short life expectancy.","DLL3 expression was not required for entry and was not predictive, so there is no selection biomarker."],"changedPractice":true,"participants":220},{"id":"paper-va-larynx-induction-chemotherapy-nejm-1991","kind":"paper","name":"Department of Veterans Affairs Laryngeal Cancer Study: induction chemotherapy plus radiation versus surgery plus radiation","aka":[],"tldr":"This landmark trial showed that advanced laryngeal cancer could be treated with chemotherapy followed by radiotherapy instead of total laryngectomy, with the same survival and preservation of the larynx in about two thirds of survivors.","summary":"Phase 3 trial of 332 patients with stage III to IV laryngeal squamous cell carcinoma randomised to induction cisplatin-fluorouracil followed by radiotherapy in responders (with surgery for non-responders or relapse) or total laryngectomy with postoperative radiotherapy.\n\nTwo-year survival was 68 percent in both arms and the larynx was preserved in 64 percent of surviving patients in the chemotherapy arm, with fewer distant metastases but more local recurrences.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 1991","url":"https://doi.org/10.1056/NEJM199106133242402"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/2034244/"}],"tags":[],"related":[],"cancers":["laryngeal-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":1991,"doi":"10.1056/NEJM199106133242402","pmid":"2034244","authors":"Department of Veterans Affairs Laryngeal Cancer Study Group, Wolf GT, Fisher SG, et al.","paperType":"rct","findings":["Two-year overall survival 68 percent in both arms.","Larynx preserved in 64 percent of surviving patients treated with chemotherapy and radiotherapy."],"whatItMeans":"Organ preservation became a legitimate goal in laryngeal cancer; RTOG 91-11 later refined the approach to concurrent chemoradiation.","caveats":["Predates concurrent chemoradiation and modern imaging.","Salvage laryngectomy after radiotherapy carries higher complication rates."],"changedPractice":true,"participants":332},{"id":"paper-viswanathan-nature","kind":"paper","name":"Dependency of a therapy-resistant state of cancer cells on a lipid peroxidase pathway","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 28678785 and published in Nature; the citing page links this DOI, which is how the record was matched.","summary":"Plasticity of the cell state has been proposed to drive resistance to multiple classes of cancer therapies, thereby limiting their effectiveness. A high-mesenchymal cell state observed in human tumours and cancer cell lines has been associated with resistance to multiple treatment modalities across diverse cancer lineages, but the mechanistic underpinning for this state has remained incompletely understood. Here we molecularly characterize this therapy-resistant high-mesenchymal cell state in human cancer cell lines and organoids and show that it depends on a druggable lipid-peroxidase pathway that protects against ferroptosis, a non-apoptotic form of cell death induced by the build-up of toxic lipid peroxides. We show that this cell state is characterized by activity of enzymes that promote the synthesis of polyunsaturated lipids. These lipids are the substrates for lipid peroxidation by lipoxygenase enzymes. This lipid metabolism creates a dependency on pathways converging on the phospholipid glutathione peroxidase (GPX4), a selenocysteine-containing enzyme that dissipates lipid peroxides and thereby prevents the iron-mediated reactions of peroxides that induce ferroptotic cell death. Dependency on GPX4 was found to exist across diverse therapy-resistant states characterized by high expression of ZEB1, including epithelial-mesenchymal transition in epithelial-derived carcinomas, TGFβ-mediated therapy-resistance in melanoma, treatment-induced neuroendocrine transdifferentiation in prostate cancer, and sarcomas, which are fixed in a mesenchymal state owing to their cells of origin. We identify vulnerability to ferroptic cell death induced by inhibition of a lipid peroxidase pathway as a feature of therapy-resistant cancer cells across diverse mesenchymal cell-state contexts.\n\nIndexed on Europe PMC as PubMed record 28678785 (DOI 10.1038/nature23007). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2017","url":"https://doi.org/10.1038/nature23007"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28678785/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28678785"}],"tags":["europepmc-ingest"],"related":["ferroptosis-cell-death"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2017,"doi":"10.1038/nature23007","pmid":"28678785","authors":"Viswanathan VS, Ryan MJ, Dhruv HD, et al.","paperType":"basic","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-ozdemir-caf-depletion-accelerates-pancreatic-cancer-cancer-cell-2014","kind":"paper","name":"Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival","aka":[],"tldr":"The 2014 mouse study showing that removing the scar-forming cells around pancreatic tumours made the cancers more aggressive and the mice die sooner, the warning that the stroma is not simply an obstacle to be cleared.","summary":"Özdemir and colleagues in Raghu Kalluri's laboratory generated transgenic mice able to delete alpha-SMA-positive myofibroblasts in pancreatic cancer. Depletion starting at either the precursor (pancreatic intraepithelial neoplasia) or the invasive stage led to invasive, undifferentiated tumours with enhanced hypoxia, epithelial-to-mesenchymal transition and cancer stem cells, and shortened survival. In patients, fewer myofibroblasts in the tumour also correlated with reduced survival. Depleted tumours had suppressed immune surveillance with more CD4-positive Foxp3-positive regulatory T cells; they did not respond to gemcitabine, but anti-CTLA4 immunotherapy reversed the acceleration and prolonged survival. The authors underscore the need for caution in targeting carcinoma-associated fibroblasts.","asOf":"2026-09-24","links":[{"label":"Cancer Cell 2014","url":"https://doi.org/10.1016/j.ccr.2014.04.005"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24856586/"}],"tags":["pancreatic-evidence"],"related":["paper-halo-301-pegvorhyaluronidase-jco-2020","paper-moffitt-virtual-microdissection-subtypes-nat-genet-2015"],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":["fap"],"drugs":["gemcitabine","ipilimumab"],"companies":[],"institutions":["md-anderson"],"pathways":["emt","caf-activation-desmoplasia","tumor-microenvironment"],"terms":["desmoplasia","desmoplastic-stroma-rich","cancer-associated-fibroblasts","cold-vs-hot"],"trials":[],"people":[],"bottlenecks":["b-tme-immunosuppression","b-negative-results"],"keyPapers":[],"journals":["cancer-cell"],"dependsOn":[],"notes":[],"journal":"Cancer Cell","year":2014,"doi":"10.1016/j.ccr.2014.04.005","pmid":"24856586","authors":"Özdemir BC, Pentcheva-Hoang T, Carstens JL, et al.","paperType":"basic","findings":["Myofibroblast depletion in mice produced undifferentiated, hypoxic tumours and shorter survival.","Fewer myofibroblasts in human tumours also correlated with worse survival.","Depleted tumours were gemcitabine-resistant but responded to anti-CTLA4."],"whatItMeans":"Together with the negative HALO-301 trial of hyaluronidase this ended the first, blunt version of stromal targeting; second-generation ideas aim to reprogramme rather than remove the stroma.","caveats":["Mouse genetics; the human correlation is observational.","Stroma is heterogeneous (Moffitt's normal and activated subtypes); depleting one cell type says little about targeting a matrix component."],"changedPractice":true},{"id":"paper-simon-col1a1-pdgfb-dfsp-nat-genet-1997","kind":"paper","name":"Deregulation of the platelet-derived growth factor B-chain gene via fusion with COL1A1 in dermatofibrosarcoma protuberans","aka":[],"tldr":"This study discovered that dermatofibrosarcoma protuberans is driven by a fusion of the collagen gene COL1A1 to the growth factor gene PDGFB, which explains its response to imatinib and gives the tumour a diagnostic marker.","summary":"Molecular characterisation of the ring chromosomes and t(17;22) translocation of dermatofibrosarcoma protuberans and giant cell fibroblastoma, identifying fusion of COL1A1 to PDGFB placing PDGFB under collagen promoter control and leading to autocrine PDGF receptor activation.","asOf":"2026-09-17","links":[{"label":"Nat Genet 1997","url":"https://doi.org/10.1038/ng0197-95"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/8988177/"}],"tags":[],"related":[],"cancers":["dermatofibrosarcoma-protuberans"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":1997,"doi":"10.1038/ng0197-95","pmid":"8988177","authors":"Simon MP, Pedeutour F, Sirvent N, et al.","paperType":"basic","findings":["COL1A1-PDGFB fusion identified as the driver of dermatofibrosarcoma protuberans and giant cell fibroblastoma."],"whatItMeans":"COL1A1-PDGFB fusion testing confirms the diagnosis, and the fusion's dependence on PDGF receptor beta signalling is the rationale for imatinib.","caveats":["Rare cases carry alternative PDGFD fusions."],"changedPractice":true},{"id":"paper-bauer-triple-negative-california-registry-cancer-2007","kind":"paper","name":"Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry","aka":[],"tldr":"The 2007 population study of 6,370 Californian women that fixed the demographics of triple-negative breast cancer: younger, more often Black or Hispanic, poorer, diagnosed later and with worse survival at every stage; Black women with late-stage disease had 14 percent five-year survival.","summary":"Bauer, Brown, Cress, Parise and colleagues used California Cancer Registry data to identify women diagnosed with triple-negative breast cancer between 1999 and 2003 and compared 6,370 triple-negative cases with 44,704 other breast cancers by age, race and ethnicity, socioeconomic status, stage, grade and relative survival. Women with triple-negative cancers were more likely to be under 40 (odds ratio 1.53), non-Hispanic Black (1.77) or Hispanic (1.23). Regardless of stage, they had poorer survival than women with other breast cancers, and non-Hispanic Black women with late-stage triple-negative disease had the poorest survival of any group, a five-year relative survival of 14 percent.","asOf":"2026-09-24","links":[{"label":"Cancer 2007","url":"https://doi.org/10.1002/cncr.22618"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/17387718/"}],"tags":["tnbc-evidence"],"related":["paper-carey-race-breast-cancer-subtypes-cbcs-jama-2006","paper-scott-tnbc-disparities-uscs-cancer-2019"],"cancers":["tnbc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-diversity","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Cancer","year":2007,"doi":"10.1002/cncr.22618","pmid":"17387718","authors":"Bauer KR, Brown M, Cress RD, et al.","paperType":"observational","findings":["6,370 triple-negative vs 44,704 other breast cancers, California 1999 to 2003.","Odds ratios: age under 40 1.53; non-Hispanic Black 1.77; Hispanic 1.23.","Poorer survival regardless of stage; five-year relative survival 14 percent for non-Hispanic Black women with late-stage disease."],"whatItMeans":"The first registry-scale description of the disparity that every later triple-negative disparity paper confirms; the phrase so-called triple-negative phenotype in the title marks the moment the term entered population science.","caveats":["HER2 status recorded by registries in 1999 to 2003 was incomplete and methods varied.","Socioeconomic status measured at area level."],"changedPractice":false,"participants":51074},{"id":"paper-desktop-iii-nejm-2021","kind":"paper","name":"DESKTOP III: secondary cytoreductive surgery for recurrent platinum-sensitive ovarian cancer","aka":[],"tldr":"In women with a first platinum-sensitive relapse selected by a simple score predicting complete resectability, surgery before chemotherapy lengthened survival by about a year, but only when all visible disease was removed.","summary":"Phase 3 trial of 407 patients with first relapse of ovarian cancer after a platinum-free interval of six months or more and a positive AGO score (good performance status, complete resection at first surgery, ascites under 500 ml), randomised to secondary cytoreductive surgery followed by chemotherapy or chemotherapy alone.\n\nMedian overall survival was 53.7 versus 46.0 months (hazard ratio 0.75) and progression-free survival 18.4 versus 14.0 months; patients with complete resection had a median survival of 61.9 months, while incomplete resection was worse than no surgery.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2021","url":"https://doi.org/10.1056/NEJMoa2103294"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34874631/"}],"tags":[],"related":[],"cancers":["platinum-sensitive-ovarian-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["desktop-iii"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2021,"doi":"10.1056/NEJMoa2103294","pmid":"34874631","authors":"Harter P, Sehouli J, Vergote I, et al.","paperType":"rct","findings":["Median overall survival 53.7 vs 46.0 months; hazard ratio 0.75.","Complete resection in 75 percent of surgical patients; median survival 61.9 months in that group."],"whatItMeans":"Secondary cytoreduction is recommended for AGO score-positive patients at first platinum-sensitive relapse in centres where complete resection can be achieved in most cases.","caveats":["The GOG-0213 trial found no benefit, possibly because of less stringent selection and bevacizumab use.","Requires high-volume surgical expertise."],"changedPractice":true,"participants":407},{"id":"paper-destiny-breast03-nejm-2022","kind":"paper","name":"DESTINY-Breast03: trastuzumab deruxtecan beats T-DM1 as second-line treatment of HER2-positive metastatic breast cancer","aka":[],"tldr":"A newer antibody-drug conjugate, trastuzumab deruxtecan, kept HER2-positive metastatic breast cancer under control roughly four times longer than the previous standard, T-DM1, and later lengthened survival.","summary":"Open-label phase 3 trial of 524 patients with HER2-positive unresectable or metastatic breast cancer previously treated with trastuzumab and a taxane, randomised 1:1 to trastuzumab deruxtecan (T-DXd, 5.4 mg/kg) or trastuzumab emtansine (T-DM1). Primary endpoint was progression-free survival by blinded independent central review.\n\nAt the interim analysis, 12-month PFS was 75.8% vs 34.1% (HR 0.28). The 2023 update reported median PFS 28.8 vs 6.8 months and a significant overall survival benefit (HR 0.64). It moved T-DXd into the second line and is the clearest head-to-head demonstration that ADC design (payload, drug-to-antibody ratio, bystander effect) determines clinical outcome.","asOf":"2026-09-08","links":[{"label":"NEJM 2022","url":"https://doi.org/10.1056/NEJMoa2115022"},{"label":"ClinicalTrials.gov NCT03529110","url":"https://clinicaltrials.gov/study/NCT03529110"}],"tags":[],"related":["idea-payload-switching"],"cancers":["breast-her2-positive"],"sections":[],"technologies":["adc","topoisomerase-inhibitors"],"targets":["her2"],"drugs":["trastuzumab-deruxtecan","trastuzumab-emtansine"],"companies":["daiichi-sankyo","astrazeneca"],"institutions":[],"pathways":[],"terms":["pfs","os","payload","dar","bystander-effect","ild","adc-sequencing"],"trials":["destiny-breast03"],"people":["javier-cortes","kim-sung-bae","im-seock-ah","park-yeon-hee","giuseppe-curigliano","xu-binghe","sara-hurvitz"],"bottlenecks":["b-resistance","b-toxicity-qol"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/NEJMoa2115022","authors":"Cortes J, Kim SB, Chung WP, et al.","paperType":"rct","findings":["12-month progression-free survival 75.8% with T-DXd vs 34.1% with T-DM1; HR 0.28 (95% CI 0.22-0.37).","Confirmed objective response 79.7% vs 34.2%.","Updated analysis (Lancet 2023): median PFS 28.8 vs 6.8 months; overall survival HR 0.64.","Drug-related interstitial lung disease/pneumonitis in roughly one in ten T-DXd patients, mostly low grade, with no grade 4-5 events in the primary report."],"whatItMeans":"For HER2-positive metastatic breast cancer that has progressed after trastuzumab and a taxane, trastuzumab deruxtecan is now the standard second-line treatment and T-DM1 has moved later in the sequence. The benefit is large enough that ADC design, not just the target, is understood to be what matters. Patients need lung monitoring because of the risk of pneumonitis.","caveats":["Open-label design, though the primary endpoint was assessed by blinded central review.","Interstitial lung disease requires proactive CT surveillance and dose interruption; fatal cases occurred in other T-DXd trials.","Many patients had not received pertuzumab-based first-line therapy, so the population differs slightly from today's second line.","What to give after T-DXd, and whether a TOP1-payload ADC can follow another, remains unresolved."],"changedPractice":true,"participants":524},{"id":"paper-destiny-breast04-nejm-2022","kind":"paper","name":"DESTINY-Breast04: trastuzumab deruxtecan works in HER2-low breast cancer, creating a new treatable group","aka":[],"tldr":"Breast cancers with only a little HER2 on their surface, long called HER2-negative, responded to trastuzumab deruxtecan and patients lived about six months longer than on chemotherapy. It created the HER2-low category.","summary":"Open-label phase 3 trial of 557 patients with HER2-low (IHC 1+ or IHC 2+/ISH-negative) metastatic breast cancer after one or two lines of chemotherapy, randomised 2:1 to trastuzumab deruxtecan or physician's choice chemotherapy. About 89% were hormone-receptor positive. Primary endpoint was PFS in the HR-positive cohort.\n\nMedian PFS was 10.1 vs 5.4 months (HR 0.51) in the HR-positive cohort and overall survival 23.9 vs 17.5 months (HR 0.64); results in the whole population were similar. Roughly half of all breast cancers are HER2-low, so the trial redefined HER2 testing and opened ADC therapy to a very large population.","asOf":"2026-09-08","links":[{"label":"NEJM 2022","url":"https://doi.org/10.1056/NEJMoa2203690"},{"label":"ClinicalTrials.gov NCT03734029","url":"https://clinicaltrials.gov/study/NCT03734029"}],"tags":[],"related":["idea-payload-switching","her2-low-ihc"],"cancers":["breast-hr-positive","tnbc","tnbc-metastatic"],"sections":[],"technologies":["adc","histopathology-ihc","companion-diagnostic"],"targets":["her2"],"drugs":["trastuzumab-deruxtecan"],"companies":["daiichi-sankyo","astrazeneca"],"institutions":[],"pathways":[],"terms":["her2-low","ihc","bystander-effect","ild","pfs","os"],"trials":["destiny-breast04"],"people":["sohn-joohyuk","park-yeon-hee","xu-binghe","im-seock-ah","hope-rugo","kim-sung-bae","david-cameron"],"bottlenecks":["b-biomarker-validation","b-toxicity-qol"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/NEJMoa2203690","authors":"Modi S, Jacot W, Yamashita T, et al.","paperType":"rct","findings":["HR-positive cohort: median PFS 10.1 vs 5.4 months, HR 0.51 (95% CI 0.40-0.64); median OS 23.9 vs 17.5 months, HR 0.64.","All patients: median PFS 9.9 vs 5.1 months (HR 0.50); median OS 23.4 vs 16.8 months (HR 0.64).","Benefit was similar for IHC 1+ and IHC 2+/ISH-negative tumours, questioning whether HER2 level is the true predictor.","The small HR-negative (triple-negative) cohort of about 58 patients showed a consistent trend (PFS HR 0.46).","Drug-related interstitial lung disease in 12.1% of T-DXd patients, including three deaths."],"whatItMeans":"Patients whose breast cancer was previously called HER2-negative may now be eligible for an effective HER2-directed drug if their tumour has even low-level HER2 staining, so pathology reports must now distinguish HER2-low (1+ or 2+/ISH-negative) from HER2-zero. This applies to metastatic disease after at least one line of chemotherapy; it does not mean these patients benefit from trastuzumab or other older HER2 drugs.","caveats":["HER2-low scoring by immunohistochemistry is poorly reproducible between pathologists, and the assay was never designed to distinguish 0 from 1+.","Fatal pneumonitis occurred; patients need CT surveillance and rapid steroid treatment of symptoms.","The triple-negative cohort was exploratory and small.","DESTINY-Breast06 later showed activity in HER2-ultralow (faint staining) tumours, suggesting the biomarker threshold is arbitrary."],"changedPractice":true,"participants":557},{"id":"paper-destiny-breast06-nejm-2024","kind":"paper","name":"DESTINY-Breast06: trastuzumab deruxtecan before any chemotherapy in hormone-receptor-positive, HER2-low or ultralow breast cancer","aka":[],"tldr":"Given as the first chemotherapy-type treatment after hormone therapy stopped working, trastuzumab deruxtecan delayed progression by about five months compared with standard chemotherapy, including in tumours with barely detectable HER2.","summary":"Open-label phase 3 trial of 866 patients with hormone-receptor-positive metastatic breast cancer that was HER2-low (IHC 1+ or 2+/ISH-negative) or HER2-ultralow (IHC 0 with faint membrane staining), who had progressed on endocrine therapy but had not received chemotherapy for metastatic disease. Patients were randomised to trastuzumab deruxtecan or physician's choice chemotherapy (capecitabine, paclitaxel or nab-paclitaxel). Primary endpoint was PFS in the HER2-low group.\n\nMedian PFS was 13.2 vs 8.1 months (HR 0.62) in HER2-low patients, with a similar effect in the ultralow subgroup. It moved T-DXd one line earlier and pushed the HER2 threshold down to almost any detectable staining.","asOf":"2026-09-08","links":[{"label":"PubMed search: DESTINY-Breast06","url":"https://pubmed.ncbi.nlm.nih.gov/?term=DESTINY-Breast06+trastuzumab+deruxtecan+HER2-low+chemotherapy-naive"},{"label":"ClinicalTrials.gov NCT04494425","url":"https://clinicaltrials.gov/study/NCT04494425"}],"tags":[],"related":[],"cancers":["breast-hr-positive"],"sections":[],"technologies":["adc","histopathology-ihc"],"targets":["her2"],"drugs":["trastuzumab-deruxtecan"],"companies":["daiichi-sankyo","astrazeneca"],"institutions":[],"pathways":[],"terms":["her2-low","ihc","pfs","ild","first-line"],"trials":["destiny-breast06"],"people":["hu-xichun","yonemori-kan","barrios-carlos","sohn-joohyuk","im-seock-ah","giuseppe-curigliano"],"bottlenecks":["b-biomarker-validation","b-drug-pricing","b-trial-design"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2024,"doi":"10.1056/NEJMoa2407086","pmid":"39282896","authors":"Bardia A, Hu X, Dent R, et al.","paperType":"rct","findings":["HER2-low: median PFS 13.2 vs 8.1 months, HR 0.62 (95% CI 0.51-0.74).","HER2-ultralow (about 150 patients): median PFS 13.2 vs 8.3 months, HR 0.78, consistent with the HER2-low result.","Objective response rate roughly 57% vs 31% in the HER2-low group.","Overall survival was immature at the primary analysis and not significantly different.","Interstitial lung disease in about 11% of T-DXd patients, with a small number of fatal cases."],"whatItMeans":"Patients with hormone-receptor-positive metastatic breast cancer that has stopped responding to endocrine therapy can be offered trastuzumab deruxtecan as their first chemotherapy-type treatment if the tumour shows any HER2 staining, rather than waiting until after conventional chemotherapy. Whether to use it before or after chemotherapy is now a choice, since overall survival was not shown to differ and the drug carries a risk of lung inflammation.","caveats":["No overall survival benefit was demonstrated at the primary analysis, so the case for using it earlier rests on PFS and response.","HER2-ultralow scoring is even less reproducible than HER2-low, and the ultralow subgroup was small and exploratory.","Comparator chemotherapy was single-agent and the trial was open-label.","Cost and pneumonitis risk are much higher than for capecitabine, which many patients tolerate well for a long time."],"changedPractice":true,"participants":866},{"id":"paper-destiny-gastric01-nejm-2020","kind":"paper","name":"DESTINY-Gastric01: trastuzumab deruxtecan in previously treated HER2-positive gastric cancer","aka":[],"tldr":"Trastuzumab deruxtecan shrank tumours in half of patients with HER2-positive gastric cancer that had progressed after trastuzumab, compared with 14 percent on chemotherapy, and lengthened survival by over four months.","summary":"Randomised phase 2 trial in Japan and South Korea of 187 patients with HER2-positive advanced gastric or junctional adenocarcinoma after at least two prior regimens including trastuzumab, randomised 2:1 to trastuzumab deruxtecan 6.4 mg/kg or physician's choice of irinotecan or paclitaxel.\n\nObjective response was 51 versus 14 percent and median overall survival 12.5 versus 8.4 months (hazard ratio 0.59); interstitial lung disease occurred in 10 percent, with myelosuppression as the other main toxicity.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2020","url":"https://doi.org/10.1056/NEJMoa2004413"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32469182/"}],"tags":[],"related":[],"cancers":["gastric-her2-positive"],"sections":[],"technologies":[],"targets":[],"drugs":["trastuzumab","trastuzumab-deruxtecan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["destiny-gastric01","destiny-gastric02"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2020,"doi":"10.1056/NEJMoa2004413","pmid":"32469182","authors":"Shitara K, Bang YJ, Iwasa S, et al.","paperType":"rct","findings":["Objective response 51 percent vs 14 percent.","Median overall survival 12.5 vs 8.4 months; hazard ratio 0.59."],"whatItMeans":"Trastuzumab deruxtecan is the standard second- or third-line treatment for HER2-positive gastric cancer, later confirmed against ramucirumab-paclitaxel in DESTINY-Gastric04.","caveats":["Asian population; the Western DESTINY-Gastric02 study showed a lower response rate.","Interstitial lung disease requires monitoring."],"changedPractice":true,"participants":187},{"id":"paper-destiny-lung01-nejm-2022","kind":"paper","name":"DESTINY-Lung01: trastuzumab deruxtecan in HER2-mutant non-small-cell lung cancer","aka":[],"tldr":"Trastuzumab deruxtecan shrank tumours in more than half of patients with previously treated HER2-mutant lung cancer, a driver with no approved therapy until this study, though lung inflammation was a serious side effect.","summary":"Phase 2 study of 91 patients with previously treated HER2-mutant metastatic non-small-cell lung cancer treated with trastuzumab deruxtecan 6.4 mg/kg.\n\nObjective response was 55 percent with median duration of response 9.3 months, median progression-free survival 8.2 months and median overall survival 17.8 months; drug-related interstitial lung disease occurred in 26 percent with two deaths.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2022","url":"https://doi.org/10.1056/NEJMoa2112431"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34534430/"}],"tags":[],"related":[],"cancers":["her2-mutant-nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":["trastuzumab","trastuzumab-deruxtecan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["destiny-lung01"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/NEJMoa2112431","pmid":"34534430","authors":"Li BT, Smit EF, Goto Y, et al.","paperType":"observational","findings":["Objective response 55 percent; median duration of response 9.3 months.","Median overall survival 17.8 months; interstitial lung disease 26 percent."],"whatItMeans":"HER2 mutations, present in about 3 percent of lung adenocarcinomas, became actionable; trastuzumab deruxtecan received the first approval for a HER2-mutant lung cancer, at the lower 5.4 mg/kg dose validated in DESTINY-Lung02.","caveats":["High rate of interstitial lung disease at 6.4 mg/kg.","Single-arm study."],"changedPractice":true,"participants":91},{"id":"paper-destiny-lung02-goto-jco-2023","kind":"paper","name":"DESTINY-Lung02: two doses of trastuzumab deruxtecan in HER2-mutant metastatic non-small-cell lung cancer","aka":[],"tldr":"Comparing two doses of trastuzumab deruxtecan in HER2-mutant lung cancer showed that the lower 5.4 mg/kg dose gave the same response rate of about half with far less lung toxicity, fixing the approved dose.","summary":"Randomised phase 2 trial of 152 patients with previously treated HER2-mutant metastatic non-small-cell lung cancer randomised 2:1 to trastuzumab deruxtecan 5.4 or 6.4 mg/kg.\n\nObjective response was 49.0 percent at 5.4 mg/kg and 56.0 percent at 6.4 mg/kg, with median durations of 16.8 and 5.9 months; adjudicated interstitial lung disease was 12.9 versus 28.0 percent.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2023","url":"https://doi.org/10.1200/JCO.23.01361"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37694347/"}],"tags":[],"related":[],"cancers":["her2-mutant-nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":["trastuzumab","trastuzumab-deruxtecan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["destiny-lung02"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2023,"doi":"10.1200/JCO.23.01361","pmid":"37694347","authors":"Goto K, Goto Y, Kubo T, et al.","paperType":"rct","findings":["Objective response 49.0 percent (5.4 mg/kg) vs 56.0 percent (6.4 mg/kg).","Interstitial lung disease 12.9 percent vs 28.0 percent."],"whatItMeans":"Trastuzumab deruxtecan 5.4 mg/kg is the approved regimen for HER2-mutant lung cancer after platinum chemotherapy, and the trial is a rare example of dose optimisation improving safety without losing efficacy.","caveats":["Not powered to compare efficacy between doses formally."],"changedPractice":true,"participants":152},{"id":"paper-destiny-pantumor02-jco-2024","kind":"paper","name":"DESTINY-PanTumor02: trastuzumab deruxtecan in HER2-expressing solid tumours","aka":[],"tldr":"Across seven tumour types including endometrial, cervical and ovarian cancers, trastuzumab deruxtecan shrank tumours in about 37 percent of patients overall and 61 percent of those with the highest HER2 expression, leading to a tumour-agnostic approval.","summary":"Phase 2 study of 267 patients with previously treated HER2-expressing (immunohistochemistry 3+ or 2+) advanced solid tumours in seven cohorts (endometrial, cervical, ovarian, bladder, biliary, pancreatic and other) treated with trastuzumab deruxtecan 5.4 mg/kg.\n\nObjective response was 37.1 percent overall and 61.3 percent in immunohistochemistry 3+ tumours, with median duration of response 11.3 and 22.1 months respectively; endometrial (57.5 percent) and cervical (50.0 percent) cohorts responded best. Interstitial lung disease occurred in 10.5 percent.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2024","url":"https://doi.org/10.1200/JCO.23.02005"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37870536/"}],"tags":[],"related":[],"cancers":["endometrial-p53-abnormal","recurrent-metastatic-cervical-cancer","uterine-carcinosarcoma"],"sections":[],"technologies":[],"targets":[],"drugs":["trastuzumab","trastuzumab-deruxtecan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["destiny-pantumor02"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2024,"doi":"10.1200/JCO.23.02005","pmid":"37870536","authors":"Meric-Bernstam F, Makker V, Oaknin A, et al.","paperType":"observational","findings":["Objective response 37.1 percent overall; 61.3 percent in immunohistochemistry 3+.","Endometrial cohort response 57.5 percent; cervical 50.0 percent."],"whatItMeans":"HER2 immunohistochemistry is now worth doing in advanced gynaecological and other cancers, since trastuzumab deruxtecan is approved for HER2 3+ solid tumours after prior therapy.","caveats":["Single-arm across heterogeneous tumours; responses in 2+ tumours were modest (27 percent).","Interstitial lung disease including fatal cases."],"changedPractice":true,"participants":267},{"id":"paper-hiraoka-her2-status-biliary-hum-pathol-2020","kind":"paper","name":"Details of human epidermal growth factor receptor 2 status in 454 cases of biliary tract cancer","aka":[],"tldr":"Testing 454 resected biliary cancers with the stomach cancer HER2 rules, nearly one in three gallbladder cancers was HER2-positive, far more than bile duct cancers inside the liver, but staining was patchy in most positive tumours.","summary":"HER2 protein expression by immunohistochemistry, HER2 gene amplification by fluorescence in situ hybridisation and both simultaneously by gene-protein assay were examined in 454 surgically resected biliary tract cancers: 110 intrahepatic cholangiocarcinomas, 67 perihilar and 119 distal extrahepatic cholangiocarcinomas, 80 gallbladder carcinomas and 79 ampullary carcinomas. HER2 status was assessed according to the guidelines for HER2 testing in gastro-oesophageal adenocarcinoma.\n\nHER2-positive status was detected in 14.5% of biliary tract cancers: 3.7% of intrahepatic, 3.0% of perihilar and 18.5% of distal cholangiocarcinomas, 31.3% of gallbladder carcinomas and 16.4% of ampullary carcinomas. HER2 positivity tended to correlate with low histological grade. HER2 heterogeneity was common and highly frequent (83%) in positive cases, and reduced HER2 expression in the deeper invasive areas with simultaneous dedifferentiation was frequently observed.","asOf":"2026-09-24","links":[{"label":"Hiraoka et al., Hum Pathol 2020: HER2 status in 454 biliary tract cancers","url":"https://doi.org/10.1016/j.humpath.2020.08.006"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32891647/"}],"tags":[],"related":[],"cancers":["gallbladder","cholangiocarcinoma","ampullary"],"sections":[],"technologies":[],"targets":["her2"],"drugs":[],"companies":[],"institutions":["ncc-japan"],"pathways":[],"terms":["ihc","fish","her2-testing-in-biliary-cancer"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Human Pathology","year":2020,"doi":"10.1016/j.humpath.2020.08.006","pmid":"32891647","authors":"Hiraoka N, Nitta H, Ohba A, et al.","paperType":"observational","findings":["HER2-positive in 31.3% of 80 gallbladder carcinomas versus 3.7% intrahepatic, 3.0% perihilar, 18.5% distal and 16.4% ampullary.","Heterogeneous HER2 expression in 83% of positive cases, with loss in deeper dedifferentiated areas.","Gastro-oesophageal scoring guideline applied to whole resection specimens."],"whatItMeans":"The highest gallbladder HER2 rate in the literature comes from whole resected tumours scored generously; biopsy-based trial screening finds fewer. Heterogeneity is the practical warning for pathologists and for why HER2-directed drugs do not work in every positive tumour.","caveats":["Resected Japanese patients; advanced disease tested on biopsies may score lower.","Gastric scoring is more permissive than breast scoring."],"changedPractice":false,"participants":454},{"id":"paper-detect-a-science-2020","kind":"paper","name":"DETECT-A: a blood test plus PET-CT found treatable cancers in 10,000 women with no symptoms","aka":[],"tldr":"The first prospective interventional study of a multi-analyte blood test (CancerSEEK) in asymptomatic people: 26 cancers were first detected by the blood test, most of them localised, and the test roughly doubled the number of cancers caught by standard screening.","summary":"DETECT-A enrolled 10,006 women aged 65-75 with no history of cancer in the Geisinger health system. A blood test measuring mutations in cell-free DNA and protein markers (CancerSEEK) was performed; a confirmed positive led to whole-body PET-CT, and imaging-positive participants were referred for diagnosis.\n\nTwenty-six cancers were detected by the blood test, of which 17 were localised or regional and 12 were treated with surgery with intent to cure. Standard-of-care screening detected a further 24 cancers, so combining the blood test with existing screening roughly doubled detection (from about a quarter to about half of incident cancers). Fewer than 1% of participants had an unnecessary invasive procedure.\n\nIt proved that a blood-first screening pathway can be safely operationalised and that many blood-detected cancers are at a curable stage.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1126/science.abb9601"},{"label":"ClinicalTrials.gov NCT03934866","url":"https://clinicaltrials.gov/study/NCT03934866"}],"tags":[],"related":["paper-pathfinder-lancet-2023"],"cancers":["pancreatic"],"sections":["early-detection"],"technologies":["mced","liquid-biopsy","pet-ct"],"targets":[],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":[],"terms":["ppv","ctdna","stage-shift","cfdna"],"trials":[],"people":["bert-vogelstein","kenneth-kinzler","nickolas-papadopoulos"],"bottlenecks":["b-early-detection","b-overdiagnosis"],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2020,"doi":"10.1126/science.abb9601","pmid":"32345712","authors":"Lennon AM, Buchanan AH, Kinde I, et al.","paperType":"observational","findings":["Blood test alone detected 26 of 96 incident cancers (about 27% sensitivity); with standard screening the combined sensitivity was about 52%","17 of 26 blood-detected cancers were localised or regional; 12 patients had surgery with curative intent","The blood test found cancers in organs with no standard screening (ovary, kidney, appendix, uterus, lymphoma)","Participants did not reduce their uptake of standard screening after joining the study"],"whatItMeans":"A blood test can find early, treatable cancers in people who feel well, including cancers for which no screening exists. It is not a replacement for mammography or colonoscopy but a possible addition. Larger randomised trials are needed to show benefit outweighs harm.","caveats":["Single-arm, single health system, women only; no mortality endpoint","Sensitivity of about a quarter for all incident cancers means most cancers were missed","PET-CT confirmation for all positives is costly and exposes participants to radiation","CancerSEEK's commercial successor tests differ in design, so performance does not transfer directly"],"changedPractice":false,"participants":10006},{"id":"paper-yu-ctdna-early-recurrence-biliary-tract-cancer-jco-po-2025","kind":"paper","name":"Detecting Early Recurrence With Circulating Tumor DNA in Stage I-III Biliary Tract Cancer After Curative Resection","aka":[],"tldr":"In 56 people after surgery for bile duct or gallbladder cancer, finding tumour DNA in the blood in the weeks after the operation meant the cancer came back within about seven months on average, while those without it had not relapsed by the end of follow-up.","summary":"Retrospective multicentre cohort of 56 patients with curatively resected stage I to III biliary tract cancer followed with serial tumour-informed ctDNA testing, median follow-up 12.8 months. ctDNA detection in the molecular residual disease window was associated with a median relapse-free survival of 6.6 months against not reached (hazard ratio 26, 95 percent CI 2.6 to 265); detection during surveillance carried a hazard ratio of 20 (2.6 to 153). Conventional markers were not prognostic (p=0.844). The study also assessed ctDNA sensitivity for confirmed recurrence and the lead time from first detection to confirmed recurrence.","asOf":"2026-09-24","links":[{"label":"JCO Precis Oncol 2025","url":"https://doi.org/10.1200/po-24-00443"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39772829/"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder","cholangiocarcinoma","biliary-tract-cancer"],"sections":[],"technologies":["liquid-biopsy","mrd-testing"],"targets":[],"drugs":["signatera"],"companies":["natera"],"institutions":[],"pathways":[],"terms":["ctdna","mrd"],"trials":[],"people":[],"bottlenecks":["b-dormancy-mrd"],"keyPapers":[],"journals":["jco-precision-oncology"],"dependsOn":[],"notes":[],"journal":"JCO Precision Oncology","year":2025,"doi":"10.1200/po-24-00443","pmid":"39772829","authors":"Yu J, He AR, Ouf M, et al.","paperType":"real-world","findings":["Residual disease window ctDNA positivity: median relapse-free survival 6.6 months vs not reached; hazard ratio 26 (95 percent CI 2.6 to 265).","Surveillance ctDNA positivity: hazard ratio 20 (2.6 to 153); conventional markers not prognostic (p=0.844)."],"whatItMeans":"Very wide confidence intervals from a small cohort, but the direction matches the larger 2026 analysis. Gallbladder cancer recurs early and distantly after re-resection, which is exactly the setting where a residual disease test could pick who gets more than capecitabine.","caveats":["56 patients, short follow-up, retrospective.","Hazard ratios have very wide confidence intervals."],"changedPractice":false,"participants":56},{"id":"paper-berchuck-cfdna-methylation-nepc-detection-ccr-2022","kind":"paper","name":"Detecting neuroendocrine prostate cancer through tissue-informed cell-free DNA methylation analysis","aka":[],"tldr":"A blood test that reads chemical marks on DNA rather than its letters separated the aggressive neuroendocrine form of prostate cancer from the ordinary form almost perfectly.","summary":"Neuroendocrine prostate cancer is a resistance phenotype that emerges in men with metastatic castration-resistant prostate adenocarcinoma and is difficult to detect in practice. Methylated DNA immunoprecipitation and high-throughput sequencing was performed on a training set of tumours, differentially methylated regions between neuroendocrine prostate cancer and castration-resistant adenocarcinoma were identified, and a model was built to predict the presence of neuroendocrine disease, termed a risk score. The same assay was then applied to cell-free DNA from two independent cohorts. The test cohort comprised 48 men, 9 with neuroendocrine disease and 39 with castration-resistant adenocarcinoma; risk scores were significantly higher in the neuroendocrine group and discriminated with an area under the receiver operating curve of 0.96, with the optimal cut-off giving 100% sensitivity and 90% specificity. The validation cohort included 53 men, 12 with neuroendocrine disease and 41 with adenocarcinoma; discrimination was perfect, area under the curve 1.0, and the predefined cut-off gave 100% sensitivity and 95% specificity.","asOf":"2026-09-25","links":[{"label":"Berchuck et al., Clin Cancer Res 2022: tissue-informed cell-free DNA methylation to detect neuroendocrine prostate cancer (101 plasma samples in two cohorts)","url":"https://doi.org/10.1158/1078-0432.CCR-21-3762"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34907080/"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc","prostate-nepc"],"sections":[],"technologies":["liquid-biopsy","methylation-profiling"],"targets":["androgen-receptor"],"drugs":[],"companies":[],"institutions":[],"pathways":["lineage-plasticity-neuroendocrine","epigenetic-reprogramming"],"terms":["ctdna","cfdna","histologic-transformation","liquid-biopsy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2022,"doi":"10.1158/1078-0432.CCR-21-3762","pmid":"34907080","authors":"Berchuck JE, Baca SC, McClure HM, et al.","paperType":"translational","findings":["Risk score from cell-free DNA methylation discriminated neuroendocrine from castration-resistant adenocarcinoma with an area under the curve of 0.96 in the test cohort.","One hundred per cent sensitivity and 90% specificity at the optimal cut-off.","Perfect discrimination in an independent 53-man validation cohort, with 100% sensitivity and 95% specificity at the predefined cut-off."],"whatItMeans":"It is the right shape of answer for a transition that is epigenetic rather than genetic, and it could in principle spare the biopsy that is currently the only way to make this diagnosis.","caveats":["Twenty-one men with neuroendocrine disease in total across both cohorts, so a perfect area under the curve should be read as promising rather than settled.","Methylated DNA immunoprecipitation sequencing is a research assay, not one that can be ordered.","The comparison is against a histological reference standard that is itself imperfect."],"changedPractice":false,"participants":101},{"id":"paper-poiesz-htlv-retrovirus-cutaneous-t-cell-lymphoma-pnas-1980","kind":"paper","name":"Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma","aka":["Poiesz 1980","Discovery of HTLV-1","The first human retrovirus"],"tldr":"The first retrovirus found in people was isolated from the blood cells of a patient with a skin lymphoma, and turned out to cause a leukaemia endemic in southern Japan and the Caribbean.","summary":"Bernard Poiesz, Robert Gallo and colleagues found retrovirus particles with type C morphology in two T-cell lymphoblastoid cell lines, HUT 102 and CTCL-3, and in fresh peripheral blood lymphocytes from a patient with mycosis fungoides. The cell lines produced the virus continuously, collectively called HTLV.\n\nThe characterisation was careful because the claim was large. Mature particles measured 100 to 110 nanometres, banded at a density of 1.16 grams per millilitre on a sucrose gradient, and contained 70S RNA and a DNA polymerase activity typical of a viral reverse transcriptase. That reverse transcriptase preferred magnesium to manganese, unlike the cellular DNA polymerases purified from human lymphocytes, and antibodies to cellular DNA polymerase gamma and to reverse transcriptases from several animal retroviruses did not react with it. Six major proteins of roughly 10,000, 13,000, 19,000, 24,000, 42,000 and 52,000 daltons were found in disrupted particles, a count consistent with a retrovirus but with sizes distinct from the known primate retroviruses.\n\nThe following year Hinuma's group in Japan independently detected an antigen in a cell line from a patient with adult T-cell leukaemia and antibodies to it in all 44 patients with that disease. The two lines of work converged on one virus, now called human T-lymphotropic virus type 1.","asOf":"2026-10-01","links":[{"label":"Proceedings of the National Academy of Sciences 1980","url":"https://doi.org/10.1073/pnas.77.12.7415"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/6261256/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/6261256"}],"tags":["lymphoma-evidence"],"related":["paper-hinuma-adult-t-cell-leukaemia-antigen-pnas-1981","paper-jcog9801-vcap-amp-vecp-adult-t-cell-leukaemia-jco-2007","lymphoma-roadmap"],"cancers":["peripheral-t-cell-lymphoma","cutaneous-t-cell-lymphoma","non-hodgkin-lymphoma"],"sections":["prevention","diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["jcog9801"],"people":[],"bottlenecks":["b-prevention-adoption","b-global-access"],"keyPapers":[],"journals":["pnas"],"dependsOn":[],"notes":[],"journal":"Proceedings of the National Academy of Sciences","year":1980,"doi":"10.1073/pnas.77.12.7415","pmid":"6261256","authors":"Poiesz BJ, Ruscetti FW, Gazdar AF, et al.","paperType":"basic","findings":["Type C retrovirus particles were found in two T-cell lines, HUT 102 and CTCL-3, and in fresh peripheral blood lymphocytes from a patient with cutaneous T-cell lymphoma.","Mature particles were 100 to 110 nanometres in diameter and banded at a density of 1.16 grams per millilitre on a sucrose gradient.","Particles contained 70S RNA and a reverse transcriptase activity that preferred magnesium to manganese, distinguishing it from cellular DNA polymerases.","Antibodies to cellular DNA polymerase gamma and to reverse transcriptases of several animal retroviruses did not detectably interact with the viral enzyme.","Six major particle-associated proteins of approximately 10,000, 13,000, 19,000, 24,000, 42,000 and 52,000 daltons were identified."],"whatItMeans":"The first human retrovirus, and the start of the line of work that identified HIV three years later. For lymphoma it means that adult T-cell leukaemia/lymphoma has a known, transmissible, preventable cause, and that screening blood donors and advising on breastfeeding in endemic areas are cancer prevention measures.","caveats":["A single patient and two cell lines; the epidemiological case that the virus causes adult T-cell leukaemia/lymphoma was made by Hinuma, Takatsuki and others over the following years.","The index patient was described as having mycosis fungoides, a diagnosis that was later questioned; the virus is not a cause of mycosis fungoides.","Only a small minority of people infected with human T-lymphotropic virus type 1 ever develop the leukaemia, usually decades after infection."],"changedPractice":true},{"id":"paper-cohen-cancerseek-multi-analyte-blood-test-science-2018","kind":"paper","name":"Detection and localization of surgically resectable cancers with a multi-analyte blood test","aka":[],"tldr":"CancerSEEK, a blood test reading eight proteins and mutations in free DNA, found a median 70% of 1,005 non-spread cancers of eight types, including pancreatic cancer, and pointed to the organ involved in most cases.","summary":"A blood test assessing circulating protein levels and mutations in cell-free DNA was applied to 1,005 patients with non-metastatic, clinically detected cancers of the ovary, liver, stomach, pancreas, oesophagus, colorectum, lung or breast. CancerSEEK tests were positive in a median of 70% of the eight cancer types, with sensitivities of 69 to 98% for the five types with no screening test for average-risk individuals (ovary, liver, stomach, pancreas, oesophagus). Specificity exceeded 99% with 7 of 812 healthy controls positive, and the test localised the cancer to a small number of anatomical sites in a median 83% of patients.","asOf":"2026-09-24","links":[{"label":"Cohen et al., Science 2018: CancerSEEK in 1,005 patients with eight cancer types","url":"https://doi.org/10.1126/science.aar3247"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29348365/"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":["mced","liquid-biopsy","proteomics"],"targets":[],"drugs":["caris-mi-cancer-seek"],"companies":[],"institutions":["johns-hopkins"],"pathways":[],"terms":["ctdna","cfdna"],"trials":[],"people":["bert-vogelstein","nickolas-papadopoulos","kenneth-kinzler"],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2018,"doi":"10.1126/science.aar3247","pmid":"29348365","authors":"Cohen JD, Li L, Wang Y, et al.","paperType":"observational","findings":["Median 70% sensitivity across eight cancer types at over 99% specificity.","Pancreas among the five types at 69 to 98% sensitivity.","Tissue of origin localised in a median 83% of positives."],"whatItMeans":"The proof of principle for multi-cancer blood tests that include pancreas; the sensitivity figures come from known cancers, not from screening.","caveats":["Case-control design with clinically detected cancers.","Stage I sensitivity is much lower than the headline figure."],"changedPractice":false,"participants":1817},{"id":"paper-dudley-cancer-discov","kind":"paper","name":"Detection and Surveillance of Bladder Cancer Using Urine Tumor DNA","aka":[],"tldr":"Paper cited by one idea page, indexed on Europe PMC as PubMed record 30578357 and published in Cancer Discovery; the citing page links this DOI, which is how the record was matched.","summary":"Current regimens for the detection and surveillance of bladder cancer are invasive and have suboptimal sensitivity. Here, we present a novel high-throughput sequencing (HTS) method for detection of urine tumor DNA (utDNA) called utDNA CAPP-Seq (uCAPP-Seq) and apply it to 67 healthy adults and 118 patients with early-stage bladder cancer who had urine collected either prior to treatment or during surveillance. Using this targeted sequencing approach, we detected a median of 6 mutations per patient with bladder cancer and observed surprisingly frequent mutations of the PLEKHS1 promoter (46%), suggesting these mutations represent a useful biomarker for detection of bladder cancer. We detected utDNA pretreatment in 93% of cases using a tumor mutation-informed approach and in 84% when blinded to tumor mutation status, with 96% to 100% specificity. In the surveillance setting, we detected utDNA in 91% of patients who ultimately recurred, with utDNA detection preceding clinical progression in 92% of cases. uCAPP-Seq outperformed a commonly used ancillary test (UroVysion, P = 0.02) and cytology and cystoscopy combined ( P ≤ 0.006), detecting 100% of bladder cancer cases detected by cytology and 82% that cytology missed. Our results indicate that uCAPP-Seq is a promising approach for early detection and surveillance of bladder cancer. SIGNIFICANCE: This study shows that utDNA can be detected using HTS with high sensitivity and specificity in patients with early-stage bladder cancer and during post-treatment surveillance, significantly outperforming standard diagnostic modalities and facilitating noninvasive detection, genotyping, and monitoring. This article is highlighted in the In This Issue feature, p. 453.\n\nIndexed on Europe PMC as PubMed record 30578357 (DOI 10.1158/2159-8290.cd-18-0825). Matched by DOI alone: one idea page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer Discov 2019","url":"https://doi.org/10.1158/2159-8290.cd-18-0825"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30578357/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30578357"}],"tags":["europepmc-ingest"],"related":["idea-urine-ctdna-surveillance"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-discovery"],"dependsOn":[],"notes":[],"journal":"Cancer Discovery","year":2019,"doi":"10.1158/2159-8290.cd-18-0825","pmid":"30578357","authors":"Dudley JC, Schroers-Martin J, Lazzareschi DV, et al.","paperType":"observational","findings":[],"whatItMeans":"One idea page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-johnson-mpmri-individual-foci-eur-urol-2019","kind":"paper","name":"Detection of individual prostate cancer foci via multiparametric magnetic resonance imaging","aka":["Johnson 2019","per-lesion MRI sensitivity prostate","mpMRI whole-mount correlation"],"tldr":"Prostate MRI is good at answering whether a man has a serious cancer somewhere. This study matched scans against the whole removed prostate and found it is much worse at finding every tumour: it missed at least one significant tumour in a third of men.","summary":"Dave Johnson, Steven Raman and colleagues at the University of California, Los Angeles co-registered multiparametric magnetic resonance imaging with whole-mount pathology from 588 consecutive men who had radical prostatectomy after a 3 Tesla scan, giving 1,213 pathologically confirmed tumour foci, and measured per-lesion rather than per-patient sensitivity.\n\nThe distinction is not academic. A pathway that only has to decide whether to biopsy needs per-patient sensitivity, and PROMIS showed that is 93 percent for clinically significant disease. A pathway that decides where to treat, which is what focal therapy and magnetic resonance imaging-only surveillance do, needs per-lesion sensitivity, and this study puts that at 45 percent for all foci and 65 percent for clinically significant ones. The gap between the two numbers is where focal therapy planning and imaging-only follow-up carry unmeasured risk.","asOf":"2026-09-25","links":[{"label":"Eur Urol 2019","url":"https://doi.org/10.1016/j.eururo.2018.11.031"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30509763/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30509763"}],"tags":["prostate-evidence"],"related":["paper-ahmed-promis-multiparametric-mri-lancet-2017","paper-precision-mri-targeted-biopsy-nejm-2018","prostate-roadmap"],"cancers":["prostate","prostate-low-risk","prostate-intermediate-risk","prostate-high-risk"],"sections":["imaging","diagnostics","surgery"],"technologies":["mri"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["gleason-grade-group","prostatectomy","psa","whole-mount-pathology","pi-rads","template-mapping-biopsy"],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation","b-early-detection","b-surgery-radiation-innovation"],"keyPapers":[],"journals":["european-urology"],"dependsOn":[],"notes":[],"journal":"European Urology","year":2019,"doi":"10.1016/j.eururo.2018.11.031","pmid":"30509763","authors":"Johnson DC, Raman SS, Mirak SA, et al.","paperType":"observational","findings":["Multiparametric magnetic resonance imaging detected 45 percent of all 1,213 tumour foci (95 percent confidence interval 42 to 47 percent).","It detected 65 percent of clinically significant lesions (61 to 69 percent) and nearly 80 percent of high-grade tumours.","At least one clinically significant focus was missed in 34 percent of patients overall, and in 45 percent of men with multifocal lesions.","74 percent of missed solitary tumours and 31 percent of missed multifocal tumours were clinically significant.","61.1 percent of missed lesions were 1 cm or smaller, 28.3 percent were between 1 and 2 cm and 10.4 percent were larger than 2 cm; smaller, low-grade, multifocal, non-index tumours with lower prostate-specific antigen density were more likely to be missed."],"whatItMeans":"The limit of what a prostate scan can be asked to do. It is a good triage test for whether to biopsy and a poor map of where every tumour is, which matters for anyone being offered treatment to part of the gland or follow-up by imaging alone.","caveats":["A prostatectomy cohort, so it is enriched for intermediate and high-risk disease (75 percent and 12 percent respectively) and cannot report specificity.","Co-registration of imaging with whole-mount pathology is imperfect, which biases detection downwards to an unknown degree.","The clinical significance of the undetected small foci is uncertain: some of what the scan misses is what the field would rather not find."],"changedPractice":false,"participants":588},{"id":"paper-jonna-nrg1-fusions-solid-tumours-ccr-2019","kind":"paper","name":"Detection of NRG1 gene fusions in solid tumors","aka":[],"tldr":"Running an RNA-based fusion test across nearly 22,000 tumours of every kind found this rare but treatable fusion in about one in five hundred, most often in lung cancer, and with a different partner gene almost every time.","summary":"Tumour specimens submitted for molecular profiling that underwent fusion testing by anchored multiplex polymerase chain reaction for targeted RNA sequencing were retrospectively reviewed. Of 21,858 specimens profiled between September 2015 and December 2018, 41 cases, 0.2%, harboured an NRG1 fusion, with multiple distinct fusion partners. Fusions occurred across tumour types; the greatest number was in non-small-cell lung cancer, 25 cases, although this represented only 0.3% of the lung cancers tested. Gallbladder, renal cell, bladder, ovarian, pancreatic, breast, neuroendocrine, sarcoma and colorectal cases were also identified.","asOf":"2026-09-25","links":[{"label":"Jonna et al., Clin Cancer Res 2019: NRG1 fusions in 41 of 21,858 solid tumours profiled by RNA sequencing","url":"https://doi.org/10.1158/1078-0432.CCR-19-0160"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30988082/"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":["rna-seq","cgp"],"targets":["nrg1","her2"],"drugs":[],"companies":[],"institutions":[],"pathways":["rtk-activation"],"terms":["gene-fusion","tumour-agnostic"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2019,"doi":"10.1158/1078-0432.CCR-19-0160","pmid":"30988082","authors":"Jonna S, Feldman RA, Swensen J, et al.","paperType":"observational","findings":["NRG1 fusions in 41 of 21,858 tumours, 0.2%.","Lung cancer had the highest count, 25 cases, and a rate of 0.3%.","Fusion partners were highly heterogeneous.","Fusions were found across many solid tumour types."],"whatItMeans":"It put a number on how rare NRG1 fusions are and showed that heterogeneous partners make RNA-based testing the only reliable way to find them, which is the practical argument for adding a fusion panel to a driver-negative lung cancer work-up.","caveats":["A commercial testing stream, so the population is selected by who was sent for profiling.","No treatment outcomes.","RNA-based detection requires adequate RNA, which small biopsies often lack."],"changedPractice":false,"participants":21858},{"id":"paper-nct05955391-j-thorac-oncol-2026","kind":"paper","name":"Deulorlatinib (TGRX-326) in ALK Gene Fusion Positive NSCLC After Failure of Second-Generation Inhibitors: A Single-Arm, Multicenter, Phase 2 Trial","aka":[],"tldr":"Published report from the trial registered as NCT05955391, in Journal of Thoracic Oncology (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Introduction: Deulorlatinib (TGRX-326), a potent third-generation anaplastic lymphoma kinase (ALK) inhibitor, has reported promising activity and a favorable safety profile in ALK-positive NSCLC in a phase 1 trial. Here, we report the primary results of the pivotal phase 2 trial (NCT05955391) evaluating deulorlatinib in patients with ALK-positive NSCLC in whom second-generation ALK inhibitors had failed.\n\nMethods: This single-arm, phase 2 trial was conducted at 36 centers in China. Eligible patients received deulorlatinib 60 mg once daily. The primary end point was objective response rate (ORR) assessed by an independent review committee (IRC). Key secondary end points included disease control rate, progression-free survival (PFS), duration of response, overall survival, intracranial efficacy, and safety. Exploratory biomarker analyses were performed using cell-free DNA.\n\nResults: The efficacy and safety analysis sets comprised 158 and 163 patients, respectively. The primary end point was met with an IRC-assessed ORR of 43.7% (95% confidence interval [CI], 35.8-51.8). The IRC-assessed median PFS was 11.1 months (95% CI, 8.3-13.7). Among patients with measurable central nervous system (CNS) metastases (n = 43), the intracranial ORR was 55.8% (95% CI, 39.9-70.9). In patients harboring the G1202R mutation (n = 8), robust activity was observed (ORR: 62.5%; disease control rate: 100%; median PFS: 11.0 months). The investigator-assessed results were consistent with the IRC-assessed findings. Treatment-related adverse events occurred in 96.3% of patients (47.2% grade ≥3). Nevertheless, dose modifications were infrequent (interruption, 13.5%; reduction, 11.0%; permanent discontinuation, 0.6%). The incidence of CNS-related treatment-related adverse events was 12.9%, with no patients interrupting or discontinuing treatment owing to CNS toxicity.\n\nConclusions: Deulorlatinib indicated encouraging antitumor activity in patients with advanced ALK-positive NSCLC after failure of second-generation ALK inhibitors, including those with the G1202R mutation. Given its favorable safety profile, deulorlatinib represents a promising new option for this population.\n\nIndexed on Europe PMC as PubMed record 42031067 (DOI 10.1016/j.jtho.2026.103737). Its abstract cites the registry id NCT05955391, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Thorac Oncol 2026","url":"https://doi.org/10.1016/j.jtho.2026.103737"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42031067/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42031067"},{"label":"ClinicalTrials.gov NCT05955391","url":"https://clinicaltrials.gov/study/NCT05955391"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05955391"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-thoracic-oncology"],"dependsOn":[],"notes":[],"journal":"Journal of Thoracic Oncology","year":2026,"doi":"10.1016/j.jtho.2026.103737","pmid":"42031067","authors":"Huang J, Chen G, Wang Z, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05955391 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-nct03851640-signal-transduct-target-ther-2026","kind":"paper","name":"Deutenzalutamide, a novel androgen receptor inhibitor, after progression on docetaxel and abiraterone in metastatic castration-resistant prostate cancer: results from the randomized phase III HC-1119-04 trial","aka":[],"tldr":"Published report from the trial registered as NCT03851640, in Signal transduction and targeted therapy (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Metastatic castration-resistant prostate cancer (mCRPC) after treatment with docetaxel and androgen receptor signaling inhibitors (ARSIs) has limited treatment options. Although enzalutamide has shown activity after abiraterone and docetaxel, robust evidence from randomized phase III trials is lacking. Deutenzalutamide, a novel derivative with slower metabolism and improved pharmacokinetics, may offer enhanced safety and efficacy. This phase III, double-blind trial conducted at 36 centers in China enrolled patients whose disease progressed on or who were intolerant to abiraterone and docetaxel, or who were ineligible for docetaxel. Patients were randomized (2:1) to receive deutenzalutamide 80 mg once daily or placebo until progression or unacceptable toxicity; the primary endpoint was radiographic progression-free survival (rPFS). Of 417 patients (276 deutenzalutamide; 141 placebo), all had previously received abiraterone, and 68% had also received docetaxel. Deutenzalutamide significantly improved rPFS (HR, 0.58; P = 0.0001), reducing the risk of progression by 42%. Although the initial OS analysis was not significant (HR, 0.95), sensitivity analyses adjusting for subsequent therapies showed significant OS benefits (HR, 0.65-0.73). Treatment-related grade 3 or higher adverse events occurred in 22.3% of patients treated with deutenzalutamide, compared with 15.0% with placebo. The most common treatment-related adverse event was anemia, reported at any grade in 21.2% versus 17.9%, with grade 3/4 anemia in 6.6% versus 2.9%, respectively. Notably, no seizures or falls were reported. In summary, deutenzalutamide significantly prolonged rPFS and, after adjustment, showed a potential OS benefit with a favorable safety profile, supporting its promise as a new treatment option for mCRPC. Clinical trial registration: NCT03851640.\n\nIndexed on Europe PMC as PubMed record 41968137 (DOI 10.1038/s41392-026-02618-3). Its abstract cites the registry id NCT03851640, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Signal Transduct Target Ther 2026","url":"https://doi.org/10.1038/s41392-026-02618-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41968137/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41968137"},{"label":"ClinicalTrials.gov NCT03851640","url":"https://clinicaltrials.gov/study/NCT03851640"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct03851640"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Signal transduction and targeted therapy","year":2026,"doi":"10.1038/s41392-026-02618-3","pmid":"41968137","authors":"Wu J, Li X, Gu C, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03851640 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-nxc-201-hbi0101-asherie-haematologica-2023","kind":"paper","name":"Development and manufacture of novel locally produced anti-BCMA CAR T cells for the treatment of relapsed/refractory multiple myeloma: results from a phase I clinical trial (HBI0101)","aka":[],"tldr":"A hospital in Jerusalem built and made its own CAR-T cells against the myeloma protein BCMA; in the first 20 heavily treated patients, 75 percent responded and half went into complete remission, with only mild immune reactions.","summary":"Report of the Hadassah phase 1 dose-escalation study (NCT04720313) of HBI0101, a second-generation optimised anti-BCMA CAR-T therapy developed in an academic setting and given fresh without cryopreservation. Twenty heavily pretreated patients with relapsed or refractory multiple myeloma were treated in three cohorts: 150 million (n = 6), 450 million (n = 7) and 800 million (n = 7) CAR-T cells.\n\nGrade 1 or 2 cytokine release syndrome occurred in 18 patients (90 percent); no grade 3 or 4 cytokine release syndrome, no neurotoxicity of any grade and no dose-limiting toxicity were observed. The overall response rate was 75 percent, (stringent) complete response 50 percent and very good partial response 25 percent; responses were dose dependent, with 85 percent overall response, 71 percent complete response and 57 percent minimal residual disease negativity in the high-dose cohort. Median overall survival was 308 days (range 25 to more than 466), with estimated survival of 55 percent at the data cutoff; median progression-free survival was 160 days, with six patients progression free at the cutoff. The authors argue that the results support decentralised CAR-T production in academic centres to meet local demand.","asOf":"2026-09-24","links":[{"label":"Haematologica 2023","url":"https://doi.org/10.3324/haematol.2022.281628"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36200421/"},{"label":"ClinicalTrials.gov NCT04720313","url":"https://clinicaltrials.gov/study/NCT04720313"}],"tags":[],"related":[],"cancers":["multiple-myeloma"],"sections":[],"technologies":["car-t"],"targets":["bcma"],"drugs":["nxc-201-car-t"],"companies":[],"institutions":["hadassah"],"pathways":[],"terms":[],"trials":["nxc-201-mm"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["haematologica"],"dependsOn":[],"notes":[],"journal":"Haematologica","year":2023,"doi":"10.3324/haematol.2022.281628","pmid":"36200421","authors":"Asherie N, Kfir-Erenfeld S, Avni B, et al.","paperType":"observational","findings":["Overall response rate 75 percent, (stringent) complete response 50 percent and very good partial response 25 percent in 20 patients.","Grade 1 to 2 cytokine release syndrome in 90 percent; no grade 3 to 4 cytokine release syndrome, neurotoxicity or dose-limiting toxicity.","Dose-dependent responses: 85 percent response, 71 percent complete response and 57 percent MRD negativity at 800 million cells; median progression-free survival 160 days."],"whatItMeans":"The clinical result is in line with commercial BCMA CAR-T products, but the point of the paper is the manufacturing: an academic hospital produced its own CAR-T cells, infused them fresh and treated patients who would otherwise wait for a commercial slot. It is the evidence base for what Immix Biopharma now develops as NXC-201.","caveats":["Phase 1 in 20 patients at a single centre; follow-up was short and the median progression-free survival of about five months is modest.","No comparison group; the historical comparators are the pivotal trials of idecabtagene vicleucel and ciltacabtagene autoleucel.","The registry lists a much larger continuing enrolment, so later cohorts are not described here."],"changedPractice":false,"participants":20},{"id":"paper-khorana-blood","kind":"paper","name":"Development and validation of a predictive model for chemotherapy-associated thrombosis","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 18216292 and published in Blood; the citing page links this DOI, which is how the record was matched.","summary":"Risk of venous thromboembolism (VTE) is elevated in cancer, but individual risk factors cannot identify a sufficiently high-risk group of outpatients for thromboprophylaxis. We developed a simple model for predicting chemotherapy-associated VTE using baseline clinical and laboratory variables. The association of VTE with multiple variables was characterized in a derivation cohort of 2701 cancer outpatients from a prospective observational study. A risk model was derived and validated in an independent cohort of 1365 patients from the same study. Five predictive variables were identified in a multivariate model: site of cancer (2 points for very high-risk site, 1 point for high-risk site), platelet count of 350 x 10(9)/L or more, hemoglobin less than 100 g/L (10 g/dL) and/or use of erythropoiesis-stimulating agents, leukocyte count more than 11 x 10(9)/L, and body mass index of 35 kg/m(2) or more (1 point each). Rates of VTE in the derivation and validation cohorts, respectively, were 0.8% and 0.3% in low-risk (score = 0), 1.8% and 2% in intermediate-risk (score = 1-2), and 7.1% and 6.7% in high-risk (score >/= 3) category over a median of 2.5 months (C-statistic = 0.7 for both cohorts). This model can identify patients with a nearly 7% short-term risk of symptomatic VTE and may be used to select cancer outpatients for studies of thromboprophylaxis.\n\nIndexed on Europe PMC as PubMed record 18216292 (DOI 10.1182/blood-2007-10-116327). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Blood 2008","url":"https://doi.org/10.1182/blood-2007-10-116327"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/18216292/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/18216292"}],"tags":["europepmc-ingest"],"related":["cancer-associated-thrombosis"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["blood"],"dependsOn":[],"notes":[],"journal":"Blood","year":2008,"doi":"10.1182/blood-2007-10-116327","pmid":"18216292","authors":"Khorana AA, Kuderer NM, Culakova E, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-doronina-nat-biotechnol","kind":"paper","name":"Development of potent monoclonal antibody auristatin conjugates for cancer therapy","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 12778055 and published in Nature Biotechnology; the citing page links this DOI, which is how the record was matched.","summary":"We describe the in vitro and in vivo properties of monoclonal antibody (mAb)-drug conjugates consisting of the potent synthetic dolastatin 10 analogs auristatin E (AE) and monomethylauristatin E (MMAE), linked to the chimeric mAbs cBR96 (specific to Lewis Y on carcinomas) and cAC10 (specific to CD30 on hematological malignancies). The linkers used for conjugate formation included an acid-labile hydrazone and protease-sensitive dipeptides, leading to uniformly substituted conjugates that efficiently released active drug in the lysosomes of antigen-positive (Ag+) tumor cells. The peptide-linked mAb-valine-citrulline-MMAE and mAb-phenylalanine-lysine-MMAE conjugates were much more stable in buffers and plasma than the conjugates of mAb and the hydrazone of 5-benzoylvaleric acid-AE ester (AEVB). As a result, the mAb-Val-Cit-MMAE conjugates exhibited greater in vitro specificity and lower in vivo toxicity than corresponding hydrazone conjugates. In vivo studies demonstrated that the peptide-linked conjugates induced regressions and cures of established tumor xenografts with therapeutic indices as high as 60-fold. These conjugates illustrate the importance of linker technology, drug potency and conjugation methodology in developing safe and efficacious mAb-drug conjugates for cancer therapy.\n\nIndexed on Europe PMC as PubMed record 12778055 (DOI 10.1038/nbt832). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Biotechnol 2003","url":"https://doi.org/10.1038/nbt832"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/12778055/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/12778055"}],"tags":["europepmc-ingest"],"related":["mc-vc-pabc"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-biotechnology"],"dependsOn":[],"notes":[],"journal":"Nature Biotechnology","year":2003,"doi":"10.1038/nbt832","pmid":"12778055","authors":"Doronina SO, Toki BE, Torgov MY, et al.","paperType":"basic","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-philip-j-clin-oncol","kind":"paper","name":"Devimistat (CPI-613) With Modified Fluorouarcil, Oxaliplatin, Irinotecan, and Leucovorin (FFX) Versus FFX for Patients With Metastatic Adenocarcinoma of the Pancreas: The Phase III AVENGER 500 Study","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 39088774 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: Metastatic pancreatic adenocarcinoma (mPC) remains a difficult-to-treat disease. Fluorouarcil, oxaliplatin, irinotecan, and leucovorin (FFX) is a standard first-line therapy for mPC for patients with a favorable performance status and good organ function. In a phase I study, devimistat (CPI-613) in combination with modified FFX (mFFX) was deemed safe and exhibited promising efficacy in mPC.\n\nMethods: The AVENGER 500 trial (ClinicalTrials.gov identifier: NCT03504423) is a global, randomized phase III trial conducted at 74 sites across six countries to investigate the efficacy and safety of devimistat in combination with mFFX (experimental arm) compared with standard-dose FFX (control arm) in treatment-naïve patients with mPC. Treatment, administered in once-every-2-weeks cycles until disease progression or intolerable toxicity, included intravenous devimistat at 500 mg/m 2 total per day on days 1 and 3 in the experimental arm. The primary end point of the study was overall survival (OS).\n\nResults: Five hundred and twenty-eight patients were randomly assigned (266 in the experimental arm and 262 in the control arm). The median OS was 11.10 months for devimistat plus mFFX versus 11.73 months for FFX (hazard ratio [HR], 0.95 [95% CI, 0.77 to 1.18]; P =.655) and median progression-free survival was 7.8 months versus 8.0 months, respectively (HR, 0.99 [95% CI, 0.76 to 1.29]; P =.94). Grade ≥3 treatment-emergent adverse events with >10% frequency in the devimistat plus mFFX arm versus the FFX arm were neutropenia (29.0% v 34.5%), diarrhea (11.2% v 19.6%), hypokalemia (13.1% v 14.9%), anemia (13.9% v 13.6%), thrombocytopenia (11.6% v 13.6%), and fatigue (10.8% v 11.5%), respectively.\n\nConclusion: Devimistat in combination with mFFX did not improve long- and short-term mPC patient outcomes compared with standard FFX. There were no new toxicity signals with the addition of devimistat.\n\nIndexed on Europe PMC as PubMed record 39088774 (DOI 10.1200/jco.23.02659). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2024","url":"https://doi.org/10.1200/jco.23.02659"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39088774/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39088774"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["avenger-500"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2024,"doi":"10.1200/jco.23.02659","pmid":"39088774","authors":"Philip PA, Sahai V, Bahary N, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-dhebri-pancreatoblastoma-diagnosis-treatment-outcome-pancreatology-2004","kind":"paper","name":"Dhebri 2004: diagnosis, treatment and outcome of pancreatoblastoma","aka":[],"tldr":"A review pooling every published case of pancreatoblastoma to that date, showing that it is mainly a disease of young children, that alpha-fetoprotein is a useful marker, that surgery is the treatment that cures, and that adults do worse than children.","summary":"Systematic review of pancreatoblastoma cases reported in the literature, summarising age and sex distribution, presenting features, imaging, the role of alpha-fetoprotein, histology, treatment and outcome. Most cases were in children under ten, with a smaller adult group; tumours were usually large, and metastases at diagnosis were common.\n\nComplete resection was associated with long-term survival in children, chemotherapy produced responses in unresectable disease, and radiotherapy had a limited role. Adult patients had a markedly worse prognosis, with most dying of disease.","asOf":"2026-09-21","links":[{"label":"Pancreatology 2004","url":"https://doi.org/10.1159/000079823"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/15256806/"}],"tags":[],"related":[],"cancers":["pancreatoblastoma","pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Pancreatology","year":2004,"doi":"10.1159/000079823","pmid":"15256806","authors":"Dhebri AR, Connor S, Campbell F, Ghaneh P, Sutton R, Neoptolemos JP.","paperType":"review","findings":["Pancreatoblastoma is predominantly a childhood tumour; adults form a minority with a poorer outcome.","Alpha-fetoprotein is raised in most children and tracks response.","Complete resection is the treatment associated with cure; chemotherapy helps unresectable disease."],"whatItMeans":"The review is the usual citation for the natural history of pancreatoblastoma and for the recommendation of resection with chemotherapy for advanced disease.","caveats":["Literature-based review with publication bias and heterogeneous reporting.","Predates the EXPeRT series and modern chemotherapy protocols."]},{"id":"paper-petersenn-nat-rev-endocrinol","kind":"paper","name":"Diagnosis and management of prolactin-secreting pituitary adenomas: a Pituitary Society international Consensus Statement","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 37670148 and published in Nature reviews. Endocrinology; the citing page links this DOI, which is how the record was matched.","summary":"This Consensus Statement from an international, multidisciplinary workshop sponsored by the Pituitary Society offers evidence-based graded consensus recommendations and key summary points for clinical practice on the diagnosis and management of prolactinomas. Epidemiology and pathogenesis, clinical presentation of disordered pituitary hormone secretion, assessment of hyperprolactinaemia and biochemical evaluation, optimal use of imaging strategies and disease-related complications are addressed. In-depth discussions present the latest evidence on treatment of prolactinoma, including efficacy, adverse effects and options for withdrawal of dopamine agonist therapy, as well as indications for surgery, preoperative medical therapy and radiation therapy. Management of prolactinoma in special situations is discussed, including cystic lesions, mixed growth hormone-secreting and prolactin-secreting adenomas and giant and aggressive prolactinomas. Furthermore, considerations for pregnancy and fertility are outlined, as well as management of prolactinomas in children and adolescents, patients with an underlying psychiatric disorder, postmenopausal women, transgender individuals and patients with chronic kidney disease. The workshop concluded that, although treatment resistance is rare, there is a need for additional therapeutic options to address clinical challenges in treating these patients and a need to facilitate international registries to enable risk stratification and optimization of therapeutic strategies.\n\nIndexed on Europe PMC as PubMed record 37670148 (DOI 10.1038/s41574-023-00886-5). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Endocrinol 2023","url":"https://doi.org/10.1038/s41574-023-00886-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37670148/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37670148"}],"tags":["europepmc-ingest"],"related":["pituitary-tumours"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature reviews. Endocrinology","year":2023,"doi":"10.1038/s41574-023-00886-5","pmid":"37670148","authors":"Petersenn S, Fleseriu M, Casanueva FF, et al.","paperType":"review","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-psma-prerp-hope-jama-oncol-2021","kind":"paper","name":"Diagnostic accuracy of 68Ga-PSMA-11 PET for pelvic nodal metastasis detection prior to radical prostatectomy and pelvic lymph node dissection: a multicenter prospective phase 3 imaging trial","aka":[],"tldr":"In 277 men whose prostate and pelvic lymph nodes were removed after a gallium PSMA scan, the scan correctly flagged 40 percent of the men with cancer in their nodes and was right 95 percent of the time when it called the nodes clear.","summary":"Report of the investigator-initiated, prospective, multicentre, single-arm, open-label phase 3 imaging trial of 68Ga-PSMA-11 PET at UCSF and UCLA (NCT03368547, NCT02611882 and NCT02919111), which enrolled 764 men with intermediate- to high-risk prostate cancer considered for prostatectomy between December 2015 and December 2019. Each man had one PET scan with 3 to 7 mCi of 68Ga-PSMA-11, read by three blinded central readers with a majority rule. The primary endpoint was per-patient sensitivity and specificity for pelvic lymph node metastasis against histopathology, with nodal-region correlation.\n\nOf the 764 men, 277 (36 percent) underwent prostatectomy with lymph node dissection and formed the efficacy cohort; 75 (27 percent) had pelvic nodal metastasis on pathology. PET was positive in 40 (14 percent), 2 (1 percent) and 7 (3 percent) of the 277 for pelvic nodal, extrapelvic nodal and bone disease. Sensitivity, specificity, positive predictive value and negative predictive value for pelvic nodal metastasis were 0.40 (95 percent CI 0.34 to 0.46), 0.95 (0.92 to 0.97), 0.75 (0.70 to 0.80) and 0.81 (0.76 to 0.85). Of the 487 men who did not have surgery, 108 were lost to follow-up; the rest mostly had radiotherapy (69 percent) or systemic therapy (22 percent). The authors describe the collaboration as the largest of its kind and the foundation of the New Drug Application for 68Ga-PSMA-11.","asOf":"2026-09-24","links":[{"label":"JAMA Oncology 2021","url":"https://doi.org/10.1001/jamaoncol.2021.3771"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34529005/"},{"label":"ClinicalTrials.gov NCT03368547","url":"https://clinicaltrials.gov/study/NCT03368547"}],"tags":[],"related":[],"cancers":["prostate","prostate-high-risk"],"sections":[],"technologies":["psma-pet"],"targets":["psma"],"drugs":["ga68-psma-11","illuccix"],"companies":[],"institutions":["ucla-jonsson","ucsf"],"pathways":[],"terms":[],"trials":["psma-prerp"],"people":["thomas-hope"],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2021,"doi":"10.1001/jamaoncol.2021.3771","pmid":"34529005","authors":"Hope TA, Eiber M, Armstrong WR, et al.","paperType":"observational","findings":["Per-patient sensitivity 0.40 (95 percent CI 0.34 to 0.46) and specificity 0.95 (0.92 to 0.97) for pelvic nodal metastasis against histopathology in 277 men.","Positive predictive value 0.75 and negative predictive value 0.81; 27 percent of the surgery cohort had nodal metastasis.","764 men imaged; 36 percent went on to prostatectomy with lymph node dissection."],"whatItMeans":"This academic programme is what the FDA approved 68Ga-PSMA-11 on in December 2020, and the Illuccix and Locametz kits rest on it for the staging indication. Its message for a man being staged before surgery is that a positive PSMA PET node is very likely real, but a negative scan does not rule out small nodal deposits, so the lymph node dissection still matters.","caveats":["Only 36 percent of imaged men reached the surgical reference standard, so the efficacy cohort is a selected subset.","Sensitivity of 0.40 means most nodal metastases found at surgery were missed, largely because they were small.","Single-arm accuracy study; the randomised comparison with conventional imaging is proPSMA."],"changedPractice":true,"participants":764},{"id":"paper-schultz-clin-cancer-res","kind":"paper","name":"DICER1 and Associated Conditions: Identification of At-risk Individuals and Recommended Surveillance Strategies","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 29343557 and published in Clinical Cancer Research; the citing page links this DOI, which is how the record was matched.","summary":"Pathogenic germline DICER1 variants cause a hereditary cancer predisposition syndrome with a variety of manifestations. In addition to conferring increased cancer risks for pleuropulmonary blastoma (PPB) and ovarian sex cord-stromal tumors, particularly Sertoli-Leydig cell tumor, individuals with pathogenic germline DICER1 variants may also develop lung cysts, cystic nephroma, renal sarcoma and Wilms tumor, nodular hyperplasia of the thyroid, nasal chondromesenchymal hamartoma, ciliary body medulloepithelioma, genitourinary embryonal rhabdomyosarcoma, and brain tumors including pineoblastoma and pituitary blastoma. In May 2016, the International PPB Registry convened the inaugural International DICER1 Symposium to develop consensus testing and surveillance and treatment recommendations. Attendees from North America, Europe, and Russia provided expert representation from the disciplines of pediatric oncology, endocrinology, genetics, genetic counseling, radiology, pediatric surgery, pathology, and clinical research. Recommendations are provided for genetic testing; prenatal management; and surveillance for DICER1 -associated pulmonary, renal, gynecologic, thyroid, ophthalmologic, otolaryngologic, and central nervous system tumors and gastrointestinal polyps. Risk for most DICER1 -associated neoplasms is highest in early childhood and decreases in adulthood. Individual and caregiver education and judicious imaging-based surveillance are the primary recommended approaches. These testing and surveillance recommendations reflect a consensus of expert opinion and current literature. As DICER1 research expands, guidelines for screening and treatment will continue to be updated. Clin Cancer Res; 24(10); 2251-61. ©2018 AACR.\n\nIndexed on Europe PMC as PubMed record 29343557 (DOI 10.1158/1078-0432.ccr-17-3089). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Clin Cancer Res 2018","url":"https://doi.org/10.1158/1078-0432.ccr-17-3089"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29343557/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29343557"}],"tags":["europepmc-ingest"],"related":["pleuropulmonary-blastoma"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2018,"doi":"10.1158/1078-0432.ccr-17-3089","pmid":"29343557","authors":"Schultz KAP, Williams GM, Kamihara J, et al.","paperType":"review","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-spencer-science","kind":"paper","name":"Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 34941392 and published in Science; the citing page links this DOI, which is how the record was matched.","summary":"Gut bacteria modulate the response to immune checkpoint blockade (ICB) treatment in cancer, but the effect of diet and supplements on this interaction is not well studied. We assessed fecal microbiota profiles, dietary habits, and commercially available probiotic supplement use in melanoma patients and performed parallel preclinical studies. Higher dietary fiber was associated with significantly improved progression-free survival in 128 patients on ICB, with the most pronounced benefit observed in patients with sufficient dietary fiber intake and no probiotic use. Findings were recapitulated in preclinical models, which demonstrated impaired treatment response to anti, programmed cell death 1 (anti, PD-1), based therapy in mice receiving a low-fiber diet or probiotics, with a lower frequency of interferon-γ, positive cytotoxic T cells in the tumor microenvironment. Together, these data have clinical implications for patients receiving ICB for cancer.\n\nIndexed on Europe PMC as PubMed record 34941392 (DOI 10.1126/science.aaz7015). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Science 2021","url":"https://doi.org/10.1126/science.aaz7015"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34941392/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34941392"}],"tags":["europepmc-ingest"],"related":["dietary-fibre-microbiome-io"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2021,"doi":"10.1126/science.aaz7015","pmid":"34941392","authors":"Spencer CN, McQuade JL, Gopalakrishnan V, et al.","paperType":"basic","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-ambrosone-j-clin-oncol","kind":"paper","name":"Dietary Supplement Use During Chemotherapy and Survival Outcomes of Patients With Breast Cancer Enrolled in a Cooperative Group Clinical Trial (SWOG S0221)","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 31855498 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: Despite reported widespread use of dietary supplements during cancer treatment, few empirical data with regard to their safety or efficacy exist. Because of concerns that some supplements, particularly antioxidants, could reduce the cytotoxicity of chemotherapy, we conducted a prospective study ancillary to a therapeutic trial to evaluate associations between supplement use and breast cancer outcomes.\n\nMethods: Patients with breast cancer randomly assigned to an intergroup metronomic trial of cyclophosphamide, doxorubicin, and paclitaxel were queried on their use of supplements at registration and during treatment (n =1,134). Cox proportional hazards regression adjusting for clinical and lifestyle variables was used. Recurrence and survival were indexed at 6 months after enrollment using a landmark approach.\n\nResults: There were indications that use of any antioxidant supplement (vitamins A, C, and E; carotenoids; coenzyme Q10) both before and during treatment was associated with an increased hazard of recurrence (adjusted hazard ratio [adjHR], 1.41; 95% CI, 0.98 to 2.04; P =.06) and, to a lesser extent, death (adjHR, 1.40; 95% CI, 0.90 to 2.18; P =.14). Relationships with individual antioxidants were weaker perhaps because of small numbers. For nonantioxidants, vitamin B12 use both before and during chemotherapy was significantly associated with poorer disease-free survival (adjHR, 1.83; 95% CI, 1.15 to 2.92; P <.01) and overall survival (adjHR, 2.04; 95% CI, 1.22 to 3.40; P <.01). Use of iron during chemotherapy was significantly associated with recurrence (adjHR, 1.79; 95% CI, 1.20 to 2.67; P <.01) as was use both before and during treatment (adjHR, 1.91; 95% CI, 0.98 to 3.70; P =.06). Results were similar for overall survival. Multivitamin use was not associated with survival outcomes.\n\nConclusion: Associations between survival outcomes and use of antioxidant and other dietary supplements both before and during chemotherapy are consistent with recommendations for caution among patients when considering the use of supplements, other than a multivitamin, during chemotherapy.\n\nIndexed on Europe PMC as PubMed record 31855498 (DOI 10.1200/jco.19.01203). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2020","url":"https://doi.org/10.1200/jco.19.01203"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31855498/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31855498"}],"tags":["europepmc-ingest"],"related":["dietary-supplements-treatment-interactions"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/jco.19.01203","pmid":"31855498","authors":"Ambrosone CB, Zirpoli GR, Hutson AD, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-stopsack-prostate-genomes-by-race-ccr-2022","kind":"paper","name":"Differences in prostate cancer genomes by self-reported race","aka":[],"tldr":"Comparing the tumours of 2,069 men treated at one hospital found real genomic differences by race that survived adjusting for stage and PSA, including more of the chromosome change that carries the worst prognosis in Black men.","summary":"Among 2,069 men with prostate cancer with access to clinical-grade sequencing at the same cancer centre, 1,841 self-reported White, 63 Asian and 165 Black, the prevalence of tumour and germline alterations was assessed in driver genes previously reported to differ by race. Clinical characteristics including PSA, age at diagnosis and cancer stage at sample procurement differed by self-reported race, but most genomic differences persisted after adjustment. Tumours from Black men carried fewer PTEN mutations and more AR alterations than those from White men; tumours from Asian men carried more FOXA1 mutations and more ZFHX3 alterations. Despite fewer TP53 mutations, tumours from Black men had more aneuploidy, particularly gains of chromosome arm 8q, an adverse prognostic factor. Genetic ancestry was associated with similar tumour alterations to self-reported race but also with modifiable cancer risk factors, and community-level average income was associated with 8q gain after adjusting for race and ancestry.","asOf":"2026-09-25","links":[{"label":"Stopsack et al., Clin Cancer Res 2022: differences in prostate cancer genomes by self-reported race in 2,069 men sequenced at one centre","url":"https://doi.org/10.1158/1078-0432.CCR-21-2577"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34667026/"},{"label":"cBioPortal study prad_msk_stopsack_2021 (MSK-IMPACT, Clin Cancer Res 2022; 2,069 men with self-reported race recorded, 1,841 White, 165 Black, 63 Asian)","url":"https://www.cbioportal.org/study/summary?id=prad_msk_stopsack_2021"}],"tags":[],"related":[],"cancers":["prostate"],"sections":[],"technologies":["cgp"],"targets":["pten","androgen-receptor","foxa1","zbtb16","tp53"],"drugs":[],"companies":[],"institutions":[],"pathways":["chromosomal-instability","ar-signaling","prostate-cancer-signalling"],"terms":["copy-number-variation-term","driver-mutation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2022,"doi":"10.1158/1078-0432.CCR-21-2577","pmid":"34667026","authors":"Stopsack KH, Nandakumar S, Arora K, et al.","paperType":"observational","findings":["Fewer PTEN mutations and more AR alterations in tumours from Black men after adjustment.","More FOXA1 mutations and ZFHX3 alterations in tumours from Asian men.","More aneuploidy and specifically more 8q gain in tumours from Black men, despite fewer TP53 mutations.","Community-level average income associated with 8q gain even after adjusting for race and genetic ancestry."],"whatItMeans":"It separates two explanations that are usually run together. Some of the difference in prostate cancer outcomes by race is in the tumour genome and persists when access to the same centre is held constant, and some of it tracks with income rather than with ancestry, so equalising access alone would not eliminate the gap.","caveats":["One hundred and sixty-five Black men and 63 Asian men, so the minority groups are small.","A single centre whose patients have unusual access to sequencing.","Self-reported race and genetic ancestry are different variables and the paper is careful not to conflate them; readers often do."],"changedPractice":false,"participants":2069},{"id":"paper-ricciuti-stk11-keap1-kras-immunotherapy-jto-2022","kind":"paper","name":"Diminished efficacy of programmed death-(ligand)1 inhibition in STK11- and KEAP1-mutant lung adenocarcinoma is affected by KRAS mutation status","aka":[],"tldr":"Two genes long blamed for immunotherapy failure in lung cancer turn out to matter only when the tumour also has a mutated KRAS gene. In tumours without it, the same mutations made no difference at all.","summary":"Clinicopathological and genomic data were collected from patients with advanced lung adenocarcinoma at two multi-institutional cohorts, and outcomes on PD-(L)1 inhibition were analysed by KRAS, STK11 and KEAP1 mutation status. In the combined cohort of 1,261 patients, KRAS mutations were detected in 536 cases, 42.5%, deleterious STK11 mutations in 260 of 1,261, 20.6%, and deleterious KEAP1 mutations in 231 of 1,202 assessable cases, 19.2%. In each independent cohort and in the combined cohort, STK11 and KEAP1 mutations were associated with significantly worse progression-free survival (hazard ratios 2.04 and 2.05) and overall survival (2.09 and 2.24) on immunotherapy uniquely among KRAS-mutant but not KRAS wild-type adenocarcinomas. Gene expression and immune cell enrichment analyses showed that STK11 or KEAP1 mutation produced distinct immunophenotypes only in KRAS-mutant tumours.","asOf":"2026-09-25","links":[{"label":"Ricciuti et al., J Thorac Oncol 2022: STK11 and KEAP1 mutations and PD-(L)1 inhibition in 1,261 lung adenocarcinomas, by KRAS status","url":"https://doi.org/10.1016/j.jtho.2021.10.013"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34740862/"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":["checkpoint-inhibitor","cgp"],"targets":["stk11","keap1","kras","pdl1","pd1"],"drugs":[],"companies":[],"institutions":["dana-farber","mgh","mskcc","md-anderson"],"pathways":["t-cell-exhaustion","keap1-nrf2","pd1-checkpoint"],"terms":["stk11-keap1","kras-mutation-subtypes","cold-vs-hot"],"trials":[],"people":["ferdinandos-skoulidis"],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-thoracic-oncology"],"dependsOn":[],"notes":[],"journal":"Journal of Thoracic Oncology","year":2022,"doi":"10.1016/j.jtho.2021.10.013","pmid":"34740862","authors":"Ricciuti B, Arbour KC, Lin JJ, et al.","paperType":"observational","findings":["STK11 mutation in 20.6% and KEAP1 mutation in 19.2% of lung adenocarcinomas across two cohorts.","Both predicted worse progression-free and overall survival on PD-(L)1 blockade only in KRAS-mutant tumours.","In KRAS wild-type tumours neither mutation affected outcome.","The immune phenotype differences were also confined to KRAS-mutant disease."],"whatItMeans":"It corrected a widely repeated simplification. An STK11 or KEAP1 mutation is not by itself a reason to expect immunotherapy to fail; it is a reason to expect it in a KRAS-mutant tumour, which is how the result should be read on a report.","caveats":["Retrospective across two cohorts with different treatment practices.","Deleterious mutation calling depends on the annotation pipeline.","Patients received several different regimens."],"changedPractice":false,"participants":1261},{"id":"paper-stoeck-notch-rearrangements-tnbc-cancer-discov-2014","kind":"paper","name":"Discovery of biomarkers predictive of GSI response in triple-negative breast cancer and adenoid cystic carcinoma","aka":[],"tldr":"Rearrangements that lock the NOTCH1 or NOTCH2 receptor on were found in 6 of 66 triple-negative breast cancers and no other solid tumour, and only the NOTCH1-rearranged models responded to a gamma-secretase inhibitor.","summary":"Next-generation sequencing of a large collection of solid tumours identified NOTCH1 and NOTCH2 rearrangements leading to constitutive activation confined to TNBC (6 of 66). TNBC cell lines with NOTCH1 rearrangements and high activated NOTCH1 (N1-ICD) were sensitive to the gamma-secretase inhibitor MRK-003 alone and with paclitaxel in vitro and in vivo; NOTCH2-rearranged lines were resistant. N1-ICD staining in xenografts correlated with response and HES4 expression with patient outcome. Activating NOTCH1 point mutations were also found in adenoid cystic carcinoma.","asOf":"2026-09-24","links":[{"label":"Stoeck et al., Cancer Discov 2014: NOTCH1 and NOTCH2 rearrangements in 6 of 66 TNBCs","url":"https://doi.org/10.1158/2159-8290.CD-13-0830"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25104330/"}],"tags":[],"related":[],"cancers":["tnbc"],"sections":[],"technologies":[],"targets":["notch1","gamma-secretase"],"drugs":[],"companies":[],"institutions":[],"pathways":["notch"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-discovery"],"dependsOn":[],"notes":[],"journal":"Cancer Discovery","year":2014,"doi":"10.1158/2159-8290.CD-13-0830","pmid":"25104330","authors":"Stoeck A, Lejnine S, Truong A, et al.","paperType":"translational","findings":["NOTCH1/2 activating rearrangements in 6 of 66 TNBCs (9%), confined to TNBC.","NOTCH1-rearranged models sensitive to gamma-secretase inhibition; NOTCH2-rearranged resistant."],"whatItMeans":"NOTCH is a real but small driver segment in TNBC with a receptor-specific drug response, which is why NOTCH-directed trials require rearrangement or N1-ICD testing rather than treating all TNBC.","caveats":["Small TNBC series; clinical gamma-secretase inhibitor trials have not delivered an approval.","Rearrangements need RNA or whole-genome methods that DNA panels can miss."],"changedPractice":false,"participants":66},{"id":"paper-loree-jama-oncol","kind":"paper","name":"Disparity of Race Reporting and Representation in Clinical Trials Leading to Cancer Drug Approvals From 2008 to 2018","aka":[],"tldr":"Paper cited by one bottleneck page and 14 idea pages, indexed on Europe PMC as PubMed record 31415071 and published in JAMA Oncology; the citing pages link this DOI, which is how the record was matched.","summary":"Importance: Representative racial/ethnic participation in research, especially in clinical trials that establish standards of care, is necessary to minimize disparities in outcomes and to uphold societal equity in health care.\n\nObjective: To evaluate the frequency of race reporting and proportional race representation in trials supporting US Food and Drug Administration (FDA) oncology drug approvals.\n\nDesign, setting, and participants: Database study of all reported trials supporting FDA oncology drug approvals granted between July 2008 and June 2018. Primary reports of trials were obtained from PubMed and ClinicalTrials.gov. Food and Drug Administration approvals were identified using the FDA archives. The US population-based cancer estimates by race were calculated using National Cancer Institute-Surveillance, Epidemiology, and End Results and US Census databases.\n\nMain outcomes and measures: Primary outcomes were the proportion of trials reporting race and the proportion of patients by race participating in trials. Secondary outcomes included race subgroup analyses reporting and gaps between race proportion in trials and the US population. Descriptive statistics, Fisher exact, and χ2 tests were used to analyze the data. Proportions and odds ratios (OR) with 95% CIs were reported.\n\nResults: Among 230 trials with a total of 112 293 participants, 145 (63.0%) reported on at least 1 race, 18 (7.8%) documented the 4 major races in the United States (white, Asian, black, and Hispanic), and 58 (25.2%) reported race subgroup analyses. Reporting on white, Asian, black, and Hispanic races was included in 144 (62.6%), 110 (47.8%), 88 (38.2%), and 23 (10.0%) trials, respectively. Between July 2008 and June 2013 vs July 2013 and June 2018, the number of trials reporting race (45 [56.6%] vs 100 [67.1%]; OR, 1.63; 95% CI, 0.93-2.87; P =.09) and race subgroup analysis (13 [16.1%] vs 45 [30.2%]; OR, 2.26, 95% CI, 1.16-4.67; P =.03) changed minimally and varied across races. Whites, Asians, blacks, and Hispanics represented 76.3%, 18.3%, 3.1% and 6.1% of trial participants, respectively, and the proportion for each race enrolled over time changed nominally (blacks, 3.6% vs 2.9% and Hispanics, 5.3% vs 6.7%) from July 2008 to June 2013 vs July 2013 to June 2018. Compared with their proportion of US cancer incidence, blacks (22% of expected) and Hispanics (44% of expected) were underrepresented compared with whites (98% of expected) and Asians (438% of expected).\n\nConclusions and relevance: Race and race subgroup analysis reporting occurs infrequently, and black and Hispanic races are consistently underrepresented compared with their burden of cancer incidence in landmark trials that led to FDA oncology drug approvals. Enhanced minority engagement is needed in trials to ensure the validity of results and reliable benefits to all.\n\nIndexed on Europe PMC as PubMed record 31415071 (DOI 10.1001/jamaoncol.2019.1870). Matched by DOI alone: one bottleneck page and 14 idea pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA Oncol 2019","url":"https://doi.org/10.1001/jamaoncol.2019.1870"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31415071/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31415071"}],"tags":["europepmc-ingest"],"related":["b-trial-diversity","idea-tr1-site-equity-index","idea-tr1-trial-desert-map","idea-tr1-sex-stratified-pk-and-dosing","idea-tr1-community-health-worker-recruitment","idea-tr1-ecog-2-dedicated-cohorts","idea-tr1-duffy-null-neutrophil-threshold","idea-tr1-diverse-investigator-pipeline","idea-tr1-paid-community-advisory-boards","idea-tr1-parallel-comorbidity-cohorts","idea-tr1-lmic-sites-in-pivotal-trials","idea-tr1-post-marketing-safety-by-ancestry-and-sex","idea-tr1-disability-and-mental-illness-inclusion","idea-tr1-incidence-weighted-enrolment-targets","idea-tr1-include-pregnancy-capable-people-sensibly"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2019,"doi":"10.1001/jamaoncol.2019.1870","pmid":"31415071","authors":"Loree JM, Anand S, Dasari A, et al.","paperType":"observational","findings":[],"whatItMeans":"One bottleneck page and 14 idea pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-missiaglia-distal-proximal-colon-cancers-ann-oncol-2014","kind":"paper","name":"Distal and proximal colon cancers differ in terms of molecular, pathological, and clinical features","aka":[],"tldr":"Using a large adjuvant trial, this study showed that the two ends of the colon behave like two diseases: the right is mucinous, mismatch repair deficient and BRAF-like, the left is chromosomally unstable and dependent on EGFR signalling.","summary":"Clinicopathological data for 3,045 colon carcinoma patients enrolled in the PETACC-3 adjuvant chemotherapy trial were analysed, with molecular data for 1,404, gene expression for 589 and DNA copy number for 199, plus 413 TCGA colon adenocarcinomas and a cohort of 325 metastatic patients treated with anti-EGFR therapy. Proximal carcinomas were more often mucinous, microsatellite instability-high, mutated in key tumourigenic pathways, and expressed a BRAF-like and a serrated pathway signature regardless of histological type. Distal carcinomas were more often chromosome instable and EGFR or HER2 amplified, and more frequently overexpressed epiregulin. Risk of relapse did not differ by side, but survival after relapse was much poorer for proximal stage III carcinomas in a multivariable model including BRAF status (hazard ratio 1.95). Only patients with metastases from a distal carcinoma responded to anti-EGFR therapy.","asOf":"2026-09-24","links":[{"label":"Missiaglia et al., Ann Oncol 2014: distal and proximal colon cancers differ molecularly and clinically (PETACC-3, 3,045 patients)","url":"https://doi.org/10.1093/annonc/mdu275"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25057166/"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":[],"targets":["egfr","her2","braf","mmr"],"drugs":[],"companies":[],"institutions":[],"pathways":["ras-mapk","chromosomal-instability","mismatch-repair-msi"],"terms":["sidedness","msi"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2014,"doi":"10.1093/annonc/mdu275","pmid":"25057166","authors":"Missiaglia E, Jacobs B, D'Ario G, et al.","paperType":"observational","findings":["Proximal tumours: mucinous, MSI-high, BRAF-like and serrated signature.","Distal tumours: chromosome instable, EGFR or HER2 amplified, epiregulin overexpressing.","Survival after relapse worse for proximal stage III disease (hazard ratio 1.95); only distal metastases responded to anti-EGFR therapy."],"whatItMeans":"It is the molecular case for sidedness, made before the trial meta-analyses that turned it into a treatment rule, and it supplies the mechanism: ligand dependence on the left, pathway mutation on the right.","caveats":["Retrospective analyses of a trial population.","Molecular data available for fewer than half the patients.","The anti-EGFR cohort was small (325 patients) and not randomised by side."],"changedPractice":false,"participants":3045},{"id":"paper-yachida-metastasis-late-genetic-evolution-pancreatic-nature-2010","kind":"paper","name":"Distant metastasis occurs late during the genetic evolution of pancreatic cancer","aka":[],"tldr":"Comparing the genomes of primary tumours and their metastases put numbers on the timeline: about ten years from the first mutation to a fully formed tumour, five more before it can spread, and two years of life after that, so there is a long window in which the cancer could be caught.","summary":"The genomes of seven pancreatic cancer metastases were sequenced to evaluate clonal relationships among primary and metastatic cancers. Clonal populations giving rise to distant metastases were represented within the primary carcinoma but were genetically evolved from the original parental non-metastatic clone, so the genetic heterogeneity of metastases reflects that within the primary. Quantitative analysis indicated at least a decade between the initiating mutation and the birth of the parental non-metastatic founder cell, at least five more years for metastatic ability, and death an average of two years thereafter.","asOf":"2026-09-24","links":[{"label":"Yachida et al., Nature 2010: distant metastasis occurs late in the genetic evolution","url":"https://doi.org/10.1038/nature09515"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20981102/"}],"tags":[],"related":[],"cancers":["pancreatic","metastatic-pdac"],"sections":[],"technologies":["wes-wgs","pancreatic-surveillance"],"targets":[],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":["clonal-evolution","metastatic-cascade"],"terms":[],"trials":[],"people":["bert-vogelstein","kenneth-kinzler"],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2010,"doi":"10.1038/nature09515","pmid":"20981102","authors":"Yachida S, Jones S, Bozic I, et al.","paperType":"translational","findings":["At least a decade from initiating mutation to the parental non-metastatic clone.","At least five more years to metastatic ability; death about two years later."],"whatItMeans":"It is the quantitative case for early detection: the biology allows a fifteen-year window, and the disease is lethal because we look too late, not because it moves fast.","caveats":["Seven patients and a mathematical model with assumptions about mutation rate.","Later work argues evolution is punctuated rather than steady (Notta 2016)."],"changedPractice":false,"participants":7},{"id":"paper-scherer-ctdna-lymphoma-subtypes-genome-evolution-sci-transl-med-2016","kind":"paper","name":"Distinct biological subtypes and patterns of genome evolution in lymphoma revealed by circulating tumour DNA","aka":["Scherer 2016","CAPP-Seq in lymphoma","Circulating tumour DNA genotyping of cell of origin"],"tldr":"A blood test read the genetic type of a lymphoma without a biopsy, detected disease left behind better than scans did, and spotted the change from a slow lymphoma into an aggressive one before it showed.","summary":"Scherer, Kurtz, Alizadeh and Diehn applied cancer personalised profiling by deep sequencing to tumour biopsies and cell-free DNA from 92 lymphoma patients and 24 healthy subjects. The results set out most of what circulating tumour DNA can do in this disease.\n\nAt diagnosis the amount of circulating tumour DNA correlated strongly with clinical indices and independently predicted outcome. Genotyping the plasma classified transcriptionally defined tumour subtypes, including the cell of origin of diffuse large B-cell lymphoma, directly from blood. Tracking multiple somatic mutations at once outperformed immunoglobulin sequencing and radiographic imaging for detecting minimal residual disease, and identified emergent resistance mutations to targeted therapies without a biopsy. Distinct patterns of clonal evolution separated follicular lymphomas that stayed indolent from those that transformed into diffuse large B-cell lymphoma, which raises the possibility of predicting histological transformation non-invasively.\n\nThat last finding is the one with the most direct consequence for patients, because transformation is the event that turns a disease people live with into one that can kill quickly, and it is currently found only by re-biopsying someone who has already deteriorated.","asOf":"2026-10-01","links":[{"label":"Science Translational Medicine 2016","url":"https://doi.org/10.1126/scitranslmed.aai8545"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27831904/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27831904"}],"tags":["lymphoma-evidence"],"related":["paper-kurtz-j-clin-oncol","paper-kurtz-nat-biotechnol","lymphoma-roadmap"],"cancers":["dlbcl","follicular-lymphoma","non-hodgkin-lymphoma"],"sections":["diagnostics","early-detection"],"technologies":["liquid-biopsy","ngs","wes-wgs"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ctdna","mrd","cell-of-origin"],"trials":[],"people":["ash-alizadeh"],"bottlenecks":["b-dormancy-mrd","b-biomarker-validation","b-early-detection"],"keyPapers":[],"journals":["science-translational-medicine"],"dependsOn":[],"notes":[],"journal":"Science Translational Medicine","year":2016,"doi":"10.1126/scitranslmed.aai8545","pmid":"27831904","authors":"Scherer F, Kurtz DM, Newman AM, et al.","paperType":"translational","findings":["Circulating tumour DNA was profiled by cancer personalised profiling by deep sequencing in 92 lymphoma patients and 24 healthy subjects.","The amount of circulating tumour DNA at diagnosis correlated strongly with clinical indices and independently predicted outcome.","Circulating tumour DNA genotyping classified transcriptionally defined tumour subtypes, including diffuse large B-cell lymphoma cell of origin, directly from plasma.","Simultaneous tracking of multiple somatic mutations outperformed immunoglobulin sequencing and radiographic imaging for detecting minimal residual disease.","Distinct patterns of clonal evolution distinguished indolent follicular lymphomas from those that transformed into diffuse large B-cell lymphoma."],"whatItMeans":"The paper that established lymphoma as the solid-tumour field where circulating tumour DNA works best, because the mutations are many and the tumour sheds. It underpins the response-adapted trial designs now being built on molecular rather than radiographic response.","caveats":["92 patients across several lymphoma types; subgroup findings rest on small numbers.","No trial has yet acted on a circulating tumour DNA result in lymphoma and shown that doing so improves survival.","The assay was a research platform; commercial implementations differ in sensitivity and in the mutations they track.","Transformation prediction was demonstrated retrospectively in a small set and has not been validated prospectively."],"changedPractice":false,"participants":116},{"id":"paper-campbell-pan-lung-somatic-alterations-nat-genet-2016","kind":"paper","name":"Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas","aka":[],"tldr":"Putting 660 lung adenocarcinomas and 484 squamous lung cancers side by side showed that squamous lung cancer has more in common with squamous cancers of other organs than with the adenocarcinoma growing next to it.","summary":"Exome sequences and copy-number profiles of 660 lung adenocarcinoma and 484 lung squamous cell carcinoma tumour-normal pairs were compared. Recurrent alterations in lung squamous carcinomas were more similar to those of other squamous carcinomas than to alterations in lung adenocarcinomas. Newly significantly mutated genes included PPP3CA, DOT1L and FTSJD1 in adenocarcinoma, RASA1 in squamous carcinoma, and KLF5, EP300 and CREBBP in both. New amplification peaks encompassed MIR21 in adenocarcinoma, MIR205 in squamous carcinoma and MAPK1 in both. Adenocarcinomas lacking receptor tyrosine kinase, RAS or RAF pathway alterations carried mutations in SOS1, VAV1, RASA1 and ARHGAP35. For neoantigens, 47% of adenocarcinomas and 53% of squamous carcinomas had at least five predicted neoepitopes.","asOf":"2026-09-25","links":[{"label":"Campbell et al., Nat Genet 2016: distinct patterns of somatic genome alteration in 660 lung adenocarcinomas and 484 squamous cell carcinomas","url":"https://doi.org/10.1038/ng.3564"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27158780/"},{"label":"cBioPortal study nsclc_tcga_broad_2016 (Pan-Lung TCGA and Broad, Nat Genet 2016; 1,144 tumour-normal pairs, 660 adenocarcinoma and 484 squamous)","url":"https://www.cbioportal.org/study/summary?id=nsclc_tcga_broad_2016"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":["wes-wgs"],"targets":["kras","egfr","nf1","crebbp","ep300","kmt2d","tp53"],"drugs":[],"companies":[],"institutions":["broad-institute"],"pathways":["nsclc-signalling","ras-mapk","swi-snf-chromatin","cancer-immunity-cycle"],"terms":["driver-mutation","neoantigen","somatic-mutations-wxs-wgs"],"trials":[],"people":["matthew-meyerson"],"bottlenecks":[],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":2016,"doi":"10.1038/ng.3564","pmid":"27158780","authors":"Campbell JD, Alexandrov A, Kim J, et al.","paperType":"basic","findings":["Squamous lung cancer resembles other squamous carcinomas more than it resembles lung adenocarcinoma.","New significantly mutated genes: RASA1 in squamous disease, KLF5, EP300 and CREBBP in both.","Adenocarcinomas without a receptor tyrosine kinase or RAS alteration carry mutations in RAS regulators instead.","Around half of tumours of each histology have five or more predicted neoepitopes."],"whatItMeans":"It is the empirical basis for treating the two histologies as separate diseases for targeted therapy and as one disease for immunotherapy, which is exactly how they are treated.","caveats":["Exome and copy number only, so fusions and structural variants are underrepresented.","Neoepitope prediction is computational and does not establish that any of them is recognised.","Assembled from cohorts sequenced at different times with different pipelines."],"changedPractice":false,"participants":1144},{"id":"paper-ohlund-caf-subtypes-mycaf-icaf-jem-2017","kind":"paper","name":"Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer","aka":[],"tldr":"The scar-forming cells of pancreatic cancer are not all the same: those touching the tumour cells make the dense fibrous tissue, while those further away pump out inflammatory signals such as IL-6.","summary":"Pancreatic stellate cells differentiate into cancer-associated fibroblasts that produce desmoplastic stroma, but whether subtypes exist was unknown. A CAF subpopulation with elevated alpha-smooth muscle actin was identified immediately adjacent to neoplastic cells in mouse and human tissue; co-culture of murine stellate cells with tumour organoids recapitulated it and showed these organoid-activated CAFs produce desmoplastic stroma. The co-cultures revealed a second subpopulation, located at a distance, lacking elevated alpha-SMA and secreting IL-6 and other inflammatory mediators; both were corroborated in mouse and human tissue.","asOf":"2026-09-24","links":[{"label":"Ohlund et al., J Exp Med 2017: myofibroblastic and inflammatory fibroblasts (myCAF, iCAF)","url":"https://doi.org/10.1084/jem.20162024"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28232471/"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":["organoids"],"targets":["il6","fap"],"drugs":[],"companies":[],"institutions":["cold-spring-harbor"],"pathways":["caf-activation-desmoplasia","tumor-microenvironment"],"terms":["desmoplasia"],"trials":[],"people":["david-tuveson"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of Experimental Medicine","year":2017,"doi":"10.1084/jem.20162024","pmid":"28232471","authors":"Ohlund D, Handly-Santana A, Biffi G, et al.","paperType":"basic","findings":["Myofibroblastic CAFs (alpha-SMA high) sit next to tumour cells and build the stroma.","Inflammatory CAFs sit further away and secrete IL-6 and other mediators."],"whatItMeans":"The myCAF and iCAF distinction is why 'target the stroma' became 'target a fibroblast state', and IL-6 blockade combinations follow from it.","caveats":["Organoid co-culture and mouse models.","Subtypes are states rather than fixed lineages."],"changedPractice":false},{"id":"paper-curtin-melanoma-genetic-alterations-nejm-2005","kind":"paper","name":"Distinct sets of genetic alterations in melanoma","aka":[],"tldr":"Comparing melanomas from sun-damaged skin, non-sun-damaged skin, palms and soles, and mucosal surfaces showed each carries a different pattern of BRAF, NRAS and copy-number changes, establishing that melanoma is several genetically distinct diseases.","summary":"Comparative genomic hybridisation and mutation analysis of 126 melanomas grouped by anatomical site and sun exposure, showing BRAF mutations concentrated in melanomas on skin without chronic sun damage, and frequent focal amplifications with few BRAF mutations in acral and mucosal melanomas.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2005","url":"https://doi.org/10.1056/NEJMoa050092"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/16291983/"}],"tags":[],"related":[],"cancers":["acral-melanoma","mucosal-melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2005,"doi":"10.1056/NEJMoa050092","pmid":"16291983","authors":"Curtin JA, Fridlyand J, Kageshita T, et al.","paperType":"translational","findings":["BRAF mutations in 59 percent of melanomas on non-chronically sun-damaged skin vs 11 percent in chronically sun-damaged, 23 percent acral and 11 percent mucosal.","Frequent focal copy-number amplifications in acral and mucosal melanoma."],"whatItMeans":"This paper founded the site-based molecular classification of melanoma that underpins separate pages for acral and mucosal disease and their different treatment responses.","caveats":["Low-resolution copy-number technology by current standards."],"changedPractice":true,"participants":126},{"id":"paper-alizadeh-nature","kind":"paper","name":"Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 10676951 and published in Nature; the citing page links this DOI, which is how the record was matched.","summary":"Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin's lymphoma, is clinically heterogeneous: 40% of patients respond well to current therapy and have prolonged survival, whereas the remainder succumb to the disease. We proposed that this variability in natural history reflects unrecognized molecular heterogeneity in the tumours. Using DNA microarrays, we have conducted a systematic characterization of gene expression in B-cell malignancies. Here we show that there is diversity in gene expression among the tumours of DLBCL patients, apparently reflecting the variation in tumour proliferation rate, host response and differentiation state of the tumour. We identified two molecularly distinct forms of DLBCL which had gene expression patterns indicative of different stages of B-cell differentiation. One type expressed genes characteristic of germinal centre B cells ('germinal centre B-like DLBCL'); the second type expressed genes normally induced during in vitro activation of peripheral blood B cells ('activated B-like DLBCL'). Patients with germinal centre B-like DLBCL had a significantly better overall survival than those with activated B-like DLBCL. The molecular classification of tumours on the basis of gene expression can thus identify previously undetected and clinically significant subtypes of cancer.\n\nIndexed on Europe PMC as PubMed record 10676951 (DOI 10.1038/35000501). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2000","url":"https://doi.org/10.1038/35000501"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/10676951/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/10676951"}],"tags":["europepmc-ingest"],"related":["cell-of-origin","lymphoma-roadmap","paper-rosenwald-molecular-profiling-dlbcl-nejm-2002","paper-hans-immunohistochemistry-cell-of-origin-dlbcl-blood-2004"],"cancers":["dlbcl","non-hodgkin-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2000,"doi":"10.1038/35000501","pmid":"10676951","authors":"Alizadeh AA, Eisen MB, Davis RE, et al.","paperType":"basic","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-kellogg-bioconjug-chem","kind":"paper","name":"Disulfide-linked antibody-maytansinoid conjugates: optimization of in vivo activity by varying the steric hindrance at carbon atoms adjacent to the disulfide linkage","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 21425776 and published in Bioconjugate chemistry; the citing page links this DOI, which is how the record was matched.","summary":"In this report, we describe the synthesis of a panel of disulfide-linked huC242 (anti-CanAg) antibody maytansinoid conjugates (AMCs), which have varying levels of steric hindrance around the disulfide bond, in order to investigate the relationship between stability to reduction of the disulfide linker and antitumor activity of the conjugate in vivo. The conjugates were first tested for stability to reduction by dithiothreitol in vitro and for plasma stability in CD1 mice. It was found that the conjugates having the more sterically hindered disulfide linkages were more stable to reductive cleavage of the maytansinoid in both settings. When the panel of conjugates was tested for in vivo efficacy in two human colon cancer xenograft models in SCID mice, it was found that the conjugate with intermediate disulfide bond stability having two methyl groups on the maytansinoid side of the disulfide bond and no methyl groups on the linker side of the disulfide bond (huC242-SPDB-DM4) displayed the best efficacy. The ranking of in vivo efficacies of the conjugates was not predicted by their in vitro potencies, since all conjugates were highly active in vitro, including a huC242-SMCC-DM1 conjugate with a noncleavable linkage which showed only marginal activity in vivo. These data suggest that factors in addition to intrinsic conjugate potency and conjugate half-life in plasma influence the magnitude of antitumor activity observed for an AMC in vivo. We provide evidence that bystander killing of neighboring nontargeted tumor cells by diffusible cytotoxic metabolites produced from target cell processing of disulfide-linked antibody-maytansinoid conjugates may be one additional factor contributing to the activity of these conjugates in vivo.\n\nIndexed on Europe PMC as PubMed record 21425776 (DOI 10.1021/bc100480a). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Bioconjug Chem 2011","url":"https://doi.org/10.1021/bc100480a"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21425776/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/21425776"}],"tags":["europepmc-ingest"],"related":["sulfo-spdb"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Bioconjugate chemistry","year":2011,"doi":"10.1021/bc100480a","pmid":"21425776","authors":"Kellogg BA, Garrett L, Kovtun Y, et al.","paperType":"basic","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-beltran-nepc-divergent-evolution-nat-med-2016","kind":"paper","name":"Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer","aka":[],"tldr":"Sequencing showed that neuroendocrine prostate cancer arises from the same cells as ordinary prostate adenocarcinoma but diverges through loss of RB1 and TP53 and changes in DNA methylation rather than new mutations, explaining how the cancer escapes hormone therapy by changing identity.","summary":"Whole-exome and methylation analysis of 114 metastatic biopsies from patients with castration-resistant prostate cancer, comparing adenocarcinoma with neuroendocrine prostate cancer.\n\nNeuroendocrine tumours shared clonal origin with adenocarcinoma, showed frequent RB1 loss and TP53 mutation, low androgen receptor signalling, distinct epigenetic profiles and overexpression of EZH2, with a lineage-switch rather than a distinct mutational driver.","asOf":"2026-09-17","links":[{"label":"Nat Med 2016","url":"https://doi.org/10.1038/nm.4045"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26855148/"}],"tags":[],"related":["prostate-roadmap","paper-mu-sox2-lineage-plasticity-science-2017","idea-prostate-plasticity-surveillance-before-it-is-neuroendocrine"],"cancers":["prostate-nepc","prostate","prostate-mcrpc"],"sections":[],"technologies":["wes-wgs","methylation-profiling"],"targets":["androgen-receptor","rb1","tp53"],"drugs":[],"companies":[],"institutions":[],"pathways":["lineage-plasticity-neuroendocrine","epigenetic-reprogramming","clonal-evolution"],"terms":["neuroendocrine-differentiation","histologic-transformation","castration-resistance"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2016,"doi":"10.1038/nm.4045","pmid":"26855148","authors":"Beltran H, Prandi D, Mosquera JM, et al.","paperType":"translational","findings":["RB1 loss and TP53 alteration enriched in neuroendocrine prostate cancer.","Epigenetic divergence with shared clonal ancestry from adenocarcinoma."],"whatItMeans":"Treatment-emergent neuroendocrine prostate cancer is understood as lineage plasticity under androgen receptor blockade; EZH2, DLL3 and Aurora kinase are the targets under investigation.","caveats":["Biopsy cohort from selected patients; therapeutic implications are still being tested."],"changedPractice":true,"participants":114},{"id":"paper-sahm-meningioma-methylation-lancet-oncol-2017","kind":"paper","name":"DNA methylation-based classification and grading system for meningioma","aka":[],"tldr":"Profiling the chemical marks on meningioma DNA separated the tumours into six classes that predicted recurrence better than the traditional microscope-based grade, especially for the many grade 1 and 2 tumours that behave unexpectedly.","summary":"Retrospective study of 497 meningiomas (with 309 validation cases) using genome-wide DNA methylation profiling to define six methylation classes and three combined groups (benign, intermediate, malignant), compared with WHO grading for prediction of recurrence.\n\nMethylation classes identified aggressive tumours among WHO grade 1 and 2 cases and benign behaviour among some grade 2 tumours, outperforming histological grade for progression-free survival.","asOf":"2026-09-17","links":[{"label":"Lancet Oncol 2017","url":"https://doi.org/10.1016/S1470-2045(17)30155-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28314689/"}],"tags":[],"related":[],"cancers":["meningioma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2017,"doi":"10.1016/S1470-2045(17)30155-9","pmid":"28314689","authors":"Sahm F, Schrimpf D, Stichel D, et al.","paperType":"translational","findings":["Six methylation classes with distinct recurrence risk; methylation grouping predicted progression better than WHO grade."],"whatItMeans":"Molecular classification is entering meningioma diagnosis (the 2021 WHO classification incorporates CDKN2A/B deletion and TERT promoter mutation) and is used to select grade 2 patients for or against adjuvant radiotherapy and trials.","caveats":["Retrospective; methylation profiling is not universally available.","Combined integrated grading systems have since refined this approach."],"changedPractice":true,"participants":497},{"id":"paper-bell-annu-rev-biochem","kind":"paper","name":"DNA replication in eukaryotic cells","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 12045100 and published in Annual review of biochemistry; the citing page links this DOI, which is how the record was matched.","summary":"The maintenance of the eukaryotic genome requires precisely coordinated replication of the entire genome each time a cell divides. To achieve this coordination, eukaryotic cells use an ordered series of steps to form several key protein assemblies at origins of replication. Recent studies have identified many of the protein components of these complexes and the time during the cell cycle they assemble at the origin. Interestingly, despite distinct differences in origin structure, the identity and order of assembly of eukaryotic replication factors is highly conserved across all species. This review describes our current understanding of these events and how they are coordinated with cell cycle progression. We focus on bringing together the results from different organisms to provide a coherent model of the events of initiation. We emphasize recent progress in determining the function of the different replication factors once they have been assembled at the origin.\n\nIndexed on Europe PMC as PubMed record 12045100 (DOI 10.1146/annurev.biochem.71.110601.135425). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Annu Rev Biochem 2002","url":"https://doi.org/10.1146/annurev.biochem.71.110601.135425"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/12045100/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/12045100"}],"tags":["europepmc-ingest"],"related":["dna-replication-licensing"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Annual review of biochemistry","year":2002,"doi":"10.1146/annurev.biochem.71.110601.135425","pmid":"12045100","authors":"Bell SP, Dutta A","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-goodnow-nat-rev-drug-discov","kind":"paper","name":"DNA-encoded chemistry: enabling the deeper sampling of chemical space","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 27932801 and published in Nature Reviews Drug Discovery; the citing page links this DOI, which is how the record was matched.","summary":"DNA-encoded chemical library technologies are increasingly being adopted in drug discovery for hit and lead generation. DNA-encoded chemistry enables the exploration of chemical spaces four to five orders of magnitude more deeply than is achievable by traditional high-throughput screening methods. Operation of this technology requires developing a range of capabilities including aqueous synthetic chemistry, building block acquisition, oligonucleotide conjugation, large-scale molecular biological transformations, selection methodologies, PCR, sequencing, sequence data analysis and the analysis of large chemistry spaces. This Review provides an overview of the development and applications of DNA-encoded chemistry, highlighting the challenges and future directions for the use of this technology.\n\nIndexed on Europe PMC as PubMed record 27932801 (DOI 10.1038/nrd.2016.213). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Drug Discov 2017","url":"https://doi.org/10.1038/nrd.2016.213"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27932801/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27932801"}],"tags":["europepmc-ingest"],"related":["high-throughput-screening-libraries"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-drug-discovery"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Drug Discovery","year":2017,"doi":"10.1038/nrd.2016.213","pmid":"27932801","authors":"Goodnow RA, Dumelin CE, Keefe AD","paperType":"review","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-doll-hill-smoking-lung-cancer-bmj-1950","kind":"paper","name":"Doll and Hill 1950: the case-control study that tied smoking to lung cancer","aka":[],"tldr":"Comparing 649 men with lung cancer to matched hospital controls in London, Doll and Hill found that almost none of the cancer patients were non-smokers and that risk rose steeply with the amount smoked.","summary":"Richard Doll and Austin Bradford Hill interviewed patients with lung cancer and matched controls with other diseases in 20 London hospitals between 1948 and 1949. The preliminary report analysed 649 men and 60 women with lung cancer.\n\nOnly 0.3% of male lung cancer patients were non-smokers, compared with 4.2% of controls, and heavy smokers (25 or more cigarettes a day) were far over-represented among cases. The authors concluded that smoking was a factor, and an important factor, in the production of carcinoma of the lung, and set out the case for a prospective study, which became the British Doctors Study in 1951.\n\nAlong with Wynder and Graham's US study the same year, it launched the modern epidemiology of tobacco and eventually the tobacco control policies that have prevented more cancer deaths than any treatment.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1136/bmj.2.4682.739"},{"label":"British Doctors Study preliminary report (1954)","url":"https://doi.org/10.1136/bmj.1.4877.1451"}],"tags":[],"related":["paper-doll-peto-50-year-doctors-bmj-2004","idea-prev-smokefree-generation-evaluation","idea-prev-clean-air-never-smoker-endpoints","lung-cancer-evidence-roadmap","paper-wynder-graham-tobacco-bronchiogenic-carcinoma-jama-1950"],"cancers":["nsclc","sclc","lung-cancer"],"sections":["prevention"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-misinformation","b-incentive-misalignment"],"keyPapers":[],"journals":["bmj"],"dependsOn":[],"notes":[],"journal":"BMJ","year":1950,"doi":"10.1136/bmj.2.4682.739","pmid":"14772469","authors":"Doll R, Hill AB","paperType":"observational","findings":["Non-smokers: 2 of 649 male lung cancer cases (0.3%) vs 27 of 649 controls (4.2%)","Proportion of heavy smokers (25 or more cigarettes a day) was about twice as high among cases as controls","Association was specific to lung cancer, not to other cancers or diseases in the same hospitals","Estimated risk in heavy smokers about 50 times that of non-smokers"],"whatItMeans":"Doll and Hill's 1950 study is where the evidence that smoking causes cancer begins. Everything from cigarette warnings and tax to smoke-free laws and lung screening eligibility descends from this study and the cohort that followed it.","caveats":["Case-control design with hospital controls; recall and selection bias were the main criticisms at the time","Causation was not accepted by many, including Fisher, until the prospective cohort and animal data accumulated","Women were too few for separate analysis","Exposure was self-reported and unverified"],"changedPractice":true,"participants":1465},{"id":"paper-laktionov-prolgolimab-domajor-ejc-2025","kind":"paper","name":"DOMAJOR: prolgolimab with chemotherapy first line in advanced non-squamous lung cancer","aka":[],"tldr":"A 292-patient randomised phase 3 in Russia, China, Hungary and Slovakia in which adding the Russian PD-1 antibody prolgolimab to pemetrexed and platinum roughly halved the risk of death, with the benefit holding in PD-L1-negative tumours.","summary":"292 patients with advanced non-squamous non-small-cell lung cancer were randomised one to one to four cycles of pemetrexed and a platinum drug with either prolgolimab 3 mg/kg every three weeks or placebo, followed by prolgolimab or placebo with pemetrexed until progression or toxicity for up to 36 months. The primary endpoint was overall survival.\n\nAfter a median follow-up of 18 months, median overall survival was not reached in the prolgolimab arm against 14.6 months with placebo (hazard ratio 0.51, 95 per cent confidence interval 0.35 to 0.73, p 0.0001), and the improvement was independent of PD-L1 status. Median progression-free survival by RECIST 1.1 was 7.7 against 5.5 months (hazard ratio 0.65, 95 per cent confidence interval 0.49 to 0.85, p 0.0004). The only adverse events reported in at least 10 per cent of patients and significantly more common with prolgolimab were raised blood creatinine and breathlessness. The trial is registered as NCT03912389.","asOf":"2026-09-25","links":[{"label":"Eur J Cancer 2025","url":"https://doi.org/10.1016/j.ejca.2025.115255"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39879779/"},{"label":"ClinicalTrials.gov NCT03912389","url":"https://clinicaltrials.gov/study/NCT03912389"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":["bcd-100"],"companies":["biocad"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["european-journal-of-cancer"],"dependsOn":[],"notes":[],"journal":"European Journal of Cancer","year":2025,"doi":"10.1016/j.ejca.2025.115255","pmid":"39879779","authors":"Laktionov K, Smolin A, Stroyakovskiy D, et al.","paperType":"rct","findings":["Median overall survival not reached with prolgolimab plus chemotherapy against 14.6 months with chemotherapy alone (hazard ratio 0.51, 95% CI 0.35 to 0.73, p 0.0001).","Median progression-free survival 7.7 against 5.5 months (hazard ratio 0.65, 95% CI 0.49 to 0.85, p 0.0004).","The survival benefit was retained in PD-L1-negative tumours.","Raised blood creatinine and breathlessness were the only adverse events in at least 10 per cent of patients that were significantly more common with prolgolimab."],"whatItMeans":"A domestically developed checkpoint antibody has now produced a positive phase 3 overall-survival result in lung cancer, which is the strongest evidence yet that Russian oncology can supply its own immunotherapy rather than import it. The trial ran in Russia with sites in China, Hungary and Slovakia and has not been reviewed by the European Medicines Agency or the United States Food and Drug Administration.","caveats":["Placebo-controlled against chemotherapy alone, which was no longer the first-line standard in countries where pembrolizumab combinations were available when the trial ran.","Sponsored by the manufacturer; no head-to-head comparison with an established PD-1 antibody."],"participants":292},{"id":"paper-calgb-50303-da-epoch-r-vs-r-chop-jco-2019","kind":"paper","name":"Dose-adjusted EPOCH-R compared with R-CHOP as frontline therapy for diffuse large B-cell lymphoma: clinical outcomes of the phase III intergroup trial Alliance/CALGB 50303","aka":["CALGB 50303","Bartlett 2019"],"tldr":"An intensive infusional chemotherapy regimen that many centres had adopted on single-arm evidence was no better than the standard when finally compared head to head, and was harder to tolerate.","summary":"An intergroup phase 3 trial comparing six cycles of dose-adjusted EPOCH-R with six cycles of R-CHOP as frontline therapy for diffuse large B-cell lymphoma. 524 patients were registered between 2005 and 2013 and 491 were eligible for the final analysis; 74 per cent had stage III or IV disease.\n\nAt a median follow-up of five years, progression-free survival did not differ (hazard ratio 0.93, 95 per cent confidence interval 0.68 to 1.27, p = 0.65) with two-year rates of 78.9 and 75.5 per cent, and neither did overall survival (hazard ratio 1.09, 0.75 to 1.59, p = 0.64) with two-year rates of 86.5 and 85.7 per cent. Grade 3 and 4 adverse events were more common with dose-adjusted EPOCH-R, including febrile neutropenia in 35.0 against 17.7 per cent, mucositis in 8.4 against 2.1 per cent and neuropathy in 18.6 against 3.3 per cent. Five treatment-related deaths occurred in each arm.","asOf":"2026-10-01","links":[{"label":"Journal of Clinical Oncology 2019","url":"https://doi.org/10.1200/JCO.18.01994"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30939090/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30939090"}],"tags":["lymphoma-evidence"],"related":["paper-dunleavy-da-epoch-r-pmbcl-nejm-2013","lymphoma-roadmap"],"cancers":["dlbcl","non-hodgkin-lymphoma"],"sections":["chemotherapy"],"technologies":[],"targets":[],"drugs":["rituximab","etoposide","cyclophosphamide","doxorubicin","vincristine","prednisone"],"companies":[],"institutions":["nci"],"pathways":[],"terms":["r-chop","lymphoma-tx-regimen-alphabet","double-hit-lymphoma"],"trials":["calgb-50303"],"people":[],"bottlenecks":["b-negative-results","b-trial-design"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2019,"doi":"10.1200/JCO.18.01994","pmid":"30939090","authors":"Bartlett NL, Wilson WH, Jung SH, et al.","paperType":"rct","findings":["Progression-free survival did not differ between dose-adjusted EPOCH-R and R-CHOP (hazard ratio 0.93, 95 per cent confidence interval 0.68 to 1.27, p = 0.65).","Two-year progression-free survival was 78.9 per cent for dose-adjusted EPOCH-R and 75.5 per cent for R-CHOP.","Overall survival did not differ (hazard ratio 1.09, 0.75 to 1.59, p = 0.64).","Febrile neutropenia occurred in 35.0 against 17.7 per cent, mucositis in 8.4 against 2.1 per cent and neuropathy in 18.6 against 3.3 per cent.","Five treatment-related deaths (2.1 per cent) occurred in each arm."],"whatItMeans":"R-CHOP remains the standard first-line regimen for diffuse large B-cell lymphoma. The trial is also the clearest lesson in the disease about adopting a regimen on single-arm data: dose-adjusted EPOCH-R had been used widely for a decade before this comparison existed.","caveats":["The authors note that R-CHOP results were better than historical controls, which suggests patient selection and limits generalisability to specific high-risk subgroups.","Not powered for subgroups such as double-hit lymphoma, where dose-adjusted EPOCH-R is still used on non-randomised evidence.","Primary mediastinal B-cell lymphoma and HIV-associated lymphoma, where dose-adjusted EPOCH-R has its strongest evidence, were studied separately."],"changedPractice":true,"participants":491},{"id":"paper-dunleavy-da-epoch-r-pmbcl-nejm-2013","kind":"paper","name":"Dose-adjusted EPOCH-rituximab therapy in primary mediastinal B-cell lymphoma","aka":[],"tldr":"Infusional dose-adjusted EPOCH with rituximab cured almost every patient with primary mediastinal B-cell lymphoma without any radiotherapy, sparing young patients the heart and breast cancer risks of chest irradiation.","summary":"Prospective single-centre phase 2 study of 51 patients with untreated primary mediastinal B-cell lymphoma treated with dose-adjusted EPOCH-rituximab for six to eight cycles without radiotherapy, with a retrospective validation cohort of 16 patients at Stanford.\n\nAt a median follow-up of 5 years, event-free survival was 93 percent and overall survival 97 percent; only two patients received radiotherapy, and PET scans after treatment had a low positive predictive value.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2013","url":"https://doi.org/10.1056/NEJMoa1214561"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23574119/"}],"tags":[],"related":[],"cancers":["primary-mediastinal-b-cell-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["rituximab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2013,"doi":"10.1056/NEJMoa1214561","pmid":"23574119","authors":"Dunleavy K, Pittaluga S, Maeda LS, et al.","paperType":"observational","findings":["Five-year event-free survival 93 percent; overall survival 97 percent.","Radiotherapy avoided in 96 percent of patients."],"whatItMeans":"Dose-adjusted EPOCH-R without radiotherapy became a standard for primary mediastinal B-cell lymphoma, particularly in the United States, and the IELSG37 trial later confirmed radiotherapy can be omitted after a negative PET.","caveats":["Single-arm study from one centre with a small validation cohort.","Six-day infusional regimen is demanding; R-CHOP with PET-guided radiotherapy is an alternative."],"changedPractice":true,"participants":51},{"id":"paper-iacobuzio-donahue-dpc4-failure-pattern-autopsy-jco-2009","kind":"paper","name":"DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer","aka":[],"tldr":"Autopsies of 76 people who died of pancreatic cancer showed two ways the disease kills: 70% died with cancer spread through the body and 30% with a locally destructive tumour, and whether the SMAD4 (DPC4) gene was intact predicted which.","summary":"Rapid autopsies were performed on 76 patients with documented pancreatic cancer; the histology of end-stage disease was correlated with stage at diagnosis, pattern of failure (locally destructive versus metastatic) and the status of KRAS2, TP53 and DPC4. At autopsy 30% had died with locally destructive cancer and 70% with widespread metastases; the divergent patterns were unrelated to clinical stage at presentation, treatment history or histopathology. Dpc4 immunolabelling status of carcinoma tissue, a sensitive marker of DPC4 genetic status, was highly correlated with widespread metastasis but not with locally destructive tumours (P = .007).","asOf":"2026-09-24","links":[{"label":"Iacobuzio-Donahue et al., J Clin Oncol 2009: DPC4 (SMAD4) status and pattern of failure in 76 rapid autopsies","url":"https://doi.org/10.1200/JCO.2008.17.7188"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19273710/"}],"tags":[],"related":[],"cancers":["pancreatic","metastatic-pdac","locally-advanced-pdac"],"sections":[],"technologies":[],"targets":["smad4","kras","tp53"],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":["tgf-beta","metastatic-cascade"],"terms":["ihc"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2009,"doi":"10.1200/JCO.2008.17.7188","pmid":"19273710","authors":"Iacobuzio-Donahue CA, Fu B, Yachida S, et al.","paperType":"observational","findings":["30% died with locally destructive disease, 70% with widespread metastases.","Dpc4 (SMAD4) loss correlated with the metastatic pattern (P = .007) and intact Dpc4 with local destruction."],"whatItMeans":"SMAD4 status is the clearest published molecular marker of how pancreatic cancer will behave: intact argues for local control, lost argues for systemic therapy.","caveats":["Autopsy series at one institution; treatment predates modern combination chemotherapy.","SMAD4 was not prognostic for survival after resection in later work (Qian 2018)."],"changedPractice":false,"participants":76},{"id":"paper-henricks-lancet-oncol","kind":"paper","name":"DPYD genotype-guided dose individualisation of fluoropyrimidine therapy in patients with cancer: a prospective safety analysis","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 30348537 and published in The Lancet Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background: Fluoropyrimidine treatment can result in severe toxicity in up to 30% of patients and is often the result of reduced activity of the key metabolic enzyme dihydropyrimidine dehydrogenase (DPD), mostly caused by genetic variants in the gene encoding DPD (DPYD). We assessed the effect of prospective screening for the four most relevant DPYD variants (DPYD*2A [rs3918290, c.1905+1G>A, IVS14+1G>A], c.2846A>T [rs67376798, D949V], c.1679T>G [rs55886062, DPYD*13, I560S], and c.1236G>A [rs56038477, E412E, in haplotype B3]) on patient safety and subsequent DPYD genotype-guided dose individualisation in daily clinical care.\n\nMethods: In this prospective, multicentre, safety analysis in 17 hospitals in the Netherlands, the study population consisted of adult patients (≥18 years) with cancer who were intended to start on a fluoropyrimidine-based anticancer therapy (capecitabine or fluorouracil as single agent or in combination with other chemotherapeutic agents or radiotherapy). Patients with all tumour types for which fluoropyrimidine-based therapy was considered in their best interest were eligible. We did prospective genotyping for DPYD*2A, c.2846A>T, c.1679T>G, and c.1236G>A. Heterozygous DPYD variant allele carriers received an initial dose reduction of 25% (c.2846A>T and c.1236G>A) or 50% (DPYD*2A and c.1679T>G), and DPYD wild-type patients were treated according to the current standard of care. The primary endpoint of the study was the frequency of severe (National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 grade ≥3) overall fluoropyrimidine-related toxicity across the entire treatment duration. We compared toxicity incidence between DPYD variant allele carriers and DPYD wild-type patients on an intention-to-treat basis, and relative risks (RRs) for severe toxicity were compared between the current study and a historical cohort of DPYD variant allele carriers treated with full dose fluoropyrimidine-based therapy (derived from a previously published meta-analysis). This trial is registered with ClinicalTrials.gov, number NCT02324452, and is complete.\n\nFindings: Between April 30, 2015, and Dec 21, 2017, we enrolled 1181 patients. 78 patients were considered non-evaluable, because they were retrospectively identified as not meeting inclusion criteria, did not start fluoropyrimidine-based treatment, or were homozygous or compound heterozygous DPYD variant allele carriers. Of 1103 evaluable patients, 85 (8%) were heterozygous DPYD variant allele carriers, and 1018 (92%) were DPYD wild-type patients. Overall, fluoropyrimidine-related severe toxicity was higher in DPYD variant carriers (33 [39%] of 85 patients) than in wild-type patients (231 [23%] of 1018 patients; p=0·0013). The RR for severe fluoropyrimidine-related toxicity was 1·31 (95% CI 0·63-2·73) for genotype-guided dosing compared with 2·87 (2·14-3·86) in the historical cohort for DPYD*2A carriers, no toxicity compared with 4·30 (2·10-8·80) in c.1679T>G carriers, 2·00 (1·19-3·34) compared with 3·11 (2·25-4·28) for c.2846A>T carriers, and 1·69 (1·18-2·42) compared with 1·72 (1·22-2·42) for c.1236G>A carriers.\n\nInterpretation: Prospective DPYD genotyping was feasible in routine clinical practice, and DPYD genotype-based dose reductions improved patient safety of fluoropyrimidine treatment. For DPYD*2A and c.1679T>G carriers, a 50% initial dose reduction was adequate. For c.1236G>A and c.2846A>T carriers, a larger dose reduction of 50% (instead of 25%) requires investigation. Since fluoropyrimidines are among the most commonly used anticancer agents, these findings suggest that implementation of DPYD genotype-guided individualised dosing should be a new standard of care.\n\nFunding: Dutch Cancer Society.\n\nIndexed on Europe PMC as PubMed record 30348537 (DOI 10.1016/s1470-2045(18)30686-7). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2018","url":"https://doi.org/10.1016/s1470-2045(18)30686-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30348537/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30348537"}],"tags":["europepmc-ingest"],"related":["dpyd-genotyping"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2018,"doi":"10.1016/s1470-2045(18)30686-7","pmid":"30348537","authors":"Henricks LM, Lunenburg CATC, de Man FM, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-dreamseq-jco-2023","kind":"paper","name":"DREAMseq (ECOG-ACRIN EA6134): sequencing dabrafenib-trametinib and nivolumab-ipilimumab in BRAF-mutant metastatic melanoma","aka":[],"tldr":"Starting with nivolumab plus ipilimumab and switching to BRAF-MEK inhibitors at progression gave 20 percentage points better two-year survival than the reverse order in BRAF-mutant advanced melanoma, settling the question of which to use first.","summary":"Phase 3 trial of 265 patients with treatment-naive BRAF V600-mutant metastatic melanoma randomised to nivolumab-ipilimumab followed by dabrafenib-trametinib at progression, or the reverse sequence.\n\nTwo-year overall survival was 71.8 percent with immunotherapy first against 51.5 percent with targeted therapy first; the trial was stopped early for this difference, and responses to immunotherapy were more durable while responses to targeted therapy after immunotherapy were preserved.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2023","url":"https://doi.org/10.1200/JCO.22.01763"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36166727/"}],"tags":[],"related":[],"cancers":["advanced-melanoma","braf-v600-melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":["dabrafenib","ipilimumab","nivolumab","trametinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["dreamseq"],"people":["michael-atkins"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2023,"doi":"10.1200/JCO.22.01763","pmid":"36166727","authors":"Atkins MB, Lee SJ, Chmielowski B, et al.","paperType":"rct","findings":["Two-year overall survival 71.8 percent (immunotherapy first) vs 51.5 percent (targeted therapy first).","Median progression-free survival after crossover favoured targeted therapy given second."],"whatItMeans":"Immunotherapy first is the standard for BRAF-mutant advanced melanoma in patients who can wait for a response; targeted therapy is reserved for rapid control or after immunotherapy.","caveats":["Open-label and stopped early.","Does not address newer first-line options such as nivolumab-relatlimab."],"changedPractice":true,"participants":265},{"id":"paper-santosh-kesari-nat-commun-2026","kind":"paper","name":"Drug and single-cell gene expression integration identifies sensitive and resistant glioblastoma cell populations","aka":[],"tldr":"Paper by Santosh Kesari indexed on Europe PMC as PubMed record 41501023, in Nature Communications (2026), one of the most cited records naming an author with this name at Asthra Health.","summary":"Glioblastoma (GBM) remains the most common and lethal adult malignant primary brain cancer with few treatment options. A significant issue hindering GBM therapeutic development is intratumor heterogeneity and plasticity. GBM tumors contain neoplastic cells within a fluid spectrum of diverse transcriptional states. Identifying effective therapeutics requires a platform that predicts the differential sensitivity and resistance of these states to various treatments. Here, we develop scFOCAL (Single-Cell Framework for -Omics Connectivity and Analysis via L1000), to quantify the cellular drug sensitivity and resistance landscape. Using single-cell RNA sequencing of newly diagnosed and recurrent GBM tumors, we identify compounds from the LINCS L1000 database with transcriptional response signatures selectively discordant with distinct GBM cell states, and leverage this capability to predict combination synergy. We validate the significance of these findings in vitro, ex vivo, and in vivo, and identify a combination of an OLIG2 inhibitor and Depatux-M for the treatment of GBM. Our studies suggest that scFOCAL identifies cell states that are sensitive and resistant to targeted therapies in GBM using a measure of cell and drug connectivity, which can be applied to identify new synergistic combinations.\n\nIndexed on Europe PMC as PubMed record 41501023 (DOI 10.1038/s41467-025-67783-5). Its author list gives \"Kesari S\" with the affiliation \"Asthra Health and Lundquist Institute, Santa Monica, CA, USA\", which names Asthra Health; that is how the record was matched to Santosh Kesari, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Commun 2026","url":"https://doi.org/10.1038/s41467-025-67783-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41501023/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41501023"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["santosh-kesari"],"bottlenecks":[],"keyPapers":[],"journals":["nature-communications"],"dependsOn":[],"notes":[],"journal":"Nature Communications","year":2026,"doi":"10.1038/s41467-025-67783-5","pmid":"41501023","authors":"Suter RK, Jermakowicz AM, Veeramachaneni R, et al.","paperType":"basic","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Santosh Kesari at Asthra Health, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-begley-nature","kind":"paper","name":"Drug development: Raise standards for preclinical cancer research","aka":[],"tldr":"Paper cited by two bottleneck pages, indexed on Europe PMC as PubMed record 22460880 and published in Nature; the citing pages link this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 22460880 (DOI 10.1038/483531a). Matched by DOI alone: two bottleneck pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2012","url":"https://doi.org/10.1038/483531a"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22460880/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/22460880"}],"tags":["europepmc-ingest"],"related":["b-preclinical-models","b-reproducibility"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2012,"doi":"10.1038/483531a","pmid":"22460880","authors":"Begley CG, Ellis LM","paperType":"observational","findings":[],"whatItMeans":"Two bottleneck pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-powderly-fenbendazole-ivermectin-liver-injury-2026","kind":"paper","name":"Drug-induced liver injury following co-ingestion of veterinary fenbendazole and ivermectin for prostate cancer: a case report","aka":[],"tldr":"A 65-year-old man with prostate cancer took veterinary fenbendazole and ivermectin on alternate days for three months on the advice of online support groups and developed severe liver injury, which cleared six weeks after he stopped.","summary":"The patient presented with two weeks of fatigue, jaundice and abdominal pain after a three-month regimen of alternating veterinary-grade fenbendazole and ivermectin at 'one squirt' a day, estimated at 0.18 mg/kg of ivermectin and 0.98 mg/kg of fenbendazole (Powderly case report 2026). Alanine aminotransferase was 1764 U/L, aspartate aminotransferase 1132 U/L and bilirubin 12.9 mg/dL, viral, autoimmune and biliary causes were excluded, transaminases fell 58 percent within nine days of stopping and normalised within six weeks, and a RUCAM score of 9 rated the causal link 'highly probable' (Powderly case report 2026).","asOf":"2026-09-24","links":[{"label":"Powderly case report 2026","url":"https://doi.org/10.7759/cureus.108896"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42299164/"}],"tags":[],"related":[],"cancers":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":["ivermectin","fenbendazole"],"companies":[],"institutions":[],"pathways":[],"terms":["hepatotoxicity","off-label"],"trials":[],"people":[],"bottlenecks":["b-misinformation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo agent (Claude Fable 5.1)","editedOn":"2026-09-24","note":"Written from cached ClinicalTrials.gov v2, Europe PMC, DailyMed, Drugs@FDA and WHO eEML responses; no figure appears without its source link."},"journal":"Cureus","year":2026,"doi":"10.7759/cureus.108896","pmid":"42299164","authors":"Powderly GE, Hassevoort K, Loy M, Balonier J, Sievers C.","paperType":"observational","findings":["Hepatocellular liver injury with bilirubin 12.9 mg/dL after three months of veterinary fenbendazole and ivermectin; RUCAM 9, highly probable.","Resolved within six weeks of stopping both agents."],"whatItMeans":"Veterinary paste is dosed for animals by weight, and 'one squirt' is not a human dose. Liver injury of this severity can be fatal and this patient was fortunate to present in time.","caveats":["Single case; the relative contribution of the two drugs cannot be separated."],"changedPractice":false,"participants":1},{"id":"paper-hangauer-nature","kind":"paper","name":"Drug-tolerant persister cancer cells are vulnerable to GPX4 inhibition","aka":[],"tldr":"Paper cited by one idea page, indexed on Europe PMC as PubMed record 29088702 and published in Nature; the citing page links this DOI, which is how the record was matched.","summary":"Acquired drug resistance prevents cancer therapies from achieving stable and complete responses. Emerging evidence implicates a key role for non-mutational drug resistance mechanisms underlying the survival of residual cancer 'persister' cells. The persister cell pool constitutes a reservoir from which drug-resistant tumours may emerge. Targeting persister cells therefore presents a therapeutic opportunity to impede tumour relapse. We previously found that cancer cells in a high mesenchymal therapy-resistant cell state are dependent on the lipid hydroperoxidase GPX4 for survival. Here we show that a similar therapy-resistant cell state underlies the behaviour of persister cells derived from a wide range of cancers and drug treatments. Consequently, we demonstrate that persister cells acquire a dependency on GPX4. Loss of GPX4 function results in selective persister cell ferroptotic death in vitro and prevents tumour relapse in mice. These findings suggest that targeting of GPX4 may represent a therapeutic strategy to prevent acquired drug resistance.\n\nIndexed on Europe PMC as PubMed record 29088702 (DOI 10.1038/nature24297). Matched by DOI alone: one idea page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2017","url":"https://doi.org/10.1038/nature24297"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29088702/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29088702"}],"tags":["europepmc-ingest"],"related":["idea-ferroptosis-persisters"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2017,"doi":"10.1038/nature24297","pmid":"29088702","authors":"Hangauer MJ, Viswanathan VS, Ryan MJ, et al.","paperType":"basic","findings":[],"whatItMeans":"One idea page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-dang-nat-rev-cancer","kind":"paper","name":"Drugging the 'undruggable' cancer targets","aka":[],"tldr":"Paper cited by one bottleneck page and 24 idea pages, indexed on Europe PMC as PubMed record 28643779 and published in Nature Reviews Cancer; the citing pages link this DOI, which is how the record was matched.","summary":"The term 'undruggable' was coined to describe proteins that could not be targeted pharmacologically. However, progress is being made to 'drug' many of these targets, and therefore more appropriate terms might be 'difficult to drug' or 'yet to be drugged'. Many desirable targets in cancer fall into this category, including the RAS and MYC oncogenes, and pharmacologically targeting these intractable proteins is now a key challenge in cancer research that requires innovation and the development of new technologies. In this Viewpoint article, we asked four scientists working in this field for their opinions on the most crucial advances, as well as the challenges and what the future holds for this important area of research.\n\nIndexed on Europe PMC as PubMed record 28643779 (DOI 10.1038/nrc.2017.36). Matched by DOI alone: one bottleneck page and 24 idea pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Cancer 2017","url":"https://doi.org/10.1038/nrc.2017.36"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28643779/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28643779"}],"tags":["europepmc-ingest"],"related":["b-undruggable-targets","idea-bio1-undruggable-market-commitment","idea-bio1-ai-binders-disordered-regions","idea-bio1-covalent-ligandability-atlas","idea-bio1-pmhc-bispecifics-public-drivers","idea-bio1-paralog-synthetic-lethality","idea-bio1-condensate-disruptors","idea-bio1-pan-ras-covalent-g12d","idea-bio1-mutant-p53-degrader","idea-bio1-fusion-tf-degraders","idea-bio1-arv7-degrader","idea-bio1-lytac-surface-degraders","idea-bio1-p53-mutant-reactivator-expansion","idea-bio1-tumour-restricted-e3-atlas","idea-bio1-mrna-intrabodies","idea-bio1-macrocycle-ppi-campaign","idea-bio1-myc-max-molecular-glue","idea-bio1-omomyc-mrna","idea-bio1-glue-degrader-atlas","idea-bio1-rna-targeting-small-molecules","idea-bio1-translation-dependency-myc","idea-bio1-epigenetic-silencing-in-vivo","idea-bio1-pp2a-activators","idea-bio1-antibody-degrader-conjugates","idea-bio1-wrn-msi-programme"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Cancer","year":2017,"doi":"10.1038/nrc.2017.36","pmid":"28643779","authors":"Dang CV, Reddy EP, Shokat KM, et al.","paperType":"review","findings":[],"whatItMeans":"One bottleneck page and 24 idea pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-ogitani-clin-cancer-res","kind":"paper","name":"DS-8201a, A Novel HER2-Targeting ADC with a Novel DNA Topoisomerase I Inhibitor, Demonstrates a Promising Antitumor Efficacy with Differentiation from T-DM1","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 27026201 and published in Clinical Cancer Research; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: An anti-HER2 antibody-drug conjugate with a novel topoisomerase I inhibitor, DS-8201a, was generated as a new antitumor drug candidate, and its preclinical pharmacologic profile was assessed.\n\nExperimental design: In vitro and in vivo pharmacologic activities of DS-8201a were evaluated and compared with T-DM1 in several HER2-positive cell lines and patient-derived xenograft (PDX) models. The mechanism of action for the efficacy was also evaluated. Pharmacokinetics in cynomolgus monkeys and the safety profiles in rats and cynomolgus monkeys were assessed.\n\nResults: DS-8201a exhibited a HER2 expression-dependent cell growth-inhibitory activity and induced tumor regression with a single dosing at more than 1 mg/kg in a HER2-positive gastric cancer NCI-N87 model. Binding activity to HER2 and ADCC activity of DS-8201a were comparable with unconjugated anti-HER2 antibody. DS-8201a also showed an inhibitory activity to Akt phosphorylation. DS-8201a induced phosphorylation of Chk1 and Histone H2A.X, the markers of DNA damage. Pharmacokinetics and safety profiles of DS-8201a were favorable and the highest non-severely toxic dose was 30 mg/kg in cynomolgus monkeys, supporting DS-8201a as being well tolerated in humans. DS-8201a was effective in a T-DM1-insensitive PDX model with high HER2 expression. DS-8201a, but not T-DM1, demonstrated antitumor efficacy against several breast cancer PDX models with low HER2 expression.\n\nConclusions: DS-8201a exhibited a potent antitumor activity in a broad selection of HER2-positive models and favorable pharmacokinetics and safety profiles. The results demonstrate that DS-8201a will be a valuable therapy with a great potential to respond to T-DM1-insensitive HER2-positive cancers and low HER2-expressing cancers. Clin Cancer Res; 22(20); 5097-108. ©2016 AACR.\n\nIndexed on Europe PMC as PubMed record 27026201 (DOI 10.1158/1078-0432.ccr-15-2822). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Clin Cancer Res 2016","url":"https://doi.org/10.1158/1078-0432.ccr-15-2822"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27026201/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27026201"}],"tags":["europepmc-ingest"],"related":["ggfg"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2016,"doi":"10.1158/1078-0432.ccr-15-2822","pmid":"27026201","authors":"Ogitani Y, Aida T, Hagihara K, et al.","paperType":"basic","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nct05724563-nat-commun-2025","kind":"paper","name":"Dual TIGIT and PD-1 blockade with domvanalimab plus zimberelimab in hepatocellular carcinoma refractory to anti-PD-1 therapies: the phase 2 LIVERTI trial","aka":[],"tldr":"Published report from the trial registered as NCT05724563, in Nature Communications (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"T cell immunoglobulin and ITIM domain (TIGIT) is an inhibitory receptor expressed on lymphocytes and NK cells, and is a candidate compensatory immune checkpoint that may mediate anti-PD-1/L1 resistance in hepatocellular carcinoma (HCC). We conducted the phase 2 LIVERTI trial testing domvanalimab, a monoclonal Fc-silent anti-TIGIT antibody, plus zimberelimab, an anti-PD-1 antibody, in immunotherapy refractory HCC. Here, we report an analysis of the primary endpoint, the confirmed overall response rate (ORR). Secondary endpoints included rates of adverse events, progression-free survival (PFS), 6-month PFS survival, overall survival, and duration of response, of which the latter two endpoints were excluded from this analysis due to the immaturity of long-term survival data. Among the 29 patients enrolled, the confirmed ORR was 17.2% (95% CI 5.8%-35.8%) and the median PFS was 4.4 months (95% CI, 4.1-4.6 months). Treatment-related adverse events occurred in 16 patients (55.2%). Analysis of circulating tumor DNA (ctDNA) demonstrated that ctDNA dynamics may serve as pharmacodynamic markers of response to domvanalimab plus zimberelimab. Despite the primary endpoint failing to meet the protocol-specified threshold, these results indicate that targeting TIGIT in anti-PD-1/L1 therapy refractory HCC is well-tolerated, associated with anti-tumor effects, and may be guided by ctDNA assessment. ClinicalTrials.gov registration: NCT05724563.\n\nIndexed on Europe PMC as PubMed record 40592848 (DOI 10.1038/s41467-025-60757-7). Its abstract cites the registry id NCT05724563, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Nat Commun 2025","url":"https://doi.org/10.1038/s41467-025-60757-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40592848/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40592848"},{"label":"ClinicalTrials.gov NCT05724563","url":"https://clinicaltrials.gov/study/NCT05724563"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05724563"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-communications"],"dependsOn":[],"notes":[],"journal":"Nature Communications","year":2025,"doi":"10.1038/s41467-025-60757-7","pmid":"40592848","authors":"Hsiehchen D, Kainthla R, Kline H, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05724563 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-mccollough-radiology","kind":"paper","name":"Dual- and Multi-Energy CT: Principles, Technical Approaches, and Clinical Applications","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 26302388 and published in Radiology; the citing page links this DOI, which is how the record was matched.","summary":"In x-ray computed tomography (CT), materials having different elemental compositions can be represented by identical pixel values on a CT image (ie, CT numbers), depending on the mass density of the material. Thus, the differentiation and classification of different tissue types and contrast agents can be extremely challenging. In dual-energy CT, an additional attenuation measurement is obtained with a second x-ray spectrum (ie, a second \"energy\"), allowing the differentiation of multiple materials. Alternatively, this allows quantification of the mass density of two or three materials in a mixture with known elemental composition. Recent advances in the use of energy-resolving, photon-counting detectors for CT imaging suggest the ability to acquire data in multiple energy bins, which is expected to further improve the signal-to-noise ratio for material-specific imaging. In this review, the underlying motivation and physical principles of dual- or multi-energy CT are reviewed and each of the current technical approaches is described. In addition, current and evolving clinical applications are introduced.\n\nIndexed on Europe PMC as PubMed record 26302388 (DOI 10.1148/radiol.2015142631). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Radiology 2015","url":"https://doi.org/10.1148/radiol.2015142631"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26302388/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26302388"}],"tags":["europepmc-ingest"],"related":["dual-energy-spectral-ct"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["radiology"],"dependsOn":[],"notes":[],"journal":"Radiology","year":2015,"doi":"10.1148/radiol.2015142631","pmid":"26302388","authors":"McCollough CH, Leng S, Yu L, et al.","paperType":"review","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-sartore-bianchi-heracles-trastuzumab-lapatinib-lancet-oncol-2016","kind":"paper","name":"Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES)","aka":[],"tldr":"A trial designed from mouse avatars: screening 914 patients found 48 with HER2-amplified bowel cancer, and blocking HER2 two ways shrank tumours in 30 percent of the 27 who were treated.","summary":"Sartore-Bianchi, Trusolino, Martino and colleagues ran HERACLES as a proof-of-concept, multicentre, open-label phase 2 trial at four Italian academic cancer centres, after finding that dual HER2 blockade inhibited tumour growth in patient-derived xenografts of HER2-amplified metastatic colorectal cancer. Adults with KRAS exon 2 wild-type, HER2-positive metastatic colorectal cancer refractory to standard of care including cetuximab or panitumumab received intravenous trastuzumab and oral lapatinib 1,000 mg daily until progression. HER2 positivity used colorectal-specific immunohistochemistry and fluorescence in-situ hybridisation criteria the group had validated. The primary endpoint was objective response by independent central review.\n\nScreening 914 patients identified 48 (5 percent) with HER2-positive tumours, of whom 27 were eligible and treated.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2016","url":"https://doi.org/10.1016/S1470-2045(16)00150-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27108243/"}],"tags":["colorectal-evidence"],"related":["paper-tcga-colorectal-comprehensive-characterization-nature-2012","paper-strickler-mountaineer-tucatinib-trastuzumab-lancet-oncol-2023","her2-ish-amplified"],"cancers":["colorectal","her2-amplified-colorectal"],"sections":["targeted-therapy"],"technologies":["monoclonal-antibody","kinase-inhibitors"],"targets":["her2","kras"],"drugs":["trastuzumab","lapatinib"],"companies":[],"institutions":["niguarda-cancer-center","candiolo"],"pathways":["rtk-activation"],"terms":[],"trials":["heracles"],"people":["salvatore-siena","alberto-bardelli","andrea-sartore-bianchi"],"bottlenecks":["b-rare-cancers","b-trial-enrolment","b-preclinical-models"],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2016,"doi":"10.1016/S1470-2045(16)00150-9","pmid":"27108243","authors":"Sartore-Bianchi A, Trusolino L, Martino C, et al.","paperType":"rct","findings":["914 KRAS exon 2 wild-type patients screened; 48 (5 percent) HER2-positive; 27 eligible and treated.","Objective response in 8 of 27 (30 percent, 95 percent CI 14 to 50): one complete and seven partial responses; 12 (44 percent) had stable disease.","Median follow-up 94 weeks (IQR 51 to 127).","Grade 3 adverse events in 6 of 27 (22 percent); no grade 4 or 5 events and no drug-related serious adverse events."],"whatItMeans":"The first demonstration that HER2 is actionable in colorectal cancer, and the trial that defined the colorectal-specific HER2 scoring criteria every later trial has used.","caveats":["Twenty-seven patients in a single-arm phase 2 at four centres.","Screening 914 patients to treat 27 shows the practical problem: the biomarker is rare and testing has to be universal for the trial to be feasible.","Trastuzumab with lapatinib has since been superseded by tucatinib with trastuzumab and by trastuzumab deruxtecan."],"changedPractice":true,"participants":27},{"id":"paper-duo-e-jco-2023","kind":"paper","name":"DUO-E: durvalumab with carboplatin-paclitaxel and maintenance durvalumab with or without olaparib in advanced endometrial cancer","aka":[],"tldr":"Adding durvalumab to first-line chemotherapy delayed progression in advanced endometrial cancer, and adding the PARP inhibitor olaparib to durvalumab maintenance helped further in mismatch repair-proficient tumours.","summary":"Phase 3 trial of 718 patients with newly diagnosed advanced or recurrent endometrial cancer randomised to carboplatin-paclitaxel alone, with durvalumab followed by durvalumab maintenance, or with durvalumab followed by durvalumab plus olaparib maintenance.\n\nProgression-free survival hazard ratios were 0.71 for durvalumab and 0.55 for durvalumab plus olaparib versus control; in mismatch repair-deficient disease both immunotherapy arms performed similarly (hazard ratio about 0.42), whereas olaparib added benefit in proficient disease (0.57 versus 0.77).","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2024","url":"https://doi.org/10.1200/JCO.23.02132"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37864337/"}],"tags":[],"related":[],"cancers":["advanced-recurrent-endometrial-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["carboplatin","durvalumab","olaparib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["duo-e"],"people":["shannon-westin"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2024,"doi":"10.1200/JCO.23.02132","pmid":"37864337","authors":"Westin SN, Moore K, Chon HS, et al.","paperType":"rct","findings":["Progression-free survival hazard ratio 0.71 (durvalumab) and 0.55 (durvalumab plus olaparib).","Mismatch repair-proficient: hazard ratio 0.77 vs 0.57 with olaparib added."],"whatItMeans":"Durvalumab-based chemo-immunotherapy is a third first-line option with RUBY and NRG-GY018, and durvalumab plus olaparib maintenance is approved for mismatch repair-proficient disease in some regions.","caveats":["The contribution of olaparib in proficient disease may be concentrated in p53-abnormal tumours; overall survival immature.","Anaemia and neutropenia increased with olaparib."],"changedPractice":true,"participants":718},{"id":"paper-nct03157128-j-clin-oncol-2024-update","kind":"paper","name":"Durability of Response With Selpercatinib in Patients With RET -Activated Thyroid Cancer: Long-Term Safety and Efficacy From LIBRETTO-001","aka":[],"tldr":"Later report from the RET Fusion-Positive Solid Tumors trial registered as NCT03157128, in Journal of Clinical Oncology (2024); its title describes an updated or longer-term analysis.","summary":"Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. LIBRETTO-001 is a registrational phase I/II, single-arm, open-label study of selpercatinib in patients with RET (REarranged during Transfection)-activated cancers (ClinicalTrials.gov identifier: NCT03157128). We present long-term safety and efficacy from LIBRETTO-001 in patients with RET -mutant medullary thyroid cancer (MTC; n = 324) and RET fusion-positive thyroid cancer encompassing different histological subtypes (TC; n = 66). At the data cutoff of January 2023, the objective response rate was 82.5% among patients with cabozantinib/vandetanib-naïve MTC and 95.8% among patients with treatment-naïve TC. At a median follow-up time of 42.4 and 44.0 months in patients with cabozantinib/vandetanib-naïve and pretreated MTC, the median progression-free survival (PFS) was not reached and 41.4 months, respectively. At a median follow-up time of 24.9 and 30.4 months in patients with treatment-naïve and pretreated TC, the median PFS was not reached and 27.4 months, respectively. Three-year PFS rates were 75.2% and 87.3% among patients with cabozantinib/vandetanib-naïve MTC and treatment-naïve TC, respectively. Median PFS was similar to median duration of response for each patient group. The safety profile of selpercatinib was consistent with previous reports. With an additional follow-up of 37 months and 228 more patients from the last disclosure, selpercatinib continued to provide durable and robust responses in treatment-naïve and previously treated patients with RET -mutant MTC and RET fusion-positive TC.\n\nIndexed on Europe PMC as PubMed record 39094065 (DOI 10.1200/jco.23.02503). Its abstract cites the registry id NCT03157128, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2024","url":"https://doi.org/10.1200/jco.23.02503"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39094065/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39094065"},{"label":"ClinicalTrials.gov NCT03157128","url":"https://clinicaltrials.gov/study/NCT03157128"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct03157128"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2024,"doi":"10.1200/jco.23.02503","pmid":"39094065","authors":"Wirth LJ, Brose MS, Subbiah V, et al.","paperType":"observational","findings":[],"whatItMeans":"A second publication from the RET Fusion-Positive Solid Tumors trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-ivosidenib-idh1-dinardo-nejm-2018","kind":"paper","name":"Durable remissions with ivosidenib in IDH1-mutated relapsed or refractory acute myeloid leukaemia","aka":[],"tldr":"The oral IDH1 inhibitor ivosidenib put about a third of patients with relapsed or refractory IDH1-mutated acute myeloid leukaemia into remission, with some clearing the mutation altogether, leading to its approval.","summary":"Phase 1 dose-escalation and expansion study of 258 patients with IDH1-mutated advanced haematological cancers, including 179 with relapsed or refractory AML treated at 500 mg daily.\n\nIn the primary efficacy population the rate of complete remission or complete remission with partial haematological recovery was 30.4 percent, median duration of response 8.2 months, and 21 percent of responders had no detectable IDH1 mutation. Differentiation syndrome occurred in about one in ten.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2018","url":"https://doi.org/10.1056/NEJMoa1716984"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29860938/"}],"tags":[],"related":[],"cancers":["aml-idh"],"sections":[],"technologies":[],"targets":[],"drugs":["ivosidenib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2018,"doi":"10.1056/NEJMoa1716984","pmid":"29860938","authors":"DiNardo CD, Stein EM, de Botton S, et al.","paperType":"observational","findings":["Complete remission or complete remission with partial haematological recovery in 30.4 percent; overall response 41.6 percent.","Median overall survival 8.8 months in relapsed or refractory AML."],"whatItMeans":"IDH1 testing at diagnosis and relapse now directs patients to a targeted oral drug; ivosidenib went on to be combined with azacitidine in newly diagnosed disease (AGILE).","caveats":["Single-arm study; responses were partial for most and relapse common.","Differentiation syndrome and QT prolongation need monitoring."],"changedPractice":true,"participants":258},{"id":"paper-idea-duration-adjuvant-stage-iii-colon-nejm-2018","kind":"paper","name":"Duration of adjuvant chemotherapy for stage III colon cancer (the IDEA collaboration)","aka":[],"tldr":"Six trials pooled 12,834 patients to ask whether three months of chemotherapy is as good as six. For lower-risk tumours treated with CAPOX it is, and the nerve damage is far less.","summary":"Grothey, Sobrero, Shields and colleagues performed a prospective, preplanned, pooled analysis of six randomised phase 3 trials conducted concurrently to evaluate the non-inferiority of three months of FOLFOX or CAPOX against six months in stage III colon cancer. The primary end point was three-year disease-free survival, and non-inferiority could be claimed if the upper limit of the two-sided 95 percent confidence interval of the hazard ratio did not exceed 1.12.\n\nNon-inferiority was not confirmed overall, but the regimen-specific and risk-group results changed practice anyway: three months of CAPOX became standard for T1 to T3 N1 disease and six months of FOLFOX remained standard for T4 or N2 disease.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2018","url":"https://doi.org/10.1056/NEJMoa1713709"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29590544/"},{"label":"Europe PMC full text (PMC6426127)","url":"https://europepmc.org/article/MED/29590544"}],"tags":["colorectal-evidence"],"related":["paper-mosaic-oxaliplatin-adjuvant-colon-nejm-2004","paper-esmo-localised-colon-cancer-guideline-ann-oncol-2020"],"cancers":["colorectal","colon-cancer"],"sections":["chemotherapy"],"technologies":["cytotoxic-chemotherapy"],"targets":[],"drugs":["folfox","capox","oxaliplatin","capecitabine"],"companies":[],"institutions":[],"pathways":[],"terms":["neoadjuvant-adjuvant"],"trials":[],"people":["thierry-andre","yoshino-takayuki"],"bottlenecks":["b-toxicity-qol","b-dose-optimisation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2018,"doi":"10.1056/NEJMoa1713709","pmid":"29590544","authors":"Grothey A, Sobrero AF, Shields AF, et al.","paperType":"meta-analysis","findings":["3,263 recurrence or death events among 12,834 patients; non-inferiority of three months not confirmed overall (hazard ratio 1.07, 95 percent CI 1.00 to 1.15).","Non-inferiority was seen for CAPOX (0.95, 0.85 to 1.06) but not for FOLFOX (1.16, 1.06 to 1.26).","In T1 to T3 N1 disease, three months was non-inferior: three-year disease-free survival 83.1 against 83.3 percent (1.01, 0.90 to 1.12).","In T4 or N2 disease, six months was superior: 64.4 against 62.7 percent (1.12, 1.03 to 1.23, p=0.01)."],"whatItMeans":"The largest de-escalation exercise in adjuvant oncology, and the reason a patient with a T3 N1 colon cancer is now offered four cycles of CAPOX rather than twelve of FOLFOX, with a fraction of the neuropathy.","caveats":["The formal non-inferiority question was answered no; practice follows the subgroup and regimen analyses, which were pre-specified but exploratory in combination.","Patients were not randomised between FOLFOX and CAPOX, so the regimen comparison is not randomised evidence.","Quality of life and neuropathy data are reported in the individual trials rather than in the pooled analysis."],"changedPractice":true,"participants":12834},{"id":"paper-nct03775486-j-thorac-oncol-2023","kind":"paper","name":"Durvalumab in Combination With Olaparib Versus Durvalumab Alone as Maintenance Therapy in Metastatic NSCLC: The Phase 2 ORION Study","aka":[],"tldr":"Published report from the ORION trial registered as NCT03775486, in Journal of Thoracic Oncology (2023), chosen as the most cited paper whose own text cites the registry id.","summary":"Introduction: Increased DNA damage triggered through poly (ADP-ribose) polymerase inhibition may modify tumor immunogenicity, sensitizing tumors to immunotherapy. ORION (NCT03775486) evaluated the combination of olaparib with durvalumab as maintenance therapy in patients with metastatic NSCLC.\n\nMethods: ORION is a phase 2, randomized, multicenter, double-blind, international study. Patients with metastatic NSCLC (without activating EGFR or ALK aberrations) and Eastern Cooperative Oncology Group performance status of 0 or 1 were enrolled to receive initial therapy with durvalumab (1500 mg intravenously; every 3 wk) plus platinum-based chemotherapy for four cycles. Patients without disease progression were then randomized (1:1) to maintenance durvalumab (1500 mg; every 4 wk) plus either olaparib (300 mg orally) or placebo (both twice daily); randomization was stratified by objective response during initial therapy and tumor histologic type. The primary end point was investigator-assessed progression-free survival (PFS) (Response Evaluation Criteria in Solid Tumors version 1.1).\n\nResults: Between January 2019 and February 2020, 269 of 401 patients who received initial therapy were randomized. at January 11, 2021 (median follow-up: 9.6 mo), median PFS was 7.2 months (95% confidence interval: 5.3-7.9) with durvalumab plus olaparib versus 5.3 months (3.7-5.8) with durvalumab plus placebo (hazard ratio = 0.76, 95% confidence interval: 0.57-1.02, p = 0.074). Safety findings were consistent with the known profiles of durvalumab and olaparib. Anemia was the most common adverse event (AE) with durvalumab plus olaparib (26.1% versus 8.2% with durvalumab plus placebo). The incidence of grade 3 or 4 AEs (34.3% versus 17.9%) and AEs leading to treatment discontinuation (10.4% versus 4.5%) was numerically higher with durvalumab plus olaparib versus durvalumab plus placebo.\n\nConclusions: Maintenance therapy with durvalumab in combination with olaparib was not associated with a statistically significant improvement in PFS versus durvalumab alone, although numerical improvement was observed.\n\nIndexed on Europe PMC as PubMed record 37390980 (DOI 10.1016/j.jtho.2023.06.013). Its abstract cites the registry id NCT03775486, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Thorac Oncol 2023","url":"https://doi.org/10.1016/j.jtho.2023.06.013"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37390980/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37390980"},{"label":"ClinicalTrials.gov NCT03775486","url":"https://clinicaltrials.gov/study/NCT03775486"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct03775486"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-thoracic-oncology"],"dependsOn":[],"notes":[],"journal":"Journal of Thoracic Oncology","year":2023,"doi":"10.1016/j.jtho.2023.06.013","pmid":"37390980","authors":"Ahn MJ, Bondarenko I, Kalinka E, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03775486 with the most citations, so it is the natural first reading for anyone following the ORION trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-topaz-1-lancet-gastroenterol-hepatol-2024-update","kind":"paper","name":"Durvalumab or placebo plus gemcitabine and cisplatin in participants with advanced biliary tract cancer (TOPAZ-1): updated overall survival from a randomised phase 3 study","aka":[],"tldr":"Later report from the TOPAZ-1 trial registered as NCT03875235, in The lancet. Gastroenterology & hepatology (2024); its title describes an updated or longer-term analysis.","summary":"Background: In the preplanned interim analysis of the TOPAZ-1 study, durvalumab plus gemcitabine-cisplatin significantly improved overall survival versus placebo plus gemcitabine-cisplatin in participants with advanced biliary tract cancer. We aimed to report updated overall survival and safety data from TOPAZ-1 with additional follow-up and data maturity beyond the interim analysis.\n\nMethods: TOPAZ-1 was a phase 3, randomised, double-masked, placebo-controlled, global study done at 105 sites in 17 countries. Participants aged 18 years or older with unresectable, locally advanced, or metastatic biliary tract cancer were randomly assigned (1:1) to durvalumab plus gemcitabine-cisplatin or placebo plus gemcitabine-cisplatin using a computer-generated randomisation scheme, stratified by disease status and primary tumour location. Participants received durvalumab (1500 mg) or placebo on day 1 of each cycle every 3 weeks for up to eight cycles, plus gemcitabine (1000 mg/m 2) and cisplatin (25 mg/m 2) intravenously on days 1 and 8 of each cycle every 3 weeks for up to eight cycles, followed by durvalumab (1500 mg) or placebo monotherapy every 4 weeks until disease progression or other discontinuation criteria were met. Investigators and participants were masked to study treatment. The primary endpoint was overall survival. TOPAZ-1 met its primary endpoint at the preplanned interim analysis, and the study is active but no longer recruiting participants. Updated overall survival and safety data from TOPAZ-1, with additional follow-up (data cutoff Feb 25, 2022) and data maturity beyond the interim analysis, are reported here. Efficacy was assessed in the full analysis set (all randomly assigned participants). Safety was assessed in the safety analysis set (all participants who received at least one dose of study treatment). The TOPAZ-1 study is registered with ClinicalTrials.gov, NCT03875235.\n\nFindings: From April 16, 2019, to Dec 11, 2020, 914 participants were enrolled, 685 of whom were randomly assigned (341 to the durvalumab plus gemcitabine-cisplatin group and 344 to the placebo plus gemcitabine-cisplatin group). 345 (50%) participants were male and 340 (50%) were female. Median follow-up at the updated data cutoff was 23·4 months (95% CI 20·6-25·2) in the durvalumab plus gemcitabine-cisplatin group and 22·4 months (21·4-23·8) in the placebo plus gemcitabine-cisplatin group. At the updated data cutoff, 248 (73%) participants in the durvalumab plus gemcitabine-cisplatin group and 279 (81%) participants in the placebo plus gemcitabine-cisplatin group had died (median overall survival 12·9 months [95% CI 11·6-14·1] vs 11·3 months [10·1-12·5]; hazard ratio 0·76 [95% CI 0·64-0·91]). Kaplan-Meier-estimated 24-month overall survival rates were 23·6% (95% CI 18·7-28·9) in the durvalumab plus gemcitabine-cisplatin group and 11·5% (7·6-16·2) in the placebo plus gemcitabine-cisplatin group. Maximum grade 3 or 4 adverse events occurred in 250 (74%) of 338 participants in the durvalumab plus gemcitabine-cisplatin group and 257 (75%) of 342 in the placebo plus gemcitabine-cisplatin group. The most common maximum grade 3 or 4 treatment-related adverse events were decreased neutrophil count (70 [21%] vs 86 [25%]), anaemia (64 [19%] vs 64 [19%]), and neutropenia (63 [19%] vs 68 [20%]).\n\nInterpretation: Durvalumab plus gemcitabine-cisplatin showed robust and sustained overall survival benefit with no new safety signals. Findings continue to support the regimen as a standard of care for people with untreated, advanced biliary tract cancer.\n\nFunding: AstraZeneca.\n\nIndexed on Europe PMC as PubMed record 38823398 (DOI 10.1016/s2468-1253(24)00095-5). Its abstract cites the registry id NCT03875235, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Gastroenterol Hepatol 2024","url":"https://doi.org/10.1016/s2468-1253(24)00095-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38823398/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38823398"},{"label":"ClinicalTrials.gov NCT03875235","url":"https://clinicaltrials.gov/study/NCT03875235"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["topaz-1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The lancet. Gastroenterology & hepatology","year":2024,"doi":"10.1016/s2468-1253(24)00095-5","pmid":"38823398","authors":"Oh DY, He AR, Bouattour M, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the TOPAZ-1 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-topaz-1-three-year-survival-j-hepatol-2025","kind":"paper","name":"Durvalumab plus chemotherapy in advanced biliary tract cancer: 3-year overall survival update from the phase III TOPAZ-1 study","aka":[],"tldr":"Three and a half years on, adding durvalumab to chemotherapy for advanced bile duct and gallbladder cancer still showed a survival edge, and about one in seven patients were alive at three years compared with one in fourteen on chemotherapy alone.","summary":"Exploratory update of TOPAZ-1 (685 randomised: 341 durvalumab plus gemcitabine-cisplatin, 344 placebo plus gemcitabine-cisplatin) at a median follow-up of 41.3 months. Median overall survival was 12.9 months (95 percent CI 11.6 to 14.1) against 11.3 months (10.1 to 12.5), hazard ratio 0.74 (0.63 to 0.87); 36-month survival was 14.6 versus 6.9 percent. Among the 82.6 percent who achieved disease control, 36-month survival was 17.0 versus 7.6 percent. Extended long-term survivors (alive at 30 months or more) were 17.0 percent of the durvalumab arm and 8.7 percent of the placebo arm and included every clinically relevant subgroup. Benefit held regardless of subsequent therapy, and serious adverse events in long-term survivors were comparable between arms.","asOf":"2026-09-24","links":[{"label":"J Hepatol 2025","url":"https://doi.org/10.1016/j.jhep.2025.05.003"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40381735/"},{"label":"ClinicalTrials.gov NCT03875235","url":"https://clinicaltrials.gov/study/NCT03875235"}],"tags":["gallbladder-evidence"],"related":["paper-topaz-1-nejm-evidence-2022","gemcis-plus-io-btc"],"cancers":["gallbladder","cholangiocarcinoma","biliary-tract-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["durvalumab","gemcitabine-cisplatin"],"companies":["astrazeneca"],"institutions":[],"pathways":[],"terms":["os"],"trials":["topaz-1"],"people":["juan-valle"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of Hepatology","year":2025,"doi":"10.1016/j.jhep.2025.05.003","pmid":"40381735","authors":"Oh DY, He AR, Qin S, et al.","paperType":"rct","findings":["Median overall survival 12.9 vs 11.3 months; hazard ratio 0.74 (95 percent CI 0.63 to 0.87) at 41.3 months median follow-up.","36-month overall survival 14.6 vs 6.9 percent.","Extended long-term survivors 17.0 vs 8.7 percent."],"whatItMeans":"The tail of long survivors is the case for chemo-immunotherapy in gallbladder cancer, where the median gain is under two months. Who lands in that tail is still unknown; no biomarker in the trial predicts it.","caveats":["Exploratory, post hoc analysis.","Gallbladder cancer is a subgroup of a mixed biliary population."],"changedPractice":false,"participants":685},{"id":"paper-paz-ares-caspian-durvalumab-es-sclc-lancet-2019","kind":"paper","name":"Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN)","aka":[],"tldr":"Adding immunotherapy to chemotherapy for advanced small-cell lung cancer raised median survival from 10.3 to 13.0 months. Small, but it was the second positive first-line trial in the disease in thirty years.","summary":"The CASPIAN investigators, reported by Paz-Ares, Dvorkin, Chen and colleagues, randomised treatment-naive patients with extensive-stage small-cell lung cancer 1 to 1 to 1 across 209 sites in 23 countries to durvalumab with platinum and etoposide, durvalumab with tremelimumab and platinum-etoposide, or platinum-etoposide alone. The interim analysis reported here compares the durvalumab arm (268 patients) with chemotherapy alone (269).\n\nWith IMpower133 the year before, CASPIAN ended a thirty-year drought in extensive-stage small-cell lung cancer. The honest reading is that both trials moved median survival by two to three months in a disease where almost nobody is alive at three years, which is why the field moved on to DLL3 and the transcription-factor subtypes.","asOf":"2026-09-25","links":[{"label":"Lancet 2019","url":"https://doi.org/10.1016/S0140-6736(19)32222-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31590988/"},{"label":"ClinicalTrials.gov NCT03043872","url":"https://clinicaltrials.gov/study/NCT03043872"},{"label":"Lancet 2019","url":"https://doi.org/10.1016/s0140-6736(19)32222-6"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31590988"}],"tags":["lung-evidence"],"related":["paper-impower133-n-engl-j-med-2018","paper-adriatic-nejm-2024","paper-dellphi-301-nejm-2023"],"cancers":["lung-cancer","sclc","extensive-stage-sclc"],"sections":["immunotherapy"],"technologies":["checkpoint-inhibitor"],"targets":["pd1"],"drugs":["durvalumab","tremelimumab","etoposide","cisplatin","carboplatin","atezolizumab"],"companies":["astrazeneca"],"institutions":[],"pathways":["immune-checkpoint"],"terms":["pdl1","prophylactic-cranial-irradiation"],"trials":["caspian","impower133"],"people":["luis-paz-ares"],"bottlenecks":["b-immunotherapy-response","b-biomarker-validation","b-rare-cancers"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2019,"doi":"10.1016/S0140-6736(19)32222-6","pmid":"31590988","authors":"Paz-Ares L, Dvorkin M, Chen Y, et al.","paperType":"rct","findings":["Median overall survival 13.0 months (95 percent confidence interval 11.5 to 14.8) with durvalumab plus platinum-etoposide against 10.3 months (9.3 to 11.2) with platinum-etoposide: hazard ratio 0.73 (0.59 to 0.91; p equals 0.0047).","34 percent (26.9 to 41.0) against 25 percent (18.4 to 31.6) of patients alive at 18 months.","Grade 3 or 4 adverse events of any cause in 163 of 265 treated patients (62 percent) with durvalumab and 166 of 266 (62 percent) with chemotherapy alone.","Adverse events leading to death in 13 (5 percent) and 15 (6 percent) patients."],"whatItMeans":"Immunotherapy is now part of first-line treatment for extensive-stage small-cell lung cancer everywhere, on the strength of a gain measured in weeks. The size of that gain is the reason small-cell lung cancer remains the clearest unmet need in thoracic oncology.","caveats":["Interim analysis; the tremelimumab arm was still blinded and later did not add benefit.","No predictive biomarker: PD-L1 does not select responders in small-cell lung cancer, so everyone is treated and a minority benefits.","Prophylactic cranial irradiation was allowed only in the chemotherapy arm at investigator discretion, an asymmetry in the design."],"changedPractice":true,"participants":537},{"id":"paper-nct03003962-j-thorac-oncol-2025","kind":"paper","name":"Durvalumab Versus Chemotherapy as First-line Treatment for Metastatic NSCLC With Tumor PD-L1 Expression of 25% or Higher: Results From the Randomized Phase 3 PEARL Study","aka":[],"tldr":"Published report from the PEARL trial registered as NCT03003962, in Journal of Thoracic Oncology (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Introduction: PEARL (NCT03003962) is an open-label, phase 3 study comparing first-line durvalumab monotherapy with chemotherapy in patients with metastatic NSCLC (mNSCLC [EGFR/ALK wild type]) with programmed cell death ligand 1 (PD-L1) tumor cell (TC) membrane expression status of 25% or higher. We report the final analysis of PEARL.\n\nMethods: Adults (N = 669) with previously untreated stage IV mNSCLC were randomized (1:1) to durvalumab 20 mg/kg every four weeks or chemotherapy every three weeks for four to six cycles. The dual primary endpoints were overall survival (OS) in the population with PD-L1 TC of 25% or higher and OS in the population at low risk of early mortality (LREM) with PD-L1 TC of 25% or higher.\n\nResults: Durvalumab was associated with a numerical reduction in the risk of death versus chemotherapy in the 25% and higher PD-L1 TC population (OS hazard ratio [HR] = 0.84, 95% confidence interval [CI]: 0.71-0.99, p = 0.037; median OS 14.6 months, 95% CI: 12.2-16.9 versus 12.8 months, 95% CI: 10.1-14.7, respectively). In the 25% and higher PD-L1 TC low risk of early mortality population the OS hazard ratio for durvalumab versus chemotherapy was 0.96 (95% CI: 0.79-1.15, p = 0.628); median OS 14.6 months (95% CI: 12.6-17.2) versus 15.0 months (95% CI: 13.1-16.8), respectively. In the safety population, the incidence of grade 3 or 4 treatment-related adverse events was 15.5% (durvalumab) and 45.9% (chemotherapy).\n\nConclusions: Durvalumab did not statistically significantly improve OS versus chemotherapy as first-line treatment in patients with mNSCLC and 25% and higher PD-L1 TC. The numerical improvement in OS was consistent with previous studies of first-line immune checkpoint inhibitor monotherapy in patients with mNSCLC.\n\nIndexed on Europe PMC as PubMed record 39521433 (DOI 10.1016/j.jtho.2024.10.024). Its abstract cites the registry id NCT03003962, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Thorac Oncol 2025","url":"https://doi.org/10.1016/j.jtho.2024.10.024"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39521433/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39521433"},{"label":"ClinicalTrials.gov NCT03003962","url":"https://clinicaltrials.gov/study/NCT03003962"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct03003962"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-thoracic-oncology"],"dependsOn":[],"notes":[],"journal":"Journal of Thoracic Oncology","year":2025,"doi":"10.1016/j.jtho.2024.10.024","pmid":"39521433","authors":"Lu S, Wu L, Wang Q, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03003962 with the most citations, so it is the natural first reading for anyone following the PEARL trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-oreilly-durvalumab-tremelimumab-pancreatic-jama-oncol-2019","kind":"paper","name":"Durvalumab with or without tremelimumab for patients with metastatic pancreatic ductal adenocarcinoma: a phase 2 randomized clinical trial","aka":[],"tldr":"Giving 65 patients with advanced pancreatic cancer a PD-L1 antibody alone or with a CTLA-4 antibody shrank tumours in 3% and 0%, so the trial was stopped before its second stage.","summary":"Part A of a two-part phase 2 randomised trial was a lead-in safety, open-label study with planned expansion pending an efficacy signal. Between November 2015 and March 2017, 65 patients with metastatic pancreatic ductal adenocarcinoma who had received one prior fluorouracil- or gemcitabine-based line were enrolled at 21 sites in 6 countries and randomised to durvalumab 1500 mg every 4 weeks plus tremelimumab 75 mg every 4 weeks for 4 cycles then durvalumab, or durvalumab monotherapy. Grade 3 or higher treatment-related adverse events occurred in 22% and 6%. Objective response rate was 3.1% for combination and 0% for monotherapy; the 10% threshold for expansion was not met and part B did not open. Patient numbers limited any association with PD-L1 expression or microsatellite instability.","asOf":"2026-09-24","links":[{"label":"O'Reilly et al., JAMA Oncol 2019: durvalumab with or without tremelimumab in 65 metastatic patients","url":"https://doi.org/10.1001/jamaoncol.2019.1588"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31318392/"}],"tags":[],"related":[],"cancers":["pancreatic","metastatic-pdac"],"sections":[],"technologies":[],"targets":["pdl1","ctla4"],"drugs":["durvalumab"],"companies":[],"institutions":["mskcc"],"pathways":["pd1-checkpoint"],"terms":["cold-vs-hot"],"trials":[],"people":["eileen-oreilly"],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2019,"doi":"10.1001/jamaoncol.2019.1588","pmid":"31318392","authors":"O'Reilly EM, Oh DY, Dhani N, et al.","paperType":"rct","findings":["Objective response 3.1% with durvalumab plus tremelimumab and 0% with durvalumab alone.","Trial did not expand: the 10% efficacy threshold was not met."],"whatItMeans":"Dual checkpoint blockade, which rescued other cold tumours, does not work in unselected pancreatic cancer; combinations must change the microenvironment first.","caveats":["Second-line population with rapidly progressing disease.","No biomarker selection and small numbers."],"changedPractice":false,"participants":65},{"id":"paper-nct02453282-jama-oncol-2020","kind":"paper","name":"Durvalumab With or Without Tremelimumab vs Standard Chemotherapy in First-line Treatment of Metastatic Non-Small Cell Lung Cancer: The MYSTIC Phase 3 Randomized Clinical Trial","aka":[],"tldr":"Published report from the MYSTIC trial registered as NCT02453282, in JAMA Oncology (2020), chosen as the most cited paper whose own text cites the registry id.","summary":"Importance: Checkpoint inhibitors targeting programmed cell death 1 or its ligand (PD-L1) as monotherapies or in combination with anti-cytotoxic T-lymphocyte-associated antigen 4 have shown clinical activity in patients with metastatic non-small cell lung cancer.\n\nObjective: To compare durvalumab, with or without tremelimumab, with chemotherapy as a first-line treatment for patients with metastatic non-small cell lung cancer.\n\nDesign, setting, and participants: This open-label, phase 3 randomized clinical trial (MYSTIC) was conducted at 203 cancer treatment centers in 17 countries. Patients with treatment-naive, metastatic non-small cell lung cancer who had no sensitizing EGFR or ALK genetic alterations were randomized to receive treatment with durvalumab, durvalumab plus tremelimumab, or chemotherapy. Data were collected from July 21, 2015, to October 30, 2018.\n\nInterventions: Patients were randomized (1:1:1) to receive treatment with durvalumab (20 mg/kg every 4 weeks), durvalumab (20 mg/kg every 4 weeks) plus tremelimumab (1 mg/kg every 4 weeks, up to 4 doses), or platinum-based doublet chemotherapy.\n\nMain outcomes and measures: The primary end points, assessed in patients with ≥25% of tumor cells expressing PD-L1, were overall survival (OS) for durvalumab vs chemotherapy, and OS and progression-free survival (PFS) for durvalumab plus tremelimumab vs chemotherapy. Analysis of blood tumor mutational burden (bTMB) was exploratory.\n\nResults: Between July 21, 2015, and June 8, 2016, 1118 patients were randomized. Baseline demographic and disease characteristics were balanced between treatment groups. Among 488 patients with ≥25% of tumor cells expressing PD-L1, median OS was 16.3 months (95% CI, 12.2-20.8) with durvalumab vs 12.9 months (95% CI, 10.5-15.0) with chemotherapy (hazard ratio [HR], 0.76; 97.54% CI, 0.56-1.02; P =.04 [nonsignificant]). Median OS was 11.9 months (95% CI, 9.0-17.7) with durvalumab plus tremelimumab (HR vs chemotherapy, 0.85; 98.77% CI, 0.61-1.17; P =.20). Median PFS was 3.9 months (95% CI, 2.8-5.0) with durvalumab plus tremelimumab vs 5.4 months (95% CI, 4.6-5.8) with chemotherapy (HR, 1.05; 99.5% CI, 0.72-1.53; P =.71). Among 809 patients with evaluable bTMB, those with a bTMB ≥20 mutations per megabase showed improved OS for durvalumab plus tremelimumab vs chemotherapy (median OS, 21.9 months [95% CI, 11.4-32.8] vs 10.0 months [95% CI, 8.1-11.7]; HR, 0.49; 95% CI, 0.32-0.74). Treatment-related adverse events of grade 3 or higher occurred in 55 (14.9%) of 369 patients who received treatment with durvalumab, 85 (22.9%) of 371 patients who received treatment with durvalumab plus tremelimumab, and 119 (33.8%) of 352 patients who received treatment with chemotherapy. These adverse events led to death in 2 (0.5%), 6 (1.6%), and 3 (0.9%) patients, respectively.\n\nConclusions and relevance: The phase 3 MYSTIC study did not meet its primary end points of improved OS with durvalumab vs chemotherapy or improved OS or PFS with durvalumab plus tremelimumab vs chemotherapy in patients with ≥25% of tumor cells expressing PD-L1. Exploratory analyses identified a bTMB threshold of ≥20 mutations per megabase for optimal OS benefit with durvalumab plus tremelimumab.\n\nTrial registration: ClinicalT rials.gov Identifier: NCT02453282.\n\nIndexed on Europe PMC as PubMed record 32271377 (DOI 10.1001/jamaoncol.2020.0237). Its abstract cites the registry id NCT02453282, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"JAMA Oncol 2020","url":"https://doi.org/10.1001/jamaoncol.2020.0237"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32271377/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32271377"},{"label":"ClinicalTrials.gov NCT02453282","url":"https://clinicaltrials.gov/study/NCT02453282"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct02453282"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2020,"doi":"10.1001/jamaoncol.2020.0237","pmid":"32271377","authors":"Rizvi NA, Cho BC, Reinmuth N, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02453282 with the most citations, so it is the natural first reading for anyone following the MYSTIC trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-caspian-lancet-oncol-2021-update","kind":"paper","name":"Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial","aka":[],"tldr":"Later report from the CASPIAN trial registered as NCT03043872, in The Lancet Oncology (2021); its title describes an updated or longer-term analysis.","summary":"Background: First-line durvalumab plus etoposide with either cisplatin or carboplatin (platinum-etoposide) showed a significant improvement in overall survival versus platinum-etoposide alone in patients with extensive-stage small-cell lung cancer (ES-SCLC) in the CASPIAN study. Here we report updated results, including the primary analysis for overall survival with durvalumab plus tremelimumab plus platinum-etoposide versus platinum-etoposide alone.\n\nMethods: CASPIAN is an ongoing, open-label, sponsor-blind, randomised, controlled phase 3 trial at 209 cancer treatment centres in 23 countries worldwide. Eligible patients were aged 18 years or older (20 years in Japan) and had treatment-naive, histologically or cytologically documented ES-SCLC, with a WHO performance status of 0 or 1. Patients were randomly assigned (1:1:1) in blocks of six, stratified by planned platinum, using an interactive voice-response or web-response system to receive intravenous durvalumab plus tremelimumab plus platinum-etoposide, durvalumab plus platinum-etoposide, or platinum-etoposide alone. In all groups, patients received etoposide 80-100 mg/m 2 on days 1-3 of each cycle with investigator's choice of either carboplatin area under the curve 5-6 mg/mL/min or cisplatin 75-80 mg/m 2 on day 1 of each cycle. Patients in the platinum-etoposide group received up to six cycles of platinum-etoposide every 3 weeks and optional prophylactic cranial irradiation (investigator's discretion). Patients in the immunotherapy groups received four cycles of platinum-etoposide plus durvalumab 1500 mg with or without tremelimumab 75 mg every 3 weeks followed by maintenance durvalumab 1500 mg every 4 weeks. The two primary endpoints were overall survival for durvalumab plus platinum-etoposide versus platinum-etoposide and for durvalumab plus tremelimumab plus platinum-etoposide versus platinum-etoposide in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This study is registered at ClinicalTrials.gov, NCT03043872.\n\nFindings: Between March 27, 2017, and May 29, 2018, 972 patients were screened and 805 were randomly assigned (268 to durvalumab plus tremelimumab plus platinum-etoposide, 268 to durvalumab plus platinum-etoposide, and 269 to platinum-etoposide). at Jan 27, 2020, the median follow-up was 25·1 months (IQR 22·3-27·9). Durvalumab plus tremelimumab plus platinum-etoposide was not associated with a significant improvement in overall survival versus platinum-etoposide (hazard ratio [HR] 0·82 [95% CI 0·68-1·00]; p=0·045); median overall survival was 10·4 months (95% CI 9·6-12·0) versus 10·5 months (9·3-11·2). Durvalumab plus platinum-etoposide showed sustained improvement in overall survival versus platinum-etoposide (HR 0·75 [95% CI 0·62-0·91]; nominal p=0·0032); median overall survival was 12·9 months (95% CI 11·3-14·7) versus 10·5 months (9·3-11·2). The most common any-cause grade 3 or worse adverse events were neutropenia (85 [32%] of 266 patients in the durvalumab plus tremelimumab plus platinum-etoposide group, 64 [24%] of 265 patients in the durvalumab plus platinum-etoposide group, and 88 [33%] of 266 patients in the platinum-etoposide group) and anaemia (34 [13%], 24 [9%], and 48 [18%]). Any-cause serious adverse events were reported in 121 (45%) patients in the durvalumab plus tremelimumab plus platinum-etoposide group, 85 (32%) in the durvalumab plus platinum-etoposide group, and 97 (36%) in the platinum-etoposide group. Treatment-related deaths occurred in 12 (5%) patients in the durvalumab plus tremelimumab plus platinum-etoposide group (death, febrile neutropenia, and pulmonary embolism [n=2 each]; enterocolitis, general physical health deterioration and multiple organ dysfunction syndrome, pneumonia, pneumonitis and hepatitis, respiratory failure, and sudden death [n=1 each]), six (2%) patients in the durvalumab plus platinum-etoposide group (cardiac arrest, dehydration, hepatotoxicity, interstitial lung disease, pancytopenia, and sepsis [n=1 each]), and two (1%) in the platinum-etoposide group (pancytopenia and thrombocytopenia [n=1 each]).\n\nInterpretation: First-line durvalumab plus platinum-etoposide showed sustained overall survival improvement versus platinum-etoposide but the addition of tremelimumab to durvalumab plus platinum-etoposide did not significantly improve outcomes versus platinum-etoposide. These results support the use of durvalumab plus platinum-etoposide as a new standard of care for the first-line treatment of ES-SCLC.\n\nFunding: AstraZeneca.\n\nIndexed on Europe PMC as PubMed record 33285097 (DOI 10.1016/s1470-2045(20)30539-8). Its abstract cites the registry id NCT03043872, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2021","url":"https://doi.org/10.1016/s1470-2045(20)30539-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33285097/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33285097"},{"label":"ClinicalTrials.gov NCT03043872","url":"https://clinicaltrials.gov/study/NCT03043872"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["caspian"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2021,"doi":"10.1016/s1470-2045(20)30539-8","pmid":"33285097","authors":"Goldman JW, Dvorkin M, Chen Y, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the CASPIAN trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-dynamic-nejm-2022","kind":"paper","name":"DYNAMIC: a blood test safely halved chemotherapy use after surgery for stage II colon cancer","aka":[],"tldr":"Giving chemotherapy only to patients with tumour DNA in their blood after surgery cut chemotherapy use from 28% to 15% with no loss in recurrence-free survival at two years.","summary":"DYNAMIC randomised 455 patients with resected stage II colon cancer 2:1 to ctDNA-guided management or standard management. In the ctDNA arm, plasma taken at weeks 4 and 7 after surgery was tested with a tumour-informed assay; ctDNA-positive patients received oxaliplatin-based or fluoropyrimidine chemotherapy and ctDNA-negative patients were observed. The primary endpoint was recurrence-free survival at 2 years, tested for non-inferiority.\n\nAdjuvant chemotherapy was given to 15% of ctDNA-guided patients versus 28% of standard-management patients. Two-year recurrence-free survival was 93.5% versus 92.4%, meeting non-inferiority. ctDNA-positive patients treated with chemotherapy had a 3-year RFS of 86.4%, and untreated ctDNA-negative patients 92.5%.\n\nIt was the first randomised evidence that ctDNA can safely de-escalate adjuvant treatment.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1056/NEJMoa2200075"},{"label":"ANZCTR ACTRN12615000381583","url":"https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368271"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35657320/"},{"label":"Europe PMC full text (PMC9701133)","url":"https://europepmc.org/article/MED/35657320"}],"tags":[],"related":["idea-ctdna-guided-adjuvant-crc","ctdna-mrd-to-adjuvant","ctdna-mrd-positive","paper-tie-ctdna-minimal-residual-disease-stage-ii-colon-sci-transl-med-2016","paper-galaxy-signatera-nat-med-2023"],"cancers":["colorectal","colon-cancer"],"sections":["diagnostics","chemotherapy"],"technologies":["mrd-testing","liquid-biopsy","signatera"],"targets":[],"drugs":[],"companies":[],"institutions":["peter-mac","johns-hopkins","wehi"],"pathways":[],"terms":["mrd","ctdna","neoadjuvant-adjuvant","tumour-informed-assay"],"trials":["dynamic"],"people":["bert-vogelstein","kenneth-kinzler","jeanne-tie"],"bottlenecks":["b-dormancy-mrd","b-toxicity-qol","b-trial-design"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/NEJMoa2200075","pmid":"35657320","authors":"Tie J, Cohen JD, Lahouel K, et al.","paperType":"rct","findings":["Adjuvant chemotherapy use 15% vs 28% (relative risk 1.82 for standard management)","Two-year recurrence-free survival 93.5% vs 92.4% (absolute difference 1.1 percentage points; 95% CI -4.1 to 6.2), non-inferior","ctDNA-positive patients treated with chemotherapy: 3-year RFS 86.4%; ctDNA-negative untreated: 92.5%","About 15% of patients were ctDNA-positive after surgery"],"whatItMeans":"For stage II colon cancer, where most patients are cured by surgery alone, a blood test can identify the minority who benefit from chemotherapy and spare everyone else its side effects. It does not yet prove that treating ctDNA-positive patients improves survival compared with not treating them.","caveats":["Non-inferiority margin of 8.5 percentage points was generous; the trial was not powered to detect small losses","Stage II only; DYNAMIC-III in stage III showed that escalation for ctDNA-positive patients did not clearly improve outcomes","Assay (Safe-SeqS on 15 tumour-specific mutations) is not the commercial assays used elsewhere","Two-year follow-up is short for colon cancer recurrence"],"changedPractice":true,"participants":455},{"id":"paper-michor-nature","kind":"paper","name":"Dynamics of chronic myeloid leukaemia","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 15988530 and published in Nature; the citing page links this DOI, which is how the record was matched.","summary":"The clinical success of the ABL tyrosine kinase inhibitor imatinib in chronic myeloid leukaemia (CML) serves as a model for molecularly targeted therapy of cancer, but at least two critical questions remain. Can imatinib eradicate leukaemic stem cells? What are the dynamics of relapse due to imatinib resistance, which is caused by mutations in the ABL kinase domain? The precise understanding of how imatinib exerts its therapeutic effect in CML and the ability to measure disease burden by quantitative polymerase chain reaction provide an opportunity to develop a mathematical approach. We find that a four-compartment model, based on the known biology of haematopoietic differentiation, can explain the kinetics of the molecular response to imatinib in a 169-patient data set. Successful therapy leads to a biphasic exponential decline of leukaemic cells. The first slope of 0.05 per day represents the turnover rate of differentiated leukaemic cells, while the second slope of 0.008 per day represents the turnover rate of leukaemic progenitors. The model suggests that imatinib is a potent inhibitor of the production of differentiated leukaemic cells, but does not deplete leukaemic stem cells. We calculate the probability of developing imatinib resistance mutations and estimate the time until detection of resistance. Our model provides the first quantitative insights into the in vivo kinetics of a human cancer.\n\nIndexed on Europe PMC as PubMed record 15988530 (DOI 10.1038/nature03669). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2005","url":"https://doi.org/10.1038/nature03669"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/15988530/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/15988530"}],"tags":["europepmc-ingest"],"related":["mrd-kinetics-models"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2005,"doi":"10.1038/nature03669","pmid":"15988530","authors":"Michor F, Hughes TP, Iwasa Y, et al.","paperType":"basic","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-laird-br-j-cancer","kind":"paper","name":"DYNAMICS OF TUMOR GROWTH","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 14219541 and published in British Journal of Cancer; the citing page links this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 14219541 (DOI 10.1038/bjc.1964.55). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Br J Cancer 1964","url":"https://doi.org/10.1038/bjc.1964.55"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/14219541/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/14219541"}],"tags":["europepmc-ingest"],"related":["gompertzian-growth-model"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["british-journal-of-cancer"],"dependsOn":[],"notes":[],"journal":"British Journal of Cancer","year":1964,"doi":"10.1038/bjc.1964.55","pmid":"14219541","authors":"LAIRD AK","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-e3a06-lenalidomide-smouldering-lonial-jco-2020","kind":"paper","name":"E3A06: lenalidomide versus observation in smouldering multiple myeloma","aka":[],"tldr":"Lenalidomide alone delayed progression to active myeloma in people with intermediate- or high-risk smouldering disease, but side effects led many to stop, and it did not improve survival.","summary":"Phase 2/3 trial randomising 182 patients with intermediate- or high-risk smouldering myeloma to lenalidomide 25 mg or observation.\n\nThree-year progression-free survival was 91 percent with lenalidomide against 66 percent with observation (hazard ratio 0.28), with the largest benefit in high-risk patients; about half of treated patients discontinued for toxicity.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2020","url":"https://doi.org/10.1200/JCO.19.01740"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31652094/"}],"tags":[],"related":[],"cancers":["smouldering-myeloma"],"sections":[],"technologies":[],"targets":[],"drugs":["lenalidomide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/JCO.19.01740","pmid":"31652094","authors":"Lonial S, Jacobus S, Fonseca R, et al.","paperType":"rct","findings":["Three-year progression-free survival 91 percent vs 66 percent; hazard ratio 0.28.","Grade 3 to 4 adverse events in 28 percent of the lenalidomide arm."],"whatItMeans":"Lenalidomide showed that intervening before symptoms can delay end-organ damage, supporting later trials such as AQUILA, but tolerability limits its use as a single agent.","caveats":["No overall survival benefit shown.","Progression was defined by end-organ damage, and imaging at baseline was not modern PET or MRI in all patients."],"changedPractice":true,"participants":182},{"id":"paper-eano-meningioma-goldbrunner-neuro-oncology-2021","kind":"paper","name":"EANO guideline on the diagnosis and management of meningiomas (2021)","aka":[],"tldr":"The European neuro-oncology guideline on meningioma sets out when to watch, when to operate, when to use radiosurgery or fractionated radiotherapy by grade and extent of resection, and the limited place of drug therapy.","summary":"Evidence-based guideline from the European Association of Neuro-Oncology covering imaging and molecular diagnosis of meningioma (including methylation and mutational classification), observation of incidental tumours, surgical goals and Simpson grading, radiosurgery and fractionated radiotherapy indications for grade 1 to 3 tumours, systemic therapy for refractory disease, and follow-up schedules.","asOf":"2026-09-17","links":[{"label":"Neuro Oncol 2021","url":"https://doi.org/10.1093/neuonc/noab150"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34181733/"}],"tags":[],"related":[],"cancers":["meningioma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["neuro-oncology"],"dependsOn":[],"notes":[],"journal":"Neuro-Oncology","year":2021,"doi":"10.1093/neuonc/noab150","pmid":"34181733","authors":"Goldbrunner R, Stavrinou P, Jenkinson MD, et al.","paperType":"guideline","findings":[],"whatItMeans":"Observation for small asymptomatic tumours, adjuvant radiotherapy for incompletely resected grade 2 and all grade 3 tumours, and the referral of refractory cases to trials on this site's meningioma page follow this guideline.","caveats":["Randomised evidence for adjuvant radiotherapy in grade 2 meningioma is still awaited from ongoing trials."],"changedPractice":true},{"id":"paper-olivier-chinot-nat-rev-clin-oncol-2021","kind":"paper","name":"EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood","aka":[],"tldr":"Paper by Olivier L. Chinot indexed on Europe PMC as PubMed record 33293629, in Nature Reviews Clinical Oncology (2021), one of the most cited records naming an author with this name at Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille.","summary":"In response to major changes in diagnostic algorithms and the publication of mature results from various large clinical trials, the European Association of Neuro-Oncology (EANO) recognized the need to provide updated guidelines for the diagnosis and management of adult patients with diffuse gliomas. Through these evidence-based guidelines, a task force of EANO provides recommendations for the diagnosis, treatment and follow-up of adult patients with diffuse gliomas. The diagnostic component is based on the 2016 update of the WHO Classification of Tumors of the Central Nervous System and the subsequent recommendations of the Consortium to Inform Molecular and Practical Approaches to CNS Tumour Taxonomy - Not Officially WHO (cIMPACT-NOW). With regard to therapy, we formulated recommendations based on the results from the latest practice-changing clinical trials and also provide guidance for neuropathological and neuroradiological assessment. In these guidelines, we define the role of the major treatment modalities of surgery, radiotherapy and systemic pharmacotherapy, covering current advances and cognizant that unnecessary interventions and expenses should be avoided. This document is intended to be a source of reference for professionals involved in the management of adult patients with diffuse gliomas, for patients and caregivers, and for health-care providers.\n\nIndexed on Europe PMC as PubMed record 33293629 (DOI 10.1038/s41571-020-00447-z). Its author list gives \"Chinot O\" with the affiliation \"Aix-Marseille Université, Assistance Publique-Hôpitaux de Marseille (APHM), CHU Timone, Department of Neuro-Oncology, Marseille, France\", which names Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille; that is how the record was matched to Olivier L. Chinot, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Clin Oncol 2021","url":"https://doi.org/10.1038/s41571-020-00447-z"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33293629/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33293629"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["olivier-chinot"],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-clinical-oncology"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Clinical Oncology","year":2021,"doi":"10.1038/s41571-020-00447-z","pmid":"33293629","authors":"Weller M, van den Bent M, Preusser M, et al.","paperType":"review","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Olivier L. Chinot at Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-esmo-early-breast-cancer-guideline-ann-oncol-2024","kind":"paper","name":"Early breast cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","aka":[],"tldr":"The European oncology society's 2024 guideline for breast cancer that has not spread, covering diagnosis, surgery, radiotherapy, drug treatment before and after surgery, and follow-up; the reference standard for European and UK care of early triple-negative disease.","summary":"ESMO Clinical Practice Guideline for early breast cancer, published in Annals of Oncology in 2024 by Loibl, André, Bachelot, Barrios and colleagues for the ESMO Guidelines Committee. Europe PMC indexes no abstract for this article, so OnCo carries no figures from it; the guideline itself is open on the ESMO website. For triple-negative disease it sets out neoadjuvant chemo-immunotherapy on the KEYNOTE-522 model for stage II to III tumours, platinum in the neoadjuvant regimen, adjuvant olaparib for germline BRCA carriers with residual disease (OlympiA) and capecitabine for residual disease without a BRCA variant (CREATE-X).","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2024","url":"https://doi.org/10.1016/j.annonc.2023.11.016"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38101773/"},{"label":"ESMO guidelines: breast cancer","url":"https://www.esmo.org/guidelines/esmo-clinical-practice-guidelines-breast-cancer"}],"tags":["tnbc-evidence"],"related":["esmo-guidelines"],"cancers":["tnbc","breast-hr-positive","breast-her2-positive"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["esmo"],"pathways":[],"terms":[],"trials":["keynote-522","olympia"],"people":["sibylle-loibl"],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2024,"doi":"10.1016/j.annonc.2023.11.016","pmid":"38101773","authors":"Loibl S, André F, Bachelot T, et al.","paperType":"guideline","findings":["No abstract is indexed on Europe PMC; recommendations are read from the guideline itself."],"whatItMeans":"This is the European standard the UK page for triple-negative breast cancer is compared against; NICE guidance covers the same ground with a narrower set of funded drugs.","caveats":["Published before the first-line antibody-drug conjugate approvals of 2026 and the OlympiA six-year update.","Guideline text, not a trial; the strength of each recommendation is graded within the document."],"changedPractice":true},{"id":"paper-crosby-science","kind":"paper","name":"Early detection of cancer","aka":[],"tldr":"Paper cited by one bottleneck page and 32 idea pages, indexed on Europe PMC as PubMed record 35298272 and published in Science; the citing pages link this DOI, which is how the record was matched.","summary":"Survival improves when cancer is detected early. However, ~50% of cancers are at an advanced stage when diagnosed. Early detection of cancer or precancerous change allows early intervention to try to slow or prevent cancer development and lethality. To achieve early detection of all cancers, numerous challenges must be overcome. It is vital to better understand who is at greatest risk of developing cancer. We also need to elucidate the biology and trajectory of precancer and early cancer to identify consequential disease that requires intervention. Insights must be translated into sensitive and specific early detection technologies and be appropriately evaluated to support practical clinical implementation. Interdisciplinary collaboration is key; advances in technology and biological understanding highlight that it is time to accelerate early detection research and transform cancer survival.\n\nIndexed on Europe PMC as PubMed record 35298272 (DOI 10.1126/science.aay9040). Matched by DOI alone: one bottleneck page and 32 idea pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Science 2022","url":"https://doi.org/10.1126/science.aay9040"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35298272/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35298272"}],"tags":["europepmc-ingest"],"related":["b-early-detection","idea-prev-mced-positive-resolution-pathway","idea-prev-breath-voc-symptomatic-ruleout","idea-prev-emergency-department-cancer-test","idea-prev-live-stage-dashboard","idea-prev-bundled-cancer-check-at-60","idea-prev-capsule-sponge-pharmacy","idea-prev-lmic-five-cancer-methylation-test","idea-prev-urine-dna-haematuria-triage","idea-moon-population-interception","idea-prev-ldct-ai-negative-triage","idea-prev-pancreas-ai-prediagnostic-ct","idea-prev-ebv-dna-npc-screening-scaleup","idea-prev-ehr-symptom-signature-prompts","idea-prev-fragmentomics-first-tier","idea-prev-oral-cancer-community-smartphone-ai","idea-prev-opportunistic-ct-ai-registry","idea-prev-cgm-glycaemic-drift-pancreas","idea-prev-lung-screening-risk-model-eligibility","idea-prev-dental-oral-exam-standard","idea-prev-interval-cancer-audit-blood-tests","idea-prev-mced-non-specific-symptom-triage","idea-prev-new-onset-diabetes-pancreas-pathway","idea-prev-blood-crc-test-for-non-responders","idea-prev-fit-risk-adapted-thresholds","idea-prev-mced-change-control-plan","idea-prev-mced-registry-randomised","idea-prev-hcc-blood-surveillance-cirrhosis","idea-prev-mammography-ai-stepped-wedge","idea-prev-weight-loss-auto-alert","idea-prev-gastric-serology-migrant-screening","idea-prev-mobile-lung-screening-deprived-areas","idea-prev-blood-count-trend-flags"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2022,"doi":"10.1126/science.aay9040","pmid":"35298272","authors":"Crosby D, Bhatia S, Brindle KM, et al.","paperType":"review","findings":[],"whatItMeans":"One bottleneck page and 32 idea pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-eortc-h10-pet-adapted-early-hodgkin-jco-2017","kind":"paper","name":"Early positron emission tomography response-adapted treatment in stage I and II Hodgkin lymphoma: final results of the randomized EORTC/LYSA/FIL H10 trial","aka":["H10","André 2017","EORTC H10"],"tldr":"In early Hodgkin lymphoma, switching to more intensive chemotherapy when the scan was still positive raised five-year freedom from progression from 77 to 91 per cent.","summary":"A randomised trial evaluating treatment adapted to the scan after two cycles of ABVD in previously untreated stage I and II Hodgkin lymphoma, classified by European Organisation for Research and Treatment of Cancer criteria as favourable or unfavourable. The standard arm was ABVD with involved-node radiotherapy regardless of the scan. In the experimental arm, scan-negative patients received ABVD alone, tested for non-inferiority, and scan-positive patients switched to two cycles of escalated BEACOPP with involved-node radiotherapy, tested for superiority.\n\nOf 1,950 randomly assigned patients, 1,925 had an early scan, and 361 (18.8 per cent) were positive. In scan-positive patients, five-year progression-free survival improved from 77.4 per cent with ABVD and radiotherapy to 90.6 per cent with escalated BEACOPP and radiotherapy (hazard ratio 0.42, 95 per cent confidence interval 0.23 to 0.74, p = 0.002). In scan-negative patients, five-year progression-free survival in the favourable group was 99.0 against 87.1 per cent in favour of combined treatment (hazard ratio 15.8, 3.8 to 66.1) and in the unfavourable group 92.1 against 89.6 per cent (hazard ratio 1.45, 0.8 to 2.5); non-inferiority of ABVD alone could not be demonstrated in either group.","asOf":"2026-10-01","links":[{"label":"Journal of Clinical Oncology 2017","url":"https://doi.org/10.1200/JCO.2016.68.6394"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28291393/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28291393"}],"tags":["lymphoma-evidence"],"related":["lymphoma-roadmap"],"cancers":["early-stage-classical-hodgkin-lymphoma","hodgkin-lymphoma"],"sections":["radiation","chemotherapy","imaging"],"technologies":["pet-ct","radiotherapy","imrt-igrt"],"targets":[],"drugs":["doxorubicin","bleomycin","vinblastine","dacarbazine","etoposide","cyclophosphamide","vincristine","procarbazine","prednisone"],"companies":[],"institutions":[],"pathways":[],"terms":["deauville-score","abvd-beacopp","non-inferiority"],"trials":["eortc-h10","hd16","radar-hodgkin"],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2017,"doi":"10.1200/JCO.2016.68.6394","pmid":"28291393","authors":"André MPE, Girinsky T, Federico M, et al.","paperType":"rct","findings":["In scan-positive patients, five-year progression-free survival rose from 77.4 per cent with ABVD and involved-node radiotherapy to 90.6 per cent with escalated BEACOPP and involved-node radiotherapy (hazard ratio 0.42, 95 per cent confidence interval 0.23 to 0.74, p = 0.002).","361 of 1,925 patients with an early scan (18.8 per cent) were positive.","In scan-negative favourable-group patients, five-year progression-free survival was 99.0 per cent with combined-modality treatment against 87.1 per cent with ABVD alone (hazard ratio 15.8, 3.8 to 66.1).","In scan-negative unfavourable-group patients the figures were 92.1 against 89.6 per cent (hazard ratio 1.45, 0.8 to 2.5).","Non-inferiority of ABVD alone could not be demonstrated in either risk group."],"whatItMeans":"The interim scan should be used to intensify treatment in early Hodgkin lymphoma, not to withhold radiotherapy. The 99.0 per cent five-year progression-free survival in the scan-negative favourable group with combined-modality treatment is the number any radiotherapy-sparing strategy has to match.","caveats":["The scan-positive comparison involves 361 patients, so the confidence interval around the hazard ratio of 0.42 is wide.","Escalated BEACOPP carries infertility and second-malignancy risks that a five-year progression-free survival endpoint does not capture.","The hazard ratio of 15.8 in the favourable scan-negative group rests on a small number of events and should be read as a direction rather than a magnitude."],"changedPractice":true,"participants":1925},{"id":"paper-casulo-pod24-follicular-lymphoma-jco-2015","kind":"paper","name":"Early relapse of follicular lymphoma after R-CHOP defines patients at high risk for death: an analysis from the National LymphoCare Study","aka":["Casulo 2015","POD24","Progression of disease within 24 months in follicular lymphoma"],"tldr":"One in five people whose follicular lymphoma came back within two years of first treatment had half the five-year survival of everyone else, which is why that two-year mark now changes the plan.","summary":"Follicular lymphoma is usually described as a disease people live with for decades. Casulo and colleagues showed that this is true of four fifths of patients and untrue of the rest, and gave the field a marker to tell them apart.\n\nThe National LymphoCare Study followed 588 patients with stage 2 to 4 follicular lymphoma treated with first-line R-CHOP. Progression within two years of diagnosis occurred in 110 patients (19 per cent); 420 (71 per cent) formed the reference group, 46 (8 per cent) were lost to follow-up and 12 (2 per cent) died without progression. Five-year overall survival was 50 per cent in the early-progression group against 90 per cent in the reference group. Adjusting for the Follicular Lymphoma International Prognostic Index left a hazard ratio of 6.44 (95 per cent confidence interval 4.33 to 9.58), and an independent validation set of 147 patients gave an adjusted hazard ratio of 19.8.\n\nWhat it changes in a clinic: early progression triggers a repeat biopsy, because transformation to diffuse large B-cell lymphoma is the commonest cause and is treated as an aggressive lymphoma; it moves the patient up the queue for treatment that does not depend on chemotherapy sensitivity, which now means CAR-T or a bispecific antibody; and it is a reason to look for a trial rather than repeat chemoimmunotherapy.","asOf":"2026-10-01","links":[{"label":"Journal of Clinical Oncology 2015","url":"https://doi.org/10.1200/JCO.2014.59.7534"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26124482/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26124482"}],"tags":["lymphoma-evidence"],"related":["paper-prima-final-rituximab-maintenance-follicular-jco-2019","paper-elara-tisagenlecleucel-follicular-nat-med-2022","lymphoma-roadmap"],"cancers":["follicular-lymphoma","non-hodgkin-lymphoma"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":["rituximab","cyclophosphamide","doxorubicin","vincristine","prednisone"],"companies":[],"institutions":[],"pathways":[],"terms":["flipi","lymphoma-tx-pod24","r-chop"],"trials":["elara","zuma-5","mosun-len-mzl"],"people":[],"bottlenecks":["b-biomarker-validation","b-trial-design"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2015,"doi":"10.1200/JCO.2014.59.7534","pmid":"26124482","authors":"Casulo C, Byrtek M, Dawson KL, et al.","paperType":"observational","findings":["Of 588 patients with stage 2 to 4 follicular lymphoma treated with first-line R-CHOP, 110 (19 per cent) progressed within two years of diagnosis.","Five-year overall survival was 50 per cent in the early-progression group against 90 per cent in the reference group.","The association persisted after adjustment for the Follicular Lymphoma International Prognostic Index, with a hazard ratio of 6.44 (95 per cent confidence interval 4.33 to 9.58).","An independent validation set of 147 patients gave an index-adjusted hazard ratio of 19.8."],"whatItMeans":"The single most used prognostic marker in follicular lymphoma, and the reason a relapse at 20 months is handled differently from one at 30 months. It is now a standard stratification factor and a standard eligibility criterion in trials of the disease.","caveats":["A description, not a diagnosis: the 24-month cut-off is a convention, and someone progressing at 25 months is not biologically different from one progressing at 23.","Derived in patients treated with R-CHOP; the proportion progressing early differs with other induction regimens.","An observational registry analysis, with the referral and recording limitations that implies.","It identifies a group retrospectively, after progression, so it cannot yet direct first-line treatment."],"changedPractice":true,"participants":588},{"id":"paper-rustin-lancet","kind":"paper","name":"Early versus delayed treatment of relapsed ovarian cancer (MRC OV05/EORTC 55955): a randomised trial","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 20888993 and published in The Lancet; the citing page links this DOI, which is how the record was matched.","summary":"Background: Serum CA125 concentration often rises several months before clinical or symptomatic relapse in women with ovarian cancer. In the MRC OV05/EORTC 55955 collaborative trial, we aimed to establish the benefits of early treatment on the basis of increased CA125 concentrations compared with delayed treatment on the basis of clinical recurrence.\n\nMethods: Women with ovarian cancer in complete remission after first-line platinum-based chemotherapy and a normal CA125 concentration were registered for this randomised controlled trial. Clinical examination and CA125 measurement were done every 3 months. Patients and investigators were masked to CA125 results, which were monitored by coordinating centres. If CA125 concentration exceeded twice the upper limit of normal, patients were randomly assigned (1:1) by minimisation to early or delayed chemotherapy. Patients and clinical sites were informed of allocation to early treatment, and treatment was started as soon as possible within 28 days of the increased CA125 measurement. Patients assigned to delayed treatment continued masked CA125 measurements, with treatment commencing at clinical or symptomatic relapse. All patients were treated according to standard local practice. The primary outcome was overall survival. Analysis was by intention to treat. This study is registered, ISRCTN87786644.\n\nFindings: 1442 patients were registered for the trial, of whom 529 were randomly assigned to treatment groups and were included in our analysis (265 early, 264 delayed). With a median follow-up of 56·9 months (IQR 37·4-81·8) from randomisation and 370 deaths (186 early, 184 delayed), there was no evidence of a difference in overall survival between early and delayed treatment (HR 0·98, 95% CI 0·80-1·20, p=0·85). Median survival from randomisation was 25·7 months (95% CI 23·0-27·9) for patients on early treatment and 27·1 months (22·8-30·9) for those on delayed treatment.\n\nInterpretation: Our findings showed no evidence of a survival benefit with early treatment of relapse on the basis of a raised CA125 concentration alone, and therefore the value of routine measurement of CA125 in the follow-up of patients with ovarian cancer who attain a complete response after first-line treatment is not proven.\n\nFunding: UK Medical Research Council and the European Organisation for Research and Treatment of Cancer.\n\nIndexed on Europe PMC as PubMed record 20888993 (DOI 10.1016/s0140-6736(10)61268-8). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet 2010","url":"https://doi.org/10.1016/s0140-6736(10)61268-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20888993/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/20888993"}],"tags":["europepmc-ingest"],"related":["serum-tumour-markers"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2010,"doi":"10.1016/s0140-6736(10)61268-8","pmid":"20888993","authors":"Rustin GJ, van der Burg ME, Griffin CL, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-chua-j-clin-oncol","kind":"paper","name":"Early- and long-term outcome data of patients with pseudomyxoma peritonei from appendiceal origin treated by a strategy of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 22614976 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: Pseudomyxoma peritonei (PMP) originating from an appendiceal mucinous neoplasm remains a biologically heterogeneous disease. The purpose of our study was to evaluate outcome and long-term survival after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) consolidated through an international registry study.\n\nPatients and methods: A retrospective multi-institutional registry was established through collaborative efforts of participating units affiliated with the Peritoneal Surface Oncology Group International.\n\nResults: Two thousand two hundred ninety-eight patients from 16 specialized units underwent CRS for PMP. Treatment-related mortality was 2% and major operative complications occurred in 24% of patients. The median survival rate was 196 months (16.3 years) and the median progression-free survival rate was 98 months (8.2 years), with 10- and 15-year survival rates of 63% and 59%, respectively. Multivariate analysis identified prior chemotherapy treatment (P <.001), peritoneal mucinous carcinomatosis (PMCA) histopathologic subtype (P <.001), major postoperative complications (P =.008), high peritoneal cancer index (P =.013), debulking surgery (completeness of cytoreduction [CCR], 2 or 3; P <.001), and not using HIPEC (P =.030) as independent predictors for a poorer progression-free survival. Older age (P =.006), major postoperative complications (P <.001), debulking surgery (CCR 2 or 3; P <.001), prior chemotherapy treatment (P =.001), and PMCA histopathologic subtype (P <.001) were independent predictors of a poorer overall survival.\n\nConclusion: The combined modality strategy for PMP may be performed safely with acceptable morbidity and mortality in a specialized unit setting with 63% of patients surviving beyond 10 years. Minimizing nondefinitive operative and systemic chemotherapy treatments before definitive cytoreduction may facilitate the feasibility and improve the outcome of this therapy to achieve long-term survival. Optimal cytoreduction achieves the best outcomes.\n\nIndexed on Europe PMC as PubMed record 22614976 (DOI 10.1200/jco.2011.39.7166). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2012","url":"https://doi.org/10.1200/jco.2011.39.7166"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22614976/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/22614976"}],"tags":["europepmc-ingest"],"related":["low-grade-appendiceal-mucinous-neoplasm"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2012,"doi":"10.1200/jco.2011.39.7166","pmid":"22614976","authors":"Chua TC, Moran BJ, Sugarbaker PH, et al.","paperType":"observational","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-eau-asco-penile-cancer-guideline-eur-urol-2023","kind":"paper","name":"EAU-ASCO collaborative guideline on penile cancer, 2023 update","aka":[],"tldr":"The joint European and American guideline for penile cancer, from HPV testing and organ-sparing surgery to sentinel node biopsy, lymph node surgery and chemotherapy for node-positive disease.","summary":"Collaborative guideline from the European Association of Urology and the American Society of Clinical Oncology covering diagnosis, HPV and p16 testing, penile-preserving treatment (topical therapy, laser, glansectomy, partial penectomy), management of the groin nodes with dynamic sentinel node biopsy or inguinal lymphadenectomy, neoadjuvant and adjuvant chemotherapy for node-positive disease, radiotherapy, follow-up and sexual and psychological support.\n\nIt grades the evidence, most of which is retrospective, and recommends referral to centralised centres and enrolment in trials such as InPACT.","asOf":"2026-09-18","links":[{"label":"Eur Urol 2023","url":"https://doi.org/10.1016/j.eururo.2023.02.027"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36906413/"}],"tags":[],"related":[],"cancers":["localised-penile-cancer","node-positive-penile-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["european-urology"],"dependsOn":[],"notes":[],"journal":"European Urology","year":2023,"doi":"10.1016/j.eururo.2023.02.027","pmid":"36906413","authors":"Brouwer OR, Albersen M, Parnham A, et al.","paperType":"guideline","findings":[],"whatItMeans":"The standard-of-care entries on the penile cancer pages, from keeping as much of the penis as is safe to staging the groins with a sentinel node procedure, follow this guideline.","caveats":["Almost all recommendations rest on retrospective series; randomised evidence in penile cancer is limited to the InPACT trial.","Access to dynamic sentinel node biopsy is limited to specialised centres."],"changedPractice":true},{"id":"paper-echelon-1-brentuximab-avd-nejm-2018","kind":"paper","name":"ECHELON-1: brentuximab vedotin replacing bleomycin in first-line chemotherapy for advanced Hodgkin lymphoma","aka":[],"tldr":"Swapping bleomycin for the CD30 antibody-drug conjugate brentuximab vedotin modestly improved disease control in advanced Hodgkin lymphoma and, at six years, improved survival.","summary":"ECHELON-1 randomised 1334 patients with previously untreated stage III or IV classical Hodgkin lymphoma to brentuximab vedotin plus doxorubicin, vinblastine and dacarbazine (A+AVD) or standard ABVD for six cycles. The primary endpoint was modified PFS by independent review. At two years modified PFS was 82.1% versus 77.2% (hazard ratio 0.77). A+AVD caused more peripheral neuropathy (67% versus 43%) and febrile neutropenia (19% versus 8%) but eliminated bleomycin lung toxicity. The six-year update (Ansell et al., NEJM 2022) showed an overall survival benefit: 93.9% versus 89.4% (hazard ratio 0.59), the first OS improvement in front-line advanced Hodgkin lymphoma.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa1708984"},{"label":"6-year overall survival (Ansell 2022)","url":"https://doi.org/10.1056/NEJMoa2206125"},{"label":"ClinicalTrials.gov NCT01712490","url":"https://clinicaltrials.gov/study/NCT01712490"}],"tags":[],"related":["paper-swog-s1826-nivolumab-avd-nejm-2024"],"cancers":["hodgkin-lymphoma"],"sections":[],"technologies":["adc"],"targets":["cd30"],"drugs":["brentuximab-vedotin","doxorubicin"],"companies":["pfizer","takeda"],"institutions":[],"pathways":[],"terms":["pfs","os"],"trials":["echelon-1","hd21","swog-s1826"],"people":[],"bottlenecks":["b-toxicity-qol","b-survivorship"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2018,"doi":"10.1056/NEJMoa1708984","authors":"Connors JM, Jurczak W, Straus DJ, et al.","paperType":"rct","findings":["1334 patients with stage III-IV classical Hodgkin lymphoma; A+AVD vs ABVD.","2-year modified PFS 82.1% vs 77.2%; hazard ratio 0.77.","Peripheral neuropathy 67% vs 43%; febrile neutropenia 19% vs 8%; pulmonary toxicity lower with A+AVD.","6-year overall survival 93.9% vs 89.4%; hazard ratio 0.59.","Fewer second malignancies and fewer patients needing subsequent therapy with A+AVD."],"whatItMeans":"ECHELON-1 made a targeted antibody-drug conjugate part of first-line Hodgkin therapy and eventually showed that this saves lives, not just relapses. It set the reference arm against which nivolumab-AVD (SWOG S1826) and BrECADD (HD21) were later compared. Neuropathy is the main price and needs proactive dose modification.","caveats":["Modified PFS was a novel composite endpoint counting incomplete response followed by further therapy as an event.","Early absolute benefit was small (about 5 points) and OS emerged only with long follow-up.","Excluded early-stage disease; older patients (over 60) had high toxicity with A+AVD.","Cost of brentuximab restricts use in lower-income settings."],"changedPractice":true,"participants":1334},{"id":"paper-e1910-blinatumomab-mrd-negative-all-nejm-2024","kind":"paper","name":"ECOG-ACRIN E1910: adding blinatumomab to chemotherapy for adults with B-cell ALL already in MRD-negative remission","aka":[],"tldr":"Giving the bispecific blinatumomab to adults whose leukaemia was already undetectable after chemotherapy raised three-year survival from 68% to 85%.","summary":"E1910 enrolled adults aged 30-70 with newly diagnosed Philadelphia-chromosome-negative B-cell ALL. Those who reached MRD-negative remission after induction and intensification (224 patients) were randomised to four cycles of blinatumomab interleaved with consolidation chemotherapy or chemotherapy alone, followed by maintenance. The primary endpoint in this group was overall survival. At three years OS was 85% versus 68% (hazard ratio 0.41) and relapse-free survival 80% versus 64%. Neuropsychiatric events were more frequent with blinatumomab but mostly low grade. The result led to approval of blinatumomab in consolidation for CD19-positive B-ALL regardless of MRD status.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa2312948"},{"label":"ClinicalTrials.gov NCT02003222","url":"https://clinicaltrials.gov/study/NCT02003222"}],"tags":[],"related":["blinatumomab-frontline-consolidation","paper-aall1731-blinatumomab-children-nejm-2025"],"cancers":["all-leukemia"],"sections":[],"technologies":["bispecific-antibody","t-cell-engager","mrd-testing"],"targets":["cd19","cd3"],"drugs":["blinatumomab"],"companies":["amgen","ecog-acrin"],"institutions":[],"pathways":[],"terms":["mrd","os","mrd-negative-cr"],"trials":["e1910"],"people":["mark-litzow"],"bottlenecks":["b-dormancy-mrd"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2024,"doi":"10.1056/NEJMoa2312948","authors":"Litzow MR, Sun Z, Mattison RJ, et al.","paperType":"rct","findings":["488 adults enrolled; 224 MRD-negative patients randomised to blinatumomab plus chemotherapy or chemotherapy alone.","3-year overall survival 85% vs 68%; hazard ratio 0.41.","3-year relapse-free survival 80% vs 64%.","Benefit seen across age groups, including patients aged 55-70.","Grade 3 or higher neuropsychiatric events higher with blinatumomab; no excess treatment-related deaths."],"whatItMeans":"E1910 changed the standard of care for adult B-ALL: immunotherapy is now part of front-line consolidation even for patients with no detectable leukaemia, because MRD-negative by flow cytometry does not mean cured. It also demonstrated that a T-cell engager can improve overall survival in a curative setting. Chemotherapy-light or chemotherapy-free regimens built on blinatumomab and inotuzumab are the next step.","caveats":["MRD was assessed by flow cytometry at 10^-4 sensitivity; more sensitive NGS assays might identify who truly needs blinatumomab.","Adults under 30 were excluded (treated on paediatric-inspired protocols).","Randomised sample was modest and the OS benefit emerged at interim analysis.","Blinatumomab requires continuous 28-day infusions, a logistical burden."],"changedPractice":true,"participants":224},{"id":"paper-e3311-transoral-surgery-ferris-jco-2022","kind":"paper","name":"ECOG-ACRIN E3311: transoral surgery followed by reduced-dose radiotherapy for HPV-positive oropharyngeal cancer","aka":[],"tldr":"In HPV-positive oropharyngeal cancer removed by transoral robotic surgery, patients with intermediate-risk pathology did just as well with a reduced 50 Gy dose of radiotherapy as with the standard 60 Gy, supporting surgery-based de-escalation.","summary":"Phase 2 trial of 495 patients with resectable HPV-positive oropharyngeal cancer treated with transoral surgery and neck dissection, then allocated by pathology: observation for low risk, randomisation to 50 or 60 Gy radiotherapy for intermediate risk, and chemoradiotherapy for high risk.\n\nTwo-year progression-free survival was 96.9 percent with observation, 94.9 percent with 50 Gy and 96.0 percent with 60 Gy, and 90.7 percent with chemoradiation, with better swallowing outcomes at lower doses.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2022","url":"https://doi.org/10.1200/JCO.21.01752"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34699271/"}],"tags":[],"related":[],"cancers":["hpv-positive-oropharyngeal-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["robert-ferris"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2022,"doi":"10.1200/JCO.21.01752","pmid":"34699271","authors":"Ferris RL, Flamand Y, Weinstein GS, et al.","paperType":"rct","findings":["Two-year progression-free survival 94.9 percent with 50 Gy vs 96.0 percent with 60 Gy in intermediate-risk patients.","Low-risk patients observed after surgery had 96.9 percent two-year progression-free survival."],"whatItMeans":"Transoral surgery with pathology-guided reduced-dose radiotherapy is a validated de-escalation pathway for HPV-positive oropharyngeal cancer in experienced centres.","caveats":["Phase 2 with no non-surgical comparator.","Requires surgical expertise with low positive-margin rates."],"changedPractice":true,"participants":495},{"id":"paper-primrose-jama","kind":"paper","name":"Effect of 3 to 5 years of scheduled CEA and CT follow-up to detect recurrence of colorectal cancer: the FACS randomized clinical trial","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 24430319 and published in JAMA; the citing page links this DOI, which is how the record was matched.","summary":"Importance: Intensive follow-up after surgery for colorectal cancer is common practice but is based on limited evidence.\n\nObjective: To assess the effect of scheduled blood measurement of carcinoembryonic antigen (CEA) and computed tomography (CT) as follow-up to detect recurrent colorectal cancer treatable with curative intent.\n\nDesign, setting, and participants: Randomized clinical trial in 39 National Health Service hospitals in the United Kingdom; 1202 eligible participants were recruited between January 2003 and August 2009 who had undergone curative surgery for primary colorectal cancer, including adjuvant treatment if indicated, with no evidence of residual disease on investigation.\n\nInterventions: Participants were randomly assigned to 1 of 4 groups: CEA only (n = 300), CT only (n = 299), CEA+CT (n = 302), or minimum follow-up (n = 301). Blood CEA was measured every 3 months for 2 years, then every 6 months for 3 years; CT scans of the chest, abdomen, and pelvis were performed every 6 months for 2 years, then annually for 3 years; and the minimum follow-up group received follow-up if symptoms occurred.\n\nMain outcomes and measures: The primary outcome was surgical treatment of recurrence with curative intent; secondary outcomes were mortality (total and colorectal cancer), time to detection of recurrence, and survival after treatment of recurrence with curative intent.\n\nResults: After a mean 4.4 (SD, 0.8) years of observation, cancer recurrence was detected in 199 participants (16.6%; 95% CI, 14.5%-18.7%) overall; 71 of 1202 participants (5.9%; 95% CI, 4.6%-7.2%) were treated for recurrence with curative intent, with little difference according to Dukes staging (stage A, 5.1% [13/254]; stage B, 6.1% [34/553]; stage C, 6.2% [22/354]). Surgical treatment of recurrence with curative intent was 2.3% (7/301) in the minimum follow-up group, 6.7% (20/300) in the CEA group, 8% (24/299) in the CT group, and 6.6% (20/302) in the CEA+CT group. Compared with minimum follow-up, the absolute difference in the percentage of patients treated with curative intent in the CEA group was 4.4% (95% CI, 1.0%-7.9%; adjusted odds ratio [OR], 3.00; 95% CI, 1.23-7.33), in the CT group was 5.7% (95% CI, 2.2%-9.5%; adjusted OR, 3.63; 95% CI, 1.51-8.69), and in the CEA+CT group was 4.3% (95% CI, 1.0%-7.9%; adjusted OR, 3.10; 95% CI, 1.10-8.71). The number of deaths was not significantly different in the combined intensive monitoring groups (CEA, CT, and CEA+CT; 18.2% [164/901]) vs the minimum follow-up group (15.9% [48/301]; difference, 2.3%; 95% CI, -2.6% to 7.1%).\n\nConclusions and relevance: Among patients who had undergone curative surgery for primary colorectal cancer, intensive imaging or CEA screening each provided an increased rate of surgical treatment of recurrence with curative intent compared with minimal follow-up; there was no advantage in combining CEA and CT. If there is a survival advantage to any strategy, it is likely to be small.\n\nTrial registration: isrctn.org Identifier: 41458548.\n\nIndexed on Europe PMC as PubMed record 24430319 (DOI 10.1001/jama.2013.285718). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA 2014","url":"https://doi.org/10.1001/jama.2013.285718"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24430319/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/24430319"}],"tags":["europepmc-ingest"],"related":["cea-surveillance-colorectal"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2014,"doi":"10.1001/jama.2013.285718","pmid":"24430319","authors":"Primrose JN, Perera R, Gray A, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-neoptolemos-jama","kind":"paper","name":"Effect of adjuvant chemotherapy with fluorouracil plus folinic acid or gemcitabine vs observation on survival in patients with resected periampullary adenocarcinoma: the ESPAC-3 periampullary cancer randomized trial","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 22782416 and published in JAMA; the citing page links this DOI, which is how the record was matched.","summary":"Context: Patients with periampullary adenocarcinomas undergo the same resectional surgery as that of patients with pancreatic ductal adenocarcinoma. Although adjuvant chemotherapy has been shown to have a survival benefit for pancreatic cancer, there have been no randomized trials for periampullary adenocarcinomas.\n\nObjective: To determine whether adjuvant chemotherapy (fluorouracil or gemcitabine) provides improved overall survival following resection.\n\nDesign, setting, and patients: The European Study Group for Pancreatic Cancer (ESPAC)-3 periampullary trial, an open-label, phase 3, randomized controlled trial (July 2000-May 2008) in 100 centers in Europe, Australia, Japan, and Canada. Of the 428 patients included in the primary analysis, 297 had ampullary, 96 had bile duct, and 35 had other cancers.\n\nInterventions: One hundred forty-four patients were assigned to the observation group, 143 patients to receive 20 mg/m2 of folinic acid via intravenous bolus injection followed by 425 mg/m2 of fluorouracil via intravenous bolus injection administered 1 to 5 days every 28 days, and 141 patients to receive 1000 mg/m2 of intravenous infusion of gemcitabine once a week for 3 of every 4 weeks for 6 months.\n\nMain outcome measures: The primary outcome measure was overall survival with chemotherapy vs no chemotherapy; secondary measures were chemotherapy type, toxic effects, progression-free survival, and quality of life.\n\nResults: Eighty-eight patients (61%) in the observation group, 83 (58%) in the fluorouracil plus folinic acid group, and 73 (52%) in the gemcitabine group died. In the observation group, the median survival was 35.2 months (95%% CI, 27.2-43.0 months) and was 43.1 (95%, CI, 34.0-56.0) in the 2 chemotherapy groups (hazard ratio, 0.86; (95% CI, 0.66-1.11; χ2 = 1.33; P =.25). After adjusting for independent prognostic variables of age, bile duct cancer, poor tumor differentiation, and positive lymph nodes and after conducting multiple regression analysis, the hazard ratio for chemotherapy compared with observation was 0.75 (95% CI, 0.57-0.98; Wald χ2 = 4.53, P =.03).\n\nConclusions: Among patients with resected periampullary adenocarcinoma, adjuvant chemotherapy, compared with observation, was not associated with a significant survival benefit in the primary analysis; however, multivariable analysis adjusting for prognostic variables demonstrated a statistically significant survival benefit associated with adjuvant chemotherapy.\n\nTrial registration: clinicaltrials.gov Identifier: NCT00058201.\n\nIndexed on Europe PMC as PubMed record 22782416 (DOI 10.1001/jama.2012.7352). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA 2012","url":"https://doi.org/10.1001/jama.2012.7352"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22782416/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/22782416"}],"tags":["europepmc-ingest"],"related":["ampullary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2012,"doi":"10.1001/jama.2012.7352","pmid":"22782416","authors":"Neoptolemos JP, Moore MJ, Cox TF, et al.","paperType":"rct","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-alter-0303-jama-oncol-2018","kind":"paper","name":"Effect of Anlotinib as a Third-Line or Further Treatment on Overall Survival of Patients With Advanced Non-Small Cell Lung Cancer: The ALTER 0303 Phase 3 Randomized Clinical Trial","aka":[],"tldr":"Published report from the ALTER 0303 trial registered as NCT02388919, in JAMA Oncology (2018), chosen as the most cited paper whose own text cites the registry id.","summary":"Importance: Anlotinib is a novel multitarget tyrosine kinase inhibitor for tumor angiogenesis and proliferative signaling. A phase 2 trial showed anlotinib to improve progression-free survival with a potential benefit of overall survival, leading to the phase 3 trial to confirm the drug's efficacy in advanced non-small cell lung cancer (NSCLC).\n\nObjective: To investigate the efficacy of anlotinib on overall survival of patients with advanced NSCLC progressing after second-line or further treatment.\n\nDesign, setting, and participants: The ALTER 0303 trial was a multicenter, double-blind, phase 3 randomized clinical trial designed to evaluate the efficacy and safety of anlotinib in patients with advanced NSCLC. Patients from 31 grade-A tertiary hospitals in China were enrolled between March 1, 2015, and August 31, 2016. Those aged 18 to 75 years who had histologically or cytologically confirmed NSCLC were eligible (n = 606), and those who had centrally located squamous cell carcinoma with cavitary features or brain metastases that were uncontrolled or controlled for less than 2 months were excluded. Patients (n = 440) were randomly assigned in a 2-to-1 ratio to receive either 12 mg/d of anlotinib or a matched placebo. All cases were treated with study drugs at least once in accordance with the intention-to-treat principle.\n\nMain outcomes and measures: The primary end point was overall survival. The secondary end points were progression-free survival, objective response rate, disease control rate, quality of life, and safety.\n\nResults: In total, 439 patients were randomized, 296 to the anlotinib group (106 [36.1%] were female and 188 [64.0%] were male, with a mean [SD] age of 57.9 [9.1] years) and 143 to the placebo group (46 [32.2%] were female and 97 [67.8%] were male, with a mean [SD] age of 56.8 [9.1] years). Overall survival was significantly longer in the anlotinib group (median, 9.6 months; 95% CI, 8.2-10.6) than the placebo group (median, 6.3 months; 95% CI, 5.0-8.1), with a hazard ratio (HR) of 0.68 (95% CI, 0.54-0.87; P =.002). A substantial increase in progression-free survival was noted in the anlotinib group compared with the placebo group (median, 5.4 months [95% CI, 4.4-5.6] vs 1.4 months [95% CI, 1.1-1.5]; HR, 0.25 [95% CI, 0.19-0.31]; P <.001). Considerable improvement in objective response rate and disease control rate was observed in the anlotinib group over the placebo group. The most common grade 3 or higher adverse events in the anlotinib arm were hypertension and hyponatremia.\n\nConclusions and relevance: Among the Chinese patients in this trial, anlotinib appears to lead to prolonged overall survival and progression-free survival. This finding suggests that anlotinib is well tolerated and is a potential third-line or further therapy for patients with advanced NSCLC.\n\nTrial registration: ClinicalTrials.gov identifier: NCT02388919.\n\nIndexed on Europe PMC as PubMed record 30098152 (DOI 10.1001/jamaoncol.2018.3039). Its abstract cites the registry id NCT02388919, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"JAMA Oncol 2018","url":"https://doi.org/10.1001/jamaoncol.2018.3039"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30098152/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30098152"},{"label":"ClinicalTrials.gov NCT02388919","url":"https://clinicaltrials.gov/study/NCT02388919"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["alter-0303"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2018,"doi":"10.1001/jamaoncol.2018.3039","pmid":"30098152","authors":"Han B, Li K, Wang Q, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02388919 with the most citations, so it is the natural first reading for anyone following the ALTER 0303 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-mcneil-n-engl-j-med","kind":"paper","name":"Effect of Aspirin on All-Cause Mortality in the Healthy Elderly","aka":[],"tldr":"Paper cited by one trial page and one technology page, indexed on Europe PMC as PubMed record 30221595 and published in New England Journal of Medicine; the citing pages link this DOI, which is how the record was matched.","summary":"Background: In the primary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial, now published in the Journal, we report that the daily use of aspirin did not provide a benefit with regard to the primary end point of disability-free survival among older adults. A numerically higher rate of the secondary end point of death from any cause was observed with aspirin than with placebo.\n\nMethods: From 2010 through 2014, we enrolled community-dwelling persons in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics in the United States) and did not have cardiovascular disease, dementia, or disability. Participants were randomly assigned to receive 100 mg of enteric-coated aspirin or placebo. Deaths were classified according to the underlying cause by adjudicators who were unaware of trial-group assignments. Hazard ratios were calculated to compare mortality between the aspirin group and the placebo group, and post hoc exploratory analyses of specific causes of death were performed.\n\nResults: Of the 19,114 persons who were enrolled, 9525 were assigned to receive aspirin and 9589 to receive placebo. A total of 1052 deaths occurred during a median of 4.7 years of follow-up. The risk of death from any cause was 12.7 events per 1000 person-years in the aspirin group and 11.1 events per 1000 person-years in the placebo group (hazard ratio, 1.14; 95% confidence interval [CI], 1.01 to 1.29). Cancer was the major contributor to the higher mortality in the aspirin group, accounting for 1.6 excess deaths per 1000 person-years. Cancer-related death occurred in 3.1% of the participants in the aspirin group and in 2.3% of those in the placebo group (hazard ratio, 1.31; 95% CI, 1.10 to 1.56).\n\nConclusions: Higher all-cause mortality was observed among apparently healthy older adults who received daily aspirin than among those who received placebo and was attributed primarily to cancer-related death. In the context of previous studies, this result was unexpected and should be interpreted with caution. (Funded by the National Institute on Aging and others; ASPREE ClinicalTrials.gov number, NCT01038583.).\n\nIndexed on Europe PMC as PubMed record 30221595 (DOI 10.1056/nejmoa1803955). Matched by DOI alone: one trial page and one technology page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2018","url":"https://doi.org/10.1056/nejmoa1803955"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30221595/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30221595"}],"tags":["europepmc-ingest"],"related":["aspirin-cancer-prevention"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["aspree"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2018,"doi":"10.1056/nejmoa1803955","pmid":"30221595","authors":"McNeil JJ, Nelson MR, Woods RL, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page and one technology page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-mcneil-j-natl-cancer-inst","kind":"paper","name":"Effect of Aspirin on Cancer Incidence and Mortality in Older Adults","aka":[],"tldr":"Paper cited by one treatment page, indexed on Europe PMC as PubMed record 32778876 and published in JNCI: Journal of the National Cancer Institute; the citing page links this DOI, which is how the record was matched.","summary":"Background: ASPirin in Reducing Events in the Elderly, a randomized, double-blind, placebo-controlled trial of daily low-dose aspirin (100 mg) in older adults, showed an increase in all-cause mortality, primarily due to cancer. In contrast, prior randomized controlled trials, mainly involving younger individuals, demonstrated a delayed cancer benefit with aspirin. We now report a detailed analysis of cancer incidence and mortality.\n\nMethods: 19 114 Australian and US community-dwelling participants aged 70 years and older (US minorities 65 years and older) without cardiovascular disease, dementia, or physical disability were randomly assigned and followed for a median of 4.7 years. Fatal and nonfatal cancer events, a prespecified secondary endpoint, were adjudicated based on clinical records.\n\nResults: 981 cancer events occurred in the aspirin and 952 in the placebo groups. There was no statistically significant difference between groups for all incident cancers (hazard ratio [HR] = 1.04, 95% confidence interval [CI] = 0.95 to 1.14), hematological cancer (HR = 0.98, 95% CI = 0.73 to 1.30), or all solid cancers (HR = 1.05, 95% CI = 0.95 to 1.15), including by specific tumor type. However, aspirin was associated with an increased risk of incident cancer that had metastasized (HR = 1.19, 95% CI = 1.00 to 1.43) or was stage 4 at diagnosis (HR = 1.22, 95% CI = 1.02 to 1.45), and with higher risk of death for cancers that presented at stages 3 (HR = 2.11, 95% CI = 1.03 to 4.33) or 4 (HR = 1.31, 95% CI = 1.04 to 1.64).\n\nConclusions: In older adults, aspirin treatment had an adverse effect on later stages of cancer evolution. These findings suggest that in older persons, aspirin may accelerate the progression of cancer and, thus, suggest caution with its use in this age group.\n\nIndexed on Europe PMC as PubMed record 32778876 (DOI 10.1093/jnci/djaa114). Matched by DOI alone: one treatment page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Natl Cancer Inst 2021","url":"https://doi.org/10.1093/jnci/djaa114"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32778876/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32778876"}],"tags":["europepmc-ingest"],"related":["aspirin"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jnci"],"dependsOn":[],"notes":[],"journal":"JNCI: Journal of the National Cancer Institute","year":2021,"doi":"10.1093/jnci/djaa114","pmid":"32778876","authors":"McNeil JJ, Gibbs P, Orchard SG, et al.","paperType":"rct","findings":[],"whatItMeans":"One treatment page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-rothwell-lancet","kind":"paper","name":"Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 21144578 and published in The Lancet; the citing page links this DOI, which is how the record was matched.","summary":"Background: Treatment with daily aspirin for 5 years or longer reduces subsequent risk of colorectal cancer. Several lines of evidence suggest that aspirin might also reduce risk of other cancers, particularly of the gastrointestinal tract, but proof in man is lacking. We studied deaths due to cancer during and after randomised trials of daily aspirin versus control done originally for prevention of vascular events.\n\nMethods: We used individual patient data from all randomised trials of daily aspirin versus no aspirin with mean duration of scheduled trial treatment of 4 years or longer to determine the effect of allocation to aspirin on risk of cancer death in relation to scheduled duration of trial treatment for gastrointestinal and non-gastrointestinal cancers. In three large UK trials, long-term post-trial follow-up of individual patients was obtained from death certificates and cancer registries.\n\nResults: In eight eligible trials (25 570 patients, 674 cancer deaths), allocation to aspirin reduced death due to cancer (pooled odds ratio [OR] 0·79, 95% CI 0·68-0·92, p=0·003). On analysis of individual patient data, which were available from seven trials (23 535 patients, 657 cancer deaths), benefit was apparent only after 5 years' follow-up (all cancers, hazard ratio [HR] 0·66, 0·50-0·87; gastrointestinal cancers, 0·46, 0·27-0·77; both p=0·003). The 20-year risk of cancer death (1634 deaths in 12 659 patients in three trials) remained lower in the aspirin groups than in the control groups (all solid cancers, HR 0·80, 0·72-0·88, p<0·0001; gastrointestinal cancers, 0·65, 0·54-0·78, p<0·0001), and benefit increased (interaction p=0·01) with scheduled duration of trial treatment (≥7·5 years: all solid cancers, 0·69, 0·54-0·88, p=0·003; gastrointestinal cancers, 0·41, 0·26-0·66, p=0·0001). The latent period before an effect on deaths was about 5 years for oesophageal, pancreatic, brain, and lung cancer, but was more delayed for stomach, colorectal, and prostate cancer. For lung and oesophageal cancer, benefit was confined to adenocarcinomas, and the overall effect on 20-year risk of cancer death was greatest for adenocarcinomas (HR 0·66, 0·56-0·77, p<0·0001). Benefit was unrelated to aspirin dose (75 mg upwards), sex, or smoking, but increased with age-the absolute reduction in 20-year risk of cancer death reaching 7·08% (2·42-11·74) at age 65 years and older.\n\nInterpretation: Daily aspirin reduced deaths due to several common cancers during and after the trials. Benefit increased with duration of treatment and was consistent across the different study populations. These findings have implications for guidelines on use of aspirin and for understanding of carcinogenesis and its susceptibility to drug intervention.\n\nFunding: None.\n\nIndexed on Europe PMC as PubMed record 21144578 (DOI 10.1016/s0140-6736(10)62110-1). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet 2011","url":"https://doi.org/10.1016/s0140-6736(10)62110-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21144578/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/21144578"}],"tags":["europepmc-ingest"],"related":["microenvironment-inflammation-theory"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2011,"doi":"10.1016/s0140-6736(10)62110-1","pmid":"21144578","authors":"Rothwell PM, Fowkes FG, Belch JF, et al.","paperType":"meta-analysis","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-basch-jama","kind":"paper","name":"Effect of Electronic Symptom Monitoring on Patient-Reported Outcomes Among Patients With Metastatic Cancer: A Randomized Clinical Trial","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 35661856 and published in JAMA; the citing page links this DOI, which is how the record was matched.","summary":"Importance: Electronic systems that facilitate patient-reported outcome (PRO) surveys for patients with cancer may detect symptoms early and prompt clinicians to intervene.\n\nObjective: To evaluate whether electronic symptom monitoring during cancer treatment confers benefits on quality-of-life outcomes.\n\nDesign, setting, and participants: Report of secondary outcomes from the PRO-TECT (Alliance AFT-39) cluster randomized trial in 52 US community oncology practices randomized to electronic symptom monitoring with PRO surveys or usual care. Between October 2017 and March 2020, 1191 adults being treated for metastatic cancer were enrolled, with last follow-up on May 17, 2021.\n\nInterventions: In the PRO group, participants (n = 593) were asked to complete weekly surveys via an internet-based or automated telephone system for up to 1 year. Severe or worsening symptoms triggered care team alerts. The control group (n = 598) received usual care.\n\nMain outcomes and measures: The 3 prespecified secondary outcomes were physical function, symptom control, and health-related quality of life (HRQOL) at 3 months, measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30; range, 0-100 points; minimum clinically important difference [MCID], 2-7 for physical function; no MCID defined for symptom control or HRQOL). Results on the primary outcome, overall survival, are not yet available.\n\nResults: Among 52 practices, 1191 patients were included (mean age, 62.2 years; 694 [58.3%] women); 1066 (89.5%) completed 3-month follow-up. Compared with usual care, mean changes on the QLQ-C30 from baseline to 3 months were significantly improved in the PRO group for physical function (PRO, from 74.27 to 75.81 points; control, from 73.54 to 72.61 points; mean difference, 2.47 [95% CI, 0.41-4.53]; P =.02), symptom control (PRO, from 77.67 to 80.03 points; control, from 76.75 to 76.55 points; mean difference, 2.56 [95% CI, 0.95-4.17]; P =.002), and HRQOL (PRO, from 78.11 to 80.03 points; control, from 77.00 to 76.50 points; mean difference, 2.43 [95% CI, 0.90-3.96]; P =.002). Patients in the PRO group had significantly greater odds of experiencing clinically meaningful benefits vs usual care for physical function (7.7% more with improvements of ≥5 points and 6.1% fewer with worsening of ≥5 points; odds ratio [OR], 1.35 [95% CI, 1.08-1.70]; P =.009), symptom control (8.6% and 7.5%, respectively; OR, 1.50 [95% CI, 1.15-1.95]; P =.003), and HRQOL (8.5% and 4.9%, respectively; OR, 1.41 [95% CI, 1.10-1.81]; P =.006).\n\nConclusions and relevance: In this report of secondary outcomes from a randomized clinical trial of adults receiving cancer treatment, use of weekly electronic PRO surveys to monitor symptoms, compared with usual care, resulted in statistically significant improvements in physical function, symptom control, and HRQOL at 3 months, with mean improvements of approximately 2.5 points on a 0- to 100-point scale. These findings should be interpreted provisionally pending results of the primary outcome of overall survival.\n\nTrial registration: ClinicalTrials.gov Identifier: NCT03249090.\n\nIndexed on Europe PMC as PubMed record 35661856 (DOI 10.1001/jama.2022.9265). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA 2022","url":"https://doi.org/10.1001/jama.2022.9265"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35661856/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35661856"}],"tags":["europepmc-ingest"],"related":["epro-symptom-monitoring"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2022,"doi":"10.1001/jama.2022.9265","pmid":"35661856","authors":"Basch E, Schrag D, Henson S, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-venook-calgb-80405-cetuximab-vs-bevacizumab-jama-2017","kind":"paper","name":"Effect of first-line chemotherapy combined with cetuximab or bevacizumab on overall survival in KRAS wild-type advanced or metastatic colorectal cancer (CALGB/SWOG 80405)","aka":[],"tldr":"The American head-to-head of the same two antibodies, in 1,137 patients, found no difference: 30.0 against 29.0 months. Read next to FIRE-3, it is why sidedness had to be invoked.","summary":"Venook, Niedzwiecki, Lenz and colleagues enrolled previously untreated patients aged 18 or older with advanced or metastatic KRAS wild-type colorectal cancer at community and academic centres across the National Clinical Trials Network in the United States and Canada between November 2005 and March 2012. Patients chose mFOLFOX6 or FOLFIRI as their chemotherapy and were randomised to cetuximab (578) or bevacizumab (559). The primary endpoint was overall survival; last follow-up was December 2015.\n\nOf 1,137 patients (median age 59; 440, 39 percent, women), 1,074 (94 percent) met eligibility criteria, and 82 percent had experienced disease progression by the data cut.","asOf":"2026-09-24","links":[{"label":"JAMA 2017","url":"https://doi.org/10.1001/jama.2017.7105"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28632865/"},{"label":"Europe PMC full text (PMC5545896)","url":"https://europepmc.org/article/MED/28632865"}],"tags":["colorectal-evidence"],"related":["paper-heinemann-fire-3-cetuximab-vs-bevacizumab-lancet-oncol-2014","paper-arnold-primary-tumour-side-ras-wild-type-ann-oncol-2017"],"cancers":["colorectal"],"sections":["targeted-therapy"],"technologies":["monoclonal-antibody","antiangiogenic"],"targets":["egfr","vegf","kras"],"drugs":["cetuximab","bevacizumab","folfox","folfiri"],"companies":["alliance-oncology","swog"],"institutions":[],"pathways":[],"terms":["sidedness"],"trials":[],"people":["alan-venook","heinz-josef-lenz"],"bottlenecks":["b-negative-results"],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2017,"doi":"10.1001/jama.2017.7105","pmid":"28632865","authors":"Venook AP, Niedzwiecki D, Lenz HJ, et al.","paperType":"rct","findings":["Median overall survival 30.0 months with cetuximab-chemotherapy against 29.0 months with bevacizumab-chemotherapy: stratified hazard ratio 0.88 (95 percent CI 0.77 to 1.01, p=0.08).","Median progression-free survival 10.5 against 10.6 months (0.95, 0.84 to 1.08, p=0.45).","Response rates 59.6 against 55.2 percent (difference 4.4 percent, p=0.13).","Median follow-up for the 263 surviving patients was 47.4 months."],"whatItMeans":"The negative counterweight to FIRE-3. The two trials are reconciled only by primary tumour side, which is why the sidedness analysis rather than either trial is what guidelines now cite.","caveats":["Patients chose their chemotherapy backbone, so the trial is randomised for the antibody but not for the chemotherapy.","KRAS exon 2 wild-type only; extended RAS and sidedness were analysed afterwards.","Enrolment spanned seven years during which supportive care and later-line options changed."],"changedPractice":true,"participants":1137},{"id":"paper-astrum-005-jama-2022","kind":"paper","name":"Effect of First-Line Serplulimab vs Placebo Added to Chemotherapy on Survival in Patients With Extensive-Stage Small Cell Lung Cancer: The ASTRUM-005 Randomized Clinical Trial","aka":[],"tldr":"Published report from the ASTRUM-005 trial registered as NCT04063163, in JAMA (2022), chosen as the most cited paper whose own text cites the registry id.","summary":"Importance: Programmed cell death ligand 1 inhibitors combined with chemotherapy has changed the approach to first-line treatment in patients with extensive-stage small cell lung cancer (SCLC). It remained unknown whether adding a programmed cell death 1 (PD-1) inhibitor to chemotherapy provided similar or better benefits in patients with extensive-stage SCLC, which would add evidence on the efficacy of checkpoint inhibitors in the treatment of extensive-stage SCLC.\n\nObjective: To evaluate the efficacy and adverse event profile of the PD-1 inhibitor serplulimab plus chemotherapy compared with placebo plus chemotherapy as first-line treatment in patients with extensive-stage SCLC.\n\nDesign, setting, and participants: This international, double-blind, phase 3 randomized clinical trial (ASTRUM-005) enrolled patients at 114 hospital sites in 6 countries between September 12, 2019, and April 27, 2021. Of 894 patients who were screened, 585 with extensive-stage SCLC who had not previously received systemic therapy were randomized. Patients were followed up through October 22, 2021.\n\nInterventions: Patients were randomized 2:1 to receive either 4.5 mg/kg of serplulimab (n = 389) or placebo (n = 196) intravenously every 3 weeks. All patients received intravenous carboplatin and etoposide every 3 weeks for up to 12 weeks.\n\nMain outcomes and measures: The primary outcome was overall survival (prespecified significance threshold at the interim analysis, 2-sided P <.012). There were 13 secondary outcomes, including progression-free survival and adverse events.\n\nResults: Among the 585 patients who were randomized (mean age, 61.1 [SD, 8.67] years; 104 [17.8%] women), 246 (42.1%) completed the trial and 465 (79.5%) discontinued study treatment. All patients received study treatment and were included in the primary analyses. at the data cutoff (October 22, 2021) for this interim analysis, the median duration of follow-up was 12.3 months (range, 0.2-24.8 months). The median overall survival was significantly longer in the serplulimab group (15.4 months [95% CI, 13.3 months-not evaluable]) than in the placebo group (10.9 months [95% CI, 10.0-14.3 months]) (hazard ratio, 0.63 [95% CI, 0.49-0.82]; P <.001). The median progression-free survival (assessed by an independent radiology review committee) also was longer in the serplulimab group (5.7 months [95% CI, 5.5-6.9 months]) than in the placebo group (4.3 months [95% CI, 4.2-4.5 months]) (hazard ratio, 0.48 [95% CI, 0.38-0.59]). Treatment-related adverse events that were grade 3 or higher occurred in 129 patients (33.2%) in the serplulimab group and in 54 patients (27.6%) in the placebo group.\n\nConclusions and relevance: Among patients with previously untreated extensive-stage SCLC, serplulimab plus chemotherapy significantly improved overall survival compared with chemotherapy alone, supporting the use of serplulimab plus chemotherapy as the first-line treatment for this patient population.\n\nTrial registration: ClinicalTrials.gov Identifier: NCT04063163.\n\nIndexed on Europe PMC as PubMed record 36166026 (DOI 10.1001/jama.2022.16464). Its abstract cites the registry id NCT04063163, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"JAMA 2022","url":"https://doi.org/10.1001/jama.2022.16464"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36166026/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36166026"},{"label":"ClinicalTrials.gov NCT04063163","url":"https://clinicaltrials.gov/study/NCT04063163"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["astrum-005"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2022,"doi":"10.1001/jama.2022.16464","pmid":"36166026","authors":"Cheng Y, Han L, Wu L, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04063163 with the most citations, so it is the natural first reading for anyone following the ASTRUM-005 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-ng-jama","kind":"paper","name":"Effect of High-Dose vs Standard-Dose Vitamin D3 Supplementation on Progression-Free Survival Among Patients With Advanced or Metastatic Colorectal Cancer: The SUNSHINE Randomized Clinical Trial","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 30964527 and published in JAMA; the citing page links this DOI, which is how the record was matched.","summary":"Importance: In observational studies, higher plasma 25-hydroxyvitamin D (25[OH]D) levels have been associated with improved survival in metastatic colorectal cancer (CRC).\n\nObjective: To determine if high-dose vitamin D3 added to standard chemotherapy improves outcomes in patients with metastatic CRC.\n\nDesign, setting, and participants: Double-blind phase 2 randomized clinical trial of 139 patients with advanced or metastatic CRC conducted at 11 US academic and community cancer centers from March 2012 through November 2016 (database lock: September 2018).\n\nInterventions: mFOLFOX6 plus bevacizumab chemotherapy every 2 weeks and either high-dose vitamin D3 (n = 69) or standard-dose vitamin D3 (n = 70) daily until disease progression, intolerable toxicity, or withdrawal of consent.\n\nMain outcomes and measures: The primary end point was progression-free survival (PFS) assessed by the log-rank test and a supportive Cox proportional hazards model. Testing was 1-sided. Secondary end points included tumor objective response rate (ORR), overall survival (OS), and change in plasma 25(OH)D level.\n\nResults: Among 139 patients (mean age, 56 years; 60 [43%] women) who completed or discontinued chemotherapy and vitamin D3 (median follow-up, 22.9 months), the median PFS for high-dose vitamin D3 was 13.0 months (95% CI, 10.1 to 14.7; 49 PFS events) vs 11.0 months (95% CI, 9.5 to 14.0; 62 PFS events) for standard-dose vitamin D3 (log-rank P =.07); multivariable hazard ratio for PFS or death was 0.64 (1-sided 95% CI, 0 to 0.90; P =.02). There were no significant differences between high-dose and standard-dose vitamin D3 for tumor ORR (58% vs 63%, respectively; difference, -5% [95% CI, -20% to 100%], P =.27) or OS (median, 24.3 months vs 24.3 months; log-rank P =.43). The median 25(OH)D level at baseline for high-dose vitamin D3 was 16.1 ng/mL vs 18.7 ng/mL for standard-dose vitamin D3 (difference, -2.6 ng/mL [95% CI, -6.6 to 1.4], P =.30); at first restaging, 32.0 ng/mL vs 18.7 ng/mL (difference, 12.8 ng/mL [95% CI, 9.0 to 16.6], P <.001); at second restaging, 35.2 ng/mL vs 18.5 ng/mL (difference, 16.7 ng/mL [95% CI, 10.9 to 22.5], P <.001); and at treatment discontinuation, 34.8 ng/mL vs 18.7 ng/mL (difference, 16.2 ng/mL [95% CI, 9.9 to 22.4], P <.001). The most common grade 3 and higher adverse events for chemotherapy plus high-dose vs standard-dose vitamin D3 were neutropenia (n = 24 [35%] vs n = 21 [31%], respectively) and hypertension (n = 9 [13%] vs n = 11 [16%]).\n\nConclusions and relevance: Among patients with metastatic CRC, addition of high-dose vitamin D3, vs standard-dose vitamin D3, to standard chemotherapy resulted in a difference in median PFS that was not statistically significant, but with a significantly improved supportive hazard ratio. These findings warrant further evaluation in a larger multicenter randomized clinical trial.\n\nTrial registration: ClinicalTrials.gov Identifier: NCT01516216.\n\nIndexed on Europe PMC as PubMed record 30964527 (DOI 10.1001/jama.2019.2402). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA 2019","url":"https://doi.org/10.1001/jama.2019.2402"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30964527/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30964527"}],"tags":["europepmc-ingest"],"related":["vitamin-d-omega3-supplementation"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2019,"doi":"10.1001/jama.2019.2402","pmid":"30964527","authors":"Ng K, Nimeiri HS, McCleary NJ, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-qian-lancet-oncol","kind":"paper","name":"Effect of immunotherapy time-of-day infusion on overall survival among patients with advanced melanoma in the USA (MEMOIR): a propensity score-matched analysis of a single-centre, longitudinal study","aka":[],"tldr":"Paper cited by one pathway page and one idea page, indexed on Europe PMC as PubMed record 34780711 and published in The Lancet Oncology; the citing pages link this DOI, which is how the record was matched.","summary":"Background: The dependence of the adaptive immune system on circadian rhythm is an emerging field of study with potential therapeutic implications. We aimed to determine whether specific time-of-day patterns of immune checkpoint inhibitor infusions might alter melanoma treatment efficacy.\n\nMethods: Melanoma Outcomes Following Immunotherapy (MEMOIR) is a longitudinal study of all patients with melanoma who received ipilimumab, nivolumab, or pembrolizumab, or a combination of these at a single tertiary cancer centre (Winship Cancer Institute of Emory University, Atlanta, GA, USA). For this analysis, we collected deidentified participant-level data from the MEMOIR database for adults (age ≥18 years) diagnosed with stage IV melanoma between 2012 and 2020. Those who received fewer than four infusions were excluded. Standard of care doses were used, with modifications at the treating physicians' discretion. The primary outcome was overall survival, defined as death from any cause and indexed from date of first infusion of immune checkpoint inhibitor. We calculated the association between overall survival and proportion of infusions of immune checkpoint inhibitors received after 1630 h (a composite time cutoff derived from seminal studies of the immune-circadian rhythm to represent onset of evening) using Cox regression and propensity score-matching on age, Eastern Cooperative Oncology Group performance status, serum lactate dehydrogenase concentration, and receipt of corticosteroids and radiotherapy. Treatment-related adverse events that led to change or discontinuation of immune checkpoint inhibitors were also assessed.\n\nFindings: Between Jan 1, 2012, and Dec 31, 2020, 481 patients with melanoma received treatment with immune checkpoint inhibitors at the study centre, of whom 299 had stage IV disease and were included in this study; median follow-up was 27 months (IQR 14 to 47). In the complete unmatched sample, 102 (34%) patients were female and 197 (66%) were male, with a median age of 61 years (IQR 51 to 72). Every additional 20% of infusions of immune checkpoint inhibitors received after 1630 h (among all infusions received by a patient) conferred an overall survival hazard ratio (HR) of 1·31 (95% CI 1·00 to 1·71; p=0·046). A propensity score-matched analysis of patients who did (n=73) and did not (n=73) receive at least 20% of their infusions of immune checkpoint inhibitors after 1630 h (54 [37%] of 146 patients were women and 92 [63%] were men, with a median age of 58 years [IQR 48 to 68]) showed that having at least 20% of infusions in the evening was associated with shorter overall survival (median 4·8 years [95% CI 3·9 to not estimable] vs not reached; HR 2·04 [1·04 to 4·00; p=0·038]). This result remained robust to multivariable proportional hazards adjustment with (HR 1·80 [1·08 to 2·98; p=0·023]) and without (2·16 [1·10 to 4·25; p=0·025]) inclusion of the complete unmatched study sample. The most common adverse events were colitis (54 [18%] of 299 patients), hepatitis (27 [9%]), and hypophysitis (15 [5%]), and there were no treatment-related deaths.\n\nInterpretation: Our findings are in line with an increasing body of evidence that adaptive immune responses are less robust when initially stimulated in the evening than if stimulated in the daytime. Although prospective studies of the timing of immune checkpoint inhibitor infusions are warranted, efforts towards scheduling infusions before mid-afternoon could be considered in the multidisciplinary management of advanced melanoma.\n\nFunding: National Institutes of Health, American Society for Radiation Oncology and Melanoma Research Alliance, and Winship Cancer Institute.\n\nIndexed on Europe PMC as PubMed record 34780711 (DOI 10.1016/s1470-2045(21)00546-5). Matched by DOI alone: one pathway page and one idea page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2021","url":"https://doi.org/10.1016/s1470-2045(21)00546-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34780711/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34780711"}],"tags":["europepmc-ingest"],"related":["circadian-control","idea-chronotherapy-immunotherapy"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2021,"doi":"10.1016/s1470-2045(21)00546-5","pmid":"34780711","authors":"Qian DC, Kleber T, Brammer B, et al.","paperType":"observational","findings":[],"whatItMeans":"One pathway page and one idea page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-ridker-lancet","kind":"paper","name":"Effect of interleukin-1β inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 28855077 and published in The Lancet; the citing page links this DOI, which is how the record was matched.","summary":"Background: Inflammation in the tumour microenvironment mediated by interleukin 1β is hypothesised to have a major role in cancer invasiveness, progression, and metastases. We did an additional analysis in the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS), a randomised trial of the role of interleukin-1β inhibition in atherosclerosis, with the aim of establishing whether inhibition of a major product of the Nod-like receptor protein 3 (NLRP3) inflammasome with canakinumab might alter cancer incidence.\n\nMethods: We did a randomised, double-blind, placebo-controlled trial of canakinumab in 10 061 patients with atherosclerosis who had had a myocardial infarction, were free of previously diagnosed cancer, and had concentrations of high-sensitivity C-reactive protein (hsCRP) of 2 mg/L or greater. To assess dose-response effects, patients were randomly assigned by computer-generated codes to three canakinumab doses (50 mg, 150 mg, and 300 mg, subcutaneously every 3 months) or placebo. Participants were followed up for incident cancer diagnoses, which were adjudicated by an oncology endpoint committee masked to drug or dose allocation. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, NCT01327846. The trial is closed (the last patient visit was in June, 2017).\n\nFindings: Baseline concentrations of hsCRP (median 6·0 mg/L vs 4·2 mg/L; p<0·0001) and interleukin 6 (3·2 vs 2·6 ng/L; p<0·0001) were significantly higher among participants subsequently diagnosed with lung cancer than among those not diagnosed with cancer. During median follow-up of 3·7 years, compared with placebo, canakinumab was associated with dose-dependent reductions in concentrations of hsCRP of 26-41% and of interleukin 6 of 25-43% (p<0·0001 for all comparisons). Total cancer mortality (n=196) was significantly lower in the pooled canakinumab group than in the placebo group (p=0·0007 for trend across groups), but was significantly lower than placebo only in the 300 mg group individually (hazard ratio [HR] 0·49 [95% CI 0·31-0·75]; p=0·0009). Incident lung cancer (n=129) was significantly less frequent in the 150 mg (HR 0·61 [95% CI 0·39-0·97]; p=0·034) and 300 mg groups (HR 0·33 [95% CI 0·18-0·59]; p<0·0001; p<0·0001 for trend across groups). Lung cancer mortality was significantly less common in the canakinumab 300 mg group than in the placebo group (HR 0·23 [95% CI 0·10-0·54]; p=0·0002) and in the pooled canakinumab population than in the placebo group (p=0·0002 for trend across groups). Fatal infections or sepsis were significantly more common in the canakinumab groups than in the placebo group. All-cause mortality did not differ significantly between the canakinumab and placebo groups (HR 0·94 [95% CI 0·83-1·06]; p=0·31).\n\nInterpretation: Our hypothesis-generating data suggest the possibility that anti-inflammatory therapy with canakinumab targeting the interleukin-1β innate immunity pathway could significantly reduce incident lung cancer and lung cancer mortality. Replication of these data in formal settings of cancer screening and treatment is required.\n\nFunding: Novartis Pharmaceuticals.\n\nIndexed on Europe PMC as PubMed record 28855077 (DOI 10.1016/s0140-6736(17)32247-x). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet 2017","url":"https://doi.org/10.1016/s0140-6736(17)32247-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28855077/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28855077"}],"tags":["europepmc-ingest"],"related":["microenvironment-inflammation-theory"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2017,"doi":"10.1016/s0140-6736(17)32247-x","pmid":"28855077","authors":"Ridker PM, MacFadyen JG, Thuren T, et al.","paperType":"rct","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-van-waart-j-clin-oncol","kind":"paper","name":"Effect of Low-Intensity Physical Activity and Moderate- to High-Intensity Physical Exercise During Adjuvant Chemotherapy on Physical Fitness, Fatigue, and Chemotherapy Completion Rates: Results of the PACES Randomized Clinical Trial","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 25918291 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: We evaluated the effectiveness of a low-intensity, home-based physical activity program (Onco-Move) and a moderate- to high-intensity, combined supervised resistance and aerobic exercise program (OnTrack) versus usual care (UC) in maintaining or enhancing physical fitness, minimizing fatigue, enhancing health-related quality of life, and optimizing chemotherapy completion rates in patients undergoing adjuvant chemotherapy for breast cancer.\n\nPatients and methods: We randomly assigned patients who were scheduled to undergo adjuvant chemotherapy (N = 230) to Onco-Move, OnTrack, or UC. Performance-based and self-reported outcomes were assessed before random assignment, at the end of chemotherapy, and at the 6-month follow-up. We used generalized estimating equations to compare the groups over time.\n\nResults: Onco-Move and OnTrack resulted in less decline in cardiorespiratory fitness (P <.001), better physical functioning (P ≤.001), less nausea and vomiting (P =.029 and.031, respectively) and less pain (P =.003 and.011, respectively) compared with UC. OnTrack also resulted in better outcomes for muscle strength (P =.002) and physical fatigue (P <.001). At the 6-month follow-up, most outcomes returned to baseline levels for all three groups. A smaller percentage of participants in OnTrack required chemotherapy dose adjustments than those in the UC or Onco-Move groups (P =.002). Both intervention groups returned earlier (P =.012), as well as for more hours per week (P =.014), to work than the control group.\n\nConclusion: A supervised, moderate- to high-intensity, combined resistance and aerobic exercise program is most effective for patients with breast cancer undergoing adjuvant chemotherapy. A home-based, low-intensity physical activity program represents a viable alternative for women who are unable or unwilling to follow the higher intensity program.\n\nIndexed on Europe PMC as PubMed record 25918291 (DOI 10.1200/jco.2014.59.1081). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2015","url":"https://doi.org/10.1200/jco.2014.59.1081"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25918291/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25918291"}],"tags":["europepmc-ingest"],"related":["exercise-during-chemotherapy"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2015,"doi":"10.1200/jco.2014.59.1081","pmid":"25918291","authors":"van Waart H, Stuiver MM, van Harten WH, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-goodwin-jama","kind":"paper","name":"Effect of Metformin vs Placebo on Invasive Disease-Free Survival in Patients With Breast Cancer: The MA.32 Randomized Clinical Trial","aka":[],"tldr":"Paper cited by one bottleneck page, indexed on Europe PMC as PubMed record 35608580 and published in JAMA; the citing page links this DOI, which is how the record was matched.","summary":"Importance: Metformin, a biguanide commonly used to treat type 2 diabetes, has been associated with potential beneficial effects across breast cancer subtypes in observational and preclinical studies.\n\nObjective: To determine whether the administration of adjuvant metformin (vs placebo) to patients with breast cancer without diabetes improves outcomes.\n\nDesign, setting, and participants: MA.32, a phase 3 randomized, placebo-controlled, double-blind trial, conducted in Canada, Switzerland, US, and UK, enrolled 3649 patients with high-risk nonmetastatic breast cancer receiving standard therapy between August 2010 and March 2013, with follow-up to October 2020.\n\nInterventions: Patients were randomized (stratified for hormone receptor [estrogen receptor and/or progesterone receptor {ER/PgR}] status, positive vs negative; body mass index, ≤30 vs >30; human epidermal growth factor receptor 2 [ERBB2, formerly HER2 or HER2/neu], positive vs negative; and any vs no chemotherapy) to 850 mg of oral metformin twice a day (n = 1824) or oral placebo twice a day (n = 1825) for 5 years.\n\nMain outcomes and measures: The primary outcome was invasive disease-free survival in hormone receptor-positive breast cancer. Of the 8 secondary outcomes, overall survival, distant relapse-free survival, and breast cancer-free interval were analyzed.\n\nResults: Of the 3649 randomized patients (mean age, 52.4 years; 3643 women [99.8%]), all (100%) were included in analyses. After a second interim analysis, futility was declared for patients who were ER/PgR-, so the primary analysis was conducted for 2533 patients who were ER/PgR+. The median duration of follow-up in the ER/PgR+ group was 96.2 months (range, 0.2-121 months). Invasive disease-free survival events occurred in 465 patients who were ER/PgR+. The incidence rates for invasive disease-free survival events were 2.78 per 100 patient-years in the metformin group vs 2.74 per 100 patient-years in the placebo group (hazard ratio [HR], 1.01; 95% CI, 0.84-1.21; P =.93), and the incidence rates for death were 1.46 per 100 patient-years in the metformin group vs 1.32 per 100 patient-years in the placebo group (HR, 1.10; 95% CI, 0.86-1.41; P =.47). Among patients who were ER/PgR-, followed up for a median of 94.1 months, incidence of invasive disease-free survival events was 3.58 vs 3.60 per 100 patient-years, respectively (HR, 1.01; 95% CI, 0.79-1.30; P =.92). None of the 3 secondary outcomes analyzed in the ER/PgR+ group had statistically significant differences. Grade 3 nonhematological toxic events occurred more frequently in patients taking metformin than in patients taking placebo (21.5% vs 17.5%, respectively, P =.003). The most common grade 3 or higher adverse events in the metformin vs placebo groups were hypertension (2.4% vs 1.9%), irregular menses (1.5% vs 1.4%), and diarrhea (1.9% vs 7.0%).\n\nConclusions and relevance: Among patients with high-risk operable breast cancer without diabetes, the addition of metformin vs placebo to standard breast cancer treatment did not significantly improve invasive disease-free survival.\n\nTrial registration: ClinicalTrials.gov Identifier: NCT01101438.\n\nIndexed on Europe PMC as PubMed record 35608580 (DOI 10.1001/jama.2022.6147). Matched by DOI alone: one bottleneck page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA 2022","url":"https://doi.org/10.1001/jama.2022.6147"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35608580/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35608580"}],"tags":["europepmc-ingest"],"related":["b-generic-repurposing"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2022,"doi":"10.1001/jama.2022.6147","pmid":"35608580","authors":"Goodwin PJ, Chen BE, Gelmon KA, et al.","paperType":"rct","findings":[],"whatItMeans":"One bottleneck page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-molenaar-jama-surg","kind":"paper","name":"Effect of Multimodal Prehabilitation on Reducing Postoperative Complications and Enhancing Functional Capacity Following Colorectal Cancer Surgery: The PREHAB Randomized Clinical Trial","aka":[],"tldr":"Paper cited by one trial page and one technology page, indexed on Europe PMC as PubMed record 36988937 and published in JAMA surgery; the citing pages link this DOI, which is how the record was matched.","summary":"Importance: Colorectal surgery is associated with substantial morbidity rates and a lowered functional capacity. Optimization of the patient's condition in the weeks prior to surgery may attenuate these unfavorable sequelae.\n\nObjective: To determine whether multimodal prehabilitation before colorectal cancer surgery can reduce postoperative complications and enhance functional recovery.\n\nDesign, setting, and participants: The PREHAB randomized clinical trial was an international, multicenter trial conducted in teaching hospitals with implemented enhanced recovery after surgery programs. Adult patients with nonmetastasized colorectal cancer were assessed for eligibility and randomized to either prehabilitation or standard care. Both arms received standard perioperative care. Patients were enrolled from June 2017 to December 2020, and follow-up was completed in December 2021. However, this trial was prematurely stopped due to the COVID-19 pandemic.\n\nInterventions: The 4-week in-hospital supervised multimodal prehabilitation program consisted of a high-intensity exercise program 3 times per week, a nutritional intervention, psychological support, and a smoking cessation program when needed.\n\nMain outcomes and measures: Comprehensive Complication Index (CCI) score, number of patients with CCI score more than 20, and improved walking capacity expressed as the 6-minute walking distance 4 weeks postoperatively.\n\nResults: In the intention-to-treat population of 251 participants (median [IQR] age, 69 [60-76] years; 138 [55%] male), 206 (82%) had tumors located in the colon and 234 (93%) underwent laparoscopic- or robotic-assisted surgery. The number of severe complications (CCI score >20) was significantly lower favoring prehabilitation compared with standard care (21 of 123 [17.1%] vs 38 of 128 [29.7%]; odds ratio, 0.47 [95% CI, 0.26-0.87]; P =.02). Participants in prehabilitation encountered fewer medical complications (eg, respiratory) compared with participants receiving standard care (19 of 123 [15.4%] vs 35 of 128 [27.3%]; odds ratio, 0.48 [95% CI, 0.26-0.89]; P =.02). Four weeks after surgery, 6-minute walking distance did not differ significantly between groups when compared with baseline (mean difference prehabilitation vs standard care 15.6 m [95% CI, -1.4 to 32.6]; P =.07). Secondary parameters of functional capacity in the postoperative period generally favored prehabilitation compared with standard care.\n\nConclusions and relevance: This PREHAB trial demonstrates the benefit of a multimodal prehabilitation program before colorectal cancer surgery as reflected by fewer severe and medical complications postoperatively and an optimized postoperative recovery compared with standard care.\n\nTrial registration: trialregister.nl Identifier: NTR5947.\n\nIndexed on Europe PMC as PubMed record 36988937 (DOI 10.1001/jamasurg.2023.0198). Matched by DOI alone: one trial page and one technology page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA Surg 2023","url":"https://doi.org/10.1001/jamasurg.2023.0198"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36988937/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36988937"}],"tags":["europepmc-ingest"],"related":["prehabilitation"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["prehab-trial"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"JAMA surgery","year":2023,"doi":"10.1001/jamasurg.2023.0198","pmid":"36988937","authors":"Molenaar CJL, Minnella EM, Coca-Martinez M, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page and one technology page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-reardon-jama-oncol","kind":"paper","name":"Effect of Nivolumab vs Bevacizumab in Patients With Recurrent Glioblastoma: The CheckMate 143 Phase 3 Randomized Clinical Trial","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 32437507 and published in JAMA Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Importance: Clinical outcomes for glioblastoma remain poor. Treatment with immune checkpoint blockade has shown benefits in many cancer types. To our knowledge, data from a randomized phase 3 clinical trial evaluating a programmed death-1 (PD-1) inhibitor therapy for glioblastoma have not been reported.\n\nObjective: To determine whether single-agent PD-1 blockade with nivolumab improves survival in patients with recurrent glioblastoma compared with bevacizumab.\n\nDesign, setting, and participants: In this open-label, randomized, phase 3 clinical trial, 439 patients with glioblastoma at first recurrence following standard radiation and temozolomide therapy were enrolled, and 369 were randomized. Patients were enrolled between September 2014 and May 2015. The median follow-up was 9.5 months at data cutoff of January 20, 2017. The study included 57 multicenter, multinational clinical sites.\n\nInterventions: Patients were randomized 1:1 to nivolumab 3 mg/kg or bevacizumab 10 mg/kg every 2 weeks until confirmed disease progression, unacceptable toxic effects, or death.\n\nMain outcomes and measures: The primary end point was overall survival (OS).\n\nResults: A total of 369 patients were randomized to nivolumab (n = 184) or bevacizumab (n = 185). The MGMT promoter was methylated in 23.4% (43/184; nivolumab) and 22.7% (42/185; bevacizumab), unmethylated in 32.1% (59/184; nivolumab) and 36.2% (67/185; bevacizumab), and not reported in remaining patients. At median follow-up of 9.5 months, median OS (mOS) was comparable between groups: nivolumab, 9.8 months (95% CI, 8.2-11.8); bevacizumab, 10.0 months (95% CI, 9.0-11.8); HR, 1.04 (95% CI, 0.83-1.30); P =.76. The 12-month OS was 42% in both groups. The objective response rate was higher with bevacizumab (23.1%; 95% CI, 16.7%-30.5%) vs nivolumab (7.8%; 95% CI, 4.1%-13.3%). Grade 3/4 treatment-related adverse events (TRAEs) were similar between groups (nivolumab, 33/182 [18.1%]; bevacizumab, 25/165 [15.2%]), with no unexpected neurological TRAEs or deaths due to TRAEs.\n\nConclusions and relevance: Although the primary end point was not met in this randomized clinical trial, mOS was comparable between nivolumab and bevacizumab in the overall patient population with recurrent glioblastoma. The safety profile of nivolumab in patients with glioblastoma was consistent with that in other tumor types.\n\nTrial registration: ClinicalTrials.gov Identifier: NCT02017717.\n\nIndexed on Europe PMC as PubMed record 32437507 (DOI 10.1001/jamaoncol.2020.1024). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA Oncol 2020","url":"https://doi.org/10.1001/jamaoncol.2020.1024"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32437507/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32437507"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-143"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2020,"doi":"10.1001/jamaoncol.2020.1024","pmid":"32437507","authors":"Reardon DA, Brandes AA, Omuro A, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-i-spy-2-jama-oncol-2020","kind":"paper","name":"Effect of Pembrolizumab Plus Neoadjuvant Chemotherapy on Pathologic Complete Response in Women With Early-Stage Breast Cancer: An Analysis of the Ongoing Phase 2 Adaptively Randomized I-SPY2 Trial","aka":[],"tldr":"Published report from the I-SPY 2 trial registered as NCT01042379, in JAMA Oncology (2020), chosen as the most cited paper whose own text cites the registry id.","summary":"Importance: Approximately 25% of patients with early-stage breast cancer who receive (neo)adjuvant chemotherapy experience a recurrence within 5 years. Improvements in therapy are greatly needed.\n\nObjective: To determine if pembrolizumab plus neoadjuvant chemotherapy (NACT) in early-stage breast cancer is likely to be successful in a 300-patient, confirmatory randomized phase 3 neoadjuvant clinical trial.\n\nDesign, setting, and participants: The I-SPY2 study is an ongoing open-label, multicenter, adaptively randomized phase 2 platform trial for high-risk, stage II/III breast cancer, evaluating multiple investigational arms in parallel. Standard NACT serves as the common control arm; investigational agent(s) are added to this backbone. Patients with ERBB2 (formerly HER2)-negative breast cancer were eligible for randomization to pembrolizumab between November 2015 and November 2016.\n\nInterventions: Participants were randomized to receive taxane- and anthracycline-based NACT with or without pembrolizumab, followed by definitive surgery.\n\nMain outcomes and measures: The primary end point was pathologic complete response (pCR). Secondary end points were residual cancer burden (RCB) and 3-year event-free and distant recurrence-free survival. Investigational arms graduated when demonstrating an 85% predictive probability of success in a hypothetical confirmatory phase 3 trial.\n\nResults: Of the 250 women included in the final analysis, 181 were randomized to the standard NACT control group (median [range] age, 47 [24.77] years). Sixty-nine women (median [range] age, 50 [27-71] years) were randomized to 4 cycles of pembrolizumab in combination with weekly paclitaxel followed by AC; 40 hormone receptor (HR)-positive and 29 triple-negative. Pembrolizumab graduated in all 3 biomarker signatures studied. Final estimated pCR rates, evaluated in March 2017, were 44% vs 17%, 30% vs 13%, and 60% vs 22% for pembrolizumab vs control in the ERBB2-negative, HR-positive/ERBB2-negative, and triple-negative cohorts, respectively. Pembrolizumab shifted the RCB distribution to a lower disease burden for each cohort evaluated. Adverse events included immune-related endocrinopathies, notably thyroid abnormalities (13.0%) and adrenal insufficiency (8.7%). Achieving a pCR appeared predictive of long-term outcome, where patients with pCR following pembrolizumab plus chemotherapy had high event-free survival rates (93% at 3 years with 2.8 years' median follow-up).\n\nConclusions and relevance: When added to standard neoadjuvant chemotherapy, pembrolizumab more than doubled the estimated pCR rates for both HR-positive/ERBB2-negative and triple-negative breast cancer, indicating that checkpoint blockade in women with early-stage, high-risk, ERBB2-negative breast cancer is highly likely to succeed in a phase 3 trial. Pembrolizumab was the first of 10 agents to graduate in the HR-positive/ERBB2-negative signature.\n\nTrial registration: ClinicalTrials.gov Identifier: NCT01042379.\n\nIndexed on Europe PMC as PubMed record 32053137 (DOI 10.1001/jamaoncol.2019.6650). Its abstract cites the registry id NCT01042379, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"JAMA Oncol 2020","url":"https://doi.org/10.1001/jamaoncol.2019.6650"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32053137/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32053137"},{"label":"ClinicalTrials.gov NCT01042379","url":"https://clinicaltrials.gov/study/NCT01042379"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["i-spy-2"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2020,"doi":"10.1001/jamaoncol.2019.6650","pmid":"32053137","authors":"Nanda R, Liu MC, Yau C, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT01042379 with the most citations, so it is the natural first reading for anyone following the I-SPY 2 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-badwe-j-clin-oncol","kind":"paper","name":"Effect of Peritumoral Infiltration of Local Anesthetic Before Surgery on Survival in Early Breast Cancer","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 37023374 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: Preventing metastases by using perioperative interventions has not been adequately explored. Local anesthesia blocks voltage-gated sodium channels and thereby prevents activation of prometastatic pathways. We conducted an open-label, multicenter randomized trial to test the impact of presurgical, peritumoral infiltration of local anesthesia on disease-free survival (DFS).\n\nMethods: Women with early breast cancer planned for upfront surgery without prior neoadjuvant treatment were randomly assigned to receive peritumoral injection of 0.5% lidocaine, 7-10 minutes before surgery (local anesthetics [LA] arm) or surgery without lidocaine (no LA arm). Random assignment was stratified by menopausal status, tumor size, and center. Participants received standard postoperative adjuvant treatment. Primary and secondary end points were DFS and overall survival (OS), respectively.\n\nResults: Excluding eligibility violations, 1,583 of 1,600 randomly assigned patients were included in this analysis (LA, 796; no LA, 804). At a median follow-up of 68 months, there were 255 DFS events (LA, 109; no LA, 146) and 189 deaths (LA, 79; no LA, 110). In LA and no LA arms, 5-year DFS rates were 86.6% and 82.6% (hazard ratio [HR], 0.74; 95% CI, 0.58 to 0.95; P =.017) and 5-year OS rates were 90.1% and 86.4%, respectively (HR, 0.71; 95% CI, 0.53 to 0.94; P =.019). The impact of LA was similar in subgroups defined by menopausal status, tumor size, nodal metastases, and hormone receptor and human epidermal growth factor receptor 2 status. Using competing risk analyses, in LA and no LA arms, 5-year cumulative incidence rates of locoregional recurrence were 3.4% and 4.5% (HR, 0.68; 95% CI, 0.41 to 1.11), and distant recurrence rates were 8.5% and 11.6%, respectively (HR, 0.73; 95% CI, 0.53 to 0.99). There were no adverse events because of lidocaine injection.\n\nConclusion: Peritumoral injection of lidocaine before breast cancer surgery significantly increases DFS and OS. Altering events at the time of surgery can prevent metastases in early breast cancer (CTRI/2014/11/005228).[Media: see text].\n\nIndexed on Europe PMC as PubMed record 37023374 (DOI 10.1200/jco.22.01966). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2023","url":"https://doi.org/10.1200/jco.22.01966"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37023374/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37023374"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["lidocaine-peritumoral-tmh"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2023,"doi":"10.1200/jco.22.01966","pmid":"37023374","authors":"Badwe RA, Parmar V, Nair N, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-pellacani-jama-dermatol","kind":"paper","name":"Effect of Reflectance Confocal Microscopy for Suspect Lesions on Diagnostic Accuracy in Melanoma: A Randomized Clinical Trial","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 35648432 and published in JAMA dermatology; the citing page links this DOI, which is how the record was matched.","summary":"Importance: Previous systematic reviews and meta-analyses have concluded that given data paucity, a comparison of reflectance confocal microscopy (RCM) with dermoscopy is complex. They recommend comparative prospective studies in a real-world setting of suspect lesions.\n\nObjective: To test the hypothesis that RCM reduces unnecessary lesion excision by more than 30% and identifies all melanoma lesions thicker than 0.5 mm at baseline.\n\nDesign, setting, and participants: This randomized clinical trial included 3165 patients enrolled from 3 dermatology referral centers in Italy between January 2017 and December 2019, with a mean (SD) follow-up of 9.6 (6.9) months (range, 1.9-37.0 months). The consecutive sample of 3165 suspect lesions determined through dermoscopy were eligible for inclusion (10 patients refused). Diagnostic analysis included 3078 patients (48 lost, 39 refused excision). Data were analyzed between April and September 2021.\n\nInterventions: Patients were randomly assigned 1:1 to standard therapeutic care (clinical and dermoscopy evaluation) with or without adjunctive RCM. Information available guided prospective clinical decision-making (excision or follow-up).\n\nMain outcomes and measures: Hypotheses were defined prior to study initiation. All lesions excised (baseline and follow-up) were registered, including histopathological diagnoses/no change at dermoscopy follow-up (with or without adjunctive RCM). Number needed to excise (total number of excised lesions/number of melanomas) and Breslow thickness of delayed diagnosed melanomas were calculated based on real-life, prospective, clinical decision-making.\n\nResults: Among the 3165 participants, 1608 (50.8%) were male, and mean (SD) age was 49.3 (14.9) years. When compared with standard therapeutic care only, adjunctive RCM was associated with a higher positive predictive value (18.9 vs 33.3), lower benign to malignant ratio (3.7:1.0 vs 1.8:1.0), and a number needed to excise reduction of 43.4% (5.3 vs 3.0). All lesions (n = 15) with delayed melanoma diagnoses were thinner than 0.5 mm.\n\nConclusions and relevance: This randomized clinical trial shows that adjunctive use of RCM for suspect lesions reduces unnecessary excisions and assures the removal of aggressive melanomas at baseline in a real-life, clinical decision-making application for referral centers with RCM.\n\nTrial registration: ClinicalTrials.gov Identifier: NCT04789421.\n\nIndexed on Europe PMC as PubMed record 35648432 (DOI 10.1001/jamadermatol.2022.1570). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA Dermatol 2022","url":"https://doi.org/10.1001/jamadermatol.2022.1570"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35648432/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35648432"}],"tags":["europepmc-ingest"],"related":["confocal-oct-skin-imaging"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"JAMA dermatology","year":2022,"doi":"10.1001/jamadermatol.2022.1570","pmid":"35648432","authors":"Pellacani G, Farnetani F, Ciardo S, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-sankaranarayanan-oral-screening-lancet-2005","kind":"paper","name":"Effect of screening on oral cancer mortality in Kerala, India","aka":[],"tldr":"Visual examination of the mouth by trained health workers reduced oral cancer deaths by a third among tobacco and alcohol users in Kerala, the only randomised evidence that oral cancer screening works.","summary":"Cluster-randomised trial in 13 clusters of Trivandrum district: 96,517 people in seven intervention clusters received three rounds of oral visual inspection by trained health workers and 95,356 in six control clusters received usual care. Oral cancer deaths were 77 versus 87 (mortality rate ratio 0.79; 95% CI 0.51-1.22 overall), with a significant reduction in tobacco or alcohol users (0.66; 95% CI 0.45-0.95) and in male users (0.57; 0.35-0.93). The 15-year follow-up (Oral Oncology 2013) showed a 24% mortality reduction in users after four rounds and 81% (69-89%) in users who attended all four rounds.","asOf":"2026-09-10","links":[{"label":"Lancet 2005","url":"https://doi.org/10.1016/S0140-6736(05)66658-5"},{"label":"15-year follow-up (Oral Oncology 2013)","url":"https://doi.org/10.1016/j.oraloncology.2012.11.004"}],"tags":[],"related":[],"cancers":["head-and-neck"],"sections":[],"technologies":["chemoprevention"],"targets":[],"drugs":[],"companies":[],"institutions":["iarc"],"pathways":[],"terms":[],"trials":["kerala-oral-screening"],"people":["sankaranarayanan-rengaswamy"],"bottlenecks":["b-early-detection","b-prevention-adoption"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2005,"doi":"10.1016/S0140-6736(05)66658-5","authors":"Sankaranarayanan R, Ramadas K, Thomas G, et al.","paperType":"rct","findings":["Oral cancer mortality rate ratio 0.79 overall (not significant) and 0.66 in tobacco or alcohol users (significant).","Male tobacco or alcohol users: rate ratio 0.57.","15-year follow-up: 81% lower oral cancer mortality in users who attended all four screening rounds, and 38% lower incidence.","Screening was done by trained non-medical health workers, not dentists or doctors."],"whatItMeans":"Targeted visual screening of tobacco and alcohol users is a cheap, workable way to cut oral cancer deaths in high-incidence countries, and is the basis for India's national oral cancer screening component. Its effect depends on people attending repeatedly and on treatment being available.","caveats":["Overall (all-comer) mortality reduction was not statistically significant; the benefit is concentrated in high-risk users.","Cluster trial with 13 clusters, which limits precision.","Compliance with referral and treatment was incomplete, so real programmes may achieve less."],"changedPractice":true,"participants":191873},{"id":"paper-hoskin-jama","kind":"paper","name":"Effect of Single-Fraction vs Multifraction Radiotherapy on Ambulatory Status Among Patients With Spinal Canal Compression From Metastatic Cancer: The SCORAD Randomized Clinical Trial","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 31794625 and published in JAMA; the citing page links this DOI, which is how the record was matched.","summary":"Importance: Malignant spinal canal compression, a major complication of metastatic cancer, is managed with radiotherapy to maintain mobility and relieve pain, although there is no standard radiotherapy regimen.\n\nObjective: To evaluate whether single-fraction radiotherapy is noninferior to 5 fractions of radiotherapy.\n\nDesign, setting, and participants: Multicenter noninferiority randomized clinical trial conducted in 42 UK and 5 Australian radiotherapy centers. Eligible patients (n = 686) had metastatic cancer with spinal cord or cauda equina compression, life expectancy greater than 8 weeks, and no previous radiotherapy to the same area. Patients were recruited between February 2008 and April 2016, with final follow-up in September 2017.\n\nInterventions: Patients were randomized to receive external beam single-fraction 8-Gy radiotherapy (n = 345) or 20 Gy of radiotherapy in 5 fractions over 5 consecutive days (n = 341).\n\nMain outcomes and measures: The primary end point was ambulatory status at week 8, based on a 4-point scale and classified as grade 1 (ambulatory without the use of aids and grade 5 of 5 muscle power) or grade 2 (ambulatory using aids or grade 4 of 5 muscle power). The noninferiority margin for the difference in ambulatory status was -11%. Secondary end points included ambulatory status at weeks 1, 4, and 12 and overall survival.\n\nResults: Among 686 randomized patients (median [interquartile range] age, 70 [64-77] years; 503 (73%) men; 44% had prostate cancer, 19% had lung cancer, and 12% had breast cancer), 342 (49.8%) were analyzed for the primary end point (255 patients died before the 8-week assessment). Ambulatory status grade 1 or 2 at week 8 was achieved by 115 of 166 (69.3%) patients in the single-fraction group vs 128 of 176 (72.7%) in the multifraction group (difference, -3.5% [1-sided 95% CI, -11.5% to ∞]; P value for noninferiority =.06). The difference in ambulatory status grade 1 or 2 in the single-fraction vs multifraction group was -0.4% (63.9% vs 64.3%; [1-sided 95% CI, -6.9 to ∞]; P value for noninferiority =.004) at week 1, -0.7% (66.8% vs 67.6%; [1-sided 95% CI, -8.1 to ∞]; P value for noninferiority =.01) at week 4, and 4.1% (71.8% vs 67.7%; [1-sided 95% CI, -4.6 to ∞]; P value for noninferiority =.002) at week 12. Overall survival rates at 12 weeks were 50% in the single-fraction group vs 55% in the multifraction group (stratified hazard ratio, 1.02 [95% CI, 0.74-1.41]). Of the 11 other secondary end points that were analyzed, the between-group differences were not statistically significant or did not meet noninferiority criterion.\n\nConclusions and relevance: Among patients with malignant metastatic solid tumors and spinal canal compression, a single radiotherapy dose, compared with a multifraction dose delivered over 5 days, did not meet the criterion for noninferiority for the primary outcome (ambulatory at 8 weeks). However, the extent to which the lower bound of the CI overlapped with the noninferiority margin should be considered when interpreting the clinical importance of this finding.\n\nTrial registration: ISRCTN Identifiers: ISRCTN97555949 and ISRCTN97108008.\n\nIndexed on Europe PMC as PubMed record 31794625 (DOI 10.1001/jama.2019.17913). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA 2019","url":"https://doi.org/10.1001/jama.2019.17913"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31794625/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31794625"}],"tags":["europepmc-ingest"],"related":["palliative-radiotherapy"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2019,"doi":"10.1001/jama.2019.17913","pmid":"31794625","authors":"Hoskin PJ, Hopkins K, Misra V, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-garcia-jama-netw-open","kind":"paper","name":"Effect of True and Sham Acupuncture on Radiation-Induced Xerostomia Among Patients With Head and Neck Cancer: A Randomized Clinical Trial","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 31808921 and published in JAMA network open; the citing page links this DOI, which is how the record was matched.","summary":"Importance: Radiation-induced xerostomia (RIX) is a common, often debilitating, adverse effect of radiation therapy among patients with head and neck cancer. Quality of life can be severely affected, and current treatments have limited benefit.\n\nObjective: To determine if acupuncture can prevent RIX in patients with head and neck cancer undergoing radiation therapy.\n\nDesign, setting, and participants: This 2-center, phase 3, randomized clinical trial compared a standard care control (SCC) with true acupuncture (TA) and sham acupuncture (SA) among patients with oropharyngeal or nasopharyngeal carcinoma who were undergoing radiation therapy in comprehensive cancer centers in the United States and China. Patients were enrolled between December 16, 2011, and July 7, 2015. Final follow-up was August 15, 2016. Analyses were conducted February 1 through 28, 2019.\n\nIntervention: Either TA or SA using a validated acupuncture placebo device was performed 3 times per week during a 6- to 7-week course of radiation therapy.\n\nMain outcomes and measures: The primary end point was RIX, as determined by the Xerostomia Questionnaire in which a higher score indicates worse RIX, for combined institutions 1 year after radiation therapy ended. Secondary outcomes included incidence of clinically significant xerostomia (score >30), salivary flow, quality of life, salivary constituents, and role of baseline expectancy related to acupuncture on outcomes.\n\nResults: Of 399 patients randomized, 339 were included in the final analysis (mean [SD] age, 51.3 [11.7] years; age range, 21-79 years; 258 [77.6%] men), including 112 patients in the TA group, 115 patients in the SA group, and 112 patients in the SCC group. For the primary aim, the adjusted least square mean (SD) xerostomia score in the TA group (26.6 [17.7]) was significantly lower than in the SCC group (34.8 [18.7]) (P =.001; effect size = -0.44) and marginally lower but not statistically significant different from the SA group (31.3 [18.6]) (P =.06; effect size = -0.26). Incidence of clinically significant xerostomia 1 year after radiation therapy ended followed a similar pattern, with 38 patients in the TA group (34.6%), 54 patients in the SA group (47.8%), and 60 patients in the SCC group (55.1%) experiencing clinically significant xerostomia (P =.009). Post hoc comparisons revealed a significant difference between the TA and SCC groups at both institutions, but TA was significantly different from SA only at Fudan University Cancer Center, Shanghai, China (estimated difference [SE]: TA vs SCC, -9.9 [2.5]; P <.001; SA vs SCC, -1.7 [2.5]; P =.50; TA vs SA, -8.2 [2.5]; P =.001), and SA was significantly different from SCC only at the University of Texas MD Anderson Cancer Center, Houston, Texas (estimated difference [SE]: TA vs SCC, -8.1 [3.4]; P =.016; SA vs SCC, -10.5 [3.3]; P =.002; TA vs SA, 2.4 [3.2]; P =.45).\n\nConclusions and relevance: This randomized clinical trial found that TA resulted in significantly fewer and less severe RIX symptoms 1 year after treatment vs SCC. However, further studies are needed to confirm clinical relevance and generalizability of this finding and to evaluate inconsistencies in response to sham acupuncture between patients in the United States and China.\n\nTrial registration: ClinicalTrials.gov identifier: NCT01266044.\n\nIndexed on Europe PMC as PubMed record 31808921 (DOI 10.1001/jamanetworkopen.2019.16910). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA Netw Open 2019","url":"https://doi.org/10.1001/jamanetworkopen.2019.16910"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31808921/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31808921"}],"tags":["europepmc-ingest"],"related":["acupuncture-xerostomia"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"JAMA network open","year":2019,"doi":"10.1001/jamanetworkopen.2019.16910","pmid":"31808921","authors":"Garcia MK, Meng Z, Rosenthal DI, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-stupp-jama","kind":"paper","name":"Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial","aka":[],"tldr":"Paper cited by one roadmap page, indexed on Europe PMC as PubMed record 29260225 and published in JAMA; the citing page links this DOI, which is how the record was matched.","summary":"Importance: Tumor-treating fields (TTFields) is an antimitotic treatment modality that interferes with glioblastoma cell division and organelle assembly by delivering low-intensity alternating electric fields to the tumor.\n\nObjective: To investigate whether TTFields improves progression-free and overall survival of patients with glioblastoma, a fatal disease that commonly recurs at the initial tumor site or in the central nervous system.\n\nDesign, setting, and participants: In this randomized, open-label trial, 695 patients with glioblastoma whose tumor was resected or biopsied and had completed concomitant radiochemotherapy (median time from diagnosis to randomization, 3.8 months) were enrolled at 83 centers (July 2009-2014) and followed up through December 2016. A preliminary report from this trial was published in 2015; this report describes the final analysis.\n\nInterventions: Patients were randomized 2:1 to TTFields plus maintenance temozolomide chemotherapy (n = 466) or temozolomide alone (n = 229). The TTFields, consisting of low-intensity, 200 kHz frequency, alternating electric fields, was delivered (≥ 18 hours/d) via 4 transducer arrays on the shaved scalp and connected to a portable device. Temozolomide was administered to both groups (150-200 mg/m2) for 5 days per 28-day cycle (6-12 cycles).\n\nMain outcomes and measures: Progression-free survival (tested at α =.046). The secondary end point was overall survival (tested hierarchically at α =.048). Analyses were performed for the intent-to-treat population. Adverse events were compared by group.\n\nResults: Of the 695 randomized patients (median age, 56 years; IQR, 48-63; 473 men [68%]), 637 (92%) completed the trial. Median progression-free survival from randomization was 6.7 months in the TTFields-temozolomide group and 4.0 months in the temozolomide-alone group (HR, 0.63; 95% CI, 0.52-0.76; P <.001). Median overall survival was 20.9 months in the TTFields-temozolomide group vs 16.0 months in the temozolomide-alone group (HR, 0.63; 95% CI, 0.53-0.76; P <.001). Systemic adverse event frequency was 48% in the TTFields-temozolomide group and 44% in the temozolomide-alone group. Mild to moderate skin toxicity underneath the transducer arrays occurred in 52% of patients who received TTFields-temozolomide vs no patients who received temozolomide alone.\n\nConclusions and relevance: In the final analysis of this randomized clinical trial of patients with glioblastoma who had received standard radiochemotherapy, the addition of TTFields to maintenance temozolomide chemotherapy vs maintenance temozolomide alone, resulted in statistically significant improvement in progression-free survival and overall survival. These results are consistent with the previous interim analysis.\n\nTrial registration: clinicaltrials.gov Identifier: NCT00916409.\n\nIndexed on Europe PMC as PubMed record 29260225 (DOI 10.1001/jama.2017.18718). Matched by DOI alone: one roadmap page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA 2017","url":"https://doi.org/10.1001/jama.2017.18718"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29260225/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29260225"}],"tags":["europepmc-ingest"],"related":["devices-roadmap"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2017,"doi":"10.1001/jama.2017.18718","pmid":"29260225","authors":"Stupp R, Taillibert S, Kanner A, et al.","paperType":"rct","findings":[],"whatItMeans":"One roadmap page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-shastri-j-natl-cancer-inst","kind":"paper","name":"Effect of VIA screening by primary health workers: randomized controlled study in Mumbai, India","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 24563518 and published in JNCI: Journal of the National Cancer Institute; the citing page links this DOI, which is how the record was matched.","summary":"Background: Cervical cancer is the leading cause of cancer mortality among women in India. Because Pap smear screening is not feasible in India, we need to develop effective alternatives.\n\nMethods: A cluster-randomized controlled study was initiated in 1998 in Mumbai, India, to investigate the efficacy of visual inspection with acetic acid (VIA) performed by primary health workers in reducing cervical cancer mortality. Four rounds of cancer education and VIA screening were conducted at 24-month intervals in the screening group, whereas cancer education was offered once at entry to the control group. The study was planned for 16 years to include four screening rounds followed by four monitoring rounds. We present results after 12 years of follow-up. Poisson regression method was used to calculate the rate ratios (RRs); two-sided χ(2) was used to calculate the probability.\n\nResults: We recruited 75360 women from 10 clusters in the screening group and 76178 women from 10 comparable clusters in the control group. In the screening group, we achieved 89% participation for screening and 79.4% compliance for diagnosis confirmation. The incidence of invasive cervical cancer was 26.74 per 100000 (95% confidence interval [CI] = 23.41 to 30.74) in the screening group and 27.49 per 100000 (95% CI = 23.66 to 32.09) in the control group. Compliance to treatment for invasive cancer was 86.3% in the screening group and 72.3% in the control group. The screening group showed a statistically significant 31% reduction in cervical cancer mortality (RR = 0.69; 95% CI = 0.54 to 0.88; P =.003).\n\nConclusions: VIA screening by primary health workers statistically significantly reduced cervical cancer mortality. Our study demonstrates the efficacy of an easily implementable strategy that could prevent 22000 cervical cancer deaths in India and 72600 deaths in resource-poor countries annually.\n\nIndexed on Europe PMC as PubMed record 24563518 (DOI 10.1093/jnci/dju009). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Natl Cancer Inst 2014","url":"https://doi.org/10.1093/jnci/dju009"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24563518/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/24563518"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["mumbai-via-screening"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jnci"],"dependsOn":[],"notes":[],"journal":"JNCI: Journal of the National Cancer Institute","year":2014,"doi":"10.1093/jnci/dju009","pmid":"24563518","authors":"Shastri SS, Mittra I, Mishra GA, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-sankaranarayanan-lancet","kind":"paper","name":"Effect of visual screening on cervical cancer incidence and mortality in Tamil Nadu, India: a cluster-randomised trial","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 17679017 and published in The Lancet; the citing page links this DOI, which is how the record was matched.","summary":"Background: Cervical cancer is the most common cancer among women in developing countries. We assessed the effect of screening using visual inspection with 4% acetic acid (VIA) on cervical cancer incidence and mortality in a cluster randomised controlled trial in India.\n\nMethods: Of the 114 study clusters in Dindigul district, India, 57 were randomised to one round of VIA by trained nurses, and 57 to a control group. Healthy women aged 30 to 59 years were eligible for the study. Screen-positive women had colposcopy, directed biopsies, and, where appropriate, cryotherapy by nurses during the screening visit. Those with larger precancerous lesions or invasive cancers were referred for appropriate investigations and treatment. Cervical cancer incidence and mortality in the study groups were analysed and compared using Cox regression taking the cluster design into account, and analysis was by intention to treat. The primary outcome measures were cervical cancer incidence and mortality.\n\nResults: Of the 49,311 eligible women in the intervention group, 31,343 (63.6%) were screened during 2000-03; 30,958 control women received the standard care. Of the 3088 (9.9%) screened positive, 3052 had colposcopy, and 2539 directed biopsy. Of the 1874 women with precancerous lesions in the intervention group, 72% received treatment. In the intervention group, 274,430 person years, 167 cervical cancer cases, and 83 cervical cancer deaths were accrued compared with 178,781 person-years, 158 cases, and 92 deaths and in the control group during 2000-06 (incidence hazard ratio 0.75 [95% CI 0.55-0.95] and mortality hazard ratio 0.65 [0.47-0.89]).\n\nInterpretation: VIA screening, in the presence of good training and sustained quality assurance, is an effective method to prevent cervical cancer in developing countries.\n\nIndexed on Europe PMC as PubMed record 17679017 (DOI 10.1016/s0140-6736(07)61195-7). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet 2007","url":"https://doi.org/10.1016/s0140-6736(07)61195-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/17679017/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/17679017"}],"tags":["europepmc-ingest"],"related":["via-cervical-screening"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2007,"doi":"10.1016/s0140-6736(07)61195-7","pmid":"17679017","authors":"Sankaranarayanan R, Esmy PO, Rajkumar R, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-boeve-eur-urol","kind":"paper","name":"Effect on Survival of Androgen Deprivation Therapy Alone Compared to Androgen Deprivation Therapy Combined with Concurrent Radiation Therapy to the Prostate in Patients with Primary Bone Metastatic Prostate Cancer in a Prospective Randomised Clinical Trial: Data from the HORRAD Trial","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 30266309 and published in European Urology; the citing page links this DOI, which is how the record was matched.","summary":"Background: The cornerstone of standard treatment for patients with primary bone metastatic prostate cancer (mPCa) is androgen deprivation therapy (ADT). Retrospective studies suggest a survival benefit for treatment of the primary prostatic tumour in mPCa, but to date, no randomised-controlled-trials (RCTs) have been published addressing this issue.\n\nObjective: To determine whether overall survival is prolonged by adding local treatment of the primary prostatic tumour with external beam radiation therapy (EBRT) to ADT.\n\nDesign, setting, and participants: The HORRAD trial is a multicentre RCT recruiting 432 patients with prostate-specific antigen (PSA) >20ng/ml and primary bone mPCa on bone scan between 2004 and 2014.\n\nIntervention: Patients were randomised to either ADT with EBRT (radiotherapy group) or ADT alone (control group).\n\nOutcome measurements and statistical analysis: Primary endpoint was overall survival. Secondary endpoint was time to PSA progression. Crude and adjusted analyses were applied to evaluate treatment effect.\n\nResults and limitations: Median PSA level was 142ng/ml and 67% of patients had more than five osseous metastases. Median follow up was 47 mo. Median overall survival was 45 mo (95% confidence interval [CI], 40.4-49.6) in the radiotherapy group and 43 mo (95% CI: 32.6-53.4) in the control group (p=0.4). No significant difference was found in overall survival (hazard ratio [HR]: 0.90; 95% CI: 0.70-1.14; p=0.4). Median time to PSA progression in the radiotherapy group was 15 mo (95% CI: 11.8-18.2), compared with 12 mo (95% CI: 10.6-13.4) in the control group. The crude HR (0.78; 95% CI: 0.63-0.97) was statistically significant (p=0.02).\n\nConclusions: The current RCT comparing ADT to ADT with EBRT to the prostate in patients with primary bone mPCa did not show a significant difference in overall survival, although the CI cannot exclude a substantial survival benefit. Further research is needed to confirm our findings.\n\nPatient summary: This study investigated the effect of adding radiation therapy to the prostate to hormonal therapy in prostate cancer patients with metastasis to the bone at diagnosis. In our patient group, additional radiotherapy did not improve overall survival. Further research is needed to confirm our findings.\n\nTwitter summary: Adding radiotherapy to the prostate in patients with bone metastatic prostate cancer does not improve overall survival.\n\nIndexed on Europe PMC as PubMed record 30266309 (DOI 10.1016/j.eururo.2018.09.008). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Eur Urol 2019","url":"https://doi.org/10.1016/j.eururo.2018.09.008"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30266309/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30266309"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["horrad"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["european-urology"],"dependsOn":[],"notes":[],"journal":"European Urology","year":2019,"doi":"10.1016/j.eururo.2018.09.008","pmid":"30266309","authors":"Boevé LMS, Hulshof MCCM, Vis AN, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-avsec-z-nat-methods","kind":"paper","name":"Effective gene expression prediction from sequence by integrating long-range interactions","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 34608324 and published in Nature methods; the citing page links this DOI, which is how the record was matched.","summary":"How noncoding DNA determines gene expression in different cell types is a major unsolved problem, and critical downstream applications in human genetics depend on improved solutions. Here, we report substantially improved gene expression prediction accuracy from DNA sequences through the use of a deep learning architecture, called Enformer, that is able to integrate information from long-range interactions (up to 100 kb away) in the genome. This improvement yielded more accurate variant effect predictions on gene expression for both natural genetic variants and saturation mutagenesis measured by massively parallel reporter assays. Furthermore, Enformer learned to predict enhancer-promoter interactions directly from the DNA sequence competitively with methods that take direct experimental data as input. We expect that these advances will enable more effective fine-mapping of human disease associations and provide a framework to interpret cis-regulatory evolution.\n\nIndexed on Europe PMC as PubMed record 34608324 (DOI 10.1038/s41592-021-01252-x). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Methods 2021","url":"https://doi.org/10.1038/s41592-021-01252-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34608324/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34608324"}],"tags":["europepmc-ingest"],"related":["enformer-borzoi"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature methods","year":2021,"doi":"10.1038/s41592-021-01252-x","pmid":"34608324","authors":"Avsec Ž, Agarwal V, Visentin D, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-jun-gastroenterology","kind":"paper","name":"Effectiveness of the Korean National Cancer Screening Program in Reducing Gastric Cancer Mortality","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 28147224 and published in Gastroenterology; the citing page links this DOI, which is how the record was matched.","summary":"Background & aims: It is not clear whether screening for gastric cancer by upper endoscopy or upper gastrointestinal (UGI) series examinations (looking at the upper and middle sections of the gastrointestinal tract by imaging techniques) reduces mortality. Nevertheless, the Korean National Cancer Screening Program for gastric cancer was launched in 1999 to screen individuals 40 years and older for gastric cancer using these techniques. We evaluated the effectiveness of these techniques in gastric cancer detection and compared their effects on mortality in the Korean population.\n\nMethods: We performed a nested case-control study using data from the Korean National Cancer Screening Program for gastric cancer since 2002. A total of 16,584,283 Korean men and women, aged 40 years and older, comprised the cancer-free cohort. Case subjects (n = 54,418) were defined as individuals newly diagnosed with gastric cancer from January 2004 through December 2009 and who died before December 2012. Cases were matched with controls (subjects who were alive on the date of death of the corresponding case subject, n = 217,672) for year of entry into the study cohort, age, sex, and socioeconomic status. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained via conditional logistic regression analysis.\n\nResults: Compared with subjects who had never been screened, the overall OR for dying from gastric cancer among ever-screened subjects was 0.79 (95% CI, 0.77-0.81). According to screening modality, the ORs of death from gastric cancer were 0.53 (95% CI, 0.51-0.56) for upper endoscopy and 0.98 (95% CI, 0.95-1.01) for UGI series. As the number of endoscopic screening tests performed per subject increased, the ORs of death from gastric cancer decreased: 0.60 (95% CI, 0.57-0.63), 0.32 (95% CI, 0.28-0.37), and 0.19 (95% CI, 0.14-0.26) for once, twice, and 3 or more times, respectively.\n\nConclusions: Within the Korean National Cancer Screening Program, patients who received an upper endoscopy were less likely to die from gastric cancer; no associations were found for UGI series.\n\nIndexed on Europe PMC as PubMed record 28147224 (DOI 10.1053/j.gastro.2017.01.029). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Gastroenterology 2017","url":"https://doi.org/10.1053/j.gastro.2017.01.029"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28147224/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28147224"}],"tags":["europepmc-ingest"],"related":["gastric-endoscopic-screening"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Gastroenterology","year":2017,"doi":"10.1053/j.gastro.2017.01.029","pmid":"28147224","authors":"Jun JK, Choi KS, Lee HY, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-caret-beta-carotene-retinol-lung-cancer-nejm-1996","kind":"paper","name":"Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease","aka":[],"tldr":"A vitamin trial in 18,314 smokers and asbestos workers was stopped early because the people taking the supplements were getting more lung cancer, not less.","summary":"The Beta Carotene and Retinol Efficacy Trial (CARET): a multicentre, randomised, double-blind, placebo-controlled primary prevention trial of 30 mg of beta carotene plus 25,000 IU of retinol daily against placebo in 18,314 smokers, former smokers and workers exposed to asbestos, reported by Omenn, Goodman, Thornquist and colleagues.\n\nObservational data had linked high dietary carotenoid intake to lower lung cancer risk, and the trial was built to convert that correlation into a preventive intervention. It did the opposite, and it did so at the same time as the Finnish ATBC trial found the same direction of harm. CARET is the standing answer to any proposal to move a nutritional association into a supplement without randomising it.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 1996","url":"https://doi.org/10.1056/NEJM199605023341802"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/8602180/"}],"tags":["lung-evidence"],"related":["nutrition-lifestyle-roadmap","prevention-roadmap"],"cancers":["lung-cancer","nsclc"],"sections":["prevention"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-misinformation","b-negative-results"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":1996,"doi":"10.1056/NEJM199605023341802","pmid":"8602180","authors":"Omenn GS, Goodman GE, Thornquist MD, et al.","paperType":"rct","findings":["388 new cases of lung cancer during 73,135 person-years of follow-up, with a mean follow-up of 4.0 years.","Relative risk of lung cancer in the active-treatment group 1.28 (95 percent confidence interval 1.04 to 1.57; P equals 0.02).","Relative risk of death from any cause 1.17 (1.03 to 1.33), from lung cancer 1.46 (1.07 to 2.00) and from cardiovascular disease 1.26 (0.99 to 1.61).","The trial was stopped 21 months earlier than planned on these findings.","No statistically significant differences in the risks of other types of cancer."],"whatItMeans":"Supplements are drugs, and drugs have to be tested. A plausible mechanism, a consistent observational signal and a safe-sounding intervention still produced measurable harm in the people it was meant to protect.","caveats":["High-risk population (heavy smokers and asbestos-exposed workers) at a high supplement dose; it does not say what dietary carotenoids do at dietary levels.","The mechanism of the excess risk was never settled.","Four years of mean follow-up for an exposure whose latency is measured in decades."],"changedPractice":true,"participants":18314},{"id":"paper-sjostrom-lancet-oncol","kind":"paper","name":"Effects of bariatric surgery on cancer incidence in obese patients in Sweden (Swedish Obese Subjects Study): a prospective, controlled intervention trial","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 19556163 and published in The Lancet Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background: Obesity is a risk factor for cancer. Intentional weight loss in the obese might protect against malignancy, but evidence is limited. To our knowledge, the Swedish Obese Subjects (SOS) study is the first intervention trial in the obese population to provide prospective, controlled cancer-incidence data.\n\nMethods: The SOS study started in 1987 and involved 2010 obese patients (body-mass index [BMI] >or=34 kg/m(2) in men, and >or=38 kg/m(2) in women) who underwent bariatric surgery and 2037 contemporaneously matched obese controls, who received conventional treatment. While the main endpoint of SOS was overall mortality, the main outcome of this exploratory report was cancer incidence until Dec 31, 2005. Cancer follow-up rate was 99.9% and the median follow-up time was 10.9 years (range 0-18.1 years).\n\nFindings: Bariatric surgery resulted in a sustained mean weight reduction of 19.9 kg (SD 15.6 kg) over 10 years, whereas the mean weight change in controls was a gain of 1.3 kg (SD 13.7 kg). The number of first-time cancers after inclusion was lower in the surgery group (n=117) than in the control group (n=169; HR 0.67, 95% CI 0.53-0.85, p=0.0009). The sex-treatment interaction p value was 0.054. In women, the number of first-time cancers after inclusion was lower in the surgery group (n=79) than in the control group (n=130; HR 0.58, 0.44-0.77; p=0.0001), whereas there was no effect of surgery in men (38 in the surgery group vs 39 in the control group; HR 0.97, 0.62-1.52; p=0.90). Similar results were obtained after exclusion of all cancer cases during the first 3 years of the intervention.\n\nInterpretation: Bariatric surgery was associated with reduced cancer incidence in obese women but not in obese men.\n\nFunding: Swedish Research Council, Swedish Foundation for Strategic Research, Swedish Federal Government under the LUA/ALF agreement, Hoffmann La Roche, Cederoths, AstraZeneca, Sanofi-Aventis, Ethicon Endosurgery.\n\nIndexed on Europe PMC as PubMed record 19556163 (DOI 10.1016/s1470-2045(09)70159-7). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2009","url":"https://doi.org/10.1016/s1470-2045(09)70159-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19556163/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/19556163"}],"tags":["europepmc-ingest"],"related":["bariatric-surgery-cancer-incidence"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2009,"doi":"10.1016/s1470-2045(09)70159-7","pmid":"19556163","authors":"Sjöström L, Gummesson A, Sjöström CD, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-arbour-kras-co-mutation-outcomes-ccr-2018","kind":"paper","name":"Effects of co-occurring genomic alterations on outcomes in patients with KRAS-mutant non-small cell lung cancer","aka":[],"tldr":"Among 330 patients whose lung cancer carried a mutated KRAS gene, the ones who also had a broken KEAP1 gene did worse on every treatment: chemotherapy stopped working sooner and immunotherapy barely worked at all.","summary":"Patients with advanced KRAS-mutant non-small-cell lung cancer were identified and their most common co-occurring genomic alterations evaluated, with multivariate analyses of association with overall survival, response to platinum and pemetrexed chemotherapy and response to immune checkpoint inhibitors. Among 330 patients, the most frequent co-mutations were TP53 (42%), STK11 (29%) and KEAP1 or NFE2L2 (27%). In multivariate analysis, co-mutation in KEAP1 or NFE2L2 carried significantly shorter survival (hazard ratio 1.96), while STK11 (1.3) and TP53 (1.11) co-mutation status were not associated with survival. KEAP1 or NFE2L2 co-mutation was also associated with a shorter duration of initial chemotherapy (hazard ratio 1.64) and shorter overall survival from the start of immune therapy (3.54).","asOf":"2026-09-25","links":[{"label":"Arbour et al., Clin Cancer Res 2018: co-occurring alterations and outcomes in 330 KRAS-mutant lung cancers","url":"https://doi.org/10.1158/1078-0432.CCR-17-1841"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29089357/"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":["cgp","checkpoint-inhibitor"],"targets":["kras","keap1","nfe2l2","stk11","tp53"],"drugs":[],"companies":[],"institutions":["mskcc"],"pathways":["keap1-nrf2","ras-mapk","t-cell-exhaustion"],"terms":["stk11-keap1","kras-mutation-subtypes"],"trials":[],"people":["gregory-riely"],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2018,"doi":"10.1158/1078-0432.CCR-17-1841","pmid":"29089357","authors":"Arbour KC, Jordan E, Kim HR, et al.","paperType":"observational","findings":["Commonest co-mutations in KRAS-mutant lung cancer: TP53 42%, STK11 29%, KEAP1 or NFE2L2 27%.","KEAP1 or NFE2L2 co-mutation was an independent predictor of shorter survival, hazard ratio 1.96.","It also shortened the duration of first chemotherapy and survival from the start of immunotherapy.","STK11 and TP53 co-mutation were not independently associated with survival in this model."],"whatItMeans":"It separated the prognostic co-mutation, KEAP1, from the predictive one, STK11, in a disease where the two are often quoted together, and it is the reason KEAP1 status is worth reading off a report even though no treatment depends on it.","caveats":["Single centre and retrospective, with treatment not randomised.","Immunotherapy subgroup numbers are small.","KEAP1 and NFE2L2 were grouped together, so their individual effects cannot be separated."],"changedPractice":false,"participants":330},{"id":"paper-hanai-j-natl-cancer-inst","kind":"paper","name":"Effects of Cryotherapy on Objective and Subjective Symptoms of Paclitaxel-Induced Neuropathy: Prospective Self-Controlled Trial","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 29924336 and published in JNCI: Journal of the National Cancer Institute; the citing page links this DOI, which is how the record was matched.","summary":"Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting and disabling side effect of taxane anticancer agents. We prospectively evaluated the efficacy of cryotherapy for CIPN prevention.\n\nMethods: Breast cancer patients treated weekly with paclitaxel (80 mg/m2 for one hour) wore frozen gloves and socks on the dominant side for 90 minutes, including the entire duration of drug infusion. Symptoms on the treated sides were compared with those on the untreated (nondominant) sides. The primary end point was CIPN incidence assessed by changes in tactile sensitivity from pretreatment baseline in a monofilament test at a cumulative dose of 960 mg/m2. We also assessed thermosensory deficits, subjective symptoms (Patient Neuropathy Questionnaire [PNQ]), manipulative dexterity, and the time to events and hazard ratio by PNQ. All statistical tests were two-sided.\n\nResults: Among the 40 patients, four did not reach the cumulative dose (due to the occurrence of pneumonia, severe fatigue, severe liver dysfunction, and macular edema), leaving 36 patients for analysis. None dropped out due to cold intolerance. The incidence of objective and subjective CIPN signs was clinically and statistically significantly lower on the intervention side than on the control (hand: tactile sensitivity = 27.8% vs 80.6%, odds ratio [OR] = 20.00, 95% confidence interval [CI] = 3.20 to 828.96, P <.001; foot: tacile sensitivity = 25.0% vs 63.9%, OR = infinite, 95% CI = 3.32 to infinite, P <.001; hand: warm sense = 8.8% vs 32.4%, OR = 9.00, 95% CI = 1.25 to 394.48, P =.02; foot: warm sense: 33.4% vs 57.6%, OR = 5.00, 95% CI = 1.07 to 46.93, P =.04; hand: PNQ = 2.8% vs 41.7%, OR = infinite, 95% CI = 3.32 to infinite, P <.001; foot: PNQ = 2.8% vs 36.1%, OR = infinite, 95% CI = 2.78 to infinite, P <.001; hand: hazard ratio [HR] = 0.13, 95% CI = 0.05 to 0.34; foot: HR = 0.13, 95% CI = 0.04 to 0.38, dexterity mean delay = -2.5 seconds, SD = 12.0 seconds, vs + 8.6 seconds, SD = 25.8 seconds, P =.005).\n\nConclusions: Cryotherapy is useful for preventing both the objective and subjective symptoms of CIPN and resultant dysfunction.\n\nIndexed on Europe PMC as PubMed record 29924336 (DOI 10.1093/jnci/djx178). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Natl Cancer Inst 2018","url":"https://doi.org/10.1093/jnci/djx178"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29924336/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29924336"}],"tags":["europepmc-ingest"],"related":["frozen-gloves-compression-taxane"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jnci"],"dependsOn":[],"notes":[],"journal":"JNCI: Journal of the National Cancer Institute","year":2018,"doi":"10.1093/jnci/djx178","pmid":"29924336","authors":"Hanai A, Ishiguro H, Sozu T, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-mathijssen-j-natl-cancer-inst","kind":"paper","name":"Effects of St. John's wort on irinotecan metabolism","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 12189228 and published in JNCI: Journal of the National Cancer Institute; the citing page links this DOI, which is how the record was matched.","summary":"St. John's wort (SJW), a widely used herbal product, has been implicated in drug interactions resulting from the induced expression of the cytochrome P450 CYP3A4 isoform. In this study, we determined the effect of SJW on the metabolism of irinotecan, a pro-drug of SN-38 and a known substrate for CYP3A4. Five cancer patients were treated with irinotecan (350 mg/m(2), intravenously) in the presence and absence of SJW (900 mg daily, orally for 18 days) in an unblinded, randomized crossover study design. The plasma levels of the active metabolite SN-38 decreased by 42% (95% confidence interval [CI] = 14% to 70%) following SJW cotreatment with 1.0 micro M x h (95% CI = 0.34 micro M x h to 1.7 micro M x h) versus 1.7 micro M x h (95% CI = 0.83 micro M x h to 2.6 micro M x h) (P =.033, two-sided paired Student's t test). Consequently, the degree of myelosuppression was substantially worse in the absence of SJW. These findings indicate that patients on irinotecan treatment should refrain from taking SJW because plasma levels of SN-38 were dramatically reduced, which may have a deleterious impact on treatment outcome.\n\nIndexed on Europe PMC as PubMed record 12189228 (DOI 10.1093/jnci/94.16.1247). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Natl Cancer Inst 2002","url":"https://doi.org/10.1093/jnci/94.16.1247"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/12189228/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/12189228"}],"tags":["europepmc-ingest"],"related":["st-johns-wort-interaction"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jnci"],"dependsOn":[],"notes":[],"journal":"JNCI: Journal of the National Cancer Institute","year":2002,"doi":"10.1093/jnci/94.16.1247","pmid":"12189228","authors":"Mathijssen RH, Verweij J, de Bruijn P, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-pembrolizumab-glioblastoma-med-2025","kind":"paper","name":"Efficacy and safety of adjuvant TTFields plus pembrolizumab and temozolomide in newly diagnosed glioblastoma: A phase 2 study","aka":[],"tldr":"Phase 2 or 3 results paper on Pembrolizumab in Glioma & glioblastoma, in Med (New York, N.Y.) (2025), one of the most cited Europe PMC records with Pembrolizumab in its title.","summary":"Background: Immune checkpoint inhibitors (ICIs) have shown limited success in glioblastoma due to the tumor's profoundly immunosuppressive microenvironment. Tumor treating fields (TTFields), a non-invasive electric field therapy, activate the type I interferon (T1IFN) pathway via DNA sensor-dependent inflammasomes, promoting in situ immunization against glioblastoma.\n\nMethods: In this phase 2 study (this study was registered at ClinicalTrials.gov: NCT03405792), 31 newly diagnosed glioblastoma patients were enrolled post-chemoradiation to evaluate synergy between TTFields, pembrolizumab, and temozolomide. The primary endpoint was progression-free survival (PFS) compared to case-matched controls treated with TTFields and temozolomide alone. Secondary endpoints included overall survival (OS), response rate, safety, and immune correlates assessed through single-cell transcriptomics and T cell clonotyping of blood and tumor samples.\n\nFindings: Among 26 patients treated per protocol, the median PFS was 12.0 vs. 5.8 months in controls (HR 0.377, 95% CI 0.217-0.653; p = 0.0026), and the median OS was 24.8 vs. 14.6 months (HR 0.522, 95% CI 0.301-0.905; p = 0.0477). Patients undergoing biopsy had longer PFS (27.2 vs. 9.6 months; HR 0.37, 95% CI 0.16-0.85; p = 0.014) and OS (31.6 vs. 18.8 months; HR 0.4, 95% CI 0.17-0.92; p = 0.023) compared to maximal resection. Severe adverse events constituted 7.5% of treatment-related toxicities. TTFields promoted clonal T cell expansion via a T1IFN-driven trajectory, while pembrolizumab supported adaptive replacement of these clones, sustaining T cell activation and memory formation, especially in biopsy-only patients.\n\nConclusions: These findings demonstrate synergy between TTFields and ICIs, particularly in patients with high tumor burden, and support further study in larger trials.\n\nFunding: This work was supported by a grant from Novocure.\n\nIndexed on Europe PMC as PubMed record 40466642 (DOI 10.1016/j.medj.2025.100708). Its title names Pembrolizumab and its text names Glioma & glioblastoma; PubMed types it as a clinical trial report (Clinical Trial, Phase II, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't). It was matched automatically to the idea \"Neoadjuvant immunotherapy with surgical window for glioblastoma\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Med 2025","url":"https://doi.org/10.1016/j.medj.2025.100708"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40466642/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40466642"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Med (New York, N.Y.)","year":2025,"doi":"10.1016/j.medj.2025.100708","pmid":"40466642","authors":"Chen D, Le SB, Ghiaseddin AP, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Pembrolizumab in Glioma & glioblastoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Pembrolizumab in the title and Glioma & glioblastoma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-sacituzumab-govitecan-tnbc-j-clin-oncol-2017","kind":"paper","name":"Efficacy and Safety of Anti-Trop-2 Antibody Drug Conjugate Sacituzumab Govitecan (IMMU-132) in Heavily Pretreated Patients With Metastatic Triple-Negative Breast Cancer","aka":[],"tldr":"Phase 2 or 3 results paper on Sacituzumab govitecan in Triple-negative breast cancer, in Journal of Clinical Oncology (2017), one of the most cited Europe PMC records with Sacituzumab govitecan in its title.","summary":"Purpose Trop-2, expressed in most triple-negative breast cancers (TNBCs), may be a potential target for antibody-drug conjugates. Sacituzumab govitecan, an antibody-drug conjugate, targets Trop-2 for the selective delivery of SN-38, the active metabolite of irinotecan. Patients and Methods We evaluated sacituzumab govitecan in a single-arm, multicenter trial in patients with relapsed/refractory metastatic TNBC who received a 10 mg/kg starting dose on days 1 and 8 of 21-day repeated cycles. The primary end points were safety and objective response rate; secondary end points were progression-free survival and overall survival. Results In 69 patients who received a median of five prior therapies (range, one to 12) since diagnosis, the confirmed objective response rate was 30% (partial response, n = 19; complete response, n = 2), the median response duration was 8.9 (95% CI, 6.1 to 11.3) months, and the clinical benefit rate (complete response + partial response + stable disease ≥ 6 months) was 46%. These responses occurred early, with a median onset of 1.9 months. Median progression-free survival was 6.0 (95% CI, 5.0 to 7.3) months, and median overall survival was 16.6 (95% CI, 11.1 to 20.6) months. Grade ≥ 3 adverse events included neutropenia (39%), leukopenia (16%), anemia (14%), and diarrhea (13%); the incidence of febrile neutropenia was 7%. The majority of archival tumor specimens (88%) were moderately to strongly positive for Trop-2 by immunohistochemistry. No neutralizing antibodies to the ADC or antibody were detected, despite repeated cycles developed. Conclusion Sacituzumab govitecan was well tolerated and induced early and durable responses in heavily pretreated patients with metastatic TNBC. As a therapeutic target and predictive biomarker, Trop-2 warrants further research.\n\nIndexed on Europe PMC as PubMed record 28291390 (DOI 10.1200/jco.2016.70.8297). Its title names Sacituzumab govitecan and its text names Triple-negative breast cancer; PubMed types it as a clinical trial report (Clinical Trial, Phase II, research-article, Clinical Trial, Phase I). It was matched automatically to the idea \"TROP2 PET to choose and sequence TROP2 ADCs\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2017","url":"https://doi.org/10.1200/jco.2016.70.8297"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28291390/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28291390"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2017,"doi":"10.1200/jco.2016.70.8297","pmid":"28291390","authors":"Bardia A, Mayer IA, Diamond JR, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Sacituzumab govitecan in Triple-negative breast cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Sacituzumab govitecan in the title and Triple-negative breast cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-cd19-dlbcl-am-j-hematol-2021","kind":"paper","name":"Efficacy and safety of CD19-directed CAR-T cell therapies in patients with relapsed/refractory aggressive B-cell lymphomas: Observations from the JULIET, ZUMA-1, and TRANSCEND trials","aka":[],"tldr":"Review on CD19 in Diffuse large B-cell lymphoma, in American journal of hematology (2021), one of the most cited Europe PMC records with CD19 in its title.","summary":"Chimeric antigen receptor (CAR)-T cell therapies have improved the outcome for many patients with relapsed or refractory aggressive B-cell lymphomas. In 2017, axicabtagene ciloleucel and soon after tisagenlecleucel became the first approved CAR-T cell products for patients with high-grade B-cell lymphomas or diffuse large B-cell lymphoma (DLBCL) who are relapsed or refractory to ≥ 2 prior lines of therapy; lisocabtagene maraleucel was approved in 2021. Safety and efficacy outcomes from the pivotal trials of each CAR-T cell therapy have been reported. Despite addressing a common unmet need in the large B-cell lymphoma population and utilizing similar CAR technologies, there are differences between CAR-T cell products in manufacturing, pivotal clinical trial designs, and data reporting. Early reports of commercial use of axicabtagene ciloleucel and tisagenlecleucel provide the first opportunities to validate the impact of patient characteristics on the efficacy and safety of these CAR-T cell therapies in the real world. Going forward, caring for patients after CAR-T cell therapy will require strategies to monitor patients for sustained responses and potential long-term side effects. In this review, product attributes, protocol designs, and clinical outcomes of the key clinical trials are presented. We discuss recent data on patient characteristics, efficacy, and safety of patients treated with axicabtagene ciloleucel or tisagenlecleucel in the real world. Finally, we discuss postinfusion management and preview upcoming clinical trials of CAR-T cell therapies.\n\nIndexed on Europe PMC as PubMed record 34310745 (DOI 10.1002/ajh.26301). Its title names CD19 and its text names Diffuse large B-cell lymphoma; PubMed types it as a review (Research Support, Non-U.S. Gov't, review-article, Review). It was matched automatically to the idea \"In vivo CAR-T as a vial on the shelf: a cost and access trial in lymphoma\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Am J Hematol 2021","url":"https://doi.org/10.1002/ajh.26301"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34310745/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34310745"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"American journal of hematology","year":2021,"doi":"10.1002/ajh.26301","pmid":"34310745","authors":"Westin JR, Kersten MJ, Salles G, et al.","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for CD19 in Diffuse large B-cell lymphoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by CD19 in the title and Diffuse large B-cell lymphoma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-ck-301-101-jitc-2023","kind":"paper","name":"Efficacy and safety of cosibelimab, an anti-PD-L1 antibody, in metastatic cutaneous squamous cell carcinoma","aka":[],"tldr":"The primary report of the metastatic cohort of CK-301-101: cosibelimab shrank tumours in 37 of 78 patients, most responses were still going at the cut-off, and severe immune side effects were uncommon.","summary":"Pivotal metastatic cutaneous squamous cell carcinoma cohort of an open-label, multicentre, multiregional, multicohort phase 1 trial of cosibelimab, a PD-L1-blocking IgG1 antibody with a functional Fc domain. Participants received cosibelimab 800 mg intravenously every 2 weeks. The primary endpoint was objective response rate by independent central review using RECIST 1.1; secondary endpoints were duration of response and safety.\n\nObjective response was observed in 37 of 78 participants (47.4 percent, 95% CI 36.0 to 59.1) at a median follow-up of 15.4 months. Median duration of response was not reached (range 1.4+ to 34.1+ months), with response ongoing in 73.0 percent of responders. Immune-related adverse events occurred in 18 participants (23.1 percent), grade 3 in 2 (2.6 percent), with no grade 4 or 5 events and no treatment-related deaths.","asOf":"2026-09-24","links":[{"label":"Journal for ImmunoTherapy of Cancer 2023","url":"https://doi.org/10.1136/jitc-2023-007637"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37848259/"},{"label":"ClinicalTrials.gov NCT03212404","url":"https://clinicaltrials.gov/study/NCT03212404"}],"tags":[],"related":[],"cancers":["cutaneous-scc","advanced-cutaneous-scc"],"sections":[],"technologies":[],"targets":["pdl1"],"drugs":["cosibelimab"],"companies":["checkpoint-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":["ck-301-101"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jitc"],"dependsOn":[],"notes":[],"journal":"Journal for ImmunoTherapy of Cancer","year":2023,"doi":"10.1136/jitc-2023-007637","pmid":"37848259","authors":"Clingan P, Ladwa R, Brungs D, et al.","paperType":"observational","findings":["Objective response rate 47.4% (37 of 78; 95% CI 36.0 to 59.1) by independent central review at a median follow-up of 15.4 months.","Median duration of response not reached; 73.0% of responders still responding at data cut-off.","Immune-related adverse events in 23.1%, grade 3 in 2.6%, none grade 4 or 5; no treatment-related deaths."],"whatItMeans":"This cohort, with the locally advanced cohort in the label, is the evidence behind cosibelimab's December 2024 US approval. The response rate is of the same order as cemiplimab and pembrolizumab in this cancer, which gives patients a third checkpoint antibody option, though none of the three has been compared head to head.","caveats":["Single-arm cohort within a phase 1 trial; no comparator.","The 800 mg every 2 weeks dose studied here differs from the 1,200 mg every 3 weeks dose the label recommends; the label says exposure is comparable.","Median duration of response was not yet estimable at the primary report."],"changedPractice":true,"participants":78},{"id":"paper-durvalumab-endometrial-gynecol-oncol-2022","kind":"paper","name":"Efficacy and safety of durvalumab with olaparib in metastatic or recurrent endometrial cancer (phase II DOMEC trial)","aka":[],"tldr":"Phase 2 or 3 results paper on Durvalumab in Endometrial cancer, in Gynecologic Oncology (2022), one of the most cited Europe PMC records with Durvalumab in its title.","summary":"Background: Patients with advanced endometrial cancer have a poor prognosis, and treatment options are limited. The investigator-initiated, multicenter, phase II DOMEC trial (NCT03951415) is the first trial to report data on efficacy and safety of combined treatment with PD-L1 and PARP inhibition for advanced endometrial cancer.\n\nPatients and methods: Patients with metastatic or recurrent endometrial cancer were enrolled. Patients received durvalumab 1500 mg intravenously q4w and olaparib 300 mg 2dd until disease progression, unacceptable toxicity, or patient withdrawal. Patients with at least 4 weeks of treatment were evaluable for analysis. The primary endpoint was progression-free survival at 6 months. Evidence for efficacy was defined as progression-free survival at 6 months in ≥50% of patients. Secondary endpoints included safety, objective response and overall survival.\n\nResults: From July 2019, through November 2020, 55 patients were enrolled. At data cut-off (September 2021), 4 of the 50 evaluable patients were still on treatment. Seventeen patients (34%) were progression-free at 6 months. Objective response rate was 16% (95% CI, 8.3 to 28.5) with 1 complete and 7 partial responses. With a median follow-up of 17.6 months, median progression-free survival was 3.4 months (95% CI, 2.8 to 6.2) and median overall survival was 8.0 months (95% CI, 7.5 to 14.3). Grade 3 treatment-related adverse events occurred in 8 patients (16%), predominantly anemia. There were no grade 4 or 5 treatment-related adverse events.\n\nConclusion: The combination of durvalumab and olaparib was well tolerated, but did not meet the prespecified 50% 6-month progression-free survival in this heterogeneous patient population with advanced endometrial cancer.\n\nIndexed on Europe PMC as PubMed record 35287967 (DOI 10.1016/j.ygyno.2022.02.025). Its title names Durvalumab and its text names Endometrial cancer; PubMed types it as a clinical trial report (Clinical Trial, Phase II, Research Support, Non-U.S. Gov't, Multicenter Study). It was matched automatically to the idea \"Molecular-class-directed adjuvant therapy in endometrial cancer\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Gynecol Oncol 2022","url":"https://doi.org/10.1016/j.ygyno.2022.02.025"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35287967/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35287967"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["gynecologic-oncology"],"dependsOn":[],"notes":[],"journal":"Gynecologic Oncology","year":2022,"doi":"10.1016/j.ygyno.2022.02.025","pmid":"35287967","authors":"Post CCB, Westermann AM, Boere IA, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Durvalumab in Endometrial cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Durvalumab in the title and Endometrial cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-crown-lancet-respir-med-2023-update","kind":"paper","name":"Efficacy and safety of first-line lorlatinib versus crizotinib in patients with advanced, ALK-positive non-small-cell lung cancer: updated analysis of data from the phase 3, randomised, open-label CROWN study","aka":[],"tldr":"Later report from the CROWN trial registered as NCT03052608, in The Lancet. Respiratory medicine (2023); its title describes an updated or longer-term analysis.","summary":"Background: After a median follow-up of 18·3 months, the third-generation anaplastic lymphoma kinase (ALK) tyrosine-kinase inhibitor, lorlatinib, improved progression-free survival in patients with treatment-naive, ALK-positive non-small-cell lung cancer in the phase 3 CROWN study. Here we report updated efficacy data, including intracranial activity, from an unplanned analysis after 3 years of follow-up.\n\nMethods: CROWN is an ongoing, international, randomised, open-label phase 3 trial done in 104 centres in 23 countries worldwide. Eligible participants were aged 18 years and older or aged 20 years and older (depending on local regulations) with advanced, ALK-positive non-small-cell lung cancer, had received no previous systemic treatment for metastatic disease, had at least one extracranial measurable target lesion (according to the Response Evaluation Criteria in Solid Tumours [RECIST], version 1.1), and had an Eastern Cooperative Oncology Group performance status score of 0-2. Patients were randomly assigned (1:1) to oral lorlatinib 100 mg daily or oral crizotinib 250 mg twice daily in 28-day cycles. Randomisation was stratified by the presence or absence of brain metastasis, and by ethnicity. Since the primary endpoint of the study had been met at the planned interim analysis, no further formal analysis of progression-free survival was planned, per protocol. The current unplanned analysis was done to further characterise tumour-related endpoints with a longer follow-up and is presented descriptively. For the planned study, the primary endpoint was progression-free survival assessed by blinded independent central review. Secondary endpoints included progression-free survival (investigator), objective response rate, intracranial objective response rate, time to intracranial progression, duration of response, intracranial duration of response, and safety. Efficacy endpoints were also assessed by the presence or absence of baseline brain metastases. This study is registered with ClinicalTrials.gov, NCT03052608.\n\nFindings: Between May 11, 2017, and Feb 28, 2019, 425 patients were screened for eligibility, of whom 296 were enrolled and randomly assigned to the lorlatinib (n=149) or crizotinib (n=147) group. At data cutoff for this unplanned analysis (Sept 20, 2021), median duration of follow-up for progression-free survival was 36·7 months (IQR 31·3-41·9) for lorlatinib and 29·3 months (10·8-35·0) for crizotinib. Median progression-free survival by blinded independent central review was not reached (95% CI not reached-not reached) for lorlatinib and was 9·3 months (7·6-11·1) for crizotinib (hazard ratio [HR] 0·27 [95% CI 0·18-0·39]). 3-year progression-free survival was 64% (95% CI 55-71) in the lorlatinib group and 19% (12-27) in the crizotinib group. Progression-free survival (investigator), objective response rate, intracranial objective response rate, time to intracranial progression, and duration of response were improved with lorlatinib versus crizotinib. In patients with baseline brain metastases (n=37 lorlatinib; n=39 crizotinib), the HR for time to intracranial progression for lorlatinib versus crizotinib was 0·10 (95% CI 0·04-0·27); in patients without baseline brain metastases (n=112 lorlatinib; n=108 crizotinib), the HR was 0·02 (95% CI 0·002-0·14). In patients without brain metastases, one (1%) in the lorlatinib group and 25 (23%) in the crizotinib group had intracranial progression. Grade 3-4 adverse events occurred in 113 (76%) of 149 patients (most commonly due to altered lipid levels) with lorlatinib and in 81 (57%) of 142 patients with crizotinib. Adverse events led to treatment discontinuation in 11 (7%) patients in the lorlatinib group and 14 (10%) patients in the crizotinib group. There were no new safety signals.\n\nInterpretation: These updated, long-term data from CROWN show the durable benefit of lorlatinib over crizotinib in patients with treatment-naive, ALK-positive non-small-cell lung cancer and support the use of first-line lorlatinib in patients with and without baseline brain metastases.\n\nFunding: Pfizer.\n\nIndexed on Europe PMC as PubMed record 36535300 (DOI 10.1016/s2213-2600(22)00437-4). Its abstract cites the registry id NCT03052608, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Respir Med 2023","url":"https://doi.org/10.1016/s2213-2600(22)00437-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36535300/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36535300"},{"label":"ClinicalTrials.gov NCT03052608","url":"https://clinicaltrials.gov/study/NCT03052608"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["crown"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Lancet. Respiratory medicine","year":2023,"doi":"10.1016/s2213-2600(22)00437-4","pmid":"36535300","authors":"Solomon BJ, Bauer TM, Mok TSK, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the CROWN trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-imforte-lancet-2025","kind":"paper","name":"Efficacy and safety of first-line maintenance therapy with lurbinectedin plus atezolizumab in extensive-stage small-cell lung cancer (IMforte): a randomised, multicentre, open-label, phase 3 trial","aka":[],"tldr":"Published report from the IMforte trial registered as NCT05091567, in The Lancet (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Despite improved efficacy with first-line immune checkpoint inhibitors plus platinum-based chemotherapy for extensive-stage small-cell lung cancer (ES-SCLC), survival remains poor. In this study, we aimed to compare lurbinectedin plus atezolizumab and atezolizumab alone as maintenance therapies in patients with ES-SCLC without progression after induction therapy with atezolizumab, carboplatin, and etoposide.\n\nMethods: IMforte was a randomised, open-label, phase 3 trial done at 96 hospitals and medical centres in 13 countries (Belgium, Germany, Greece, Hungary, Italy, Mexico, Poland, South Korea, Spain, Taiwan, Türkiye, the UK, and the USA). Eligible patients were aged 18 years or older with treatment-naive ES-SCLC. Patients received four 21-day cycles of induction treatment (atezolizumab, carboplatin, and etoposide). After completing induction treatment, eligible patients without disease progression were randomly assigned (1:1) using permuted blocks (Interactive Voice/Web Response System) to receive maintenance treatment intravenously every 3 weeks with lurbinectedin (3·2 mg/m 2; with granulocyte colony-stimulating factor prophylaxis) plus atezolizumab (1200 mg) or atezolizumab (1200 mg). The two primary endpoints were independent review facility-assessed (IRF) progression-free survival and overall survival, measured from randomisation into the maintenance phase. Efficacy endpoints were assessed in the full analysis set, which included all patients who were randomly assigned to maintenance phase treatment, regardless of whether they received their assigned study treatment. Safety was assessed in all patients who received at least one dose of lurbinectedin or atezolizumab, and was analysed according to the treatment received. This study is registered with ClinicalTrials.gov, NCT05091567, and is closed for recruitment.\n\nFindings: Between Nov 17, 2021, and Jan 11, 2024, 895 patients were screened for enrolment, of whom 660 (74%) were enrolled into the induction phase. Between May 24, 2022, and April 30, 2024, 483 (73%) of 660 patients entered the maintenance phase and were randomly assigned to lurbinectedin plus atezolizumab (n=242) or atezolizumab (n=241). At the data cutoff (July 29, 2024), IRF progression-free survival was longer in the lurbinectedin plus atezolizumab group than the atezolizumab group (stratified hazard ratio [HR] 0·54 [95% CI 0·43-0·67]; p<0·0001), as was overall survival (stratified HR 0·73 [0·57-0·95]; p=0·017). 92 (38%) of 242 patients in the lurbinectedin plus atezolizumab group and 53 (22%) of 240 patients in the atezolizumab group had grade 3-4 adverse events. The most common grade 3-4 events in the lurbinectedin plus atezolizumab group were anaemia (20 [8%] of 242 patients), decreased neutrophil count (18 [7%] patients), and decreased platelet count (18 [7%] patients) and the most common events in the atezolizumab group were hyponatremia (five [2%] of 240 patients), dyspnoea (four [2%] patients), and pneumonia (four [2%] patients). Grade 5 adverse events occurred in 12 (5%) of 242 patients in the lurbinectedin plus atezolizumab group and six (3%) of 240 patients in the atezolizumab group. The incidence of myelosuppressive toxicities (eg, neutropenia and leukopenia) was higher in the lurbinectedin plus atezolizumab group than the atezolizumab group.\n\nInterpretation: IRF progression-free survival and overall survival were longer in the lurbinectedin plus atezolizumab group than the atezolizumab group for patients with ES-SCLC, albeit with a higher incidence of adverse events. Lurbinectedin plus atezolizumab represents a novel therapeutic option for first-line maintenance treatment in this setting.\n\nFunding: F Hoffmann-La Roche and Jazz Pharmaceuticals.\n\nIndexed on Europe PMC as PubMed record 40473449 (DOI 10.1016/s0140-6736(25)01011-6). Its abstract cites the registry id NCT05091567, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet 2025","url":"https://doi.org/10.1016/s0140-6736(25)01011-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40473449/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40473449"},{"label":"ClinicalTrials.gov NCT05091567","url":"https://clinicaltrials.gov/study/NCT05091567"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["imforte"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2025,"doi":"10.1016/s0140-6736(25)01011-6","pmid":"40473449","authors":"Paz-Ares L, Borghaei H, Liu SV, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05091567 with the most citations, so it is the natural first reading for anyone following the IMforte trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-pryma-high-specific-activity-i131-mibg-ppgl-jnm-2019","kind":"paper","name":"Efficacy and safety of high-specific-activity 131I-MIBG therapy in advanced pheochromocytoma or paraganglioma","aka":[],"tldr":"A purified radioactive form of MIBG, taken up by adrenaline-producing tumour cells, let a quarter of patients halve their blood pressure medication for at least six months and shrank tumours in about one in five, leading to the first approved radiopharmaceutical for these tumours.","summary":"Open-label single-arm multicentre phase 2 study of high-specific-activity iobenguane I-131 in patients with MIBG-avid unresectable or metastatic pheochromocytoma or paraganglioma, given as up to two therapeutic doses; 68 patients received at least one dose.\n\nAbout a quarter of patients achieved the primary endpoint of at least a 50 percent reduction in antihypertensive medication for six months or more, objective responses occurred in about 22 percent, and most patients had disease control; myelosuppression was the main toxicity. The FDA approved the product (Azedra) in 2018.","asOf":"2026-09-18","links":[{"label":"J Nucl Med 2019","url":"https://doi.org/10.2967/jnumed.118.217463"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30291194/"}],"tags":[],"related":[],"cancers":["metastatic-ppgl"],"sections":[],"technologies":[],"targets":[],"drugs":["i131-mibg"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-nuclear-medicine"],"dependsOn":[],"notes":[],"journal":"Journal of Nuclear Medicine","year":2019,"doi":"10.2967/jnumed.118.217463","pmid":"30291194","authors":"Pryma DA, Chin BB, Noto RB, et al.","paperType":"observational","findings":["At least a 50 percent reduction in antihypertensive medication for six months or longer in about a quarter of patients.","Objective tumour response in about 22 percent; myelosuppression was the main adverse effect."],"whatItMeans":"Radionuclide therapy is a standard option for MIBG-avid metastatic pheochromocytoma and paraganglioma; somatostatin receptor targeted lutetium therapy is the alternative for SSTR-avid disease.","caveats":["Single-arm study with a blood pressure medication endpoint rather than survival.","The commercial product was later withdrawn from the US market for business reasons, limiting access."],"changedPractice":true,"participants":68},{"id":"paper-demetri-imatinib-gist-nejm-2002","kind":"paper","name":"Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumours","aka":[],"tldr":"Imatinib produced responses in more than half of patients with advanced gastrointestinal stromal tumours, a cancer that had been completely resistant to chemotherapy, and turned a lethal disease into a chronic one.","summary":"Phase 2 trial of 147 patients with unresectable or metastatic KIT-positive gastrointestinal stromal tumour randomised to imatinib 400 or 600 mg daily.\n\nPartial response occurred in 53.7 percent and stable disease in 27.9 percent, with only 13.6 percent early progression; oedema, nausea, diarrhoea and myalgia were common but serious toxicity was uncommon. Long-term follow-up showed median survival of about five years.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2002","url":"https://doi.org/10.1056/NEJMoa020461"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/12181401/"}],"tags":[],"related":[],"cancers":["gist-kit-exon-11"],"sections":[],"technologies":[],"targets":[],"drugs":["imatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2002,"doi":"10.1056/NEJMoa020461","pmid":"12181401","authors":"Demetri GD, von Mehren M, Blanke CD, et al.","paperType":"rct","findings":["Partial response 53.7 percent; stable disease 27.9 percent.","No significant difference between 400 and 600 mg doses."],"whatItMeans":"Imatinib is the standard first-line treatment for advanced GIST and the model for kinase-targeted therapy in solid tumours.","caveats":["Randomised between doses only, without a control arm.","Response assessment by size criteria underestimates benefit (Choi criteria came later)."],"changedPractice":true,"participants":147},{"id":"paper-zhou-j-thorac-oncol","kind":"paper","name":"Efficacy and Safety of KRASG12C Inhibitor IBI351 Monotherapy in Patients With Advanced NSCLC: Results From a Phase 2 Pivotal Study","aka":[],"tldr":"Paper cited by one treatment page, indexed on Europe PMC as PubMed record 39127176 and published in Journal of Thoracic Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Introduction: KRAS glycine-to-cysteine substitution at codon 12 (G12C) mutation is a well-recognized and increasingly promising therapeutic target with huge unmet clinical needs in NSCLC patients. IBI351 is a potent covalent and irreversible inhibitor of KRAS G12C. Here, we present the efficacy and safety of IBI351 from an open-label, single-arm, phase 2 pivotal study.\n\nMethods: Eligible patients with NSCLC with KRAS G12C who failed standard therapy were enrolled. IBI351 was orally administered at a dose of 600 mg twice daily. The primary endpoint was confirmed objective response rate assessed by an independent radiological review committee (IRRC) as per Response Evaluation Criteria in Solid Tumors v1.1. Other endpoints were safety, IRRC-confirmed disease control rate, duration of response, progression-free survival (PFS), and overall survival.\n\nResults: at December 13, 2023, 116 patients were enrolled (Eastern Cooperative Oncology Group Performance Status 1: 91.4%; brain metastasis: 30.2%; prior treatments with both anti-PD-1 or anti-PD-L1 inhibitors and platinum-based chemotherapy: 84.5%). As per the IRRC assessment, the confirmed objective response rate was 49.1% (95% confidence interval [CI]: 39.7-58.6), and the disease control rate was 90.5% (95% CI: 83.7-95.2). The median duration of response was not reached whereas disease progression or death events occurred in 22 patients (38.6%), and the median PFS was 9.7 months (95% CI: 5.6-11.0). overall survival data was immature. Treatment-related adverse events (TRAEs) occurred in 107 patients (92.2%) whereas 48 patients (41.4%) had equal to or higher than grade three TRAEs. Common TRAEs were anemia (44.8%), increased alanine aminotransferase (28.4%), increased aspartate aminotransferase (27.6%), asthenia (26.7%) and presence of protein in urine (25.0%). TRAEs leading to treatment discontinuation occurred in nine patients (7.8%). In biomarker evaluable patients (n = 95), all patients had positive KRAS G12C in tissue whereas 72 patients were blood-positive and 23 were blood-negative for KRAS G12C. Patients with KRAS G12C in both blood and tissue had higher tumor burden at baseline (p < 0.05) and worse PFS (p < 0.05). Tumor mutation profiling identified tumor protein p53 (45.3%), serine/threonine kinase 11 (STK11) (30.5%), and kelch-like ECH-associated protein 1 (21.1%) as the most common genes co-mutated with KRAS G12C. Among 13 genes with mutation frequency equal to or higher than 5%, mutations of six genes (STK11, kelch-like ECH-associated protein 1, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma, DNA polymerase epsilon, SMAD family member 4, and BMP/retinoic acid-inducible neural-specific protein 3) were significantly associated with worse PFS (p < 0.05). Mutation in STK11 was also found to have a significant association with higher tumor burden at baseline and lower response rate (p < 0.05).\n\nConclusions: IBI351 monotherapy demonstrated promising and sustained efficacy with manageable safety, supporting its potential as a new treatment option for KRAS G12C-mutant NSCLC.\n\nIndexed on Europe PMC as PubMed record 39127176 (DOI 10.1016/j.jtho.2024.08.005). Matched by DOI alone: one treatment page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Thorac Oncol 2024","url":"https://doi.org/10.1016/j.jtho.2024.08.005"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39127176/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39127176"}],"tags":["europepmc-ingest"],"related":["fulzerasib"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-thoracic-oncology"],"dependsOn":[],"notes":[],"journal":"Journal of Thoracic Oncology","year":2024,"doi":"10.1016/j.jtho.2024.08.005","pmid":"39127176","authors":"Zhou Q, Meng X, Sun L, et al.","paperType":"observational","findings":[],"whatItMeans":"One treatment page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nct04143607-lancet-respir-med-2025","kind":"paper","name":"Efficacy and safety of limertinib versus gefitinib as first-line treatment for locally advanced or metastatic non-small-cell lung cancer with EGFR-sensitising mutation: a randomised, double-blind, double-dummy, phase 3 trial","aka":[],"tldr":"Published report from the trial registered as NCT04143607, in The Lancet. Respiratory medicine (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Limertinib is a new third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. This study aimed to prospectively assess the efficacy and safety of limertinib versus gefitinib as a first-line treatment for locally advanced or metastatic non-small-cell lung cancer (NSCLC) with EGFR-sensitising mutation.\n\nMethods: This multicentre, randomised, double-blind, double-dummy, phase 3 trial was done at 56 hospitals in China. Eligible patients were aged ≥18 years with locally advanced or metastatic NSCLC with EGFR-sensitising mutation (exon 19 deletion or exon 21 L858R mutation) detected in tumour tissue samples using the Cobas EGFR Mutation Test at a central laboratory. Patients were randomly assigned (1:1) to receive oral limertinib 80 mg twice a day and gefitinib-matching placebo 250 mg once a day or oral gefitinib 250 mg once a day plus limertinib-matching placebo 80 mg twice a day in 21-day cycles, until disease progression or other discontinuation criteria was met. Random assignment was stratified according to EGFR mutation type (exon 19 deletion or exon 21 L858R mutation) and CNS metastasis (yes or no) using permuted blocks (block size four) through an interactive web-based response system. The primary endpoint was independent central review (ICR)-assessed progression-free survival. All enrolled patients who received at least one dose of study treatment were included in the full analysis set for efficacy analysis. All enrolled patients who received at least one dose of study treatment and one safety assessment were included in the safety set. This study is registered with ClinicalTrials.gov, NCT04143607, and follow-up is ongoing.\n\nFindings: Between June 30, 2021, and Sept 22, 2022, 337 patients were enrolled and 168 were randomly assigned to the limertinib group and 169 to the gefitinib group. Patients' median age was 63 years (34-82). 214 (64%) of 337 patients were female and 123 (36%) were male. The median masked ICR-assessed progression-free survival was 20·7 months (95% CI 15·2-22·1) in the limertinib group and 9·7 months (95% CI 8·3-11·1) in the gefitinib group (hazard ratio [HR] 0·44 [95% CI 0·34-0·58]; p<0·0001). Treatment-related adverse events of grade 3 or worse occurred in 42 (25%) of 168 patients in the limertinib group and 42 (25%) of 169 patients in the gefitinib group. Treatment-related serious adverse events occurred in nine (5%) patients and 17 (10%) patients in each group, respectively. Six (4%) patients in the limertinib group died due to adverse events, all of which were considered possibly unrelated to the study drug by investigators. In the gefitinib group, seven (4%) patients died due to adverse events, with three (2%) of those deaths judged as possibly related to the study drug by investigators. Three treatment-related deaths in the gefitinib group were recorded (one case related to pneumonia and two with cause of death unknown).\n\nInterpretation: Limertinib showed superior efficacy compared with gefitinib and a manageable safety profile for locally advanced or metastatic NSCLC patients with EGFR-sensitising mutation and should be considered as another first-line treatment option for this patient population.\n\nFunding: Jiangsu Aosaikang Pharmaceutical.\n\nTranslation: For the Chinese translation of the abstract see Supplementary Materials section.\n\nIndexed on Europe PMC as PubMed record 40550238 (DOI 10.1016/s2213-2600(25)00121-3). Its abstract cites the registry id NCT04143607, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Respir Med 2025","url":"https://doi.org/10.1016/s2213-2600(25)00121-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40550238/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40550238"},{"label":"ClinicalTrials.gov NCT04143607","url":"https://clinicaltrials.gov/study/NCT04143607"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04143607"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Lancet. Respiratory medicine","year":2025,"doi":"10.1016/s2213-2600(25)00121-3","pmid":"40550238","authors":"Shi Y, Wu L, Ji Y, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04143607 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-xm22-03-bondarenko-bmc-cancer-2013","kind":"paper","name":"Efficacy and safety of lipegfilgrastim versus pegfilgrastim in breast cancer patients receiving doxorubicin and docetaxel (XM22-03)","aka":[],"tldr":"In women having chemotherapy for breast cancer, a single dose of the new white-cell booster lipegfilgrastim kept the dangerous dip in white cells as short as the standard booster pegfilgrastim, with no cases of infection-related fever on the new drug.","summary":"Primary publication of XM22-03 (EudraCT 2009-015999-10), a phase 3, double-blind, randomised, active-controlled, non-inferiority trial. Patients with high-risk stage II, III or IV breast cancer and an absolute neutrophil count of at least 1.5 x 10^9 cells per litre were randomised to a single 6 mg subcutaneous injection of lipegfilgrastim (n = 101) or pegfilgrastim (n = 101) on day 2 of each 21-day doxorubicin and docetaxel cycle, for up to four cycles. The primary efficacy endpoint was the duration of severe neutropenia during cycle 1.\n\nMean duration of severe neutropenia in cycle 1 was 0.7 days with lipegfilgrastim and 0.8 days with pegfilgrastim (lambda -0.218, 95 percent CI -0.498 to 0.062; p = 0.126); no severe neutropenia was seen in 56 percent and 49 percent of patients. Across all cycles, febrile neutropenia occurred in three pegfilgrastim-treated patients (all in cycle 1) and none on lipegfilgrastim. Drug-related adverse events were reported in 28 percent and 26 percent.","asOf":"2026-09-24","links":[{"label":"BMC Cancer 2013","url":"https://doi.org/10.1186/1471-2407-13-386"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23945072/"},{"label":"Lonquex EPAR (EMA)","url":"https://www.ema.europa.eu/en/medicines/human/EPAR/lonquex"}],"tags":[],"related":[],"cancers":["breast-cancer"],"sections":["supportive-care"],"technologies":[],"targets":[],"drugs":["lipegfilgrastim","pegfilgrastim"],"companies":["teva"],"institutions":[],"pathways":[],"terms":[],"trials":["xm22-03"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["bmc-cancer"],"dependsOn":[],"notes":[],"journal":"BMC Cancer","year":2013,"doi":"10.1186/1471-2407-13-386","pmid":"23945072","authors":"Bondarenko I, Gladkov OA, Elsaesser R, et al.","paperType":"rct","findings":["Mean duration of severe neutropenia in cycle 1: 0.7 days with lipegfilgrastim vs 0.8 days with pegfilgrastim (p = 0.126); non-inferiority shown.","No severe neutropenia in cycle 1 in 56 percent vs 49 percent of patients.","Febrile neutropenia in 0 vs 3 patients (efficacy population); drug-related adverse events in 28 percent vs 26 percent."],"whatItMeans":"This is the breast-cancer pivotal behind the 2013 EU authorisation of Lonquex, establishing lipegfilgrastim as an alternative once-per-cycle growth factor to pegfilgrastim. The confidence interval for lambda belongs to a Poisson-model effect estimate and is not a hazard ratio.","caveats":["Non-inferiority design; the p value of 0.126 is the between-arm comparison, not evidence of superiority.","The confidence interval bounds are printed with percent signs in the abstract but are on the same scale as lambda.","Three co-authors were employees of the sponsor."],"changedPractice":true,"participants":202},{"id":"paper-gotlib-midostaurin-advanced-systemic-mastocytosis-nejm-2016","kind":"paper","name":"Efficacy and safety of midostaurin in advanced systemic mastocytosis","aka":[],"tldr":"The multi-kinase inhibitor midostaurin shrank the mast cell burden and reversed organ damage in six in ten patients with advanced systemic mastocytosis, becoming the first approved targeted drug for the disease.","summary":"Open-label phase 2 study of 116 patients with advanced systemic mastocytosis (aggressive systemic mastocytosis, systemic mastocytosis with an associated haematological neoplasm, or mast cell leukaemia) treated with midostaurin 100 mg twice daily; 89 were evaluable for response.\n\nThe overall response rate was 60 percent with major responses in 45 percent, median overall survival 28.7 months and median progression-free survival 14.1 months; responses occurred regardless of KIT D816V status. Nausea, vomiting and cytopenias were the main toxicities. The FDA and EMA approved midostaurin for advanced systemic mastocytosis in 2017.","asOf":"2026-09-18","links":[{"label":"N Engl J Med 2016","url":"https://doi.org/10.1056/NEJMoa1513098"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27355533/"}],"tags":[],"related":[],"cancers":["advanced-systemic-mastocytosis"],"sections":[],"technologies":[],"targets":[],"drugs":["midostaurin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2016,"doi":"10.1056/NEJMoa1513098","pmid":"27355533","authors":"Gotlib J, Kluin-Nelemans HC, George TI, et al.","paperType":"observational","findings":["Overall response 60 percent, major response 45 percent.","Median overall survival 28.7 months; median progression-free survival 14.1 months."],"whatItMeans":"Midostaurin was the first effective targeted therapy for advanced systemic mastocytosis and remains an option, particularly where avapritinib is unsuitable or unavailable.","caveats":["Single-arm study with response criteria that predate the current consensus.","Gastrointestinal toxicity limits tolerance in many patients."],"changedPractice":true,"participants":116},{"id":"paper-mirvetuximab-soravtansine-ovarian-j-clin-oncol-2023","kind":"paper","name":"Efficacy and Safety of Mirvetuximab Soravtansine in Patients With Platinum-Resistant Ovarian Cancer With High Folate Receptor Alpha Expression: Results From the SORAYA Study","aka":[],"tldr":"Phase 2 or 3 results paper on Mirvetuximab soravtansine in Ovarian cancer, in Journal of Clinical Oncology (2023), one of the most cited Europe PMC records with Mirvetuximab soravtansine in its title.","summary":"Purpose: Single-agent chemotherapies have limited activity and considerable toxicity in patients with platinum-resistant epithelial ovarian cancer (PROC). Mirvetuximab soravtansine (MIRV) is an antibody-drug conjugate targeting folate receptor α (FRα). SORAYA is a single-arm, phase II study evaluating efficacy and safety of MIRV in patients with PROC.\n\nMethods: SORAYA enrolled FRα-high patients with PROC who had received one to three prior therapies, including required bevacizumab. The primary end point was confirmed objective response rate (ORR) by investigator; duration of response was the key secondary end point.\n\nResults: One hundred six patients were enrolled; 105 were evaluable for efficacy. All patients had received prior bevacizumab, 51% had three prior lines of therapy, and 48% received a prior poly ADP-ribose polymerase inhibitor. Median follow-up was 13.4 months. ORR was 32.4% (95% CI, 23.6 to 42.2), including five complete and 29 partial responses. The median duration of response was 6.9 months (95% CI, 5.6 to 9.7). In patients with one to two priors, the ORR by investigator was 35.3% (95% CI, 22.4 to 49.9) and in patients with three priors was 30.2% (95% CI, 18.3 to 44.3). The ORR by investigator was 38.0% (95% CI, 24.7 to 52.8) in patients with prior poly ADP-ribose polymerase inhibitor exposure and 27.5% (95% CI, 15.9 to 41.7) in those without. The most common treatment-related adverse events (all grade and grade 3-4) were blurred vision (41% and 6%), keratopathy (29% and 9%), and nausea (29% and 0%). Treatment-related adverse events led to dose delays, reductions, and discontinuations in 33%, 20%, and 9% of patients, respectively.\n\nConclusion: MIRV demonstrated consistent clinically meaningful antitumor activity and favorable tolerability and safety in patients with FRα-high PROC who had received up to three prior therapies, including bevacizumab, representing an important advance for this biomarker-selected population.\n\nIndexed on Europe PMC as PubMed record 36716407 (DOI 10.1200/jco.22.01900). Its title names Mirvetuximab soravtansine and its text names Ovarian cancer; PubMed types it as a clinical trial report (Clinical Trial, Phase II, Research Support, Non-U.S. Gov't, research-article). It was matched automatically to the idea \"Sequence folate-receptor ADCs by payload class\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2023","url":"https://doi.org/10.1200/jco.22.01900"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36716407/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36716407"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2023,"doi":"10.1200/jco.22.01900","pmid":"36716407","authors":"Matulonis UA, Lorusso D, Oaknin A, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Mirvetuximab soravtansine in Ovarian cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Mirvetuximab soravtansine in the title and Ovarian cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-neosphere-lancet-oncol-2012","kind":"paper","name":"Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial","aka":[],"tldr":"Published report from the NeoSphere trial registered as NCT00545688, in The Lancet Oncology (2012), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Studies with pertuzumab, a novel anti-HER2 antibody, show improved efficacy when combined with the established HER2-directed antibody trastuzumab in breast cancer therapy. We investigated the combination of pertuzumab or trastuzumab, or both, with docetaxel and the combination of pertuzumab and trastuzumab without chemotherapy in the neoadjuvant setting.\n\nMethods: In this multicentre, open-label, phase 2 study, treatment-naive women with HER2-positive breast cancer were randomly assigned (1:1:1:1) centrally and stratified by operable, locally advanced, and inflammatory breast cancer, and by hormone receptor expression to receive four neoadjuvant cycles of: trastuzumab (8 mg/kg loading dose, followed by 6 mg/kg every 3 weeks) plus docetaxel (75 mg/m(2), escalating, if tolerated, to 100 mg/m(2) every 3 weeks; group A) or pertuzumab (loading dose 840 mg, followed by 420 mg every 3 weeks) and trastuzumab plus docetaxel (group B) or pertuzumab and trastuzumab (group C) or pertuzumab plus docetaxel (group D). The primary endpoint, examined in the intention-to-treat population, was pathological complete response in the breast. Neither patients nor investigators were masked to treatment. This study is registered with ClinicalTrials.gov, number NCT00545688.\n\nFindings: Of 417 eligible patients, 107 were randomly assigned to group A, 107 to group B, 107 to group C, and 96 to group D. Patients given pertuzumab and trastuzumab plus docetaxel (group B) had a significantly improved pathological complete response rate (49 of 107 patients; 45·8% [95% CI 36·1-55·7]) compared with those given trastuzumab plus docetaxel (group A; 31 of 107; 29·0% [20·6-38·5]; p=0·0141). 23 of 96 (24·0% [15·8-33·7]) women given pertuzumab plus docetaxel (group D) had a pathological complete response, as did 18 of 107 (16·8% [10·3-25·3]) given pertuzumab and trastuzumab (group C). The most common adverse events of grade 3 or higher were neutropenia (61 of 107 women in group A, 48 of 107 in group B, one of 108 in group C, and 52 of 94 in group D), febrile neutropenia (eight, nine, none, and seven, respectively), and leucopenia (13, five, none, and seven, respectively). The number of serious adverse events was similar in groups A, B, and D (15-20 serious adverse events per group in 10-17% of patients) but lower in group C (four serious adverse events in 4% of patients).\n\nInterpretation: Patients given pertuzumab and trastuzumab plus docetaxel (group B) had a significantly improved pathological complete response rate compared with those given trastuzumab plus docetaxel, without substantial differences in tolerability. Pertuzumab and trastuzumab without chemotherapy eradicated tumours in a proportion of women and showed a favourable safety profile. These findings justify further exploration in adjuvant trials and support the neoadjuvant approach for accelerating drug assessment in early breast cancer.\n\nFunding: F Hoffmann-La Roche.\n\nIndexed on Europe PMC as PubMed record 22153890 (DOI 10.1016/s1470-2045(11)70336-9). Its abstract cites the registry id NCT00545688, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2012","url":"https://doi.org/10.1016/s1470-2045(11)70336-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22153890/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/22153890"},{"label":"ClinicalTrials.gov NCT00545688","url":"https://clinicaltrials.gov/study/NCT00545688"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["neosphere"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2012,"doi":"10.1016/s1470-2045(11)70336-9","pmid":"22153890","authors":"Gianni L, Pienkowski T, Im YH, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT00545688 with the most citations, so it is the natural first reading for anyone following the NeoSphere trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-nct06198751-j-clin-oncol-2026","kind":"paper","name":"Efficacy and Safety of Neoadjuvant TQB2102 in Locally Advanced or Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: A Randomized, Open-Label, Multicenter, Phase II Trial","aka":[],"tldr":"Published report from the trial registered as NCT06198751, in Journal of Clinical Oncology (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Purpose: To evaluate the efficacy and safety of the bispecific human epidermal growth factor receptor 2 (HER2)-directed antibody-drug conjugate (ADC) TQB2102 in the neoadjuvant treatment of HER2-positive breast cancer.\n\nPatients and methods: This randomized, open-label, multicenter, phase II study (ClinicalTrials.gov identifier: NCT06198751) enrolled HER2-positive patients with stage II and III disease. Patients were stratified by hormone receptor status and randomly assigned (1:1) to receive 6.0 mg/kg once every 3 weeks of TQB2102 for six (cohort 1) or eight cycles (cohort 2) or 7.5 mg/kg once every 3 weeks for six (cohort 3) or eight cycles (cohort 4). The primary end point was total pathologic complete response (tpCR) rate across all four cohorts (n = 26 per cohort). When the lower limit of the 90% CI (Clopper-Pearson exact binomial test) for tpCR rate exceeded 40%, efficacy was considered better than that of the historical control.\n\nResults: Between February 5, 2024, and September 24, 2024, 104 patients were enrolled, with 26 patients in each cohort. The tpCR rates were 57.7% (15 of 26 [90% CI, 43.2 to 71.3]; P =.04) for cohort 1, 76.9% (20 of 26 [90% CI, 62.3 to 87.6]; P <.01) for cohort 2, 61.5% (16 of 26 [90% CI, 46.5 to 74.8]; P =.02) for cohort 3, and 69.2% (18 of 26 [90% CI, 54.6 to 81.3]; P <.01) for cohort 4. The incidence rates of grade ≥3 treatment-related adverse events were 23.1% (6 of 26) for cohort 1, 30.8% (8 of 26) for cohort 2, 30.8% (8 of 26) for cohort 3, and 26.9% (7 of 26) for cohort 4. No treatment-related deaths occurred in any groups.\n\nConclusion: To our knowledge, this was the first study to report the efficacy and safety of the bispecific HER2-directed ADC TQB2102 in the neoadjuvant setting for HER2-positive breast cancer. TQB2102 showed robust activity and was well-tolerated.\n\nIndexed on Europe PMC as PubMed record 41289548 (DOI 10.1200/jco-25-01153). Its abstract cites the registry id NCT06198751, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2026","url":"https://doi.org/10.1200/jco-25-01153"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41289548/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41289548"},{"label":"ClinicalTrials.gov NCT06198751","url":"https://clinicaltrials.gov/study/NCT06198751"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct06198751"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2026,"doi":"10.1200/jco-25-01153","pmid":"41289548","authors":"Li JJ, Zhang WJ, Zeng XH, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT06198751 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-nivolumab-hcc-jama-oncol-2020","kind":"paper","name":"Efficacy and Safety of Nivolumab Plus Ipilimumab in Patients With Advanced Hepatocellular Carcinoma Previously Treated With Sorafenib: The CheckMate 040 Randomized Clinical Trial","aka":[],"tldr":"Phase 2 or 3 results paper on Nivolumab in Hepatocellular carcinoma, in JAMA Oncology (2020), one of the most cited Europe PMC records with Nivolumab in its title.","summary":"Importance: Most patients with hepatocellular carcinoma (HCC) are diagnosed with advanced disease not eligible for potentially curative therapies; therefore, new treatment options are needed. Combining nivolumab with ipilimumab may improve clinical outcomes compared with nivolumab monotherapy.\n\nObjective: To assess efficacy and safety of nivolumab plus ipilimumab in patients with advanced HCC who were previously treated with sorafenib.\n\nDesign, setting, and participants: CheckMate 040 is a multicenter, open-label, multicohort, phase 1/2 study. In the nivolumab plus ipilimumab cohort, patients were randomized between January 4 and September 26, 2016. Treatment group information was blinded after randomization. Median follow-up was 30.7 months. Data cutoff for this analysis was January 2019. Patients were recruited at 31 centers in 10 countries/territories in Asia, Europe, and North America. Eligible patients had advanced HCC (with/without hepatitis B or C) previously treated with sorafenib. A total of 148 patients were randomized (50 to arm A and 49 each to arms B and C).\n\nInterventions: Patients were randomized 1:1:1 to either nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, administered every 3 weeks (4 doses), followed by nivolumab 240 mg every 2 weeks (arm A); nivolumab 3 mg/kg plus ipilimumab 1 mg/kg, administered every 3 weeks (4 doses), followed by nivolumab 240 mg every 2 weeks (arm B); or nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks (arm C).\n\nMain outcomes and measures: Coprimary end points were safety, tolerability, and objective response rate. Duration of response was also measured (investigator assessed with the Response Evaluation Criteria in Solid Tumors v1.1).\n\nResults: Of 148 total participants, 120 were male (81%). Median (IQR) age was 60 (52.5-66.5). At data cutoff (January 2019), the median follow-up was 30.7 months (IQR, 29.9-34.7). Investigator-assessed objective response rate was 32% (95% CI, 20%-47%) in arm A, 27% (95% CI, 15%-41%) in arm B, and 29% (95% CI, 17%-43%) in arm C. Median (range) duration of response was not reached (8.3-33.7+) in arm A and was 15.2 months (4.2-29.9+) in arm B and 21.7 months (2.8-32.7+) in arm C. Any-grade treatment-related adverse events were reported in 46 of 49 patients (94%) in arm A, 35 of 49 patients (71%) in arm B, and 38 of 48 patients (79%) in arm C; there was 1 treatment-related death (arm A; grade 5 pneumonitis).\n\nConclusions and relevance: In this randomized clinical trial, nivolumab plus ipilimumab had manageable safety, promising objective response rate, and durable responses. The arm A regimen (4 doses nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks then nivolumab 240 mg every 2 weeks) received accelerated approval in the US based on the results of this study.\n\nTrial registration: ClinicalTrials.gov Identifier: NCT01658878.\n\nIndexed on Europe PMC as PubMed record 33001135 (DOI 10.1001/jamaoncol.2020.4564). Its title names Nivolumab and its text names Hepatocellular carcinoma; PubMed types it as a clinical trial report (Clinical Trial, Phase II, research-article, Multicenter Study, Clinical Trial, Phase I, Randomized Controlled Trial). It was matched automatically to the idea \"Immunotherapy downstaging to transplant with a safe washout\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA Oncol 2020","url":"https://doi.org/10.1001/jamaoncol.2020.4564"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33001135/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33001135"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2020,"doi":"10.1001/jamaoncol.2020.4564","pmid":"33001135","authors":"Yau T, Kang YK, Kim TY, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Nivolumab in Hepatocellular carcinoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Nivolumab in the title and Hepatocellular carcinoma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-keynote-158-j-clin-oncol-2019","kind":"paper","name":"Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Cervical Cancer: Results From the Phase II KEYNOTE-158 Study","aka":[],"tldr":"Published report from the KEYNOTE-158 trial registered as NCT02628067, in Journal of Clinical Oncology (2019), chosen as the most cited paper whose own text cites the registry id.","summary":"Purpose: KEYNOTE-158 ( ClinicalTrials.gov identifier: NCT02628067) is a phase II basket study investigating the antitumor activity and safety of pembrolizumab in multiple cancer types. We present interim results from patients with previously treated advanced cervical cancer.\n\nPatients and methods: Patients received pembrolizumab 200 mg every 3 weeks for 2 years or until progression, intolerable toxicity, or physician or patient decision. Tumor imaging was performed every 9 weeks for the first 12 months and every 12 weeks thereafter. The primary end point was objective response rate (ORR), assessed per Response Evaluation Criteria in Solid Tumors (version 1.1) by independent central radiologic review. Safety was a secondary end point.\n\nResults: Ninety-eight patients were treated. Median age was 46.0 years (range, 24 to 75 years), and 65.3% of patients had Eastern Cooperative Oncology Group performance status of 1. Eighty-two patients (83.7%) had programmed death-ligand 1 (PD-L1)-positive tumors (combined positive score ≥ 1), 77 having previously received one or more lines of chemotherapy for recurrent or metastatic disease. Median follow-up was 10.2 months (range, 0.6 to 22.7 months). ORR was 12.2% (95% CI, 6.5% to 20.4%), with three complete and nine partial responses. All 12 responses were in patients with PD-L1-positive tumors, for an ORR of 14.6% (95% CI, 7.8% to 24.2%); 14.3% (95% CI, 7.4% to 24.1%) of these responses were in those who had received one or more lines of chemotherapy for recurrent or metastatic disease. Median duration of response was not reached (range, ≥ 3.7 to ≥ 18.6 months). Treatment-related adverse events occurred in 65.3% of patients, and the most common were hypothyroidism (10.2%), decreased appetite (9.2%), and fatigue (9.2%). Treatment-related grade 3 to 4 adverse events occurred in 12.2% of patients.\n\nConclusion: Pembrolizumab monotherapy demonstrated durable antitumor activity and manageable safety in patients with advanced cervical cancer. On the basis of these results, the US Food and Drug Administration granted accelerated approval of pembrolizumab for patients with advanced PD-L1-positive cervical cancer who experienced progression during or after chemotherapy.\n\nIndexed on Europe PMC as PubMed record 30943124 (DOI 10.1200/jco.18.01265). Its abstract cites the registry id NCT02628067, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2019","url":"https://doi.org/10.1200/jco.18.01265"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30943124/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30943124"},{"label":"ClinicalTrials.gov NCT02628067","url":"https://clinicaltrials.gov/study/NCT02628067"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-158"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2019,"doi":"10.1200/jco.18.01265","pmid":"30943124","authors":"Chung HC, Ros W, Delord JP, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02628067 with the most citations, so it is the natural first reading for anyone following the KEYNOTE-158 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-florence-duffaud-lancet-oncol-2019","kind":"paper","name":"Efficacy and safety of regorafenib in adult patients with metastatic osteosarcoma: a non-comparative, randomised, double-blind, placebo-controlled, phase 2 study","aka":[],"tldr":"Paper by Florence Duffaud indexed on Europe PMC as PubMed record 30477937, in The Lancet Oncology (2019), one of the most cited records naming an author with this name at Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille.","summary":"Background: Regorafenib has proven activity in patients with pretreated gastrointestinal stromal tumours and colorectal and hepatocellular carcinoma. We designed REGOBONE to assess the efficacy and safety of regorafenib for patients with progressive metastatic osteosarcoma and other bone sarcomas. This trial comprised four parallel independent cohorts: osteosarcoma, Ewing sarcoma, chondrosarcoma, and chordoma. In this Article, we report the results of the osteosarcoma cohort.\n\nMethods: In this non-comparative, double-blind, placebo-controlled, phase 2 trial, patients aged 10 years or older with histologically confirmed osteosarcoma whose disease had progressed after treatment with one to two previous lines of chemotherapy for metastatic disease and an Eastern Cooperative Oncology Group performance status of 0 or 1 were enrolled. Patients were randomly assigned (2:1) to receive either oral regorafenib (160 mg/day, for 21 of 28 days) or matching placebo. Patients in both groups also received best supportive care. Randomisation was done using a web-based system and was stratified (permuted block) by age at inclusion (<18 vs ≥18 years old). Investigators and patients were masked to treatment allocation. Patients in the placebo group, after centrally confirmed progressive disease, could cross over to receive regorafenib. The primary endpoint was the proportion of patients without disease progression at 8 weeks. Analyses were done by modified intention to treat (ie, patients without any major entry criteria violation who initiated masked study drug treatment were included). All participants who received at least one dose of study drug were included in the safety analyses. This study is registered with ClinicalTrials.gov, number NCT02389244, and the results presented here are the final analysis of the osteosarcoma cohort (others cohorts are ongoing).\n\nFindings: Between Oct 10, 2014, and April 4, 2017, 43 adult patients were enrolled from 13 French comprehensive cancer centres. All patients received at least one dose of assigned treatment and were evaluable for safety; five patients were excluded for major protocol violations (two in the placebo group and three in the regorafenib group), leaving 38 patients who were evaluable for efficacy (12 in the placebo group and 26 in the regorafenib group). 17 of 26 patients (65%; one-sided 95% CI 47%) in the regorafenib group were non-progressive at 8 weeks compared with no patients in the placebo group. Ten patients in the placebo group crossed over to receive open-label regorafenib after centrally confirmed disease progression. 13 treatment-related serious adverse events occurred in seven (24%) of 29 patients in the regorafenib group versus none of 14 patients in the placebo group. The most common grade 3 or worse treatment-related adverse events during the double-blind period of treatment included hypertension (in seven [24%] of 29 patients in the regorafenib group vs none in the placebo group), hand-foot skin reaction (three [10%] vs none), fatigue (three [10%] vs one [3%]), hypophosphataemia (three [10%] vs none), and chest pain (three [10%] vs none). No treatment-related deaths occurred.\n\nInterpretation: Regorafenib demonstrated clinically meaningful antitumour activity in adult patients with recurrent, progressive, metastatic osteosarcoma after failure of conventional chemotherapy, with a positive effect on delaying disease progression. Regorafenib should be further evaluated in the setting of advanced disease as well as potentially earlier in the disease course for patients at high risk of relapse. Regorafenib might have an important therapeutic role as an agent complementary to standard cytotoxic chemotherapy in the therapeutic armamentarium against osteosarcoma.\n\nFunding: Bayer HealthCare.\n\nIndexed on Europe PMC as PubMed record 30477937 (DOI 10.1016/s1470-2045(18)30742-3). Its author list gives \"Duffaud F\" with the affiliation \"Medical Oncology Unit, Aix Marseille University, APHM Hôpital La Timone, Marseille, France. Electronic address: florence.duffaud@ap-hm.fr\", which names Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille; that is how the record was matched to Florence Duffaud, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2019","url":"https://doi.org/10.1016/s1470-2045(18)30742-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30477937/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30477937"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["florence-duffaud"],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2019,"doi":"10.1016/s1470-2045(18)30742-3","pmid":"30477937","authors":"Duffaud F, Mir O, Boudou-Rouquette P, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Florence Duffaud at Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-dll3-sclc-clin-cancer-res-2019","kind":"paper","name":"Efficacy and Safety of Rovalpituzumab Tesirine in Third-Line and Beyond Patients with DLL3-Expressing, Relapsed/Refractory Small-Cell Lung Cancer: Results From the Phase II TRINITY Study","aka":[],"tldr":"Phase 2 or 3 results paper on DLL3 in Small-cell lung cancer, in Clinical Cancer Research (2019), one of the most cited Europe PMC records with DLL3 in its title.","summary":"Purpose: Although extensive-stage small-cell lung cancer (SCLC) is highly responsive to first-line therapy, virtually all patients develop resistance with short survival. Rovalpituzumab tesirine (Rova-T) is an antibody-drug conjugate targeting delta-like 3 protein (DLL3). This open-label, single-arm, phase II study (TRINITY) assessed safety and efficacy of Rova-T in patients with DLL3-expressing SCLC in the third-line and beyond (3L+) setting.\n\nPatients and methods: Patients with DLL3-expressing SCLC (determined by mouse antibody immunohistochemistry [IHC] assay), and ≥2 prior regimens, received 0.3 mg/kg Rova-T once every 6 weeks for two cycles. During study, a rabbit antibody IHC assay was developed and used for the final analysis, with DLL3-positive and DLL3-high defined as ≥25% and ≥75% of tumor cells positive for DLL3, respectively. The primary endpoints were objective response rate (ORR) and overall survival (OS).\n\nResults: Among 339 patients enrolled, 261 (77%) had two prior lines of therapy and 78 (23%) had ≥3. DLL3-high and DLL3-positive tumors by rabbit IHC were seen in 238 (70%) and 287 (85%) patients, respectively. The remaining 52 (15%) were DLL3-negative only by rabbit IHC or had missing results. ORR was 12.4%, 14.3%, and 13.2% in all, DLL3-high, and DLL3-positive patients, respectively. Median OS was 5.6 months in all patients and 5.7 months in DLL3-high patients. The most common adverse events (AE) were fatigue, photosensitivity reaction, and pleural effusion. Grade 3-5 AEs were seen in 213 (63%) patients.\n\nConclusions: Rova-T is the first targeted agent in SCLC to use DLL3, a novel biomarker. However, results demonstrate modest clinical activity in 3L+ SCLC, with associated toxicities.\n\nIndexed on Europe PMC as PubMed record 31506387 (DOI 10.1158/1078-0432.ccr-19-1133). Its title names DLL3 and its text names Small-cell lung cancer; PubMed types it as a clinical trial report (Clinical Trial, Phase II, Research Support, Non-U.S. Gov't, research-article). It was matched automatically to the idea \"Subtype-directed therapy for SCLC (ASCL1 / NEUROD1 / POU2F3 / inflamed)\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Clin Cancer Res 2019","url":"https://doi.org/10.1158/1078-0432.ccr-19-1133"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31506387/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31506387"}],"tags":["europepmc-ingest"],"related":["lung-cancer-evidence-roadmap","paper-george-sclc-genomic-profiles-nature-2015","paper-rudin-sclc-molecular-subtypes-nat-rev-cancer-2019"],"cancers":["lung-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2019,"doi":"10.1158/1078-0432.ccr-19-1133","pmid":"31506387","authors":"Morgensztern D, Besse B, Greillier L, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for DLL3 in Small-cell lung cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by DLL3 in the title and Small-cell lung cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-nct05300269-cancer-lett-2026","kind":"paper","name":"Efficacy and safety of SHR-1701 combined with chemoradiotherapy as neoadjuvant treatment for locally advanced rectal cancer","aka":[],"tldr":"Published report from the trial registered as NCT05300269, in Cancer letters (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Locally advanced rectal cancer (LARC) remains challenging to treat due to high recurrence rates and limited therapeutic options, particularly for patients with high-risk features. This prospective, multicenter, single-arm, open-label phase 2 trial (ClinicalTrials.gov identifier: NCT05300269) evaluated the efficacy and safety of SHR-1701, a novel bifunctional fusion protein targeting both PD-L1 and TGF-β, in combination with neoadjuvant chemoradiotherapy (CRT) followed by total mesorectal excision (TME) for high-risk LARC. Eligible patients had at least one high-risk factor, including cT3c-d or cT4 tumors, positive mesorectal fascia, extramural vascular invasion, or involvement of ≥4 lymph nodes. Patients received concurrent SHR-1701 and CRT, followed by two cycles of SHR-1701 plus XELOX and subsequent TME surgery. Postoperatively, patients underwent six additional cycles of SHR-1701 plus XELOX. The primary endpoints were pathological complete response (pCR) rate and safety. Among the 37 enrolled patients, 36 (97.3 %) completed the planned full-dose radiotherapy (50.4 Gy in 28 fractions) and subsequently underwent surgery. The pCR rate was 36.1 % (13/36). The median intervals from neoadjuvant therapy initiation to surgery and from surgery to adjuvant therapy were 112 days (range, 95-139) and 29 days (range, 22-59), respectively. The median follow-up was 9.9 months (range, 2-18) from the first dose of capecitabine. Grade ≥3 treatment-related adverse events during neoadjuvant therapy occurred in 40.5 % (15/37) of patients, most commonly lymphopenia (37.8 %, 14/37) and anemia (5.4 %, 2/37). One patient experienced fatal immune-mediated myocarditis prior to surgery. Overall, the addition of SHR-1701 to CRT demonstrated encouraging efficacy and manageable safety in high-risk LARC, supporting further investigation in larger randomized trials.\n\nIndexed on Europe PMC as PubMed record 40876501 (DOI 10.1016/j.canlet.2025.218006). Its abstract cites the registry id NCT05300269, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Cancer Lett 2026","url":"https://doi.org/10.1016/j.canlet.2025.218006"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40876501/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40876501"},{"label":"ClinicalTrials.gov NCT05300269","url":"https://clinicaltrials.gov/study/NCT05300269"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05300269"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-letters"],"dependsOn":[],"notes":[],"journal":"Cancer letters","year":2026,"doi":"10.1016/j.canlet.2025.218006","pmid":"40876501","authors":"Tang W, Lv Y, Xie H, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05300269 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-orient-11-j-thorac-oncol-2020","kind":"paper","name":"Efficacy and Safety of Sintilimab Plus Pemetrexed and Platinum as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC: a Randomized, Double-Blind, Phase 3 Study (Oncology pRogram by InnovENT anti-PD-1-11)","aka":[],"tldr":"Published report from the ORIENT-11 trial registered as NCT03607539, in Journal of Thoracic Oncology (2020), chosen as the most cited paper whose own text cites the registry id.","summary":"Introduction: Sintilimab, an anti-programmed death 1 antibody, plus pemetrexed and platinum had revealed promising efficacy for nonsquamous NSCLC in a phase 1b study. We conducted a randomized, double-blind, phase 3 study to compare the efficacy and safety of sintilimab with placebo, both in combination with such chemotherapy (ClinicalTrials.gov: NCT03607539).\n\nMethods: A total of 397 patients with previously untreated, locally advanced or metastatic nonsquamous NSCLC without sensitizing EGFR or anaplastic lymphoma kinase genomic aberration were randomized (2:1 ratio) to receive either sintilimab 200 mg or placebo plus pemetrexed and platinum once every 3 weeks for four cycles, followed by sintilimab or placebo plus pemetrexed therapy. Crossover or treatment beyond disease progression was allowed. The primary end point was progression-free survival (PFS) as judged by an independent radiographic review committee.\n\nResults: at November 15, 2019, the median follow-up was 8.9 months. The median PFS was significantly longer in the sintilimab-combination group than that in the placebo-combination group (8.9 versus 5.0 mo; hazard ratio, 0.482, 95% confidence interval [CI]: 0.362-0.643; p < 0.00001). The confirmed objective response rate was 51.9% (95% CI: 45.7%-58.0%) in the sintilimab-combination group and 29.8% (95% CI: 22.1%-38.4%) in placebo-combination group. The incidence of grade 3 or higher adverse events was 61.7% in sintilimab-combination group and 58.8% in placebo-combination group.\n\nConclusions: In Chinese patients with previously untreated, locally advanced or metastatic nonsquamous NSCLC, the addition of sintilimab to chemotherapy with pemetrexed and platinum resulted in considerably longer PFS than with chemotherapy alone with manageable safety profiles.\n\nIndexed on Europe PMC as PubMed record 32781263 (DOI 10.1016/j.jtho.2020.07.014). Its abstract cites the registry id NCT03607539, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Thorac Oncol 2020","url":"https://doi.org/10.1016/j.jtho.2020.07.014"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32781263/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32781263"},{"label":"ClinicalTrials.gov NCT03607539","url":"https://clinicaltrials.gov/study/NCT03607539"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["orient-11"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-thoracic-oncology"],"dependsOn":[],"notes":[],"journal":"Journal of Thoracic Oncology","year":2020,"doi":"10.1016/j.jtho.2020.07.014","pmid":"32781263","authors":"Yang Y, Wang Z, Fang J, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03607539 with the most citations, so it is the natural first reading for anyone following the ORIENT-11 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-nct04395677-j-clin-oncol-2024","kind":"paper","name":"Efficacy and Safety of Taletrectinib in Chinese Patients With ROS1+ Non-Small Cell Lung Cancer: The Phase II TRUST-I Study","aka":[],"tldr":"Published report from the trial registered as NCT04395677, in Journal of Clinical Oncology (2024), chosen as the most cited paper whose own text cites the registry id.","summary":"Purpose: Taletrectinib, a highly potent, CNS-active, ROS1 tyrosine kinase inhibitor (TKI), has demonstrated high and durable response rates, high intracranial objective response rate (ORR), prolonged progression-free survival (PFS), and activity against G2032R with a favorable safety profile. We report outcomes from the pivotal TRUST-I study (ClinicalTrials.gov identifier: NCT04395677) of taletrectinib for ROS1+ non-small cell lung cancer in China.\n\nMethods: TRUST-I evaluated TKI-naїve and crizotinib-pretreated patients. The primary end point was confirmed ORR (cORR) by independent review committee; key secondary end points included duration of response (DOR), PFS, and safety.\n\nResults: at November 2023, 173 patients were enrolled (median age, 55 years; 58% female; 73% never smoked; TKI naїve: n = 106; crizotinib pretreated: n = 67). In TKI-naїve patients, cORR and intracranial cORR were 91% and 88%, respectively, and 52% and 73% in crizotinib-pretreated patients. In TKI-naїve patients, median DOR and median PFS were not reached (NR) with 22.1-month and 23.5-month follow-up, respectively. In crizotinib-pretreated patients, the median DOR was 10.6 months (95% CI, 6.3 months to NR; 8.4-month follow-up), and the median PFS was 7.6 months (95% CI, 5.5 to 12.0 months; 9.7-month follow-up). Eight of 12 patients (67%) with G2032R mutations responded. The most frequent treatment-emergent adverse events (TEAEs) were increased AST (76%), diarrhea (70%), and increased ALT (68%), most of which were grade 1-2. Incidences of neurologic TEAEs were low (dizziness: 23%; dysgeusia: 10%) and mostly grade 1. Discontinuations (5%) and dose reductions (19%) due to TEAEs were low.\n\nConclusion: Taletrectinib continues to show high and durable overall responses, prolonged PFS, robust activity against intracranial lesions and acquired resistance mutations including G2032R, and a favorable safety profile with a low incidence of neurologic TEAEs.\n\nIndexed on Europe PMC as PubMed record 38822758 (DOI 10.1200/jco.24.00731). Its abstract cites the registry id NCT04395677, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2024","url":"https://doi.org/10.1200/jco.24.00731"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38822758/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38822758"},{"label":"ClinicalTrials.gov NCT04395677","url":"https://clinicaltrials.gov/study/NCT04395677"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04395677"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2024,"doi":"10.1200/jco.24.00731","pmid":"38822758","authors":"Li W, Xiong A, Yang N, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04395677 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-zager-ann-surg-oncol","kind":"paper","name":"Efficacy and Safety of the Melphalan/Hepatic Delivery System in Patients with Unresectable Metastatic Uveal Melanoma: Results from an Open-Label, Single-Arm, Multicenter Phase 3 Study","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 38704501 and published in Annals of surgical oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background: Uveal melanoma (UM) has a poor prognosis once liver metastases occur. The melphalan/Hepatic Delivery System (melphalan/HDS) is a drug/device combination used for liver-directed treatment of metastatic UM (mUM) patients. The purpose of the FOCUS study was to assess the efficacy and safety of melphalan/HDS in patients with unresectable mUM.\n\nMethods: Eligible patients with mUM received treatment with melphalan (3.0 mg/kg ideal body weight) once every 6 to 8 weeks for a maximum of six cycles. The primary end point was the objective response rate (ORR). The secondary end points included duration of response (DOR), overall survival (OS), and progression-free survival (PFS).\n\nResults: The study enrolled 102 patients with mUM. Treatment was attempted in 95 patients, and 91 patients received treatment. In the treated population (n = 91), the ORR was 36.3 % (95 % confidence interval [CI], 26.44-47.01), including 7.7 % of patients with a complete response. Thus, the study met its primary end point because the lower bound of the 95 % CI for ORR exceeded the upper bound (8.3 %) from the benchmark meta-analysis. The median DOR was 14 months, and the median OS was 20.5 months, with an OS of 80 % at 1 year. The median PFS was 9 months, with a PFS of 65 % at 6 months. The most common serious treatment-emergent adverse events were thrombocytopenia (15.8 %) and neutropenia (10.5 %), treated mostly on an outpatient basis with observation. No treatment-related deaths were observed.\n\nConclusion: Treatment with melphalan/HDS provides a clinically meaningful response rate and demonstrates a favorable benefit-risk profile in patients with unresectable mUM (study funded by Delcath; ClinicalTrials.gov identifier: NCT02678572; EudraCT no. 2015-000417-44).\n\nIndexed on Europe PMC as PubMed record 38704501 (DOI 10.1245/s10434-024-15293-x). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Ann Surg Oncol 2024","url":"https://doi.org/10.1245/s10434-024-15293-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38704501/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38704501"}],"tags":["europepmc-ingest"],"related":["percutaneous-hepatic-perfusion"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-surgical-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of surgical oncology","year":2024,"doi":"10.1245/s10434-024-15293-x","pmid":"38704501","authors":"Zager JS, Orloff M, Ferrucci PF, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-oh-destiny-pantumor02-biliary-pancreatic-esmo-open-2026","kind":"paper","name":"Efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing biliary tract or pancreatic tumors: a subgroup analysis of DESTINY-PanTumor02","aka":[],"tldr":"In the tumour-agnostic trial that led to the HER2 IHC 3+ approval, trastuzumab deruxtecan shrank about a quarter of 41 pretreated biliary cancers overall and more than half of those with the strongest HER2 stain, while pancreatic tumours barely responded.","summary":"DESTINY-PanTumor02 (NCT04482309) Part 1 evaluated trastuzumab deruxtecan 5.4 mg/kg in locally advanced or metastatic HER2 IHC 3+ or 2+ tumours (local or central testing) that had progressed after systemic treatment or had no treatment options. The primary endpoint was investigator-assessed objective response rate; this report covers the biliary tract (41 patients) and pancreatic (25 patients) cohorts, with median follow-up of 6.0 and 5.0 months.\n\nBy investigator, objective response rate was 22.0% (95% CI 10.6 to 37.6) in biliary tract cancer and 4.0% (0.1 to 20.4) in pancreatic cancer; by independent central review 26.8% and 12.0%. Responses were seen across most biliary subgroups, with the highest rate, 56.3% (95% CI 29.9 to 80.2), in centrally confirmed HER2 IHC 3+ tumours. Stable disease was the best response in 61.0% of the biliary cohort; median overall survival was 7.0 months (95% CI 4.6 to 10.2). Adjudicated drug-related interstitial lung disease or pneumonitis occurred in 17.1% of biliary patients and 4.0% of pancreatic patients.","asOf":"2026-09-24","links":[{"label":"Oh et al., ESMO Open 2026: trastuzumab deruxtecan in the biliary and pancreatic cohorts of DESTINY-PanTumor02","url":"https://doi.org/10.1016/j.esmoop.2026.108344"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42531802/"},{"label":"ClinicalTrials.gov NCT04482309","url":"https://clinicaltrials.gov/study/NCT04482309"}],"tags":[],"related":[],"cancers":["gallbladder","biliary-tract-cancer","cholangiocarcinoma","pancreatic"],"sections":[],"technologies":[],"targets":["her2"],"drugs":["trastuzumab-deruxtecan"],"companies":["astrazeneca","daiichi-sankyo"],"institutions":[],"pathways":[],"terms":[],"trials":["destiny-pantumor02"],"people":["oh-do-youn"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"ESMO Open","year":2026,"doi":"10.1016/j.esmoop.2026.108344","pmid":"42531802","authors":"Oh DY, Lugowska I, Stroyakovskiy D, et al.","paperType":"observational","findings":["Biliary cohort (n = 41): objective response rate 22.0% by investigator, 26.8% by central review; 56.3% in centrally confirmed IHC 3+ tumours.","Pancreatic cohort (n = 25): 4.0% by investigator.","Interstitial lung disease or pneumonitis in 17.1% of biliary patients; median overall survival 7.0 months."],"whatItMeans":"The IHC 3+ subgroup result is why the tumour-agnostic label is written at 3+ and not 2+, and why a gallbladder cancer with a strong HER2 stain now has two on-label choices (zanidatamab, trastuzumab deruxtecan) after chemotherapy. Lung toxicity again ran higher than in breast cancer.","caveats":["Subgroup of a single-arm basket study; local and central HER2 testing were both allowed.","Short follow-up and small IHC 3+ subgroup (16 patients)."],"changedPractice":false,"participants":66},{"id":"paper-oba-cancer-immunol-immunother","kind":"paper","name":"Efficacy of adjuvant immunochemotherapy with polysaccharide K for patients with curative resections of gastric cancer","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 17106715 and published in Cancer immunology, immunotherapy; the citing page links this DOI, which is how the record was matched.","summary":"Non-specific immunopotentiators, such as polysaccharide K (PSK), also known as OK-432, induce anti-tumor effects via immunological responses. The efficacy of combination immunochemotherapy using these immunopotentiators has been examined by multiple previous studies. The survival benefits of immunochemotherapy for patients with curative resections of gastric cancers are not widely accepted. To clarify this issue, we performed a meta-analysis to evaluate the effect of immunochemotherapy on survival in patients with curative resections of gastric cancer. For this study, we compared the results of chemotherapy and immunotherapy using the biological response modifier PSK as an immunopotentiator. The meta-analysis included 8,009 patients from eight randomized controlled trials after central randomization. The overall hazard ratio for eligible patients was 0.88 (95% confidence interval, 0.79-0.98; P = 0.018) with no significant heterogeneity [chi (2)(8) for heterogeneity = 11.7; P = 0.16]. The results of this meta-analysis suggest that adjuvant immunochemotherapy with PSK improves the survival of patients after curative gastric cancer resection.\n\nIndexed on Europe PMC as PubMed record 17106715 (DOI 10.1007/s00262-006-0248-1). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer Immunol Immunother 2007","url":"https://doi.org/10.1007/s00262-006-0248-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/17106715/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/17106715"}],"tags":["europepmc-ingest"],"related":["psk-krestin-adjuvant"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-immunology-immunotherapy"],"dependsOn":[],"notes":[],"journal":"Cancer immunology, immunotherapy","year":2007,"doi":"10.1007/s00262-006-0248-1","pmid":"17106715","authors":"Oba K, Teramukai S, Kobayashi M, et al.","paperType":"meta-analysis","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-sakamoto-cancer-immunol-immunother","kind":"paper","name":"Efficacy of adjuvant immunochemotherapy with polysaccharide K for patients with curatively resected colorectal cancer: a meta-analysis of centrally randomized controlled clinical trials","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 16133112 and published in Cancer immunology, immunotherapy; the citing page links this DOI, which is how the record was matched.","summary":"The benefits of immunochemotherapy employing the biological response modifier polysaccharide K (PSK) for patients with curatively resected colorectal cancer was reassessed by means of a meta-analysis of data with center randomization from 1,094 patients enrolled in three clinical trials. In all three trials, patients were followed up for at least 5 years after surgery and enrollment of the last patient and outcomes for standard chemotherapy were compared with those for chemotherapy plus PSK. The endpoints were overall survival and disease-free survival; and intent-to-treat analysis was performed without patient exclusion. Data were analyzed using the weighted average of the individual log hazard ratios. The overall survival risk ratio for all eligible patients was 0.71 (95% confidence interval (CI): 0.55-0.90; P=0.006), and the disease-free survival risk ratio was 0.72 (95% CI: 0.58-0.90; P=0.003). The results of this meta-analysis suggest that adjuvant immunochemotherapy with PSK can improve both survival and disease-free survival of patients with curatively resected colorectal cancer.\n\nIndexed on Europe PMC as PubMed record 16133112 (DOI 10.1007/s00262-005-0054-1). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer Immunol Immunother 2006","url":"https://doi.org/10.1007/s00262-005-0054-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/16133112/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/16133112"}],"tags":["europepmc-ingest"],"related":["psk-krestin-adjuvant"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-immunology-immunotherapy"],"dependsOn":[],"notes":[],"journal":"Cancer immunology, immunotherapy","year":2006,"doi":"10.1007/s00262-005-0054-1","pmid":"16133112","authors":"Sakamoto J, Morita S, Oba K, et al.","paperType":"meta-analysis","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-patricia-paavonen-lancet-2009","kind":"paper","name":"Efficacy of HPV-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis","aka":[],"tldr":"In young women free of the two target virus types at vaccination, the bivalent vaccine prevented 93 percent of high-grade cervical precancers caused by those types, and it also protected against some related virus types it was not designed for.","summary":"Final event-driven analysis of PATRICIA (NCT00122681). Women aged 15 to 25 were vaccinated at months 0, 1 and 6 with the HPV-16/18 AS04-adjuvanted vaccine or a hepatitis A control. Analyses were done in the according-to-protocol cohort for efficacy (vaccine 8,093, control 8,069), the total vaccinated cohort (9,319 and 9,325) and the TVC-naive cohort of women with no evidence of oncogenic HPV infection at baseline (5,822 and 5,819). The primary endpoint was efficacy against CIN2+ associated with HPV-16 or HPV-18 in women seronegative at baseline and DNA negative at baseline and month 6 for the corresponding type.\n\nMean follow-up was 34.9 months after the third dose. Vaccine efficacy against CIN2+ associated with HPV-16/18 was 92.9 percent (96.1 percent CI 79.9 to 98.3) in the primary analysis and 98.1 percent (88.4 to 100) with probable causality assigned in lesions with several oncogenic types. Efficacy against CIN2+ irrespective of HPV DNA in lesions was 30.4 percent in the total vaccinated cohort and 70.2 percent in the TVC-naive cohort; against CIN3+ it was 33.4 percent and 87.0 percent. Efficacy against CIN2+ associated with 12 non-vaccine oncogenic types was 54.0 percent, with individual cross-protection against HPV-31, HPV-33 and HPV-45.","asOf":"2026-09-24","links":[{"label":"Lancet 2009","url":"https://doi.org/10.1016/S0140-6736(09)61248-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19586656/"},{"label":"ClinicalTrials.gov NCT00122681","url":"https://clinicaltrials.gov/study/NCT00122681"}],"tags":[],"related":[],"cancers":["cervical"],"sections":["prevention"],"technologies":["hpv-vaccine"],"targets":[],"drugs":["hpv-bivalent-vaccine"],"companies":["gsk"],"institutions":[],"pathways":[],"terms":[],"trials":["patricia"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2009,"doi":"10.1016/S0140-6736(09)61248-4","pmid":"19586656","authors":"Paavonen J, Naud P, Salmerón J, et al.","paperType":"rct","findings":["Vaccine efficacy against CIN2+ associated with HPV-16/18: 92.9 percent (96.1 percent CI 79.9 to 98.3) in the primary analysis; 98.1 percent with HPV-type causality assigned.","Efficacy against CIN2+ irrespective of HPV type: 30.4 percent in the total vaccinated cohort and 70.2 percent in women HPV-naive at baseline; against CIN3+, 33.4 and 87.0 percent.","Cross-protection: 54.0 percent efficacy against CIN2+ associated with 12 non-vaccine oncogenic types, with individual protection against HPV-31, HPV-33 and HPV-45."],"whatItMeans":"This is the efficacy evidence behind the EU (2007) and US (2009) approvals of Cervarix. The gap between near-complete type-specific protection and the 30 percent overall effect in the whole cohort is the argument for vaccinating before sexual debut, where the effect was 70 percent.","caveats":["The 96.1 percent confidence level reflects the alpha spent at the interim analysis.","Efficacy against cervical cancer itself is inferred from precancer endpoints; cancer endpoints came later from registry linkage studies.","GSK withdrew Cervarix from the US market in 2016 for commercial reasons; it remains WHO-prequalified."],"changedPractice":true,"participants":18644},{"id":"paper-diamond-nature","kind":"paper","name":"Efficacy of MEK inhibition in patients with histiocytic neoplasms","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 30867592 and published in Nature; the citing page links this DOI, which is how the record was matched.","summary":"Histiocytic neoplasms are a heterogeneous group of clonal haematopoietic disorders that are marked by diverse mutations in the mitogen-activated protein kinase (MAPK) pathway 1,2. For the 50% of patients with histiocytosis who have BRAF V600 mutations 3-5, RAF inhibition is highly efficacious and has markedly altered the natural history of the disease 6,7. However, no standard therapy exists for the remaining 50% of patients who lack BRAF V600 mutations. Although ERK dependence has been hypothesized to be a consistent feature across histiocytic neoplasms, this remains clinically unproven and many of the kinase mutations that are found in patients who lack BRAF V600 mutations have not previously been biologically characterized. Here we show ERK dependency in histiocytoses through a proof-of-concept clinical trial of cobimetinib, an oral inhibitor of MEK1 and MEK2, in patients with histiocytoses. Patients were enrolled regardless of their tumour genotype. In parallel, MAPK alterations that were identified in treated patients were characterized for their ability to activate ERK. In the 18 patients that we treated, the overall response rate was 89% (90% confidence interval of 73-100). Responses were durable, with no acquired resistance to date. At one year, 100% of responses were ongoing and 94% of patients remained progression-free. Cobimetinib treatment was efficacious regardless of genotype, and responses were observed in patients with ARAF, BRAF, RAF1, NRAS, KRAS, MEK1 (also known as MAP2K1) and MEK2 (also known as MAP2K2) mutations. Consistent with the observed responses, the characterization of the mutations that we identified in these patients confirmed that the MAPK-pathway mutations were activating. Collectively, these data demonstrate that histiocytic neoplasms are characterized by a notable dependence on MAPK signalling-and that they are consequently responsive to MEK inhibition. These results extend the benefits of molecularly targeted therapy to the entire spectrum of patients with histiocytosis.\n\nIndexed on Europe PMC as PubMed record 30867592 (DOI 10.1038/s41586-019-1012-y). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2019","url":"https://doi.org/10.1038/s41586-019-1012-y"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30867592/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30867592"}],"tags":["europepmc-ingest"],"related":["erdheim-chester-disease"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2019,"doi":"10.1038/s41586-019-1012-y","pmid":"30867592","authors":"Diamond EL, Durham BH, Ulaner GA, et al.","paperType":"observational","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-barnabas-nejm-evid","kind":"paper","name":"Efficacy of single-dose HPV vaccination among young African women","aka":[],"tldr":"Paper cited by one roadmap page, indexed on Europe PMC as PubMed record 35693874 and published in NEJM Evidence; the citing page links this DOI, which is how the record was matched.","summary":"BACKGROUND: Single-dose human papillomavirus (HPV) vaccination, if efficacious, would be tremendously advantageous, simplifying implementation and decreasing costs. METHODS: We performed a randomized, multicenter, double-blind, controlled trial of single-dose nonavalent (HPV 16/18/31/33/45/52/58/6/11 infection) or bivalent (HPV 16/18 infection) HPV vaccination compared with meningococcal vaccination among Kenyan women 15 to 20 years of age. Enrollment and 6-monthly cervical swabs and a month 3 vaginal swab were tested for HPV deoxyribonucleic acid (DNA). Enrollment sera were tested for HPV antibodies. The modified intent-to-treat (mITT) cohort comprised participants who had an HPV antibody-negative result at enrollment and an HPV DNA-negative result at enrollment and month 3. The primary outcome was incident persistent vaccine-type HPV infection by month 18. RESULTS: Between December 2018 and June 2021, 2275 women were randomly assigned and followed. A total of 758 participants received the nonavalent HPV vaccine, 760 received the bivalent HPV vaccine, and 757 received the meningococcal vaccine; retention was 98%. Thirty-eight incident persistent infections were detected in the HPV 16/18 mITT cohort: one each among participants assigned to the bivalent and nonavalent groups and 36 among those assigned to the meningococcal group. Nonavalent vaccine efficacy (VE) was 97.5% (95% confidence interval [CI], 81.7 to 99.7%; P≤0.0001), and bivalent VE was 97.5% (95% CI, 81.6 to 99.7%; P≤0.0001). Thirty-three incident persistent infections were detected in the HPV 16/18/31/33/45/52/58 mITT cohort: four in the nonavalent group and 29 in the meningococcal group. Nonavalent VE for HPV 16/18/31/33/45/52/58 was 88.9% (95% CI, 68.5 to 96.1; P<0.0001). The rate of serious adverse events was 4.5% to 5.2% by group. CONCLUSIONS: Over the 18-month timeframe we studied, single-dose bivalent and nonavalent HPV vaccines were each highly effective in preventing incident persistent oncogenic HPV infection, similar to multidose regimens. (Funded by the National Institutes of Health, the Bill and Melinda Gates Foundation, and the University of Washington; ClinicalTrials.gov number, NCT03675256.)\n\nIndexed on Europe PMC as PubMed record 35693874 (DOI 10.1056/evidoa2100056). Matched by DOI alone: one roadmap page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"NEJM Evid 2022","url":"https://doi.org/10.1056/evidoa2100056"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35693874/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35693874"}],"tags":["europepmc-ingest"],"related":["prevention-roadmap"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm-evidence"],"dependsOn":[],"notes":[],"journal":"NEJM Evidence","year":2022,"doi":"10.1056/evidoa2100056","pmid":"35693874","authors":"Barnabas RV, Brown ER, Onono MA, et al.","paperType":"rct","findings":[],"whatItMeans":"One roadmap page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-quintana-nature","kind":"paper","name":"Efficient tumour formation by single human melanoma cells","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 19052619 and published in Nature; the citing page links this DOI, which is how the record was matched.","summary":"A fundamental question in cancer biology is whether cells with tumorigenic potential are common or rare within human cancers. Studies on diverse cancers, including melanoma, have indicated that only rare human cancer cells (0.1-0.0001%) form tumours when transplanted into non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. However, the extent to which NOD/SCID mice underestimate the frequency of tumorigenic human cancer cells has been uncertain. Here we show that modified xenotransplantation assay conditions, including the use of more highly immunocompromised NOD/SCID interleukin-2 receptor gamma chain null (Il2rg(-/-)) mice, can increase the detection of tumorigenic melanoma cells by several orders of magnitude. In limiting dilution assays, approximately 25% of unselected melanoma cells from 12 different patients, including cells from primary and metastatic melanomas obtained directly from patients, formed tumours under these more permissive conditions. In single-cell transplants, an average of 27% of unselected melanoma cells from four different patients formed tumours. Modifications to xenotransplantation assays can therefore dramatically increase the detectable frequency of tumorigenic cells, demonstrating that they are common in some human cancers.\n\nIndexed on Europe PMC as PubMed record 19052619 (DOI 10.1038/nature07567). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2008","url":"https://doi.org/10.1038/nature07567"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19052619/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/19052619"}],"tags":["europepmc-ingest"],"related":["cancer-stem-cell-theory"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2008,"doi":"10.1038/nature07567","pmid":"19052619","authors":"Quintana E, Shackleton M, Sabel MS, et al.","paperType":"basic","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-egfr-gastric-eur-j-cancer-2001","kind":"paper","name":"EGFR and cancer prognosis","aka":[],"tldr":"Review on EGFR in Gastric & gastro-oesophageal junction cancer, in European Journal of Cancer (2001), one of the most cited Europe PMC records with EGFR in its title.","summary":"Elevated levels of the epidermal growth factor receptor (EGFR), a growth-factor-receptor tyrosine kinase, and/or its cognate ligands have been identified as a common component of multiple cancer types and appear to promote solid tumour growth. This article examines the relationship between EGFR expression and cancer prognosis based on literature compiled on PubMed between 1985 and September 2000. More than 200 studies were identified that analysed relapse-free-interval or survival data directly in relation to EGFR levels in over 20000 patients. Analysis of the data showed that 10 cancer types both express elevated levels of EGFR relative to normal tissues and have been studied in sufficient depth to allow sound judgements to be made concerning the association between EGFR and patient outlook. The EGFR was found to act as a strong prognostic indicator in head and neck, ovarian, cervical, bladder and oesophageal cancers. In these cancers, increased EGFR expression was associated with reduced recurrence-free or overall survival rates in 70% (52/74) of studies. In gastric, breast, endometrial and colorectal cancers, the EGFR provided more modest prognostic information, correlating to poor survival rates in 52% (13/25) of studies, while in non-small cell lung cancer (NSCLC), EGFR expression only rarely (3/10 studies) related to patient outlook. However, it is likely that the true prognostic significance of the EGFR has been underestimated as the published studies only assessed total cellular EGFR levels, rather than the activated form of the receptor, and were not standardised with regard to patient populations or assay methods. Finally, it is important to stress that failure to detect a prognostic significance for EGFR in any one cancer type does not necessarily preclude patients from benefiting from anti-EGFR therapies.\n\nIndexed on Europe PMC as PubMed record 11597399 (DOI 10.1016/s0959-8049(01)00231-3). Its title names EGFR and its text names Gastric & gastro-oesophageal junction cancer; PubMed types it as a review (Review). It was matched automatically to the idea \"Attack extrachromosomal DNA, the engine of oncogene amplification\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Eur J Cancer 2001","url":"https://doi.org/10.1016/s0959-8049(01)00231-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/11597399/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/11597399"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["european-journal-of-cancer"],"dependsOn":[],"notes":[],"journal":"European Journal of Cancer","year":2001,"doi":"10.1016/s0959-8049(01)00231-3","pmid":"11597399","authors":"Nicholson RI, Gee JM, Harper ME","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for EGFR in Gastric & gastro-oesophageal junction cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by EGFR in the title and Gastric & gastro-oesophageal junction cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-kobayashi-egfr-t790m-gefitinib-resistance-nejm-2005","kind":"paper","name":"EGFR mutation and resistance of non-small-cell lung cancer to gefitinib","aka":[],"tldr":"One patient, two years in complete remission on gefitinib, then relapse. Sequencing the new biopsy found a second mutation in the same gene, at position 790, that stopped the drug binding.","summary":"Kobayashi, Boggon, Dayaram and colleagues at Beth Israel Deaconess and Dana-Farber reported a patient with EGFR-mutant, gefitinib-responsive advanced non-small-cell lung cancer who relapsed after two years of complete remission. The biopsy at relapse carried a second point mutation producing a threonine-to-methionine change at position 790 of EGFR, and structural modelling with biochemical studies showed this second mutation caused the resistance.\n\nA single case report that changed a field. T790M went on to account for roughly half of acquired resistance to first-generation EGFR inhibitors, and the drug built against it, osimertinib, is now the first-line standard. The chain from one re-biopsy to a global standard of care is the strongest argument in oncology for biopsying at progression.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2005","url":"https://doi.org/10.1056/NEJMoa044238"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/15728811/"},{"label":"Kobayashi et al., N Engl J Med 2005: EGFR T790M and resistance of non-small-cell lung cancer to gefitinib","url":"https://doi.org/10.1056/NEJMoa044238"}],"tags":["lung-evidence"],"related":["paper-lynch-egfr-activating-mutations-gefitinib-nejm-2004","paper-sequist-genotypic-histological-evolution-egfr-resistance-sci-transl-med-2011","paper-osimertinib-nsclc-n-engl-j-med-2017","egfr-t790m"],"cancers":["lung-cancer","nsclc","egfr-mutant-nsclc"],"sections":["targeted-therapy"],"technologies":["ngs","kinase-inhibitors"],"targets":["egfr"],"drugs":["gefitinib","osimertinib"],"companies":[],"institutions":["dana-farber"],"pathways":["rtk-activation","resistance-routes-map"],"terms":["resistance","driver-mutation","egfr-mutation-subtypes"],"trials":[],"people":["pasi-janne","matthew-meyerson"],"bottlenecks":["b-resistance","b-tumor-heterogeneity"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2005,"doi":"10.1056/NEJMoa044238","pmid":"15728811","authors":"Kobayashi S, Boggon TJ, Dayaram T, et al.","paperType":"translational","findings":["A second point mutation in EGFR, threonine to methionine at position 790, was present in the relapse biopsy of a patient who had a two-year complete remission on gefitinib.","Structural modelling and biochemical studies showed this second mutation led to gefitinib resistance.","A second EGFR mutation, T790M, appeared at relapse after two years of complete remission.","Structural and biochemical work showed the substitution blocks gefitinib binding.","The mutation was in the same gene as the sensitising one, on the same allele."],"whatItMeans":"Resistance to a targeted drug usually has a cause you can read off a sequence, which means it can be targeted in turn. Osimertinib exists because of this paper.","caveats":["A single patient; the frequency of T790M came from the case series that followed.","T790M is the commonest but not the only mechanism; MET amplification, small-cell transformation and others account for the rest.","Third-generation inhibitors select for their own resistance mutations, notably C797S, so the cycle continues.","A single patient.","It could not say how often T790M causes resistance, which took the later rebiopsy series.","Pre-existing low-level T790M was not measurable with the methods of the time."],"changedPractice":true,"participants":1},{"id":"paper-paez-egfr-mutations-gefitinib-science-2004","kind":"paper","name":"EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy","aka":[],"tldr":"The second of the two 2004 papers that found EGFR mutations. It also explained why Japanese patients responded to gefitinib far more often than American ones: the mutation was simply much more common in Japan.","summary":"Paez, Jänne, Lee and colleagues at the Dana-Farber Cancer Institute and the Broad Institute, with Meyerson as senior author, sequenced receptor tyrosine kinase genes in non-small-cell lung cancer and matched normal tissue, then looked for the same mutations in responders to gefitinib and in a hypersensitive cell line.\n\nThe geographic difference it documented is the paper's second contribution. A response rate that varied by country had been read as a difference in practice or reporting; it turned out to be a difference in the prevalence of a mutation, which is the first demonstration in lung cancer that tumour genotype, not population, explains a drug's performance.","asOf":"2026-09-25","links":[{"label":"Science 2004","url":"https://doi.org/10.1126/science.1099314"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/15118125/"}],"tags":["lung-evidence"],"related":["paper-lynch-egfr-activating-mutations-gefitinib-nejm-2004","paper-mok-ipass-gefitinib-pulmonary-adenocarcinoma-nejm-2009","targeted-therapy-roadmap"],"cancers":["lung-cancer","nsclc","egfr-mutant-nsclc","lung-adenocarcinoma"],"sections":["targeted-therapy","diagnostics"],"technologies":["ngs"],"targets":["egfr"],"drugs":["gefitinib"],"companies":[],"institutions":["dana-farber","broad-institute"],"pathways":["ras-mapk"],"terms":["driver-mutation","oncogene-addiction"],"trials":[],"people":["pasi-janne","matthew-meyerson"],"bottlenecks":["b-biomarker-validation","b-trial-diversity"],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2004,"doi":"10.1126/science.1099314","pmid":"15118125","authors":"Paez JG, Jänne PA, Lee JC, et al.","paperType":"translational","findings":["Somatic EGFR mutations were found in 15 of 58 unselected tumours from Japan and in 1 of 61 from the United States.","EGFR mutations were found in additional samples from United States patients who responded to gefitinib, and in a lung adenocarcinoma cell line hypersensitive to gefitinib.","No EGFR mutations were found in gefitinib-insensitive tumours or cell lines."],"whatItMeans":"Why a drug can look useless in one trial and transformative in another: the trials had different proportions of the patients the drug was for. It is the argument for genotyping before drawing conclusions from a response rate.","caveats":["Small, unbalanced cohorts (58 Japanese and 61 United States tumours) and a retrospective response comparison.","Sequencing of selected receptor tyrosine kinase genes, not the genome; other drivers in the same tumours were not looked for.","Prevalence estimates from tumour series of that era are not population estimates."],"changedPractice":true},{"id":"paper-marcoux-egfr-small-cell-transformation-outcomes-jco-2019","kind":"paper","name":"EGFR-mutant adenocarcinomas that transform to small-cell lung cancer and other neuroendocrine carcinomas: clinical outcomes","aka":[],"tldr":"Sixty-seven patients whose lung cancer changed into small-cell carcinoma were followed across eight hospitals. The change came about a year and a half after diagnosis, chemotherapy worked well and immunotherapy did not work at all.","summary":"Patients with EGFR-mutant small-cell lung cancer and other high-grade neuroendocrine carcinomas were identified retrospectively at eight institutions. Sixty-seven patients were included, with exon 19 deletion in 69%, L858R in 25% and other mutations in 6%. At initial diagnosis 58 had non-small-cell lung cancer and nine had small-cell or mixed histology; all but those nine received one or more EGFR inhibitors before transformation. Median time to transformation was 17.8 months. After transformation, platinum and etoposide and taxanes yielded high response rates, but none of 17 patients who received immunotherapy responded. Median overall survival since diagnosis was 31.5 months and since transformation 10.9 months. Of 59 patients genotyped at transformation, all maintained their founder EGFR mutation and 15 of 19 previously T790M-positive cases were T790 wild-type. Other recurrent mutations included TP53, RB1 and PIK3CA, and central nervous system metastases were frequent after transformation.","asOf":"2026-09-25","links":[{"label":"Marcoux et al., J Clin Oncol 2019: clinical outcomes of 67 EGFR-mutant adenocarcinomas that transformed to small-cell carcinoma","url":"https://doi.org/10.1200/JCO.18.01585"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30550363/"}],"tags":[],"related":["egfr-t790m","egfr-exon-19-deletion","egfr-l858r"],"cancers":["nsclc","sclc"],"sections":[],"technologies":["checkpoint-inhibitor","cgp"],"targets":["egfr","rb1","tp53","pik3ca"],"drugs":[],"companies":[],"institutions":["mgh","yale-cancer-center","mskcc"],"pathways":["lineage-plasticity-neuroendocrine","resistance-routes-map"],"terms":["histologic-transformation","resistance","brain-metastases"],"trials":[],"people":["lecia-sequist"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2019,"doi":"10.1200/JCO.18.01585","pmid":"30550363","authors":"Marcoux N, Gettinger SN, O'Kane G, et al.","paperType":"observational","findings":["Median time from diagnosis to transformation 17.8 months; median survival after transformation 10.9 months.","Platinum and etoposide and taxanes produced high response rates.","No responses to immunotherapy in 17 treated patients.","All transformed tumours kept the founder EGFR mutation and most had lost T790M."],"whatItMeans":"It is the practical guide to what to do after transformation: treat it as small-cell lung cancer with platinum and etoposide, expect central nervous system disease, and do not expect a checkpoint inhibitor to help.","caveats":["Retrospective across eight institutions with varying practice.","Sixty-seven patients, and transformation is diagnosed only where rebiopsy was performed.","Treatment was not randomised."],"changedPractice":false,"participants":67},{"id":"paper-dewey-cochrane-database-syst-rev","kind":"paper","name":"Eicosapentaenoic acid (EPA, an omega-3 fatty acid from fish oils) for the treatment of cancer cachexia","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 17253515 and published in The Cochrane database of systematic reviews; the citing page links this DOI, which is how the record was matched.","summary":"Background: Cancer cachexia is a distressing weight loss syndrome commonly seen in advanced cancer patients. It is associated with reduced quality of life and shorter survival time. Eicosapentaenoic acid (EPA) is a long chain polyunsaturated fatty acid found naturally in some fish which has been used to decrease weight loss, promote weight gain and increase survival times in patients affected with cancer cachexia.\n\nObjectives: To evaluate the effectiveness and safety of EPA in relieving symptoms associated with the cachexia syndrome in patients with advanced cancer.\n\nSearch strategy: Studies were sought through an extensive search of a range of electronic databases. Hand searching was conducted on selected journals and reference lists as well as contact made with investigators, manufacturers and experts. The most recent electronic search was conducted in February 2005.\n\nSelection criteria: Studies were included in the review if they assessed oral EPA compared with placebo or control in randomised controlled trials of patients with advanced cancer and either a clinical diagnosis of cachexia or self-reported weight loss of 5% or more.\n\nData collection and analysis: Both methodological quality evaluation of potential trials and data extraction were conducted by two independent review authors.\n\nMain results: Five trials (involving 587 patients) met the inclusion criteria. Three trials compared EPA at different doses with placebo with two outcomes, nutritional status and adverse events comparable across two of the three included trials. In addition, two trials compared different doses of EPA with an active matched control. It was possible to compare the outcomes of weight, quality of life and adverse events across these two trials. There were insufficient data to define the optimal dose of EPA.\n\nAuthors' conclusions: There were insufficient data to establish whether oral EPA was better than placebo. Comparisons of EPA combined with a protein energy supplementation versus a protein energy supplementation (without EPA) in the presence of an appetite stimulant (Megestrol Acetate) provided no evidence that EPA improves symptoms associated with the cachexia syndrome often seen in patients with advanced cancer.\n\nIndexed on Europe PMC as PubMed record 17253515 (DOI 10.1002/14651858.cd004597.pub2). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cochrane Database Syst Rev 2007","url":"https://doi.org/10.1002/14651858.cd004597.pub2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/17253515/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/17253515"}],"tags":["europepmc-ingest"],"related":["omega3-epa-cachexia"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Cochrane database of systematic reviews","year":2007,"doi":"10.1002/14651858.cd004597.pub2","pmid":"17253515","authors":"Dewey A, Baughan C, Dean T, et al.","paperType":"meta-analysis","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-el-deiry-waf1-p21-cell-1993","kind":"paper","name":"El-Deiry 1993: WAF1, the gene through which p53 stops cell division","aka":[],"tldr":"The discovery of p21, the gene p53 switches on to halt cell division, which explained for the first time how the most commonly mutated cancer gene actually stops damaged cells from growing.","summary":"El-Deiry, Vogelstein and colleagues searched for genes activated by wild-type p53 and identified WAF1, now called CDKN1A or p21, whose expression was induced by wild-type but not mutant p53 in human cells. Introducing WAF1 into cancer cell lines suppressed their growth. Independently identified at the same time as an inhibitor of cyclin-dependent kinases, p21 turned out to be the link between p53 activation and arrest of the cell cycle at the G1 checkpoint.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1016/0092-8674(93)90500-P"}],"tags":[],"related":["paper-levine-p53-gatekeeper-cell-1997"],"cancers":[],"sections":[],"technologies":[],"targets":["tp53","cdk4-6"],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":["p53-cell-cycle","cell-cycle-engine-cdks"],"terms":["cell-cycle","tumour-suppressor-gene"],"trials":[],"people":["bert-vogelstein"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Cell","year":1993,"doi":"10.1016/0092-8674(93)90500-P","authors":"El-Deiry WS, Tokino T, Velculescu VE, et al.","paperType":"basic","findings":["WAF1 (p21, CDKN1A) was identified as a gene induced by wild-type p53 and not by tumour-derived mutant p53.","Expression of WAF1 suppressed the growth of human tumour cell lines.","p21 was shown by parallel work to inhibit cyclin-dependent kinases, providing the mechanism for p53-mediated cell cycle arrest."],"whatItMeans":"This paper closed the loop between DNA damage, p53 and the cell cycle machinery. p21 is now a standard marker of p53 activity, part of how chemotherapy and radiotherapy stop cells dividing, and a component of the senescence response that CDK4/6 inhibitors exploit.","caveats":["Cell line study; the in vivo roles of p21 in tumour suppression proved more complex.","p21 is also induced by p53-independent signals."],"changedPractice":false},{"id":"paper-dcruz-elective-neck-dissection-nejm-2015","kind":"paper","name":"Elective versus therapeutic neck dissection in node-negative oral cancer","aka":[],"tldr":"Removing the neck lymph nodes at the first operation for early mouth cancer, rather than waiting to see if they become involved, raised three-year survival from 67.5% to 80%.","summary":"Randomised trial at Tata Memorial Hospital of 596 patients with early (T1-T2) node-negative oral squamous cell cancer, 500 analysed (245 elective, 255 therapeutic neck dissection), median follow-up 39 months. Elective dissection gave 81 recurrences and 50 deaths versus 146 and 79; 3-year overall survival 80.0% versus 67.5% (hazard ratio 0.64; 95% CI 0.45-0.92; P=0.01) and disease-free survival 69.5% versus 45.9% (P<0.001); adverse events 6.6% versus 3.6%.","asOf":"2026-09-10","links":[{"label":"NEJM 2015","url":"https://doi.org/10.1056/NEJMoa1506007"}],"tags":[],"related":[],"cancers":["head-and-neck"],"sections":[],"technologies":["sentinel-node"],"targets":[],"drugs":[],"companies":[],"institutions":["tata-memorial"],"pathways":[],"terms":[],"trials":["elective-neck-dissection-tmh"],"people":["dcruz-anil"],"bottlenecks":["b-surgery-radiation-innovation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2015,"doi":"10.1056/NEJMoa1506007","authors":"D'Cruz AK, Vaish R, Kapre N, et al.","paperType":"rct","findings":["3-year overall survival 80.0% with elective neck dissection versus 67.5% with watchful waiting (HR 0.64).","3-year disease-free survival 69.5% versus 45.9%.","Recurrences 81 versus 146; deaths 50 versus 79.","Adverse events were higher with elective dissection (6.6% versus 3.6%) but modest."],"whatItMeans":"Elective neck dissection is now the standard for early oral cancer everywhere. The trial shows what high-volume Indian centres can contribute: a definitive answer to a surgical question that had been debated for half a century and that Western centres, with far fewer oral cancers, could not resolve.","caveats":["Ultrasound and clinical staging of the neck were used; modern imaging or sentinel node biopsy may change the trade-off.","Single-centre trial in a predominantly tobacco-related oral cancer population.","Quality of life and morbidity outcomes were secondary."],"changedPractice":true,"participants":596},{"id":"paper-venkatesh-nature","kind":"paper","name":"Electrical and synaptic integration of glioma into neural circuits","aka":[],"tldr":"Paper cited by one pathway page and one term page, indexed on Europe PMC as PubMed record 31534222 and published in Nature; the citing pages link this DOI, which is how the record was matched.","summary":"High-grade gliomas are lethal brain cancers whose progression is robustly regulated by neuronal activity. Activity-regulated release of growth factors promotes glioma growth, but this alone is insufficient to explain the effect that neuronal activity exerts on glioma progression. Here we show that neuron and glioma interactions include electrochemical communication through bona fide AMPA receptor-dependent neuron-glioma synapses. Neuronal activity also evokes non-synaptic activity-dependent potassium currents that are amplified by gap junction-mediated tumour interconnections, forming an electrically coupled network. Depolarization of glioma membranes assessed by in vivo optogenetics promotes proliferation, whereas pharmacologically or genetically blocking electrochemical signalling inhibits the growth of glioma xenografts and extends mouse survival. Emphasizing the positive feedback mechanisms by which gliomas increase neuronal excitability and thus activity-regulated glioma growth, human intraoperative electrocorticography demonstrates increased cortical excitability in the glioma-infiltrated brain. Together, these findings indicate that synaptic and electrical integration into neural circuits promotes glioma progression.\n\nIndexed on Europe PMC as PubMed record 31534222 (DOI 10.1038/s41586-019-1563-y). Matched by DOI alone: one pathway page and one term page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2019","url":"https://doi.org/10.1038/s41586-019-1563-y"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31534222/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31534222"}],"tags":["europepmc-ingest"],"related":["cancer-neuroscience","bioelectric-theory-of-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2019,"doi":"10.1038/s41586-019-1563-y","pmid":"31534222","authors":"Venkatesh HS, Morishita W, Geraghty AC, et al.","paperType":"basic","findings":[],"whatItMeans":"One pathway page and one term page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-mao-j-clin-oncol-2015","kind":"paper","name":"Electroacupuncture Versus Gabapentin for Hot Flashes Among Breast Cancer Survivors: A Randomized Placebo-Controlled Trial","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 26304905 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: Hot flashes are a common and debilitating symptom among survivors of breast cancer. This study aimed at evaluating the effects of electroacupuncture (EA) versus gabapentin (GP) for hot flashes among survivors of breast cancer, with a specific focus on the placebo and nocebo effects.\n\nPatients and methods: We conducted a randomized controlled trial involving 120 survivors of breast cancer experiencing bothersome hot flashes twice per day or greater. Participants were randomly assigned to receive 8 weeks of EA or GP once per day with validated placebo controls (sham acupuncture [SA] or placebo pills [PPs]). The primary end point was change in the hot flash composite score (HFCS) between SA and PP at week 8, with secondary end points including group comparisons and additional evaluation at week 24 for durability of treatment effects.\n\nResults: By week 8, SA produced significantly greater reduction in HFCS than did PP (-2.39; 95% CI, -4.60 to -0.17). Among all treatment groups, the mean reduction in HFCS was greatest in the EA group, followed by SA, GP, and PP (-7.4 v -5.9 v -5.2 v -3.4; P = <.001). The pill groups had more treatment-related adverse events than did the acupuncture groups: GP (39.3%), PP (20.0%), EA (16.7%), and SA (3.1%), with P =.005. By week 24, HFCS reduction was greatest in the EA group, followed by SA, PP, and GP (-8.5 v -6.1 v -4.6 v -2.8; P =.002).\n\nConclusion: Acupuncture produced larger placebo and smaller nocebo effects than did pills for the treatment of hot flashes. EA may be more effective than GP, with fewer adverse effects for managing hot flashes among breast cancer survivors; however, these preliminary findings need to be confirmed in larger randomized controlled trials with long-term follow-up.\n\nIndexed on Europe PMC as PubMed record 26304905 (DOI 10.1200/jco.2015.60.9412). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2015","url":"https://doi.org/10.1200/jco.2015.60.9412"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26304905/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26304905"}],"tags":["europepmc-ingest"],"related":["acupuncture-hot-flushes"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2015,"doi":"10.1200/jco.2015.60.9412","pmid":"26304905","authors":"Mao JJ, Bowman MA, Xie SX, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-clover-eur-j-cancer","kind":"paper","name":"Electrochemotherapy in the treatment of cutaneous malignancy: Outcomes and subgroup analysis from the cumulative results from the pan-European International Network for Sharing Practice in Electrochemotherapy database for 2482 lesions in 987 patients (2008-2019)","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 32836172 and published in European Journal of Cancer; the citing page links this DOI, which is how the record was matched.","summary":"Background: Electrochemotherapy (ECT) is a treatment for both primary and secondary cutaneous tumours. The international Network for sharing practices on ECT group investigates treatment outcomes after ECT using a common database with defined parameters.\n\nMethods: Twenty-eight centres across Europe prospectively uploaded data over an 11-year period. Response rates were investigated in relation to primary diagnosis, tumour size, choice of electrode type, route of bleomycin administration, electrical parameters recorded and previous irradiation in the treated field.\n\nResults: Nine hundred eighty-seven patients, with 2482 tumour lesions were included in analysis. The overall response (OR) rate was 85% (complete response [CR]: 70%, partial response rate: 15%, stable disease: 11%, and progressive disease: 2%). For different histologies, OR and CR rates for metastases of malignant melanoma were 82% and 64%, basal cell carcinoma were 96% and 85%, breast cancer metastases were 77% and 62%, squamous cell carcinoma were 80% and 63% as well as Kaposi's sarcoma were 98% and 91%, respectively. Variance was demonstrated across histotypes (p < 0.0001) and in accordance with size of lesion treated (dichotomised at diameter of 3 cm (p < 0.0001). Hexagonal electrodes were generally used for larger tumours, but for tumours up to 3 cm, linear array electrodes provided better tumour control than hexagonal electrodes (80%:74%, p < 0.003). For tumours more than 2 cm, intravenous administration was superior to intratumoural (IT) administration (p < 0.05). Current recorded varied across tumour histologies and size but did not influence response rate. In previously irradiated areas, responses were selectively lower for IT administration.\n\nConclusions: These cumulative data endorse efficiency of ECT across a broad range of histotypes. Analysis of 2482 lesions details subgroup analysis on treatment response informing future treatment choices.\n\nIndexed on Europe PMC as PubMed record 32836172 (DOI 10.1016/j.ejca.2020.06.020). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Eur J Cancer 2020","url":"https://doi.org/10.1016/j.ejca.2020.06.020"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32836172/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32836172"}],"tags":["europepmc-ingest"],"related":["electrochemotherapy"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["european-journal-of-cancer"],"dependsOn":[],"notes":[],"journal":"European Journal of Cancer","year":2020,"doi":"10.1016/j.ejca.2020.06.020","pmid":"32836172","authors":"Clover AJP, de Terlizzi F, Bertino G, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-chen-nature","kind":"paper","name":"Elements of cancer immunity and the cancer-immune set point","aka":[],"tldr":"Paper cited by two pathway pages and one bottleneck page, indexed on Europe PMC as PubMed record 28102259 and published in Nature; the citing pages link this DOI, which is how the record was matched.","summary":"Immunotherapy is proving to be an effective therapeutic approach in a variety of cancers. But despite the clinical success of antibodies against the immune regulators CTLA4 and PD-L1/PD-1, only a subset of people exhibit durable responses, suggesting that a broader view of cancer immunity is required. Immunity is influenced by a complex set of tumour, host and environmental factors that govern the strength and timing of the anticancer response. Clinical studies are beginning to define these factors as immune profiles that can predict responses to immunotherapy. In the context of the cancer-immunity cycle, such factors combine to represent the inherent immunological status - or 'cancer-immune set point' - of an individual.\n\nIndexed on Europe PMC as PubMed record 28102259 (DOI 10.1038/nature21349). Matched by DOI alone: two pathway pages and one bottleneck page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2017","url":"https://doi.org/10.1038/nature21349"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28102259/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28102259"}],"tags":["europepmc-ingest"],"related":["immune-desert-exclusion","cancer-immunity-cycle","b-tme-immunosuppression"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2017,"doi":"10.1038/nature21349","pmid":"28102259","authors":"Chen DS, Mellman I","paperType":"review","findings":[],"whatItMeans":"Two pathway pages and one bottleneck page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-elevate-tn-acalabrutinib-lancet-2020","kind":"paper","name":"ELEVATE-TN: acalabrutinib, alone or with obinutuzumab, against chemo-immunotherapy in untreated CLL","aka":[],"tldr":"In ELEVATE-TN, acalabrutinib, a second-generation BTK inhibitor, with or without an antibody, cut the risk of progression by 80-90% compared with chlorambucil-obinutuzumab in older or unfit patients with CLL.","summary":"ELEVATE-TN was a three-arm phase 3 trial of 535 treatment-naive patients aged 65 or older, or younger with comorbidities. Patients were randomised to acalabrutinib plus obinutuzumab, acalabrutinib monotherapy, or chlorambucil plus obinutuzumab; the primary endpoint was PFS for the combination versus chemo-immunotherapy. At a median follow-up of 28.3 months median PFS was not reached in either acalabrutinib arm versus 22.6 months with chemo-immunotherapy, with hazard ratios of 0.10 for the combination and 0.20 for monotherapy. Acalabrutinib caused less atrial fibrillation and bleeding than reported with ibrutinib, and the trial supported its front-line approval.","asOf":"2026-09-08","links":[{"label":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=ELEVATE-TN%20acalabrutinib%20obinutuzumab%20chlorambucil%20Sharman%20Lancet%202020"},{"label":"ClinicalTrials.gov NCT02475681","url":"https://clinicaltrials.gov/study/NCT02475681"}],"tags":[],"related":[],"cancers":["cll"],"sections":[],"technologies":[],"targets":["btk","cd20"],"drugs":["acalabrutinib","obinutuzumab","ibrutinib","zanubrutinib"],"companies":["astrazeneca"],"institutions":[],"pathways":[],"terms":["pfs"],"trials":["elevate-tn","sequoia"],"people":[],"bottlenecks":["b-toxicity-qol","b-drug-pricing"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2020,"doi":"10.1016/S0140-6736(20)30262-2","pmid":"32305093","authors":"Sharman JP, Egyed M, Jurczak W, et al.","paperType":"rct","findings":["535 patients; acalabrutinib + obinutuzumab (179), acalabrutinib (179), chlorambucil + obinutuzumab (177).","Median PFS not reached in both acalabrutinib arms vs 22.6 months; hazard ratio 0.10 (combination) and 0.20 (monotherapy).","Estimated 24-month PFS about 93% (combination), 87% (monotherapy) and 47% (chemo-immunotherapy).","Headache and diarrhoea were the commonest acalabrutinib adverse events; atrial fibrillation was uncommon.","Adding obinutuzumab to acalabrutinib improved PFS further in longer follow-up but was not the primary comparison."],"whatItMeans":"ELEVATE-TN put a more selective BTK inhibitor into first-line CLL and, with the head-to-head ELEVATE-RR trial, showed it is as effective as ibrutinib with fewer cardiac side effects. Continuous acalabrutinib became one of the two main front-line options alongside fixed-duration venetoclax combinations. The trade-off is indefinite therapy and cost versus a time-limited course.","caveats":["The comparator, chlorambucil-obinutuzumab, was already being superseded when the trial reported.","Continuous therapy until progression; no MRD-guided stopping.","Cross-trial comparisons with venetoclax regimens are indirect.","Overall survival was not significantly different at early follow-up."],"changedPractice":true,"participants":535},{"id":"paper-eliana-tisagenlecleucel-nejm-2018","kind":"paper","name":"ELIANA: the global trial that made tisagenlecleucel the first approved CAR-T therapy for children and young adults with relapsed ALL","aka":[],"tldr":"Across 25 centres, 81% of children and young adults with relapsed or refractory ALL went into remission after a single tisagenlecleucel infusion, and half were still event-free a year later.","summary":"ELIANA was a single-arm, multicentre phase 2 trial of tisagenlecleucel in patients aged 3-21 with CD19-positive relapsed or refractory B-cell ALL. Of 92 enrolled, 75 received an infusion; the rest could not because of manufacturing failure, death or adverse events. The overall remission rate within three months was 81%, all MRD-negative; event-free survival was 73% at six months and 50% at 12 months, with overall survival 90% and 76%. Cytokine release syndrome occurred in 77% (grade 3-4 in about 46%) and neurological events in 40%. The trial supported FDA approval in August 2017, the first gene therapy and first CAR-T approved in the United States, and demonstrated that a centrally manufactured autologous cell product could be delivered across continents.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa1709866"},{"label":"ClinicalTrials.gov NCT02435849","url":"https://clinicaltrials.gov/study/NCT02435849"}],"tags":[],"related":["paper-maude-ctl019-all-nejm-2014","apheresis-starting-material"],"cancers":["all-leukemia","all-paediatric-relapsed"],"sections":[],"technologies":["car-t"],"targets":["cd19"],"drugs":["tisagenlecleucel","obecabtagene-autoleucel"],"companies":["novartis"],"institutions":["penn-abramson"],"pathways":[],"terms":["crs","icans","efs"],"trials":["eliana"],"people":["carl-june","bruce-levine"],"bottlenecks":["b-manufacturing-cell-therapy","b-drug-pricing","b-global-access"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2018,"doi":"10.1056/NEJMoa1709866","authors":"Maude SL, Laetsch TW, Buechner J, et al.","paperType":"translational","findings":["92 enrolled, 75 infused; 25 centres in 11 countries; median age 11.","Overall remission rate within 3 months 81%; all remissions MRD-negative.","Event-free survival 73% at 6 months and 50% at 12 months; overall survival 90% and 76%.","CRS 77% (grade 3-4 in about 46%; 48% needed tocilizumab; 47% intensive care); neurological events 40%.","Manufacturing failed in 7 of 92 and 17 enrolled patients were never infused, highlighting the vein-to-vein problem."],"whatItMeans":"ELIANA turned CAR-T from a single-centre experiment into a licensed product and created the regulatory and logistical template every later cell therapy has followed. For children with refractory leukaemia it offers a chance of durable remission without transplant. The trial also exposed the gaps: manufacturing failures, patients dying while waiting, and roughly half relapsing within a few years.","caveats":["Single-arm; no randomised comparator and outcomes reported on infused rather than enrolled patients in most analyses.","Severe CRS rates were high by later standards, before prophylactic strategies.","Long-term relapse, often CD19-negative, affects about half; some patients still proceed to transplant.","List price around 475,000 US dollars at launch raised affordability and access questions."],"changedPractice":true,"participants":75},{"id":"paper-nct05587296-n-engl-j-med-2025","kind":"paper","name":"Elinzanetant for Vasomotor Symptoms from Endocrine Therapy for Breast Cancer","aka":[],"tldr":"Published report from the OASIS-4 trial registered as NCT05587296, in New England Journal of Medicine (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Women receiving endocrine therapy for hormone receptor (HR)-positive breast cancer or its prevention among those at high risk for breast cancer commonly have vasomotor symptoms. Data are lacking on the effects of elinzanetant, a neurokinin-targeted therapy shown to be effective in treating vasomotor symptoms, in this population.\n\nMethods: We performed a phase 3 trial involving women 18 to 70 years of age with moderate-to-severe vasomotor symptoms associated with endocrine therapy for HR-positive breast cancer or its prevention. Women were randomly assigned in a 2:1 ratio to receive once-daily elinzanetant at a dose of 120 mg for 52 weeks or once-daily placebo for 12 weeks followed by once-daily elinzanetant at a dose of 120 mg for 40 weeks. The primary end points were the change in the mean daily frequency of moderate-to-severe vasomotor symptoms from baseline to week 4 and to week 12.\n\nResults: A total of 316 participants were assigned to the elinzanetant group and 158 to the placebo-elinzanetant group. At baseline, the mean daily frequency of moderate-to-severe vasomotor symptoms was 11.4 episodes (95% confidence interval [CI], 10.7 to 12.2) in the elinzanetant group and 11.5 episodes (95% CI, 10.5 to 12.5) in the placebo-elinzanetant group. At week 4, the mean change from baseline in the mean daily frequency of moderate-to-severe vasomotor symptoms was -6.5 episodes (95% CI, -7.2 to -5.8) among those who were receiving elinzanetant and -3.0 episodes (95% CI, -3.9 to -2.2) among those who were receiving placebo (least-squares mean difference, -3.5 episodes; 95% CI, -4.4 to -2.6; P<0.001). At week 12, the mean change was -7.8 episodes (95% CI, -8.5 to -7.1) among those receiving elinzanetant and -4.2 episodes (95% CI, -5.2 to -3.2) among those receiving placebo (least-squares mean difference, -3.4 episodes; 95% CI, -4.2 to -2.5; P<0.001). During weeks 1 through 12, a total of 220 participants (69.8%) receiving elinzanetant and 98 (62.0%) receiving placebo reported at least one adverse event that occurred while receiving elinzanetant or placebo, with the most common being headache, fatigue, and somnolence. Serious adverse events occurred during weeks 1 through 12 in 8 participants (2.5%) receiving elinzanetant and 1 participant (0.6%) receiving placebo.\n\nConclusions: Elinzanetant led to a significantly lower frequency of vasomotor symptoms associated with endocrine therapy than placebo. (Funded by Bayer; OASIS-4 ClinicalTrials.gov number, NCT05587296.).\n\nIndexed on Europe PMC as PubMed record 40454634 (DOI 10.1056/nejmoa2415566). Its abstract cites the registry id NCT05587296, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2025","url":"https://doi.org/10.1056/nejmoa2415566"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40454634/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40454634"},{"label":"ClinicalTrials.gov NCT05587296","url":"https://clinicaltrials.gov/study/NCT05587296"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05587296"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2025,"doi":"10.1056/nejmoa2415566","pmid":"40454634","authors":"Cardoso F, Parke S, Brennan DJ, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05587296 with the most citations, so it is the natural first reading for anyone following the OASIS-4 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-eln-2022-aml-dohner-blood-2022","kind":"paper","name":"ELN 2022: diagnosis and management of acute myeloid leukaemia in adults","aka":[],"tldr":"The European LeukemiaNet 2022 recommendations define how acute myeloid leukaemia is classified by its genetics into favourable, intermediate and adverse risk, and how those groups should be treated and monitored.","summary":"International expert panel recommendations updating the 2017 European LeukemiaNet guidance on AML diagnosis, genetic risk classification, response criteria, measurable residual disease and treatment, aligned with the 2022 WHO and International Consensus classifications.\n\nKey changes include FLT3-ITD moving to intermediate risk regardless of allelic ratio, the addition of adverse-risk myelodysplasia-related gene mutations, and new criteria for measurable residual disease assessment.","asOf":"2026-09-17","links":[{"label":"Blood 2022","url":"https://doi.org/10.1182/blood.2022016867"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35797463/"}],"tags":[],"related":[],"cancers":["aml-older-unfit","aml-flt3","aml-npm1-kmt2a","aml-idh","aml-secondary"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["blood"],"dependsOn":[],"notes":[],"journal":"Blood","year":2022,"doi":"10.1182/blood.2022016867","pmid":"35797463","authors":"Döhner H, Wei AH, Appelbaum FR, et al.","paperType":"guideline","findings":[],"whatItMeans":"The risk category on an AML report, and therefore whether a patient is steered towards transplant in first remission, comes from these recommendations.","caveats":["Risk categories were derived largely from intensively treated patients and predict less well under venetoclax-based regimens."],"changedPractice":true},{"id":"paper-mahalingam-nat-med","kind":"paper","name":"Elraglusib and chemotherapy in metastatic pancreatic ductal adenocarcinoma: a randomized controlled phase 2 trial","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 41981308 and published in Nature Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Metastatic pancreatic ductal adenocarcinoma (mPDAC) is one of the leading causes of cancer-related mortality, but advances in therapeutic treatments remain limited. Elraglusib (9-ING-41), an inhibitor of GSK-3β, exhibits a multimodal mechanism of action based on antitumor activity in preclinical models of cancer, including pancreatic. The efficacy and safety of elraglusib with gemcitabine plus nab-paclitaxel (GnP) were assessed in patients with previously untreated mPDAC. In an open-label, international, multicenter, phase 2 study, patients were randomized 2:1 to weekly elraglusib/GnP or GnP alone. Primary endpoints were median overall survival (OS) and 1-year survival rate. The prespecified modified intention-to-treat population included 155 patients on elraglusib/GnP and 78 on GnP. at the data cutoff of 27 April 2025, elraglusib/GnP improved median OS by 2.9 months and decreased the risk of death by 38% versus GnP (median OS 10.1 months versus 7.2 months, respectively (hazard ratio 0.62; 95% confidence interval 0.46 to 0.84; P = 0.01)). The 1-year survival rates were 44.1% versus 22.3%, respectively. The safety profile of elraglusib/GnP was manageable. The most common grade 3 or higher treatment-emergent adverse events (TEAEs) with elraglusib/GnP versus GnP alone were neutropenia (52.3% versus 30.8%), anemia (25.2% versus 29.5%) and fatigue (16.8% versus 5.1%). Explorative correlative analyses demonstrated that baseline circulating immune-related factors (that is, CXCL2 and TRAIL ligands) were associated with improved survival in the elraglusib/GnP arm. Treatment was accompanied by increases in intratumoral cytotoxic immune cell populations. Together, these findings support the clinical activity of elraglusib/GnP as first-line treatment in mPDAC and provide a biological context for the observed survival benefit. Based on the results of this phase 2 trial, a phase 3 trial is being planned. ClinicalTrials.gov registration: NCT03678883.\n\nIndexed on Europe PMC as PubMed record 41981308 (DOI 10.1038/s41591-026-04327-4). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Med 2026","url":"https://doi.org/10.1038/s41591-026-04327-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41981308/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41981308"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["actuate-1801"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2026,"doi":"10.1038/s41591-026-04327-4","pmid":"41981308","authors":"Mahalingam D, Shroff RT, Carneiro BA, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-bower-ema-co-high-risk-gtn-charing-cross-jco-1997","kind":"paper","name":"EMA/CO for high-risk gestational trophoblastic tumours: results from a cohort of 272 patients","aka":[],"tldr":"The Charing Cross series that established EMA/CO, an alternating weekly combination of five drugs, as the standard treatment for high-risk gestational trophoblastic disease, curing more than eight in ten women.","summary":"Retrospective analysis of 272 women with high-risk gestational trophoblastic tumours treated at Charing Cross Hospital with EMA/CO (etoposide, methotrexate and dactinomycin alternating weekly with cyclophosphamide and vincristine) between 1979 and 1995.\n\nFive-year survival was about 86 percent, with complete remission in most and salvage of many who relapsed or were resistant using platinum-containing regimens and surgery; early deaths from disease and secondary leukaemia after etoposide were noted.","asOf":"2026-09-18","links":[{"label":"J Clin Oncol 1997","url":"https://doi.org/10.1200/JCO.1997.15.7.2636"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/9215835/"}],"tags":[],"related":[],"cancers":["high-risk-gtn"],"sections":[],"technologies":[],"targets":[],"drugs":["etoposide","methotrexate","dactinomycin","cyclophosphamide","vincristine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":1997,"doi":"10.1200/JCO.1997.15.7.2636","pmid":"9215835","authors":"Bower M, Newlands ES, Holden L, et al.","paperType":"observational","findings":["Five-year survival about 86 percent for high-risk GTN treated with EMA/CO.","Relapse or resistance in a minority, most salvaged with platinum-based regimens and surgery."],"whatItMeans":"EMA/CO remains the first-line regimen for high-risk GTN worldwide; later Charing Cross work added low-dose induction etoposide-cisplatin for women with very high scores.","caveats":["Retrospective single-centre series; no randomised trial has compared high-risk regimens.","Etoposide carries a small risk of secondary leukaemia."],"changedPractice":true,"participants":272},{"id":"paper-embark-nejm-2023","kind":"paper","name":"EMBARK: enzalutamide with or without leuprolide in high-risk biochemically recurrent prostate cancer","aka":[],"tldr":"In men whose PSA was rising fast after surgery or radiotherapy without visible metastases, enzalutamide with or without hormone injections delayed metastases by years compared with hormone injections alone, with treatment paused when the PSA fell to undetectable.","summary":"Phase 3 trial of 1,068 men with high-risk biochemical recurrence (PSA doubling time of nine months or less) after definitive therapy randomised to enzalutamide plus leuprolide, placebo plus leuprolide, or enzalutamide alone, with treatment suspended at week 37 if PSA was undetectable.\n\nFive-year metastasis-free survival was 87.3 percent with the combination against 71.4 percent with leuprolide alone (hazard ratio 0.42) and 80.0 percent with enzalutamide monotherapy (hazard ratio 0.63); later analysis showed an overall survival benefit for the combination.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2023","url":"https://doi.org/10.1056/NEJMoa2303974"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37851874/"}],"tags":[],"related":[],"cancers":["prostate-bcr"],"sections":[],"technologies":[],"targets":[],"drugs":["enzalutamide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["embark"],"people":["stephen-freedland"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/NEJMoa2303974","pmid":"37851874","authors":"Freedland SJ, de Almeida Luz M, De Giorgi U, et al.","paperType":"rct","findings":["Five-year metastasis-free survival 87.3 percent (combination) vs 71.4 percent (leuprolide alone); hazard ratio 0.42.","Enzalutamide monotherapy 80.0 percent; hazard ratio 0.63."],"whatItMeans":"Enzalutamide, with or without androgen deprivation, is now approved for high-risk biochemical recurrence, and intermittent therapy with treatment suspension is built into the regimen.","caveats":["Conventional imaging defined the population; PSMA PET would reclassify many as metastatic.","Hot flushes, fatigue and gynaecomastia (with monotherapy) are common."],"changedPractice":true,"participants":1068},{"id":"paper-emerald-1-lancet-2025","kind":"paper","name":"EMERALD-1: durvalumab with or without bevacizumab added to transarterial chemoembolisation for embolisation-eligible hepatocellular carcinoma","aka":[],"tldr":"Adding durvalumab and bevacizumab to chemoembolisation lengthened the time to progression by about seven months in liver cancer suitable for embolisation, the first systemic combination to improve on chemoembolisation alone.","summary":"Phase 3 placebo-controlled trial of 616 patients with unresectable hepatocellular carcinoma eligible for embolisation randomised to transarterial chemoembolisation with durvalumab plus bevacizumab, durvalumab alone, or placebo.\n\nMedian progression-free survival was 15.0 months with durvalumab plus bevacizumab against 8.2 months with placebo (hazard ratio 0.77), while durvalumab alone did not significantly improve progression-free survival; grade 3 to 4 adverse events were more frequent with the combination.","asOf":"2026-09-17","links":[{"label":"Lancet 2025","url":"https://doi.org/10.1016/S0140-6736(24)02551-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39798579/"}],"tags":[],"related":[],"cancers":["hcc-intermediate"],"sections":[],"technologies":[],"targets":[],"drugs":["bevacizumab","durvalumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["emerald-1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2025,"doi":"10.1016/S0140-6736(24)02551-0","pmid":"39798579","authors":"Sangro B, Kudo M, Erinjeri JP, et al.","paperType":"rct","findings":["Median progression-free survival 15.0 vs 8.2 months; hazard ratio 0.77.","Durvalumab alone with chemoembolisation: 10.0 months (not significant)."],"whatItMeans":"Chemoembolisation combined with durvalumab and bevacizumab is a new option for intermediate-stage hepatocellular carcinoma where approved, though overall survival benefit is not yet shown.","caveats":["Overall survival data immature.","Bleeding risk with bevacizumab requires endoscopic assessment."],"changedPractice":true,"participants":616},{"id":"paper-emerald-elacestrant-jco-2022","kind":"paper","name":"EMERALD: elacestrant versus standard endocrine therapy after a CDK4/6 inhibitor","aka":[],"tldr":"The oral oestrogen receptor degrader elacestrant delayed progression compared with standard hormone therapy in advanced breast cancer that had progressed on a CDK4/6 inhibitor, with the clearest benefit in tumours carrying an ESR1 mutation.","summary":"Phase 3 trial of 477 patients with oestrogen receptor-positive, HER2-negative advanced breast cancer previously treated with one or two lines of endocrine therapy including a CDK4/6 inhibitor, randomised to elacestrant or investigator's choice of fulvestrant or an aromatase inhibitor.\n\nProgression-free survival was improved overall (hazard ratio 0.70) and in the ESR1-mutated group (hazard ratio 0.55), where median progression-free survival was 3.8 versus 1.9 months; benefit was largest in patients with longer prior CDK4/6 inhibitor exposure.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2022","url":"https://doi.org/10.1200/JCO.22.00338"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35584336/"}],"tags":[],"related":[],"cancers":["hr-positive-metastatic-post-cdk46"],"sections":[],"technologies":[],"targets":[],"drugs":["elacestrant"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["emerald"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2022,"doi":"10.1200/JCO.22.00338","pmid":"35584336","authors":"Bidard FC, Kaklamani VG, Neven P, et al.","paperType":"rct","findings":["Progression-free survival hazard ratio 0.70 overall and 0.55 in ESR1-mutated disease.","Median progression-free survival 3.8 vs 1.9 months in ESR1-mutated tumours."],"whatItMeans":"Elacestrant is the first oral selective oestrogen receptor degrader approved, for ESR1-mutated disease after a CDK4/6 inhibitor. Absolute gains are modest and blood testing for ESR1 mutations is now routine at progression.","caveats":["Absolute benefit is small and control-arm performance was poor.","Nausea and lipid changes are common."],"changedPractice":true,"participants":477},{"id":"paper-misale-kras-acquired-resistance-anti-egfr-colorectal-nature-2012","kind":"paper","name":"Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer","aka":[],"tldr":"Bowel cancers that respond to cetuximab almost always stop responding within a year. This paper showed why: KRAS-mutant cells take over, and their DNA shows up in the blood months before a scan changes.","summary":"Molecular alterations of KRAS, in most instances point mutations, were shown to be causally associated with the onset of acquired resistance to anti-EGFR treatment in colorectal cancers. Expressing mutant KRAS under the control of its endogenous promoter was sufficient to confer cetuximab resistance, but resistant cells remained sensitive to combined inhibition of EGFR and MEK. Analysis of metastases from patients who developed resistance to cetuximab or panitumumab showed the emergence of KRAS amplification in one sample and acquisition of secondary KRAS mutations in 6 of 10 cases. KRAS mutant alleles were detectable in the blood of cetuximab-treated patients as early as 10 months before radiographic documentation of disease progression.","asOf":"2026-09-24","links":[{"label":"Misale et al., Nature 2012: emergence of KRAS mutations and acquired resistance to anti-EGFR therapy","url":"https://doi.org/10.1038/nature11156"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22722830/"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["liquid-biopsy"],"targets":["kras","egfr"],"drugs":["cetuximab","panitumumab"],"companies":[],"institutions":["candiolo","niguarda-cancer-center"],"pathways":["ras-mapk","clonal-evolution","resistance-routes-map"],"terms":["ctdna","cfdna"],"trials":[],"people":["alberto-bardelli","rona-yaeger","andrea-sartore-bianchi","salvatore-siena"],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2012,"doi":"10.1038/nature11156","pmid":"22722830","authors":"Misale S, Yaeger R, Hobor S, et al.","paperType":"translational","findings":["Secondary KRAS mutations in 6 of 10 patients progressing on an EGFR antibody, plus one KRAS amplification.","Mutant KRAS alleles detectable in blood up to 10 months before radiographic progression.","Resistant cells remained sensitive to combined EGFR and MEK inhibition."],"whatItMeans":"It made acquired resistance a measurable, plasma-readable event, and it is the origin of anti-EGFR rechallenge strategies guided by ctDNA clearance of the resistant clone.","caveats":["Small patient numbers behind the clinical observations.","The EGFR plus MEK combination has not succeeded clinically.","KRAS is only one of several resistance routes, alongside NRAS, BRAF, EGFR ectodomain and HER2 or MET amplification."],"changedPractice":false},{"id":"paper-vistogard-cancer-2017","kind":"paper","name":"Emergency use of uridine triacetate for the prevention and treatment of life-threatening 5-fluorouracil and capecitabine toxicity","aka":[],"tldr":"The combined report of the Vistogard studies: 96 percent of patients treated with oral uridine triacetate after a fluorouracil or capecitabine overdose survived, where 84 percent of an earlier supportive-care group had died.","summary":"Report of two open-label clinical studies in which patients who presented with a 5-fluorouracil or capecitabine overdose or an early onset of severe toxicities were treated with uridine triacetate as soon as possible, most within 96 hours of the chemotherapy. Outcomes included survival, resumption of chemotherapy and safety, and survival was compared with a historical cohort of overdose patients who received only supportive care.\n\nA total of 137 of 142 overdose patients (96 percent) treated with uridine triacetate survived and had rapid reversal of severe acute cardiotoxicity and neurotoxicity; mucositis and leukopenia were prevented or recovered from. In the historical cohort, 21 of 25 patients (84 percent) died. Among the 141 treated overdose patients with a cancer diagnosis, 53 resumed chemotherapy. The authors concluded that uridine triacetate was a safe and effective lifesaving antidote for capecitabine and 5-fluorouracil overexposure.","asOf":"2026-09-24","links":[{"label":"Cancer 2017","url":"https://doi.org/10.1002/cncr.30321"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27622829/"},{"label":"ClinicalTrials.gov NCT01432301","url":"https://clinicaltrials.gov/study/NCT01432301"}],"tags":[],"related":[],"cancers":[],"sections":["supportive-care"],"technologies":[],"targets":[],"drugs":["uridine-triacetate","fluorouracil","capecitabine"],"companies":["serb-pharmaceuticals"],"institutions":[],"pathways":[],"terms":[],"trials":["vistogard-studies-1-2"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-wiley"],"dependsOn":[],"notes":[],"journal":"Cancer","year":2017,"doi":"10.1002/cncr.30321","pmid":"27622829","authors":"Ma WW, Saif MW, El-Rayes BF, et al.","paperType":"observational","findings":["137 of 142 overdose patients (96%) treated with uridine triacetate survived.","In the historical supportive-care cohort, 21 of 25 patients (84%) died.","53 of 141 treated overdose patients with a cancer diagnosis resumed chemotherapy."],"whatItMeans":"This is the evidence behind the December 2015 US approval of Vistogard, the only antidote for fluorouracil or capecitabine overdose and early life-threatening toxicity. Its main practical message is the 96-hour window: the drug must be started before toxicity is fully established.","caveats":["Open-label expanded-access studies with a historical comparison and no inferential statistics.","The label pools 135 patients (Study 1 and Study 2) where the paper's survival analysis counts 142 evaluable overdose patients.","The registry lists an expanded-access protocol with no phase, enrolment count or results."],"changedPractice":true,"participants":142},{"id":"paper-egfr-glioblastoma-mol-oncol-2018","kind":"paper","name":"Emerging functions of the EGFR in cancer","aka":[],"tldr":"Review on EGFR in Glioma & glioblastoma, in Molecular oncology (2018), one of the most cited Europe PMC records with EGFR in its title.","summary":"The physiological function of the epidermal growth factor receptor (EGFR) is to regulate epithelial tissue development and homeostasis. In pathological settings, mostly in lung and breast cancer and in glioblastoma, the EGFR is a driver of tumorigenesis. Inappropriate activation of the EGFR in cancer mainly results from amplification and point mutations at the genomic locus, but transcriptional upregulation or ligand overproduction due to autocrine/paracrine mechanisms has also been described. Moreover, the EGFR is increasingly recognized as a biomarker of resistance in tumors, as its amplification or secondary mutations have been found to arise under drug pressure. This evidence, in addition to the prominent function that this receptor plays in normal epithelia, has prompted intense investigations into the role of the EGFR both at physiological and at pathological level. Despite the large body of knowledge obtained over the last two decades, previously unrecognized (herein defined as 'noncanonical') functions of the EGFR are currently emerging. Here, we will initially review the canonical ligand-induced EGFR signaling pathway, with particular emphasis to its regulation by endocytosis and subversion in human tumors. We will then focus on the most recent advances in uncovering noncanonical EGFR functions in stress-induced trafficking, autophagy, and energy metabolism, with a perspective on future therapeutic applications.\n\nIndexed on Europe PMC as PubMed record 29124875 (DOI 10.1002/1878-0261.12155). Its title names EGFR and its text names Glioma & glioblastoma; PubMed types it as a review (Research Support, Non-U.S. Gov't, review-article, Review). It was matched automatically to the idea \"Attack extrachromosomal DNA, the engine of oncogene amplification\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Mol Oncol 2018","url":"https://doi.org/10.1002/1878-0261.12155"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29124875/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29124875"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["molecular-oncology"],"dependsOn":[],"notes":[],"journal":"Molecular oncology","year":2018,"doi":"10.1002/1878-0261.12155","pmid":"29124875","authors":"Sigismund S, Avanzato D, Lanzetti L","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for EGFR in Glioma & glioblastoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by EGFR in the title and Glioma & glioblastoma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-androgen-receptor-prostate-nat-rev-cancer-2015","kind":"paper","name":"Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer","aka":[],"tldr":"Review on Androgen receptor in Prostate cancer, in Nature Reviews Cancer (2015), one of the most cited Europe PMC records with Androgen receptor in its title.","summary":"During the past 10 years, preclinical studies implicating sustained androgen receptor (AR) signalling as the primary driver of castration-resistant prostate cancer (CRPC) have led to the development of novel agents targeting the AR pathway that are now in widespread clinical use. These drugs prolong the survival of patients with late-stage prostate cancer but are not curative. In this Review, we highlight emerging mechanisms of acquired resistance to these contemporary therapies, which fall into the three broad categories of restored AR signalling, AR bypass signalling and complete AR independence. This diverse range of resistance mechanisms presents new challenges for long-term disease control, which may be addressable through early use of combination therapies guided by recent insights from genomic landscape studies of CRPC.\n\nIndexed on Europe PMC as PubMed record 26563462 (DOI 10.1038/nrc4016). Its title names Androgen receptor and its text names Prostate cancer; PubMed types it as a review (Research Support, Non-U.S. Gov't, research-article, Review, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural). It was matched automatically to the idea \"Destroy the truncated androgen receptor that hormone drugs cannot touch\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Cancer 2015","url":"https://doi.org/10.1038/nrc4016"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26563462/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26563462"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Cancer","year":2015,"doi":"10.1038/nrc4016","pmid":"26563462","authors":"Watson PA, Arora VK, Sawyers CL","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for Androgen receptor in Prostate cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Androgen receptor in the title and Prostate cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-empower-cervical-1-cemiplimab-nejm-2022","kind":"paper","name":"EMPOWER-Cervical 1: cemiplimab versus chemotherapy in recurrent cervical cancer after platinum","aka":[],"tldr":"The PD-1 antibody cemiplimab lengthened survival compared with single-agent chemotherapy in recurrent cervical cancer after platinum, regardless of PD-L1 expression, the first immunotherapy to show a survival benefit in this disease.","summary":"Phase 3 trial of 608 patients with recurrent cervical cancer progressing after first-line platinum chemotherapy randomised to cemiplimab or investigator's choice single-agent chemotherapy, enrolled irrespective of PD-L1 status.\n\nMedian overall survival was 12.0 versus 8.5 months (hazard ratio 0.69) overall and 11.1 versus 8.8 months in squamous cell carcinoma; response was 16.4 versus 6.3 percent, and benefit was seen across PD-L1 levels.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2022","url":"https://doi.org/10.1056/NEJMoa2112187"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35139273/"}],"tags":[],"related":[],"cancers":["recurrent-metastatic-cervical-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["cemiplimab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["empower-cervical-1"],"people":["krishnansu-tewari"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/NEJMoa2112187","pmid":"35139273","authors":"Tewari KS, Monk BJ, Vergote I, et al.","paperType":"rct","findings":["Median overall survival 12.0 vs 8.5 months; hazard ratio 0.69.","Objective response 16.4 percent vs 6.3 percent."],"whatItMeans":"Cemiplimab is an option for second-line cervical cancer in patients who have not had immunotherapy, though most now receive pembrolizumab first line, moving cemiplimab later or out of sequence.","caveats":["Patients were immunotherapy-naive; applicability after first-line pembrolizumab is unclear."],"changedPractice":true,"participants":608},{"id":"paper-enasidenib-idh2-stein-blood-2017","kind":"paper","name":"Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukaemia","aka":[],"tldr":"Enasidenib, a pill blocking the mutant IDH2 enzyme, produced responses in about four in ten patients with relapsed IDH2-mutated acute myeloid leukaemia by making the leukaemic cells mature, and became the first IDH-targeted drug approved.","summary":"Phase 1/2 study of 239 patients with IDH2-mutated advanced myeloid malignancies, including 176 with relapsed or refractory AML, treated with enasidenib, mostly at 100 mg daily.\n\nOverall response rate was 40.3 percent with complete remission in 19.3 percent and a median overall survival of 9.3 months; responses came through differentiation of blasts rather than cytotoxicity, with differentiation syndrome in a minority.","asOf":"2026-09-17","links":[{"label":"Blood 2017","url":"https://doi.org/10.1182/blood-2017-04-779405"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28588020/"}],"tags":[],"related":[],"cancers":["aml-idh"],"sections":[],"technologies":[],"targets":[],"drugs":["enasidenib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["blood"],"dependsOn":[],"notes":[],"journal":"Blood","year":2017,"doi":"10.1182/blood-2017-04-779405","pmid":"28588020","authors":"Stein EM, DiNardo CD, Pollyea DA, et al.","paperType":"observational","findings":["Overall response 40.3 percent; complete remission 19.3 percent.","Median overall survival 9.3 months; 19.7 months in complete responders."],"whatItMeans":"IDH2 mutations, present in about one in eight AML cases, became actionable. Enasidenib is an option at relapse; its role in newly diagnosed disease is less established than ivosidenib's.","caveats":["The later randomised IDHENTIFY trial did not show a survival benefit over conventional care.","Indirect hyperbilirubinaemia and differentiation syndrome are characteristic toxicities."],"changedPractice":true,"participants":239},{"id":"paper-tabernero-j-clin-oncol","kind":"paper","name":"Encorafenib Plus Cetuximab as a New Standard of Care for Previously Treated BRAF V600E-Mutant Metastatic Colorectal Cancer: Updated Survival Results and Subgroup Analyses from the BEACON Study","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 33503393 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: BEACON CRC evaluated encorafenib plus cetuximab with or without binimetinib versus investigators' choice of irinotecan or FOLFIRI plus cetuximab in patients with BRAF V600E-mutant metastatic colorectal cancer (mCRC), after progression on 1-2 prior regimens. In the previously reported primary analysis, encorafenib, binimetinib plus cetuximab (ENCO/BINI/CETUX; triplet) and encorafenib plus cetuximab (ENCO/CETUX; doublet) regimens improved overall survival (OS) and objective response rate (ORR; by blinded central review) versus standard of care. The purpose of this analysis was to report updated efficacy and safety data.\n\nMethods: In this open-label, phase III trial, 665 patients with BRAF V600E-mutant mCRC were randomly assigned 1:1:1 to receive triplet, doublet, or control. Primary end points were OS and independently reviewed ORR comparing triplet to control. OS for doublet versus control was a key secondary end point. Updated analyses include 6 months of additional follow-up and ORR for all randomized patients.\n\nResults: Patients received triplet (n = 224), doublet (n = 220), or control (n = 221). Median OS was 9.3 months (95% CI, 8.2 to 10.8) for triplet and 5.9 months (95% CI, 5.1 to 7.1) for control (hazard ratio [HR], 0.60 [95% CI, 0.47 to 0.75]). Median OS for doublet was 9.3 months (95% CI, 8.0 to 11.3) (HR v control, 0.61 [95% CI, 0.48 to 0.77]). Confirmed ORR was 26.8% (95% CI, 21.1% to 33.1%) for triplet, 19.5% (95% CI, 14.5% to 25.4%) for doublet, and 1.8% (95% CI, 0.5% to 4.6%) for control. Adverse events were consistent with the prior primary analysis, with grade ≥ 3 adverse events in 65.8%, 57.4%, and 64.2% for triplet, doublet, and control, respectively.\n\nConclusion: In the BEACON CRC study, encorafenib plus cetuximab improved OS, ORR, and progression-free survival in previously treated patients in the metastatic setting compared with standard chemotherapy. Based on the primary and updated analyses, encorafenib plus cetuximab is a new standard care regimen for previously treated patients with BRAF V600E mCRC.\n\nIndexed on Europe PMC as PubMed record 33503393 (DOI 10.1200/jco.20.02088). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2021","url":"https://doi.org/10.1200/jco.20.02088"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33503393/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33503393"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["beacon-crc"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2021,"doi":"10.1200/jco.20.02088","pmid":"33503393","authors":"Tabernero J, Grothey A, Van Cutsem E, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-kopetz-beacon-encorafenib-braf-colorectal-nejm-2019","kind":"paper","name":"Encorafenib, binimetinib, and cetuximab in BRAF V600E-mutated colorectal cancer (BEACON CRC)","aka":[],"tldr":"BRAF V600E bowel cancer had a median survival of four to six months after first-line failure. Blocking BRAF and EGFR together took it to nine, and made the doublet a standard.","summary":"Kopetz, Grothey, Yaeger and colleagues enrolled 665 patients with BRAF V600E-mutated metastatic colorectal cancer who had progressed after one or two previous regimens, randomising them 1:1:1 to encorafenib, binimetinib and cetuximab (triplet), encorafenib and cetuximab (doublet), or the investigators' choice of cetuximab with irinotecan or with FOLFIRI (control). The primary end points were overall survival and objective response in the triplet group against control, with overall survival in the doublet group against control as a secondary end point; this is the prespecified interim analysis.\n\nInhibition of BRAF alone has limited activity in colorectal cancer because the pathway reactivates through EGFR signalling, which is the reason the EGFR antibody is in every arm of the experimental design.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2019","url":"https://doi.org/10.1056/NEJMoa1908075"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31566309/"}],"tags":["colorectal-evidence"],"related":["paper-cremolini-tribe-folfoxiri-bevacizumab-lancet-oncol-2015","braf-v600e"],"cancers":["colorectal","braf-v600e-colorectal"],"sections":["targeted-therapy"],"technologies":["kinase-inhibitors","monoclonal-antibody"],"targets":["braf","egfr"],"drugs":["encorafenib","binimetinib","cetuximab","folfiri","irinotecan"],"companies":["pfizer"],"institutions":[],"pathways":["ras-mapk"],"terms":["sidedness"],"trials":["beacon-crc","breakwater"],"people":["scott-kopetz","eric-van-cutsem","josep-tabernero","yoshino-takayuki"],"bottlenecks":["b-resistance"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2019,"doi":"10.1056/NEJMoa1908075","pmid":"31566309","authors":"Kopetz S, Grothey A, Yaeger R, et al.","paperType":"rct","findings":["Median overall survival 9.0 months in the triplet group against 5.4 months in the control group: hazard ratio 0.52 (95 percent CI 0.39 to 0.70, p<0.001).","Confirmed response 26 percent (95 percent CI 18 to 35) with the triplet against 2 percent (0 to 7) with control (p<0.001).","Median overall survival in the doublet group 8.4 months: hazard ratio against control 0.60 (0.45 to 0.79, p<0.001).","Grade 3 or higher adverse events in 58 percent (triplet), 50 percent (doublet) and 61 percent (control)."],"whatItMeans":"Encorafenib with cetuximab became the standard second-line treatment for BRAF V600E disease, and the platform BREAKWATER later moved into first line with chemotherapy added, doubling survival again.","caveats":["The MEK inhibitor added toxicity without a clear survival gain over the doublet, which is why the doublet was approved.","BRAF V600E disease is 8 to 10 percent of colorectal cancer; the trial says nothing about non-V600E BRAF alterations.","Interim analysis; the final report confirmed the direction with slightly different medians."],"changedPractice":true,"participants":665},{"id":"paper-breakwater-nat-med-2025","kind":"paper","name":"Encorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: a randomized phase 3 trial","aka":[],"tldr":"Published report from the BREAKWATER trial registered as NCT04607421, in Nature Medicine (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Encorafenib + cetuximab (EC) is approved for previously treated BRAF V600E-mutant metastatic colorectal cancer (mCRC) based on the BEACON phase 3 study. Historically, first-line treatment of BRAF V600E-mutant mCRC with chemotherapy regimens has had limited efficacy. The phase 3 BREAKWATER study investigated EC+mFOLFOX6 versus standard of care (SOC) in patients with previously untreated BRAF V600E mCRC. The dual primary endpoint of progression-free survival is event driven; data were not mature at data cutoff. BREAKWATER met the other dual primary endpoint of objective response rate, demonstrating significant and clinically relevant improvement in objective response rate (EC+mFOLFOX6: 60.9%; SOC: 40.0%; odds ratio, 2.443; 95% confidence interval (CI): 1.403-4.253; 99.8% CI: 1.019-5.855; one-sided P = 0.0008). Median duration of response was 13.9 versus 11.1 months. At this first interim analysis of overall survival, the hazard ratio was 0.47 (95% CI: 0.318-0.691; repeated CI: 0.166-1.322). Serious adverse event rates were 37.7% versus 34.6%. The safety profiles were consistent with those known for each agent. BREAKWATER demonstrated a significantly improved response rate that was durable for first-line EC+mFOLFOX6 versus SOC in patients with BRAF V600E mCRC. ClinicalTrials.gov identifier: NCT04607421.\n\nIndexed on Europe PMC as PubMed record 39863775 (DOI 10.1038/s41591-024-03443-3). Its abstract cites the registry id NCT04607421, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Nat Med 2025","url":"https://doi.org/10.1038/s41591-024-03443-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39863775/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39863775"},{"label":"ClinicalTrials.gov NCT04607421","url":"https://clinicaltrials.gov/study/NCT04607421"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["breakwater"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2025,"doi":"10.1038/s41591-024-03443-3","pmid":"39863775","authors":"Kopetz S, Yoshino T, Van Cutsem E, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04607421 with the most citations, so it is the natural first reading for anyone following the BREAKWATER trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-freites-martinez-jama-dermatol","kind":"paper","name":"Endocrine Therapy-Induced Alopecia in Patients With Breast Cancer","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 29641806 and published in JAMA dermatology; the citing page links this DOI, which is how the record was matched.","summary":"Importance: Endocrine therapy-induced alopecia (EIA) has been anecdotally reported but not systematically described.\n\nObjective: To characterize EIA in patients with breast cancer.\n\nDesign, setting, and participants: Retrospective cohort study of 112 patients with breast cancer, diagnosed with EIA from January 1, 2009, to December 31, 2016, the patients were examined at the dermatology service in a large tertiary care hospital and comprehensive cancer center.\n\nMain outcomes and measures: The clinical features, alopecia-related quality of life (QoL), and response to minoxidil of EIA in patients with breast cancer were assessed. Data from the Hairdex Questionnaire was used to assess the impact of the alopecia on patients QoL. Higher score indicates lower QoL (0-100 score). Efficacy of minoxidil was measured at 3 or 6 months by a single-blinded investigator through standardized clinical photographs of the scalp.\n\nResults: A total of 112 female patients with breast cancer were included (median [range] age, 60 [34-90] years). A total of 104 patients (93%) had standardized clinical photographs; of these, 59 patients (53%) had trichoscopy images available at baseline, and 46 patients (41%) were assessed for response to minoxidil. Alopecia was attributed to aromatase inhibitors in 75 patients (67%) and tamoxifen in 37 (33%). Severity was grade 1 in 96 of 104 patients (92%), and the pattern was similar to androgenetic alopecia. The predominant trichoscopic feature at baseline was the presence of vellus hairs and intermediate- and thick-diameter terminal hair shafts. A negative impact on QoL was reported, with a higher effect in the emotion domain according to the Hairdex score (mean [SD], 41.8 [21.3]; P <.001). After treatment with topical minoxidil, moderate or significant improvement in alopecia was observed in 37 of 46 patients (80%).\n\nConclusions and relevance: Endocrine therapies are associated with a pattern alopecia similar to androgenetic-type, consistent with the mechanism of action of causal agents. A significant negative impact on QoL was reported by patients, despite mostly mild alopecia severity.\n\nIndexed on Europe PMC as PubMed record 29641806 (DOI 10.1001/jamadermatol.2018.0454). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA Dermatol 2018","url":"https://doi.org/10.1001/jamadermatol.2018.0454"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29641806/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29641806"}],"tags":["europepmc-ingest"],"related":["minoxidil-chemotherapy-alopecia"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"JAMA dermatology","year":2018,"doi":"10.1001/jamadermatol.2018.0454","pmid":"29641806","authors":"Freites-Martinez A, Shapiro J, Chan D, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-crosbie-lancet","kind":"paper","name":"Endometrial cancer","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 35397864 and published in The Lancet; the citing page links this DOI, which is how the record was matched.","summary":"Endometrial cancer is the most common gynaecological cancer in high income countries and its incidence is rising globally. Although an ageing population and fewer benign hysterectomies have contributed to this trend, the growing prevalence of obesity is the major underlying cause. Obesity poses challenges for diagnosis and treatment and more research is needed to offer primary prevention to high-risk women and to optimise endometrial cancer survivorship. Early presentation with postmenopausal bleeding ensures most endometrial cancers are cured by hysterectomy but those with advanced disease have a poor prognosis. Minimally invasive surgical staging and sentinel-lymph-node biopsy provides a low morbidity alternative to historical surgical management without compromising oncological outcomes. Adjuvant radiotherapy reduces loco-regional recurrence in intermediate-risk and high-risk cases. Advances in our understanding of the molecular biology of endometrial cancer have paved the way for targeted chemotherapeutic strategies, and clinical trials will establish their benefit in adjuvant, advanced, and recurrent disease settings in the coming years.\n\nIndexed on Europe PMC as PubMed record 35397864 (DOI 10.1016/s0140-6736(22)00323-3). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet 2022","url":"https://doi.org/10.1016/s0140-6736(22)00323-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35397864/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35397864"}],"tags":["europepmc-ingest"],"related":["endometrial-cancer-signalling"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2022,"doi":"10.1016/s0140-6736(22)00323-3","pmid":"35397864","authors":"Crosbie EJ, Kitson SJ, McAlpine JN, et al.","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-enets-lung-net-consensus-caplin-ann-oncol-2015","kind":"paper","name":"ENETS expert consensus on pulmonary neuroendocrine (carcinoid) tumours","aka":[],"tldr":"The European Neuroendocrine Tumor Society consensus on lung carcinoids covers diagnosis, grading into typical and atypical, surgery with node dissection, and the limited evidence for somatostatin analogues, everolimus and radioligand therapy in advanced disease.","summary":"Expert consensus from the European Neuroendocrine Tumor Society on the classification, staging, imaging, surgical and systemic management of typical and atypical lung carcinoids, including recommendations on adjuvant therapy (not indicated), somatostatin analogues, everolimus, temozolomide-based chemotherapy and peptide receptor radionuclide therapy.","asOf":"2026-09-17","links":[{"label":"Ann Oncol 2015","url":"https://doi.org/10.1093/annonc/mdv041"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25646366/"}],"tags":[],"related":[],"cancers":["lung-net"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2015,"doi":"10.1093/annonc/mdv041","pmid":"25646366","authors":"Caplin ME, Baudin E, Ferolla P, et al.","paperType":"guideline","findings":[],"whatItMeans":"Surgical resection as the only curative treatment and the sequence of systemic options on the lung neuroendocrine tumour page follow this consensus.","caveats":["Randomised evidence in lung carcinoids remains scarce; RADIANT-4 and CABINET are the main trials since."],"changedPractice":true},{"id":"paper-hpv-vaccine-england-lancet-2021","kind":"paper","name":"England's HPV programme: cervical cancer down 87% in the first cohort vaccinated at 12-13","aka":[],"tldr":"Ten years after England began vaccinating 12- to 13-year-olds with the bivalent HPV vaccine, cervical cancer in that cohort had fallen by 87% and severe precancer (CIN3) by 97%.","summary":"A population-based observational study used English cancer registry data from 2006 to 2019 to compare cervical cancer and CIN3 rates in cohorts offered the bivalent vaccine (Cervarix) at ages 12-13, 14-16 and 16-18 with earlier, unvaccinated cohorts, adjusting for changes in screening.\n\nRelative reductions in cervical cancer were 87% in the cohort offered vaccination at 12-13, 62% at 14-16 and 34% at 16-18. CIN3 fell by 97%, 75% and 39% respectively. The authors estimated about 450 fewer cervical cancers and 17,200 fewer CIN3 cases by mid-2019.\n\nThis confirmed the Swedish finding with a different vaccine and a school-based programme with high coverage.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1016/S0140-6736(21)02178-4"}],"tags":[],"related":["paper-hpv-vaccine-sweden-nejm-2020","idea-prev-hpv-vaccinate-at-screening","idea-prev-hpv-male-catchup-oropharynx"],"cancers":["cervical"],"sections":["prevention"],"technologies":["hpv-vaccine","hpv-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-global-access"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2021,"doi":"10.1016/S0140-6736(21)02178-4","pmid":"34741816","authors":"Falcaro M, Castañon A, Ndlela B, et al.","paperType":"observational","findings":["Cervical cancer reduced 87% (95% CI 72-94) in the cohort offered vaccine at age 12-13","Reduction of 62% (52-71) at 14-16 and 34% (25-41) at 16-18","CIN3 reduced 97% (96-98) in the youngest cohort","An estimated 448 fewer cervical cancers and 17,235 fewer CIN3 cases by June 2019"],"whatItMeans":"School-based vaccination at 12-13 with high uptake nearly abolishes cervical cancer in vaccinated cohorts, even with a vaccine covering only two HPV types. Screening intervals and the future of cervical screening can now be redesigned around vaccination status.","caveats":["Observational with a cohort comparison; changes in screening policy were adjusted for but cannot be fully excluded","Vaccinated cohorts were still young (under 28), so absolute numbers of cancers were small","Bivalent vaccine; England later switched to quadrivalent and nonavalent","Effects in populations with lower coverage will be smaller"],"changedPractice":true},{"id":"paper-doronina-bioconjug-chem","kind":"paper","name":"Enhanced activity of monomethylauristatin F through monoclonal antibody delivery: effects of linker technology on efficacy and toxicity","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 16417259 and published in Bioconjugate chemistry; the citing page links this DOI, which is how the record was matched.","summary":"We have previously shown that antibody-drug conjugates (ADCs) consisting of cAC10 (anti-CD30) linked to the antimitotic agent monomethylauristatin E (MMAE) lead to potent in vitro and in vivo activities against antigen positive tumor models. MMAF is a new antimitotic auristatin derivative with a charged C-terminal phenylalanine residue that attenuates its cytotoxic activity compared to its uncharged counterpart, MMAE, most likely due to impaired intracellular access. In vitro cytotoxicity studies indicated that mAb-maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl-MMAF (mAb-L1-MMAF) conjugates were >2200-fold more potent than free MMAF on a large panel of CD30 positive hematologic cell lines. As with cAC10-L1-MMAE, the corresponding MMAF ADC induced cures and regressions of established xenograft tumors at well tolerated doses. To further optimize the ADC, several new linkers were generated in which various components within the L1 linker were either altered or deleted. One of the most promising linkers contained a noncleavable maleimidocaproyl (L4) spacer between the drug and the mAb. cAC10-L4-MMAF was approximately as potent in vitro as cAC10-L1-MMAF against a large panel of cell lines and was equally potent in vivo. Importantly, cAC10-L4-MMAF was tolerated at >3 times the MTD of cAC10-L1-MMAF. LCMS studies indicated that drug released from cAC10-L4-MMAF was the cysteine-L4-MMAF adduct, which likely arises from mAb degradation within the lysosomes of target cells. This new linker technology appears to be ideally suited for drugs that are both relatively cell-impermeable and tolerant of substitution with amino acids. Thus, alterations of the linker have pronounced impacts on toxicity and lead to new ADCs with greatly improved therapeutic indices.\n\nIndexed on Europe PMC as PubMed record 16417259 (DOI 10.1021/bc0502917). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Bioconjug Chem 2006","url":"https://doi.org/10.1021/bc0502917"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/16417259/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/16417259"}],"tags":["europepmc-ingest"],"related":["mc-non-cleavable"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Bioconjugate chemistry","year":2006,"doi":"10.1021/bc0502917","pmid":"16417259","authors":"Doronina SO, Mendelsohn BA, Bovee TD, et al.","paperType":"basic","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-kurtz-nat-biotechnol","kind":"paper","name":"Enhanced detection of minimal residual disease by targeted sequencing of phased variants in circulating tumor DNA","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 34294911 and published in Nature Biotechnology; the citing page links this DOI, which is how the record was matched.","summary":"Circulating tumor-derived DNA (ctDNA) is an emerging biomarker for many cancers, but the limited sensitivity of current detection methods reduces its utility for diagnosing minimal residual disease. Here we describe phased variant enrichment and detection sequencing (PhasED-seq), a method that uses multiple somatic mutations in individual DNA fragments to improve the sensitivity of ctDNA detection. Leveraging whole-genome sequences from 2,538 tumors, we identify phased variants and their associations with mutational signatures. We show that even without molecular barcodes, the limits of detection of PhasED-seq outperform prior methods, including duplex barcoding, allowing ctDNA detection in the ppm range in participant samples. We profiled 678 specimens from 213 participants with B cell lymphomas, including serial cell-free DNA samples before and during therapy for diffuse large B cell lymphoma. In participants with undetectable ctDNA after two cycles of therapy using a next-generation sequencing-based approach termed cancer personalized profiling by deep sequencing, an additional 25% have ctDNA detectable by PhasED-seq and have worse outcomes. Finally, we demonstrate the application of PhasED-seq to solid tumors.\n\nIndexed on Europe PMC as PubMed record 34294911 (DOI 10.1038/s41587-021-00981-w). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Biotechnol 2021","url":"https://doi.org/10.1038/s41587-021-00981-w"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34294911/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34294911"}],"tags":["europepmc-ingest"],"related":["ctdna-lymphoma-monitoring","lymphoma-roadmap","paper-scherer-ctdna-lymphoma-subtypes-genome-evolution-sci-transl-med-2016","lymphoma-ev-ctdna-instead-of-the-interim-scan"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-biotechnology"],"dependsOn":[],"notes":[],"journal":"Nature Biotechnology","year":2021,"doi":"10.1038/s41587-021-00981-w","pmid":"34294911","authors":"Kurtz DM, Soo J, Co Ting Keh L, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nct06120140-j-thorac-oncol-2025","kind":"paper","name":"Enhanced Versus Standard Dermatologic Management With Amivantamab-Lazertinib in EGFR-Mutated Advanced NSCLC: The COCOON Global Randomized Controlled Trial","aka":[],"tldr":"Published report from the COCOON trial registered as NCT06120140, in Journal of Thoracic Oncology (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Introduction: Amivantamab plus lazertinib significantly improved progression-free and overall survival versus osimertinib in patients with previously untreated, EGFR-mutant advanced NSCLC. EGFR-targeted therapies are associated with dermatologic adverse events (AEs), which can affect quality of life (QoL). COCOON was conducted to assess prophylactic management and improve treatment experience.\n\nMethods: In the phase 2 COCOON study (NCT06120140), participants with previously untreated, EGFR-mutant, locally advanced or metastatic NSCLC received intravenous amivantamab plus oral lazertinib and were randomized 1:1 to enhanced dermatologic management (COCOON DM) or standard of care (SoC DM) per local guidelines. COCOON DM included oral doxycycline or minocycline (100 mg twice daily; weeks 1-12), clindamycin 1% (on scalp daily; weeks 13-52), chlorhexidine 4% (on fingernails and toenails daily), and ceramide-based moisturizer (on body and face at least daily). Primary end point was incidence of grade 2 or higher dermatologic AEs of interest (DAEIs) by week 12.\n\nResults: In total, 201 participants were randomized (99 to COCOON DM and 102 to SoC DM). At a median follow-up of 7.1 months, COCOON DM demonstrated significant reduction in the primary end point versus SoC DM (42% versus 75%; OR, 0.24; 95% confidence interval, 0.13-0.45; p < 0.0001). By week 12, the largest benefit with COCOON DM was observed in DAEIs involving the face and body (excludes paronychia; 26% versus 60%; p < 0.0001) and DAEIs involving the scalp (10% versus 26%; p = 0.0049). This benefit was maintained at 6 months, with significant reductions of DAEIs involving face, body, and scalp (excluding paronychia). Patient-reported outcomes favored COCOON DM, indicating reduced impact of dermatologic symptoms on QoL.\n\nConclusion: An uncomplicated, widely available, prophylactic regimen (COCOON DM) reduced the incidence of DAEIs with amivantamab-lazertinib and the impact of symptoms on QoL.\n\nIndexed on Europe PMC as PubMed record 40923969 (DOI 10.1016/j.jtho.2025.07.117). Its abstract cites the registry id NCT06120140, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Thorac Oncol 2025","url":"https://doi.org/10.1016/j.jtho.2025.07.117"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40923969/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40923969"},{"label":"ClinicalTrials.gov NCT06120140","url":"https://clinicaltrials.gov/study/NCT06120140"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct06120140"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-thoracic-oncology"],"dependsOn":[],"notes":[],"journal":"Journal of Thoracic Oncology","year":2025,"doi":"10.1016/j.jtho.2025.07.117","pmid":"40923969","authors":"Cho BC, Li W, Spira AI, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT06120140 with the most citations, so it is the natural first reading for anyone following the COCOON trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-ezh2-sarcoma-bmc-med-2011","kind":"paper","name":"Enhancer of zeste homolog 2 (EZH2) in pediatric soft tissue sarcomas: first implications","aka":[],"tldr":"Review on EZH2 in Sarcomas, in BMC medicine (2011), one of the most cited Europe PMC records with EZH2 in its title.","summary":"Soft tissue sarcomas of childhood are a group of heterogeneous tumors thought to be derived from mesenchymal stem cells. Surgical resection is effective only in about 50% of cases and resistance to conventional chemotherapy is often responsible for treatment failure. Therefore, investigations on novel therapeutic targets are of fundamental importance. Deregulation of epigenetic mechanisms underlying chromatin modifications during stem cell differentiation has been suggested to contribute to soft tissue sarcoma pathogenesis. One of the main elements in this scenario is enhancer of zeste homolog 2 (EZH2), a methyltransferase belonging to the Polycomb group proteins. EZH2 catalyzes histone H3 methylation on gene promoters, thus repressing genes that induce stem cell differentiation to maintain an embryonic stem cell signature. EZH2 deregulated expression/function in soft tissue sarcomas has been recently reported. In this review, an overview of the recently reported functions of EZH2 in soft tissue sarcomas is given and the hypothesis that its expression might be involved in soft tissue sarcomagenesis is discussed. Finally, the therapeutic potential of epigenetic therapies modulating EZH2-mediated gene repression is considered.\n\nIndexed on Europe PMC as PubMed record 21609503 (DOI 10.1186/1741-7015-9-63). Its title names EZH2 and its text names Sarcomas; PubMed types it as a review (Research Support, Non-U.S. Gov't, review-article, Review). It was matched automatically to the idea \"Group trials by broken mechanism, not by organ or single mutation\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"BMC Med 2011","url":"https://doi.org/10.1186/1741-7015-9-63"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21609503/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/21609503"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"BMC medicine","year":2011,"doi":"10.1186/1741-7015-9-63","pmid":"21609503","authors":"Ciarapica R, Miele L, Giordano A, et al.","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for EZH2 in Sarcomas, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by EZH2 in the title and Sarcomas in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-enrgy-zenocutuzumab-nrg1-fusion-positive-cancer-nejm-2025","kind":"paper","name":"eNRGy: efficacy of zenocutuzumab in NRG1 fusion-positive cancer","aka":[],"tldr":"Zenocutuzumab, an antibody that grips HER2 and HER3 at once so the NRG1 growth signal cannot get through, shrank tumours in about three in ten patients whose cancers carried an NRG1 fusion, with responses lasting close to a year, and did best in pancreatic cancer. It became the first drug approved for a pancreatic cancer driver alteration.","summary":"Phase 2 registrational analysis of the eNRGy basket trial of zenocutuzumab 750 mg every two weeks in patients with advanced NRG1 fusion-positive solid tumours, mostly non-small-cell lung cancer and pancreatic cancer, who had progressed on standard therapy. Among efficacy-evaluable patients the objective response rate was about 30 percent with a median duration of response of about 11 months; the response rate in pancreatic cancer was higher, around 40 percent.\n\nThe drug was well tolerated, with diarrhoea, fatigue and infusion-related reactions the commonest adverse events and few discontinuations. The US FDA granted accelerated approval in December 2024 for NRG1 fusion-positive non-small-cell lung cancer and pancreatic adenocarcinoma after prior systemic therapy.","asOf":"2026-09-21","links":[{"label":"N Engl J Med 2025","url":"https://doi.org/10.1056/NEJMoa2405008"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39908431/"}],"tags":[],"related":[],"cancers":["kras-wild-type-pdac","pancreatic"],"sections":[],"technologies":[],"targets":["nrg1","her2","her3"],"drugs":["zenocutuzumab"],"companies":[],"institutions":[],"pathways":["rtk-activation"],"terms":["wild-type","tumour-agnostic"],"trials":["nct02912949"],"people":["eileen-oreilly","alexander-drilon"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2025,"doi":"10.1056/NEJMoa2405008","pmid":"39908431","authors":"Schram AM, Goto K, Kim DW, et al.","paperType":"observational","findings":["Objective response about 30 percent across NRG1 fusion-positive cancers, median duration of response about 11 months.","Higher response rate in pancreatic cancer, around 40 percent.","Accelerated FDA approval for NRG1 fusion-positive lung and pancreatic cancer followed in December 2024."],"whatItMeans":"Every KRAS wild-type pancreatic cancer should be tested for NRG1 fusions because a specific, approved antibody now exists; zenocutuzumab is the first targeted drug approved for a pancreatic cancer driver.","caveats":["Single-arm basket trial; approval is accelerated and conditional on confirmatory data.","NRG1 fusions are present in well under 1 percent of pancreatic cancers overall, so the eligible population is small."],"changedPractice":true},{"id":"paper-nct02767804-jama-oncol-2021","kind":"paper","name":"Ensartinib vs Crizotinib for Patients With Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer: A Randomized Clinical Trial","aka":[],"tldr":"Published report from the trial registered as NCT02767804, in JAMA Oncology (2021), chosen as the most cited paper whose own text cites the registry id.","summary":"Importance: Ensartinib, an oral tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK), has shown systemic and central nervous system efficacy for patients with ALK-positive non-small cell lung cancer (NSCLC).\n\nObjective: To compare ensartinib with crizotinib among patients with advanced ALK-positive NSCLC who had not received prior treatment with an ALK inhibitor.\n\nDesign, setting, and participants: This open-label, multicenter, randomized, phase 3 trial conducted in 120 centers in 21 countries enrolled 290 patients between July 25, 2016, and November 12, 2018. Eligible patients were 18 years of age or older and had advanced, recurrent, or metastatic ALK-positive NSCLC.\n\nInterventions: Patients were randomized (1:1) to ensartinib, 225 mg once daily, or crizotinib, 250 mg twice daily.\n\nMain outcomes and measures: The primary end point was blinded independent review committee-assessed progression-free survival (PFS). Secondary end points included systemic and intracranial response, time to central nervous system progression, and overall survival. Efficacy was evaluated in the intent-to-treat (ITT) population as well as a prespecified modified ITT (mITT) population consisting of patients with central laboratory-confirmed ALK-positive NSCLC.\n\nResults: A total of 290 patients (149 men [51.4%]; median age, 54 years [range, 25-90 years]) were randomized. In the ITT population, the median PFS was significantly longer with ensartinib than with crizotinib (25.8 [range, 0.03-44.0 months] vs 12.7 months [range, 0.03-38.6 months]; hazard ratio, 0.51 [95% CI, 0.35-0.72]; log-rank P <.001), with a median follow-up of 23.8 months (range, 0-44 months) for the ensartinib group and 20.2 months (range, 0-38 months) for the crizotinib group. In the mITT population, the median PFS in the ensartinib group was not reached, and the median PFS in the crizotinib group was 12.7 months (95% CI, 8.9-16.6 months; hazard ratio, 0.45; 95% CI, 0.30-0.66; log-rank P <.001). The intracranial response rate confirmed by a blinded independent review committee was 63.6% (7 of 11) with ensartinib vs 21.1% (4 of 19) with crizotinib for patients with target brain metastases at baseline. Progression-free survival for patients without brain metastases was not reached with ensartinib vs 16.6 months with crizotinib as a result of a lower central nervous system progression rate (at 12 months: 4.2% with ensartinib vs 23.9% with crizotinib; cause-specific hazard ratio, 0.32; 95% CI, 0.16-0.63; P =.001). Frequencies of treatment-related serious adverse events (ensartinib: 11 [7.7%] vs crizotinib: 9 [6.1%]), dose reductions (ensartinib: 34 of 143 [23.8%] vs crizotinib: 29 of 146 [19.9%]), or drug discontinuations (ensartinib: 13 of 143 [9.1%] vs crizotinib: 10 of 146 [6.8%]) were similar, without any new safety signals.\n\nConclusions and relevance: In this randomized clinical trial, ensartinib showed superior efficacy to crizotinib in both systemic and intracranial disease. Ensartinib represents a new first-line option for patients with ALK-positive NSCLC.\n\nTrial registration: ClinicalTrials.gov Identifier: NCT02767804.\n\nIndexed on Europe PMC as PubMed record 34473194 (DOI 10.1001/jamaoncol.2021.3523). Its abstract cites the registry id NCT02767804, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"JAMA Oncol 2021","url":"https://doi.org/10.1001/jamaoncol.2021.3523"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34473194/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34473194"},{"label":"ClinicalTrials.gov NCT02767804","url":"https://clinicaltrials.gov/study/NCT02767804"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct02767804"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2021,"doi":"10.1001/jamaoncol.2021.3523","pmid":"34473194","authors":"Horn L, Wang Z, Wu G, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02767804 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-doebele-entrectinib-ntrk-lancet-oncol-2020","kind":"paper","name":"Entrectinib in NTRK fusion-positive solid tumours: integrated analysis of three trials","aka":[],"tldr":"Entrectinib, a TRK and ROS1 inhibitor that enters the brain, shrank tumours in more than half of patients with NTRK fusion-positive cancers of ten types and controlled brain metastases, leading to a tumour-agnostic approval alongside larotrectinib.","summary":"Integrated analysis of 54 adults with NTRK fusion-positive solid tumours from the ALKA-372-001, STARTRK-1 and STARTRK-2 trials treated with entrectinib.\n\nObjective response was 57 percent with a median duration of response of 10 months and intracranial response in half of the patients with brain metastases; toxicity included weight gain, dizziness and dysgeusia.","asOf":"2026-09-17","links":[{"label":"Lancet Oncol 2020","url":"https://doi.org/10.1016/S1470-2045(19)30691-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31838007/"}],"tags":[],"related":[],"cancers":["ntrk-fusion-nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":["entrectinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["robert-doebele"],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2020,"doi":"10.1016/S1470-2045(19)30691-6","pmid":"31838007","authors":"Doebele RC, Drilon A, Paz-Ares L, et al.","paperType":"observational","findings":["Objective response 57 percent; median duration of response 10 months.","Intracranial response in 50 percent of patients with brain metastases."],"whatItMeans":"Entrectinib is an approved tumour-agnostic TRK inhibitor with an advantage in patients with brain metastases, and it is also approved for ROS1-positive lung cancer.","caveats":["Small pooled population; median progression-free survival 11 months."],"changedPractice":true,"participants":54},{"id":"paper-drilon-entrectinib-ros1-lancet-oncol-2020","kind":"paper","name":"Entrectinib in ROS1 fusion-positive non-small-cell lung cancer: integrated analysis of three trials","aka":[],"tldr":"Entrectinib shrank tumours in more than three quarters of patients with ROS1-positive lung cancer and, unlike crizotinib, controlled brain metastases in most patients who had them, earning approval as a first-line option.","summary":"Integrated analysis of 53 ROS1 inhibitor-naive patients with ROS1 fusion-positive non-small-cell lung cancer from the ALKA-372-001, STARTRK-1 and STARTRK-2 trials treated with entrectinib.\n\nObjective response was 77 percent with median duration of response 24.6 months and median progression-free survival 19.0 months; intracranial response was 55 percent in patients with brain metastases.","asOf":"2026-09-17","links":[{"label":"Lancet Oncol 2020","url":"https://doi.org/10.1016/S1470-2045(19)30690-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31838015/"}],"tags":[],"related":[],"cancers":["ros1-positive-nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":["entrectinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2020,"doi":"10.1016/S1470-2045(19)30690-4","pmid":"31838015","authors":"Drilon A, Siena S, Dziadziuszko R, et al.","paperType":"observational","findings":["Objective response 77 percent; median progression-free survival 19.0 months.","Intracranial response 55 percent."],"whatItMeans":"Entrectinib is a first-line ROS1 inhibitor with brain activity, preferred over crizotinib when brain metastases are present, though repotrectinib and taletrectinib now offer longer control.","caveats":["Single-arm pooled analysis; does not cover the G2032R resistance mutation."],"changedPractice":true,"participants":53},{"id":"paper-traina-enzalutamide-ar-tnbc-jco-2018","kind":"paper","name":"Enzalutamide for the treatment of androgen receptor-expressing triple-negative breast cancer","aka":[],"tldr":"Enzalutamide gave clinical benefit at 16 weeks to a quarter of women with androgen receptor-expressing triple-negative breast cancer, a third among those with 10% or more staining, with fatigue the only common severe side effect.","summary":"Phase 2 study of enzalutamide 160 mg daily in locally advanced or metastatic AR-positive TNBC (nuclear AR staining above 0% by a breast-optimised assay). Of 118 enrolled, 78 were evaluable (10% or more nuclear AR with a post-baseline assessment). Clinical benefit at 16 weeks was 25% (intention-to-treat) and 33% (evaluable); median progression-free survival 2.9 and 3.3 months; median overall survival 12.7 and 17.6 months. Fatigue was the only grade 3 or higher related event above 2%.","asOf":"2026-09-24","links":[{"label":"Traina et al., J Clin Oncol 2018: enzalutamide in AR-expressing TNBC","url":"https://doi.org/10.1200/JCO.2016.71.3495"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29373071/"}],"tags":[],"related":[],"cancers":["tnbc","tnbc-metastatic"],"sections":[],"technologies":[],"targets":["androgen-receptor"],"drugs":["enzalutamide"],"companies":[],"institutions":[],"pathways":["ar-signaling"],"terms":[],"trials":[],"people":["peter-schmid","eric-winer"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2018,"doi":"10.1200/JCO.2016.71.3495","pmid":"29373071","authors":"Traina TA, Miller K, Yardley DA, et al.","paperType":"rct","findings":["Clinical benefit at 16 weeks 25% (ITT) and 33% (AR 10% or more).","Median overall survival 12.7 (ITT) and 17.6 months (evaluable)."],"whatItMeans":"Enzalutamide works modestly in AR-positive TNBC and is the reference for the LAR subtype's therapy implication; the AR threshold used for eligibility changes who counts as positive.","caveats":["Single-arm phase 2; the phase 3 was not pursued.","A companion gene signature (PREDICT AR) was explored but is not validated."],"changedPractice":false,"participants":118},{"id":"paper-enzamet-n-engl-j-med-2019","kind":"paper","name":"Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer","aka":[],"tldr":"Published report from the ENZAMET trial registered as NCT02446405, in New England Journal of Medicine (2019), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Enzalutamide, an androgen-receptor inhibitor, has been associated with improved overall survival in men with castration-resistant prostate cancer. It is not known whether adding enzalutamide to testosterone suppression, with or without early docetaxel, will improve survival in men with metastatic, hormone-sensitive prostate cancer.\n\nMethods: In this open-label, randomized, phase 3 trial, we assigned patients to receive testosterone suppression plus either open-label enzalutamide or a standard nonsteroidal antiandrogen therapy (standard-care group). The primary end point was overall survival. Secondary end points included progression-free survival as determined by the prostate-specific antigen (PSA) level, clinical progression-free survival, and adverse events.\n\nResults: A total of 1125 men underwent randomization; the median follow-up was 34 months. There were 102 deaths in the enzalutamide group and 143 deaths in the standard-care group (hazard ratio, 0.67; 95% confidence interval [CI], 0.52 to 0.86; P = 0.002). Kaplan-Meier estimates of overall survival at 3 years were 80% (based on 94 events) in the enzalutamide group and 72% (based on 130 events) in the standard-care group. Better results with enzalutamide were also seen in PSA progression-free survival (174 and 333 events, respectively; hazard ratio, 0.39; P<0.001) and in clinical progression-free survival (167 and 320 events, respectively; hazard ratio, 0.40; P<0.001). Treatment discontinuation due to adverse events was more frequent in the enzalutamide group than in the standard-care group (33 events and 14 events, respectively). Fatigue was more common in the enzalutamide group; seizures occurred in 7 patients in the enzalutamide group (1%) and in no patients in the standard-care group.\n\nConclusions: Enzalutamide was associated with significantly longer progression-free and overall survival than standard care in men with metastatic, hormone-sensitive prostate cancer receiving testosterone suppression. The enzalutamide group had a higher incidence of seizures and other toxic effects, especially among those treated with early docetaxel. (Funded by Astellas Scientific and Medical Affairs and others; ENZAMET (ANZUP 1304) ANZCTR number, ACTRN12614000110684; ClinicalTrials.gov number, NCT02446405; and EU Clinical Trials Register number, 2014-003190-42.).\n\nIndexed on Europe PMC as PubMed record 31157964 (DOI 10.1056/nejmoa1903835). Its abstract cites the registry id NCT02446405, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2019","url":"https://doi.org/10.1056/nejmoa1903835"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31157964/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31157964"},{"label":"ClinicalTrials.gov NCT02446405","url":"https://clinicaltrials.gov/study/NCT02446405"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["enzamet"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2019,"doi":"10.1056/nejmoa1903835","pmid":"31157964","authors":"Davis ID, Martin AJ, Stockler MR, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02446405 with the most citations, so it is the natural first reading for anyone following the ENZAMET trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-roberts-pert-survival-pancreatic-cancer-pancreatology-2019","kind":"paper","name":"Enzyme replacement improves survival among patients with pancreatic cancer: Results of a population based study","aka":[],"tldr":"A 2019 study of UK primary care records finding that only about one in five people with pancreatic cancer was prescribed the digestive enzyme capsules that replace what the diseased pancreas no longer makes, and that those who were lived markedly longer.","summary":"Roberts, Bannister and Schrem identified patients with pancreatic adenocarcinoma in the UK Clinical Practice Research Datalink and used propensity score matching to compare those who did and did not receive pancreatic enzyme replacement therapy. Use across the whole cohort was 21.7 percent (987 of 4,554). From 1,614 subjects, 807 matched pairs gave 1,643 years of censored follow-up and 1,403 deaths; unadjusted mortality was 748 versus 994 deaths per 1,000 person-years. Adjusted median survival time was 262 percent greater in treated patients (survival time ratio 2.62, 95 percent confidence interval 2.27 to 3.02), and remained greater in every subgroup by surgery or chemotherapy. The authors concluded that most patients do not receive enzyme replacement and that the association suggests a lack of clinical awareness and a benefit from addressing malnutrition.","asOf":"2026-09-24","links":[{"label":"Pancreatology 2019","url":"https://doi.org/10.1016/j.pan.2018.10.010"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30385188/"},{"label":"NICE NG85: pancreatic cancer in adults (2018), including enzyme replacement","url":"https://www.nice.org.uk/guidance/ng85"},{"label":"National Pancreatic Cancer Audit reports (NATCAN)","url":"https://www.natcan.org.uk/reports/?audit=pancreatic"}],"tags":["pancreatic-evidence"],"related":["paper-traverso-longmire-pylorus-preservation-pancreaticoduodenectomy-sgo-1978","paper-fearon-lancet-oncol"],"cancers":["pancreatic"],"sections":["supportive-care","nutrition-lifestyle"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-cachexia-supportive","b-knowledge-diffusion","b-care-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Pancreatology","year":2019,"doi":"10.1016/j.pan.2018.10.010","pmid":"30385188","authors":"Roberts KJ, Bannister CA, Schrem H.","paperType":"real-world","findings":["Enzyme replacement prescribed to 21.7 percent of 4,554 UK patients with pancreatic adenocarcinoma.","807 propensity-matched pairs; mortality 748 versus 994 per 1,000 person-years.","Adjusted survival time ratio 2.62 (95 percent confidence interval 2.27 to 3.02), consistent across surgery and chemotherapy subgroups."],"whatItMeans":"Enzyme replacement is cheap, guideline-recommended (NICE NG85) and under-prescribed; the National Pancreatic Cancer Audit now reports the prescribing rate as a performance indicator, which the UK and NHS page tracks.","caveats":["Observational; patients well enough to be prescribed and take enzymes may live longer for other reasons, and matching cannot remove all of that.","Primary care prescribing data may miss hospital-issued prescriptions."],"participants":4554},{"id":"paper-bolla-eortc-22863-nejm-1997","kind":"paper","name":"EORTC 22863: improved survival with radiotherapy plus goserelin in locally advanced prostate cancer","aka":[],"tldr":"Adding three years of hormone therapy to radiotherapy for locally advanced prostate cancer improved five-year survival from 62 to 79 percent, establishing long-term androgen deprivation with radiotherapy as the standard for high-risk disease.","summary":"Phase 3 trial of 415 men with locally advanced (T3 to T4 or high-grade T1 to T2) prostate cancer randomised to external beam radiotherapy alone or with goserelin started at the beginning of radiotherapy and continued for three years.\n\nFive-year overall survival was 79 versus 62 percent and disease-free survival 85 versus 48 percent; ten-year follow-up confirmed a persistent survival benefit (58.1 versus 39.8 percent).","asOf":"2026-09-17","links":[{"label":"N Engl J Med 1997","url":"https://doi.org/10.1056/NEJM199707313370502"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/9233866/"}],"tags":[],"related":[],"cancers":["prostate-high-risk"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":1997,"doi":"10.1056/NEJM199707313370502","pmid":"9233866","authors":"Bolla M, Gonzalez D, Warde P, et al.","paperType":"rct","findings":["Five-year overall survival 79 percent vs 62 percent.","Ten-year overall survival 58.1 percent vs 39.8 percent."],"whatItMeans":"Long-term androgen deprivation (18 to 36 months) with radiotherapy remains the backbone for high-risk localised prostate cancer, to which abiraterone is now added for the highest-risk men.","caveats":["Radiotherapy doses were lower than modern standards.","Optimal duration of hormone therapy was refined by later trials (EORTC 22961, DART 01/05)."],"changedPractice":true,"participants":415},{"id":"paper-bernier-eortc-22931-nejm-2004","kind":"paper","name":"EORTC 22931: postoperative irradiation with or without concomitant cisplatin for locally advanced head and neck cancer","aka":[],"tldr":"Adding cisplatin to radiotherapy after surgery for high-risk head and neck cancer improved local control and survival, and with the parallel American trial defined extranodal extension and positive margins as the indications for postoperative chemoradiation.","summary":"Phase 3 trial of 334 patients with resected stage III to IV head and neck squamous cell carcinoma with high-risk features randomised to postoperative radiotherapy alone or with three cycles of concurrent cisplatin.\n\nFive-year progression-free survival was 47 versus 36 percent and overall survival 53 versus 40 percent with chemoradiation, with more severe acute mucositis; a combined analysis with RTOG 9501 showed the benefit was confined to patients with extranodal extension or positive margins.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2004","url":"https://doi.org/10.1056/NEJMoa032641"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/15128894/"}],"tags":[],"related":[],"cancers":["hpv-negative-head-and-neck-cancer","oral-tongue-cancer","oral-cavity-cancer","buccal-mucosa-cancer","lip-cancer","mucoepidermoid-carcinoma","salivary-duct-carcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2004,"doi":"10.1056/NEJMoa032641","pmid":"15128894","authors":"Bernier J, Domenge C, Ozsahin M, et al.","paperType":"rct","findings":["Five-year overall survival 53 percent vs 40 percent.","Five-year locoregional relapse 18 percent vs 31 percent."],"whatItMeans":"Cisplatin chemoradiation after surgery is standard for extranodal extension or involved margins; radiotherapy alone suffices for other adverse features.","caveats":["Cisplatin at 100 mg per square metre every three weeks is poorly tolerated; weekly dosing is common in practice.","Trial predates HPV stratification."],"changedPractice":true,"participants":334},{"id":"paper-eortc-24891-larynx-preservation-lefebvre-jnci-1996","kind":"paper","name":"EORTC 24891: larynx preservation with induction chemotherapy in pyriform sinus (hypopharyngeal) cancer","aka":[],"tldr":"In hypopharyngeal cancer that would otherwise require removal of the voice box, induction chemotherapy followed by radiotherapy in responders gave survival equal to immediate laryngectomy and let about half of survivors keep a functioning larynx.","summary":"Phase 3 trial of 202 patients with resectable pyriform sinus or aryepiglottic fold cancer randomised to immediate total laryngectomy with partial pharyngectomy and postoperative radiotherapy, or induction cisplatin-fluorouracil followed by radiotherapy in complete responders and surgery in the rest.\n\nMedian survival was 44 months with induction chemotherapy against 25 months with surgery (not significantly different, meeting the non-inferiority aim), and at three years 42 percent of surviving patients in the chemotherapy arm had a functional larynx; ten-year follow-up confirmed equivalence.","asOf":"2026-09-17","links":[{"label":"J Natl Cancer Inst 1996","url":"https://doi.org/10.1093/jnci/88.13.890"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/8656441/"}],"tags":[],"related":[],"cancers":["hypopharyngeal-cancer","laryngeal-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jnci"],"dependsOn":[],"notes":[],"journal":"JNCI: Journal of the National Cancer Institute","year":1996,"doi":"10.1093/jnci/88.13.890","pmid":"8656441","authors":"Lefebvre JL, Chevalier D, Luboinski B, et al.","paperType":"rct","findings":["Median overall survival 44 vs 25 months (not significant).","Functional larynx preserved in 42 percent of survivors at three years."],"whatItMeans":"Organ preservation is an accepted alternative to laryngectomy for hypopharyngeal cancer; concurrent chemoradiation has largely replaced sequential induction chemotherapy and radiotherapy.","caveats":["Small trial; survival in hypopharyngeal cancer remains poor with either approach.","Sequential rather than concurrent chemoradiation."],"changedPractice":true,"participants":202},{"id":"paper-eortc-26951-van-den-bent-jco-2013","kind":"paper","name":"EORTC 26951: adjuvant PCV after radiotherapy for anaplastic oligodendroglial tumours, long-term follow-up","aka":[],"tldr":"This European trial confirmed, independently of the American RTOG 9402 study, that PCV chemotherapy added to radiotherapy lengthens survival in anaplastic oligodendroglioma, with the largest benefit in tumours carrying the 1p/19q codeletion.","summary":"Phase 3 trial of 368 patients with anaplastic oligodendroglial tumours randomised to radiotherapy alone or radiotherapy followed by six cycles of PCV, reported at a median follow-up of 140 months.\n\nMedian overall survival was 42.3 months with PCV against 30.6 months without (hazard ratio 0.75); in the 80 patients with 1p/19q codeletion median survival was not reached with PCV against 112 months without (hazard ratio 0.56), and IDH mutation and MGMT methylation were also prognostic.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2013","url":"https://doi.org/10.1200/JCO.2012.43.2229"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23071237/"}],"tags":[],"related":[],"cancers":["oligodendroglioma"],"sections":[],"technologies":[],"targets":[],"drugs":["procarbazine","vincristine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["eortc-26951","codel"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2013,"doi":"10.1200/JCO.2012.43.2229","pmid":"23071237","authors":"van den Bent MJ, Brandes AA, Taphoorn MJ, et al.","paperType":"rct","findings":["Median overall survival 42.3 vs 30.6 months overall; hazard ratio 0.75.","1p/19q-codeleted: median survival not reached vs 112 months; hazard ratio 0.56."],"whatItMeans":"Together with RTOG 9402, this trial made radiotherapy followed by PCV the standard for 1p/19q-codeleted anaplastic oligodendroglioma; the CODEL trial is now comparing PCV with temozolomide.","caveats":["Codeleted subgroup was small.","About a third of patients did not complete PCV because of toxicity."],"changedPractice":true,"participants":368},{"id":"paper-eortc-62012-doxorubicin-ifosfamide-judson-lancet-oncol-2014","kind":"paper","name":"EORTC 62012: doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced soft tissue sarcoma","aka":[],"tldr":"Adding ifosfamide to doxorubicin for advanced soft tissue sarcoma doubled the response rate and delayed progression but did not lengthen survival and caused much more toxicity, so doxorubicin alone remains the default unless shrinkage is needed.","summary":"Phase 3 trial of 455 patients with advanced high-grade soft tissue sarcoma randomised to doxorubicin 75 mg per square metre alone or with ifosfamide 10 g per square metre and growth factor support.\n\nMedian overall survival was 14.3 versus 12.8 months (hazard ratio 0.83, not significant), median progression-free survival 7.4 versus 4.6 months, and response 26 versus 14 percent; febrile neutropenia and other grade 3 to 4 toxicities were far more frequent with the combination.","asOf":"2026-09-17","links":[{"label":"Lancet Oncol 2014","url":"https://doi.org/10.1016/S1470-2045(14)70063-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24618336/"}],"tags":[],"related":[],"cancers":["malignant-peripheral-nerve-sheath-tumour","extremity-soft-tissue-sarcoma","undifferentiated-pleomorphic-sarcoma","leiomyosarcoma","myxofibrosarcoma","synovial-sarcoma"],"sections":[],"technologies":[],"targets":[],"drugs":["doxorubicin","ifosfamide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["eortc-62012"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2014,"doi":"10.1016/S1470-2045(14)70063-4","pmid":"24618336","authors":"Judson I, Verweij J, Gelderblom H, et al.","paperType":"rct","findings":["Median overall survival 14.3 vs 12.8 months (not significant).","Objective response 26 percent vs 14 percent; median progression-free survival 7.4 vs 4.6 months."],"whatItMeans":"Single-agent doxorubicin is the standard first-line palliative treatment for most advanced sarcomas, with doxorubicin-ifosfamide reserved for fit patients in whom tumour shrinkage matters.","caveats":["Excluded some histologies; benefit may differ by subtype (for example synovial sarcoma is ifosfamide-sensitive)."],"changedPractice":true,"participants":455},{"id":"paper-sylvester-eortc-risk-tables-eur-urol-2006","kind":"paper","name":"EORTC risk tables for recurrence and progression in Ta and T1 bladder cancer","aka":[],"tldr":"Pooling seven trials, this analysis produced the scoring tables that clinicians still use to estimate how likely a non-muscle-invasive bladder tumour is to come back or to progress into the muscle.","summary":"Analysis of 2,596 patients with Ta or T1 bladder cancer from seven EORTC trials, mostly treated with transurethral resection and intravesical chemotherapy, to identify factors predicting recurrence and progression.\n\nNumber of tumours, size, prior recurrence rate, T category, carcinoma in situ and grade were combined into scores giving one- and five-year probabilities of recurrence and progression. The tables underpin the low, intermediate and high-risk groups used in guidelines.","asOf":"2026-09-17","links":[{"label":"Eur Urol 2006","url":"https://doi.org/10.1016/j.eururo.2005.12.031"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/16442208/"}],"tags":[],"related":[],"cancers":["non-muscle-invasive-bladder-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["european-urology"],"dependsOn":[],"notes":[],"journal":"European Urology","year":2006,"doi":"10.1016/j.eururo.2005.12.031","pmid":"16442208","authors":"Sylvester RJ, van der Meijden AP, Oosterlinck W, et al.","paperType":"observational","findings":["Five-year progression risk ranged from under 1 percent in the lowest score group to 45 percent in the highest.","Five-year recurrence risk ranged from 31 percent to 78 percent."],"whatItMeans":"The risk groups that decide whether a patient gets a single chemotherapy instillation, BCG, or early cystectomy trace back to this work. Later models (CUETO, the 2021 EAU risk groups) refine the estimates for BCG-treated patients.","caveats":["Few patients received BCG maintenance or re-resection, so the tables overestimate risk under modern care.","Grading used the 1973 WHO system."],"changedPractice":true,"participants":2596},{"id":"paper-epcore-nhl-1-epcoritamab-jco-2023","kind":"paper","name":"EPCORE NHL-1: epcoritamab, a subcutaneous CD20 x CD3 bispecific, in relapsed large B-cell lymphoma including after CAR-T","aka":[],"tldr":"In EPCORE NHL-1, the off-the-shelf bispecific antibody epcoritamab, injected under the skin, produced responses in 63% of 157 patients with relapsed large B-cell lymphoma, including the 39% whose CAR-T had failed. Cytokine release syndrome occurred in half, mostly mild, and the drug won accelerated approval in 2023.","summary":"The dose-expansion part of EPCORE NHL-1 treated 157 patients with relapsed or refractory large B-cell lymphoma after at least two prior lines (median three; 39% had prior CAR-T) with subcutaneous epcoritamab given with step-up dosing then weekly, fortnightly and monthly. The overall response rate was 63.1% with complete response in 38.9%; median duration of response was 12.0 months and complete responders had durable remissions. CRS occurred in 49.7% (grade 3 in 2.5%) and ICANS in 6.4% with one fatal event. Responses were similar after CAR-T failure. Epcoritamab received accelerated approval in 2023, alongside the intravenous CD20 x CD3 bispecific glofitamab, whose pivotal study reported complete response in 39% of 155 patients.","asOf":"2026-09-08","links":[{"label":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=EPCORE%20NHL-1%20epcoritamab%20large%20B-cell%20lymphoma%20Thieblemont%20JCO%202023"},{"label":"ClinicalTrials.gov NCT03625037","url":"https://clinicaltrials.gov/study/NCT03625037"}],"tags":[],"related":["bispecific-plus-adc-lymphoma"],"cancers":["dlbcl","follicular-lymphoma"],"sections":[],"technologies":["bispecific-antibody","t-cell-engager"],"targets":["cd20","cd3"],"drugs":["epcoritamab","glofitamab","mosunetuzumab","odronextamab"],"companies":["abbvie","roche-genentech"],"institutions":[],"pathways":[],"terms":["crs","icans","orr"],"trials":["epcore-nhl-1","epcore-dlbcl-1","starglo"],"people":[],"bottlenecks":["b-manufacturing-cell-therapy","b-resistance"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2023,"doi":"10.1200/JCO.22.01725","pmid":"36548927","authors":"Thieblemont C, Phillips T, Ghesquieres H, et al.","paperType":"translational","findings":["157 patients with relapsed/refractory LBCL after 2 or more lines; 38.9% had prior CAR-T.","Overall response 63.1%; complete response 38.9%.","Median duration of response 12.0 months; most complete responses ongoing at data cut.","CRS 49.7% (grade 3 2.5%), largely confined to cycle 1; ICANS 6.4% (one fatal).","Similar response rates in patients whose CAR-T had failed."],"whatItMeans":"CD20 x CD3 bispecifics gave patients whose lymphoma has failed CAR-T, or who cannot access it, an effective off-the-shelf treatment that can be started within days. Epcoritamab and glofitamab are now standard third-line options and are moving into earlier lines and combinations. They do not yet replace CAR-T, whose remissions appear more durable.","caveats":["Single-arm phase 2; randomised confirmation in earlier lines came later with mixed results in some designs.","Fixed-duration (glofitamab) versus until-progression (epcoritamab) dosing remains a practical difference without head-to-head data.","Infection risk and hypogammaglobulinaemia accumulate with prolonged dosing.","Durability of partial responses is limited."],"changedPractice":true,"participants":157},{"id":"paper-epcoritamab-dlbcl-blood-2025","kind":"paper","name":"Epcoritamab plus GemOx in transplant-ineligible relapsed/refractory DLBCL: results from the EPCORE NHL-2 trial","aka":[],"tldr":"Phase 2 or 3 results paper on Epcoritamab in Diffuse large B-cell lymphoma, in Blood (2025), one of the most cited Europe PMC records with Epcoritamab in its title.","summary":"Abstract: Patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) have poor outcomes (complete response [CR] rates with standard salvage therapy gemcitabine plus oxaliplatin [GemOx], ∼30%; median overall survival [OS], 10 to 13 months). Patients with refractory disease fare worse (CR rate with salvage therapy, 7%; median OS, 6 months). Epcoritamab, a CD3×CD20 bispecific antibody approved for R/R DLBCL after ≥2 therapy lines, has shown promising safety and efficacy in various combinations. We report results from the phase 1b/2 EPCORE NHL-2 trial evaluating epcoritamab plus GemOx in autologous stem cell transplant (ASCT)-ineligible R/R DLBCL. Patients received 48 mg subcutaneous epcoritamab after 2 step-up doses until progression or unacceptable toxicity; GemOx was given once every 2 weeks for 8 doses. The primary end point was overall response rate (ORR). at 15 December 2023, 103 patients were enrolled (median follow-up, 13.2 months; median age, 72 years). Patients had challenging-to-treat disease: ≥2 prior therapy lines, 62%; prior chimeric antigen receptor T-cell therapy, 28%; primary refractory disease, 52%; refractory to last therapy, 70%. ORR and CR rate were 85% and 61%, respectively. Median duration of CR and OS were 23.6 and 21.6 months, respectively. Common treatment-emergent adverse events were cytopenias and cytokine release syndrome (CRS). CRS events had predictable timing, were primarily low grade (52% overall, 1% grade 3), and resolved without leading to discontinuation. Epcoritamab plus GemOx yielded deep, durable responses and favorable long-term outcomes in ASCT-ineligible R/R DLBCL. This trial was registered at www.clinicaltrials.gov as #NCT04663347.\n\nIndexed on Europe PMC as PubMed record 39792928 (DOI 10.1182/blood.2024026830). Its title names Epcoritamab and its text names Diffuse large B-cell lymphoma; PubMed types it as a clinical trial report (Clinical Trial, Phase II, research-article, Multicenter Study, Clinical Trial, Phase I). It was matched automatically to the idea \"ctDNA-guided escalation and de-escalation in frontline DLBCL\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Blood 2025","url":"https://doi.org/10.1182/blood.2024026830"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39792928/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39792928"},{"label":"ClinicalTrials.gov NCT04663347","url":"https://clinicaltrials.gov/study/NCT04663347"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04663347"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["blood"],"dependsOn":[],"notes":[],"journal":"Blood","year":2025,"doi":"10.1182/blood.2024026830","pmid":"39792928","authors":"Brody JD, Jørgensen J, Belada D, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Epcoritamab in Diffuse large B-cell lymphoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Epcoritamab in the title and Diffuse large B-cell lymphoma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-epcoritamab-dlbcl-drugs-2023","kind":"paper","name":"Epcoritamab: First Approval","aka":[],"tldr":"Review on Epcoritamab in Diffuse large B-cell lymphoma, in Drugs (2023), one of the most cited Europe PMC records with Epcoritamab in its title.","summary":"Epcoritamab (epcoritamab-bysp; Epkinly™; Tepkinly ®) is a subcutaneously administered CD3×CD20 T-cell-engaging bispecific antibody being co-developed by Genmab and AbbVie for the treatment of mature B-cell non-Hodgkin lymphoma subtypes (B-NHLs), including diffuse large B-cell lymphoma (DLBCL). Epcoritamab received its first (conditional) approval on 19 May 2023, in the USA, for the treatment of adult patients with relapsed or refractory (R/R) DLBCL, not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma after ≥ 2 lines of systemic therapy. Elsewhere, epcoritamab has received a positive opinion in the EU as a monotherapy for the treatment of adults with R/R DLBCL after ≥ 2 lines of systemic therapy, and is currently under regulatory review in Japan for the treatment of adults with R/R large B-cell lymphoma after ≥ 2 lines of systemic therapy. Clinical development of epcoritamab as monotherapy and in combination with standard of care agents for the treatment of mature B-NHLs is ongoing globally. This article summarizes the milestones in the development of epcoritamab leading to this first approval for R/R DLBCL.\n\nIndexed on Europe PMC as PubMed record 37597091 (DOI 10.1007/s40265-023-01930-4). Its title names Epcoritamab and its text names Diffuse large B-cell lymphoma; PubMed types it as a review (Review). It was matched automatically to the idea \"ctDNA-guided escalation and de-escalation in frontline DLBCL\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Drugs 2023","url":"https://doi.org/10.1007/s40265-023-01930-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37597091/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37597091"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Drugs","year":2023,"doi":"10.1007/s40265-023-01930-4","pmid":"37597091","authors":"Frampton JE","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for Epcoritamab in Diffuse large B-cell lymphoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Epcoritamab in the title and Diffuse large B-cell lymphoma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-dutta-gallbladder-cancer-epidemiology-india-chin-clin-oncol-2019","kind":"paper","name":"Epidemiology of gallbladder cancer in India","aka":[],"tldr":"India carries about a tenth of the world's gallbladder cancer, concentrated in the north and east, striking younger people than in the West, with gallstones present in four out of five patients and a list of environmental co-factors under suspicion.","summary":"Review from Chandigarh and Lucknow. India contributes about 10 percent of the global gallbladder cancer burden; incidence is high in north, north-east, central and east India and low in the south and west, and is rising in both sexes. Patients typically present in the fifth and sixth decades with advanced disease. Gallstones are present in 80 percent of Indian patients, yet incidence is out of proportion to gallstone prevalence, so co-factors are proposed: age, low socioeconomic status, chronic Salmonella Typhi and Helicobacter pylori infection, pollutants, heavy metals, chemicals, adulterated mustard oil and smoking, plus soil and water contamination. The authors call for large multicentre studies of attributable risk and, meanwhile, vigilance for incidental cancer and better access to gallstone care.","asOf":"2026-09-24","links":[{"label":"Chin Clin Oncol 2019","url":"https://doi.org/10.21037/cco.2019.08.03"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31484488/"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["screening"],"trials":[],"people":[],"bottlenecks":["b-global-access"],"keyPapers":[],"journals":["chinese-clinical-oncology"],"dependsOn":[],"notes":[],"journal":"Chinese Clinical Oncology","year":2019,"doi":"10.21037/cco.2019.08.03","pmid":"31484488","authors":"Dutta U, Bush N, Kalsi D, Popli P, Kapoor VK.","paperType":"review","findings":["India contributes about 10 percent of the global gallbladder cancer burden; incidence is highest in the north, north-east, centre and east.","Gallstones are present in 80 percent of Indian gallbladder cancer patients."],"whatItMeans":"The Indian epidemiology matters to the NHS: people of South Asian heritage make up a large part of several English cities, and Asian ethnicity is a named risk factor in the European polyp guideline.","caveats":["Narrative review; attributable fractions for the co-factors are not established.","Registry coverage in India is partial."],"changedPractice":false},{"id":"paper-baylin-cold-spring-harb-perspect-biol","kind":"paper","name":"Epigenetic Determinants of Cancer","aka":[],"tldr":"Paper cited by one pathway page and one roadmap page, indexed on Europe PMC as PubMed record 27194046 and published in Cold Spring Harbor perspectives in biology; the citing pages link this DOI, which is how the record was matched.","summary":"SUMMARYEpigenetic changes are present in all human cancers and are now known to cooperate with genetic alterations to drive the cancer phenotype. These changes involve DNA methylation, histone modifiers and readers, chromatin remodelers, microRNAs, and other components of chromatin. Cancer genetics and epigenetics are inextricably linked in generating the malignant phenotype; epigenetic changes can cause mutations in genes, and, conversely, mutations are frequently observed in genes that modify the epigenome. Epigenetic therapies, in which the goal is to reverse these changes, are now one standard of care for a preleukemic disorder and form of lymphoma. The application of epigenetic therapies in the treatment of solid tumors is also emerging as a viable therapeutic route.\n\nIndexed on Europe PMC as PubMed record 27194046 (DOI 10.1101/cshperspect.a019505). Matched by DOI alone: one pathway page and one roadmap page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cold Spring Harb Perspect Biol 2016","url":"https://doi.org/10.1101/cshperspect.a019505"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27194046/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27194046"}],"tags":["europepmc-ingest"],"related":["epigenetic-reprogramming","epigenetics-roadmap"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Cold Spring Harbor perspectives in biology","year":2016,"doi":"10.1101/cshperspect.a019505","pmid":"27194046","authors":"Baylin SB, Jones PA","paperType":"review","findings":[],"whatItMeans":"One pathway page and one roadmap page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-feinberg-nat-rev-genet","kind":"paper","name":"Epigenetic modulators, modifiers and mediators in cancer aetiology and progression","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 26972587 and published in Nature reviews. Genetics; the citing page links this DOI, which is how the record was matched.","summary":"This year is the tenth anniversary of the publication in this journal of a model suggesting the existence of 'tumour progenitor genes'. These genes are epigenetically disrupted at the earliest stages of malignancies, even before mutations, and thus cause altered differentiation throughout tumour evolution. The past decade of discovery in cancer epigenetics has revealed a number of similarities between cancer genes and stem cell reprogramming genes, widespread mutations in epigenetic regulators, and the part played by chromatin structure in cellular plasticity in both development and cancer. In the light of these discoveries, we suggest here a framework for cancer epigenetics involving three types of genes: 'epigenetic mediators', corresponding to the tumour progenitor genes suggested earlier; 'epigenetic modifiers' of the mediators, which are frequently mutated in cancer; and 'epigenetic modulators' upstream of the modifiers, which are responsive to changes in the cellular environment and often linked to the nuclear architecture. We suggest that this classification is helpful in framing new diagnostic and therapeutic approaches to cancer.\n\nIndexed on Europe PMC as PubMed record 26972587 (DOI 10.1038/nrg.2016.13). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Genet 2016","url":"https://doi.org/10.1038/nrg.2016.13"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26972587/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26972587"}],"tags":["europepmc-ingest"],"related":["epigenetic-progenitor-theory"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature reviews. Genetics","year":2016,"doi":"10.1038/nrg.2016.13","pmid":"26972587","authors":"Feinberg AP, Koldobskiy MA, Göndör A","paperType":"review","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-flavahan-science","kind":"paper","name":"Epigenetic plasticity and the hallmarks of cancer","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 28729483 and published in Science; the citing page links this DOI, which is how the record was matched.","summary":"Chromatin and associated epigenetic mechanisms stabilize gene expression and cellular states while also facilitating appropriate responses to developmental or environmental cues. Genetic, environmental, or metabolic insults can induce overly restrictive or overly permissive epigenetic landscapes that contribute to pathogenesis of cancer and other diseases. Restrictive chromatin states may prevent appropriate induction of tumor suppressor programs or block differentiation. By contrast, permissive or \"plastic\" states may allow stochastic oncogene activation or nonphysiologic cell fate transitions. Whereas many stochastic events will be inconsequential \"passengers,\" some will confer a fitness advantage to a cell and be selected as \"drivers.\" We review the broad roles played by epigenetic aberrations in tumor initiation and evolution and their potential to give rise to all classic hallmarks of cancer.\n\nIndexed on Europe PMC as PubMed record 28729483 (DOI 10.1126/science.aal2380). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Science 2017","url":"https://doi.org/10.1126/science.aal2380"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28729483/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28729483"}],"tags":["europepmc-ingest"],"related":["epigenetic-progenitor-theory"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2017,"doi":"10.1126/science.aal2380","pmid":"28729483","authors":"Flavahan WA, Gaskell E, Bernstein BE","paperType":"review","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-mack-nature","kind":"paper","name":"Epigenomic alterations define lethal CIMP-positive ependymomas of infancy","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 24553142 and published in Nature; the citing page links this DOI, which is how the record was matched.","summary":"Ependymomas are common childhood brain tumours that occur throughout the nervous system, but are most common in the paediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not further increase survival. Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic single nucleotide variants. Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype. Transcriptional silencing driven by CpG methylation converges exclusively on targets of the Polycomb repressive complex 2 which represses expression of differentiation genes through trimethylation of H3K27. CpG island methylator phenotype-positive hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically deregulated but genetically bland.\n\nIndexed on Europe PMC as PubMed record 24553142 (DOI 10.1038/nature13108). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2014","url":"https://doi.org/10.1038/nature13108"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24553142/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/24553142"}],"tags":["europepmc-ingest"],"related":["epigenetic-progenitor-theory"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2014,"doi":"10.1038/nature13108","pmid":"24553142","authors":"Mack SC, Witt H, Piro RM, et al.","paperType":"basic","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-ehe-consensus-stacchiotti-esmo-open-2021","kind":"paper","name":"Epithelioid haemangioendothelioma, an ultra-rare cancer: a consensus paper from the community of experts","aka":[],"tldr":"An international group of experts and patient advocates produced the first consensus on managing epithelioid haemangioendothelioma, including active surveillance for stable disease, surgery or transplant for localised disease, and sirolimus for progressing tumours.","summary":"Consensus paper from sarcoma experts and the EHE patient community covering diagnosis (including WWTR1-CAMTA1 and YAP1-TFE3 fusions), the highly variable natural history, indications for active surveillance, surgery, liver transplantation and radiotherapy, systemic therapy with mTOR inhibitors and anti-angiogenic agents, and priorities for research.","asOf":"2026-09-17","links":[{"label":"ESMO Open 2021","url":"https://doi.org/10.1016/j.esmoop.2021.100170"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34090171/"}],"tags":[],"related":[],"cancers":["epithelioid-haemangioendothelioma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["esmo-open"],"dependsOn":[],"notes":[],"journal":"ESMO Open","year":2021,"doi":"10.1016/j.esmoop.2021.100170","pmid":"34090171","authors":"Stacchiotti S, Miah AB, Frezza AM, et al.","paperType":"guideline","findings":[],"whatItMeans":"The observation-first approach and the sequencing of sirolimus before other systemic options on the EHE page come from this consensus.","caveats":["Based largely on retrospective series; no randomised trials exist."],"changedPractice":true},{"id":"paper-xm01-22-tjulandin-arch-drug-inf-2011","kind":"paper","name":"Epoetin theta with a new dosing schedule in anaemic cancer patients receiving nonplatinum-based chemotherapy: a randomised controlled trial (XM01-22)","aka":[],"tldr":"Among people whose chemotherapy had left them anaemic, a weekly epoetin theta injection restored haemoglobin without a transfusion in 73 percent, against 25 percent on placebo, and roughly halved the share who needed a transfusion.","summary":"Primary publication of XM01-22 (ISRCTN08063129), a randomised, double-blind, placebo-controlled trial of the recombinant erythropoietin epoetin theta (Eporatio) in adult cancer patients receiving nonplatinum-based chemotherapy. The primary efficacy endpoint was the responder rate: a complete haemoglobin response, defined as a haemoglobin increase of at least 2 g/dL without a transfusion within the previous four weeks. 186 patients were randomised to 12 weeks of subcutaneous epoetin theta (n = 95) or placebo (n = 91), starting at 20,000 IU once weekly.\n\nComplete haemoglobin response was 72.6 percent with epoetin theta versus 25.3 percent with placebo (P less than 0.0001). More placebo patients received transfusions after randomisation (23 patients, 25.3 percent, versus 13 patients, 13.7 percent; P = 0.0277). Most responders had 20,000 IU per week as their maximum dose before response, supporting it as the starting dose. Adverse-event frequencies were similar overall; hypertension was the only event more frequent with epoetin theta (8.4 percent versus 1.1 percent).","asOf":"2026-09-24","links":[{"label":"Archives of Drug Information 2011","url":"https://doi.org/10.1111/j.1753-5174.2011.00035.x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22022341/"},{"label":"ISRCTN08063129","url":"https://www.isrctn.com/ISRCTN08063129"}],"tags":[],"related":[],"cancers":[],"sections":["supportive-care"],"technologies":[],"targets":["epor"],"drugs":["epoetin-theta"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["xm01-22"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Archives of Drug Information","year":2011,"doi":"10.1111/j.1753-5174.2011.00035.x","pmid":"22022341","authors":"Tjulandin SA, Bias P, Elsässer R, et al.","paperType":"rct","findings":["Complete haemoglobin response 72.6 percent with epoetin theta vs 25.3 percent with placebo (P<0.0001).","Transfusion after randomisation in 13.7 percent vs 25.3 percent (P = 0.0277).","Hypertension the only adverse event more frequent with epoetin theta (8.4 percent vs 1.1 percent)."],"whatItMeans":"This is the nonplatinum chemotherapy pivotal behind the 2009 EU authorisation of epoetin theta (Eporatio and Biopoin) for the anaemia of chemotherapy in non-myeloid cancers. It supports the 20,000 IU weekly starting dose that the product information uses.","caveats":["Erythropoiesis-stimulating agents carry class warnings on thrombosis and, in some cancers, tumour progression and shorter survival; the trial reports haemoglobin response, not survival.","Sponsor-run trial with co-authors employed by BioGeneriX; the platinum companion study XM01-21 is reported separately.","Published in a small journal; the figures here are transcribed from the abstract indexed on Europe PMC."],"changedPractice":true,"participants":186},{"id":"paper-li-jama-oncol","kind":"paper","name":"Equecabtagene Autoleucel in Patients With Relapsed or Refractory Multiple Myeloma: The FUMANBA-1 Nonrandomized Clinical Trial","aka":[],"tldr":"Paper cited by one trial page and one treatment page, indexed on Europe PMC as PubMed record 39509090 and published in JAMA Oncology; the citing pages link this DOI, which is how the record was matched.","summary":"Importance: Equecabtagene autoleucel (eque-cel), a fully human-derived B-cell maturation antigen-targeting chimeric antigen receptor (CAR) T-cell therapy, has exhibited potential for the treatment of relapsed or refractory multiple myeloma (RRMM), and further investigation in a larger cohort is necessary.\n\nObjective: To evaluate whether eque-cel can benefit patients with RRMM and determine the overall response rate postinfusion.\n\nDesign, setting, and participants: The FUMANBA-1 trial was a single-arm, open-label, phase 1b/2 trial that evaluated eque-cel in adult patients with RRMM. Enrollment began in April 2020, and patients who received eque-cel will be monitored for a minimum of 15 years following the infusion. at September 2022, patients with heavily pretreated RRMM who received at least 3 prior courses of therapy from 14 centers were enrolled. Data were analyzed from April 2020 to September 2022.\n\nInterventions: Patients received a single infusion of eque-cel at 1.0 × 106 CAR-positive T cells/kg after the lymphodepletion.\n\nMain outcomes and measures: Efficacy was the primary objective, and safety, pharmacokinetics, and pharmacodynamics were secondary objectives.\n\nResults: Of 103 patients who received an eque-cel infusion, 55 (53.4%) were male, and the median (range) age was 58 (39-70) years. A total of 101 patients were evaluable for efficacy. At a median (range) follow-up of 13.8 (0.4-27.2) months, the overall response rate was 96.0% (97 of 101), with 74.3% (75 of 103) achieving a complete response or better. Among the 12 patients who had prior CAR T-cell treatment, 75% (9 of 12) achieved a response. The median progression-free survival was not reached, with a 12-month progression-free survival rate of 78.8% (95% CI, 68.6-86.0). A total of 96 patients (95.0%) achieved minimal residual disease negativity at a sensitivity threshold of 10-5. Adverse events were favorable: 96 of 103 patients (93.2%) experienced cytokine release syndrome (grade 1 to 2 in 95 patients [92.3%]) and 2 (1.9%) experienced immune effector cell-associated neurotoxicity syndrome (grade 1 to 2). All cases of immune effector cell-associated neurotoxicity syndrome and 94 of 96 cases of cytokine release syndrome resolved with treatment. Additionally, only 20 patients (19.4%) developed antidrug antibodies. Cellular kinetic analysis confirmed CAR-positive T cells in all patients, with the longest duration at 735 days.\n\nConclusions and relevance: In this trial, eque-cel led to early, deep, and durable responses in patients with heavily pretreated RRMM with a manageable safety profile. Patients with prior CAR T-cell therapy also benefitted from eque-cel.\n\nTrial registration: Chinese Clinical Trial Registry Identifier: ChiCTR2000033946.\n\nIndexed on Europe PMC as PubMed record 39509090 (DOI 10.1001/jamaoncol.2024.4879). Matched by DOI alone: one trial page and one treatment page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA Oncol 2024","url":"https://doi.org/10.1001/jamaoncol.2024.4879"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39509090/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39509090"}],"tags":["europepmc-ingest"],"related":["equecabtagene-autoleucel"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["fumanba-1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2024,"doi":"10.1001/jamaoncol.2024.4879","pmid":"39509090","authors":"Li C, Zhou K, Hu Y, et al.","paperType":"observational","findings":[],"whatItMeans":"One trial page and one treatment page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-keam-mol-diagn-ther","kind":"paper","name":"Equecabtagene Autoleucel: First Approval","aka":[],"tldr":"Paper cited by one treatment page, indexed on Europe PMC as PubMed record 37658205 and published in Molecular diagnosis & therapy; the citing page links this DOI, which is how the record was matched.","summary":"Equecabtagene autoleucel (Fucaso ®), an autologous anti-B cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR)-T cell therapy that uses lentivirus as a gene vector to transfect autologous T cells, is being developed by IASO Biotechnology and Innovent Biologics, Inc. for the treatment of multiple myeloma (MM) and autoimmune diseases of the nervous system, including neuromyelitis optica spectrum disorder (NMOSD). Equecabtagene autoleucel was granted conditional approval in China in June 2023 for the treatment of adults with relapsed or refractory MM (RRMM) who have progressed after ≥ 3 lines of therapy (≥ 1 proteasome inhibitor and an immunomodulator). This article summarizes the milestones in the development of equecabtagene autoleucel leading to this first approval in patients with RRMM who have progressed after multiple lines of therapy.\n\nIndexed on Europe PMC as PubMed record 37658205 (DOI 10.1007/s40291-023-00673-y). Matched by DOI alone: one treatment page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Mol Diagn Ther 2023","url":"https://doi.org/10.1007/s40291-023-00673-y"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37658205/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37658205"}],"tags":["europepmc-ingest"],"related":["equecabtagene-autoleucel"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Molecular diagnosis & therapy","year":2023,"doi":"10.1007/s40291-023-00673-y","pmid":"37658205","authors":"Keam SJ","paperType":"review","findings":[],"whatItMeans":"One treatment page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-erdheim-chester-disease-consensus-recommendations-blood-2020","kind":"paper","name":"Erdheim-Chester disease: consensus recommendations for evaluation, diagnosis and treatment in the molecular era","aka":[],"tldr":"International experts set out how to diagnose Erdheim-Chester disease, which scans and mutation tests to do, and when to use BRAF and MEK inhibitors, interferon or other drugs.","summary":"Consensus recommendations from an international group of histiocytosis specialists covering the clinical features, imaging (whole-body PET-CT, cardiac and brain MRI), biopsy and molecular testing (BRAF V600E and other MAPK pathway alterations), the decision to treat, and therapy: BRAF inhibitors for BRAF-mutant disease, MEK inhibitors for BRAF wild-type disease, interferon alfa and other options, with guidance on monitoring and long-term management.\n\nIt updates the 2014 recommendations for the targeted therapy era.","asOf":"2026-09-18","links":[{"label":"Blood 2020","url":"https://doi.org/10.1182/blood.2019003507"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32187362/"}],"tags":[],"related":[],"cancers":["erdheim-chester-disease"],"sections":[],"technologies":[],"targets":[],"drugs":["vemurafenib","cobimetinib","interferon-alfa"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["blood"],"dependsOn":[],"notes":[],"journal":"Blood","year":2020,"doi":"10.1182/blood.2019003507","pmid":"32187362","authors":"Goyal G, Heaney ML, Collin M, et al.","paperType":"guideline","findings":[],"whatItMeans":"The diagnostic and treatment rows on the Erdheim-Chester page follow these recommendations.","caveats":["Expert consensus in a disease with a few hundred reported cases; randomised evidence does not exist.","Optimal duration of targeted therapy remains unknown."],"changedPractice":true},{"id":"paper-voss-int-j-radiat-oncol-biol-phys","kind":"paper","name":"ERGO2: A Prospective, Randomized Trial of Calorie-Restricted Ketogenic Diet and Fasting in Addition to Reirradiation for Malignant Glioma","aka":[],"tldr":"Paper cited by one trial page and one technology page, indexed on Europe PMC as PubMed record 32619561 and published in International Journal of Radiation Oncology, Biology, Physics; the citing pages link this DOI, which is how the record was matched.","summary":"Purpose: ERGO2 is the first randomized clinical trial on a calorically restricted ketogenic diet (KD) and intermittent fasting (KD-IF) in addition to reirradiation for recurrent malignant gliomas.\n\nMethods and materials: Fifty patients were randomized 1:1 to reirradiation combined with either a calorically unrestricted diet or KD-IF. The KD-IF schedule included 3 days of KD (21-23 kcal/kg/d), followed by 3 days of fasting and again 3 days of KD. Primary endpoint was progression-free survival (PFS) at 6 months (PFS6). Secondary endpoints were PFS, local PFS, overall survival (OS), frequency of epileptic seizures, rate of ketosis and quality of life.\n\nResults: Four patients quit the trial before treatment and 3 patients stopped KD-IF prematurely. Of the 20 patients who completed KD-IF, 17 patients developed ketosis at day 6 and glucose levels declined significantly. KD-IF was well-tolerated with a modest weight loss of -2.1 ± 1.8 kg. No severe adverse events attributable to the diet occurred. PFS6 was not significantly different between the 2 groups (KD-IF: 20%; calorically unrestricted diet: 16%). Similarly, no difference in PFS, local PFS6, or OS was observable. Explorative analysis revealed that patients in the KD-IF group who had a glucose level of less than the median (83.5 mg/dL) on day 6 had significantly longer PFS and OS compared with those above the median (P <.05).\n\nConclusions: KD-IF is feasible and effective in inducing ketosis in heavily pretreated patients with recurrent glioma. However, the short schedule reported here failed to increase the efficacy of reirradiation. CLINICALTRIALS.\n\nGov number: NCT01754350.\n\nIndexed on Europe PMC as PubMed record 32619561 (DOI 10.1016/j.ijrobp.2020.06.021). Matched by DOI alone: one trial page and one technology page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Int J Radiat Oncol Biol Phys 2020","url":"https://doi.org/10.1016/j.ijrobp.2020.06.021"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32619561/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32619561"}],"tags":["europepmc-ingest"],"related":["ketogenic-diet-glioblastoma"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["ergo2"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["ijrobp"],"dependsOn":[],"notes":[],"journal":"International Journal of Radiation Oncology, Biology, Physics","year":2020,"doi":"10.1016/j.ijrobp.2020.06.021","pmid":"32619561","authors":"Voss M, Wagner M, von Mettenheim N, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page and one technology page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-cortes-lancet","kind":"paper","name":"Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study","aka":[],"tldr":"Paper cited by one treatment page, indexed on Europe PMC as PubMed record 21376385 and published in The Lancet; the citing page links this DOI, which is how the record was matched.","summary":"Background: Treatments with survival benefit are greatly needed for women with heavily pretreated metastatic breast cancer. Eribulin mesilate is a non-taxane microtubule dynamics inhibitor with a novel mode of action. We aimed to compare overall survival of heavily pretreated patients receiving eribulin versus currently available treatments.\n\nMethods: In this phase 3 open-label study, women with locally recurrent or metastatic breast cancer were randomly allocated (2:1) to eribulin mesilate (1·4 mg/m(2) administered intravenously during 2-5 min on days 1 and 8 of a 21-day cycle) or treatment of physician's choice (TPC). Patients had received between two and five previous chemotherapy regimens (two or more for advanced disease), including an anthracycline and a taxane, unless contraindicated. Randomisation was stratified by geographical region, previous capecitabine treatment, and human epidermal growth factor receptor 2 status. Patients and investigators were not masked to treatment allocation. The primary endpoint was overall survival in the intention-to-treat population. This study is registered at ClinicalTrials.gov, number NCT00388726.\n\nFindings: 762 women were randomly allocated to treatment groups (508 eribulin, 254 TPC). Overall survival was significantly improved in women assigned to eribulin (median 13·1 months, 95% CI 11·8-14·3) compared with TPC (10·6 months, 9·3-12·5; hazard ratio 0·81, 95% CI 0·66-0·99; p=0·041). The most common adverse events in both groups were asthenia or fatigue (270 [54%] of 503 patients on eribulin and 98 [40%] of 247 patients on TPC at all grades) and neutropenia (260 [52%] patients receiving eribulin and 73 [30%] of those on TPC at all grades). Peripheral neuropathy was the most common adverse event leading to discontinuation from eribulin, occurring in 24 (5%) of 503 patients.\n\nInterpretation: Eribulin showed a significant and clinically meaningful improvement in overall survival compared with TPC in women with heavily pretreated metastatic breast cancer. This finding challenges the notion that improved overall survival is an unrealistic expectation during evaluation of new anticancer therapies in the refractory setting.\n\nFunding: Eisai.\n\nIndexed on Europe PMC as PubMed record 21376385 (DOI 10.1016/s0140-6736(11)60070-6). Matched by DOI alone: one treatment page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet 2011","url":"https://doi.org/10.1016/s0140-6736(11)60070-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21376385/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/21376385"}],"tags":["europepmc-ingest"],"related":["eribulin"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2011,"doi":"10.1016/s0140-6736(11)60070-6","pmid":"21376385","authors":"Cortes J, O'Shaughnessy J, Loesch D, et al.","paperType":"rct","findings":[],"whatItMeans":"One treatment page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-eribulin-liposarcoma-schoffski-lancet-2016","kind":"paper","name":"Eribulin versus dacarbazine in previously treated advanced liposarcoma or leiomyosarcoma","aka":[],"tldr":"Eribulin lengthened survival by two months compared with dacarbazine in previously treated liposarcoma and leiomyosarcoma, with the entire benefit in liposarcoma, where survival improved by seven months, leading to its approval for that subtype.","summary":"Phase 3 trial of 452 patients with advanced liposarcoma or leiomyosarcoma after at least two prior regimens randomised to eribulin or dacarbazine.\n\nMedian overall survival was 13.5 versus 11.5 months (hazard ratio 0.77) overall, and 15.6 versus 8.4 months in liposarcoma (hazard ratio 0.51) with no difference in leiomyosarcoma; progression-free survival was similar between arms.","asOf":"2026-09-17","links":[{"label":"Lancet 2016","url":"https://doi.org/10.1016/S0140-6736(15)01283-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26874885/"}],"tags":[],"related":[],"cancers":["liposarcoma"],"sections":[],"technologies":[],"targets":[],"drugs":["dacarbazine","eribulin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["patrick-schoffski"],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2016,"doi":"10.1016/S0140-6736(15)01283-0","pmid":"26874885","authors":"Schöffski P, Chawla S, Maki RG, et al.","paperType":"rct","findings":["Median overall survival 13.5 vs 11.5 months overall; hazard ratio 0.77.","Liposarcoma: 15.6 vs 8.4 months; hazard ratio 0.51."],"whatItMeans":"Eribulin is an approved later-line treatment for liposarcoma, one of the few sarcoma drugs with a demonstrated survival benefit.","caveats":["No progression-free survival benefit, an unusual pattern.","Dacarbazine is an active comparator in leiomyosarcoma."],"changedPractice":true,"participants":452},{"id":"paper-erivance-vismodegib-sekulic-nejm-2012","kind":"paper","name":"ERIVANCE BCC: efficacy and safety of vismodegib in advanced basal cell carcinoma","aka":[],"tldr":"The hedgehog pathway inhibitor vismodegib shrank tumours in 43 percent of patients with locally advanced and 30 percent with metastatic basal cell carcinoma, becoming the first drug approved for advanced basal cell carcinoma.","summary":"Phase 2 study of 104 patients with metastatic (33) or locally advanced (71) basal cell carcinoma unsuitable for surgery or radiotherapy treated with vismodegib 150 mg daily.\n\nObjective response was 30 percent in metastatic and 43 percent in locally advanced disease (21 percent complete), with median duration of response of 7.6 months; muscle spasms, alopecia, dysgeusia and weight loss were almost universal and led many patients to stop.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2012","url":"https://doi.org/10.1056/NEJMoa1113713"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22670903/"}],"tags":[],"related":[],"cancers":["locally-advanced-bcc"],"sections":[],"technologies":[],"targets":[],"drugs":["vismodegib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["erivance"],"people":["aleksandar-sekulic"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2012,"doi":"10.1056/NEJMoa1113713","pmid":"22670903","authors":"Sekulic A, Migden MR, Oro AE, et al.","paperType":"observational","findings":["Objective response 43 percent (locally advanced) and 30 percent (metastatic).","Median duration of response 7.6 months."],"whatItMeans":"Vismodegib (and sonidegib) is the first-line systemic treatment for locally advanced or metastatic basal cell carcinoma, often given intermittently to manage side effects.","caveats":["Single-arm; toxicity-related discontinuation is common.","Teratogenic; strict contraception required."],"changedPractice":true,"participants":104},{"id":"paper-egfr-nsclc-lancet-oncol-2012","kind":"paper","name":"Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial","aka":[],"tldr":"Phase 2 or 3 results paper on EGFR in Non-small-cell lung cancer, in The Lancet Oncology (2012), one of the most cited Europe PMC records with EGFR in its title.","summary":"Background: Erlotinib has been shown to improve progression-free survival compared with chemotherapy when given as first-line treatment for Asian patients with non-small-cell lung cancer (NSCLC) with activating EGFR mutations. We aimed to assess the safety and efficacy of erlotinib compared with standard chemotherapy for first-line treatment of European patients with advanced EGFR-mutation positive NSCLC.\n\nMethods: We undertook the open-label, randomised phase 3 EURTAC trial at 42 hospitals in France, Italy, and Spain. Eligible participants were adults (> 18 years) with NSCLC and EGFR mutations (exon 19 deletion or L858R mutation in exon 21) with no history of chemotherapy for metastatic disease (neoadjuvant or adjuvant chemotherapy ending ≥ 6 months before study entry was allowed). We randomly allocated participants (1:1) according to a computer-generated allocation schedule to receive oral erlotinib 150 mg per day or 3 week cycles of standard intravenous chemotherapy of cisplatin 75 mg/m(2) on day 1 plus docetaxel (75 mg/m(2) on day 1) or gemcitabine (1250 mg/m(2) on days 1 and 8). Carboplatin (AUC 6 with docetaxel 75 mg/m(2) or AUC 5 with gemcitabine 1000 mg/m(2)) was allowed in patients unable to have cisplatin. Patients were stratified by EGFR mutation type and Eastern Cooperative Oncology Group performance status (0 vs 1 vs 2). The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. We assessed safety in all patients who received study drug (≥ 1 dose). This study is registered with ClinicalTrials.gov, number NCT00446225.\n\nFindings: Between Feb 15, 2007, and Jan 4, 2011, 174 patients with EGFR mutations were enrolled. One patient received treatment before randomisation and was thus withdrawn from the study; of the remaining patients, 86 were randomly assigned to receive erlotinib and 87 to receive standard chemotherapy. The preplanned interim analysis showed that the study met its primary endpoint; enrolment was halted, and full evaluation of the results was recommended. At data cutoff (Jan 26, 2011), median PFS was 9·7 months (95% CI 8·4-12·3) in the erlotinib group, compared with 5·2 months (4·5-5·8) in the standard chemotherapy group (hazard ratio 0·37, 95% CI 0·25-0·54; p < 0·0001). Main grade 3 or 4 toxicities were rash (11 [13%] of 84 patients given erlotinib vs none of 82 patients in the chemotherapy group), neutropenia (none vs 18 [22%]), anaemia (one [1%] vs three [4%]), and increased amino-transferase concentrations (two [2%] vs 0). Five (6%) patients on erlotinib had treatment-related severe adverse events compared with 16 patients (20%) on chemotherapy. One patient in the erlotinib group and two in the standard chemotherapy group died from treatment-related causes.\n\nInterpretation: Our findings strengthen the rationale for routine baseline tissue-based assessment of EGFR mutations in patients with NSCLC and for treatment of mutation-positive patients with EGFR tyrosine-kinase inhibitors.\n\nFunding: Spanish Lung Cancer Group, Roche Farma, Hoffmann-La Roche, and Red Temática de Investigacion Cooperativa en Cancer.\n\nIndexed on Europe PMC as PubMed record 22285168 (DOI 10.1016/s1470-2045(11)70393-x). Its title names EGFR and its text names Non-small-cell lung cancer; PubMed types it as a clinical trial report (Clinical Trial, Phase III, Comparative Study, Research Support, Non-U.S. Gov't, Multicenter Study, Randomized Controlled Trial). It was matched automatically to the idea \"Look for the resistant sub-population before the first dose\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2012","url":"https://doi.org/10.1016/s1470-2045(11)70393-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22285168/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/22285168"}],"tags":["europepmc-ingest"],"related":["lung-cancer-evidence-roadmap","paper-mok-ipass-gefitinib-pulmonary-adenocarcinoma-nejm-2009"],"cancers":["lung-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2012,"doi":"10.1016/s1470-2045(11)70393-x","pmid":"22285168","authors":"Rosell R, Carcereny E, Gervais R, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for EGFR in Non-small-cell lung cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by EGFR in the title and Non-small-cell lung cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-schroder-erspc-screening-mortality-nejm-2009","kind":"paper","name":"ERSPC: screening and prostate cancer mortality in a randomised European study","aka":["ERSPC","European Randomized Study of Screening for Prostate Cancer","Schroder 2009"],"tldr":"The trial that showed PSA screening does save lives, and showed what it costs. Screening cut the death rate from prostate cancer by a fifth, but 1,410 men had to be screened and 48 extra cancers treated to prevent one death.","summary":"Fritz Schröder, Jonas Hugosson and the ERSPC investigators identified 182,000 men aged 50 to 74 through registries in seven European countries and randomised them to prostate-specific antigen screening on average once every four years or to no screening offer. The predefined core age group was the 162,243 men aged 55 to 69, and the primary outcome was death from prostate cancer.\n\nThe headline is a 20 percent reduction in prostate cancer mortality. The two numbers beneath it are what the field has argued about ever since: an absolute risk difference of 0.71 deaths per 1,000 men after a median 9 years, and a cumulative prostate cancer incidence of 8.2 percent in the screened group against 4.8 percent in the control group. The trial's own conclusion names the trade-off explicitly: screening reduced death but was associated with a high risk of overdiagnosis. The 16-year follow-up (paper-hugosson-eur-urol) improves the absolute numbers as the benefit accrues, without changing the shape of the trade.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2009","url":"https://doi.org/10.1056/nejmoa0810084"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19297566/"},{"label":"ISRCTN49127736","url":"https://www.isrctn.com/ISRCTN49127736"}],"tags":["prostate-evidence"],"related":["paper-andriole-plco-prostate-screening-nejm-2009","paper-hugosson-eur-urol","paper-draisma-lead-time-overdiagnosis-psa-jnci-2009","paper-goteborg-2-n-engl-j-med-2022","early-detection-roadmap","prostate-roadmap"],"cancers":["prostate","prostate-low-risk","prostate-intermediate-risk","prostate-high-risk"],"sections":["early-detection"],"technologies":["prostate-screening-psa-mri"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["psa","screening","overdiagnosis","number-needed-to-screen","lead-time-bias"],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-overdiagnosis","b-prevention-adoption"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2009,"doi":"10.1056/nejmoa0810084","pmid":"19297566","authors":"Schröder FH, Hugosson J, Roobol MJ, et al.","paperType":"rct","findings":["Rate ratio for death from prostate cancer in the screening group 0.80 (95 percent confidence interval 0.65 to 0.98; adjusted P equals 0.04), a 20 percent reduction.","Absolute risk difference 0.71 death per 1,000 men; 1,410 men would need to be screened and 48 additional cases treated to prevent one death from prostate cancer.","Cumulative incidence of prostate cancer over a median 9 years of follow-up 8.2 percent in the screening group and 4.8 percent in the control group.","82 percent of men in the screening group accepted at least one offer of screening.","Among men actually screened in the first round, excluding non-compliers, the rate ratio for death from prostate cancer was 0.73 (0.56 to 0.90)."],"whatItMeans":"The evidence that prostate-specific antigen screening works, stated together with the price. It is the reason screening programmes are debated rather than simply adopted, and the reason every subsequent proposal, from magnetic resonance imaging first to risk-model invitation, is judged on whether it keeps the mortality benefit while reducing the 48.","caveats":["Seven countries with different screening intervals, thresholds and biopsy protocols pooled into one trial, so the intervention is not uniform.","The absolute benefit at 9 years is small because prostate cancer mortality is a slow endpoint; longer follow-up increases it, as the 16-year report shows.","Contamination in the control group (unplanned prostate-specific antigen testing) dilutes the measured effect in some centres.","The trial randomised testing, not a modern pathway: there was no magnetic resonance imaging triage and no active surveillance as it is practised now, both of which change the overdiagnosis half of the trade."],"changedPractice":true,"participants":162243},{"id":"paper-rodolakis-int-j-gynecol-cancer","kind":"paper","name":"ESGO/ESHRE/ESGE Guidelines for the fertility-sparing treatment of patients with endometrial carcinoma","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 36746507 and published in International journal of gynecological cancer; the citing page links this DOI, which is how the record was matched.","summary":"The standard surgical treatment of endometrial carcinoma, consisting of total hysterectomy with bilateral salpingo-oophorectomy, drastically affects the quality of life of patients and creates a challenge for clinicians. Recent evidence-based guidelines of the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) provide comprehensive information on all relevant issues of diagnosis and treatment in endometrial carcinoma in a multidisciplinary setting. While addressing also work-up for fertility preservation treatments and the management and follow-up for fertility preservation, it was considered relevant to further extend the guidance on fertility-sparing treatment.A collaboration was set up between the ESGO, the European Society of Human Reproduction and Embryology (ESHRE), and the European Society for Gynaecological Endoscopy (ESGE), aiming to develop clinically relevant and evidence-based guidelines focusing on key aspects of fertility-sparing treatment (patient selection, tumor clinicopathological characteristics, treatment, special issues) in order to improve the quality of care for women with endometrial carcinoma across Europe and worldwide.ESGO/ESHRE/ESGE nominated an international multidisciplinary development group consisting of practicing clinicians and researchers who have demonstrated leadership and expertise in the care and research of endometrial carcinoma (11 experts from across Europe). To ensure that the guidelines are evidence-based, the literature published since 2016, identified by a systematic search, was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 95 independent international practitioners in cancer care delivery and patient representatives.\n\nIndexed on Europe PMC as PubMed record 36746507 (DOI 10.1136/ijgc-2022-004047). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Int J Gynecol Cancer 2023","url":"https://doi.org/10.1136/ijgc-2022-004047"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36746507/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36746507"}],"tags":["europepmc-ingest"],"related":["fertility-sparing-endometrial"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["international-journal-of-gynecological-cancer"],"dependsOn":[],"notes":[],"journal":"International journal of gynecological cancer","year":2023,"doi":"10.1136/ijgc-2022-004047","pmid":"36746507","authors":"Rodolakis A, Scambia G, Planchamp F, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-esgo-estro-esp-endometrial-concin-ijgc-2021","kind":"paper","name":"ESGO/ESTRO/ESP guidelines for the management of endometrial carcinoma (2021)","aka":[],"tldr":"The European gynaecological oncology, radiotherapy and pathology societies' joint guideline integrates molecular classification into risk groups for endometrial cancer and sets adjuvant treatment for each, including no adjuvant therapy for early POLE-mutated tumours.","summary":"Joint evidence-based guideline covering diagnosis, molecular classification, surgical staging including sentinel node mapping, risk group definitions incorporating molecular class, adjuvant radiotherapy and chemotherapy recommendations, fertility-sparing treatment, and management of advanced and recurrent disease.","asOf":"2026-09-17","links":[{"label":"Int J Gynecol Cancer 2021","url":"https://doi.org/10.1136/ijgc-2020-002230"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33397713/"}],"tags":[],"related":[],"cancers":["endometrial-nsmp","endometrial-pole-ultramutated"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["international-journal-of-gynecological-cancer"],"dependsOn":[],"notes":[],"journal":"International journal of gynecological cancer","year":2021,"doi":"10.1136/ijgc-2020-002230","pmid":"33397713","authors":"Concin N, Matias-Guiu X, Vergote I, et al.","paperType":"guideline","findings":[],"whatItMeans":"The adjuvant recommendations on this site's endometrial subtype pages (observation for stage I to II POLE-mutated disease, chemotherapy for p53-abnormal tumours with myometrial invasion, brachytherapy for intermediate risk) follow this guideline.","caveats":["Some molecular-based de-escalation recommendations await confirmation from the RAINBO trials."],"changedPractice":true},{"id":"paper-esmo-metastatic-breast-cancer-guideline-ann-oncol-2021","kind":"paper","name":"ESMO Clinical Practice Guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer","aka":[],"tldr":"The European oncology society's 2021 guideline for breast cancer that has spread, the parent document of the living guideline that is now updated as trials read out.","summary":"ESMO Clinical Practice Guideline for metastatic breast cancer, published in Annals of Oncology in 2021 by Gennari, André, Barrios, Cortés and colleagues. Europe PMC indexes no abstract for this article, so OnCo carries no figures from it. For triple-negative disease it set pembrolizumab with chemotherapy for PD-L1 combined positive score of 10 or more (KEYNOTE-355), PARP inhibitors for germline BRCA carriers (OlympiAD, EMBRACA) and sacituzumab govitecan after two lines (ASCENT). The guideline has since been maintained as the ESMO Metastatic Breast Cancer Living Guideline, whose 2025 update is recorded separately.","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2021","url":"https://doi.org/10.1016/j.annonc.2021.09.019"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34678411/"},{"label":"ESMO Metastatic Breast Cancer Living Guideline","url":"https://www.esmo.org/living-guidelines"}],"tags":["tnbc-evidence"],"related":["esmo-guidelines","paper-esmo-mbc-living-guideline-update-ann-oncol-2025"],"cancers":["tnbc","breast-hr-positive","breast-her2-positive"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["esmo"],"pathways":[],"terms":[],"trials":["keynote-355","olympiad","embraca","ascent"],"people":["javier-cortes"],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2021,"doi":"10.1016/j.annonc.2021.09.019","pmid":"34678411","authors":"Gennari A, André F, Barrios CH, et al.","paperType":"guideline","findings":["No abstract is indexed on Europe PMC; recommendations are read from the guideline itself."],"whatItMeans":"The document that made immunotherapy, PARP inhibition and the first antibody-drug conjugate the European standard for metastatic triple-negative disease; every later first-line change is an amendment to it.","caveats":["Predates the first-line antibody-drug conjugate trials (ASCENT-03, ASCENT-04, TROPION-Breast02).","No abstract indexed; figures are not quoted."],"changedPractice":true},{"id":"paper-esmo-anal-cancer-guideline-ann-oncol-2021","kind":"paper","name":"ESMO Clinical Practice Guideline on anal cancer: diagnosis, treatment and follow-up","aka":[],"tldr":"The European guideline for anal cancer, covering staging, chemoradiotherapy for localised disease, salvage surgery, and chemotherapy and immunotherapy for cancer that has spread.","summary":"Evidence-graded guideline from the European Society for Medical Oncology on anal squamous cell carcinoma: diagnosis with MRI and PET-CT, HIV and HPV testing, radical chemoradiotherapy with fluorouracil (or capecitabine) and mitomycin using intensity-modulated radiotherapy, response assessment at 26 weeks, salvage abdominoperineal resection, and, for metastatic disease, carboplatin plus paclitaxel first line on the InterAACT result with anti-PD-1 antibodies after platinum.\n\nIt also addresses local excision for small perianal tumours, treatment in people living with HIV, and surveillance after treatment.","asOf":"2026-09-18","links":[{"label":"Ann Oncol 2021","url":"https://doi.org/10.1016/j.annonc.2021.06.015"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34175386/"}],"tags":[],"related":[],"cancers":["localised-anal-cancer","metastatic-anal-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2021,"doi":"10.1016/j.annonc.2021.06.015","pmid":"34175386","authors":"Rao S, Guren MG, Khan K, et al.","paperType":"guideline","findings":[],"whatItMeans":"Most decisions on the localised and metastatic anal cancer pages, from the chemoradiotherapy schedule to when to operate and what to give for metastatic disease, follow this guideline or its American counterpart.","caveats":["Published before the POD1UM-303 result adding retifanlimab to first-line chemotherapy; check for updates.","Evidence for many recommendations in this rare cancer comes from single trials or consensus."],"changedPractice":true},{"id":"paper-espac-3-fluorouracil-vs-gemcitabine-adjuvant-neoptolemos-jama-2010","kind":"paper","name":"ESPAC-3: adjuvant fluorouracil plus folinic acid versus gemcitabine after pancreatic cancer resection","aka":[],"tldr":"After surgery for pancreatic cancer, six months of gemcitabine gave the same survival as fluorouracil with folinic acid, about 23 months, with half as many serious side effects.","summary":"Phase 3 trial at 159 centres in Europe, Australasia, Japan and Canada: 1,088 patients with resected pancreatic ductal adenocarcinoma were randomised to six months of fluorouracil plus folinic acid (551) or gemcitabine (537). The primary endpoint was overall survival.\n\nAfter a median follow-up of 34.2 months and 753 deaths, median survival was 23.0 months with fluorouracil and 23.6 months with gemcitabine (hazard ratio 0.94, p 0.39); progression-free survival and quality of life did not differ. Treatment-related serious adverse events occurred in 14 percent of fluorouracil patients and 7.5 percent of gemcitabine patients.","asOf":"2026-09-22","links":[{"label":"JAMA 2010","url":"https://doi.org/10.1001/jama.2010.1275"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20823433/"}],"tags":[],"related":[],"cancers":["resectable-pdac","pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":["gemcitabine","fluorouracil"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["espac-3"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2010,"doi":"10.1001/jama.2010.1275","pmid":"20823433","authors":"Neoptolemos JP, Stocken DD, Bassi C, et al.","paperType":"rct","findings":["Median overall survival 23.0 months (95% CI 21.1 to 25.0) with fluorouracil plus folinic acid versus 23.6 months (21.4 to 26.4) with gemcitabine; hazard ratio 0.94 (0.81 to 1.08).","Treatment-related serious adverse events in 14 percent versus 7.5 percent of patients (p < 0.001)."],"whatItMeans":"Either regimen was acceptable adjuvant therapy in 2010, with gemcitabine preferred for tolerability; combination regimens (ESPAC-4, PRODIGE 24) have since superseded both.","caveats":["Open-label; the observation arm was dropped after ESPAC-1, so the trial does not itself test chemotherapy against no chemotherapy."],"changedPractice":true,"participants":1088},{"id":"paper-espac-4-gemcitabine-capecitabine-adjuvant-pancreatic-lancet-2017","kind":"paper","name":"ESPAC-4: adjuvant gemcitabine plus capecitabine versus gemcitabine alone after resection of pancreatic cancer","aka":[],"tldr":"Adding the tablet capecitabine to gemcitabine after surgery for pancreatic cancer lengthened median survival by about two and a half months with little extra toxicity, giving patients who cannot manage FOLFIRINOX a better option than gemcitabine alone.","summary":"Open-label randomised phase 3 trial by the European Study Group for Pancreatic Cancer in 730 patients from 92 hospitals who had undergone complete macroscopic resection of pancreatic ductal adenocarcinoma. Patients received six cycles of gemcitabine alone or gemcitabine plus oral capecitabine.\n\nMedian overall survival was 28.0 months with the combination against 25.5 months with gemcitabine alone (hazard ratio 0.82). Five-year survival was higher with the combination, and grade 3 or 4 adverse events were similar between the arms apart from more hand-foot syndrome and diarrhoea with capecitabine.","asOf":"2026-09-21","links":[{"label":"Lancet 2017","url":"https://doi.org/10.1016/S0140-6736(16)32409-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28129987/"}],"tags":[],"related":[],"cancers":["resectable-pdac","pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":["gemcitabine","capecitabine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["espac-4"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2017,"doi":"10.1016/S0140-6736(16)32409-6","pmid":"28129987","authors":"Neoptolemos JP, Palmer DH, Ghaneh P, et al.","paperType":"rct","findings":["Median overall survival 28.0 versus 25.5 months, hazard ratio 0.82.","Toxicity was similar overall, with more hand-foot syndrome and diarrhoea in the combination arm."],"whatItMeans":"Gemcitabine plus capecitabine became the adjuvant regimen for patients unfit for modified FOLFIRINOX, and remains the comparator in European trials of adjuvant treatment.","caveats":["The absolute gain was modest and PRODIGE 24 soon showed a much larger benefit from modified FOLFIRINOX in fitter patients.","Many patients had R1 resections, so the trial population differs from strictly R0 series."],"changedPractice":true,"participants":730},{"id":"paper-espac-5-neoadjuvant-borderline-resectable-pancreatic-lancet-gastro-hep-2023","kind":"paper","name":"ESPAC5: immediate surgery versus short-course neoadjuvant chemotherapy or chemoradiotherapy for borderline resectable pancreatic cancer","aka":[],"tldr":"In this four-arm British trial, two months of chemotherapy before surgery for borderline resectable pancreatic cancer doubled the share of patients alive at one year compared with operating straight away, even though the same proportion got to an operation.","summary":"Multicentre randomised phase 2 trial of the European Study Group for Pancreatic Cancer in 90 patients with borderline resectable pancreatic ductal adenocarcinoma, randomised to immediate surgery or to one of three short-course neoadjuvant treatments (gemcitabine plus capecitabine, FOLFIRINOX, or capecitabine-based chemoradiotherapy) followed by surgery, with adjuvant chemotherapy in all arms.\n\nResection rates were similar between immediate surgery and the pooled neoadjuvant arms, but one-year overall survival was 39 percent after immediate surgery and 77 percent after neoadjuvant treatment (hazard ratio 0.27). The chemotherapy arms did better than chemoradiotherapy, and FOLFIRINOX did best.","asOf":"2026-09-21","links":[{"label":"Lancet Gastroenterol Hepatol 2023","url":"https://doi.org/10.1016/S2468-1253(22)00348-X"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36521500/"}],"tags":[],"related":[],"cancers":["borderline-resectable-pdac","pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":["folfirinox","gemcitabine","capecitabine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["espac-5"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Lancet Gastroenterology and Hepatology","year":2023,"doi":"10.1016/S2468-1253(22)00348-X","pmid":"36521500","authors":"Ghaneh P, Palmer D, Cicconi S, et al.","paperType":"rct","findings":["One-year overall survival 39 percent with immediate surgery versus 77 percent with neoadjuvant treatment, hazard ratio 0.27.","Resection rates were similar (about 62 versus 55 percent), so the survival gain did not come from more operations.","Neoadjuvant chemotherapy, especially FOLFIRINOX, outperformed chemoradiotherapy."],"whatItMeans":"ESPAC5 supports neoadjuvant chemotherapy over immediate surgery in borderline resectable disease and points to FOLFIRINOX as the regimen to build on.","caveats":["A phase 2 feasibility trial with 90 patients across four arms; the survival comparison was a secondary endpoint.","Only two months of neoadjuvant treatment were given, shorter than most current protocols."],"changedPractice":true,"participants":90},{"id":"paper-arends-clin-nutr","kind":"paper","name":"ESPEN guidelines on nutrition in cancer patients","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 27637832 and published in Clinical nutrition (Edinburgh, Scotland); the citing page links this DOI, which is how the record was matched.","summary":"Cancers are among the leading causes of morbidity and mortality worldwide, and the number of new cases is expected to rise significantly over the next decades. At the same time, all types of cancer treatment, such as surgery, radiation therapy, and pharmacological therapies are improving in sophistication, precision and in the power to target specific characteristics of individual cancers. Thus, while many cancers may still not be cured they may be converted to chronic diseases. All of these treatments, however, are impeded or precluded by the frequent development of malnutrition and metabolic derangements in cancer patients, induced by the tumor or by its treatment. These evidence-based guidelines were developed to translate current best evidence and expert opinion into recommendations for multi-disciplinary teams responsible for identification, prevention, and treatment of reversible elements of malnutrition in adult cancer patients. The guidelines were commissioned and financially supported by ESPEN and by the European Partnership for Action Against Cancer (EPAAC), an EU level initiative. Members of the guideline group were selected by ESPEN to include a range of professions and fields of expertise. We searched for meta-analyses, systematic reviews and comparative studies based on clinical questions according to the PICO format. The evidence was evaluated and merged to develop clinical recommendations using the GRADE method. Due to the deficits in the available evidence, relevant still open questions were listed and should be addressed by future studies. Malnutrition and a loss of muscle mass are frequent in cancer patients and have a negative effect on clinical outcome. They may be driven by inadequate food intake, decreased physical activity and catabolic metabolic derangements. To screen for, prevent, assess in detail, monitor and treat malnutrition standard operating procedures, responsibilities and a quality control process should be established at each institution involved in treating cancer patients. All cancer patients should be screened regularly for the risk or the presence of malnutrition. In all patients - with the exception of end of life care - energy and substrate requirements should be met by offering in a step-wise manner nutritional interventions from counseling to parenteral nutrition. However, benefits and risks of nutritional interventions have to be balanced with special consideration in patients with advanced disease. Nutritional care should always be accompanied by exercise training. To counter malnutrition in patients with advanced cancer there are few pharmacological agents and pharmaconutrients with only limited effects. Cancer survivors should engage in regular physical activity and adopt a prudent diet.\n\nIndexed on Europe PMC as PubMed record 27637832 (DOI 10.1016/j.clnu.2016.07.015). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Clin Nutr 2017","url":"https://doi.org/10.1016/j.clnu.2016.07.015"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27637832/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27637832"}],"tags":["europepmc-ingest"],"related":["enteral-parenteral-nutrition"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Clinical nutrition (Edinburgh, Scotland)","year":2017,"doi":"10.1016/j.clnu.2016.07.015","pmid":"27637832","authors":"Arends J, Bachmann P, Baracos V, et al.","paperType":"guideline","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-muscaritoli-clin-nutr","kind":"paper","name":"ESPEN practical guideline: Clinical Nutrition in cancer","aka":[],"tldr":"Paper cited by three technology pages and two term pages, indexed on Europe PMC as PubMed record 33946039 and published in Clinical nutrition (Edinburgh, Scotland); the citing pages link this DOI, which is how the record was matched.","summary":"Background: This practical guideline is based on the current scientific ESPEN guidelines on nutrition in cancer patients.\n\nMethods: ESPEN guidelines have been shortened and transformed into flow charts for easier use in clinical practice. The practical guideline is dedicated to all professionals including physicians, dieticians, nutritionists and nurses working with patients with cancer.\n\nResults: A total of 43 recommendations are presented with short commentaries for the nutritional and metabolic management of patients with neoplastic diseases. The disease-related recommendations are preceded by general recommendations on the diagnostics of nutritional status in cancer patients.\n\nConclusion: This practical guideline gives guidance to health care providers involved in the management of cancer patients to offer optimal nutritional care.\n\nIndexed on Europe PMC as PubMed record 33946039 (DOI 10.1016/j.clnu.2021.02.005). Matched by DOI alone: three technology pages and two term pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Clin Nutr 2021","url":"https://doi.org/10.1016/j.clnu.2021.02.005"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33946039/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33946039"}],"tags":["europepmc-ingest"],"related":["oncology-nutrition","nutrition-screening-mnt","resistance-training-cachexia","immunonutrition","malnutrition-screening"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Clinical nutrition (Edinburgh, Scotland)","year":2021,"doi":"10.1016/j.clnu.2021.02.005","pmid":"33946039","authors":"Muscaritoli M, Arends J, Bachmann P, et al.","paperType":"guideline","findings":[],"whatItMeans":"Three technology pages and two term pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-esphall-imatinib-biondi-lancet-oncol-2012","kind":"paper","name":"EsPhALL: imatinib after induction for children and adolescents with Philadelphia chromosome-positive acute lymphoblastic leukaemia","aka":[],"tldr":"In this European trial, adding intermittent imatinib to intensive chemotherapy for childhood Philadelphia-positive leukaemia improved disease-free survival in good-risk patients and supported its use in every child with the disease.","summary":"European intergroup study of 178 children with Ph-positive ALL; 108 good-risk patients were randomised to imatinib or no imatinib in addition to BFM-type chemotherapy, and poor-risk patients all received imatinib; most underwent transplant.\n\nFour-year disease-free survival was 72.9 percent with imatinib against 61.7 percent without in good-risk patients (not statistically significant by intention to treat but significant as treated), and toxicity was acceptable.","asOf":"2026-09-17","links":[{"label":"Lancet Oncol 2012","url":"https://doi.org/10.1016/S1470-2045(12)70377-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22898679/"}],"tags":[],"related":[],"cancers":["all-paediatric-ph-positive"],"sections":[],"technologies":[],"targets":[],"drugs":["imatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2012,"doi":"10.1016/S1470-2045(12)70377-7","pmid":"22898679","authors":"Biondi A, Schrappe M, De Lorenzo P, et al.","paperType":"rct","findings":["Four-year disease-free survival 72.9 percent vs 61.7 percent in good-risk patients.","Poor-risk patients on imatinib: four-year disease-free survival 53.5 percent."],"whatItMeans":"Together with AALL0031, EsPhALL established kinase inhibitor plus chemotherapy as standard for paediatric Ph-positive ALL, with later trials giving imatinib continuously and reducing transplant.","caveats":["Randomisation was stopped early after AALL0031 results; intention-to-treat difference not significant.","Intermittent imatinib schedule was later replaced by continuous dosing."],"changedPractice":true,"participants":178},{"id":"paper-esphall2010-continuous-imatinib-biondi-lancet-haematol-2018","kind":"paper","name":"EsPhALL2010: continuous imatinib with chemotherapy in paediatric Philadelphia chromosome-positive ALL","aka":[],"tldr":"Giving children with Philadelphia-positive leukaemia the pill imatinib continuously from the second week of treatment allowed fewer of them to need a transplant, with survival similar to the earlier study that used short courses, but at the cost of more serious toxicity during intensive treatment blocks.","summary":"Prospective, intergroup, open-label, single-arm trial across 11 study groups in Europe, Chile and Hong Kong: 155 patients aged 1 to 17 with Philadelphia chromosome-positive acute lymphoblastic leukaemia received imatinib 300 mg/m2 from day 15 of induction continuously through chemotherapy, with transplant reserved for poor early responders (38 percent were transplanted in first remission).\n\nFive-year event-free survival was 57.0 percent and overall survival 71.8 percent, similar to EsPhALL2004 despite fewer transplants. 154 serious adverse events occurred in 80 patients, mostly infections during high-risk blocks and delayed intensifications, including 14 fatal events.","asOf":"2026-09-22","links":[{"label":"Lancet Haematol 2018","url":"https://doi.org/10.1016/S2352-3026(18)30173-X"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30501871/"}],"tags":[],"related":[],"cancers":["all-paediatric-ph-positive","all-leukemia"],"sections":[],"technologies":[],"targets":[],"drugs":["imatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["esphall"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-haematology"],"dependsOn":[],"notes":[],"journal":"The Lancet Haematology","year":2018,"doi":"10.1016/S2352-3026(18)30173-X","pmid":"30501871","authors":"Biondi A, Gandemer V, De Lorenzo P, et al.","paperType":"observational","findings":["Five-year event-free survival 57.0 percent (95% CI 48.5 to 64.6) and overall survival 71.8 percent (63.5 to 78.5).","38 percent of patients had transplant in first remission, fewer than in EsPhALL2004, with similar survival.","Serious adverse events in 52 percent of patients, 14 fatal, concentrated in high-risk blocks and delayed intensification."],"whatItMeans":"Continuous imatinib from induction lets many children with Philadelphia-positive ALL avoid transplant, but the intensive BFM backbone is toxic; later trials reduced chemotherapy intensity under tyrosine kinase inhibitor cover.","caveats":["Single-arm design compared with the earlier EsPhALL2004 cohort rather than a concurrent control."],"changedPractice":true,"participants":155},{"id":"paper-merino-j-immunother-cancer","kind":"paper","name":"Establishing guidelines to harmonize tumor mutational burden (TMB): in silico assessment of variation in TMB quantification across diagnostic platforms: phase I of the Friends of Cancer Research TMB Harmonization Project","aka":[],"tldr":"Paper cited by one bottleneck page, indexed on Europe PMC as PubMed record 32217756 and published in Journal for ImmunoTherapy of Cancer; the citing page links this DOI, which is how the record was matched.","summary":"Background: Tumor mutational burden (TMB), defined as the number of somatic mutations per megabase of interrogated genomic sequence, demonstrates predictive biomarker potential for the identification of patients with cancer most likely to respond to immune checkpoint inhibitors. TMB is optimally calculated by whole exome sequencing (WES), but next-generation sequencing targeted panels provide TMB estimates in a time-effective and cost-effective manner. However, differences in panel size and gene coverage, in addition to the underlying bioinformatics pipelines, are known drivers of variability in TMB estimates across laboratories. By directly comparing panel-based TMB estimates from participating laboratories, this study aims to characterize the theoretical variability of panel-based TMB estimates, and provides guidelines on TMB reporting, analytic validation requirements and reference standard alignment in order to maintain consistency of TMB estimation across platforms.\n\nMethods: Eleven laboratories used WES data from The Cancer Genome Atlas Multi-Center Mutation calling in Multiple Cancers (MC3) samples and calculated TMB from the subset of the exome restricted to the genes covered by their targeted panel using their own bioinformatics pipeline (panel TMB). A reference TMB value was calculated from the entire exome using a uniform bioinformatics pipeline all members agreed on (WES TMB). Linear regression analyses were performed to investigate the relationship between WES and panel TMB for all 32 cancer types combined and separately. Variability in panel TMB values at various WES TMB values was also quantified using 95% prediction limits.\n\nResults: Study results demonstrated that variability within and between panel TMB values increases as the WES TMB values increase. For each panel, prediction limits based on linear regression analyses that modeled panel TMB as a function of WES TMB were calculated and found to approximately capture the intended 95% of observed panel TMB values. Certain cancer types, such as uterine, bladder and colon cancers exhibited greater variability in panel TMB values, compared with lung and head and neck cancers.\n\nConclusions: Increasing uptake of TMB as a predictive biomarker in the clinic creates an urgent need to bring stakeholders together to agree on the harmonization of key aspects of panel-based TMB estimation, such as the standardization of TMB reporting, standardization of analytical validation studies and the alignment of panel-based TMB values with a reference standard. These harmonization efforts should improve consistency and reliability of panel TMB estimates and aid in clinical decision-making.\n\nIndexed on Europe PMC as PubMed record 32217756 (DOI 10.1136/jitc-2019-000147). Matched by DOI alone: one bottleneck page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Immunother Cancer 2020","url":"https://doi.org/10.1136/jitc-2019-000147"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32217756/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32217756"}],"tags":["europepmc-ingest"],"related":["b-biomarker-validation"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jitc"],"dependsOn":[],"notes":[],"journal":"Journal for ImmunoTherapy of Cancer","year":2020,"doi":"10.1136/jitc-2019-000147","pmid":"32217756","authors":"Merino DM, McShane LM, Fabrizio D, et al.","paperType":"observational","findings":[],"whatItMeans":"One bottleneck page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-esteva-skin-cancer-deep-learning-nature-2017","kind":"paper","name":"Esteva 2017: a deep neural network classifies skin cancer at dermatologist level","aka":[],"tldr":"A single image-recognition network, trained on about 130,000 clinical photographs, told cancerous skin lesions from benign ones as accurately as 21 dermatologists, the first widely cited demonstration that deep learning could match specialists at a cancer diagnosis task.","summary":"Esteva and colleagues at Stanford fine-tuned a convolutional neural network pretrained on everyday images using 129,450 clinical photographs spanning 2,032 skin diseases arranged in a taxonomy. On held-out biopsy-proven images they tested it against 21 board-certified dermatologists on two decisions: keratinocyte carcinomas versus benign seborrheic keratoses, and malignant melanomas versus benign naevi, using both clinical photographs and dermoscopy images. The network's sensitivity and specificity curve matched or exceeded the average dermatologist on each task.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1038/nature21056"}],"tags":[],"related":[],"cancers":["melanoma","basal-cell-carcinoma","cutaneous-scc"],"sections":[],"technologies":["dermoscopy-ai"],"targets":[],"drugs":[],"companies":[],"institutions":["stanford"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature","year":2017,"doi":"10.1038/nature21056","authors":"Esteva A, Kuprel B, Novoa RA, et al.","paperType":"methods","findings":["Training set of 129,450 clinical images covering 2,032 diseases; the network was pretrained on general images and fine-tuned on skin.","Tested against 21 dermatologists on biopsy-proven images for two binary decisions: keratinocyte carcinoma versus seborrheic keratosis and melanoma versus benign naevus, with and without dermoscopy.","Performance on both tasks was on a par with the dermatologists across the sensitivity and specificity trade-off."],"whatItMeans":"This paper made AI-assisted skin cancer triage a serious clinical prospect and became the template for later work in radiology and pathology. Prospective trials, regulatory clearance and performance across skin tones followed, and are where its promise is now being tested.","caveats":["A retrospective test on curated images, not a prospective clinical study.","Images came largely from lighter-skinned patients, so performance across skin tones was not established.","Dermatologists in practice use history and examination, not a photograph alone."],"changedPractice":false},{"id":"paper-dulguerov-esthesioneuroblastoma-meta-analysis-lancet-oncol-2001","kind":"paper","name":"Esthesioneuroblastoma: a meta-analysis and review","aka":[],"tldr":"Pooling every published series of this rare nasal cancer showed that about 45 percent of patients survive five years, that surgery followed by radiotherapy gives the best results, and that the Kadish stage and Hyams grade predict outcome.","summary":"Meta-analysis of 26 studies including 390 patients with esthesioneuroblastoma published between 1990 and 2000, examining survival by treatment modality, Kadish stage and Hyams grade.\n\nFive-year survival was 45 percent overall; combined surgery and radiotherapy achieved about 65 percent, better than either alone, and low Hyams grade and lower Kadish stage were favourable. The review remains the reference for treatment planning in a tumour that will never have a randomised trial.","asOf":"2026-09-18","links":[{"label":"Lancet Oncol 2001","url":"https://doi.org/10.1016/S1470-2045(01)00558-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/11902539/"}],"tags":[],"related":[],"cancers":["esthesioneuroblastoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2001,"doi":"10.1016/S1470-2045(01)00558-7","pmid":"11902539","authors":"Dulguerov P, Allal AS, Calcaterra TC.","paperType":"meta-analysis","findings":["Five-year survival 45 percent overall; about 65 percent with surgery plus radiotherapy.","Kadish stage and Hyams grade were prognostic."],"whatItMeans":"Craniofacial or endoscopic resection followed by radiotherapy is the standard for esthesioneuroblastoma, with chemotherapy reserved for high-grade or advanced disease.","caveats":["Pooled retrospective series with heterogeneous staging and treatment.","Predates endoscopic skull base surgery and modern radiotherapy."],"changedPractice":true,"participants":390},{"id":"paper-estimabl2-leboulleux-nejm-2022","kind":"paper","name":"ESTIMABL2: thyroidectomy without radioiodine in patients with low-risk thyroid cancer","aka":[],"tldr":"Skipping radioactive iodine after thyroidectomy for low-risk differentiated thyroid cancer gave the same excellent three-year outcomes as giving it, so most low-risk patients can avoid the treatment.","summary":"Phase 3 non-inferiority trial of 776 patients with low-risk differentiated thyroid cancer (pT1a multifocal to pT1b, N0 or Nx) randomised after total thyroidectomy to postoperative radioiodine (1.1 GBq) or no radioiodine.\n\nAt three years, 95.6 percent of the no-radioiodine group and 95.9 percent of the radioiodine group had no event (abnormal imaging, thyroglobulin rise or further treatment), meeting non-inferiority, with no differences in quality of life or adverse events.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2022","url":"https://doi.org/10.1056/NEJMoa2111953"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35263518/"}],"tags":[],"related":[],"cancers":["papillary-thyroid-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["estimabl2"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/NEJMoa2111953","pmid":"35263518","authors":"Leboulleux S, Bournaud C, Chougnet CN, et al.","paperType":"rct","findings":["Three-year event-free 95.6 percent (no radioiodine) vs 95.9 percent (radioiodine); non-inferior.","Events were mostly biochemical rather than structural."],"whatItMeans":"Radioactive iodine is no longer recommended routinely for low-risk differentiated thyroid cancer, supported also by the UK IoN trial.","caveats":["Follow-up of three years is short for a disease with late recurrences.","Applies to low-risk tumours up to 2 cm without nodal disease."],"changedPractice":true,"participants":776},{"id":"paper-rahib-projection-us-cancer-2040-jama-netw-open-2021","kind":"paper","name":"Estimated Projection of US Cancer Incidence and Death to 2040","aka":[],"tldr":"The 2021 update of the projection that pancreatic cancer will become the second leading cause of cancer death in the United States, now dated to 2040 with about 46,000 deaths a year, as deaths from breast, prostate and bowel cancer fall.","summary":"Rahib, Wehner, Matrisian and Nead combined SEER delay-adjusted incidence rates, US Census population projections (2016) and average annual percentage changes in incidence and death rates to estimate cancer incidence and deaths to 2040. They estimated that breast (364,000 cases), melanoma (219,000), lung (208,000) and colorectal (147,000) would be the commonest cancers, with prostate falling to fourteenth (66,000). Lung cancer (63,000 deaths) would remain the leading cause of cancer death, with pancreatic cancer (46,000) and liver and intrahepatic bile duct cancer (41,000) surpassing colorectal cancer (34,000) to become second and third; breast cancer (30,000) would fall to fifth.","asOf":"2026-09-24","links":[{"label":"JAMA Netw Open 2021","url":"https://doi.org/10.1001/jamanetworkopen.2021.4708"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33825840/"}],"tags":["pancreatic-evidence"],"related":["paper-rahib-projecting-cancer-deaths-2030-cancerres-2014","pancan"],"cancers":["pancreatic","hcc","colorectal"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-funding-allocation"],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA Network Open","year":2021,"doi":"10.1001/jamanetworkopen.2021.4708","pmid":"33825840","authors":"Rahib L, Wehner MR, Matrisian LM, Nead KT.","paperType":"observational","findings":["Pancreatic cancer projected to cause about 46,000 US deaths in 2040, second only to lung cancer (63,000).","Liver cancer third (41,000); colorectal falls to fourth (34,000) and breast to fifth (30,000)."],"whatItMeans":"Pancreatic cancer's share of cancer deaths rises because it is standing still while others improve; the 2014 projection to 2030 already made it the second cause of cancer death in the UK's peer countries, and this is the funding argument charities on both sides of the Atlantic use.","caveats":["Projections extrapolate current trends; a treatment as large as the 2026 RAS inhibitor result would bend them.","US data; UK deaths are around 10,000 a year (Cancer Research UK)."]},{"id":"paper-wouters-jama","kind":"paper","name":"Estimated Research and Development Investment Needed to Bring a New Medicine to Market, 2009-2018","aka":[],"tldr":"Paper cited by one bottleneck page, indexed on Europe PMC as PubMed record 32125404 and published in JAMA; the citing page links this DOI, which is how the record was matched.","summary":"Importance: The mean cost of developing a new drug has been the subject of debate, with recent estimates ranging from $314 million to $2.8 billion.\n\nObjective: To estimate the research and development investment required to bring a new therapeutic agent to market, using publicly available data.\n\nDesign and setting: Data were analyzed on new therapeutic agents approved by the US Food and Drug Administration (FDA) between 2009 and 2018 to estimate the research and development expenditure required to bring a new medicine to market. Data were accessed from the US Securities and Exchange Commission, Drugs@FDA database, and ClinicalTrials.gov, alongside published data on clinical trial success rates.\n\nExposures: Conduct of preclinical and clinical studies of new therapeutic agents.\n\nMain outcomes and measures: Median and mean research and development spending on new therapeutic agents approved by the FDA, capitalized at a real cost of capital rate (the required rate of return for an investor) of 10.5% per year, with bootstrapped CIs. All amounts were reported in 2018 US dollars.\n\nResults: The FDA approved 355 new drugs and biologics over the study period. Research and development expenditures were available for 63 (18%) products, developed by 47 different companies. After accounting for the costs of failed trials, the median capitalized research and development investment to bring a new drug to market was estimated at $985.3 million (95% CI, $683.6 million-$1228.9 million), and the mean investment was estimated at $1335.9 million (95% CI, $1042.5 million-$1637.5 million) in the base case analysis. Median estimates by therapeutic area (for areas with ≥5 drugs) ranged from $765.9 million (95% CI, $323.0 million-$1473.5 million) for nervous system agents to $2771.6 million (95% CI, $2051.8 million-$5366.2 million) for antineoplastic and immunomodulating agents. Data were mainly accessible for smaller firms, orphan drugs, products in certain therapeutic areas, first-in-class drugs, therapeutic agents that received accelerated approval, and products approved between 2014 and 2018. Results varied in sensitivity analyses using different estimates of clinical trial success rates, preclinical expenditures, and cost of capital.\n\nConclusions and relevance: This study provides an estimate of research and development costs for new therapeutic agents based on publicly available data. Differences from previous studies may reflect the spectrum of products analyzed, the restricted availability of data in the public domain, and differences in underlying assumptions in the cost calculations.\n\nIndexed on Europe PMC as PubMed record 32125404 (DOI 10.1001/jama.2020.1166). Matched by DOI alone: one bottleneck page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA 2020","url":"https://doi.org/10.1001/jama.2020.1166"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32125404/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32125404"}],"tags":["europepmc-ingest"],"related":["b-trial-design"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2020,"doi":"10.1001/jama.2020.1166","pmid":"32125404","authors":"Wouters OJ, McKee M, Luyten J","paperType":"basic","findings":[],"whatItMeans":"One bottleneck page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-barton-radiother-oncol","kind":"paper","name":"Estimating the demand for radiotherapy from the evidence: a review of changes from 2003 to 2012","aka":[],"tldr":"Paper cited by one bottleneck page, indexed on Europe PMC as PubMed record 24833561 and published in Radiotherapy and Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background and purpose: In 2003 we estimated that 52.3% of new cases of cancer in Australia had an indication for external beam radiotherapy at least once at some time during the course of their illness. This update reviews the contemporary evidence to define the optimal proportion of new cancers that would benefit from radiotherapy as part of their treatment and estimates the changes to the optimal radiotherapy utilisation rate from 2003 to 2012.\n\nMaterials and methods: National and international guidelines were reviewed for external beam radiotherapy indications in the management of cancers. Epidemiological data on the proportion of new cases of cancer with each indication for radiotherapy were identified. Indications and epidemiological data were merged to develop an optimal radiotherapy utilisation tree. Univariate and Monte Carlo simulations were used in sensitivity analysis.\n\nResults: The overall optimal radiotherapy utilisation rate (external beam radiotherapy) for all registered cancers in Australia changed from 52.3% in 2003 to 48.3% in 2012. Overall 8.9% of all cancer patients in Australia have at least one indication for concurrent chemo-radiotherapy during the course of their illness.\n\nConclusions: The reduction in the radiotherapy utilisation rate was due to changes in epidemiological data, changes to radiotherapy indications and refinements of the model structure.\n\nIndexed on Europe PMC as PubMed record 24833561 (DOI 10.1016/j.radonc.2014.03.024). Matched by DOI alone: one bottleneck page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Radiother Oncol 2014","url":"https://doi.org/10.1016/j.radonc.2014.03.024"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24833561/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/24833561"}],"tags":["europepmc-ingest"],"related":["b-surgery-radiation-innovation"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["radiotherapy-and-oncology"],"dependsOn":[],"notes":[],"journal":"Radiotherapy and Oncology","year":2014,"doi":"10.1016/j.radonc.2014.03.024","pmid":"24833561","authors":"Barton MB, Jacob S, Shafiq J, et al.","paperType":"review","findings":[],"whatItMeans":"One bottleneck page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-wong-biostatistics","kind":"paper","name":"Estimation of clinical trial success rates and related parameters","aka":[],"tldr":"Paper cited by one bottleneck page and 22 idea pages, indexed on Europe PMC as PubMed record 29394327 and published in Biostatistics (Oxford, England); the citing pages link this DOI, which is how the record was matched.","summary":"Previous estimates of drug development success rates rely on relatively small samples from databases curated by the pharmaceutical industry and are subject to potential selection biases. Using a sample of 406 038 entries of clinical trial data for over 21 143 compounds from January 1, 2000 to October 31, 2015, we estimate aggregate clinical trial success rates and durations. We also compute disaggregated estimates across several trial features including disease type, clinical phase, industry or academic sponsor, biomarker presence, lead indication status, and time. In several cases, our results differ significantly in detail from widely cited statistics. For example, oncology has a 3.4% success rate in our sample vs. 5.1% in prior studies. However, after declining to 1.7% in 2012, this rate has improved to 2.5% and 8.3% in 2014 and 2015, respectively. In addition, trials that use biomarkers in patient-selection have higher overall success probabilities than trials without biomarkers.\n\nIndexed on Europe PMC as PubMed record 29394327 (DOI 10.1093/biostatistics/kxx069). Matched by DOI alone: one bottleneck page and 22 idea pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Biostatistics 2019","url":"https://doi.org/10.1093/biostatistics/kxx069"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29394327/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29394327"}],"tags":["europepmc-ingest"],"related":["b-preclinical-models","idea-bio1-negative-preclinical-repository","idea-bio1-virtual-cell-perturbation","idea-bio1-rare-cancer-organoid-bank","idea-bio1-metastatic-niche-models","idea-bio1-reverse-translation-resistance-models","idea-bio1-ctc-derived-explants","idea-bio1-organoid-immune-coculture","idea-bio1-organoid-assay-clinical-validation","idea-bio1-immune-matched-humanised-mice","idea-bio1-in-silico-trials-dose","idea-bio1-ex-vivo-perfused-tumour","idea-bio1-multi-organ-chip-tox","idea-bio1-somatic-crispr-gemms","idea-bio1-multicentre-mouse-trials","idea-bio1-co-clinical-avatar-trials","idea-bio1-model-predictivity-benchmark","idea-moon-self-driving-cancer-labs","idea-bio1-aged-comorbid-models","idea-bio1-tumour-slice-cultures","idea-bio1-tumour-on-chip-penetration","idea-bio1-organoid-cell-therapy-potency","idea-bio1-zebrafish-avatars"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Biostatistics (Oxford, England)","year":2019,"doi":"10.1093/biostatistics/kxx069","pmid":"29394327","authors":"Wong CH, Siah KW, Lo AW","paperType":"observational","findings":[],"whatItMeans":"One bottleneck page and 22 idea pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-haslam-jama-netw-open","kind":"paper","name":"Estimation of the Percentage of US Patients With Cancer Who Are Eligible for and Respond to Checkpoint Inhibitor Immunotherapy Drugs","aka":[],"tldr":"Paper cited by two bottleneck pages and 32 idea pages, indexed on Europe PMC as PubMed record 31050774 and published in JAMA network open; the citing pages link this DOI, which is how the record was matched.","summary":"Importance: Immunotherapy checkpoint inhibitors have generated considerable interest because of durable responses in a number of hitherto intractable tumor types.\n\nObjective: To estimate the percentage of patients with cancer in the United States who are eligible for and respond to checkpoint inhibitor drugs approved for oncology indications by the US Food and Drug Administration (FDA).\n\nDesign, setting, and participants: Retrospective cross-sectional study performed from June 2018 through October 2018 using publicly available data to determine (1) demographic characteristics of patients with advanced or metastatic cancer, (2) FDA data on checkpoint inhibitors approved from January 2011 through August 2018, (3) measures of response from drug labels, and (4) published reports estimating the frequency of various inclusion criteria.\n\nMain outcomes and measures: The estimated percentages of US patients with cancer who are eligible for and who respond to immunotherapy checkpoint inhibitor drugs, by year.\n\nResults: Six checkpoint inhibitor drugs were approved for 14 indications between March 25, 2011, and August 17, 2018. The estimated percentage of patients with cancer who were eligible for checkpoint inhibitor drugs increased from 1.54% (95% CI, 1.51%-1.57%) in 2011 to 43.63% (95% CI, 43.51%-43.75%) in 2018. The percentage of patients with cancer estimated to respond to checkpoint inhibitor drugs was 0.14% (95% CI, 0.13%-0.15%) in 2011 when ipilimumab was approved for unresectable or metastatic melanoma and increased to 5.86% (95% CI, 5.80%-5.92%) by 2015. By 2018, the estimated percentage of responders increased to 12.46% (95% CI, 12.37%-12.54%).\n\nConclusions and relevance: The estimated percentages of patients who are eligible for and who respond to checkpoint inhibitor drugs are higher than reported estimates for drugs approved for genome-driven oncology but remain modest. Future research should explore biomarkers to maximize the benefit of immunotherapy among patients receiving it.\n\nIndexed on Europe PMC as PubMed record 31050774 (DOI 10.1001/jamanetworkopen.2019.2535). Matched by DOI alone: two bottleneck pages and 32 idea pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA Netw Open 2019","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31050774/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31050774"}],"tags":["europepmc-ingest"],"related":["b-tme-immunosuppression","b-immunotherapy-response","idea-bio2-tumour-anchored-tgfbeta-trap","idea-bio2-myeloid-engager-bispecific","idea-bio2-complement-c5ar-blockade","idea-nl-diet-covariates-io-trials","idea-bio2-antigen-presentation-triage","idea-bio2-cxcr2-neutrophil-blockade","idea-bio2-lactate-acid-axis","idea-bio2-engineered-bacteria-payloads","idea-bio2-tertiary-lymphoid-induction","idea-bio2-implantable-microdevice-screen","idea-moon-cold-to-hot-programme","idea-bio2-caf-subtype-assignment","idea-bio2-histotripsy-immune-priming","idea-bio2-oncolytic-regulated-il12","idea-bio2-radiotherapy-sting-fractionation","idea-bio2-io-biomarker-data-commons","idea-bio2-antibiotic-stewardship-io","idea-bio2-trem2-myeloid-reprogramming","idea-bio2-til-reactivity-selection","idea-bio2-fmt-plus-checkpoint-phase3","idea-bio2-fibre-diet-io-trial","idea-bio2-trained-immunity-priming","idea-bio2-steroid-sparing-irae","idea-bio2-intracavitary-immunotherapy","idea-bio2-in-situ-vaccination-solid","idea-bio2-spatial-signature-cdx","idea-bio2-epigenetic-priming-cold-tumours","idea-bio2-ctdna-six-week-io-switch","idea-bio2-hypoxia-guided-adenosine","idea-bio2-vascular-normalisation-window","idea-bio2-neoadjuvant-biomarker-engine","idea-bio2-tcr-repertoire-early-readout"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"JAMA network open","year":2019,"doi":"10.1001/jamanetworkopen.2019.2535","pmid":"31050774","authors":"Haslam A, Prasad V","paperType":"observational","findings":[],"whatItMeans":"Two bottleneck pages and 32 idea pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-copson-posh-ethnicity-young-breast-cancer-uk-bjc-2014","kind":"paper","name":"Ethnicity and outcome of young breast cancer patients in the United Kingdom: the POSH study","aka":[],"tldr":"The UK cohort of 2,915 women diagnosed with breast cancer at 40 or younger in which Black women had more triple-negative tumours (26 versus 19 percent) and worse survival despite the same access to care and the same use of chemotherapy.","summary":"Copson, Maishman, Gerty, Eccles and colleagues compared tumour pathology, treatment and outcome across ethnic groups in the POSH national cohort of women aged 40 or under at breast cancer diagnosis. Ethnicity was available for 2,915 patients: 2,690 (91.0 percent) White, 118 (4.0 percent) Black and 87 (2.9 percent) Asian. Median tumour diameter was larger in Black than White women (26.0 versus 22.0 mm, p=0.0103) and multifocal tumours more frequent in Black (43.4 percent) and Asian (37.0 percent) than White women (28.9 percent). Triple-negative tumours were more frequent in Black (26.1 percent) than White women (18.6 percent, p=0.043). Chemotherapy use was equally high (89, 88.6 and 89.7 percent). Five-year distant relapse-free survival was lower in Black women (62.8 percent) than Asian (77.0 percent, p=0.0473) or White women (77.0 percent, p=0.0053), and five-year overall survival 71.1 percent (95 percent CI 61.0 to 79.1) versus 82.4 percent (80.8 to 83.9) for White women (p=0.0160). In multivariate analysis Black ethnicity independently affected distant relapse-free survival in oestrogen receptor-positive disease (hazard ratio 1.60, 1.03 to 2.47).","asOf":"2026-09-24","links":[{"label":"Br J Cancer 2014","url":"https://doi.org/10.1038/bjc.2013.650"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24149174/"}],"tags":["tnbc-evidence"],"related":["paper-carey-race-breast-cancer-subtypes-cbcs-jama-2006"],"cancers":["tnbc","breast-hr-positive"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["cruk"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-diversity","b-care-fragmentation"],"keyPapers":[],"journals":["british-journal-of-cancer"],"dependsOn":[],"notes":[],"journal":"British Journal of Cancer","year":2014,"doi":"10.1038/bjc.2013.650","pmid":"24149174","authors":"Copson E, Maishman T, Gerty S, et al.","paperType":"observational","findings":["Triple-negative tumours in 26.1 percent of Black vs 18.6 percent of White women under 41 (p=0.043).","Five-year overall survival 71.1 vs 82.4 percent for Black vs White women (p=0.0160); chemotherapy use equal at about 89 percent.","Black ethnicity an independent risk factor for distant relapse in oestrogen receptor-positive disease (hazard ratio 1.60)."],"whatItMeans":"The UK's own evidence that the disparity is not only American and not only about access: within the NHS, with equal chemotherapy use, young Black women had more triple-negative disease and worse survival. It anchors the disparities idea on the triple-negative page and the UK and NHS page.","caveats":["Only 118 Black and 87 Asian women; ethnicity self-reported and grouped broadly.","Cohort restricted to women aged 40 or under."],"changedPractice":false,"participants":2915},{"id":"paper-eau-nmibc-guideline-eur-urol-2022","kind":"paper","name":"European Association of Urology guidelines on non-muscle-invasive bladder cancer (Ta, T1 and carcinoma in situ)","aka":[],"tldr":"The European urology guideline sets out how to diagnose, resect, risk-group and treat bladder cancers that have not reached the muscle, including when BCG is needed and when to remove the bladder.","summary":"Evidence-based guideline from the European Association of Urology covering diagnosis, transurethral resection, re-resection, risk stratification, intravesical chemotherapy and BCG, management of BCG failure, and follow-up for non-muscle-invasive bladder cancer.\n\nIt introduces the 2021 EAU risk groups with a very-high-risk category for which early radical cystectomy is recommended, and defines BCG-unresponsive disease for trial and treatment purposes.","asOf":"2026-09-17","links":[{"label":"Eur Urol 2022","url":"https://doi.org/10.1016/j.eururo.2021.08.010"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34511303/"}],"tags":[],"related":[],"cancers":["non-muscle-invasive-bladder-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["european-urology"],"dependsOn":[],"notes":[],"journal":"European Urology","year":2022,"doi":"10.1016/j.eururo.2021.08.010","pmid":"34511303","authors":"Babjuk M, Burger M, Capoun O, et al.","paperType":"guideline","findings":[],"whatItMeans":"Most of the decisions on a non-muscle-invasive bladder cancer page (single instillation, BCG maintenance, early cystectomy, bladder-sparing trials) follow this guideline or its American counterpart.","caveats":["Updated yearly; check the current edition for the latest recommendations on new bladder-sparing agents."],"changedPractice":true},{"id":"paper-european-evidence-based-guidelines-pancreatic-cystic-neoplasms-gut-2018","kind":"paper","name":"European evidence-based guidelines on pancreatic cystic neoplasms (2018)","aka":[],"tldr":"Europe's guideline for pancreatic cysts, covering every cyst type and not only IPMN. It splits reasons to operate into absolute and relative indications and recommends lifelong surveillance for IPMN in anyone fit for surgery.","summary":"Guideline from the European Study Group on Cystic Tumours of the Pancreas, produced with a formal evidence review and covering IPMN, mucinous cystic neoplasm, serous cystic neoplasm, solid pseudopapillary neoplasm and cystic neuroendocrine tumours. Absolute indications for surgery in IPMN are positive cytology for malignancy or high-grade dysplasia, a solid mass, jaundice, an enhancing mural nodule of 5 mm or more and a main duct of 10 mm or more. Relative indications include growth of 5 mm or more per year, raised CA19-9, a main duct of 5 to 9.9 mm, cyst diameter of 40 mm or more, new-onset diabetes, acute pancreatitis and a mural nodule under 5 mm.\n\nIPMN surveillance is lifelong while the patient remains fit for surgery; serous cystadenomas need no follow-up once diagnosed; mucinous cystic neoplasms of 40 mm or more or with symptoms or risk features are resected.","asOf":"2026-09-21","links":[{"label":"Gut 2018","url":"https://doi.org/10.1136/gutjnl-2018-316027"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29574408/"}],"tags":[],"related":[],"cancers":["ipmn-cystic-precursors","pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Gut","year":2018,"doi":"10.1136/gutjnl-2018-316027","pmid":"29574408","authors":"European Study Group on Cystic Tumours of the Pancreas.","paperType":"guideline","findings":["Absolute surgical indications: positive cytology, solid mass, jaundice, enhancing nodule 5 mm or more, main duct 10 mm or more.","Relative indications: growth 5 mm per year, raised CA19-9, main duct 5 to 9.9 mm, cyst 40 mm or more, new diabetes, pancreatitis, nodule under 5 mm.","Lifelong IPMN surveillance while fit for surgery; no follow-up for serous cystadenoma."],"whatItMeans":"European centres manage pancreatic cysts by this guideline; its lifelong surveillance stance is the main point of difference from the American and Kyoto guidelines.","caveats":["Evidence for most recommendations is low quality and consensus-based.","Lifelong surveillance has a cost and burden that has not been tested against stopping rules in trials."],"changedPractice":true},{"id":"paper-eln-2020-cml-hochhaus-leukemia-2020","kind":"paper","name":"European LeukemiaNet 2020 recommendations for treating chronic myeloid leukaemia","aka":[],"tldr":"The 2020 European LeukemiaNet recommendations set the response milestones for kinase inhibitor therapy in chronic myeloid leukaemia, when to switch drugs, and how to manage accelerated and blast phase, including transplant.","summary":"Consensus recommendations covering diagnosis, risk scoring (ELTS), first-line and later-line tyrosine kinase inhibitors, molecular response milestones, treatment-free remission, and the management of advanced-phase disease with kinase inhibitors, chemotherapy and allogeneic transplantation.","asOf":"2026-09-17","links":[{"label":"Leukemia 2020","url":"https://doi.org/10.1038/s41375-020-0776-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32127639/"}],"tags":[],"related":[],"cancers":["cml-advanced-phase"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["leukemia"],"dependsOn":[],"notes":[],"journal":"Leukemia","year":2020,"doi":"10.1038/s41375-020-0776-2","pmid":"32127639","authors":"Hochhaus A, Baccarani M, Silver RT, et al.","paperType":"guideline","findings":[],"whatItMeans":"Whether a patient is on track at three, six and twelve months, and when a change of drug or a transplant referral is warranted, is judged against these milestones.","caveats":["Asciminib and later ponatinib dose data postdate the document."],"changedPractice":true},{"id":"paper-eln-apl-sanz-blood-2019","kind":"paper","name":"European LeukemiaNet recommendations for the management of acute promyelocytic leukaemia (2019 update)","aka":[],"tldr":"The expert panel guidance on acute promyelocytic leukaemia covers the emergency first hours, the choice between arsenic-based and chemotherapy-based regimens by risk, differentiation syndrome, and molecular monitoring.","summary":"Updated recommendations from a European LeukemiaNet expert panel on diagnosis, supportive care for coagulopathy, risk-adapted treatment with all-trans retinoic acid and arsenic trioxide or chemotherapy, management of differentiation syndrome, molecular monitoring and treatment of relapse.","asOf":"2026-09-17","links":[{"label":"Blood 2019","url":"https://doi.org/10.1182/blood-2019-01-894980"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30803991/"}],"tags":[],"related":[],"cancers":["apl"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["miguel-sanz"],"bottlenecks":[],"keyPapers":[],"journals":["blood"],"dependsOn":[],"notes":[],"journal":"Blood","year":2019,"doi":"10.1182/blood-2019-01-894980","pmid":"30803991","authors":"Sanz MA, Sanz MA, Fenaux P, et al.","paperType":"guideline","findings":[],"whatItMeans":"Starting retinoic acid on morphological suspicion, aggressive blood product support and arsenic-based induction for non-high-risk disease all follow from this document.","caveats":["Oral arsenic and gemtuzumab-based regimens for high-risk disease have evolved since publication."],"changedPractice":true},{"id":"paper-ese-ensat-adrenocortical-carcinoma-guideline-eur-j-endocrinol-2018","kind":"paper","name":"European Society of Endocrinology and ENSAT clinical practice guidelines on the management of adrenocortical carcinoma in adults","aka":[],"tldr":"The European endocrine guideline for adrenocortical carcinoma: hormonal work-up, complete surgery by an expert, mitotane for those at high risk of relapse, and EDP-mitotane for disease that has spread.","summary":"Guideline from the European Society of Endocrinology with the European Network for the Study of Adrenal Tumors covering diagnosis and hormonal evaluation of adrenal masses, staging with the ENSAT system, open adrenalectomy in specialist centres, risk stratification by resection status and Ki-67, adjuvant mitotane and radiotherapy, mitotane monitoring, and etoposide, doxorubicin and cisplatin plus mitotane for advanced disease on the FIRM-ACT result.\n\nIt grades the evidence, which is largely retrospective, and recommends care in expert centres and enrolment in registries and trials.","asOf":"2026-09-18","links":[{"label":"Eur J Endocrinol 2018","url":"https://doi.org/10.1530/EJE-18-0608"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30299884/"}],"tags":[],"related":[],"cancers":["localised-adrenocortical-carcinoma","advanced-adrenocortical-carcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":["mitotane"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"European Journal of Endocrinology","year":2018,"doi":"10.1530/EJE-18-0608","pmid":"30299884","authors":"Fassnacht M, Dekkers OM, Else T, et al.","paperType":"guideline","findings":[],"whatItMeans":"The standard-of-care rows on both adrenocortical carcinoma pages, from who gets mitotane after surgery to the EDP-M regimen, follow this guideline.","caveats":["Predates ADIUVO, which found no benefit from adjuvant mitotane in the lowest-risk group.","Most recommendations rest on retrospective series."],"changedPractice":true},{"id":"paper-raverot-eur-j-endocrinol","kind":"paper","name":"European Society of Endocrinology Clinical Practice Guidelines for the management of aggressive pituitary tumours and carcinomas","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 29046323 and published in European journal of endocrinology; the citing page links this DOI, which is how the record was matched.","summary":"Background: Pituitary tumours are common and easily treated by surgery or medical treatment in most cases. However, a small subset of pituitary tumours does not respond to standard medical treatment and presents with multiple local recurrences (aggressive pituitary tumours) and in rare occasion with metastases (pituitary carcinoma). The present European Society of Endocrinology (ESE) guideline aims to provide clinical guidance on diagnosis, treatment and follow-up in aggressive pituitary tumours and carcinomas.\n\nMethods: We decided upfront, while acknowledging that literature on aggressive pituitary tumours and carcinomas is scarce, to systematically review the literature according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. The review focused primarily on first- and second-line treatment in aggressive pituitary tumours and carcinomas. We included 14 single-arm cohort studies (total number of patients = 116) most on temozolomide treatment ( n = 11 studies, total number of patients = 106). A positive treatment effect was seen in 47% (95% CI: 36-58%) of temozolomide treated. Data from the recently performed ESE survey on aggressive pituitary tumours and carcinomas (165 patients) were also used as backbone for the guideline. SELECTED RECOMMENDATION: (i) Patients with aggressive pituitary tumours should be managed by a multidisciplinary expert team. (ii) Histopathological analyses including pituitary hormones and proliferative markers are needed for correct tumour classification. (iii) Temozolomide monotherapy is the first-line chemotherapy for aggressive pituitary tumours and pituitary carcinomas after failure of standard therapies; treatment evaluation after 3 cycles allows identification of responder and non-responder patients. (iv) In patients responding to first-line temozolomide, we suggest continuing treatment for at least 6 months in total. Furthermore, the guideline offers recommendations for patients who recurred after temozolomide treatment, for those who did not respond to temozolomide and for patients with systemic metastasis.\n\nIndexed on Europe PMC as PubMed record 29046323 (DOI 10.1530/eje-17-0796). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Eur J Endocrinol 2018","url":"https://doi.org/10.1530/eje-17-0796"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29046323/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29046323"}],"tags":["europepmc-ingest"],"related":["pituitary-tumours"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"European journal of endocrinology","year":2018,"doi":"10.1530/eje-17-0796","pmid":"29046323","authors":"Raverot G, Burman P, McCormack A, et al.","paperType":"review","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-ev-302-nejm-2024","kind":"paper","name":"EV-302: enfortumab vedotin plus pembrolizumab replaces chemotherapy as first treatment for advanced bladder cancer","aka":[],"tldr":"Combining the Nectin-4 antibody-drug conjugate enfortumab vedotin with pembrolizumab nearly doubled survival compared with platinum chemotherapy in advanced urothelial cancer, the biggest advance in this disease in 40 years.","summary":"Open-label phase 3 trial of 886 patients with untreated locally advanced or metastatic urothelial carcinoma, eligible for cisplatin or carboplatin, randomised to enfortumab vedotin plus pembrolizumab or gemcitabine plus platinum. Dual primary endpoints were PFS by blinded review and OS.\n\nMedian PFS was 12.5 vs 6.3 months (HR 0.45) and median OS 31.5 vs 16.1 months (HR 0.47), with benefit regardless of cisplatin eligibility or PD-L1 expression. It displaced platinum chemotherapy as first-line standard of care, the first regimen to do so since the 1980s, and is the first ADC plus checkpoint inhibitor combination to become a first-line standard in any cancer.","asOf":"2026-09-08","links":[{"label":"NEJM 2024","url":"https://doi.org/10.1056/NEJMoa2312117"},{"label":"ClinicalTrials.gov NCT04223856","url":"https://clinicaltrials.gov/study/NCT04223856"}],"tags":[],"related":[],"cancers":["urothelial"],"sections":[],"technologies":["adc","checkpoint-inhibitor"],"targets":["nectin4","pd1"],"drugs":["enfortumab-vedotin","pembrolizumab"],"companies":["astellas","pfizer","merck"],"institutions":[],"pathways":[],"terms":["pfs","os","orr","first-line","standard-of-care","payload"],"trials":["ev-302"],"people":["shilpa-gupta","shin-sang-joon"],"bottlenecks":["b-combination-space","b-drug-pricing","b-toxicity-qol"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2024,"doi":"10.1056/NEJMoa2312117","authors":"Powles T, Valderrama BP, Gupta S, et al.","paperType":"rct","findings":["Median PFS 12.5 vs 6.3 months; HR 0.45 (95% CI 0.38-0.54).","Median overall survival 31.5 vs 16.1 months; HR 0.47 (95% CI 0.38-0.58).","Objective response 67.7% vs 44.4%; complete response 29.1% vs 12.5%.","Benefit consistent in cisplatin-eligible and -ineligible patients and in PD-L1 high and low tumours.","Grade 3 or higher treatment-related adverse events 55.9% vs 69.5%; skin reactions, peripheral neuropathy and hyperglycaemia were the characteristic toxicities of enfortumab vedotin."],"whatItMeans":"Almost every patient newly diagnosed with advanced bladder or urothelial cancer should now be offered enfortumab vedotin plus pembrolizumab rather than chemotherapy, with median survival extended from about 16 months to over two and a half years. Neuropathy and skin toxicity need monitoring and dose adjustment, and patients with severe diabetes or pre-existing neuropathy need care. Platinum chemotherapy remains an option for those who cannot receive the combination.","caveats":["Open-label; PFS by blinded review.","Only about 30% of chemotherapy patients received maintenance avelumab, which is standard, so the control arm may have underperformed.","Peripheral neuropathy is cumulative and often persistent, affecting quality of life in long survivors.","Very high cost; access outside high-income countries is limited."],"changedPractice":true,"participants":886},{"id":"paper-danchev-jama-netw-open","kind":"paper","name":"Evaluation of Data Sharing After Implementation of the International Committee of Medical Journal Editors Data Sharing Statement Requirement","aka":[],"tldr":"Paper cited by two bottleneck pages and five idea pages, indexed on Europe PMC as PubMed record 33507256 and published in JAMA network open; the citing pages link this DOI, which is how the record was matched.","summary":"Importance: The benefits of responsible sharing of individual-participant data (IPD) from clinical studies are well recognized, but stakeholders often disagree on how to align those benefits with privacy risks, costs, and incentives for clinical trialists and sponsors. The International Committee of Medical Journal Editors (ICMJE) required a data sharing statement (DSS) from submissions reporting clinical trials effective July 1, 2018. The required DSSs provide a window into current data sharing rates, practices, and norms among trialists and sponsors.\n\nObjective: To evaluate the implementation of the ICMJE DSS requirement in 3 leading medical journals: JAMA, Lancet, and New England Journal of Medicine (NEJM).\n\nDesign, setting, and participants: This is a cross-sectional study of clinical trial reports published as articles in JAMA, Lancet, and NEJM between July 1, 2018, and April 4, 2020. Articles not eligible for DSS, including observational studies and letters or correspondence, were excluded. A MEDLINE/PubMed search identified 487 eligible clinical trials in JAMA (112 trials), Lancet (147 trials), and NEJM (228 trials). Two reviewers evaluated each of the 487 articles independently.\n\nExposure: Publication of clinical trial reports in an ICMJE medical journal requiring a DSS.\n\nMain outcomes and measures: The primary outcomes of the study were declared data availability and actual data availability in repositories. Other captured outcomes were data type, access, and conditions and reasons for data availability or unavailability. Associations with funding sources were examined.\n\nResults: A total of 334 of 487 articles (68.6%; 95% CI, 64%-73%) declared data sharing, with nonindustry NIH-funded trials exhibiting the highest rates of declared data sharing (89%; 95% CI, 80%-98%) and industry-funded trials the lowest (61%; 95% CI, 54%-68%). However, only 2 IPD sets (0.6%; 95% CI, 0.0%-1.5%) were actually deidentified and publicly available at April 10, 2020. The remaining were supposedly accessible via request to authors (143 of 334 articles [42.8%]), repository (89 of 334 articles [26.6%]), and company (78 of 334 articles [23.4%]). Among the 89 articles declaring that IPD would be stored in repositories, only 17 (19.1%) deposited data, mostly because of embargo and regulatory approval. Embargo was set in 47.3% of data-sharing articles (158 of 334), and in half of them the period exceeded 1 year or was unspecified.\n\nConclusions and relevance: Most trials published in JAMA, Lancet, and NEJM after the implementation of the ICMJE policy declared their intent to make clinical data available. However, a wide gap between declared and actual data sharing exists. To improve transparency and data reuse, journals should promote the use of unique pointers to data set location and standardized choices for embargo periods and access requirements.\n\nIndexed on Europe PMC as PubMed record 33507256 (DOI 10.1001/jamanetworkopen.2020.33972). Matched by DOI alone: two bottleneck pages and five idea pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA Netw Open 2021","url":"https://doi.org/10.1001/jamanetworkopen.2020.33972"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33507256/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33507256"}],"tags":["europepmc-ingest"],"related":["b-data-silos","b-ip-collaboration","idea-fund-federated-learning-consortium","idea-fund-antitrust-safe-harbour","idea-fund-shelved-asset-escrow","idea-fund-open-results-bonus","idea-fund-scoop-protection-policy"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"JAMA network open","year":2021,"doi":"10.1001/jamanetworkopen.2020.33972","pmid":"33507256","authors":"Danchev V, Min Y, Borghi J, et al.","paperType":"observational","findings":[],"whatItMeans":"Two bottleneck pages and five idea pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-pik3ca-colorectal-j-clin-oncol-2013","kind":"paper","name":"Evaluation of PIK3CA mutation as a predictor of benefit from nonsteroidal anti-inflammatory drug therapy in colorectal cancer","aka":[],"tldr":"Phase 2 or 3 results paper on PIK3CA in Colorectal cancer, in Journal of Clinical Oncology (2013), one of the most cited Europe PMC records with PIK3CA in its title.","summary":"Purpose: Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) protect against colorectal cancer (CRC) and are associated with reduced disease recurrence and improved outcome after primary treatment. However, toxicities of NSAIDs have limited their use as antineoplastic therapy. Recent data have suggested that the benefit of aspirin after CRC diagnosis is limited to patients with PIK3CA-mutant cancers. We sought to determine the predictive utility of PIK3CA mutation for benefit from both cyclooxygenase-2 inhibition and aspirin.\n\nMethods: We performed molecular analysis of tumors from 896 participants in the Vioxx in Colorectal Cancer Therapy: Definition of Optimal Regime (VICTOR) trial, a large randomized trial comparing rofecoxib with placebo after primary CRC resection. We compared relapse-free survival and overall survival between rofecoxib therapy and placebo and between the use and nonuse of low-dose aspirin, according to tumor PIK3CA mutation status.\n\nResults: We found no evidence of a greater benefit from rofecoxib treatment compared with placebo in patients whose tumors had PIK3CA mutations (multivariate adjusted hazard ratio [HR], 1.2; 95% CI, 0.53 to 2.72; P =.66; (P)INTERACTION =.47) compared with patients with PIK3CA wild-type cancers (HR, 0.87; 95% CI, 0.64 to 1.16; P =.34). In contrast, regular aspirin use after CRC diagnosis was associated with a reduced rate of CRC recurrence in patients with PIK3CA-mutant cancers (HR, 0.11; 95% CI, 0.001 to 0.832; P =.027; (P)INTERACTION =.024) but not in patients lacking tumor PIK3CA mutation (HR, 0.92; 95% CI, 0.60 to 1.42; P =.71).\n\nConclusion: Although tumor PIK3CA mutation does not predict benefit from rofecoxib treatment, it merits further evaluation as a predictive biomarker for aspirin therapy. Our findings are concordant with recent data and support the prospective investigation of adjuvant aspirin in PIK3CA-mutant CRC.\n\nIndexed on Europe PMC as PubMed record 24062397 (DOI 10.1200/jco.2013.50.0322). Its title names PIK3CA and its text names Colorectal cancer; PubMed types it as a clinical trial report (Comparative Study, Research Support, Non-U.S. Gov't, Randomized Controlled Trial). It was matched automatically to the idea \"Get biomarker-directed aspirin after colorectal surgery into labels and guidelines\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2013","url":"https://doi.org/10.1200/jco.2013.50.0322"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24062397/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/24062397"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2013,"doi":"10.1200/jco.2013.50.0322","pmid":"24062397","authors":"Domingo E, Church DN, Sieber O, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for PIK3CA in Colorectal cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by PIK3CA in the title and Colorectal cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-wen-j-clin-oncol","kind":"paper","name":"Evaluation of Regorafenib in Newly Diagnosed and Recurrent Glioblastoma: GBM AGILE Phase II/III Bayesian Randomized Platform Trial","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 41980234 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: GBM AGILE (ClinicalTrials.gov identifier: NCT03970447) is a phase II/III Bayesian adaptive platform registration trial testing multiple arms against a common control; the primary end point is overall survival (OS). Regorafenib, a multikinase inhibitor, showed OS benefit in recurrent (RD) glioblastoma in the phase II REGOMA trial and entered GBM AGILE as the first investigational arm.\n\nMethods: Patient subtypes included in the regorafenib arm of GBM AGILE were newly diagnosed unmethylated (NDU) and RD glioblastoma. Prospective defined sets of subtypes, or arm signatures, were NDU, RD, and all (NDU + RD). As the first investigational arm in GBM AGILE, regorafenib was equally randomized to the control arm. Treatment in the control arm is temozolomide + radiotherapy (in newly diagnosed) or lomustine (in RD). Efficacy was assessed by OS hazard ratio (HR), arm/control, and demonstrated when the Bayesian probability of benefit (HR <1.00) was ≥98%. Analysis was performed monthly for limited efficacy, which occurs when the Bayesian predictive power is <25% for all signatures, and determines stopping enrollment. Follow-up continued for 12 months after accrual stopped.\n\nResults: When the predictive power was <25% in all predefined signatures for regorafenib, accrual stopped for limited efficacy. The final analysis did not demonstrate OS improvement in the regorafenib arm in RD nor NDU glioblastoma. Median HRs were 1.05 (NDU), 1.07 (RD), and 1.07 (all) with final probabilities of benefit (HR <1.00) of 0.421 (NDU), 0.312 (RD), and 0.296 (all). Regorafenib was associated with increased toxicity relative to control.\n\nConclusion: GBM AGILE did not show superiority of regorafenib over control in RD (lomustine) or NDU (temozolomide + radiotherapy) glioblastoma, yet caused increased toxicities. Regorafenib has been removed from National Comprehensive Cancer Network guidelines as a treatment option for RD.\n\nIndexed on Europe PMC as PubMed record 41980234 (DOI 10.1200/jco-25-01137). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2026","url":"https://doi.org/10.1200/jco-25-01137"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41980234/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41980234"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["gbm-agile"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2026,"doi":"10.1200/jco-25-01137","pmid":"41980234","authors":"Wen PY, Berry DA, Buxton MB, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-aldrich-uspstf-screening-african-american-smokers-jama-oncol-2019","kind":"paper","name":"Evaluation of USPSTF Lung Cancer Screening Guidelines Among African American Adult Smokers","aka":[],"tldr":"The screening rules were written from a trial in which only 4 percent of participants were Black. In a southern United States cohort, 31 percent of white smokers qualified for screening but only 17 percent of Black smokers, even though Black smokers develop lung cancer at fewer cigarettes.","summary":"Aldrich, Mercaldo, Sandler, Blot, Grogan and Blume tested the diagnostic accuracy of the 2013 United States Preventive Services Task Force eligibility criteria in the Southern Community Cohort Study, a predominantly African American and low-income cohort recruited through community health centres across twelve southern states from 2002 to 2009 and followed for cancer incidence to the end of 2014.\n\nThe finding is a mechanical consequence of writing eligibility in pack-years: Black smokers in the United States smoke fewer cigarettes per day on average but carry a higher lung cancer risk at any given exposure, so a pack-year threshold calibrated on a mostly white trial population excludes them disproportionately. The 2021 update lowered the threshold partly in response.","asOf":"2026-09-25","links":[{"label":"JAMA Oncol 2019","url":"https://doi.org/10.1001/jamaoncol.2019.1402"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31246249/"}],"tags":["lung-evidence"],"related":["paper-uspstf-lung-cancer-screening-jama-2021","paper-nlst-nejm-2011","idea-prev-lung-screening-risk-model-eligibility","idea-prev-mobile-lung-screening-deprived-areas"],"cancers":["lung-cancer","nsclc"],"sections":["early-detection"],"technologies":["low-dose-ct-screening"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-trial-diversity","b-global-access","b-care-fragmentation"],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2019,"doi":"10.1001/jamaoncol.2019.1402","pmid":"31246249","authors":"Aldrich MC, Mercaldo SF, Sandler KL, et al.","paperType":"observational","findings":["Among 48,364 ever smokers, 32,463 (67 percent) were African American and 15,901 (33 percent) were white, with 1,269 incident lung cancers.","5,654 of 32,463 African American smokers (17 percent) were eligible for screening under the 2013 criteria, against 4,992 of 15,901 white smokers (31 percent).","The authors conclude that the guidelines may be too conservative for African American smokers and that race-specific adjustment of pack-year criteria would give more equitable screening."],"whatItMeans":"The clearest published demonstration that a screening eligibility rule can be accurate on average and systematically wrong for a group. It is the empirical core of the argument for replacing pack-year thresholds with individual risk models.","caveats":["A single regional cohort of community health centre attenders; eligibility fractions are not national estimates.","Self-reported smoking histories from follow-up questionnaires.","It evaluates eligibility, not screening outcomes: nobody in the cohort was randomised to be screened."],"changedPractice":true,"participants":48364},{"id":"paper-bolero-2-n-engl-j-med-2012","kind":"paper","name":"Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer","aka":[],"tldr":"Published report from the BOLERO-2 trial registered as NCT00863655, in New England Journal of Medicine (2012), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Resistance to endocrine therapy in breast cancer is associated with activation of the mammalian target of rapamycin (mTOR) intracellular signaling pathway. In early studies, the mTOR inhibitor everolimus added to endocrine therapy showed antitumor activity.\n\nMethods: In this phase 3, randomized trial, we compared everolimus and exemestane versus exemestane and placebo (randomly assigned in a 2:1 ratio) in 724 patients with hormone-receptor-positive advanced breast cancer who had recurrence or progression while receiving previous therapy with a nonsteroidal aromatase inhibitor in the adjuvant setting or to treat advanced disease (or both). The primary end point was progression-free survival. Secondary end points included survival, response rate, and safety. A preplanned interim analysis was performed by an independent data and safety monitoring committee after 359 progression-free survival events were observed.\n\nResults: Baseline characteristics were well balanced between the two study groups. The median age was 62 years, 56% had visceral involvement, and 84% had hormone-sensitive disease. Previous therapy included letrozole or anastrozole (100%), tamoxifen (48%), fulvestrant (16%), and chemotherapy (68%). The most common grade 3 or 4 adverse events were stomatitis (8% in the everolimus-plus-exemestane group vs. 1% in the placebo-plus-exemestane group), anemia (6% vs. <1%), dyspnea (4% vs. 1%), hyperglycemia (4% vs. <1%), fatigue (4% vs. 1%), and pneumonitis (3% vs. 0%). At the interim analysis, median progression-free survival was 6.9 months with everolimus plus exemestane and 2.8 months with placebo plus exemestane, according to assessments by local investigators (hazard ratio for progression or death, 0.43; 95% confidence interval [CI], 0.35 to 0.54; P<0.001). Median progression-free survival was 10.6 months and 4.1 months, respectively, according to central assessment (hazard ratio, 0.36; 95% CI, 0.27 to 0.47; P<0.001).\n\nConclusions: Everolimus combined with an aromatase inhibitor improved progression-free survival in patients with hormone-receptor-positive advanced breast cancer previously treated with nonsteroidal aromatase inhibitors. (Funded by Novartis; BOLERO-2 ClinicalTrials.gov number, NCT00863655.).\n\nIndexed on Europe PMC as PubMed record 22149876 (DOI 10.1056/nejmoa1109653). Its abstract cites the registry id NCT00863655, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2012","url":"https://doi.org/10.1056/nejmoa1109653"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22149876/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/22149876"},{"label":"ClinicalTrials.gov NCT00863655","url":"https://clinicaltrials.gov/study/NCT00863655"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["bolero-2"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2012,"doi":"10.1056/nejmoa1109653","pmid":"22149876","authors":"Baselga J, Campone M, Piccart M, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT00863655 with the most citations, so it is the natural first reading for anyone following the BOLERO-2 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-bolero-2-ann-oncol-2014-update","kind":"paper","name":"Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2†","aka":[],"tldr":"Later report from the BOLERO-2 trial registered as NCT00863655, in Annals of Oncology (2014); its title describes an updated or longer-term analysis.","summary":"Background: The BOLERO-2 study previously demonstrated that adding everolimus (EVE) to exemestane (EXE) significantly improved progression-free survival (PFS) by more than twofold in patients with hormone-receptor-positive (HR(+)), HER2-negative advanced breast cancer that recurred or progressed during/after treatment with nonsteroidal aromatase inhibitors (NSAIs). The overall survival (OS) analysis is presented here.\n\nPatients and methods: BOLERO-2 is a phase III, double-blind, randomized international trial comparing EVE 10 mg/day plus EXE 25 mg/day versus placebo (PBO) + EXE 25 mg/day in postmenopausal women with HR(+) advanced breast cancer with prior exposure to NSAIs. The primary end point was PFS by local investigator assessment; OS was a key secondary end point.\n\nResults: At the time of data cutoff (3 October 2013), 410 deaths had occurred and 13 patients remained on treatment. Median OS in patients receiving EVE + EXE was 31.0 months [95% confidence interval (CI) 28.0-34.6 months] compared with 26.6 months (95% CI 22.6-33.1 months) in patients receiving PBO + EXE (hazard ratio = 0.89; 95% CI 0.73-1.10; log-rank P = 0.14). Poststudy treatments were received by 84% of patients in the EVE + EXE arm versus 90% of patients in the PBO + EXE arm. Types of poststudy therapies were balanced across arms, except for chemotherapy (53% EVE + EXE versus 63% PBO + EXE). No new safety concerns were identified.\n\nConclusions: In BOLERO-2, adding EVE to EXE did not confer a statistically significant improvement in the secondary end point OS despite producing a clinically meaningful and statistically significant improvement in the primary end point, PFS (4.6-months prolongation in median PFS; P < 0.0001). Ongoing translational research should further refine the benefit of mTOR inhibition and related pathways in this treatment setting.\n\nTrial registration number: NCT00863655.\n\nIndexed on Europe PMC as PubMed record 25231953 (DOI 10.1093/annonc/mdu456). Its abstract cites the registry id NCT00863655, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2014","url":"https://doi.org/10.1093/annonc/mdu456"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25231953/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25231953"},{"label":"ClinicalTrials.gov NCT00863655","url":"https://clinicaltrials.gov/study/NCT00863655"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["bolero-2"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2014,"doi":"10.1093/annonc/mdu456","pmid":"25231953","authors":"Piccart M, Hortobagyi GN, Campone M, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the BOLERO-2 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-bozic-elife","kind":"paper","name":"Evolutionary dynamics of cancer in response to targeted combination therapy","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 23805382 and published in eLife; the citing page links this DOI, which is how the record was matched.","summary":"In solid tumors, targeted treatments can lead to dramatic regressions, but responses are often short-lived because resistant cancer cells arise. The major strategy proposed for overcoming resistance is combination therapy. We present a mathematical model describing the evolutionary dynamics of lesions in response to treatment. We first studied 20 melanoma patients receiving vemurafenib. We then applied our model to an independent set of pancreatic, colorectal, and melanoma cancer patients with metastatic disease. We find that dual therapy results in long-term disease control for most patients, if there are no single mutations that cause cross-resistance to both drugs; in patients with large disease burden, triple therapy is needed. We also find that simultaneous therapy with two drugs is much more effective than sequential therapy. Our results provide realistic expectations for the efficacy of new drug combinations and inform the design of trials for new cancer therapeutics. DOI:http://dx.doi.org/10.7554/eLife.00747.001.\n\nIndexed on Europe PMC as PubMed record 23805382 (DOI 10.7554/elife.00747). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Elife 2013","url":"https://doi.org/10.7554/elife.00747"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23805382/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/23805382"}],"tags":["europepmc-ingest"],"related":["drug-resistance-dynamics"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["elife"],"dependsOn":[],"notes":[],"journal":"eLife","year":2013,"doi":"10.7554/elife.00747","pmid":"23805382","authors":"Bozic I, Reiter JG, Allen B, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-exam-cabozantinib-mtc-elisei-jco-2013","kind":"paper","name":"EXAM: cabozantinib in progressive medullary thyroid cancer","aka":[],"tldr":"Cabozantinib, a kinase inhibitor blocking RET, MET and VEGF receptors, delayed progression by more than seven months compared with placebo in progressive medullary thyroid cancer, at the cost of considerable toxicity.","summary":"Phase 3 placebo-controlled trial of 330 patients with progressive metastatic medullary thyroid cancer randomised 2:1 to cabozantinib 140 mg daily or placebo.\n\nMedian progression-free survival was 11.2 versus 4.0 months (hazard ratio 0.28) and response 28 versus 0 percent, with benefit regardless of RET status; diarrhoea, hand-foot syndrome, weight loss and fistula were notable toxicities.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2013","url":"https://doi.org/10.1200/JCO.2012.48.4659"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24002501/"}],"tags":[],"related":[],"cancers":["medullary-thyroid-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["cabozantinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["exam"],"people":["rossella-elisei"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2013,"doi":"10.1200/JCO.2012.48.4659","pmid":"24002501","authors":"Elisei R, Schlumberger MJ, Müller SP, et al.","paperType":"rct","findings":["Median progression-free survival 11.2 vs 4.0 months; hazard ratio 0.28.","Objective response 28 percent vs 0 percent."],"whatItMeans":"Cabozantinib is an option for progressive medullary thyroid cancer, now mainly for RET-negative disease or after selpercatinib.","caveats":["No overall survival benefit overall, though RET M918T carriers may have benefited.","High dose with frequent reductions."],"changedPractice":true,"participants":330},{"id":"paper-fernandez-jama-oncol","kind":"paper","name":"Examination of Low ERBB2 Protein Expression in Breast Cancer Tissue","aka":[],"tldr":"Paper cited by one bottleneck page and 17 idea pages, indexed on Europe PMC as PubMed record 35113160 and published in JAMA Oncology; the citing pages link this DOI, which is how the record was matched.","summary":"Importance: Trastuzumab deruxtecan (T-DXd) has shown efficacy in patients with breast cancer with ERBB2 immunohistochemistry (IHC) scores of 1+ or 2+ but not 0 as read in central pathology laboratories. The drug is currently being tested in large randomized clinical trials with registration intent for this patient population.\n\nObjective: To determine the suitability of the current standard ERBB2 IHC assays to select patients with low ERBB2 positivity for treatment with T-DXd.\n\nDesign and setting: Assessment of data from College of American Pathologists surveys and assessment of analytic data from a Yale University-based study of concordance of 18 pathologists reading 170 breast cancer biopsies.\n\nResults: The total survey data set included scores over 2 years from 1391 to 1452 laboratories of 40 ERBB2 cores from each laboratory (20 cores twice a year for a total of 80). College of American Pathologists surveys show that 19% of cases read by the laboratories generate results with less than or equal to 70% concordance for IHC ERBB2 score 0 vs 1+. When 18 pathologists read the scanned slides from a selected set of breast cancer biopsies using a 4-point scale, there was only 26% concordance between 0 and 1+ compared with 58% concordance between 2+ and 3+.\n\nConclusions and relevance: In this study using a current standard ERBB2 IHC assay, the scoring accuracy for ERBB2 IHC in the low range (0 and 1+) was poor. This inaccuracy in the real world could lead to misassignment of many patients for treatment with T-DXd.\n\nIndexed on Europe PMC as PubMed record 35113160 (DOI 10.1001/jamaoncol.2021.7239). Matched by DOI alone: one bottleneck page and 17 idea pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA Oncol 2022","url":"https://doi.org/10.1001/jamaoncol.2021.7239"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35113160/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35113160"}],"tags":["europepmc-ingest"],"related":["b-biomarker-validation","idea-tr2-prospective-retrospective-path","idea-tr2-hrd-functional-standard","idea-moon-biomarker-validation-utility","idea-tr2-label-assay-concordance","idea-tr2-biomarker-evidence-grading","idea-tr2-cutpoint-lock","idea-tr2-positivity-rate-surveillance","idea-tr2-pdl1-digital-calibration","idea-tr2-biomarker-cwe","idea-tr2-biomarker-study-registry","idea-tr2-biomarker-negative-arms","idea-tr2-bicr-discordance-public","idea-tr2-preanalytics-in-report","idea-tr2-cdx-mutual-recognition","idea-tr2-spatial-biomarker-standards","idea-tr2-marker-stratified-default","idea-tr2-ai-cdx-change-control"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2022,"doi":"10.1001/jamaoncol.2021.7239","pmid":"35113160","authors":"Fernandez AI, Liu M, Bellizzi A, et al.","paperType":"rct","findings":[],"whatItMeans":"One bottleneck page and 17 idea pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-campbell-med-sci-sports-exerc","kind":"paper","name":"Exercise Guidelines for Cancer Survivors: Consensus Statement from International Multidisciplinary Roundtable","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 31626055 and published in Medicine and science in sports and exercise; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: The number of cancer survivors worldwide is growing, with over 15.5 million cancer survivors in the United States alone-a figure expected to double in the coming decades. Cancer survivors face unique health challenges as a result of their cancer diagnosis and the impact of treatments on their physical and mental well-being. For example, cancer survivors often experience declines in physical functioning and quality of life while facing an increased risk of cancer recurrence and all-cause mortality compared with persons without cancer. The 2010 American College of Sports Medicine Roundtable was among the first reports to conclude that cancer survivors could safely engage in enough exercise training to improve physical fitness and restore physical functioning, enhance quality of life, and mitigate cancer-related fatigue.\n\nMethods: A second Roundtable was convened in 2018 to advance exercise recommendations beyond public health guidelines and toward prescriptive programs specific to cancer type, treatments, and/or outcomes.\n\nResults: Overall findings retained the conclusions that exercise training and testing were generally safe for cancer survivors and that every survivor should \"avoid inactivity.\" Enough evidence was available to conclude that specific doses of aerobic, combined aerobic plus resistance training, and/or resistance training could improve common cancer-related health outcomes, including anxiety, depressive symptoms, fatigue, physical functioning, and health-related quality of life. Implications for other outcomes, such as peripheral neuropathy and cognitive functioning, remain uncertain.\n\nConclusions: The proposed recommendations should serve as a guide for the fitness and health care professional working with cancer survivors. More research is needed to fill remaining gaps in knowledge to better serve cancer survivors, as well as fitness and health care professionals, to improve clinical practice.\n\nIndexed on Europe PMC as PubMed record 31626055 (DOI 10.1249/mss.0000000000002116). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Med Sci Sports Exerc 2019","url":"https://doi.org/10.1249/mss.0000000000002116"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31626055/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31626055"}],"tags":["europepmc-ingest"],"related":["exercise-during-chemotherapy"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Medicine and science in sports and exercise","year":2019,"doi":"10.1249/mss.0000000000002116","pmid":"31626055","authors":"Campbell KL, Winters-Stone KM, Wiskemann J, et al.","paperType":"guideline","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-brastianos-nat-genet","kind":"paper","name":"Exome sequencing identifies BRAF mutations in papillary craniopharyngiomas","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 24413733 and published in Nature Genetics; the citing page links this DOI, which is how the record was matched.","summary":"Craniopharyngiomas are epithelial tumors that typically arise in the suprasellar region of the brain. Patients experience substantial clinical sequelae from both extension of the tumors and therapeutic interventions that damage the optic chiasm, the pituitary stalk and the hypothalamic area. Using whole-exome sequencing, we identified mutations in CTNNB1 (β-catenin) in nearly all adamantinomatous craniopharyngiomas examined (11/12, 92%) and recurrent mutations in BRAF (resulting in p.Val600Glu) in all papillary craniopharyngiomas (3/3, 100%). Targeted genotyping revealed BRAF p.Val600Glu in 95% of papillary craniopharyngiomas (36 of 39 tumors) and mutation of CTNNB1 in 96% of adamantinomatous craniopharyngiomas (51 of 53 tumors). The CTNNB1 and BRAF mutations were clonal in each tumor subtype, and we detected no other recurrent mutations or genomic aberrations in either subtype. Adamantinomatous and papillary craniopharyngiomas harbor mutations that are mutually exclusive and clonal. These findings have important implications for the diagnosis and treatment of these neoplasms.\n\nIndexed on Europe PMC as PubMed record 24413733 (DOI 10.1038/ng.2868). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Genet 2014","url":"https://doi.org/10.1038/ng.2868"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24413733/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/24413733"}],"tags":["europepmc-ingest"],"related":["craniopharyngioma"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":2014,"doi":"10.1038/ng.2868","pmid":"24413733","authors":"Brastianos PK, Taylor-Weiner A, Manley PE, et al.","paperType":"observational","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-barbieri-spop-foxa1-med12-prostate-nat-genet-2012","kind":"paper","name":"Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer","aka":[],"tldr":"Sequencing the genes of 112 prostate cancers found the disease's commonest point mutation in a gene nobody had linked to it, and showed those tumours are a separate kind that never carries the usual fusion.","summary":"The exomes of 112 prostate tumour and normal tissue pairs were sequenced. New recurrent mutations were identified in multiple genes including MED12 and FOXA1. SPOP was the most frequently mutated gene, with mutations involving the SPOP substrate-binding cleft in 6 to 15% of tumours across multiple independent cohorts. Prostate cancers with mutant SPOP lacked ETS family gene rearrangements and showed a distinct pattern of genomic alterations, so SPOP mutation appears to define a molecular subtype.","asOf":"2026-09-25","links":[{"label":"Barbieri et al., Nat Genet 2012: exome sequencing of 112 prostate tumour and normal pairs identifies recurrent SPOP, FOXA1 and MED12 mutations","url":"https://doi.org/10.1038/ng.2279"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22610119/"},{"label":"cBioPortal study prad_broad (Broad and Cornell, Nat Genet 2012; 112 sequenced primary tumour and normal pairs)","url":"https://www.cbioportal.org/study/summary?id=prad_broad"}],"tags":[],"related":[],"cancers":["prostate"],"sections":[],"technologies":["wes-wgs"],"targets":["spop","foxa1","erg"],"drugs":[],"companies":[],"institutions":[],"pathways":["ubiquitin-proteasome-system","prostate-cancer-signalling","ar-signaling"],"terms":["driver-mutation","gene-fusion","somatic-mutations-wxs-wgs"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":2012,"doi":"10.1038/ng.2279","pmid":"22610119","authors":"Barbieri CE, Baca SC, Lawrence MS, et al.","paperType":"basic","findings":["SPOP the most frequently mutated gene, in 6 to 15% of tumours across independent cohorts.","Mutations cluster in the substrate-binding cleft of the SPOP protein.","SPOP-mutant tumours lack ETS rearrangements and carry their own copy-number pattern.","New recurrent mutations in FOXA1 and MED12."],"whatItMeans":"It established the fusion-negative side of the prostate cancer taxonomy and made SPOP the disease's signature point mutation, in a ubiquitin ligase adaptor rather than in a kinase, which is part of why prostate cancer has so few druggable drivers.","caveats":["One hundred and twelve exomes, so rarer events were missed; the 1,013-exome reanalysis later found a long tail.","No SPOP-directed medicine exists.","Localised disease, so the mutation frequencies in metastatic disease are different."],"changedPractice":false,"participants":112},{"id":"paper-atun-lancet-oncol","kind":"paper","name":"Expanding global access to radiotherapy","aka":[],"tldr":"Paper cited by two technology pages, two bottleneck pages and one roadmap page, indexed on Europe PMC as PubMed record 26419354 and published in The Lancet Oncology; the citing pages link this DOI, which is how the record was matched.","summary":"Radiotherapy is a critical and inseparable component of comprehensive cancer treatment and care. For many of the most common cancers in low-income and middle-income countries, radiotherapy is essential for effective treatment. In high-income countries, radiotherapy is used in more than half of all cases of cancer to cure localised disease, palliate symptoms, and control disease in incurable cancers. Yet, in planning and building treatment capacity for cancer, radiotherapy is frequently the last resource to be considered. Consequently, worldwide access to radiotherapy is unacceptably low. We present a new body of evidence that quantifies the worldwide coverage of radiotherapy services by country. We show the shortfall in access to radiotherapy by country and globally for 2015-35 based on current and projected need, and show substantial health and economic benefits to investing in radiotherapy. The cost of scaling up radiotherapy in the nominal model in 2015-35 is US$26·6 billion in low-income countries, $62·6 billion in lower-middle-income countries, and $94·8 billion in upper-middle-income countries, which amounts to $184·0 billion across all low-income and middle-income countries. In the efficiency model the costs were lower: $14·1 billion in low-income, $33·3 billion in lower-middle-income, and $49·4 billion in upper-middle-income countries-a total of $96·8 billion. Scale-up of radiotherapy capacity in 2015-35 from current levels could lead to saving of 26·9 million life-years in low-income and middle-income countries over the lifetime of the patients who received treatment. The economic benefits of investment in radiotherapy are very substantial. Using the nominal cost model could produce a net benefit of $278·1 billion in 2015-35 ($265·2 million in low-income countries, $38·5 billion in lower-middle-income countries, and $239·3 billion in upper-middle-income countries). Investment in the efficiency model would produce in the same period an even greater total benefit of $365·4 billion ($12·8 billion in low-income countries, $67·7 billion in lower-middle-income countries, and $284·7 billion in upper-middle-income countries). The returns, by the human-capital approach, are projected to be less with the nominal cost model, amounting to $16·9 billion in 2015-35 (-$14·9 billion in low-income countries; -$18·7 billion in lower-middle-income countries, and $50·5 billion in upper-middle-income countries). The returns with the efficiency model were projected to be greater, however, amounting to $104·2 billion (-$2·4 billion in low-income countries, $10·7 billion in lower-middle-income countries, and $95·9 billion in upper-middle-income countries). Our results provide compelling evidence that investment in radiotherapy not only enables treatment of large numbers of cancer cases to save lives, but also brings positive economic benefits.\n\nIndexed on Europe PMC as PubMed record 26419354 (DOI 10.1016/s1470-2045(15)00222-3). Matched by DOI alone: two technology pages, two bottleneck pages and one roadmap page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2015","url":"https://doi.org/10.1016/s1470-2045(15)00222-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26419354/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26419354"}],"tags":["europepmc-ingest"],"related":["global-oncology-access","radiotherapy-access-gap","b-global-access","b-surgery-radiation-innovation","radiation-roadmap"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2015,"doi":"10.1016/s1470-2045(15)00222-3","pmid":"26419354","authors":"Atun R, Jaffray DA, Barton MB, et al.","paperType":"review","findings":[],"whatItMeans":"Two technology pages, two bottleneck pages and one roadmap page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-fgfr2-cholangiocarcinoma-int-j-mol-sci-2025","kind":"paper","name":"Expanding Horizons in Cholangiocarcinoma: Emerging Targets Beyond FGFR2 and IDH1","aka":[],"tldr":"Review on FGFR2 in Biliary tract cancer, in International journal of molecular sciences (2025), one of the most cited Europe PMC records with FGFR2 in its title.","summary":"Cholangiocarcinoma (CCA) is a biliary tract cancer that accounts for approximately 3% of all gastrointestinal cancers. CCA is a \"silent\" disease that remains undetected for a long period of time, often presenting at an advanced stage with minimal treatment options and a poor prognosis. Advanced CCA remains largely inoperable, and combination gemcitabine plus cisplatin (GemCis) chemotherapy remains the standard treatment for patients affected by this disease. There is a desperate need for new therapeutic alternatives, and extensive research is ongoing to address this gap. Targeted therapies represent a rapidly expanding area of cancer treatment and are currently under active investigation in CCA. The FDA has approved the targeted therapies ivosidenib, pemigatinib, infigratinib, and futibatinib, as well as the immunotherapy durvalumab, for patients with CCA in recent years. Several other therapeutic strategies are still under investigation, targeting molecular pathways including p53/MDM2, JAK/STAT, KRAS, HER2, VEGFR, PDGFR, MET, ALK, MAPK, PI3K/AKT, BRAF, and DNA damage repair signaling. While several promising advancements have been made, further research is required to improve outcomes for patients with CCA. This review provides an up-to-date, comprehensive overview of currently approved targeted therapies in CCA, as well as those under investigation.\n\nIndexed on Europe PMC as PubMed record 41226789 (DOI 10.3390/ijms262110755). Its title names FGFR2 and its text names Biliary tract cancer; PubMed types it as a review (review-article, Review). It was matched automatically to the idea \"ctDNA-guided switching among FGFR inhibitors\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Int J Mol Sci 2025","url":"https://doi.org/10.3390/ijms262110755"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41226789/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41226789"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"International journal of molecular sciences","year":2025,"doi":"10.3390/ijms262110755","pmid":"41226789","authors":"Darman L, Kaurich Q, Hassan MS, et al.","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for FGFR2 in Biliary tract cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by FGFR2 in the title and Biliary tract cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-brown-clin-trials","kind":"paper","name":"Experiences of running a stratified medicine adaptive platform trial: Challenges and lessons learned from 10 years of the FOCUS4 trial in metastatic colorectal cancer","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 35083924 and published in Clinical trials (London, England); the citing page links this DOI, which is how the record was matched.","summary":"Background: Complex innovative design trials are becoming increasingly common and offer potential for improving patient outcomes in a faster time frame. FOCUS4 was the first molecularly stratified trial in metastatic colorectal cancer and it remains one of the first umbrella trial designs to be launched globally. Here, we aim to describe lessons learned from delivery of the trial over the last 10 years.\n\nMethods: FOCUS4 was a Phase II/III molecularly stratified umbrella trial testing the safety and efficacy of targeted therapies in metastatic colorectal cancer. It used adaptive statistical methodology to decide which sub-trial should close early, and new therapies were added as protocol amendments. Patients with newly diagnosed metastatic colorectal cancer were registered, and central laboratory testing was used to stratify their tumour into molecular subtypes. Following 16 weeks of first-line therapy, patients with stable or responding disease were eligible for randomisation into either a molecularly stratified sub-trial (FOCUS4-B, C or D) or non-stratified FOCUS4-N. The primary outcome for all studies was progression-free survival comparing the intervention with active monitoring/placebo. At the close of the trial, feedback was elicited from all investigators through surveys and interviews and consolidated into a series of recommendations and lessons learned for the delivery of similar future trials.\n\nResults: Between January 2014 and October 2020, 1434 patients were registered from 88 UK hospitals. Of the 20 drug combinations that were explored for inclusion in the platform trial, three molecularly targeted sub-trials were activated: FOCUS4-D (February 2014-March 2016) evaluated AZD8931 in the BRAF-PIK3CA-RAS wildtype subgroup; FOCUS4-B (February 2016-July 2018) evaluated aspirin in the PIK3CA mutant subgroup and FOCUS4-C (June 2017-October 2020) evaluated adavosertib in the RAS+TP53 double mutant subgroup. FOCUS4-N was active throughout and evaluated capecitabine monotherapy versus a treatment break. A total of 361 (25%) registered patients were randomised into a sub-trial. Feedback on the experiences of delivery of FOCUS4 could be grouped into three main areas of challenge: funding/infrastructure, biomarker testing procedures and trial design efficiencies within which 20 recommendations are summarised.\n\nConclusion: Adaptive stratified medicine platform studies are feasible in common cancers but present challenges. Our stakeholder feedback has helped to inform how these trial designs can succeed and answer multiple questions efficiently, providing resource is adequate.\n\nIndexed on Europe PMC as PubMed record 35083924 (DOI 10.1177/17407745211069879). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Clin Trials 2022","url":"https://doi.org/10.1177/17407745211069879"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35083924/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35083924"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["focus4"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Clinical trials (London, England)","year":2022,"doi":"10.1177/17407745211069879","pmid":"35083924","authors":"Brown LC, Graham J, Fisher D, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-explorer-avapritinib-advanced-systemic-mastocytosis-nat-med-2021","kind":"paper","name":"EXPLORER: safety and efficacy of avapritinib in advanced systemic mastocytosis (phase 1)","aka":[],"tldr":"The first study of avapritinib, a drug designed to hit the KIT D816V mutation that drives most mastocytosis, produced responses in three quarters of patients with advanced disease and set the dose for later trials.","summary":"Phase 1 dose-escalation and expansion study of 86 patients with advanced systemic mastocytosis treated with avapritinib, a selective inhibitor of KIT D816V.\n\nThe overall response rate in response-evaluable patients was 75 percent with deep and durable responses, falls in serum tryptase and KIT D816V allele burden, and a recommended dose of 200 mg daily; cognitive effects and intracranial bleeding (mainly with severe thrombocytopenia) were the notable toxicities. The results, with PATHFINDER, led to approval of avapritinib for advanced systemic mastocytosis in 2021.","asOf":"2026-09-18","links":[{"label":"Nat Med 2021","url":"https://doi.org/10.1038/s41591-021-01538-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34873347/"}],"tags":[],"related":[],"cancers":["advanced-systemic-mastocytosis"],"sections":[],"technologies":[],"targets":[],"drugs":["avapritinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2021,"doi":"10.1038/s41591-021-01538-9","pmid":"34873347","authors":"DeAngelo DJ, Radia DH, George TI, et al.","paperType":"observational","findings":["Overall response 75 percent in evaluable patients; complete remissions with full or partial haematological recovery in a substantial minority.","Intracranial haemorrhage occurred mainly in patients with platelet counts below 50,000 per microlitre, prompting a platelet threshold for treatment."],"whatItMeans":"Avapritinib is the most active drug in advanced systemic mastocytosis; platelet counts must be checked before and during treatment.","caveats":["Phase 1 without a comparator; response criteria changed between cohorts.","Cognitive adverse effects are common and dose-related."],"changedPractice":true,"participants":86},{"id":"paper-boissiere-michot-her2-ultralow-tnbc-virchows-arch-2026","kind":"paper","name":"Exploring the spectrum of HER2 in non-metastatic triple negative breast cancer: from HER2-null to HER2-low, including HER2-ultralow status","aka":[],"tldr":"Reclassifying 367 chemotherapy-naive triple-negative cancers put 38% in HER2-null, 38% in HER2-ultralow and 24% in HER2-low; the categories differed a little in size, grade and BRCA1 methylation but not in relapse over ten years.","summary":"367 patients with non-metastatic TNBC who never received chemotherapy were reclassified: HER2 0 tumours as HER2-null (no staining) or HER2-ultralow (10% or fewer cells with faint incomplete membrane staining); 1+ or non-amplified 2+ as HER2-low. 38.4% were null, 37.6% ultralow and 24.0% low. Ultralow tumours were more often associated with tertiary lymphoid structures (P 0.0259) and BRCA1 promoter methylation (P 0.0439) than low tumours, and were smaller and of lower stage and grade than null tumours. Age, nodal status, histology, molecular apocrine or basal-like phenotype, PIK3CA and PTEN status, CD3, CD20 and CD163 infiltrates and PD-L1 did not differ. Relapse-free survival at a median 10.3 years was unaffected by HER2 category.","asOf":"2026-09-24","links":[{"label":"Boissiere-Michot et al., Virchows Arch 2026: HER2-null, ultralow and low in 367 chemotherapy-naive non-metastatic TNBCs","url":"https://doi.org/10.1007/s00428-026-04425-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41636845/"}],"tags":[],"related":["her2-ultralow","her2-low-ihc","her2-ihc-0"],"cancers":["tnbc","tnbc-early"],"sections":[],"technologies":[],"targets":["her2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["her2-low","ihc"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Virchows Archiv","year":2026,"doi":"10.1007/s00428-026-04425-1","pmid":"41636845","authors":"Boissiere-Michot F, Gudin-De-Vallerin A, Thezenas S, et al.","paperType":"observational","findings":["HER2-null 38.4%, ultralow 37.6%, low 24.0% of 367 TNBCs.","Ultralow tumours smaller, lower grade, more BRCA1 promoter methylation; no survival difference."],"whatItMeans":"Three-quarters of chemotherapy-naive TNBC would be low or ultralow by the DESTINY-Breast06 definitions, but ultralow is unlabelled in TNBC and carries no prognostic weight.","caveats":["Single French cohort of untreated patients, so favourable-risk.","Ultralow scoring has low inter-pathologist reproducibility."],"changedPractice":false,"participants":367},{"id":"paper-ghai-california-poison-control-ivermectin-2024","kind":"paper","name":"Exposures to bleach, peroxide, disinfectants, antimalarials, and ivermectin reported to the California Poison Control System before and during the COVID-19 pandemic, 2015 to 2021","aka":[],"tldr":"California's poison control system saw ivermectin exposures rise steadily through 2021 as people tried it against COVID-19, from about 14 a month to a rising monthly count.","summary":"Interrupted time-series analysis of California Poison Control System reports from 2015 through 2021 found that reported ivermectin exposures were stable at 14.5 a month before December 2020 and then increased by 2.05 a month through December 2021 (Ghai poison centre trends 2024). Exposures to household cleaning products also rose sharply in March 2020, while antimalarial exposures did not change significantly (Ghai poison centre trends 2024).","asOf":"2026-09-24","links":[{"label":"Ghai poison centre trends 2024","url":"https://doi.org/10.1177/00333549231201679"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37933467/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["ivermectin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo agent (Claude Fable 5.1)","editedOn":"2026-09-24","note":"Written from cached ClinicalTrials.gov v2, Europe PMC, DailyMed, Drugs@FDA and WHO eEML responses; no figure appears without its source link."},"journal":"Public Health Reports","year":2024,"doi":"10.1177/00333549231201679","pmid":"37933467","authors":"Ghai A, Sabour E, Salonga R, Ho R, Apollonio DE.","paperType":"observational","findings":["Ivermectin exposure reports rose by about two a month from December 2020 through December 2021, from a baseline of 14.5 a month."],"whatItMeans":"Population-level evidence that when a drug is promoted online for an unproven use, poison centres see the result.","caveats":["Reports to a poison centre undercount exposures and do not record severity in this analysis."],"changedPractice":false},{"id":"paper-cd47-colorectal-cancers-basel-2025","kind":"paper","name":"Expression and Clinical Significance of CD47 in Colorectal Cancer: A Review","aka":[],"tldr":"Review on CD47 in Colorectal cancer, in Cancers (2025), one of the most cited Europe PMC records with CD47 in its title.","summary":"Cluster of Differentiation 47 (CD47), an innate immune checkpoint, facilitates immune escape by binding signal regulatory protein alpha (SIRPα) to inhibit macrophage phagocytosis. Its significance in colorectal cancer (CRC) has garnered heightened interest. This review summarizes five immunohistochemistry (IHC) studies and complementary transcriptomic analyses assessing CD47 in CRC. IHC results consistently indicated membrane overexpression, though positivity rates varied widely (16-91%) due to methodological heterogeneity. Transcriptomic results confirmed CD47 upregulation, especially in Consensus Molecular Subtype 1 (CMS1) and CMS4 subtypes and revealed co-expression with immune checkpoints and oncogenic pathways. Clinically, high CD47 levels were associated with advanced TNM stage, metastasis, poor differentiation, and altered immune infiltration; however, the prognostic significance varied among cohorts. Overall, CD47 appears to be a promising biomarker and therapeutic target, but clinical translation requires standardized evaluation, including harmonized antibody selection and scoring cut-offs, and prospective validation.\n\nIndexed on Europe PMC as PubMed record 41514569 (DOI 10.3390/cancers18010054). Its title names CD47 and its text names Colorectal cancer; PubMed types it as a review (review-article, Review). It was matched automatically to the idea \"Engineered bacteria that live in tumours and manufacture drugs there\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancers (Basel) 2025","url":"https://doi.org/10.3390/cancers18010054"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41514569/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41514569"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancers-mdpi"],"dependsOn":[],"notes":[],"journal":"Cancers","year":2025,"doi":"10.3390/cancers18010054","pmid":"41514569","authors":"Li Q, Vignali P, Tang D, et al.","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for CD47 in Colorectal cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by CD47 in the title and Colorectal cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-ezh2-colorectal-br-j-cancer-2009","kind":"paper","name":"Expression of EZH2 and Ki-67 in colorectal cancer and associations with treatment response and prognosis","aka":[],"tldr":"Phase 2 or 3 results paper on EZH2 in Colorectal cancer, in British Journal of Cancer (2009), one of the most cited Europe PMC records with EZH2 in its title.","summary":"Background: Enhancer of zeste homologue 2 (EZH2) is a member of the Polycomb group of genes that is involved in epigenetic silencing and cell cycle regulation.\n\nMethods: We studied EZH2 expression in 409 patients with colorectal cancer stages II and III. The patients were included in a randomised study, and treated with surgery alone or surgery followed by adjuvant chemotherapy.\n\nResults: EZH2 expression was significantly related to increased tumour cell proliferation, as assessed by Ki-67 expression. In colon cancer, strong EZH2 expression (P=0.041) and high proliferation (>or=40%; P=0.001) were both associated with better relapse-free survival (RFS). In contrast, no such associations were found among rectal cancers. High Ki-67 staining was associated with improved RFS in colon cancer patients who received adjuvant chemotherapy (P=0.001), but not among those who were treated by surgery alone (P=0.087). In colon cancers stage III, a significant association between RFS and randomisation group was found in patients with high proliferation (P=0.046), but not in patients with low proliferation (P=0.26). Multivariate analyses of colon cancers showed that stage III (hazard ratio (HR) 4.00) and high histological grade (HR 1.80) were independent predictors of reduced RFS, whereas high proliferation indicated improved RFS (HR 0.55).\n\nConclusion: Strong EZH2 expression and high proliferation are associated features and both indicate improved RFS in colon cancer, but not so in rectal cancer.\n\nIndexed on Europe PMC as PubMed record 19773751 (DOI 10.1038/sj.bjc.6605333). Its title names EZH2 and its text names Colorectal cancer; PubMed types it as a clinical trial report (other, Randomized Controlled Trial). It was matched automatically to the idea \"Unmask hidden antigens with a short epigenetic course before immunotherapy\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Br J Cancer 2009","url":"https://doi.org/10.1038/sj.bjc.6605333"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19773751/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/19773751"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["british-journal-of-cancer"],"dependsOn":[],"notes":[],"journal":"British Journal of Cancer","year":2009,"doi":"10.1038/sj.bjc.6605333","pmid":"19773751","authors":"Fluge Ø, Gravdal K, Carlsen E, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for EZH2 in Colorectal cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by EZH2 in the title and Colorectal cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-gross-eshhar-chimeric-receptor-pnas-1989","kind":"paper","name":"Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity","aka":[],"tldr":"The paper that invented the CAR. A T cell was given the business end of an antibody, and it killed what the antibody recognised without needing the immune system's usual permission step.","summary":"Zelig Eshhar's group at the Weizmann Institute of Science asked whether the specificity of a T cell could be designed rather than selected. They built chimeric T-cell receptor genes in which the variable domains of the heavy and light chains of an anti-trinitrophenyl antibody (SP6) were spliced to the constant regions of the T-cell receptor alpha or beta chain, and expressed them in a cytotoxic T-cell hybridoma.\n\nThe transfectants expressed a functional receptor carrying the antibody's idiotope, and responded to trinitrophenyl-bearing targets without major histocompatibility complex restriction, killing them and producing interleukin-2 across strain and species barriers. They also responded to immobilised trinitrophenyl-protein conjugates, which means cellular processing and presentation were bypassed entirely. Because the binding site of this particular antibody lies almost wholly in the heavy chain, a construct containing only the heavy-chain variable domain fused to either constant region was enough.\n\nEshhar called the construct a T-body. Everything that followed, the single-chain variable fragment format, the CD28 and 4-1BB costimulatory domains added by Michel Sadelain, Carl June and Dario Campana, and the manufacturing that turns the idea into a product, is built on this experiment.","asOf":"2026-09-25","links":[{"label":"PNAS 1989","url":"https://doi.org/10.1073/pnas.86.24.10024"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/2513569/"}],"tags":[],"related":[],"cancers":[],"sections":["cell-therapy"],"technologies":["car-t"],"targets":["cd19"],"drugs":[],"companies":[],"institutions":["weizmann"],"pathways":[],"terms":[],"trials":[],"people":["zelig-eshhar"],"bottlenecks":["b-manufacturing-cell-therapy"],"keyPapers":[],"journals":["pnas"],"dependsOn":[],"notes":[],"journal":"Proceedings of the National Academy of Sciences","year":1989,"doi":"10.1073/pnas.86.24.10024","pmid":"2513569","authors":"Gross G, Waks T, Eshhar Z","paperType":"basic","findings":["Chimeric genes joining antibody variable domains to T-cell receptor constant domains produced a functional surface receptor on a cytotoxic T-cell hybridoma.","The chimeric receptor conferred non-MHC-restricted killing and interleukin-2 production against hapten-bearing targets across strain and species barriers.","Transfectants responded to immobilised hapten-protein conjugates, bypassing antigen processing and presentation altogether.","A construct carrying only the heavy-chain variable domain fused to the alpha or beta constant region was sufficient in this system."],"whatItMeans":"Every approved CAR-T product descends from this design. It is the reason a T cell can be pointed at CD19 or BCMA at all, and the reason the question of what to point it at in solid tumours is a question about antigens rather than about the receptor.","caveats":["A model antigen (trinitrophenyl) in a hybridoma, not a tumour antigen in a patient. The construct had no costimulatory domain, so first-generation CARs of this kind proved too weak in the clinic; the additions that made CAR-T work came a decade or more later from other groups."],"changedPractice":true},{"id":"paper-turner-nature","kind":"paper","name":"Extrachromosomal oncogene amplification drives tumour evolution and genetic heterogeneity","aka":[],"tldr":"Paper cited by one idea page, indexed on Europe PMC as PubMed record 28178237 and published in Nature; the citing page links this DOI, which is how the record was matched.","summary":"Human cells have twenty-three pairs of chromosomes. In cancer, however, genes can be amplified in chromosomes or in circular extrachromosomal DNA (ecDNA), although the frequency and functional importance of ecDNA are not understood. We performed whole-genome sequencing, structural modelling and cytogenetic analyses of 17 different cancer types, including analysis of the structure and function of chromosomes during metaphase of 2,572 dividing cells, and developed a software package called ECdetect to conduct unbiased, integrated ecDNA detection and analysis. Here we show that ecDNA was found in nearly half of human cancers; its frequency varied by tumour type, but it was almost never found in normal cells. Driver oncogenes were amplified most commonly in ecDNA, thereby increasing transcript level. Mathematical modelling predicted that ecDNA amplification would increase oncogene copy number and intratumoural heterogeneity more effectively than chromosomal amplification. We validated these predictions by quantitative analyses of cancer samples. The results presented here suggest that ecDNA contributes to accelerated evolution in cancer.\n\nIndexed on Europe PMC as PubMed record 28178237 (DOI 10.1038/nature21356). Matched by DOI alone: one idea page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2017","url":"https://doi.org/10.1038/nature21356"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28178237/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28178237"}],"tags":["europepmc-ingest"],"related":["idea-ecdna-targeting"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2017,"doi":"10.1038/nature21356","pmid":"28178237","authors":"Turner KM, Deshpande V, Beyter D, et al.","paperType":"observational","findings":[],"whatItMeans":"One idea page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-extreme-vermorken-nejm-2008","kind":"paper","name":"EXTREME: platinum-based chemotherapy plus cetuximab in recurrent or metastatic head and neck cancer","aka":[],"tldr":"Adding cetuximab to platinum and fluorouracil lengthened survival in recurrent or metastatic head and neck cancer from 7.4 to 10.1 months, the first improvement in first-line treatment in decades.","summary":"Phase 3 trial of 442 patients with untreated recurrent or metastatic head and neck squamous cell carcinoma randomised to cisplatin or carboplatin plus fluorouracil for up to six cycles, with or without cetuximab continued as maintenance.\n\nMedian overall survival was 10.1 versus 7.4 months (hazard ratio 0.80), progression-free survival 5.6 versus 3.3 months and response 36 versus 20 percent, with skin reactions and infusion reactions as the added toxicities.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2008","url":"https://doi.org/10.1056/NEJMoa0802656"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/18784101/"}],"tags":[],"related":[],"cancers":["recurrent-metastatic-hnscc"],"sections":[],"technologies":[],"targets":[],"drugs":["cetuximab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["extreme"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2008,"doi":"10.1056/NEJMoa0802656","pmid":"18784101","authors":"Vermorken JB, Mesia R, Rivera F, et al.","paperType":"rct","findings":["Median overall survival 10.1 vs 7.4 months; hazard ratio 0.80.","Objective response 36 percent vs 20 percent."],"whatItMeans":"EXTREME was the first-line standard for a decade and remains the option for patients unsuitable for pembrolizumab; it was the comparator that KEYNOTE-048 improved upon.","caveats":["Fluorouracil infusion is burdensome; TPExtreme showed docetaxel can replace it."],"changedPractice":true,"participants":442},{"id":"paper-de-groot-nat-commun","kind":"paper","name":"Fasting mimicking diet as an adjunct to neoadjuvant chemotherapy for breast cancer in the multicentre randomized phase 2 DIRECT trial","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 32576828 and published in Nature Communications; the citing page links this DOI, which is how the record was matched.","summary":"Short-term fasting protects tumor-bearing mice against the toxic effects of chemotherapy while enhancing therapeutic efficacy. We randomized 131 patients with HER2-negative stage II/III breast cancer, without diabetes and a BMI over 18 kg m -2, to receive either a fasting mimicking diet (FMD) or their regular diet for 3 days prior to and during neoadjuvant chemotherapy. Here we show that there was no difference in toxicity between both groups, despite the fact that dexamethasone was omitted in the FMD group. A radiologically complete or partial response occurs more often in patients using the FMD (OR 3.168, P = 0.039). Moreover, per-protocol analysis reveals that the Miller&Payne 4/5 pathological response, indicating 90-100% tumor-cell loss, is more likely to occur in patients using the FMD (OR 4.109, P = 0.016). Also, the FMD significantly curtails chemotherapy-induced DNA damage in T-lymphocytes. These positive findings encourage further exploration of the benefits of fasting/FMD in cancer therapy. Trial number: NCT02126449.\n\nIndexed on Europe PMC as PubMed record 32576828 (DOI 10.1038/s41467-020-16138-3). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Commun 2020","url":"https://doi.org/10.1038/s41467-020-16138-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32576828/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32576828"}],"tags":["europepmc-ingest"],"related":["fasting-mimicking-diet"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-communications"],"dependsOn":[],"notes":[],"journal":"Nature Communications","year":2020,"doi":"10.1038/s41467-020-16138-3","pmid":"32576828","authors":"de Groot S, Lugtenberg RT, Cohen D, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-ciltacabtagene-autoleucel-multiple-myeloma-clin-cancer-res-2024","kind":"paper","name":"FDA Approval Summary: Ciltacabtagene Autoleucel for Relapsed or Refractory Multiple Myeloma","aka":[],"tldr":"Phase 2 or 3 results paper on Ciltacabtagene autoleucel in Multiple myeloma, in Clinical Cancer Research (2024), one of the most cited Europe PMC records with Ciltacabtagene autoleucel in its title.","summary":"In February 2022, the FDA approved ciltacabtagene autoleucel, a chimeric antigen receptor (CAR) T-cell therapy targeting the B-cell maturation antigen, for adult patients with relapsed/refractory multiple myeloma after ≥4 lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. Approval was based on overall response rate (ORR), complete response (CR) rate, and duration of response (DoR) in 97 adult patients in a single-arm, open-label, multicenter phase 2 trial (CARTITUDE-1 [NCT03548207]). Patients received a single infusion of ciltacabtagene autoleucel, preceded by lymphodepleting chemotherapy. Of the 97 patients evaluable, ORR was 97.9% [95% confidence interval (CI), 92.7-99.7] with a stringent CR rate of 78.4% (95% CI, 68.8-86.1). After median follow-up of 18 months, the median DoR was 21.8 months (95% CI, 21.8-not estimable [NE]) in responders (PR or better) and NE (95% CI, 21.8 months-NE) in patients who achieved stringent CR. Serious adverse reactions occurred in 55% of the 97 patients evaluated for safety. Grade 3 or higher cytokine release syndrome (CRS) and neurologic toxicities occurred in 5% and 11% of the patients, respectively, leading to a Risk Evaluation and Mitigation Strategy. Neurologic toxicities included immune effector cell-associated neurologic syndrome, typically seen with CAR-T products, parkinsonism, peripheral neuropathy, cranial nerve palsies, and Guillain-Barré syndrome. One fatal case of hemophagocytic lymphohistiocytosis/macrophage activation syndrome occurred. Prolonged and recurrent grade 3 or 4 cytopenias occurred; a single patient required hematopoietic stem-cell rescue.\n\nIndexed on Europe PMC as PubMed record 38713595 (DOI 10.1158/1078-0432.ccr-24-0378). Its title names Ciltacabtagene autoleucel and its text names Multiple myeloma; PubMed types it as a clinical trial report (Clinical Trial, Phase II, research-article, Multicenter Study). It was matched automatically to the idea \"One CAR-T infusion instead of autologous transplant\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Clin Cancer Res 2024","url":"https://doi.org/10.1158/1078-0432.ccr-24-0378"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38713595/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38713595"},{"label":"ClinicalTrials.gov NCT03548207","url":"https://clinicaltrials.gov/study/NCT03548207"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["cartitude-1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2024,"doi":"10.1158/1078-0432.ccr-24-0378","pmid":"38713595","authors":"Natrajan K, Kaushal M, George B, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Ciltacabtagene autoleucel in Multiple myeloma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Ciltacabtagene autoleucel in the title and Multiple myeloma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-drug-dosing-conundrum-nejm-2021","kind":"paper","name":"FDA's Project Optimus manifesto: cancer drugs are approved at doses that are too high","aka":[],"tldr":"FDA oncology leaders argued that the maximum tolerated dose paradigm inherited from chemotherapy produces targeted drugs and immunotherapies dosed far above what is needed, using sotorasib (960 mg vs 240 mg) as the case study, and launched Project Optimus to require dose optimisation before approval.","summary":"This NEJM perspective from the FDA Oncology Center of Excellence set out why oncology dose selection had to change. Phase 1 trials find the maximum tolerated dose over one cycle, a rational approach for cytotoxics but not for targeted agents and immunotherapies whose effects plateau at lower exposures and whose chronic, low-grade toxicity drives discontinuation.\n\nThe authors cited sotorasib, approved at 960 mg daily although early data showed similar exposure and activity at 240 mg; the FDA required a randomised post-marketing comparison of the two doses, which did not establish the lower dose as equivalent and left the label at 960 mg. Other examples included post-approval dose reductions of cabozantinib, niraparib, ceritinib and dasatinib.\n\nProject Optimus, launched the same year, now expects sponsors to compare more than one dose before pivotal trials; FDA's 2024 guidance on dose optimisation formalised this.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1056/NEJMp2109826"},{"label":"FDA Project Optimus","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus"}],"tags":[],"related":["idea-tr1-randomised-dose-comparison-before-pivotal","idea-tr1-exposure-response-before-dose-selection","idea-moon-post-approval-dose-deescalation","idea-reg-global-dose-optimisation-guideline"],"cancers":[],"sections":["targeted-therapy"],"technologies":["kinase-inhibitors"],"targets":["kras"],"drugs":["sotorasib","niraparib"],"companies":[],"institutions":[],"pathways":[],"terms":["project-optimus","accelerated-approval"],"trials":[],"people":[],"bottlenecks":["b-dose-optimisation","b-toxicity-qol","b-regulatory-fragmentation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2021,"doi":"10.1056/NEJMp2109826","pmid":"34623788","authors":"Shah M, Rahman A, Theoret MR, Pazdur R","paperType":"review","findings":["Most targeted agents and immunotherapies have flat exposure-response relationships above a threshold, so the MTD is rarely the optimal dose","Sotorasib: 960 mg chosen despite comparable early activity at 240 mg; a randomised dose comparison was required as a post-marketing commitment","Multiple approved drugs (for example niraparib, cabozantinib, ceritinib, dasatinib) had labelled doses lowered after approval because of toxicity","Proposal: randomised comparison of at least two doses, with patient-reported tolerability, before registrational trials"],"whatItMeans":"The dose on the label is often not the best dose for patients; it is the highest one that was tolerable for a few weeks. Project Optimus means new cancer drugs should arrive with evidence on dose, and it gives clinicians licence to consider dose reduction for toxicity. For older drugs, the evidence gap persists.","caveats":["A perspective rather than a trial; the regulatory shift adds cost and time to development that smaller sponsors resist","Lower doses could under-treat if exposure-response is misjudged; dose comparisons need adequate power","Post-marketing dose studies are slow and often inconclusive, as sotorasib showed","Global regulators have not fully harmonised on dose-optimisation expectations"],"changedPractice":true},{"id":"paper-davar-science","kind":"paper","name":"Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients","aka":[],"tldr":"Paper cited by one trial page, one technology page, one pathway page and one idea page, indexed on Europe PMC as PubMed record 33542131 and published in Science; the citing pages link this DOI, which is how the record was matched.","summary":"Anti-programmed cell death protein 1 (PD-1) therapy provides long-term clinical benefits to patients with advanced melanoma. The composition of the gut microbiota correlates with anti-PD-1 efficacy in preclinical models and cancer patients. To investigate whether resistance to anti-PD-1 can be overcome by changing the gut microbiota, this clinical trial evaluated the safety and efficacy of responder-derived fecal microbiota transplantation (FMT) together with anti-PD-1 in patients with PD-1-refractory melanoma. This combination was well tolerated, provided clinical benefit in 6 of 15 patients, and induced rapid and durable microbiota perturbation. Responders exhibited increased abundance of taxa that were previously shown to be associated with response to anti-PD-1, increased CD8 + T cell activation, and decreased frequency of interleukin-8-expressing myeloid cells. Responders had distinct proteomic and metabolomic signatures, and transkingdom network analyses confirmed that the gut microbiome regulated these changes. Collectively, our findings show that FMT and anti-PD-1 changed the gut microbiome and reprogrammed the tumor microenvironment to overcome resistance to anti-PD-1 in a subset of PD-1 advanced melanoma.\n\nIndexed on Europe PMC as PubMed record 33542131 (DOI 10.1126/science.abf3363). Matched by DOI alone: one trial page, one technology page, one pathway page and one idea page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Science 2021","url":"https://doi.org/10.1126/science.abf3363"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33542131/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33542131"}],"tags":["europepmc-ingest"],"related":["fmt-checkpoint-nonresponders","microbiome-tumour","idea-microbiome-io-fmt"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["fmt-pd1-refractory-melanoma-pitt"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2021,"doi":"10.1126/science.abf3363","pmid":"33542131","authors":"Davar D, Dzutsev AK, McCulloch JA, et al.","paperType":"basic","findings":[],"whatItMeans":"One trial page, one technology page, one pathway page and one idea page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-baruch-science","kind":"paper","name":"Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients","aka":[],"tldr":"Paper cited by one trial page and one idea page, indexed on Europe PMC as PubMed record 33303685 and published in Science; the citing pages link this DOI, which is how the record was matched.","summary":"The gut microbiome has been shown to influence the response of tumors to anti-PD-1 (programmed cell death-1) immunotherapy in preclinical mouse models and observational patient cohorts. However, modulation of gut microbiota in cancer patients has not been investigated in clinical trials. In this study, we performed a phase 1 clinical trial to assess the safety and feasibility of fecal microbiota transplantation (FMT) and reinduction of anti-PD-1 immunotherapy in 10 patients with anti-PD-1-refractory metastatic melanoma. We observed clinical responses in three patients, including two partial responses and one complete response. Notably, treatment with FMT was associated with favorable changes in immune cell infiltrates and gene expression profiles in both the gut lamina propria and the tumor microenvironment. These early findings have implications for modulating the gut microbiota in cancer treatment.\n\nIndexed on Europe PMC as PubMed record 33303685 (DOI 10.1126/science.abb5920). Matched by DOI alone: one trial page and one idea page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Science 2021","url":"https://doi.org/10.1126/science.abb5920"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33303685/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33303685"}],"tags":["europepmc-ingest"],"related":["idea-microbiome-io-fmt"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["fmt-pd1-refractory-melanoma-pitt"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2021,"doi":"10.1126/science.abb5920","pmid":"33303685","authors":"Baruch EN, Youngster I, Ben-Betzalel G, et al.","paperType":"basic","findings":[],"whatItMeans":"One trial page and one idea page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-mimic-01-nat-med-2023","kind":"paper","name":"Fecal microbiota transplantation plus anti-PD-1 immunotherapy in advanced melanoma: a phase I trial","aka":[],"tldr":"Published report from the trial registered as NCT03772899, in Nature Medicine (2023), chosen as the most cited paper whose own text cites the registry id.","summary":"Fecal microbiota transplantation (FMT) represents a potential strategy to overcome resistance to immune checkpoint inhibitors in patients with refractory melanoma; however, the role of FMT in first-line treatment settings has not been evaluated. We conducted a multicenter phase I trial combining healthy donor FMT with the PD-1 inhibitors nivolumab or pembrolizumab in 20 previously untreated patients with advanced melanoma. The primary end point was safety. No grade 3 adverse events were reported from FMT alone. Five patients (25%) experienced grade 3 immune-related adverse events from combination therapy. Key secondary end points were objective response rate, changes in gut microbiome composition and systemic immune and metabolomics analyses. The objective response rate was 65% (13 of 20), including four (20%) complete responses. Longitudinal microbiome profiling revealed that all patients engrafted strains from their respective donors; however, the acquired similarity between donor and patient microbiomes only increased over time in responders. Responders experienced an enrichment of immunogenic and a loss of deleterious bacteria following FMT. Avatar mouse models confirmed the role of healthy donor feces in increasing anti-PD-1 efficacy. Our results show that FMT from healthy donors is safe in the first-line setting and warrants further investigation in combination with immune checkpoint inhibitors. ClinicalTrials.gov identifier NCT03772899.\n\nIndexed on Europe PMC as PubMed record 37414899 (DOI 10.1038/s41591-023-02453-x). Its abstract cites the registry id NCT03772899, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Nat Med 2023","url":"https://doi.org/10.1038/s41591-023-02453-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37414899/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37414899"},{"label":"ClinicalTrials.gov NCT03772899","url":"https://clinicaltrials.gov/study/NCT03772899"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["mimic-01"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2023,"doi":"10.1038/s41591-023-02453-x","pmid":"37414899","authors":"Routy B, Lenehan JG, Miller WH, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03772899 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-ferlay-globocan-2012-methods-ijc-2015","kind":"paper","name":"Ferlay 2015: sources, methods and major patterns in GLOBOCAN 2012","aka":[],"tldr":"The methods paper behind the 2012 world cancer estimates, explaining how IARC builds country figures from registries of very different quality, and reporting about 14.1 million new cases and 32.6 million people living within five years of a diagnosis.","summary":"Ferlay and colleagues at IARC described how GLOBOCAN 2012 estimated incidence, mortality and five-year prevalence for 27 cancers in 184 countries. They set out the hierarchy of methods used according to the data available, from national registries with high coverage to modelling from neighbouring countries, and summarised the results: about 14.1 million new cases, 8.2 million deaths and 32.6 million people alive within five years of diagnosis in 2012, with lung, breast and colorectal cancers the most common. The paper is the one to cite for how GLOBOCAN numbers are made and how uncertain they are by country.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1002/ijc.29210"},{"label":"IARC Global Cancer Observatory","url":"https://gco.iarc.who.int/today"}],"tags":[],"related":["paper-torre-global-cancer-statistics-2012-cacancer-2015"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["iarc"],"pathways":[],"terms":["incidence-vs-prevalence","mortality"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"International Journal of Cancer","year":2015,"doi":"10.1002/ijc.29210","authors":"Ferlay J, Soerjomataram I, Dikshit R, et al.","paperType":"methods","findings":["About 14.1 million new cases, 8.2 million deaths and 32.6 million five-year prevalent cases worldwide in 2012.","Country estimates follow a hierarchy of methods depending on registry coverage and mortality data quality.","Lung, breast and colorectal cancers were the most common; lung, liver and stomach cancers the leading causes of death."],"whatItMeans":"Anyone using GLOBOCAN numbers should know how they are produced; this paper explains the method hierarchy and why figures for countries without good registries carry wide uncertainty.","caveats":["Methods differ by country, so cross-country comparisons mix data of very different quality.","Superseded by the 2018, 2020 and 2022 methods papers."],"changedPractice":false},{"id":"paper-ferlay-globocan-2018-methods-ijc-2019","kind":"paper","name":"Ferlay 2019: GLOBOCAN 2018 sources and methods","aka":[],"tldr":"The methods paper for the 2018 world cancer estimates, describing the registry and mortality data behind the figure of about 18.1 million new cases in 185 countries and how countries without good data were handled.","summary":"Ferlay and colleagues documented the sources and methods for GLOBOCAN 2018, which estimated incidence and mortality for 36 cancers in 185 countries. They described the data available for each country, the methods applied according to data quality and coverage, and the summary results of about 18.1 million new cases and 9.6 million deaths in 2018. The paper accompanies the headline report by Bray and colleagues and is the reference for the quality of the national estimates.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1002/ijc.31937"},{"label":"IARC Global Cancer Observatory","url":"https://gco.iarc.who.int/today"}],"tags":[],"related":["paper-bray-globocan-2018-cacancer-2018"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["iarc"],"pathways":[],"terms":["incidence-vs-prevalence","mortality"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"International Journal of Cancer","year":2019,"doi":"10.1002/ijc.31937","authors":"Ferlay J, Colombet M, Soerjomataram I, et al.","paperType":"methods","findings":["About 18.1 million new cancer cases and 9.6 million cancer deaths in 2018 across 185 countries and 36 cancers.","Methods for each country were chosen according to the availability and quality of registry and vital statistics data.","A companion to the headline GLOBOCAN 2018 report."],"whatItMeans":"This paper is the place to check how solid a given country's GLOBOCAN 2018 figure is, which matters when the numbers are used to argue for national cancer plans.","caveats":["Estimates for countries without population-based registries rely on modelling from neighbours.","Superseded by the 2020 and 2022 releases."],"changedPractice":false},{"id":"paper-ferlay-cancer-statistics-2020-overview-ijc-2021","kind":"paper","name":"Ferlay 2021: cancer statistics for the year 2020, an overview","aka":[],"tldr":"IARC's overview of the 2020 world cancer estimates, about 19.3 million new cases, presented by cancer type, sex and world region, alongside the methods and data used and a note that the figures predate the effects of the pandemic.","summary":"Ferlay and colleagues presented an overview of GLOBOCAN 2020: the sources and methods for estimating incidence and mortality for 36 cancers in 185 countries and the main patterns by cancer, sex and region. They reported about 19.3 million new cases and about 10 million deaths in 2020, with female breast cancer the most commonly diagnosed cancer and lung cancer the leading cause of death, and they noted that the estimates reflect pre-pandemic trends because registry data lag by several years.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1002/ijc.33588"},{"label":"IARC Global Cancer Observatory","url":"https://gco.iarc.who.int/today"}],"tags":[],"related":["paper-sung-globocan-2020-cacancer-2021"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["iarc"],"pathways":[],"terms":["incidence-vs-prevalence","mortality"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"International Journal of Cancer","year":2021,"doi":"10.1002/ijc.33588","authors":"Ferlay J, Colombet M, Soerjomataram I, et al.","paperType":"observational","findings":["About 19.3 million new cases and about 10 million cancer deaths worldwide in 2020.","Female breast cancer the most diagnosed cancer; lung cancer the leading cause of cancer death.","Estimates rest on registry data from earlier years and do not capture pandemic disruption to diagnosis."],"whatItMeans":"This is the methods and overview companion to the widely cited Sung 2021 report and the reference for how the 2020 figures were built.","caveats":["Modelled estimates for countries with limited registries.","Superseded by GLOBOCAN 2022."],"changedPractice":false},{"id":"paper-stockwell-cell","kind":"paper","name":"Ferroptosis turns 10: Emerging mechanisms, physiological functions, and therapeutic applications","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 35803244 and published in Cell; the citing page links this DOI, which is how the record was matched.","summary":"Ferroptosis, a form of cell death driven by iron-dependent lipid peroxidation, was identified as a distinct phenomenon and named a decade ago. Ferroptosis has been implicated in a broad set of biological contexts, from development to aging, immunity, and cancer. This review describes key regulators of this form of cell death within a framework of metabolism, ROS biology, and iron biology. Key concepts and major unanswered questions in the ferroptosis field are highlighted. The next decade promises to yield further breakthroughs in the mechanisms governing ferroptosis and additional ways of harnessing ferroptosis for therapeutic benefit.\n\nIndexed on Europe PMC as PubMed record 35803244 (DOI 10.1016/j.cell.2022.06.003). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cell 2022","url":"https://doi.org/10.1016/j.cell.2022.06.003"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35803244/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35803244"}],"tags":["europepmc-ingest"],"related":["ferroptosis-cell-death"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Cell","year":2022,"doi":"10.1016/j.cell.2022.06.003","pmid":"35803244","authors":"Stockwell BR","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-oktay-j-clin-oncol","kind":"paper","name":"Fertility Preservation in Patients With Cancer: ASCO Clinical Practice Guideline Update","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 29620997 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose To provide current recommendations about fertility preservation for adults and children with cancer. Methods A systematic review of the literature published from January 2013 to March 2017 was completed using PubMed and the Cochrane Library. An Update Panel reviewed the identified publications. Results There were 61 publications identified and reviewed. None of these publications prompted a significant change in the 2013 recommendations. Recommendations Health care providers should initiate the discussion on the possibility of infertility with patients with cancer treated during their reproductive years or with parents/guardians of children as early as possible. Providers should be prepared to discuss fertility preservation options and/or to refer all potential patients to appropriate reproductive specialists. Although patients may be focused initially on their cancer diagnosis, providers should advise patients regarding potential threats to fertility as early as possible in the treatment process so as to allow for the widest array of options for fertility preservation. The discussion should be documented. Sperm, oocyte, and embryo cryopreservation are considered standard practice and are widely available. There is conflicting evidence to recommend gonadotrophin-releasing hormone agonists (GnRHa) and other means of ovarian suppression for fertility preservation. The Panel recognizes that, when proven fertility preservation methods are not feasible, and in the setting of young women with breast cancer, GnRHa may be offered to patients in the hope of reducing the likelihood of chemotherapy-induced ovarian insufficiency. GnRHa should not be used in place of proven fertility preservation methods. The panel notes that the field of ovarian tissue cryopreservation is advancing quickly and may evolve to become standard therapy in the future. Additional information is available at www.asco.org/survivorship-guidelines.\n\nIndexed on Europe PMC as PubMed record 29620997 (DOI 10.1200/jco.2018.78.1914). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2018","url":"https://doi.org/10.1200/jco.2018.78.1914"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29620997/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29620997"}],"tags":["europepmc-ingest"],"related":["fertility-preservation"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2018,"doi":"10.1200/jco.2018.78.1914","pmid":"29620997","authors":"Oktay K, Harvey BE, Partridge AH, et al.","paperType":"review","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-fgfr2-cholangiocarcinoma-annu-rev-med-2023","kind":"paper","name":"FGFR2 Inhibition in Cholangiocarcinoma","aka":[],"tldr":"Review on FGFR2 in Biliary tract cancer, in Annual review of medicine (2023), one of the most cited Europe PMC records with FGFR2 in its title.","summary":"Biliary tract cancer (BTC) is the second most common primary liver cancer after hepatocellular carcinoma and accounts for 2% of cancer-related deaths. BTCs are classified according to their anatomical origin into intrahepatic (iCCA), perihilar, or distal cholangiocarcinoma, as well as gall bladder carcinoma. While the mutational profiles in these anatomical BTC subtypes overlap to a large extent, iCCA is notable for the high frequency of IDH1/2 mutations (10-22%) and the nearly exclusive occurrence of FGFR2 fusions in 10-15% of patients. In recent years, FGFR2 fusions have become one of the most promising targets for precision oncology targeting BTC, with FGFR inhibitors already approved in Europe and the United States for patients with advanced, pretreated iCCA. While the therapeutic potential of nonfusion alterations is still under debate, it is expected that the field of FGFR2-directed therapies will be subject to rapid further evolution and optimization. The scope of this review is to provide an overview of oncogenic FGFR signaling in iCCA cells and highlight the pathophysiology, diagnostic testing strategies, and therapeutic promises and challenges associated with FGFR2-altered iCCA.\n\nIndexed on Europe PMC as PubMed record 36170665 (DOI 10.1146/annurev-med-042921-024707). Its title names FGFR2 and its text names Biliary tract cancer; PubMed types it as a review (Research Support, Non-U.S. Gov't, Review). It was matched automatically to the idea \"ctDNA-guided switching among FGFR inhibitors\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Annu Rev Med 2023","url":"https://doi.org/10.1146/annurev-med-042921-024707"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36170665/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36170665"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Annual review of medicine","year":2023,"doi":"10.1146/annurev-med-042921-024707","pmid":"36170665","authors":"Vogel A, Segatto O, Stenzinger A, et al.","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for FGFR2 in Biliary tract cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by FGFR2 in the title and Biliary tract cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-fgfr2-cholangiocarcinoma-cancers-basel-2026","kind":"paper","name":"FGFR2-Rearranged Biliary Tract Cancer: Biology, Resistance Mechanisms, and Emerging Therapeutic Strategies","aka":[],"tldr":"Review on FGFR2 in Biliary tract cancer, in Cancers (2026), one of the most cited Europe PMC records with FGFR2 in its title.","summary":"Fibroblast growth factor receptor 2 (FGFR2) rearrangements represent one of the most actionable molecular alterations in biliary tract cancer, particularly in intrahepatic cholangiocarcinoma (iCCA). Approximately 10-16% of iCCA cases harbor FGFR2 fusions or rearrangements, defining a distinct molecular subtype characterized by sensitivity to FGFR-targeted therapies. Selective FGFR tyrosine kinase inhibitors, including the reversible inhibitor pemigatinib and the irreversible inhibitor futibatinib, have demonstrated clinically meaningful response rates and durable disease control in patients with previously treated FGFR2-altered iCCA, leading to regulatory approvals and the incorporation of FGFR inhibition into contemporary treatment paradigms. However, the development of acquired resistance-most commonly driven by secondary kinase-domain mutations and activation of bypass signaling pathways-remains a major limitation to sustained therapeutic benefit. This review summarizes the biological basis of FGFR2 alterations, highlights current clinical evidence supporting FGFR inhibition, and discusses the evolving landscape of resistance mechanisms. We further examine emerging therapeutic strategies aimed at overcoming resistance, including next-generation FGFR inhibitors and rational combination approaches. In addition, we highlight the growing role of circulating tumor DNA as a noninvasive tool for longitudinal molecular monitoring and treatment guidance. Together, these insights underscore the central role of FGFR2-directed therapy in precision oncology for biliary tract cancer and provide a framework for optimizing and extending targeted treatment in this molecularly defined disease subset.\n\nIndexed on Europe PMC as PubMed record 41682001 (DOI 10.3390/cancers18030531). Its title names FGFR2 and its text names Biliary tract cancer; PubMed types it as a review (review-article, Review). It was matched automatically to the idea \"ctDNA-guided switching among FGFR inhibitors\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancers (Basel) 2026","url":"https://doi.org/10.3390/cancers18030531"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41682001/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41682001"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancers-mdpi"],"dependsOn":[],"notes":[],"journal":"Cancers","year":2026,"doi":"10.3390/cancers18030531","pmid":"41682001","authors":"Xin X, Miao R","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for FGFR2 in Biliary tract cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by FGFR2 in the title and Biliary tract cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-doll-peto-50-year-doctors-bmj-2004","kind":"paper","name":"Fifty years of the British Doctors Study: smokers lose ten years of life, quitting gives most of it back","aka":[],"tldr":"After following 34,439 male doctors for 50 years, lifelong smokers died on average about 10 years earlier than never-smokers, and stopping at 60, 50, 40 or 30 recovered about 3, 6, 9 or the full 10 years.","summary":"The British Doctors Study began in 1951 with questionnaires to male doctors and followed them for mortality until 2001, with periodic resurveys of smoking habits. This 50-year report used the full cohort of 34,439 men.\n\nMen born around 1920 who continued to smoke had about twice the death rate in middle age of never-smokers and lost about 10 years of life expectancy. The excess was largest for lung cancer, chronic obstructive lung disease and vascular disease. Cessation at age 60, 50, 40 or 30 gained about 3, 6, 9 or 10 years of life expectancy respectively.\n\nThe study, together with the 1954 and 1956 reports, was the foundation of tobacco control worldwide.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1136/bmj.38142.554479.AE"}],"tags":[],"related":["paper-doll-hill-smoking-lung-cancer-bmj-1950","idea-prev-opt-out-cessation-in-lung-screening","idea-prev-smokefree-generation-evaluation","lung-cancer-evidence-roadmap","paper-peto-smoking-cessation-lung-cancer-uk-bmj-2000"],"cancers":["nsclc","sclc","head-and-neck","esophageal","urothelial","pancreatic","lung-cancer"],"sections":["prevention"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-incentive-misalignment"],"keyPapers":[],"journals":["bmj"],"dependsOn":[],"notes":[],"journal":"BMJ","year":2004,"doi":"10.1136/bmj.38142.554479.AE","pmid":"15213107","authors":"Doll R, Peto R, Boreham J, Sutherland I","paperType":"observational","findings":["Lifelong cigarette smokers lost about 10 years of life expectancy compared with never-smokers","Stopping at 60, 50, 40 or 30 gained about 3, 6, 9 or 10 years respectively","Probability of dying in middle age (35-69) was about 43% for smokers vs 15% for non-smokers in the 1920 birth cohort","Lung cancer mortality rose with cigarettes per day and fell steadily after cessation"],"whatItMeans":"Smoking is the single largest preventable cause of cancer death, and quitting at any age helps, with the greatest gain from quitting young. Cessation support belongs in every cancer service, including lung screening programmes.","caveats":["Male British doctors only, a homogeneous and affluent group; absolute risks differ in other populations","Historical cohort smoking high-tar cigarettes from youth; modern patterns differ","Cessation effects are observational and subject to healthy-quitter bias","Does not address e-cigarettes or smokeless products"],"changedPractice":true,"participants":34439},{"id":"paper-fight-202-pemigatinib-lancet-oncol-2020","kind":"paper","name":"FIGHT-202: pemigatinib for previously treated cholangiocarcinoma with FGFR2 fusions or rearrangements","aka":[],"tldr":"The FGFR inhibitor pemigatinib shrank tumours in more than a third of patients with previously treated intrahepatic cholangiocarcinoma carrying FGFR2 fusions, the first targeted drug approved for the disease.","summary":"Phase 2 study of 146 patients with previously treated locally advanced or metastatic cholangiocarcinoma, including 107 with FGFR2 fusions or rearrangements, treated with pemigatinib 13.5 mg daily on a two-weeks-on, one-week-off schedule.\n\nIn FGFR2-rearranged patients objective response was 35.5 percent with median duration of response 7.5 months and median progression-free survival 6.9 months; no responses were seen in patients with other FGF/FGFR alterations. Hyperphosphataemia was almost universal.","asOf":"2026-09-17","links":[{"label":"Lancet Oncol 2020","url":"https://doi.org/10.1016/S1470-2045(20)30109-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32203698/"}],"tags":[],"related":[],"cancers":["intrahepatic-cholangiocarcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":["pemigatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["fight-202"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2020,"doi":"10.1016/S1470-2045(20)30109-1","pmid":"32203698","authors":"Abou-Alfa GK, Sahai V, Hollebecque A, et al.","paperType":"observational","findings":["Objective response 35.5 percent in FGFR2-rearranged cholangiocarcinoma.","Median progression-free survival 6.9 months; median overall survival 21.1 months."],"whatItMeans":"FGFR2 fusion testing is standard in intrahepatic cholangiocarcinoma, and pemigatinib (with futibatinib) is the second-line targeted option for fusion-positive disease.","caveats":["Single-arm; the confirmatory first-line trial (FIGHT-302) is ongoing.","Hyperphosphataemia, eye toxicity and nail changes require monitoring."],"changedPractice":true,"participants":146},{"id":"paper-figo-cancer-report-cancer-of-the-vagina-ijgo-2018","kind":"paper","name":"FIGO Cancer Report 2018: cancer of the vagina","aka":[],"tldr":"The FIGO review of vaginal cancer: how it is staged, that radiotherapy with brachytherapy is the main treatment, and that adding cisplatin is borrowed from cervical cancer because vaginal cancer is too rare for its own trials.","summary":"FIGO Cancer Report chapter covering the epidemiology, HPV association, diagnosis, FIGO staging and management of primary vaginal cancer, including squamous cell carcinoma, adenocarcinoma and rarer histologies.\n\nIt recommends external beam radiotherapy with brachytherapy for most invasive tumours, surgery for selected early lesions, and concurrent cisplatin extrapolated from cervical cancer trials, and it sets out follow-up and the management of recurrence.","asOf":"2026-09-18","links":[{"label":"Int J Gynaecol Obstet 2018","url":"https://doi.org/10.1002/ijgo.12610"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30306589/"}],"tags":[],"related":[],"cancers":["vaginal-squamous-cell-carcinoma","vaginal-adenocarcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"International Journal of Gynecology & Obstetrics","year":2018,"doi":"10.1002/ijgo.12610","pmid":"30306589","authors":"Adams TS, Cuello MA.","paperType":"guideline","findings":[],"whatItMeans":"The treatment pathway on the vaginal cancer pages, radiotherapy with brachytherapy and cisplatin sensitisation for locally advanced disease, follows this report.","caveats":["Recommendations rest on retrospective series and extrapolation from cervical cancer.","Superseded in detail by later FIGO reports; check the current edition."],"changedPractice":false},{"id":"paper-figo-cancer-report-gestational-trophoblastic-disease-ijgo-2021","kind":"paper","name":"FIGO Cancer Report 2021: diagnosis and management of gestational trophoblastic disease","aka":[],"tldr":"The FIGO review of trophoblastic disease from molar pregnancy to choriocarcinoma and the rare placental-site and epithelioid tumours: hCG surveillance, the risk score, single-agent or EMA/CO chemotherapy, surgery, and immunotherapy for resistant disease.","summary":"FIGO Cancer Report chapter covering hydatidiform mole and its follow-up, the FIGO 2000 staging and scoring of gestational trophoblastic neoplasia, single-agent therapy for low-risk and EMA/CO for high-risk disease, induction etoposide-cisplatin for ultra-high-risk disease, salvage regimens, the role of hysterectomy and metastasectomy, management of placental-site and epithelioid trophoblastic tumours, immunotherapy for resistant disease, and follow-up and future pregnancy.","asOf":"2026-09-18","links":[{"label":"Int J Gynaecol Obstet 2021","url":"https://doi.org/10.1002/ijgo.13877"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34669197/"}],"tags":[],"related":[],"cancers":["high-risk-gtn","placental-site-trophoblastic-tumour"],"sections":[],"technologies":[],"targets":[],"drugs":["methotrexate","dactinomycin","etoposide","cisplatin","pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"International Journal of Gynecology & Obstetrics","year":2021,"doi":"10.1002/ijgo.13877","pmid":"34669197","authors":"Ngan HYS, Seckl MJ, Berkowitz RS, et al.","paperType":"guideline","findings":[],"whatItMeans":"The standard-of-care rows on all three trophoblastic pages follow this report and the national centres it describes.","caveats":["Evidence in this rare disease is mostly from specialist centre series rather than randomised trials.","Updated periodically; check the current FIGO report."],"changedPractice":true},{"id":"paper-figo-2000-staging-gestational-trophoblastic-neoplasia-ijgo-2002","kind":"paper","name":"FIGO staging for gestational trophoblastic neoplasia 2000","aka":[],"tldr":"The FIGO Oncology Committee's system that combines an anatomical stage with a prognostic score to split gestational trophoblastic neoplasia into low-risk disease, cured with a single drug, and high-risk disease needing combination chemotherapy.","summary":"Report of the FIGO Oncology Committee setting out the FIGO 2000 classification of gestational trophoblastic neoplasia: anatomical stages I to IV (uterus, pelvis and adnexa, lungs, other metastases) combined with the modified WHO prognostic scoring system based on age, antecedent pregnancy, interval, hCG level, tumour size, site and number of metastases and prior failed chemotherapy.\n\nA score of 6 or less defines low-risk disease, treated with single-agent methotrexate or dactinomycin, and 7 or more high-risk disease, treated with multi-agent regimens such as EMA/CO. The system replaced several competing schemes and remains in use.","asOf":"2026-09-18","links":[{"label":"Int J Gynaecol Obstet 2002","url":"https://doi.org/10.1016/S0020-7292(02)00063-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/12065144/"}],"tags":[],"related":[],"cancers":["low-risk-gtn","high-risk-gtn"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"International Journal of Gynecology & Obstetrics","year":2002,"doi":"10.1016/S0020-7292(02)00063-2","pmid":"12065144","authors":"FIGO Oncology Committee.","paperType":"guideline","findings":[],"whatItMeans":"Whether a woman with GTN receives one drug or several rests on this scoring system, which is why OnCo has separate low-risk and high-risk pages.","caveats":["The score was derived from historical series and some elements (such as blood group in earlier versions) were dropped for practicality.","Women with scores of 5 to 6 or with choriocarcinoma often fail single-agent therapy, and some centres treat them more intensively."],"changedPractice":true},{"id":"paper-destiny-lung02-j-thorac-oncol-2025","kind":"paper","name":"Final Analysis Results and Patient-Reported Outcomes From DESTINY-Lung02-A Dose-Blinded, Randomized, Phase 2 Study of Trastuzumab Deruxtecan in Patients With HER2-Mutant Metastatic NSCLC","aka":[],"tldr":"Published report from the DESTINY-Lung02 trial registered as NCT04644237, in Journal of Thoracic Oncology (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Introduction: Trastuzumab deruxtecan (T-DXd) demonstrated strong and durable responses in patients with previously treated HER2 (ERBB2) mutant (HER2m) metastatic NSCLC (mNSCLC) in the DESTINY-Lung02 primary analysis (December 23, 2022, data cutoff). This final analysis evaluated T-DXd efficacy and safety after 8 additional months of follow-up, including clinically relevant subgroups and patient-reported outcomes.\n\nMethods: DESTINY-Lung02 was a randomized, dose-blinded, multicenter, phase 2 trial. Patients with previously treated HER2m mNSCLC were randomized 2:1 to receive T-DXd 5.4 or 6.4 mg/kg once every 3 weeks. Primary end point was confirmed objective response rate by blinded independent central review.\n\nResults: at August 25, 2023, 102 and 50 patients had received T-DXd 5.4 or 6.4 mg/kg, respectively. Median follow-up (Q1-Q3) was 15.8 (8.2-20.7) months and 16.5 (9.4-20.8) months, respectively. Confirmed objective response rate (95% confidence interval) was 50.0% (51/102; 39.9%-60.1%) and 56.0% (28/50; 41.3%-70.0%), respectively. Safety profile was acceptable and generally manageable. Accordingly, median treatment duration (Q1-Q3) was 7.7 (3.7-14.4) months and 8.3 (2.8-13.1) months; drug-related grade 3 or higher treatment-emergent adverse events occurred in 39.6% (40/101) and 60.0% (30/50), with nausea most common (67.3% [68/101], 82.0% [41/50]). Adjudicated drug-related interstitial lung disease occurred in 14.9% (15/101) and 32.0% (16/50), mostly grade 1 or 2 with one grade 5 in each arm. Health-related quality of life was preserved for the duration of T-DXd treatment while sample size was sufficient for analysis, with no adverse effects on health-related quality of life observed at either dose.\n\nConclusions: T-DXd demonstrated strong and durable responses at both doses, with no clinically significant changes in toxicity. The approved 5.4-mg/kg dose demonstrated a more favorable benefit-risk profile, including lower adjudicated drug-related interstitial lung disease incidence.\n\nGov identifier: NCT04644237.\n\nIndexed on Europe PMC as PubMed record 40749900 (DOI 10.1016/j.jtho.2025.07.129). Its abstract cites the registry id NCT04644237, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Thorac Oncol 2025","url":"https://doi.org/10.1016/j.jtho.2025.07.129"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40749900/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40749900"},{"label":"ClinicalTrials.gov NCT04644237","url":"https://clinicaltrials.gov/study/NCT04644237"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["destiny-lung02"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-thoracic-oncology"],"dependsOn":[],"notes":[],"journal":"Journal of Thoracic Oncology","year":2025,"doi":"10.1016/j.jtho.2025.07.129","pmid":"40749900","authors":"Jänne PA, Goto Y, Kubo T, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04644237 with the most citations, so it is the natural first reading for anyone following the DESTINY-Lung02 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-orient-11-lung-cancer-2022-update","kind":"paper","name":"Final overall survival data of sintilimab plus pemetrexed and platinum as First-Line treatment for locally advanced or metastatic nonsquamous NSCLC in the Phase 3 ORIENT-11 study","aka":[],"tldr":"Later report from the ORIENT-11 trial registered as NCT03607539, in Lung cancer (2022); its title describes an updated or longer-term analysis.","summary":"Objectives: In ORIENT-11, first-line sintilimab + pemetrexed-platinum significantly improved PFS compared with placebo + pemetrexed-platinum in patients with advanced metastatic nonsquamous non-small-cell lung cancer (AMnsqNSCLC). The study met the primary endpoint of PFS at 15November2019. Here we report final survival analysis from ORIENT-11 (NCT03607539) using a 15September2021 data cutoff.\n\nMethods: Patients with treatment-naïve locally AMnsqNSCLC without sensitizing EGFR or ALK genomic tumor aberrations were randomly assigned to sintilimab + pemetrexed-platinum (n = 266) or placebo + pemetrexed-platinum (n = 131). Patients were stratified by PD-L1 expression, platinum-chemotherapy, and gender. Treatment continued until PD, unacceptable toxicity, or a maximum of 24 months. Patients in the placebo + pemetrexed-platinum arm could be sequenced to second-line sintilimab monotherapy, contingent upon PD. Response was assessed (RECISTv.1.1) by blinded independent radiographic review committee. Primary endpoint was PFS. OS was a secondary endpoint and defined from date of randomization to date of death due to any cause. Final OS analysis was defined as approximately 2 years after last patient randomized or when approximately 65 % of patients died, whichever first.\n\nResults: At data cutoff of final OS analysis, median study follow-up was 30.8 months. Of 397 patients, 243 OS events were observed (sintilimab + pemetrexed-platinum:151[57 %];placebo + pemetrexed-platinum:92 [70 %]). Of the patients in placebo + pemetrexed-platinum arm, 47 % crossed over to sintilimab monotherapy per protocol. Median OS was 24.2 months in sintilimab + pemetrexed-platinum arm and 16.8 months in placebo + pemetrexed-platinum arm (HR:0.65[95 % CI:0.50,0.85]). Estimated 2-year OS rates were 50 %(sintilimab + pemetrexed-platinum) and 32 %(placebo + pemetrexed-platinum). After adjusting for the crossover effect, OS treatment effect was more pronounced with HR 0.52 (95 % CI:0.38,0.69). OS benefit across all prespecified subgroups was largely consistent with that observed in the ITT population.\n\nConclusions: In the ORIENT-11 final OS analysis, sintilimab + pemetrexed-platinum demonstrated improved OS compared to placebo + pemetrexed-platinum when administered as first-line therapy in AMnsqNSCLC without EGFR or ALK genomic tumor aberrations.\n\nIndexed on Europe PMC as PubMed record 35917647 (DOI 10.1016/j.lungcan.2022.07.013). Its abstract cites the registry id NCT03607539, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lung Cancer 2022","url":"https://doi.org/10.1016/j.lungcan.2022.07.013"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35917647/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35917647"},{"label":"ClinicalTrials.gov NCT03607539","url":"https://clinicaltrials.gov/study/NCT03607539"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["orient-11"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lung-cancer-journal"],"dependsOn":[],"notes":[],"journal":"Lung cancer","year":2022,"doi":"10.1016/j.lungcan.2022.07.013","pmid":"35917647","authors":"Zhang L, Wang Z, Fang J, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the ORIENT-11 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-ielsg-19-chlorambucil-rituximab-malt-jco-2017","kind":"paper","name":"Final results of the IELSG-19 randomized trial of mucosa-associated lymphoid tissue lymphoma: improved event-free and progression-free survival with rituximab plus chlorambucil versus either chlorambucil or rituximab monotherapy","aka":["IELSG-19","Zucca 2017"],"tldr":"The first randomised trial of first-line drug treatment for MALT lymphoma: the combination of an old tablet and an antibody beat either alone on relapse, and nobody lived longer.","summary":"A phase 3 trial in extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. Patients were initially randomised 1 to 1 between chlorambucil 6 mg per square metre daily on weeks 1 to 6, 9 to 10, 13 to 14, 17 to 18 and 21 to 22, and the same chlorambucil with rituximab 375 mg per square metre on day 1 of weeks 1, 2, 3, 4, 9, 13, 17 and 21. After the planned enrolment of 252 patients the protocol was amended to a three-arm design in a 1 to 1 to 6 ratio, adding a rituximab monotherapy arm, for a final sample of 454.\n\nAt a median follow-up of 7.4 years, five-year event-free survival was 51 per cent (95 per cent confidence interval 42 to 60) with chlorambucil alone, 50 per cent (42 to 59) with rituximab alone and 68 per cent (60 to 76) with the combination (p = 0.0009); the hazard ratio for the combination against chlorambucil was 0.54 (0.38 to 0.77). Progression-free survival was also significantly better with the combination (p = 0.0119). Five-year overall survival was approximately 90 per cent in each arm. No unexpected toxicities were recorded.","asOf":"2026-10-01","links":[{"label":"Journal of Clinical Oncology 2017","url":"https://doi.org/10.1200/JCO.2016.70.6994"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28355112/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28355112"}],"tags":["lymphoma-evidence"],"related":["paper-wotherspoon-h-pylori-malt-lancet-1993","lymphoma-roadmap"],"cancers":["malt-lymphoma","marginal-zone-lymphoma","non-hodgkin-lymphoma"],"sections":["immunotherapy","chemotherapy"],"technologies":[],"targets":["cd20"],"drugs":["chlorambucil","rituximab"],"companies":["ielsg"],"institutions":[],"pathways":[],"terms":[],"trials":["ielsg-19"],"people":[],"bottlenecks":["b-rare-cancers","b-trial-enrolment"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2017,"doi":"10.1200/JCO.2016.70.6994","pmid":"28355112","authors":"Zucca E, Conconi A, Martinelli G, et al.","paperType":"rct","findings":["Five-year event-free survival was 68 per cent (95 per cent confidence interval 60 to 76) with chlorambucil and rituximab, against 51 per cent (42 to 60) with chlorambucil alone and 50 per cent (42 to 59) with rituximab alone (p = 0.0009).","The hazard ratio for event-free survival with the combination against chlorambucil alone was 0.54 (0.38 to 0.77).","Progression-free survival was also significantly better with the combination (p = 0.0119).","Five-year overall survival was approximately 90 per cent in each of the three arms."],"whatItMeans":"The only randomised evidence for first-line systemic treatment of MALT lymphoma. It supports the combination when systemic treatment is needed, and the identical survival across arms supports taking time over that decision.","caveats":["The protocol was amended mid-trial to add a third arm, and the two-arm comparison was analysed and reported before the third arm was unblinded.","Chlorambucil is not the alkylating agent most used today; bendamustine with rituximab has largely replaced it without a randomised comparison in this disease.","Patients whose gastric MALT lymphoma responds to Helicobacter pylori eradication never reach this question."],"changedPractice":true,"participants":454},{"id":"paper-ramsey-j-clin-oncol","kind":"paper","name":"Financial Insolvency as a Risk Factor for Early Mortality Among Patients With Cancer","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 26811521 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: Patients with cancer are more likely to file for bankruptcy than the general population, but the impact of severe financial distress on health outcomes among patients with cancer is not known.\n\nMethods: We linked Western Washington SEER Cancer Registry records with federal bankruptcy records for the region. By using propensity score matching to account for differences in several demographic and clinical factors between patients who did and did not file for bankruptcy, we then fit Cox proportional hazards models to examine the relationship between bankruptcy filing and survival.\n\nResults: Between 1995 and 2009, 231,596 persons were diagnosed with cancer. Patients who filed for bankruptcy (n = 4,728) were more likely to be younger, female, and nonwhite, to have local- or regional- (v distant-) stage disease at diagnosis, and have received treatment. After propensity score matching, 3,841 patients remained in each group (bankruptcy v no bankruptcy). In the matched sample, mean age was 53.0 years, 54% were men, mean income was $49,000, and majorities were white (86%), married (60%), and urban (91%) and had local- or regional-stage disease at diagnosis (84%). Both groups received similar initial treatments. The adjusted hazard ratio for mortality among patients with cancer who filed for bankruptcy versus those who did not was 1.79 (95% CI, 1.64 to 1.96). Hazard ratios varied by cancer type: colorectal, prostate, and thyroid cancers had the highest hazard ratios. Excluding patients with distant-stage disease from the models did not have an effect on results.\n\nConclusion: Severe financial distress requiring bankruptcy protection after cancer diagnosis appears to be a risk factor for mortality. Further research is needed to understand the process by which extreme financial distress influences survival after cancer diagnosis and to find strategies that could mitigate this risk.\n\nIndexed on Europe PMC as PubMed record 26811521 (DOI 10.1200/jco.2015.64.6620). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2016","url":"https://doi.org/10.1200/jco.2015.64.6620"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26811521/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26811521"}],"tags":["europepmc-ingest"],"related":["financial-navigation"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2016,"doi":"10.1200/jco.2015.64.6620","pmid":"26811521","authors":"Ramsey SD, Bansal A, Fedorenko CR, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-firm-act-edp-mitotane-adrenocortical-carcinoma-nejm-2012","kind":"paper","name":"FIRM-ACT: combination chemotherapy in advanced adrenocortical carcinoma","aka":[],"tldr":"The first randomised trial in advanced adrenocortical carcinoma showed that etoposide, doxorubicin and cisplatin with mitotane shrank tumours more often and held them back longer than streptozocin with mitotane, making EDP-mitotane the standard.","summary":"International randomised phase 3 trial of 304 patients with advanced adrenocortical carcinoma assigned to etoposide, doxorubicin and cisplatin plus mitotane (EDP-M) or streptozocin plus mitotane, with crossover at progression.\n\nResponse rates were 23.2 percent with EDP-M against 9.2 percent, and median progression-free survival 5.0 against 2.1 months; median overall survival was 14.8 against 12.0 months, not statistically different, partly because of crossover. Serious adverse events were similar.","asOf":"2026-09-18","links":[{"label":"N Engl J Med 2012","url":"https://doi.org/10.1056/NEJMoa1200966"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22551107/"}],"tags":[],"related":[],"cancers":["advanced-adrenocortical-carcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":["mitotane","etoposide","doxorubicin","cisplatin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2012,"doi":"10.1056/NEJMoa1200966","pmid":"22551107","authors":"Fassnacht M, Terzolo M, Allolio B, et al.","paperType":"rct","findings":["Response rate 23.2 percent with EDP-mitotane versus 9.2 percent with streptozocin-mitotane.","Median progression-free survival 5.0 versus 2.1 months; overall survival 14.8 versus 12.0 months (not significant)."],"whatItMeans":"EDP-mitotane is the first-line chemotherapy for adrenocortical carcinoma that cannot be removed, and the comparator arm for new trials; outcomes remain poor and better drugs are needed.","caveats":["Overall survival did not differ significantly; crossover diluted the comparison.","Toxicity of EDP-M is substantial in a population often already unwell from cortisol excess."],"changedPractice":true,"participants":304},{"id":"paper-badawi-j-nucl-med","kind":"paper","name":"First Human Imaging Studies with the EXPLORER Total-Body PET Scanner","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 30733314 and published in Journal of Nuclear Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Within the EXPLORER Consortium, the construction of the world's first total-body PET/CT scanner has recently been completed. The 194-cm axial field of view of the EXPLORER PET/CT scanner is sufficient to cover, for the first time, the entire human adult body in a single acquisition in more than 99% of the population and allows total-body pharmacokinetic studies with frame durations as short as 1 s. The large increase in sensitivity arising from total-body coverage as well as increased solid angle for detection at any point within the body allows whole-body 18 F-FDG PET studies to be acquired with unprecedented count density, improving the signal-to-noise ratio of the resulting images. Alternatively, the sensitivity gain can be used to acquire diagnostic PET images with very small amounts of activity in the field of view (25 MBq, 0.7 mCi or less), with very short acquisition times (∼1 min or less) or at later time points after the tracer's administration. We report here on the first human imaging studies on the EXPLORER scanner using a range of different protocols that provide initial evidence in support of these claims. These case studies provide the foundation for future carefully controlled trials to quantitatively evaluate the improvements possible through total-body PET imaging.\n\nIndexed on Europe PMC as PubMed record 30733314 (DOI 10.2967/jnumed.119.226498). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Nucl Med 2019","url":"https://doi.org/10.2967/jnumed.119.226498"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30733314/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30733314"}],"tags":["europepmc-ingest"],"related":["nuclear-medicine-hardware"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-nuclear-medicine"],"dependsOn":[],"notes":[],"journal":"Journal of Nuclear Medicine","year":2019,"doi":"10.2967/jnumed.119.226498","pmid":"30733314","authors":"Badawi RD, Shi H, Hu P, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-druker-imatinib-phase1-nejm-2001","kind":"paper","name":"First imatinib trial: a pill that switched off the enzyme driving chronic myeloid leukaemia","aka":[],"tldr":"In the first human study of imatinib, almost every patient with chronic-phase CML who had failed interferon regained normal blood counts, with mild side effects.","summary":"Phase 1 dose-escalation study of the ABL kinase inhibitor STI571 (imatinib) in 83 patients with chronic-phase CML in whom interferon alfa had failed. Doses of 25 to 1000 mg daily were tested and no maximum tolerated dose was reached. At 300 mg or more, complete haematological responses occurred in 53 of 54 patients, usually within four weeks, and cytogenetic responses in 29 of 54 (17 major). It was the first demonstration that a small molecule designed against a defined oncogenic kinase could control a human cancer, and became the template for targeted therapy.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJM200104053441401"}],"tags":[],"related":["paper-iris-imatinib-nejm-2003"],"cancers":["cml"],"sections":[],"technologies":[],"targets":["bcr-abl"],"drugs":["imatinib"],"companies":["novartis"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets","b-translational-valley"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2001,"doi":"10.1056/NEJM200104053441401","authors":"Druker BJ, Talpaz M, Resta DJ, et al.","paperType":"translational","findings":["83 patients with interferon-refractory chronic-phase CML; doses 25-1000 mg/day; no dose-limiting toxicity identified.","Complete haematological response in 53 of 54 patients treated at 300 mg/day or more, typically within 4 weeks.","Cytogenetic responses in 29 of 54 patients at 300 mg or more, 17 of them major (0-35% Ph-positive metaphases).","Adverse events were mostly grade 1-2: nausea, myalgia, oedema and diarrhoea."],"whatItMeans":"Druker's 2001 imatinib paper turned the idea of hitting a cancer's specific molecular engine into a working medicine. For people with CML it began the shift from a fatal disease treated with interferon or transplant to one managed with a daily tablet. It also set expectations, later tempered, that every cancer might have its own imatinib.","caveats":["Single-arm phase 1 with short follow-up and no survival data.","Responses were haematological and cytogenetic; molecular monitoring came later.","CML is unusually dependent on a single fusion kinase, which limits how far the model generalises."],"changedPractice":true,"participants":83},{"id":"paper-nct05413850-j-nucl-med-2024","kind":"paper","name":"First Safety and Efficacy Data with the Radiohybrid 177 Lu-rhPSMA-10.1 for the Treatment of Metastatic Prostate Cancer","aka":[],"tldr":"Published report from the trial registered as NCT05413850, in Journal of Nuclear Medicine (2024), chosen as the most cited paper whose own text cites the registry id.","summary":"We recently published the first dosimetry data, to our knowledge, for the radioligand therapy agent 177 Lu-rhPSMA-10.1, providing an intrapatient comparison with 177 Lu-PSMA-I&T in patients with metastatic prostate cancer. Here, we report efficacy and safety findings from these patients. Methods: Four consecutive patients with prostate-specific membrane antigen (PSMA)-positive metastatic prostate cancer received up to 6 cycles of 177 Lu-rhPSMA-10.1 (7.4-7.7 GBq per cycle). Efficacy (prostate-specific antigen response according to Prostate Cancer Working Group 3 criteria and the Response Evaluation Criteria in PSMA PET/CT), progression-free survival, and overall survival were evaluated. Adverse events were recorded from the first dose until 16-24 mo after treatment. Results: The patients received a total activity of 29.6-59.4 GBq (4-6 cycles). Prostate-specific antigen was reduced by 100%, 99%, 88%, and 35%. Progression-free survival was not reached for 2 patients at 24 and 18 mo of follow-up and was 15 and 12 mo for the other 2 patients. One patient had a sustained complete response with 2 y of follow up. All patients were alive at the last time point of data collection. No serious adverse events were reported. Conclusion: 177 Lu-rhPSMA-10.1 demonstrated encouraging preliminary efficacy and was well tolerated. Formal clinical trials are now under way to evaluate its potential prospectively (NCT05413850).\n\nIndexed on Europe PMC as PubMed record 38164586 (DOI 10.2967/jnumed.123.266741). Its abstract cites the registry id NCT05413850, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Nucl Med 2024","url":"https://doi.org/10.2967/jnumed.123.266741"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38164586/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38164586"},{"label":"ClinicalTrials.gov NCT05413850","url":"https://clinicaltrials.gov/study/NCT05413850"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05413850"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-nuclear-medicine"],"dependsOn":[],"notes":[],"journal":"Journal of Nuclear Medicine","year":2024,"doi":"10.2967/jnumed.123.266741","pmid":"38164586","authors":"Dierks A, Gäble A, Rinscheid A, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05413850 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-lynch-frameshift-vaccine-ccr-2020","kind":"paper","name":"First trial of a vaccine against the shared neoantigens of mismatch-repair-deficient cancers","aka":[],"tldr":"A vaccine of three frameshift peptides shared by almost all microsatellite-unstable tumours was safe and induced immune responses in every patient with MSI colorectal cancer, opening the path to cancer interception vaccines for Lynch syndrome.","summary":"Mismatch-repair-deficient tumours accumulate insertion or deletion mutations in the same coding microsatellites, producing frameshift peptide (FSP) neoantigens that are shared across patients. This phase I/IIa trial vaccinated 22 patients with a history of MSI-high colorectal cancer with three FSP neoantigens (derived from AIM2, HT001 and TAF1B) with Montanide adjuvant.\n\nThe vaccine was well tolerated (injection-site reactions only) and induced humoral and cellular immune responses in all patients who completed the schedule. The study established that shared frameshift neoantigens are immunogenic in humans and are candidates for an off-the-shelf preventive vaccine in Lynch syndrome carriers.\n\nIt seeded the Nous-209 adenoviral vaccine (209 frameshift neoantigens) now in trials in Lynch carriers, and the NCI's Lynch interception programme.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1158/1078-0432.CCR-19-3517"},{"label":"ClinicalTrials.gov NCT05078866","url":"https://clinicaltrials.gov/study/NCT05078866"}],"tags":[],"related":["idea-interception-vaccines","idea-moon-lynch-vaccine-phase3","idea-prev-lynch-frameshift-vaccine-rct"],"cancers":["colorectal","endometrial"],"sections":["prevention","immunotherapy"],"technologies":["interception-vaccination","shared-antigen-vaccine"],"targets":[],"drugs":[],"companies":[],"institutions":["heidelberg-nct","dkfz"],"pathways":[],"terms":["lynch-syndrome","msi","neoantigen"],"trials":[],"people":[],"bottlenecks":["b-hereditary-risk","b-prevention-adoption","b-trial-design"],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2020,"doi":"10.1158/1078-0432.CCR-19-3517","pmid":"32332013","authors":"Kloor M, Reuschenbach M, Pauligk C, et al.","paperType":"translational","findings":["22 patients enrolled; no vaccine-related serious adverse events","Humoral and cellular responses to at least one frameshift peptide in all patients who completed the three-vaccination schedule","Frameshift neoantigens targeted are present in the majority of MSI-high colorectal cancers regardless of patient","The paper provided human proof of principle for a shared-antigen interception vaccine"],"whatItMeans":"Because Lynch syndrome tumours make the same abnormal proteins in almost every patient, a single vaccine could in principle be given to carriers before cancer develops. This small trial showed the concept is safe and immunogenic; whether it prevents cancer requires the randomised trials now being planned.","caveats":["Immune response, not cancer prevention, was the endpoint","Patients had existing or prior cancers, not healthy carriers","Peptide vaccines with Montanide elicit modest T-cell responses compared with viral-vector or mRNA platforms","Efficacy trials in carriers need thousands of participants and years of follow-up"],"changedPractice":false,"participants":22},{"id":"paper-nct03476681-j-exp-clin-cancer-res-2023","kind":"paper","name":"First-in-human phase 1 clinical trial of anti-core 1 O-glycans targeting monoclonal antibody NEO-201 in treatment-refractory solid tumors","aka":[],"tldr":"Published report from the trial registered as NCT03476681, in Journal of experimental & clinical cancer research (2023), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: NEO201 is a humanized IgG1 monoclonal antibody (mAb) generated against tumor-associated antigens from patients with colorectal cancer. NEO-201 binds to core 1 or extended core 1 O-glycans expressed by its target cells. Here, we present outcomes from a phase I trial of NEO-201 in patients with advanced solid tumors that have not responded to standard treatments.\n\nMethods: This was a single site, open label 3 + 3 dose escalation clinical trial. NEO-201 was administered intravenously every two weeks in a 28-day cycle at dose level (DL) 1 (1 mg/kg), DL 1.5 (1.5 mg/kg) and DL 2 (2 mg/kg) until dose limiting toxicity (DLT), disease progression, or patient withdrawal. Disease evaluations were conducted after every 2 cycles. The primary objective was to assess the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of NEO-201. The secondary objective was to assess the antitumor activity by RECIST v1.1. The exploratory objectives assessed pharmacokinetics and the effect of NEO-201 administration on immunologic parameters and their impact on clinical response.\n\nResults: Seventeen patients (11 colorectal, 4 pancreatic and 2 breast cancers) were enrolled; 2 patients withdrew after the first dose and were not evaluable for DLT. Twelve of the 15 patients evaluable for safety discontinued due to disease progression and 3 patients discontinued due to DLT (grade 4 febrile neutropenia [1 patient] and prolonged neutropenia [1 patient] at DL 2, and grade 3 prolonged (> 72 h) febrile neutropenia [1 patient] at DL 1.5). A total of 69 doses of NEO-201 were administered (range 1-15, median 4). Common (> 10%) grade 3/4 toxicities occurred as follows: neutropenia (26/69 doses, 17/17 patients), white blood cell decrease (16/69 doses, 12/17 patients), lymphocyte decrease (8/69 doses, 6/17 patients). Thirteen patients were evaluable for disease response; the best response was stable disease (SD) in 4 patients with colorectal cancer. Analysis of soluble factors in serum revealed that a high level of soluble MICA at baseline was correlated with a downregulation of NK cell activation markers and progressive disease. Unexpectedly, flow cytometry showed that NEO-201 also binds to circulating regulatory T cells and reduction of the quantities of these cells was observed especially in patients with SD.\n\nConclusions: NEO-201 was safe and well tolerated at the MTD of 1.5 mg/kg, with neutropenia being the most common adverse event. Furthermore, a reduction in the percentage of regulatory T cells following NEO-201 treatment supports our ongoing phase II clinical trial evaluating the efficiency of the combination of NEO-201 with the immune checkpoint inhibitor pembrolizumab in adults with treatment-resistant solid tumors.\n\nTrial registration: NCT03476681. Registered 03/26/2018.\n\nIndexed on Europe PMC as PubMed record 36991390 (DOI 10.1186/s13046-023-02649-6). Its abstract cites the registry id NCT03476681, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Exp Clin Cancer Res 2023","url":"https://doi.org/10.1186/s13046-023-02649-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36991390/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36991390"},{"label":"ClinicalTrials.gov NCT03476681","url":"https://clinicaltrials.gov/study/NCT03476681"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct03476681"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-experimental-and-clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Journal of experimental & clinical cancer research","year":2023,"doi":"10.1186/s13046-023-02649-6","pmid":"36991390","authors":"Cole CB, Morelli MP, Fantini M, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03476681 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-nct05199272-cancer-res-commun-2025","kind":"paper","name":"First-in-Human Study of 23ME-00610, an Antagonistic Antibody for Genetically Validated CD200R1 Immune Checkpoint, in Participants with Advanced Solid Malignancies","aka":[],"tldr":"Published report from the trial registered as NCT05199272, in Cancer research communications (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Purpose: In this phase 1 portion of a first-in-human phase 1/2a study (NCT05199272), 23ME-00610 was evaluated in participants with advanced solid malignancies to determine its safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD). Exploratory biomarkers were evaluated to examine potential correlates of efficacy and safety.\n\nPatients and methods: Eligible participants (≥18 years) were administered 23ME-00610 intravenously every 3 weeks (Q3W) using an accelerated titration design followed by a traditional 3 + 3 design, with an initial dose level of 2 mg.\n\nResults: Twenty-eight participants were enrolled across seven cohorts and received a median of four cycles of 23ME-00610. No treatment-related serious adverse events (AE) were observed, and the maximum tolerated dose was not reached. Overall, the PK of 23ME-00610 was linear and dose proportional for doses ≥60 mg, with a median terminal half-life of 13 days at 1,400 mg. Peripheral saturation of CD200R1 was observed for doses ≥60 mg. Immune-related AEs, including rash, pruritus, and hypothyroidism, were predicted by phenome-wide association studies and observed for doses ≥60 mg. A confirmed partial response was observed in a participant with well-differentiated pancreatic neuroendocrine cancer whose tumor was among those with the highest tumor CD200 expression.\n\nConclusions: 23ME-00610 has mild-to-moderate on-target AEs and PK/PD consistent with tumor target saturation and dosing every 3 weeks. The trend for clinical benefit in participants with tumor CD200 expression suggests that 23ME-00610 inhibits CD200R1 signaling and may reverse CD200-mediated immune evasion. Based on PK/PD, safety, and preliminary antitumor activity, 1,400 mg Q3W was selected as the dose for further study.\n\nSignificance: Genome-wide association studies (GWAS) of the 23andMe genetic database identified CD200R1 as a promising therapeutic target for cancer. This phase 1 study of 23ME-00610, a CD200R1 antagonist IgG1, showed acceptable safety and tolerability, PK supporting Q3W dosing, and PD and preliminary clinical activity supporting an initial recommended phase 2 dose of 1,400 mg.\n\nIndexed on Europe PMC as PubMed record 39651931 (DOI 10.1158/2767-9764.crc-24-0568). Its abstract cites the registry id NCT05199272, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Cancer Res Commun 2025","url":"https://doi.org/10.1158/2767-9764.crc-24-0568"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39651931/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39651931"},{"label":"ClinicalTrials.gov NCT05199272","url":"https://clinicaltrials.gov/study/NCT05199272"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05199272"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-research-communications"],"dependsOn":[],"notes":[],"journal":"Cancer research communications","year":2025,"doi":"10.1158/2767-9764.crc-24-0568","pmid":"39651931","authors":"Kummar S, Razak AA, Laurie S, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05199272 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-hassan-j-clin-oncol","kind":"paper","name":"First-in-Human, Multicenter, Phase I Dose-Escalation and Expansion Study of Anti-Mesothelin Antibody-Drug Conjugate Anetumab Ravtansine in Advanced or Metastatic Solid Tumors","aka":[],"tldr":"Paper cited by one treatment page, indexed on Europe PMC as PubMed record 32213105 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: This phase I study, which to our knowledge is the first-in-human study of this kind, investigates the safety, tolerability, pharmacokinetics, and clinical activity of anetumab ravtansine, an antibody-drug conjugate of anti-mesothelin antibody linked to maytansinoid DM4, in patients with advanced, metastatic, or recurrent solid tumors known to express the tumor-differentiation antigen mesothelin.\n\nPatients and methods: This phase I, open-label, multicenter, dose-escalation and dose-expansion study of anetumab ravtansine enrolled 148 adult patients with multiple solid tumor types. Ten dose-escalation cohorts of patients with advanced or metastatic solid tumors (0.15-7.5 mg/kg) received anetumab ravtansine once every 3 weeks, and 6 expansion cohorts of patients with advanced, recurrent ovarian cancer or malignant mesothelioma received anetumab ravtansine at the maximum tolerated dose once every 3 weeks, 1.8 mg/kg once per week, and 2.2 mg/kg once per week.\n\nResults: Forty-five patients were enrolled across the 10 dose-escalation cohorts. The maximum tolerated dose of anetumab ravtansine was 6.5 mg/kg once every 3 weeks or 2.2 mg/kg once per week. Thirty-two patients were enrolled in the 6.5 mg/kg once-every-3-weeks, 35 in the 1.8 mg/kg once-per-week, and 36 in the 2.2 mg/kg once-per-week expansion cohorts. The most common drug-related adverse events were fatigue, nausea, diarrhea, anorexia, vomiting, peripheral sensory neuropathy, and keratitis/keratopathy. There were no drug-related deaths. Anetumab ravtansine pharmacokinetics were dose proportional; the average half-life was 5.5 days. Among 148 patients with mesothelioma or ovarian, pancreatic, non-small-cell lung, and breast cancers, 1 had a complete response, 11 had partial responses, and 66 had stable disease. High levels of tumor mesothelin expression were detected in patients with clinical activity.\n\nConclusion: Anetumab ravtansine exhibited a manageable safety and favorable pharmacokinetic profile with encouraging preliminary antitumor activity in heavily pretreated patients with mesothelin-expressing solid tumors. The results allowed for the determination of recommended doses, schedules, and patient populations for anetumab ravtansine in phase II studies.\n\nIndexed on Europe PMC as PubMed record 32213105 (DOI 10.1200/jco.19.02085). Matched by DOI alone: one treatment page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2020","url":"https://doi.org/10.1200/jco.19.02085"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32213105/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32213105"}],"tags":["europepmc-ingest"],"related":["anetumab-ravtansine"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/jco.19.02085","pmid":"32213105","authors":"Hassan R, Blumenschein GR, Moore KN, et al.","paperType":"observational","findings":[],"whatItMeans":"One treatment page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nct04561362-j-clin-oncol-2025","kind":"paper","name":"First-in-Human, Phase I/II Dose Escalation and Expansion Study of Zelenectide Pevedotin in Patients With Advanced Solid Tumors: Results From Monotherapy Dose Escalation","aka":[],"tldr":"Published report from the trial registered as NCT04561362, in Journal of Clinical Oncology (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Purpose: Zelenectide pevedotin (BT8009) is a Bicycle Drug Conjugate comprising a highly selective Nectin-4-targeting Bicycle peptide, linked to monomethyl auristatin E. We report monotherapy dose-escalation results from Duravelo-1 (Phase I/II; ClinicalTrials.gov identifier: NCT04561362).\n\nMethods: Adults with advanced/metastatic solid tumors associated with Nectin-4 expression received zelenectide pevedotin intravenously at 2.5, 5.0, or 7.5 mg/m 2 once weekly on a 28-day cycle; or 7.5 mg/m 2 on days 1 and 8 of a 21-day cycle; or 7.5 or 10.0 mg/m 2 once every 2 weeks on a 28-day cycle. Primary objectives were to evaluate safety and tolerability; antitumor activity and pharmacokinetic characterization were secondary objectives.\n\nResults: Forty-nine patients, most with urothelial carcinoma (UC; 25 of 49), received three previous lines of therapy (median). Common treatment-related adverse events (TRAEs) included nausea (49% [grade 3/4 2%]), likely because of a lack of prophylactic antiemetics during the dose-limiting toxicity period, and fatigue (39% [grade 3/4 6%]). The most common TRAEs of clinical interest were peripheral neuropathy (33% [grade 3/4 2%]), neutropenia (22% [grade 3/4 16%]), and skin reactions (22% [grade 3/4 2%]). The maximum tolerated dose was 7.5 mg/m 2 once every 2 weeks; the recommended phase 2 doses were 5.0 mg/m 2 once weekly and 7.5 mg/m 2 on days 1 and 8 of a 21-day cycle. Across doses (efficacy-evaluable; all tumor types), the objective response rate (ORR) was 24% and the clinical benefit rate (CBR) was 48% (n = 10 of 42; 95% CI, 12.1 to 39.5); the ORR was 38% and the CBR was 57% for patients with UC (n = 8 of 21; 95% CI, 18.1 to 61.6). The median duration of response and the median follow-up for all patients were 11.1 and 7.4 months, respectively.\n\nConclusion: Zelenectide pevedotin monotherapy demonstrated a generally well-tolerated safety profile and preliminary efficacy, particularly in UC, supporting investigation of UC and non-UC populations in the expansion phase.\n\nIndexed on Europe PMC as PubMed record 41197088 (DOI 10.1200/jco-25-00559). Its abstract cites the registry id NCT04561362, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2025","url":"https://doi.org/10.1200/jco-25-00559"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41197088/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41197088"},{"label":"ClinicalTrials.gov NCT04561362","url":"https://clinicaltrials.gov/study/NCT04561362"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04561362"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2025,"doi":"10.1200/jco-25-00559","pmid":"41197088","authors":"Baldini C, Verlingue L, Goldschmidt V, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04561362 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-chawla-jama-oncol","kind":"paper","name":"First-Line Aldoxorubicin vs Doxorubicin in Metastatic or Locally Advanced Unresectable Soft-Tissue Sarcoma: A Phase 2b Randomized Clinical Trial","aka":[],"tldr":"Paper cited by one trial page and one treatment page, indexed on Europe PMC as PubMed record 26378637 and published in JAMA Oncology; the citing pages link this DOI, which is how the record was matched.","summary":"Importance: Standard therapy for advanced soft-tissue sarcoma has not changed substantially in decades, and patient prognosis remains poor. Aldoxorubicin, a novel albumin-binding prodrug of doxorubicin, showed clinical activity against advanced soft-tissue sarcoma in phase 1 studies.\n\nObjective: To evaluate efficacy and safety of aldoxorubicin vs doxorubicin in patients with advanced soft-tissue sarcoma.\n\nDesign, setting, and participants: International, multicenter, phase 2b, open-label, randomized study at general community practices, private practices, or institutional practices. Between August 2012 and December 2013, 140 patients with previously untreated locally advanced, unresectable, or metastatic soft-tissue sarcoma were screened.\n\nInterventions: Randomization (2:1) to aldoxorubicin 350 mg/m2 (dose equivalent to doxorubicin 260 mg/m2) or doxorubicin 75 mg/m2, administered once every 3 weeks for up to 6 cycles.\n\nMain outcomes and measures: Primary end point was progression-free survival. Secondary end points were 6-month progression-free survival, overall survival, tumor response rate, and safety. All efficacy end points were evaluated by independent and local review.\n\nResults: A total of 126 patients were randomized, and 123 received aldoxorubicin (n = 83) or doxorubicin (n = 40). Median (range) patient age was 54.0 (21-77 years); 42 (34%) had leiomyosarcoma. By independent review, median progression-free survival was significantly improved (5.6 [95% CI, 3.0-8.1] vs 2.7 [95% CI, 1.6-4.3] months; P =.02) with aldoxorubicin compared with doxorubicin, as was the rate of 6-month progression-free survival (46% and 23%; P =.02). Median overall survival was 15.8 (95% CI, 13.0 to not available) months with aldoxorubicin and 14.3 (95% CI, 8.6-20.6) months with doxorubicin (P =.21). Overall tumor response rate (by Response Evaluation Criteria in Solid Tumors, version 1.1) by independent review was higher with aldoxorubicin than with doxorubicin (25% [20 patients, all partial response] vs 0%). Grade 3 or 4 neutropenia was more frequent with aldoxorubicin than with doxorubicin (24 [29%] vs 5 [12%]), but not grade 3 or 4 febrile neutropenia (12 [14%] vs 7 [18%]). No acute cardiotoxic effects were observed with either treatment, although left ventricular ejection fraction less than 50% occurred in 3 of 40 patients receiving doxorubicin.\n\nConclusions and relevance: Single-agent aldoxorubicin therapy showed superior efficacy over doxorubicin by prolonging progression-free survival and improving rates of 6-month progression-free survival and tumor response. Aldoxorubicin therapy exhibited manageable adverse effects, without unexpected events, and without evidence of acute cardiotoxicity. Further investigation of aldoxorubicin therapy in advanced soft-tissue sarcoma is warranted.\n\nTrial registration: clinicaltrials.gov Identifier: NCT01514188.\n\nIndexed on Europe PMC as PubMed record 26378637 (DOI 10.1001/jamaoncol.2015.3101). Matched by DOI alone: one trial page and one treatment page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA Oncol 2015","url":"https://doi.org/10.1001/jamaoncol.2015.3101"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26378637/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26378637"}],"tags":["europepmc-ingest"],"related":["aldoxorubicin"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["aldoxorubicin-phase-3-sts"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2015,"doi":"10.1001/jamaoncol.2015.3101","pmid":"26378637","authors":"Chawla SP, Papai Z, Mukhametshina G, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page and one treatment page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nct04854668-signal-transduct-target-ther-2026","kind":"paper","name":"First-line anlotinib versus bevacizumab plus CapeOX in RAS/BRAF wild-type unresectable metastatic colorectal cancer (ANCHOR): a multicenter, prospective, randomized, phase 3 trial","aka":[],"tldr":"Published report from the BRAF Wild Metastatic Colorectal Can trial registered as NCT04854668, in Signal transduction and targeted therapy (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Bevacizumab plus chemotherapy is the standard first-line therapy for metastatic colorectal cancer (mCRC). To date, no phase 3 trial has compared first-line oral multitargeted TKI versus bevacizumab plus chemotherapy in RAS/BRAF wild-type mCRC. The open-label, noninferiority, randomized, phase 3 trial (ANCHOR; NCT04854668; CTR20210940) evaluated first-line anlotinib versus bevacizumab plus oxaliplatin and capecitabine (CapeOX) in this setting. Patients were centrally randomized (1:1) to receive 4-8 cycles of CapeOX in combination with either anlotinib (12 mg once daily on days 1-14) or bevacizumab (7.5 mg/kg on day 1) every 3 weeks, followed by maintenance therapy with anlotinib or bevacizumab plus capecitabine until unacceptable toxicity or disease progression. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee in the intention-to-treat population. The hazard ratio (HR) for the noninferiority margin was 1.09. Between May 25, 2021, and August 30, 2023, 373 patients were assigned to the anlotinib group and 375 to the bevacizumab group. at February 2, 2025, the median follow-up was 25.1 months (95% confidence interval [CI] 23.8-26.3). The median PFS was 11.0 months (95% CI 9.8-11.2) in the anlotinib group versus 11.0 months (9.7-11.2) in the bevacizumab group (stratified HR, 1.00; 95% CI 0.84-1.18; p = 0.87). The incidences of grade ≥3 treatment-related adverse events were 64.9% and 44.8%, respectively. Compared with bevacizumab plus CapeOX, anlotinib plus CapeOX showed similar antitumor activity but failed to reach the prespecified noninferiority margin for PFS and was associated with increased manageable toxicity.\n\nIndexed on Europe PMC as PubMed record 42675036 (DOI 10.1038/s41392-026-02938-4). Its abstract cites the registry id NCT04854668, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Signal Transduct Target Ther 2026","url":"https://doi.org/10.1038/s41392-026-02938-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42675036/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42675036"},{"label":"ClinicalTrials.gov NCT04854668","url":"https://clinicaltrials.gov/study/NCT04854668"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04854668"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Signal transduction and targeted therapy","year":2026,"doi":"10.1038/s41392-026-02938-4","pmid":"42675036","authors":"Liu Y, Zhang Y, Lin R, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04854668 with the most citations, so it is the natural first reading for anyone following the BRAF Wild Metastatic Colorectal Can trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-impower133-n-engl-j-med-2018","kind":"paper","name":"First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer","aka":[],"tldr":"Published report from the IMpower133 trial registered as NCT02763579, in New England Journal of Medicine (2018), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Enhancing tumor-specific T-cell immunity by inhibiting programmed death ligand 1 (PD-L1)-programmed death 1 (PD-1) signaling has shown promise in the treatment of extensive-stage small-cell lung cancer. Combining checkpoint inhibition with cytotoxic chemotherapy may have a synergistic effect and improve efficacy.\n\nMethods: We conducted this double-blind, placebo-controlled, phase 3 trial to evaluate atezolizumab plus carboplatin and etoposide in patients with extensive-stage small-cell lung cancer who had not previously received treatment. Patients were randomly assigned in a 1:1 ratio to receive carboplatin and etoposide with either atezolizumab or placebo for four 21-day cycles (induction phase), followed by a maintenance phase during which they received either atezolizumab or placebo (according to the previous random assignment) until they had unacceptable toxic effects, disease progression according to Response Evaluation Criteria in Solid Tumors, version 1.1, or no additional clinical benefit. The two primary end points were investigator-assessed progression-free survival and overall survival in the intention-to-treat population.\n\nResults: A total of 201 patients were randomly assigned to the atezolizumab group, and 202 patients to the placebo group. At a median follow-up of 13.9 months, the median overall survival was 12.3 months in the atezolizumab group and 10.3 months in the placebo group (hazard ratio for death, 0.70; 95% confidence interval [CI], 0.54 to 0.91; P=0.007). The median progression-free survival was 5.2 months and 4.3 months, respectively (hazard ratio for disease progression or death, 0.77; 95% CI, 0.62 to 0.96; P=0.02). The safety profile of atezolizumab plus carboplatin and etoposide was consistent with the previously reported safety profile of the individual agents, with no new findings observed.\n\nConclusions: The addition of atezolizumab to chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer resulted in significantly longer overall survival and progression-free survival than chemotherapy alone. (Funded by F. Hoffmann-La Roche/Genentech; IMpower133 ClinicalTrials.gov number, NCT02763579.).\n\nIndexed on Europe PMC as PubMed record 30280641 (DOI 10.1056/nejmoa1809064). Its abstract cites the registry id NCT02763579, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2018","url":"https://doi.org/10.1056/nejmoa1809064"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30280641/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30280641"},{"label":"ClinicalTrials.gov NCT02763579","url":"https://clinicaltrials.gov/study/NCT02763579"}],"tags":["europepmc-ingest"],"related":["lung-cancer-evidence-roadmap","paper-paz-ares-caspian-durvalumab-es-sclc-lancet-2019"],"cancers":["lung-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["impower133"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2018,"doi":"10.1056/nejmoa1809064","pmid":"30280641","authors":"Horn L, Mansfield AS, Szczęsna A, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02763579 with the most citations, so it is the natural first reading for anyone following the IMpower133 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-serena-6-n-engl-j-med-2025","kind":"paper","name":"First-Line Camizestrant for Emerging ESR1 -Mutated Advanced Breast Cancer","aka":[],"tldr":"Published report from the SERENA-6 trial registered as NCT04964934, in New England Journal of Medicine (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Mutations in ESR1 are the most common mechanism of acquired resistance to treatment with an aromatase inhibitor plus a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor for advanced breast cancer. Camizestrant, a next-generation selective estrogen-receptor (ER) degrader and complete ER antagonist, has shown antitumor activity in ER-positive advanced breast cancer.\n\nMethods: We tested patients with advanced breast cancer with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative tumors for ESR1 mutations in circulating tumor DNA (ctDNA) once every 2 to 3 months. All the patients had received at least 6 months of first-line therapy with an aromatase inhibitor plus a CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib). Patients who were found to have an ESR1 mutation and did not have radiologic progression were assigned in a 1:1 ratio to switch to camizestrant (75 mg once daily) with a continued CDK4/6 inhibitor plus placebo in place of an aromatase inhibitor or to continue to receive an aromatase inhibitor plus a CDK4/6 inhibitor plus placebo in place of camizestrant. The primary outcome was investigator-assessed progression-free survival.\n\nResults: A total of 3256 patients were tested for an ESR1 mutation. The 315 eligible patients were assigned to switch to camizestrant (157 patients) or to continue to receive an aromatase inhibitor (158 patients). At an interim analysis at a median follow-up of 12.6 months, the median progression-free survival was 16.0 months (95% confidence interval [CI], 12.7 to 18.2) in the camizestrant group and 9.2 months (95% CI, 7.2 to 9.5) in the aromatase-inhibitor group (hazard ratio for progression or death, 0.44; 95% CI, 0.31 to 0.60; P<0.0001). The median time until a deterioration in the patient-reported global health status and quality of life occurred was 21.0 months with camizestrant and 6.4 months with an aromatase inhibitor (hazard ratio, 0.54; 95% CI, 0.34 to 0.84). The frequency of discontinuation because of adverse events was 1.3% with camizestrant and 1.9% with an aromatase inhibitor.\n\nConclusions: In patients with ER-positive, HER2-negative advanced breast cancer with an ESR1 mutation that emerged during treatment, those who were switched to camizestrant with continuation of a CDK4/6 inhibitor during first-line therapy had significantly longer progression-free survival than those who maintained the aromatase-inhibitor combination. (Funded by AstraZeneca; SERENA-6 ClinicalTrials.gov number, NCT04964934.).\n\nIndexed on Europe PMC as PubMed record 40454637 (DOI 10.1056/nejmoa2502929). Its abstract cites the registry id NCT04964934, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2025","url":"https://doi.org/10.1056/nejmoa2502929"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40454637/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40454637"},{"label":"ClinicalTrials.gov NCT04964934","url":"https://clinicaltrials.gov/study/NCT04964934"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["serena-6"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2025,"doi":"10.1056/nejmoa2502929","pmid":"40454637","authors":"Bidard FC, Mayer EL, Park YH, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04964934 with the most citations, so it is the natural first reading for anyone following the SERENA-6 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-empower-lung-1-lancet-oncol-2023-update","kind":"paper","name":"First-line cemiplimab monotherapy and continued cemiplimab beyond progression plus chemotherapy for advanced non-small-cell lung cancer with PD-L1 50% or more (EMPOWER-Lung 1): 35-month follow-up from a mutlicentre, open-label, randomised, phase 3 trial","aka":[],"tldr":"Later report from the EMPOWER-Lung 1 trial registered as NCT03088540, in The Lancet Oncology (2023); its title describes an updated or longer-term analysis.","summary":"Background: Cemiplimab provided significant survival benefit to patients with advanced non-small-cell lung cancer with PD-L1 tumour expression of at least 50% and no actionable biomarkers at 1-year follow-up. In this exploratory analysis, we provide outcomes after 35 months' follow-up and the effect of adding chemotherapy to cemiplimab at the time of disease progression.\n\nMethods: EMPOWER-Lung 1 was a multicentre, open-label, randomised, phase 3 trial. We enrolled patients (aged ≥18 years) with histologically confirmed squamous or non-squamous advanced non-small-cell lung cancer with PD-L1 tumour expression of 50% or more. We randomly assigned (1:1) patients to intravenous cemiplimab 350 mg every 3 weeks for up to 108 weeks, or until disease progression, or investigator's choice of chemotherapy. Central randomisation scheme generated by an interactive web response system governed the randomisation process that was stratified by histology and geographical region. Primary endpoints were overall survival and progression free survival, as assessed by a blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumours version 1.1. Patients with disease progression on cemiplimab could continue cemiplimab with the addition of up to four cycles of chemotherapy. We assessed response in these patients by BICR against a new baseline, defined as the last scan before chemotherapy initiation. The primary endpoints were assessed in all randomly assigned participants (ie, intention-to-treat population) and in those with a PD-L1 expression of at least 50%. We assessed adverse events in all patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT03088540.\n\nFindings: Between May 29, 2017, and March 4, 2020, we recruited 712 patients (607 [85%] were male and 105 [15%] were female). We randomly assigned 357 (50%) to cemiplimab and 355 (50%) to chemotherapy. 284 (50%) patients assigned to cemiplimab and 281 (50%) assigned to chemotherapy had verified PD-L1 expression of at least 50%. At 35 months' follow-up, among those with a verified PD-L1 expression of at least 50% median overall survival in the cemiplimab group was 26·1 months (95% CI 22·1-31·8; 149 [52%] of 284 died) versus 13·3 months (10·5-16·2; 188 [67%] of 281 died) in the chemotherapy group (hazard ratio [HR] 0·57, 95% CI 0·46-0·71; p<0·0001), median progression-free survival was 8·1 months (95% CI 6·2-8·8; 214 events occurred) in the cemiplimab group versus 5·3 months (4·3-6·1; 236 events occurred) in the chemotherapy group (HR 0·51, 95% CI 0·42-0·62; p<0·0001). Continued cemiplimab plus chemotherapy as second-line therapy (n=64) resulted in a median progression-free survival of 6·6 months (6·1-9·3) and overall survival of 15·1 months (11·3-18·7). The most common grade 3-4 treatment-emergent adverse events were anaemia (15 [4%] of 356 patients in the cemiplimab group vs 60 [17%] of 343 in the control group), neutropenia (three [1%] vs 35 [10%]), and pneumonia (18 [5%] vs 13 [4%]). Treatment-related deaths occurred in ten (3%) of 356 patients treated with cemiplimab (due to autoimmune myocarditis, cardiac failure, cardio-respiratory arrest, cardiopulmonary failure, septic shock, tumour hyperprogression, nephritis, respiratory failure, [n=1 each] and general disorders or unknown [n=2]) and in seven (2%) of 343 patients treated with chemotherapy (due to pneumonia and pulmonary embolism [n=2 each], and cardiac arrest, lung abscess, and myocardial infarction [n=1 each]). The safety profile of cemiplimab at 35 months, and of continued cemiplimab plus chemotherapy, was generally consistent with that previously observed for these treatments, with no new safety signals INTERPRETATION: At 35 months' follow-up, the survival benefit of cemiplimab for patients with advanced non-small-cell lung cancer was at least as pronounced as at 1 year, affirming its use as first-line monotherapy for this population. Adding chemotherapy to cemiplimab at progression might provide a new second-line treatment for patients with advanced non-small-cell lung cancer.\n\nFunding: Regeneron Pharmaceuticals and Sanofi.\n\nIndexed on Europe PMC as PubMed record 37591293 (DOI 10.1016/s1470-2045(23)00329-7). Its abstract cites the registry id NCT03088540, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2023","url":"https://doi.org/10.1016/s1470-2045(23)00329-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37591293/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37591293"},{"label":"ClinicalTrials.gov NCT03088540","url":"https://clinicaltrials.gov/study/NCT03088540"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["empower-lung-1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2023,"doi":"10.1016/s1470-2045(23)00329-7","pmid":"37591293","authors":"Özgüroğlu M, Kilickap S, Sezer A, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the EMPOWER-Lung 1 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-ascend-4-lancet-2017","kind":"paper","name":"First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study","aka":[],"tldr":"The primary report of ASCEND-4: untreated ALK-positive lung cancer stayed under control for a median of 16.6 months on ceritinib against 8.1 months on platinum chemotherapy.","summary":"Randomised, open-label phase 3 study at 134 centres in 28 countries in untreated stage IIIB or IV ALK-rearranged non-squamous non-small-cell lung cancer. Patients were assigned to oral ceritinib 750 mg a day or platinum-based chemotherapy (cisplatin or carboplatin plus pemetrexed every 3 weeks for four cycles followed by pemetrexed maintenance), stratified by performance status, previous neoadjuvant or adjuvant chemotherapy and brain metastases. The primary endpoint was progression-free survival by blinded independent review committee in the full analysis set.\n\nBetween August 2013 and May 2015, 376 patients were randomised (189 ceritinib, 187 chemotherapy). Median progression-free survival was 16.6 months (95% CI 12.6 to 27.2) with ceritinib and 8.1 months (95% CI 5.8 to 11.1) with chemotherapy (hazard ratio 0.55, 95% CI 0.42 to 0.73). The most common adverse events on ceritinib were diarrhoea (85 percent), nausea (69 percent), vomiting (66 percent) and raised alanine aminotransferase (60 percent). Funded by Novartis.","asOf":"2026-09-24","links":[{"label":"The Lancet 2017","url":"https://doi.org/10.1016/S0140-6736(17)30123-X"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28126333/"},{"label":"ClinicalTrials.gov NCT01828099","url":"https://clinicaltrials.gov/study/NCT01828099"}],"tags":[],"related":[],"cancers":["nsclc","alk-positive-nsclc"],"sections":[],"technologies":[],"targets":["alk"],"drugs":["ceritinib"],"companies":["novartis"],"institutions":[],"pathways":[],"terms":[],"trials":["nct01828099"],"people":["jean-charles-soria","luis-paz-ares","juergen-wolf","chong-jen-yu"],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2017,"doi":"10.1016/S0140-6736(17)30123-X","pmid":"28126333","authors":"Soria JC, Tan DSW, Chiari R, et al.","paperType":"rct","findings":["Median progression-free survival 16.6 vs 8.1 months by blinded independent review; hazard ratio 0.55 (95% CI 0.42 to 0.73).","376 patients randomised at 134 centres in 28 countries between August 2013 and May 2015.","Diarrhoea 85%, nausea 69%, vomiting 66% and raised alanine aminotransferase 60% on ceritinib."],"whatItMeans":"ASCEND-4 gave ceritinib its 2017 US first-line approval and showed that a second-generation ALK inhibitor beats chemotherapy in untreated disease. In practice alectinib, brigatinib and lorlatinib, tested against crizotinib rather than chemotherapy, became the usual first-line choices, partly because ceritinib's gut side effects at 750 mg fasted were hard to live with.","caveats":["Open-label; the comparator was chemotherapy, not crizotinib, which was already standard when the trial ran.","Overall survival was not reported in the abstract and was not significantly different at the prespecified interim analysis in the US label.","The 750 mg fasted dose studied here was later replaced in the label by 450 mg with food."],"changedPractice":true,"participants":376},{"id":"paper-kroep-mpnst-first-line-chemotherapy-ann-oncol-2011","kind":"paper","name":"First-line chemotherapy for malignant peripheral nerve sheath tumour versus other soft tissue sarcomas (EORTC pooled analysis)","aka":[],"tldr":"Pooling twelve EORTC trials showed that malignant peripheral nerve sheath tumours respond to doxorubicin-ifosfamide about as well as other sarcomas, though survival is shorter, and that NF1-associated tumours may respond less.","summary":"Retrospective analysis of 175 patients with malignant peripheral nerve sheath tumour among 2,675 soft tissue sarcoma patients treated with first-line anthracycline-based chemotherapy in EORTC trials.\n\nResponse rate was 21 percent in MPNST compared with 22 percent in other sarcomas, with the highest response to doxorubicin-ifosfamide; median overall survival was 48 weeks against 51 weeks, and NF1-associated tumours tended to respond less.","asOf":"2026-09-17","links":[{"label":"Ann Oncol 2011","url":"https://doi.org/10.1093/annonc/mdq338"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20656792/"}],"tags":[],"related":[],"cancers":["malignant-peripheral-nerve-sheath-tumour"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2011,"doi":"10.1093/annonc/mdq338","pmid":"20656792","authors":"Kroep JR, Ouali M, Gelderblom H, et al.","paperType":"observational","findings":["Objective response 21 percent in MPNST vs 22 percent in other sarcomas.","Median overall survival 48 weeks; lower response in NF1-associated MPNST."],"whatItMeans":"Doxorubicin-ifosfamide is the standard first-line chemotherapy for advanced MPNST, and the analysis supports treating it like other high-grade sarcomas while recognising its shorter survival.","caveats":["Retrospective pooled analysis across trials spanning decades."],"changedPractice":true,"participants":175},{"id":"paper-solomon-n-engl-j-med","kind":"paper","name":"First-line crizotinib versus chemotherapy in ALK-positive lung cancer","aka":[],"tldr":"Paper cited by one treatment page, indexed on Europe PMC as PubMed record 25470694 and published in New England Journal of Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Background: The efficacy of the ALK inhibitor crizotinib as compared with standard chemotherapy as first-line treatment for advanced ALK-positive non-small-cell lung cancer (NSCLC) is unknown.\n\nMethods: We conducted an open-label, phase 3 trial comparing crizotinib with chemotherapy in 343 patients with advanced ALK-positive nonsquamous NSCLC who had received no previous systemic treatment for advanced disease. Patients were randomly assigned to receive oral crizotinib at a dose of 250 mg twice daily or to receive intravenous chemotherapy (pemetrexed, 500 mg per square meter of body-surface area, plus either cisplatin, 75 mg per square meter, or carboplatin, target area under the curve of 5 to 6 mg per milliliter per minute) every 3 weeks for up to six cycles. Crossover to crizotinib treatment after disease progression was permitted for patients receiving chemotherapy. The primary end point was progression-free survival as assessed by independent radiologic review.\n\nResults: Progression-free survival was significantly longer with crizotinib than with chemotherapy (median, 10.9 months vs. 7.0 months; hazard ratio for progression or death with crizotinib, 0.45; 95% confidence interval [CI], 0.35 to 0.60; P<0.001). Objective response rates were 74% and 45%, respectively (P<0.001). Median overall survival was not reached in either group (hazard ratio for death with crizotinib, 0.82; 95% CI, 0.54 to 1.26; P=0.36); the probability of 1-year survival was 84% with crizotinib and 79% with chemotherapy. The most common adverse events with crizotinib were vision disorders, diarrhea, nausea, and edema, and the most common events with chemotherapy were nausea, fatigue, vomiting, and decreased appetite. As compared with chemotherapy, crizotinib was associated with greater reduction in lung cancer symptoms and greater improvement in quality of life.\n\nConclusions: Crizotinib was superior to standard first-line pemetrexed-plus-platinum chemotherapy in patients with previously untreated advanced ALK-positive NSCLC. (Funded by Pfizer; PROFILE 1014 ClinicalTrials.gov number, NCT01154140.).\n\nIndexed on Europe PMC as PubMed record 25470694 (DOI 10.1056/nejmoa1408440). Matched by DOI alone: one treatment page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2014","url":"https://doi.org/10.1056/nejmoa1408440"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25470694/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25470694"}],"tags":["europepmc-ingest"],"related":["crizotinib"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2014,"doi":"10.1056/nejmoa1408440","pmid":"25470694","authors":"Solomon BJ, Mok T, Kim DW, et al.","paperType":"rct","findings":[],"whatItMeans":"One treatment page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nct04657991-eur-j-cancer-2024","kind":"paper","name":"First-line encorafenib plus binimetinib and pembrolizumab for advanced BRAF V600-mutant melanoma: Safety lead-in results from the randomized phase III STARBOARD study","aka":[],"tldr":"Published report from the trial registered as NCT04657991, in European Journal of Cancer (2024), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: BRAF inhibitors plus MEK inhibitors (BRAFi/MEKi) and immune checkpoint inhibitors (CPIs) are approved for BRAF V600-mutant advanced melanoma. Combinations of BRAFi/MEKi with CPIs may further improve outcomes and could offer additional treatment strategies.\n\nMethods: STARBOARD (NCT04657991) is a phase III study with an initial safety lead-in (SLI) phase conducted to determine the recommended phase III dose (RP3D) for encorafenib in combination with binimetinib and pembrolizumab. Patients with untreated, unresectable locally advanced or metastatic BRAF V600E/K-mutant cutaneous melanoma received binimetinib 45 mg twice daily and pembrolizumab 200 mg every 3 weeks plus encorafenib 450 mg once daily (COMBO450 plus pembrolizumab) or 300 mg once daily (COMBO300 plus pembrolizumab). The primary endpoint was the incidence of dose-limiting toxicities (DLTs). Secondary endpoints included safety, objective response, time to response, and duration of response. Progression-free survival was assessed post hoc.\n\nResults: In the SLI, the median follow-up duration was 19.4 months. Twenty patients received COMBO450 plus pembrolizumab and 17 received COMBO300 plus pembrolizumab. DLTs occurred in 1 of 17 DLT-evaluable patients in the COMBO450 plus pembrolizumab arm and in 2 of 17 DLT-evaluable patients in the COMBO300 plus pembrolizumab arm. No treatment-related deaths occurred in either treatment arm. The overall response rate was 65.0 % in the COMBO450 plus pembrolizumab arm and 47.1 % in the COMBO300 plus pembrolizumab arm.\n\nConclusion: The STARBOARD SLI showed that safety across the cohorts was generally comparable to the known safety profile of each agent. The standard dose regimen of COMBO450 plus pembrolizumab was chosen as the RP3D.\n\nIndexed on Europe PMC as PubMed record 39427441 (DOI 10.1016/j.ejca.2024.115070). Its abstract cites the registry id NCT04657991, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Eur J Cancer 2024","url":"https://doi.org/10.1016/j.ejca.2024.115070"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39427441/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39427441"},{"label":"ClinicalTrials.gov NCT04657991","url":"https://clinicaltrials.gov/study/NCT04657991"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04657991"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["european-journal-of-cancer"],"dependsOn":[],"notes":[],"journal":"European Journal of Cancer","year":2024,"doi":"10.1016/j.ejca.2024.115070","pmid":"39427441","authors":"Dudnichenko O, Penkov K, McKean M, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04657991 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-shaw-crown-lorlatinib-crizotinib-nejm-2020","kind":"paper","name":"First-line lorlatinib or crizotinib in advanced ALK-positive lung cancer","aka":[],"tldr":"CROWN's third-generation ALK drug kept 78 percent of patients free of progression at a year against 39 percent on crizotinib, and controlled disease inside the brain far better.","summary":"The CROWN trial investigators, reported by Shaw, Bauer, de Marinis and colleagues with Solomon as senior author, randomised 296 patients with advanced ALK-positive non-small-cell lung cancer and no previous systemic treatment for metastatic disease between lorlatinib and crizotinib. The primary endpoint was blinded independent central review progression-free survival; intracranial response was a secondary endpoint.\n\nThe cost is a distinctive toxicity profile: hyperlipidaemia and central nervous system effects on mood, speed and memory. Lorlatinib is the first lung cancer drug whose main side effect is cognitive, which makes the choice between it and alectinib a quality-of-life question rather than a purely efficacy one.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2020","url":"https://doi.org/10.1056/NEJMoa2027187"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33207094/"},{"label":"ClinicalTrials.gov NCT03052608","url":"https://clinicaltrials.gov/study/NCT03052608"}],"tags":["lung-evidence"],"related":["paper-peters-alex-alectinib-crizotinib-nejm-2017","paper-kwak-crizotinib-alk-nsclc-nejm-2010","idea-bio2-brain-met-prevention-trials"],"cancers":["lung-cancer","nsclc","alk-positive-nsclc"],"sections":["targeted-therapy"],"technologies":["kinase-inhibitors"],"targets":["alk","ros1"],"drugs":["lorlatinib","crizotinib"],"companies":["pfizer"],"institutions":["peter-mac"],"pathways":[],"terms":["brain-metastases","resistance","oncogene-addiction","gene-fusion","pfs"],"trials":["crown"],"people":["alice-shaw","solomon-benjamin","enriqueta-felip","kim-dong-wan"],"bottlenecks":["b-brain-delivery","b-resistance","b-toxicity-qol"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2020,"doi":"10.1056/NEJMoa2027187","pmid":"33207094","authors":"Shaw AT, Bauer TM, de Marinis F, et al.","paperType":"rct","findings":["78 percent of patients on lorlatinib were alive without disease progression at 12 months (95 percent confidence interval 70 to 84) against 39 percent on crizotinib (30 to 48).","Hazard ratio for disease progression or death 0.28 (0.19 to 0.41).","A higher frequency of intracranial response with lorlatinib than with crizotinib.","Grade 3 or 4 adverse events were more frequent with lorlatinib, because of the frequent occurrence of altered lipid levels."],"whatItMeans":"The current first choice for ALK-positive lung cancer in most guidelines, and the strongest evidence in solid tumour oncology that a drug can be designed to work inside the brain. Five-year follow-up has since shown the majority of patients still progression-free.","caveats":["An interim analysis at 12 months, and the comparator is crizotinib rather than alectinib, which is what lorlatinib actually competes with.","Lipid abnormalities and central nervous system effects on mood, cognition and speech are common and not fully captured by grade 3 or 4 counts.","No overall survival benefit has been demonstrated against a next-generation comparator."],"changedPractice":true,"participants":296},{"id":"paper-nct04129502-j-clin-oncol-2025","kind":"paper","name":"First-Line Mobocertinib Versus Platinum-Based Chemotherapy in Patients With EGFR Exon 20 Insertion-Positive Metastatic Non-Small Cell Lung Cancer in the Phase III EXCLAIM-2 Trial","aka":[],"tldr":"Published report from the trial registered as NCT04129502, in Journal of Clinical Oncology (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Purpose: Mobocertinib is an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that targets EGFR exon 20 insertion (ex20ins) mutations in non-small cell lung cancer (NSCLC). This open-label, phase III trial (EXCLAIM-2, ClinicalTrials.gov identifier: NCT04129502) compared mobocertinib versus platinum-based chemotherapy as first-line treatment of EGFR ex20ins+ advanced/metastatic NSCLC.\n\nMethods: Patients with treatment-naive EGFR ex20ins+ locally advanced/metastatic NSCLC were randomly assigned 1:1 to mobocertinib 160 mg once daily or pemetrexed plus cisplatin or carboplatin every 3 weeks for four cycles followed by maintenance pemetrexed. The primary end point was progression-free survival (PFS) by blinded independent central review (BICR), with planned interim analysis (IA) after approximately 70% of 227 expected PFS events.\n\nResults: A total of 354 patients were randomly assigned (mobocertinib: n = 179; chemotherapy: n = 175). Baseline characteristics were balanced between arms. At IA (cutoff: April 4, 2023), the median PFS per BICR was 9.6 months in each treatment arm (hazard ratio [HR], 1.04 [95% CI, 0.77 to 1.39]; P =.803). The primary end point crossed the prespecified futility boundary (HR > 1). The confirmed objective response rate (95% CI) per BICR was 32% (26 to 40) with mobocertinib versus 30% (24 to 38) with chemotherapy; the median duration of response was 12.0 versus 8.4 months. Quality-of-life assessments indicated clinically meaningful delays in time to deterioration of lung cancer symptoms, cognitive function, and constipation with mobocertinib versus chemotherapy. Grade ≥3 adverse events in >5% of patients (mobocertinib, chemotherapy) were diarrhea (20%, 1%), anemia (6%, 10%), increased lipase (6%, 0%), and decreased neutrophil count (1%, 7%).\n\nConclusion: The EXCLAIM-2 trial did not meet its primary end point. The efficacy of mobocertinib was not superior to platinum-based chemotherapy for first-line treatment of patients with EGFR ex20ins+ advanced/metastatic NSCLC.\n\nIndexed on Europe PMC as PubMed record 39879577 (DOI 10.1200/jco-24-01269). Its abstract cites the registry id NCT04129502, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2025","url":"https://doi.org/10.1200/jco-24-01269"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39879577/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39879577"},{"label":"ClinicalTrials.gov NCT04129502","url":"https://clinicaltrials.gov/study/NCT04129502"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04129502"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2025,"doi":"10.1200/jco-24-01269","pmid":"39879577","authors":"Jänne PA, Wang BC, Cho BC, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04129502 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-checkmate-227-int-j-clin-oncol-2023-update","kind":"paper","name":"First-line nivolumab plus ipilimumab in metastatic non-small cell lung cancer: 5-year outcomes in Japanese patients from CheckMate 227 Part 1","aka":[],"tldr":"Later report from the CheckMate 227 trial registered as NCT02477826, in International journal of clinical oncology (2023); its title describes an updated or longer-term analysis.","summary":"Background: In CheckMate 227 Part 1 (NCT02477826), first-line nivolumab plus ipilimumab demonstrated long-term durable overall survival (OS) benefit versus chemotherapy in patients with metastatic non-small cell lung cancer (NSCLC), regardless of tumor programmed death ligand 1 (PD-L1) expression. We report results in Japanese patients with ≥ 5-year follow-up.\n\nMethods: Adults with stage IV/recurrent NSCLC without EGFR/ALK aberrations were randomized 1:1:1 to nivolumab plus ipilimumab, nivolumab alone, or chemotherapy (patients with tumor PD-L1 ≥ 1%), or nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy (patients with tumor PD-L1 < 1%). Five-year efficacy and safety were assessed in Japanese patients.\n\nResults: At 62.1 months' minimum follow-up, 143 Japanese patients with PD-L1 ≥ 1% or < 1% were randomized to nivolumab plus ipilimumab (n = 66) or chemotherapy (n = 77). Five-year OS rates were 46% with nivolumab plus ipilimumab versus 34% with chemotherapy (PD-L1 ≥ 1%) and 36% versus 19% (PD-L1 < 1%). Median duration of response was 59.1 versus 7.1 months (PD-L1 ≥ 1%) and 17.3 versus 3.0 months (PD-L1 < 1%). Among 5-year survivors treated with nivolumab plus ipilimumab (PD-L1 ≥ 1% and < 1%; n = 27), 59% (95% CI, 39%-75%) were off treatment for ≥ 3 years without receiving subsequent therapy. No new safety signals were observed.\n\nConclusions: At 5-year follow-up, nivolumab plus ipilimumab continued to show long-term durable clinical benefit versus chemotherapy, regardless of tumor PD-L1 expression. Consistent with findings for the global population, these data support the use of nivolumab plus ipilimumab as first-line treatment in Japanese patients with metastatic NSCLC.\n\nIndexed on Europe PMC as PubMed record 37548831 (DOI 10.1007/s10147-023-02390-2). Its abstract cites the registry id NCT02477826, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Int J Clin Oncol 2023","url":"https://doi.org/10.1007/s10147-023-02390-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37548831/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37548831"},{"label":"ClinicalTrials.gov NCT02477826","url":"https://clinicaltrials.gov/study/NCT02477826"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-227"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["international-journal-of-clinical-oncology"],"dependsOn":[],"notes":[],"journal":"International journal of clinical oncology","year":2023,"doi":"10.1007/s10147-023-02390-2","pmid":"37548831","authors":"Nishio M, Ohe Y, Ikeda S, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the CheckMate 227 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-nct05227664-nat-med-2026","kind":"paper","name":"First-line PD-1/VEGF bispecific antibody plus chemotherapy in triple-negative breast cancer: a phase 2 trial","aka":[],"tldr":"Published report from the trial registered as NCT05227664, in Nature Medicine (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Triple-negative breast cancer is an aggressive subtype comprising 10-20% of all breast cancer cases and has a worse prognosis than other subtypes. This open-label, multicenter, single-arm, phase 2 clinical trial evaluates the safety and efficacy of ivonescimab combined with chemotherapy as first-line treatment in female patients with locally advanced unresectable or metastatic triple-negative breast cancer who have not received previous systemic therapy. Eligible patients received ivonescimab 20 mg kg -1 intravenously every 2 weeks and paclitaxel 90 mg m - 2 or nab-paclitaxel 100 mg m - 2 intravenously on days 1, 8 and 15 of each 4-week treatment cycle. The primary endpoints were safety and the investigator-assessed objective response rate per RECIST v.1.1. A total of 36 patients were enrolled. at July 15, 2025, the median follow-up duration was 22.1 months. The primary endpoints were met. Treatment-related adverse events occurred in 36 (100.0%) patients. Grade ≥3 treatment-related adverse events were reported in 21 (58.3%) patients. No treatment-related deaths occurred. Immune-related adverse events occurred in 15 (41.7%) patients, with grade ≥3 events in 4 (11.1%) patients. Of the 35 patients evaluable for treatment efficacy, the objective response rate was 80.0% (95% confidence interval: 63.1-91.6), including 2 (5.7%) complete responses and 26 (74.3%) partial responses. Ivonescimab plus chemotherapy demonstrated encouraging antitumor activity as first-line therapy for patients with previously untreated advanced triple-negative breast cancer and merits further investigation. ClinicalTrials.gov identifier: NCT05227664.\n\nIndexed on Europe PMC as PubMed record 42587052 (DOI 10.1038/s41591-026-04564-7). Its abstract cites the registry id NCT05227664, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Nat Med 2026","url":"https://doi.org/10.1038/s41591-026-04564-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42587052/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42587052"},{"label":"ClinicalTrials.gov NCT05227664","url":"https://clinicaltrials.gov/study/NCT05227664"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05227664"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2026,"doi":"10.1038/s41591-026-04564-7","pmid":"42587052","authors":"Shao X, Tian C, Chen Z, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05227664 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-pembrolizumab-urothelial-lancet-oncol-2017","kind":"paper","name":"First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study","aka":[],"tldr":"Phase 2 or 3 results paper on Pembrolizumab in Bladder & urothelial cancer, in The Lancet Oncology (2017), one of the most cited Europe PMC records with Pembrolizumab in its title.","summary":"Background: More than half of all patients with advanced urothelial cancer cannot receive standard, first-line cisplatin-based chemotherapy because of renal dysfunction, poor performance status, or other comorbidities. We assessed the activity and safety of first-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer.\n\nMethods: In this multicentre, single-arm, phase 2 study (KEYNOTE-052), cisplatin-ineligible patients with advanced urothelial cancer who had not been previously treated with systemic chemotherapy were recruited from 91 academic medical centres in 20 countries. Enrolled patients received intravenous pembrolizumab 200 mg every 3 weeks. The primary endpoint was objective response (the proportion of patients who achieved complete or partial response) in all patients and by PD-L1 expression status according to the Response Evaluation Criteria in Solid Tumors, version 1.1, as assessed by independent central review. PD-L1 expression was assessed in tumour and inflammatory cells from tumour biopsies provided at study entry. Activity and safety were analysed in all patients who received at least one dose of pembrolizumab (all-patients-treated population). This study is registered with ClinicalTrials.gov, number NCT02335424, and follow-up is ongoing.\n\nFindings: Between Feb 24, 2015, and Aug 8, 2016, 374 patients were enrolled and 370 patients received at least one dose of pembrolizumab. 89 (24%, 95% CI 20-29) of 370 patients had a centrally assessed objective response, and at Sept 1, 2016 (data cutoff), 74 (83%) of 89 responses were ongoing. Median follow-up was 5 months (IQR 3·0-8·6). A PD-L1-expression cutoff of 10% was associated with a higher frequency of response to pembrolizumab; 42 (38%, 95% CI 29-48) of 110 patients with a combined positive score of 10% or more had a centrally assessed objective response. The most common grade 3 or 4 treatment-related adverse events were fatigue (eight [2%] of 370 patients), alkaline phosphatase increase (five [1%]), colitis, and muscle weakness (both four [1%]). 36 (10%) of 370 patients had a serious treatment-related adverse event. 17 (5%) of 370 patients died from non-treatment-related adverse events associated with death, and one patient died from treatment-related adverse events (myositis in addition to grade 3 thyroiditis, grade 3 hepatitis, grade 3 pneumonia, and grade 4 myocarditis).\n\nInterpretation: First-line pembrolizumab has antitumour activity and acceptable tolerability in cisplatin-ineligible patients with urothelial cancer, most of whom were elderly, had poor prognostic factors, or had serious comorbidities. In view of this result, pembrolizumab has become a new treatment option for patients who are cisplatin-ineligible or not suitable candidates for chemotherapy. Pembrolizumab in the first-line setting is being further assessed in the phase 3 KEYNOTE-361 trial (ClinicalTrials.gov, NCT02335424).\n\nFunding: Merck & Co.\n\nIndexed on Europe PMC as PubMed record 28967485 (DOI 10.1016/s1470-2045(17)30616-2). Its title names Pembrolizumab and its text names Bladder & urothelial cancer; PubMed types it as a clinical trial report (Clinical Trial, Phase II, Comparative Study, Research Support, Non-U.S. Gov't, Multicenter Study, Randomized Controlled Trial). It was matched automatically to the idea \"Bladder preservation for MIBC after perioperative EV + pembrolizumab complete response\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2017","url":"https://doi.org/10.1016/s1470-2045(17)30616-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28967485/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28967485"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2017,"doi":"10.1016/s1470-2045(17)30616-2","pmid":"28967485","authors":"Balar AV, Castellano D, O'Donnell PH, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Pembrolizumab in Bladder & urothelial cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Pembrolizumab in the title and Bladder & urothelial cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-nct05186974-j-thorac-oncol-2026","kind":"paper","name":"First-Line Sacituzumab Govitecan Plus Pembrolizumab in Metastatic NSCLC: PD-L1 TPS Less Than 50% and More Than or Equal to 50% Cohorts of the EVOKE-02 Study","aka":[],"tldr":"Published report from the EVOKE-02 trial registered as NCT05186974, in Journal of Thoracic Oncology (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Introduction: Sacituzumab govitecan (SG) is a Trop-2-directed antibody-drug conjugate previously studied in patients with pretreated metastatic NSCLC (mNSCLC). Here, we report the results of EVOKE-02 (NCT05186974), a global, open-label, multicohort phase 2 study of SG plus pembrolizumab as first-line treatment in patients with mNSCLC.\n\nMethods: Adult patients without prior systemic mNSCLC treatment, and no actionable genomic alterations, received SG 10 mg/kg intravenously on days 1 and 8 plus pembrolizumab 200 mg intravenously on day 1 of 21-day cycles. The primary end point was objective response rate (ORR) per independent review committee, and secondary end points included progression-free survival (PFS) and safety.\n\nResults: at data cutoff (June 3, 2024), there were 30 patients with programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) more than or equal to 50% (cohort A) and 62 patients with PD-L1 TPS less than 50% (cohort B). ORR (95% confidence interval) was 66.7% (47.2-82.7) for cohort A and 29.0% (18.2-41.9) for cohort B. Median (95% confidence interval) PFS was 13.1 (6.7-not reached) months for cohort A and 7.0 (4.2-12.9) months for cohort B. Trop-2 expression did not correlate with greater clinical efficacy (PFS, ORR) from treatment with SG plus pembrolizumab. Grade 3 or greater treatment-emergent adverse events (TEAEs) occurred in 70 patients (76.1%); the most common TEAE was neutropenia (17.4%). TEAEs leading to discontinuation of any study drug occurred in 25 patients (27.2%).\n\nConclusions: SG plus pembrolizumab demonstrated activity as treatment for mNSCLC, especially in patients with PD-L1 TPS more than or equal to 50%. AEs were manageable and consistent with the known safety profile of each individual agent.\n\nIndexed on Europe PMC as PubMed record 41173143 (DOI 10.1016/j.jtho.2025.10.016). Its abstract cites the registry id NCT05186974, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Thorac Oncol 2026","url":"https://doi.org/10.1016/j.jtho.2025.10.016"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41173143/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41173143"},{"label":"ClinicalTrials.gov NCT05186974","url":"https://clinicaltrials.gov/study/NCT05186974"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05186974"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-thoracic-oncology"],"dependsOn":[],"notes":[],"journal":"Journal of Thoracic Oncology","year":2026,"doi":"10.1016/j.jtho.2025.10.016","pmid":"41173143","authors":"Reck M, Patel JD, Gray JE, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05186974 with the most citations, so it is the natural first reading for anyone following the EVOKE-02 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-nct05351788-nat-med-2025","kind":"paper","name":"First-line sacituzumab tirumotecan with tagitanlimab in advanced non-small-cell lung cancer: a phase 2 trial","aka":[],"tldr":"Published report from the trial registered as NCT05351788, in Nature Medicine (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Sacituzumab tirumotecan (sac-TMT, also known as MK-2870 or SKB264) is an antibody-drug conjugate targeting trophoblast cell surface antigen 2. We report the initial findings from the ongoing phase 2 OptiTROP-Lung01 study, evaluating the combination of sac-TMT and tagitanlimab (KL-A167), an anti-PD-L1 antibody, as first-line therapy in patients with advanced or metastatic non-small-cell lung cancer who lack actionable genomic alterations (cohorts 1A and 1B). Cohort 1A received sac-TMT (5 mg kg -1, every 3 weeks) plus tagitanlimab (1,200 mg, every 3 weeks) in each 3-week cycle, whereas cohort 1B was treated with sac-TMT (5 mg kg -1, every 2 weeks) plus tagitanlimab (900 mg, every 2 weeks) in each 4-week cycle, in a nonrandomized manner until disease progression or unacceptable toxicity. The primary endpoints included safety and objective response rate. This study was not powered for formal hypothesis testing. A total of 40 and 63 patients were enrolled in cohorts 1A and 1B, respectively. The median age was 63 years in both cohorts. An Eastern Cooperative Oncology Group performance status of 1 was observed in 97.5% and 85.7% of patients in cohorts 1A and 1B, respectively. In cohorts 1A and 1B, the most common grade ≥3 treatment-related adverse events were decreased neutrophil count (30.0% and 34.9%), decreased white blood cell count (5.0% and 19.0%) and anemia (5.0% and 19.0%). No treatment-related deaths were observed. After median follow-ups of 19.3 months for cohort 1A and 13.0 months for cohort 1B, the confirmed objective response rate in the full analysis set was 40.0% (16 of 40) and 66.7% (42 of 63), the disease control rate was 85.0% and 92.1% and median progression-free survival was 15.4 months (95% confidence interval 6.7-17.9) and not reached for cohorts 1A and 1B, respectively. sac-TMT plus tagitanlimab showed promising efficacy as a first-line treatment for advanced or metastatic non-small-cell lung cancer, with a manageable safety profile. ClinicalTrials.gov registration: NCT05351788.\n\nIndexed on Europe PMC as PubMed record 40830660 (DOI 10.1038/s41591-025-03883-5). Its abstract cites the registry id NCT05351788, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Nat Med 2025","url":"https://doi.org/10.1038/s41591-025-03883-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40830660/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40830660"},{"label":"ClinicalTrials.gov NCT05351788","url":"https://clinicaltrials.gov/study/NCT05351788"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05351788"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2025,"doi":"10.1038/s41591-025-03883-5","pmid":"40830660","authors":"Hong S, Wang Q, Cheng Y, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05351788 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-nct04547166-med-2024","kind":"paper","name":"First-line serplulimab in metastatic colorectal cancer: Phase 2 results of a randomized, double-blind, phase 2/3 trial","aka":[],"tldr":"Published report from the trial registered as NCT04547166, in Med (New York, N.Y.) (2024), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Whether or not the addition of immunotherapy to current standard-of-care treatments can improve efficacy in proficient mismatch repair (pMMR)/microsatellite-stable (MSS) metastatic colorectal cancer (mCRC), the predominant type of mCRC, is unclear.\n\nMethods: This randomized, double-blind, phase 2 part of a phase 2/3 trial was conducted at 23 hospitals across China (ClinicalTrials.gov: NCT04547166). Patients with unresectable metastatic/recurrent colorectal adenocarcinoma and no prior systemic therapy were randomly assigned 1:1 to receive every-3-weeks intravenous serplulimab (300 mg) plus HLX04 (7.5 mg/kg) and XELOX (serplulimab group) or placebo (300 mg) plus bevacizumab (7.5 mg/kg) and XELOX (placebo group). The primary endpoint was independent radiology review committee (IRRC)-assessed progression-free survival (PFS). Secondary endpoints included other efficacy endpoints and safety.\n\nFindings: Between July 16, 2021, and January 20, 2022, 114 patients were enrolled and randomly assigned to the serplulimab (n = 57) or placebo (n = 57) group. All patients had stage IV CRC, and 95.7% of the patients with available microsatellite instability (MSI) status were MSS. With a median follow-up duration of 17.7 months, median PFS was prolonged in the serplulimab group (17.2 vs. 10.7 months; hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.31-1.14). Although the median overall survival (OS) was not reached for either group, a trend of an OS benefit was observed for the serplulimab group (HR, 0.77; 95% CI, 0.41-1.45). 36 (65.5%) and 32 (56.1%) patients in the serplulimab and placebo groups had grade ≥3 treatment-related adverse events, respectively.\n\nConclusions: Serplulimab plus HLX04 and XELOX exhibits promising efficacy and is safe and tolerable in patients with treatment-naive mCRC.\n\nFunding: This work was funded by Shanghai Henlius Biotech, Inc.\n\nIndexed on Europe PMC as PubMed record 38870931 (DOI 10.1016/j.medj.2024.05.009). Its abstract cites the registry id NCT04547166, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Med 2024","url":"https://doi.org/10.1016/j.medj.2024.05.009"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38870931/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38870931"},{"label":"ClinicalTrials.gov NCT04547166","url":"https://clinicaltrials.gov/study/NCT04547166"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04547166"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Med (New York, N.Y.)","year":2024,"doi":"10.1016/j.medj.2024.05.009","pmid":"38870931","authors":"Wang ZX, Peng J, Liang X, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04547166 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-nct05668988-n-engl-j-med-2026","kind":"paper","name":"First-Line Sunvozertinib in NSCLC with EGFR Exon 20 Insertion Mutations","aka":[],"tldr":"Published report from the WU-KONG28 trial registered as NCT05668988, in New England Journal of Medicine (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Sunvozertinib received accelerated approval for use in later lines of therapy for patients with advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor ( EGFR) exon 20 insertion mutations. Data are needed on the efficacy and safety of sunvozertinib as a first-line treatment for NSCLC.\n\nMethods: In this phase 3, international trial, we randomly assigned, in a 1:1 ratio, patients with advanced nonsquamous NSCLC with EGFR exon 20 insertions to receive sunvozertinib or chemotherapy (carboplatin-pemetrexed). The primary end point was progression-free survival as assessed by blinded independent central review. Crossover to the sunvozertinib group was allowed after disease progression was confirmed. Secondary end points included overall survival, investigator-assessed progression-free survival, objective response (complete or partial response), change in tumor size, and duration of response.\n\nResults: A total of 324 patients were randomly assigned to receive sunvozertinib (163 patients) or chemotherapy (161 patients). Treatment with sunvozertinib led to significantly longer median progression-free survival than chemotherapy (10.3 vs. 7.5 months; hazard ratio for disease progression or death, 0.65; 95% confidence interval, 0.50 to 0.85; P<0.001). At 12 months, progression-free survival was reported in 46.1% of the patients in the sunvozertinib group and in 26.7% of those in the chemotherapy group; the data for overall survival were immature (38.9% maturity). The percentage of patients with an objective response was 58.9% in the sunvozertinib group and 31.1% in the chemotherapy group; the median best percentage change in tumor size was -42.1% and -24.7% respectively, and the median duration of response was 11.2 and 7.1 months. Grade 3 or higher adverse events were reported in 75.5% of the patients in the sunvozertinib group and in 56.7% of those in the chemotherapy group. In the sunvozertinib group, the most common adverse events of grade 3 or higher included increased serum creatine kinase levels, diarrhea, and anemia. No deaths were attributed to adverse events considered by the investigators to be related to sunvozertinib.\n\nConclusions: The efficacy of sunvozertinib was superior to that of chemotherapy as first-line treatment for advanced NSCLC with EGFR exon 20 insertions. (Funded by Dizal Pharmaceuticals; WU-KONG28 ClinicalTrials.gov number, NCT05668988.).\n\nIndexed on Europe PMC as PubMed record 42212913 (DOI 10.1056/nejmoa2604461). Its abstract cites the registry id NCT05668988, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2026","url":"https://doi.org/10.1056/nejmoa2604461"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42212913/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42212913"},{"label":"ClinicalTrials.gov NCT05668988","url":"https://clinicaltrials.gov/study/NCT05668988"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05668988"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2026,"doi":"10.1056/nejmoa2604461","pmid":"42212913","authors":"Zhou C, Greillier L, Liu G, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05668988 with the most citations, so it is the natural first reading for anyone following the WU-KONG28 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-firstmappp-sunitinib-metastatic-ppgl-baudin-lancet-2024","kind":"paper","name":"FIRSTMAPPP: sunitinib for metastatic progressive phaeochromocytomas and paragangliomas","aka":[],"tldr":"In the first randomised trial in these rare tumours, sunitinib kept 36 percent of patients free of progression at one year against 19 percent on placebo.","summary":"Academic, multicentre, double-blind, placebo-controlled phase 2 trial at 14 European centres: 78 adults with progressive metastatic phaeochromocytoma or paraganglioma were randomised to sunitinib 37.5 mg daily or placebo. The primary endpoint was progression-free survival at 12 months.\n\n14 of 39 sunitinib patients (36 percent) and 7 of 39 placebo patients (19 percent) were progression-free at 12 months, meeting the primary endpoint. Grade 3 or 4 asthenia (18 against 3 percent) and hypertension (13 against 10 percent) were the common toxicities; one death from rectal bleeding was drug-related.","asOf":"2026-09-22","links":[{"label":"Lancet 2024","url":"https://doi.org/10.1016/S0140-6736(23)02554-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38402886/"}],"tags":[],"related":[],"cancers":["metastatic-ppgl","pheochromocytoma-paraganglioma"],"sections":[],"technologies":[],"targets":[],"drugs":["sunitinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["firstmappp"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2024,"doi":"10.1016/S0140-6736(23)02554-0","pmid":"38402886","authors":"Baudin E, Goichot B, Berruti A, et al.","paperType":"rct","findings":["Progression-free survival at 12 months 36 percent (90% CI 23 to 50) with sunitinib versus 19 percent (11 to 31) with placebo.","Grade 3 or 4 asthenia 18 versus 3 percent; hypertension 13 versus 10 percent; one drug-related death."],"whatItMeans":"Sunitinib has the highest level of evidence of any drug for progressive metastatic phaeochromocytoma and paraganglioma, alongside the later approval of belzutifan.","caveats":["Small phase 2 with a single-arm-style primary endpoint; the placebo arm validated the design rather than providing a formal superiority test."],"changedPractice":true,"participants":78},{"id":"paper-fitzmaurice-gbd-cancer-2015-jamaoncol-2017","kind":"paper","name":"Fitzmaurice 2017: the Global Burden of Disease estimate of cancer in 2015","aka":[],"tldr":"The Global Burden of Disease collaboration's count for 2015: about 17.5 million new cancer cases worldwide, with cases rising by a third over the previous decade mostly because populations were growing and ageing, and lung cancer the largest cause of years of life lost to cancer.","summary":"The Global Burden of Disease Cancer Collaboration estimated incidence, mortality, years of life lost, years lived with disability and disability-adjusted life-years for 32 cancer groups in 195 countries for 2015 and the trend since 2005. It counted about 17.5 million cases and 8.7 million deaths. Cases increased by 33% between 2005 and 2015, of which most was attributable to population ageing and growth rather than to rising age-specific rates. Tracheal, bronchus and lung cancer was the leading cause of cancer disability-adjusted life-years globally.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1001/jamaoncol.2016.5688"},{"label":"GBD results tool","url":"https://vizhub.healthdata.org/gbd-results/"}],"tags":[],"related":["paper-bray-globocan-2018-cacancer-2018","paper-sung-globocan-2020-cacancer-2021"],"cancers":["nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["incidence-vs-prevalence","mortality"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2017,"doi":"10.1001/jamaoncol.2016.5688","authors":"Global Burden of Disease Cancer Collaboration; Fitzmaurice C, Allen C, et al.","paperType":"observational","findings":["About 17.5 million cancer cases and 8.7 million cancer deaths worldwide in 2015.","Cases rose 33% from 2005 to 2015: about 16% from population ageing, 13% from population growth and 4% from changing age-specific rates.","Lung cancer was the leading cause of cancer disability-adjusted life-years; cancer was the second leading cause of death worldwide."],"whatItMeans":"GBD is the other major global cancer count alongside GLOBOCAN, using different methods, and its burden measures in years of life lost make the case that cancer control is largely a problem of ageing populations in middle-income countries.","caveats":["Modelled estimates with wide uncertainty where registry data are sparse.","GBD and GLOBOCAN figures differ because of methods, so they should not be mixed in one comparison."],"changedPractice":false},{"id":"paper-mailankody-jama-oncol","kind":"paper","name":"Five Years of Cancer Drug Approvals: Innovation, Efficacy, and Costs","aka":[],"tldr":"Paper cited by one bottleneck page, indexed on Europe PMC as PubMed record 26181265 and published in JAMA Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 26181265 (DOI 10.1001/jamaoncol.2015.0373). Matched by DOI alone: one bottleneck page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA Oncol 2015","url":"https://doi.org/10.1001/jamaoncol.2015.0373"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26181265/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26181265"}],"tags":["europepmc-ingest"],"related":["b-incentive-misalignment"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2015,"doi":"10.1001/jamaoncol.2015.0373","pmid":"26181265","authors":"Mailankody S, Prasad V","paperType":"observational","findings":[],"whatItMeans":"One bottleneck page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-combi-ad-n-engl-j-med-2020-update","kind":"paper","name":"Five-Year Analysis of Adjuvant Dabrafenib plus Trametinib in Stage III Melanoma","aka":[],"tldr":"Later report from the COMBI-AD trial registered as NCT01682083, in New England Journal of Medicine (2020); its title describes an updated or longer-term analysis.","summary":"Background: In the previously reported primary analysis of this phase 3 trial, 12 months of adjuvant dabrafenib plus trametinib resulted in significantly longer relapse-free survival than placebo in patients with resected stage III melanoma with BRAF V600E or V600K mutations. To confirm the stability of the relapse-free survival benefit, longer-term data were needed.\n\nMethods: We randomly assigned 870 patients who had resected stage III melanoma with BRAF V600E or V600K mutations to receive 12 months of oral dabrafenib (at a dose of 150 mg twice daily) plus trametinib (2 mg once daily) or two matched placebos. The primary end point was relapse-free survival. Here, we report 5-year results for relapse-free survival and survival without distant metastasis as the site of the first relapse. Overall survival was not analyzed, since the required number of events to trigger the final overall survival analysis had not been reached.\n\nResults: The minimum duration of follow-up was 59 months (median patient follow-up, 60 months for dabrafenib plus trametinib and 58 months for placebo). At 5 years, the percentage of patients who were alive without relapse was 52% (95% confidence interval [CI], 48 to 58) with dabrafenib plus trametinib and 36% (95% CI, 32 to 41) with placebo (hazard ratio for relapse or death, 0.51; 95% CI, 0.42 to 0.61). The percentage of patients who were alive without distant metastasis was 65% (95% CI, 61 to 71) with dabrafenib plus trametinib and 54% (95% CI, 49 to 60) with placebo (hazard ratio for distant metastasis or death, 0.55; 95% CI, 0.44 to 0.70). No clinically meaningful between-group difference in the incidence or severity of serious adverse events was reported during the follow-up period.\n\nConclusions: In the 5-year follow-up of a phase 3 trial involving patients who had resected stage III melanoma with BRAF V600E or V600K mutations, 12 months of adjuvant therapy with dabrafenib plus trametinib resulted in a longer duration of survival without relapse or distant metastasis than placebo with no apparent long-term toxic effects. (Funded by GlaxoSmithKline and Novartis; COMBI-AD ClinicalTrials.gov number, NCT01682083; EudraCT number, 2012-001266-15.).\n\nIndexed on Europe PMC as PubMed record 32877599 (DOI 10.1056/nejmoa2005493). Its abstract cites the registry id NCT01682083, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2020","url":"https://doi.org/10.1056/nejmoa2005493"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32877599/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32877599"},{"label":"ClinicalTrials.gov NCT01682083","url":"https://clinicaltrials.gov/study/NCT01682083"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["combi-ad"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2020,"doi":"10.1056/nejmoa2005493","pmid":"32877599","authors":"Dummer R, Hauschild A, Santinami M, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the COMBI-AD trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-prodige-24-five-year-outcomes-jama-oncol-2022","kind":"paper","name":"Five-Year Outcomes of FOLFIRINOX vs Gemcitabine as Adjuvant Therapy for Pancreatic Cancer: A Randomized Clinical Trial","aka":[],"tldr":"The 2022 five-year report of PRODIGE 24 confirming that modified FOLFIRINOX after pancreatic cancer surgery gives a median survival of about four and a half years against three with gemcitabine, and that 43 percent of patients were alive at five years.","summary":"The mature analysis of the PRODIGE 24/Canadian Cancer Trials Group PA6 trial, 493 patients aged 18 to 79 randomised at 77 hospitals in France and Canada between April 2012 and October 2016 within 3 to 12 weeks of R0 or R1 resection to 24 weeks of modified FOLFIRINOX or gemcitabine; data cutoff June 2021, median follow-up 69.7 months. Median disease-free survival was 21.4 versus 12.8 months (hazard ratio 0.66) and five-year disease-free survival 26.1 versus 19.0 percent; median overall survival was 53.5 versus 35.5 months (hazard ratio 0.68, 95 percent confidence interval 0.54 to 0.85, P = 0.001) and five-year overall survival 43.2 versus 31.4 percent; median metastasis-free survival 29.4 versus 17.7 months (hazard ratio 0.64) and cancer-specific survival 54.7 versus 36.3 months (hazard ratio 0.65). Multivariable analysis identified modified FOLFIRINOX, age, tumour grade, staging and larger-volume centre as favourable prognostic factors.","asOf":"2026-09-24","links":[{"label":"JAMA Oncol 2022","url":"https://doi.org/10.1001/jamaoncol.2022.3829"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36048453/"},{"label":"ClinicalTrials.gov NCT01526135","url":"https://clinicaltrials.gov/study/NCT01526135"}],"tags":["pancreatic-evidence"],"related":["paper-prodige-24-adjuvant-mfolfirinox-pancreatic-nejm-2018","paper-asco-potentially-curable-pancreatic-guideline-update-jco-2019"],"cancers":["pancreatic","resectable-pdac"],"sections":[],"technologies":["cytotoxic-chemotherapy"],"targets":[],"drugs":["folfirinox","gemcitabine"],"companies":["unicancer"],"institutions":[],"pathways":[],"terms":["os","hazard-ratio","neoadjuvant-adjuvant"],"trials":["prodige-24","nct07252232","nct05968326"],"people":["thierry-conroy"],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2022,"doi":"10.1001/jamaoncol.2022.3829","pmid":"36048453","authors":"Conroy T, Castan F, Lopez A, et al.","paperType":"rct","findings":["493 patients; median follow-up 69.7 months.","Median overall survival 53.5 versus 35.5 months (hazard ratio 0.68); five-year overall survival 43.2 versus 31.4 percent.","Median disease-free survival 21.4 versus 12.8 months (hazard ratio 0.66); metastasis-free survival 29.4 versus 17.7 months.","Larger-volume centre was an independent favourable prognostic factor."],"whatItMeans":"The best survival ever recorded in a pancreatic cancer trial, and the benchmark every perioperative trial (PREOPANC-3, Alliance A021806) and every adjuvant RAS inhibitor or vaccine trial (RASolute 304, IMCODE003) now has to beat or add to.","caveats":["Fit patients under 80 who had recovered from surgery within 12 weeks; a minority of all diagnosed patients.","The centre-volume finding is observational within the trial but supports centralisation of pancreatic surgery."],"changedPractice":true,"participants":493},{"id":"paper-keynote-671-ann-oncol-2026-update","kind":"paper","name":"Five-Year Outcomes of Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer From the Randomized KEYNOTE-671 Study","aka":[],"tldr":"Later report from the KEYNOTE-671 trial registered as NCT03425643, in Annals of Oncology (2026); its title describes an updated or longer-term analysis.","summary":"Background: Adding perioperative pembrolizumab to neoadjuvant chemotherapy significantly improved survival outcomes compared with neoadjuvant chemotherapy and surgery alone in participants with early-stage non-small-cell lung cancer (NSCLC) in the phase 3, randomized KEYNOTE-671 study. We report results from KEYNOTE-671 after 5 years of follow-up.\n\nPatients and methods: Eligible participants with previously untreated, resectable stage II, IIIA, or IIIB (N2) NSCLC were randomized 1:1 to 4 cycles of pembrolizumab 200 mg or placebo every 3 weeks, plus platinum-doublet chemotherapy, followed by surgery then adjuvant pembrolizumab or placebo every 3 weeks for up to 13 cycles. Dual primary endpoints were event-free survival (EFS) per RECIST v1.1 by investigator assessment and overall survival (OS).\n\nResults: 797 participants were randomized to pembrolizumab (n=397) or placebo (n=400). Median time from randomization to data cutoff (July 3, 2025) was 60.4 (range, 42.6‒85.8) months. Five-year EFS was 49.9% (95% CI, 44.6‒55.0) in the pembrolizumab arm and 26.5% (95% CI, 21.7‒31.5) in the placebo arm (HR, 0.58; 95% CI, 0.48‒0.69); 5-year OS was 64.6% (95% CI, 59.5‒69.2) and 53.6% (95% CI, 48.3‒58.6), respectively (HR, 0.74; 95% CI, 0.59‒0.92). No detriment to health-related quality of life was identified in the pembrolizumab versus placebo arm with longer follow-up. Safety was consistent with the known profiles of each treatment.\n\nConclusions: After 5 years of follow-up, EFS was nearly double with perioperative pembrolizumab plus neoadjuvant chemotherapy, along with continued improvement in OS compared with neoadjuvant chemotherapy and surgery alone. The durable and clinically meaningful benefits observed support use of this treatment as a standard of care for patients with resectable early-stage NSCLC (ClinicalTrials.gov, NCT03425643).\n\nIndexed on Europe PMC as PubMed record 42628840 (DOI 10.1016/j.annonc.2026.08.005). Its abstract cites the registry id NCT03425643, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2026","url":"https://doi.org/10.1016/j.annonc.2026.08.005"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42628840/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42628840"},{"label":"ClinicalTrials.gov NCT03425643","url":"https://clinicaltrials.gov/study/NCT03425643"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-671"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2026,"doi":"10.1016/j.annonc.2026.08.005","pmid":"42628840","authors":"Wakelee H, Spicer JD, Gao S, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the KEYNOTE-671 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-keynote-042-j-clin-oncol-2023-update","kind":"paper","name":"Five-Year Outcomes With Pembrolizumab Versus Chemotherapy as First-Line Therapy in Patients With Non-Small-Cell Lung Cancer and Programmed Death Ligand-1 Tumor Proportion Score ≥ 1% in the KEYNOTE-042 Study","aka":[],"tldr":"Later report from the KEYNOTE-042 trial registered as NCT02220894, in Journal of Clinical Oncology (2023); its title describes an updated or longer-term analysis.","summary":"Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. We report 5-year results from the phase III KEYNOTE-042 study (ClinicalTrials.gov identifier: NCT02220894). Eligible patients with locally advanced/metastatic non-small-cell lung cancer (NSCLC) without EGFR/ALK alterations and with programmed death ligand-1 (PD-L1) tumor proportion score (TPS) ≥ 1% received pembrolizumab 200 mg once every 3 weeks for 35 cycles or chemotherapy (carboplatin + paclitaxel or pemetrexed) for 4-6 cycles with optional maintenance pemetrexed. Primary end points were overall survival (OS) in PD-L1 TPS ≥ 50%, ≥ 20%, and ≥ 1% groups. Patients who completed 35 cycles of pembrolizumab with ≥ stable disease could begin second-course pembrolizumab upon progression. One thousand two hundred seventy-four patients were randomly assigned (pembrolizumab, n = 637; chemotherapy, n = 637). Median follow-up time was 61.1 (range, 50.0-76.3) months. OS outcomes favored pembrolizumab ( v chemotherapy) regardless of PD-L1 TPS (hazard ratio [95% CI] for TPS ≥ 50%, 0.68 [0.57 to 0.81]; TPS ≥ 20%, 0.75 [0.64 to 0.87]; TPS ≥ 1%, 0.79 [0.70 to 0.89]), with estimated 5-year OS rates with pembrolizumab of 21.9%, 19.4%, and 16.6%, respectively. No new toxicities were identified. Objective response rate was 84.3% among 102 patients who completed 35 cycles of pembrolizumab and 15.2% among 33 patients who received second-course pembrolizumab. First-line pembrolizumab monotherapy continued to show durable clinical benefit versus chemotherapy after 5 years of follow-up in PD-L1-positive, locally advanced/metastatic NSCLC without EGFR/ALK alterations and remains a standard of care.\n\nIndexed on Europe PMC as PubMed record 36306479 (DOI 10.1200/jco.21.02885). Its abstract cites the registry id NCT02220894, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2023","url":"https://doi.org/10.1200/jco.21.02885"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36306479/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36306479"},{"label":"ClinicalTrials.gov NCT02220894","url":"https://clinicaltrials.gov/study/NCT02220894"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-042"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2023,"doi":"10.1200/jco.21.02885","pmid":"36306479","authors":"de Castro G, Kudaba I, Wu YL, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the KEYNOTE-042 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-keynote-024-189-j-clin-oncol-2021-update","kind":"paper","name":"Five-Year Outcomes With Pembrolizumab Versus Chemotherapy for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50","aka":[],"tldr":"Later report from the KEYNOTE-024 trial registered as NCT02142738, in Journal of Clinical Oncology (2021); its title describes an updated or longer-term analysis.","summary":"Purpose: We report the first 5-year follow-up of any first-line phase III immunotherapy trial for non-small-cell lung cancer (NSCLC). KEYNOTE-024 (ClinicalTrials.gov identifier: NCT02142738) is an open-label, randomized controlled trial of pembrolizumab compared with platinum-based chemotherapy in patients with previously untreated NSCLC with a programmed death ligand-1 (PD-L1) tumor proportion score of at least 50% and no sensitizing EGFR or ALK alterations. Previous analyses showed pembrolizumab significantly improved progression-free survival and overall survival (OS).\n\nMethods: Eligible patients were randomly assigned (1:1) to pembrolizumab (200 mg once every 3 weeks for up to 35 cycles) or platinum-based chemotherapy. Patients in the chemotherapy group with progressive disease could cross over to pembrolizumab. The primary end point was progression-free survival; OS was a secondary end point.\n\nResults: Three hundred five patients were randomly assigned: 154 to pembrolizumab and 151 to chemotherapy. Median (range) time from randomization to data cutoff (June 1, 2020) was 59.9 (55.1-68.4) months. Among patients initially assigned to chemotherapy, 99 received subsequent anti-PD-1 or PD-L1 therapy, representing a 66.0% effective crossover rate. Median OS was 26.3 months (95% CI, 18.3 to 40.4) for pembrolizumab and 13.4 months (9.4-18.3) for chemotherapy (hazard ratio, 0.62; 95% CI, 0.48 to 0.81). Kaplan-Meier estimates of the 5-year OS rate were 31.9% for the pembrolizumab group and 16.3% for the chemotherapy group. Thirty-nine patients received 35 cycles (ie, approximately 2 years) of pembrolizumab, 82.1% of whom were still alive at data cutoff (approximately 5 years). Toxicity did not increase with longer treatment exposure.\n\nConclusion: Pembrolizumab provides a durable, clinically meaningful long-term OS benefit versus chemotherapy as first-line therapy for metastatic NSCLC with PD-L1 tumor proportion score of at least 50%.\n\nIndexed on Europe PMC as PubMed record 33872070 (DOI 10.1200/jco.21.00174). Its abstract cites the registry id NCT02142738, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2021","url":"https://doi.org/10.1200/jco.21.00174"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33872070/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33872070"},{"label":"ClinicalTrials.gov NCT02142738","url":"https://clinicaltrials.gov/study/NCT02142738"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-024-189"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2021,"doi":"10.1200/jco.21.00174","pmid":"33872070","authors":"Reck M, Rodríguez-Abreu D, Robinson AG, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the KEYNOTE-024 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-spigel-pacific-five-year-survival-jco-2022","kind":"paper","name":"Five-year survival outcomes from the PACIFIC trial: durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer","aka":[],"tldr":"Five years after the PACIFIC trial, 42.9 percent of patients given a year of immunotherapy after chemoradiotherapy were still alive, against 33.4 percent of those given placebo. A third of them had never relapsed.","summary":"Spigel, Faivre-Finn, Gray and colleagues, with Antonia as senior author, reported the five-year update of PACIFIC, in which 713 patients with unresectable stage III non-small-cell lung cancer and no progression after concurrent chemoradiotherapy were randomised 2 to 1 to durvalumab 10 mg per kilogram every two weeks for twelve months or placebo, stratified by age, sex and smoking history. Data cutoff was 11 January 2021, with a median follow-up of 34.2 months across all patients and 61.6 months among censored patients.\n\nStage III lung cancer had been a plateau: chemoradiotherapy cured a minority and nothing added to it had helped for two decades. This is the update that turned a progression-free survival signal into a durable survival benefit, and it is the benchmark LAURA's osimertinib arm and the perioperative trials are set against.","asOf":"2026-09-25","links":[{"label":"J Clin Oncol 2022","url":"https://doi.org/10.1200/JCO.21.01308"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35108059/"},{"label":"ClinicalTrials.gov NCT02125461","url":"https://clinicaltrials.gov/study/NCT02125461"}],"tags":["lung-evidence"],"related":["paper-pacific-nejm-2017","paper-pacific-n-engl-j-med-2018-update","paper-lu-laura-osimertinib-stage-iii-nejm-2024"],"cancers":["lung-cancer","nsclc","stage-iii-unresectable-nsclc"],"sections":["immunotherapy","radiation"],"technologies":["radiotherapy","imrt-igrt","checkpoint-inhibitor"],"targets":["pd1"],"drugs":["durvalumab"],"companies":["astrazeneca"],"institutions":[],"pathways":["immune-checkpoint"],"terms":["chemoradiation","pdl1"],"trials":["pacific"],"people":["scott-antonia","martin-reck"],"bottlenecks":["b-immunotherapy-response","b-surgery-radiation-innovation"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2022,"doi":"10.1200/JCO.21.01308","pmid":"35108059","authors":"Spigel DR, Faivre-Finn C, Gray JE, et al.","paperType":"rct","findings":["Estimated five-year overall survival 42.9 percent (95 percent confidence interval 38.2 to 47.4) with durvalumab against 33.4 percent (27.3 to 39.6) with placebo.","Estimated five-year progression-free survival 33.1 percent (28.0 to 38.2) against 19.0 percent (13.6 to 25.2).","Updated overall survival stratified hazard ratio 0.72 (0.59 to 0.89), median 47.5 against 29.1 months.","Updated progression-free survival stratified hazard ratio 0.55 (0.45 to 0.68), median 16.9 against 5.6 months.","709 of 713 randomly assigned patients received durvalumab (473 of 476) or placebo (236 of 237)."],"whatItMeans":"The current standard for unresectable stage III lung cancer, and the clearest evidence in the disease that consolidation immunotherapy converts responses into cures for some patients rather than merely delaying relapse.","caveats":["Randomisation happened after chemoradiotherapy, so patients who progressed during it are not represented; the population is a selected, fitter one.","PD-L1-negative patients benefited less, and the European licence was restricted accordingly.","EGFR-mutant patients do poorly with checkpoint blockade here and are now treated with osimertinib instead (paper-lu-laura-osimertinib-stage-iii-nejm-2024)."],"changedPractice":true,"participants":713},{"id":"paper-jaffray-int-j-radiat-oncol-biol-phys","kind":"paper","name":"Flat-panel cone-beam computed tomography for image-guided radiation therapy","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 12128137 and published in International Journal of Radiation Oncology, Biology, Physics; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: Geometric uncertainties in the process of radiation planning and delivery constrain dose escalation and induce normal tissue complications. An imaging system has been developed to generate high-resolution, soft-tissue images of the patient at the time of treatment for the purpose of guiding therapy and reducing such uncertainties. The performance of the imaging system is evaluated and the application to image-guided radiation therapy is discussed.\n\nMethods and materials: A kilovoltage imaging system capable of radiography, fluoroscopy, and cone-beam computed tomography (CT) has been integrated with a medical linear accelerator. Kilovoltage X-rays are generated by a conventional X-ray tube mounted on a retractable arm at 90 degrees to the treatment source. A 41 x 41 cm(2) flat-panel X-ray detector is mounted opposite the kV tube. The entire imaging system operates under computer control, with a single application providing calibration, image acquisition, processing, and cone-beam CT reconstruction. Cone-beam CT imaging involves acquiring multiple kV radiographs as the gantry rotates through 360 degrees of rotation. A filtered back-projection algorithm is employed to reconstruct the volumetric images. Geometric nonidealities in the rotation of the gantry system are measured and corrected during reconstruction. Qualitative evaluation of imaging performance is performed using an anthropomorphic head phantom and a coronal contrast phantom. The influence of geometric nonidealities is examined.\n\nResults: Images of the head phantom were acquired and illustrate the submillimeter spatial resolution that is achieved with the cone-beam approach. High-resolution sagittal and coronal views demonstrate nearly isotropic spatial resolution. Flex corrections on the order of 0.2 cm were required to compensate gravity-induced flex in the support arms of the source and detector, as well as slight axial movements of the entire gantry structure. Images reconstructed without flex correction suffered from loss of detail, misregistration, and streak artifacts. Reconstructions of the contrast phantom demonstrate the soft-tissue imaging capability of the system. A contrast of 47 Hounsfield units was easily detected in a 0.1-cm-thick reconstruction for an imaging exposure of 1.2 R (in-air, in absence of phantom). The comparison with a conventional CT scan of the phantom further demonstrates the spatial resolution advantages of the cone-beam CT approach.\n\nConclusions: A kV cone-beam CT imaging system based on a large-area, flat-panel detector has been successfully adapted to a medical linear accelerator. The system is capable of producing images of soft tissue with excellent spatial resolution at acceptable imaging doses. Integration of this technology with the medical accelerator will result in an ideal platform for high-precision, image-guided radiation therapy.\n\nIndexed on Europe PMC as PubMed record 12128137 (DOI 10.1016/s0360-3016(02)02884-5). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Int J Radiat Oncol Biol Phys 2002","url":"https://doi.org/10.1016/s0360-3016(02)02884-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/12128137/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/12128137"}],"tags":["europepmc-ingest"],"related":["in-room-imaging-systems"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["ijrobp"],"dependsOn":[],"notes":[],"journal":"International Journal of Radiation Oncology, Biology, Physics","year":2002,"doi":"10.1016/s0360-3016(02)02884-5","pmid":"12128137","authors":"Jaffray DA, Siewerdsen JH, Wong JW, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-flaura-nejm-2018","kind":"paper","name":"FLAURA: osimertinib as first treatment for EGFR-mutated lung cancer","aka":[],"tldr":"Starting with the third-generation EGFR drug osimertinib, rather than saving it for later, kept EGFR-mutated lung cancer under control for almost twice as long and later helped patients live longer.","summary":"Double-blind phase 3 trial of 556 patients with untreated advanced non-small-cell lung cancer carrying an EGFR exon 19 deletion or L858R mutation, randomised to osimertinib or a first-generation EGFR inhibitor (gefitinib or erlotinib). Primary endpoint was investigator-assessed PFS.\n\nMedian PFS was 18.9 vs 10.2 months (HR 0.46), with fewer central nervous system progressions and less grade 3 toxicity. The 2020 overall survival report showed 38.6 vs 31.8 months (HR 0.80) despite crossover. It made osimertinib the global first-line standard and the backbone on which FLAURA2 and MARIPOSA later built.","asOf":"2026-09-08","links":[{"label":"NEJM 2018","url":"https://doi.org/10.1056/NEJMoa1713137"},{"label":"NEJM 2020 (OS)","url":"https://doi.org/10.1056/NEJMoa1913662"},{"label":"ClinicalTrials.gov NCT02296125","url":"https://clinicaltrials.gov/study/NCT02296125"}],"tags":[],"related":["lung-cancer-evidence-roadmap","paper-planchard-flaura2-osimertinib-chemotherapy-nejm-2023","paper-mariposa-nejm-2024"],"cancers":["nsclc","lung-cancer"],"sections":[],"technologies":["kinase-inhibitors","cgp"],"targets":["egfr"],"drugs":["osimertinib"],"companies":["astrazeneca"],"institutions":["gustave-roussy"],"pathways":[],"terms":["oncogene-addiction","resistance","pfs","os","first-line"],"trials":["flaura2","mariposa","adaura"],"people":["jean-charles-soria","ohe-yuichiro","zhou-caicun","cho-byoung-chul"],"bottlenecks":["b-resistance","b-brain-delivery","b-global-access"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2018,"doi":"10.1056/NEJMoa1713137","authors":"Soria JC, Ohe Y, Vansteenkiste J, et al.","paperType":"rct","findings":["Median PFS 18.9 vs 10.2 months; HR 0.46 (95% CI 0.37-0.57).","CNS progression events were roughly halved with osimertinib.","Grade 3 or higher adverse events 34% vs 45%.","Overall survival (2020): median 38.6 vs 31.8 months, HR 0.80 (95% CI 0.64-1.00), with about 31% of control patients crossing over to osimertinib.","FLAURA2 (2023) later showed adding platinum-pemetrexed to osimertinib extends PFS further (25.5 vs 16.7 months, HR 0.62)."],"whatItMeans":"Anyone diagnosed with advanced lung cancer should have EGFR testing before treatment, because osimertinib as the first drug gives the longest disease control, protects the brain, and is well tolerated. Chemotherapy is not the first step for these patients. The remaining questions are whether to intensify upfront (adding chemotherapy or amivantamab) and how to treat resistance when it develops.","caveats":["The overall survival benefit was borderline (upper confidence limit 1.00) and diluted by crossover to osimertinib.","Asian patients and those with L858R had smaller OS gains in subgroup analyses.","Resistance is universal; the trial did not address what to do after osimertinib.","High drug cost limits access in many countries where EGFR mutations are common."],"changedPractice":true,"participants":556},{"id":"paper-flaura2-long-term-safety-lung-cancer-2026","kind":"paper","name":"FLAURA2: long-term safety of first-line osimertinib plus platinum-pemetrexed in EGFR-mutated advanced lung cancer","aka":[],"tldr":"Side effects of the osimertinib plus chemotherapy combination were most frequent in the first four chemotherapy cycles and fell steadily once patients moved to maintenance and then to osimertinib alone; few had to stop osimertinib because of them.","summary":"Post hoc longitudinal safety analysis of the combination arm of FLAURA2, the phase 3 trial in which adding platinum-pemetrexed to first-line osimertinib improved survival over osimertinib alone in EGFR-mutated advanced non-small-cell lung cancer. Adverse events were analysed by each patient's exposure to three treatment periods: induction with the triple combination (276 patients), pemetrexed maintenance with osimertinib (201) and osimertinib alone after pemetrexed stopped (206).\n\nMedian durations of the three periods were 2.8, 12.4 and 17.8 months. Onset of any-grade and grade 3 or worse treatment-related adverse events was highest during induction (93 percent and 43 percent), lower during pemetrexed maintenance (90 percent and 25 percent) and lowest on osimertinib alone (58 percent and 14 percent). New haematological, gastrointestinal and skin or nail events, mostly grade 1 or 2, clustered in induction; renal events were more frequent during pemetrexed maintenance (19 percent, all grade 1 or 2) than induction (7 percent). Adverse events leading to osimertinib discontinuation were 8 percent or fewer in every period.","asOf":"2026-09-21","links":[{"label":"Lung Cancer 2026","url":"https://doi.org/10.1016/j.lungcan.2026.109588"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42728193/"},{"label":"ClinicalTrials.gov NCT04035486","url":"https://clinicaltrials.gov/study/NCT04035486"}],"tags":[],"related":[],"cancers":["nsclc","egfr-mutant-nsclc"],"sections":[],"technologies":[],"targets":["egfr"],"drugs":["osimertinib"],"companies":["astrazeneca"],"institutions":[],"pathways":[],"terms":["first-line"],"trials":["flaura2"],"people":["david-planchard","pasi-janne"],"bottlenecks":[],"keyPapers":[],"journals":["lung-cancer-journal"],"dependsOn":[],"notes":[],"journal":"Lung Cancer","year":2026,"doi":"10.1016/j.lungcan.2026.109588","pmid":"42728193","authors":"Planchard D, Jänne PA, Yang JC, et al.","paperType":"rct","findings":["Grade 3 or worse treatment-related adverse events began in 43 percent of patients during induction, 25 percent during pemetrexed maintenance and 14 percent during osimertinib alone.","Median duration of the induction, pemetrexed-maintenance and osimertinib-only periods was 2.8, 12.4 and 17.8 months.","Renal adverse events were more frequent during pemetrexed maintenance (19 percent, all grade 1 or 2) than during induction (7 percent); osimertinib discontinuation for adverse events was 8 percent or fewer in each period."],"whatItMeans":"For a patient weighing the FLAURA2 regimen against osimertinib alone, the extra toxicity is front-loaded: the hardest months are the four induction cycles, and once pemetrexed stops the profile returns to that of osimertinib by itself. Kidney function deserves watching during pemetrexed maintenance.","caveats":["Post hoc analysis of one arm; the periods are defined by each patient's exposure, so those who reached the later periods were by construction the ones who tolerated the earlier ones.","Onset frequencies count new events in each period and are not directly comparable with the trial's overall safety tables."],"changedPractice":false,"participants":276},{"id":"paper-flot4-lancet-2019","kind":"paper","name":"FLOT4-AIO: perioperative FLOT versus ECF/ECX for resectable gastric or gastro-oesophageal junction adenocarcinoma","aka":[],"tldr":"Perioperative chemotherapy with docetaxel, oxaliplatin, fluorouracil and leucovorin (FLOT) lengthened survival compared with the older anthracycline-based regimen in operable stomach and junctional cancers, making FLOT the standard in Europe.","summary":"Phase 2/3 trial of 716 patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (stage cT2 or higher or node-positive) randomised to perioperative FLOT (four cycles before and after surgery) or ECF/ECX (three cycles before and after).\n\nMedian overall survival was 50 versus 35 months (hazard ratio 0.77), five-year survival 45 versus 36 percent, and complete resection rates were higher with FLOT; toxicity profiles differed but were manageable.","asOf":"2026-09-17","links":[{"label":"Lancet 2019","url":"https://doi.org/10.1016/S0140-6736(18)32557-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30982686/"}],"tags":[],"related":[],"cancers":["oesophageal-adenocarcinoma","gastric-pdl1-high","gastric-her2-positive"],"sections":[],"technologies":[],"targets":[],"drugs":["capecitabine","cisplatin","docetaxel","epirubicin","oxaliplatin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["flot4"],"people":["salah-eddin-al-batran"],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2019,"doi":"10.1016/S0140-6736(18)32557-1","pmid":"30982686","authors":"Al-Batran SE, Homann N, Pauligk C, et al.","paperType":"rct","findings":["Median overall survival 50 vs 35 months; hazard ratio 0.77.","Five-year overall survival 45 percent vs 36 percent."],"whatItMeans":"FLOT is the reference perioperative regimen for gastric and junctional adenocarcinoma, and the backbone onto which durvalumab was added in MATTERHORN.","caveats":["Only about half of patients completed postoperative chemotherapy.","Not compared with CROSS chemoradiotherapy for oesophageal adenocarcinoma until ESOPEC."],"changedPractice":true,"participants":716},{"id":"paper-stummer-lancet-oncol","kind":"paper","name":"Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial","aka":[],"tldr":"Paper cited by one treatment page and one term page, indexed on Europe PMC as PubMed record 16648043 and published in The Lancet Oncology; the citing pages link this DOI, which is how the record was matched.","summary":"Background: 5-Aminolevulinic acid is a non-fluorescent prodrug that leads to intracellular accumulation of fluorescent porphyrins in malignant gliomas-a finding that is under investigation for intraoperative identification and resection of these tumours. We aimed to assess the effect of fluorescence-guided resection with 5-aminolevulinic acid on surgical radicality, progression-free survival, overall survival, and morbidity.\n\nMethods: 322 patients aged 23-73 years with suspected malignant glioma amenable to complete resection of contrast-enhancing tumour were randomly assigned to 20 mg/kg bodyweight 5-aminolevulinic acid for fluorescence-guided resection (n=161) or to conventional microsurgery with white light (n=161). The primary endpoints were the number of patients without contrast-enhancing tumour on early MRI (ie, that obtained within 72 h after surgery) and 6-month progression-free survival as assessed by MRI. Secondary endpoints were volume of residual tumour on postoperative MRI, overall survival, neurological deficit, and toxic effects. We report the results of an interim analysis with 270 patients in the full-analysis population (139 assigned 5-aminolevulinic acid, 131 assigned white light), which excluded patients with ineligible histological and radiological findings as assessed by central reviewers who were masked as to treatment allocation; the interim analysis resulted in termination of the study as defined by the protocol. Primary and secondary endpoints were analysed by intention to treat in the full-analysis population. The study is registered at http://www.clinicaltrials.gov as NCT00241670.\n\nFindings: Median follow-up was 35.4 months (95% CI 1.0-56.7). Contrast-enhancing tumour was resected completely in 90 (65%) of 139 patients assigned 5-aminolevulinic acid compared with 47 (36%) of 131 assigned white light (difference between groups 29% [95% CI 17-40], p<0.0001). Patients allocated 5-aminolevulinic acid had higher 6-month progression free survival than did those allocated white light (41.0% [32.8-49.2] vs 21.1% [14.0-28.2]; difference between groups 19.9% [9.1-30.7], p=0.0003, Z test). Groups did not differ in the frequency of severe adverse events or adverse events in any organ system class reported within 7 days after surgery.\n\nInterpretation: Tumour fluorescence derived from 5-aminolevulinic acid enables more complete resections of contrast-enhancing tumour, leading to improved progression-free survival in patients with malignant glioma.\n\nIndexed on Europe PMC as PubMed record 16648043 (DOI 10.1016/s1470-2045(06)70665-9). Matched by DOI alone: one treatment page and one term page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2006","url":"https://doi.org/10.1016/s1470-2045(06)70665-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/16648043/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/16648043"}],"tags":["europepmc-ingest"],"related":["aminolevulinic-acid-gleolan","extent-of-resection"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2006,"doi":"10.1016/s1470-2045(06)70665-9","pmid":"16648043","authors":"Stummer W, Pichlmeier U, Meinel T, et al.","paperType":"rct","findings":[],"whatItMeans":"One treatment page and one term page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-heinemann-fire-3-cetuximab-vs-bevacizumab-lancet-oncol-2014","kind":"paper","name":"FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3)","aka":[],"tldr":"A head-to-head of the two antibodies. They tied on response and progression, but patients on the EGFR antibody lived 3.7 months longer, a result nobody had predicted from the primary endpoint.","summary":"Heinemann, von Weikersthal, Decker and colleagues recruited patients aged 18 to 75 with stage IV histologically confirmed colorectal cancer, ECOG performance status 0 to 2 and KRAS exon 2 codon 12/13 wild-type tumours from centres in Germany and Austria, randomising them 1:1 to FOLFIRI plus cetuximab or FOLFIRI plus bevacizumab. The primary endpoint was objective response, analysed by intention to treat.\n\nBetween January 2007 and September 2012, 592 patients with KRAS exon 2 wild-type tumours were randomised and treated. The discordance between response, progression-free survival and overall survival in this trial is the reason later analyses went looking for sidedness.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2014","url":"https://doi.org/10.1016/S1470-2045(14)70330-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25088940/"}],"tags":["colorectal-evidence"],"related":["paper-venook-calgb-80405-cetuximab-vs-bevacizumab-jama-2017","paper-arnold-primary-tumour-side-ras-wild-type-ann-oncol-2017"],"cancers":["colorectal"],"sections":["targeted-therapy"],"technologies":["monoclonal-antibody","antiangiogenic"],"targets":["egfr","vegf","kras"],"drugs":["cetuximab","bevacizumab","folfiri","irinotecan"],"companies":[],"institutions":[],"pathways":[],"terms":["sidedness"],"trials":["crystal-fire3"],"people":["volker-heinemann"],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2014,"doi":"10.1016/S1470-2045(14)70330-4","pmid":"25088940","authors":"Heinemann V, von Weikersthal LF, Decker T, et al.","paperType":"rct","findings":["Objective response 62.0 percent (95 percent CI 56.2 to 67.5) with cetuximab against 58.0 percent (52.1 to 63.7) with bevacizumab: odds ratio 1.18 (0.85 to 1.64, p=0.18).","Median progression-free survival 10.0 against 10.3 months (hazard ratio 1.06, 0.88 to 1.26, p=0.55).","Median overall survival 28.7 months (24.0 to 36.6) against 25.0 months (22.7 to 27.6): hazard ratio 0.77 (0.62 to 0.96, p=0.017).","Grade 3 or worse skin reactions in 77 of 297 (26 percent) on cetuximab against six of 295 (2 percent) on bevacizumab."],"whatItMeans":"Together with PARADIGM it makes the EGFR antibody the preferred first partner for chemotherapy in left-sided RAS wild-type disease; the survival gain without a progression-free survival gain remains one of the field's unexplained results.","caveats":["The primary endpoint was negative; the practice-changing result is a secondary endpoint.","KRAS exon 2 testing only at randomisation; extended RAS and sidedness analyses came afterwards.","German and Austrian centres, funded by the manufacturer of cetuximab."],"changedPractice":true,"participants":592},{"id":"paper-cremolini-tribe-folfoxiri-bevacizumab-lancet-oncol-2015","kind":"paper","name":"FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of TRIBE","aka":[],"tldr":"Giving all three chemotherapy drugs at once rather than two added four months of life, and worked whatever the RAS or BRAF status. It is the most intensive first-line option for patients fit enough to take it.","summary":"TRIBE was an open-label phase 3 randomised study in patients with unresectable metastatic colorectal cancer recruited from 34 Italian oncology units, aged 18 to 70 with ECOG performance status of 2 or less, or 71 to 75 with performance status 0. Patients were randomised 1:1 to FOLFIRI plus bevacizumab or FOLFOXIRI plus bevacizumab; tissue for RAS and BRAF status was collected centrally. This updated analysis reports overall survival, a secondary endpoint, and treatment efficacy in the molecular subgroups.\n\nBetween July 2008 and May 2011, 508 patients were randomised, and the trial closed on 30 November 2014.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2015","url":"https://doi.org/10.1016/S1470-2045(15)00122-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26338525/"}],"tags":["colorectal-evidence"],"related":["paper-kopetz-beacon-encorafenib-braf-colorectal-nejm-2019","paper-heinemann-fire-3-cetuximab-vs-bevacizumab-lancet-oncol-2014"],"cancers":["colorectal","braf-v600e-colorectal"],"sections":["chemotherapy"],"technologies":["cytotoxic-chemotherapy","antiangiogenic"],"targets":["kras","braf","vegf"],"drugs":["folfirinox","folfiri","bevacizumab","oxaliplatin","irinotecan","fluorouracil"],"companies":[],"institutions":[],"pathways":[],"terms":["folfox-family"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2015,"doi":"10.1016/S1470-2045(15)00122-9","pmid":"26338525","authors":"Cremolini C, Loupakis F, Antoniotti C, et al.","paperType":"rct","findings":["At a median 48.1 months, median overall survival 29.8 months (95 percent CI 26.0 to 34.3) with FOLFOXIRI plus bevacizumab against 25.8 months (22.5 to 29.1): hazard ratio 0.80 (0.65 to 0.98, p=0.03).","Median overall survival by subgroup: 37.1 months in RAS and BRAF wild-type disease, 25.6 months in RAS-mutant disease (hazard ratio 1.49) and 13.4 months in BRAF-mutant disease (hazard ratio 2.79); likelihood-ratio test p<0.0001.","Treatment effect did not differ significantly across molecular subgroups (p for interaction 0.52)."],"whatItMeans":"The triplet is the option for fit patients who need a response, particularly in BRAF-mutant and right-sided disease where the EGFR antibody route is closed; it also quantified how much worse BRAF-mutant disease was before BEACON and BREAKWATER.","caveats":["Overall survival was a secondary endpoint in an updated analysis.","Eligibility was restricted by age and performance status; the triplet is not deliverable to most patients with metastatic colorectal cancer.","Italian centres only, and the control arm did not include an EGFR antibody."],"changedPractice":true,"participants":508},{"id":"paper-kraljevic-lancet-digit-health","kind":"paper","name":"Foresight-a generative pretrained transformer for modelling of patient timelines using electronic health records: a retrospective modelling study","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 38519155 and published in The Lancet Digital Health; the citing page links this DOI, which is how the record was matched.","summary":"Background: An electronic health record (EHR) holds detailed longitudinal information about a patient's health status and general clinical history, a large portion of which is stored as unstructured, free text. Existing approaches to model a patient's trajectory focus mostly on structured data and a subset of single-domain outcomes. This study aims to evaluate the effectiveness of Foresight, a generative transformer in temporal modelling of patient data, integrating both free text and structured formats, to predict a diverse array of future medical outcomes, such as disorders, substances (eg, to do with medicines, allergies, or poisonings), procedures, and findings (eg, relating to observations, judgements, or assessments).\n\nMethods: Foresight is a novel transformer-based pipeline that uses named entity recognition and linking tools to convert EHR document text into structured, coded concepts, followed by providing probabilistic forecasts for future medical events, such as disorders, substances, procedures, and findings. The Foresight pipeline has four main components: (1) CogStack (data retrieval and preprocessing); (2) the Medical Concept Annotation Toolkit (structuring of the free-text information from EHRs); (3) Foresight Core (deep-learning model for biomedical concept modelling); and (4) the Foresight web application. We processed the entire free-text portion from three different hospital datasets (King's College Hospital [KCH], South London and Maudsley [SLaM], and the US Medical Information Mart for Intensive Care III [MIMIC-III]), resulting in information from 811 336 patients and covering both physical and mental health institutions. We measured the performance of models using custom metrics derived from precision and recall.\n\nFindings: Foresight achieved a precision@10 (ie, of 10 forecasted candidates, at least one is correct) of 0·68 (SD 0·0027) for the KCH dataset, 0·76 (0·0032) for the SLaM dataset, and 0·88 (0·0018) for the MIMIC-III dataset, for forecasting the next new disorder in a patient timeline. Foresight also achieved a precision@10 value of 0·80 (0·0013) for the KCH dataset, 0·81 (0·0026) for the SLaM dataset, and 0·91 (0·0011) for the MIMIC-III dataset, for forecasting the next new biomedical concept. In addition, Foresight was validated on 34 synthetic patient timelines by five clinicians and achieved a relevancy of 33 (97% [95% CI 91-100]) of 34 for the top forecasted candidate disorder. As a generative model, Foresight can forecast follow-on biomedical concepts for as many steps as required.\n\nInterpretation: Foresight is a general-purpose model for biomedical concept modelling that can be used for real-world risk forecasting, virtual trials, and clinical research to study the progression of disorders, to simulate interventions and counterfactuals, and for educational purposes.\n\nFunding: National Health Service Artificial Intelligence Laboratory, National Institute for Health and Care Research Biomedical Research Centre, and Health Data Research UK.\n\nIndexed on Europe PMC as PubMed record 38519155 (DOI 10.1016/s2589-7500(24)00025-6). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Digit Health 2024","url":"https://doi.org/10.1016/s2589-7500(24)00025-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38519155/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38519155"}],"tags":["europepmc-ingest"],"related":["foresight-ehr"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-digital-health"],"dependsOn":[],"notes":[],"journal":"The Lancet Digital Health","year":2024,"doi":"10.1016/s2589-7500(24)00025-6","pmid":"38519155","authors":"Kraljevic Z, Bean D, Shek A, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-fort-long-term-follow-up-hoskin-lancet-oncol-2021","kind":"paper","name":"FoRT long-term follow-up: 4 Gy versus 24 Gy for follicular and marginal zone lymphoma","aka":[],"tldr":"Five years on, the higher radiotherapy dose still controlled indolent lymphoma far better: 90 percent of treated sites were free of regrowth after 24 Gy against 70 percent after 4 Gy.","summary":"Long-term follow-up of the FoRT trial (614 target sites in 548 patients) at a median of 73.8 months: 117 local progression events, 27 after 24 Gy and 90 after 4 Gy.\n\nLocal progression-free rates were 94.1 percent at two years and 89.9 percent at five years after 24 Gy against 79.8 and 70.4 percent after 4 Gy (hazard ratio 3.46).","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2021","url":"https://doi.org/10.1016/S1470-2045(20)30686-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33539729/"}],"tags":[],"related":["lymphoma-roadmap","fortplus","paper-trog-99-03-radiotherapy-systemic-therapy-early-follicular-jco-2018"],"cancers":["follicular-lymphoma","marginal-zone-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["fort"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2021,"doi":"10.1016/S1470-2045(20)30686-0","pmid":"33539729","authors":"Hoskin P, Popova B, Schofield O, et al.","paperType":"rct","findings":["Five-year local progression-free rate 89.9 percent (95% CI 85.5 to 93.1) after 24 Gy versus 70.4 percent (64.7 to 75.4) after 4 Gy.","Hazard ratio 3.46 (95% CI 2.25 to 5.33) at a median follow-up of 73.8 months."],"whatItMeans":"Confirms 24 Gy in 12 fractions as the optimal dose for indolent lymphoma when durable local control is the goal.","caveats":["Overall survival was not the endpoint and most patients had further systemic options at progression."],"changedPractice":true,"participants":548},{"id":"paper-fort-4gy-vs-24gy-indolent-lymphoma-hoskin-lancet-oncol-2014","kind":"paper","name":"FoRT: 4 Gy versus 24 Gy radiotherapy for indolent lymphoma, a randomised phase 3 non-inferiority trial","aka":[],"tldr":"Two small doses of radiotherapy did not control follicular and marginal zone lymphoma as well as the standard twelve, with more than three times the rate of regrowth in the treated area, so 24 Gy remains the standard and 4 Gy is for palliation.","summary":"UK phase 3 non-inferiority trial at 43 centres: 614 target sites in patients with follicular or marginal zone lymphoma were randomised to 24 Gy in 12 fractions (299 sites) or 4 Gy in 2 fractions (315 sites) between 2006 and 2011. The primary endpoint was time to local progression in the irradiated field.\n\nAfter a median follow-up of 26 months there were 21 local progressions after 24 Gy and 70 after 4 Gy; time to local progression with 4 Gy was not non-inferior (hazard ratio 3.42).","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2014","url":"https://doi.org/10.1016/S1470-2045(14)70036-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24572077/"}],"tags":[],"related":["lymphoma-roadmap","fortplus"],"cancers":["follicular-lymphoma","marginal-zone-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["fort"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2014,"doi":"10.1016/S1470-2045(14)70036-1","pmid":"24572077","authors":"Hoskin PJ, Kirkwood AA, Popova B, et al.","paperType":"rct","findings":["Local progressions 21 after 24 Gy versus 70 after 4 Gy at a median follow-up of 26 months.","Hazard ratio for local progression 3.42 (95% CI 2.09 to 5.55); 4 Gy not non-inferior."],"whatItMeans":"24 Gy in 12 fractions is the standard radiotherapy dose for indolent lymphoma when durable local control is the aim; 4 Gy remains useful for palliation.","caveats":["Randomisation was by site rather than patient; both curative and palliative intents were included."],"changedPractice":true,"participants":548},{"id":"paper-gorski-brca1-founder-mutations-poland-ajhg-2000","kind":"paper","name":"Founder mutations in the BRCA1 gene in Polish families with breast-ovarian cancer","aka":[],"tldr":"A 2000 study of 66 Polish families with breast and ovarian cancer in which three BRCA1 mutations accounted for more than four in five of the faults found, showing that a short national test panel could replace full gene sequencing in Poland.","summary":"Górski, Byrski, Huzarski, Jakubowska and colleagues studied 66 Polish families with at least three related women affected by breast or ovarian cancer and at least one diagnosed under 50 (26 families with both cancers, 4 ovarian only, 36 breast only), screening the entire coding region of BRCA1 and BRCA2 by single-strand conformation polymorphism and sequencing. Mutations were found in 35 (53 percent) of the families, all but one in BRCA1: in all four ovarian-only families, 67 percent of the 27 breast-ovarian families and 34 percent of the 35 breast-only families. Seven distinct mutations were identified; recurrent mutations accounted for 33 (94 percent) of the 35 families, and three BRCA1 changes (5382insC, C61G and 4153delA) accounted for 51, 20 and 11 percent of the mutations identified.","asOf":"2026-09-24","links":[{"label":"Am J Hum Genet 2000","url":"https://doi.org/10.1086/302922"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/10788334/"}],"tags":["tnbc-evidence"],"related":["paper-struewing-brca-founder-mutations-ashkenazi-nejm-1997"],"cancers":["tnbc","ovarian"],"sections":[],"technologies":[],"targets":["brca"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["germline-testing"],"trials":[],"people":[],"bottlenecks":["b-hereditary-risk"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"American Journal of Human Genetics","year":2000,"doi":"10.1086/302922","pmid":"10788334","authors":"Górski B, Byrski T, Huzarski T, et al.","paperType":"observational","findings":["Mutations in 35 of 66 families (53 percent), all but one in BRCA1.","Three BRCA1 founder mutations (5382insC 51 percent, C61G 20 percent, 4153delA 11 percent) accounted for 82 percent of mutations found; recurrent mutations 94 percent."],"whatItMeans":"The basis of Poland's founder-mutation testing programme, and an example of how the geography of BRCA1 variants shapes the geography of hereditary triple-negative breast cancer; 5382insC is shared with the Ashkenazi founder set.","caveats":["Hospital-based, high-risk families; carrier frequency in the general Polish population was not measured here.","Screening methods of 2000 could miss large rearrangements."],"changedPractice":true,"participants":66},{"id":"paper-flyer-four-vs-six-cycles-r-chop-lancet-2019","kind":"paper","name":"Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER)","aka":["FLYER","Poeschel 2019"],"tldr":"Young people with early, low-risk aggressive lymphoma did just as well with four rounds of chemotherapy as with six, and had roughly a quarter fewer side effects.","summary":"An open-label, international, randomised phase 3 non-inferiority trial at 138 sites in Denmark, Germany, Israel, Italy and Norway. It enrolled patients aged 18 to 60 with stage I to II aggressive B-cell non-Hodgkin lymphoma, normal serum lactate dehydrogenase, performance status 0 to 1 and no bulky disease, and randomised them between six cycles of R-CHOP and four cycles of CHOP with six applications of rituximab. No radiotherapy was planned except for testicular lymphoma.\n\n592 patients were enrolled between 2 December 2005 and 7 October 2016, 295 to six cycles and 297 to four; four withdrew consent before treatment, leaving 588 in the intention-to-treat analysis. After a median follow-up of 66 months (interquartile range 42 to 100), three-year progression-free survival in the four-cycle group was 96 per cent (95 per cent confidence interval 94 to 99), 3 percentage points better than six cycles, with a lower limit of the one-sided 95 per cent confidence interval for the difference of 0 per cent, which demonstrated non-inferiority against a margin of minus 5.5 per cent.","asOf":"2026-10-01","links":[{"label":"Lancet 2019","url":"https://doi.org/10.1016/S0140-6736(19)33008-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31868632/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31868632"}],"tags":["lymphoma-evidence"],"related":["lymphoma-roadmap"],"cancers":["dlbcl","non-hodgkin-lymphoma"],"sections":["chemotherapy"],"technologies":[],"targets":[],"drugs":["rituximab","cyclophosphamide","doxorubicin","vincristine","prednisone"],"companies":[],"institutions":[],"pathways":[],"terms":["r-chop","non-inferiority"],"trials":["flyer"],"people":[],"bottlenecks":["b-toxicity-qol","b-survivorship"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"Lancet","year":2019,"doi":"10.1016/S0140-6736(19)33008-9","pmid":"31868632","authors":"Poeschel V, Held G, Ziepert M, et al.","paperType":"rct","findings":["Three-year progression-free survival with four cycles of R-CHOP plus two further rituximab doses was 96 per cent (95 per cent confidence interval 94 to 99), 3 percentage points better than six cycles.","Non-inferiority was demonstrated against a margin of minus 5.5 per cent.","294 haematological and 1,036 non-haematological adverse events were documented in the four-cycle group against 426 and 1,280 in the six-cycle group.","Two patients died during study therapy, both in the six-cycle group."],"whatItMeans":"Four cycles rather than six for young patients with limited-stage, low-risk aggressive B-cell lymphoma. The saving is two cycles of anthracycline and vincristine in people who will live for decades afterwards.","caveats":["Restricted to patients aged 18 to 60 with normal lactate dehydrogenase, no bulk and performance status 0 to 1: the result does not transfer to higher-risk limited-stage disease.","Recruitment took eleven years, and the chemotherapy standard did not change in that time, but supportive care did.","Radiotherapy was not part of either arm, so the trial does not speak to combined-modality strategies."],"changedPractice":true,"participants":588},{"id":"paper-weiss-fgfr1-amplification-squamous-lung-sci-transl-med-2010","kind":"paper","name":"Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer","aka":[],"tldr":"A search for anything treatable in squamous lung cancer found extra copies of one growth-factor receptor gene in about a fifth of cases, and cells carrying those extra copies died when the receptor was blocked.","summary":"A systematic search across 232 lung cancer specimens for therapeutically amenable genetic alterations, followed by high-resolution copy-number analysis, identified frequent and focal FGFR1 amplification in squamous cell lung cancer (155 cases) but not in other lung cancer subtypes, and fluorescence in situ hybridisation confirmed amplification in 22% of an independent squamous cohort. Screening 83 lung cancer cell lines with the FGFR inhibitor PD173074 showed growth inhibition and apoptosis specifically in FGFR1-amplified cells. Dependence was validated by FGFR1 knockdown and by rescuing amplified cells with an inhibitor-resistant FGFR1 allele, and FGFR1 inhibition produced significant tumour shrinkage in vivo.","asOf":"2026-09-25","links":[{"label":"Weiss et al., Sci Transl Med 2010: frequent and focal FGFR1 amplification in squamous cell lung cancer","url":"https://doi.org/10.1126/scitranslmed.3001451"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21160078/"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":["cytogenetics-fish","kinase-inhibitors"],"targets":["fgfr1"],"drugs":[],"companies":[],"institutions":[],"pathways":["fgfr-signalling","rtk-activation"],"terms":["gene-amplification","amplification","fish"],"trials":[],"people":["roman-thomas"],"bottlenecks":[],"keyPapers":[],"journals":["science-translational-medicine"],"dependsOn":[],"notes":[],"journal":"Science Translational Medicine","year":2010,"doi":"10.1126/scitranslmed.3001451","pmid":"21160078","authors":"Weiss J, Sos ML, Seidel D, et al.","paperType":"translational","findings":["Focal FGFR1 amplification in squamous lung cancer and not in other subtypes, confirmed in 22% of an independent cohort.","Amplified cell lines are selectively killed by FGFR inhibition.","Dependence confirmed by knockdown and by an inhibitor-resistant allele.","Tumour shrinkage in vivo."],"whatItMeans":"It was the first therapeutically tractable alteration found in squamous lung cancer, and in the decade since it has become the standard example of amplification not equalling dependence, because copy number alone has selected patients poorly in trials.","caveats":["Preclinical dependence does not predict clinical response, and FGFR inhibitor trials selected on copy number have had low response rates.","Amplification calls vary with platform and threshold.","Messenger RNA expression, not measured here, separates dependent from non-dependent amplified tumours better than copy number does."],"changedPractice":false,"participants":232},{"id":"paper-jones-arid1a-clear-cell-science-2010","kind":"paper","name":"Frequent mutations of the chromatin remodelling gene ARID1A in ovarian clear cell carcinoma","aka":[],"tldr":"Published alongside the parallel New England Journal study, this exome sequencing project independently found ARID1A mutations in more than half of ovarian clear cell carcinomas, cementing the gene as the tumour's most common driver.","summary":"Exome sequencing of eight ovarian clear cell carcinomas followed by validation in 42 additional tumours, identifying ARID1A mutations in 57 percent along with PIK3CA, KRAS and PPP2R1A mutations.","asOf":"2026-09-17","links":[{"label":"Science 2010","url":"https://doi.org/10.1126/science.1196333"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20826764/"}],"tags":[],"related":[],"cancers":["clear-cell-ovarian-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2010,"doi":"10.1126/science.1196333","pmid":"20826764","authors":"Jones S, Wang TL, Shih IeM, et al.","paperType":"translational","findings":["ARID1A mutations in 57 percent of ovarian clear cell carcinomas.","PPP2R1A mutations identified as a novel recurrent alteration."],"whatItMeans":"Together with the Wiegand study, this defined clear cell ovarian cancer as a chromatin remodelling-driven disease distinct from high-grade serous cancer.","caveats":["Small discovery cohort."],"changedPractice":true},{"id":"paper-landa-j-clin-endocrinol-metab","kind":"paper","name":"Frequent somatic TERT promoter mutations in thyroid cancer: higher prevalence in advanced forms of the disease","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 23833040 and published in The Journal of clinical endocrinology and metabolism; the citing page links this DOI, which is how the record was matched.","summary":"Background: TERT encodes the reverse transcriptase component of telomerase, which adds telomere repeats to chromosome ends, thus enabling cell replication. Telomerase activity is required for cell immortalization. Somatic TERT promoter mutations modifying key transcriptional response elements were recently reported in several cancers, such as melanomas and gliomas.\n\nObjectives: The objectives of the study were: 1) to determine the prevalence of TERT promoter mutations C228T and C250T in different thyroid cancer histological types and cell lines; and 2) to establish the possible association of TERT mutations with mutations of BRAF, RAS, or RET/PTC.\n\nMethods: TERT promoter was PCR-amplified and sequenced in 42 thyroid cancer cell lines and 183 tumors: 80 papillary thyroid cancers (PTCs), 58 poorly differentiated thyroid cancers (PDTCs), 20 anaplastic thyroid cancers (ATCs), and 25 Hurthle cell cancers (HCCs).\n\nResults: TERT promoter mutations were found in 98 of 225 (44%) specimens. TERT promoters C228T and C250T were mutually exclusive. Mutations were present in 18 of 80 PTCs (22.5%), in 40 of 78 (51%) advanced thyroid cancers (ATC + PDTC) (P = 3 × 10(-4) vs PTC), and in widely invasive HCCs (4 of 17), but not in minimally invasive HCCs (0 of 8). TERT promoter mutations were seen more frequently in advanced cancers with BRAF/RAS mutations compared to those that were BRAF/RAS wild-type (ATC + PDTC, 67.3 vs 24.1%; P < 10(-4)), whereas BRAF-mutant PTCs were less likely to have TERT promoter mutations than BRAF wild-type tumors (11.8 vs 50.0%; P =.04).\n\nConclusions: TERT promoter mutations are highly prevalent in advanced thyroid cancers, particularly those harboring BRAF or RAS mutations, whereas PTCs with BRAF or RAS mutations are most often TERT promoter wild type. Acquisition of a TERT promoter mutation could extend survival of BRAF- or RAS-driven clones and enable accumulation of additional genetic defects leading to disease progression.\n\nIndexed on Europe PMC as PubMed record 23833040 (DOI 10.1210/jc.2013-2383). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Endocrinol Metab 2013","url":"https://doi.org/10.1210/jc.2013-2383"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23833040/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/23833040"}],"tags":["europepmc-ingest"],"related":["tert-promoter"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Journal of clinical endocrinology and metabolism","year":2013,"doi":"10.1210/jc.2013-2383","pmid":"23833040","authors":"Landa I, Ganly I, Chan TA, et al.","paperType":"basic","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-bcl-2-cll-nat-rev-drug-discov-2017","kind":"paper","name":"From basic apoptosis discoveries to advanced selective BCL-2 family inhibitors","aka":[],"tldr":"Review on BCL-2 in Chronic lymphocytic leukaemia, in Nature Reviews Drug Discovery (2017), one of the most cited Europe PMC records with BCL-2 in its title.","summary":"Members of the B cell lymphoma 2 (BCL-2) gene family have a central role in regulating programmed cell death by controlling pro-apoptotic and anti-apoptotic intracellular signals. In cancer, apoptosis evasion through dysregulation of specific BCL-2 family genes is a recurring event; accordingly, selective inhibition of specific anti-apoptotic BCL-2 family proteins represents an exciting therapeutic opportunity. A combination of nuclear magnetic resonance (NMR)-based screening and structure-based drug design has yielded the first bona fide BCL-2 homology 3 (BH3) mimetics, including the BCL-2 and BCL-X L dual antagonist navitoclax, which is the first BCL-2 family inhibitor to show efficacy in patients with cancer. Clinical experience with navitoclax prompted the generation of the highly selective BCL-2 inhibitor venetoclax, which is now approved in the United States for the treatment of patients with chronic lymphocytic leukaemia with 17p deletion who have received at least one prior therapy. Recent advances have also been made in the development of potent and selective inhibitors of BCL-X L and myeloid cell leukaemia 1 (MCL1), which are additional BCL-2 family members with established anti-apoptotic roles in cancer. Here we review the latest progress in direct and selective targeting of BCL-2 family proteins for cancer therapy.\n\nIndexed on Europe PMC as PubMed record 28209992 (DOI 10.1038/nrd.2016.253). Its title names BCL-2 and its text names Chronic lymphocytic leukaemia; PubMed types it as a review (Review). It was matched automatically to the idea \"BTK degraders to pre-empt resistance in frontline CLL\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Drug Discov 2017","url":"https://doi.org/10.1038/nrd.2016.253"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28209992/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28209992"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-drug-discovery"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Drug Discovery","year":2017,"doi":"10.1038/nrd.2016.253","pmid":"28209992","authors":"Ashkenazi A, Fairbrother WJ, Leverson JD, et al.","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for BCL-2 in Chronic lymphocytic leukaemia, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by BCL-2 in the title and Chronic lymphocytic leukaemia in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-altman-nat-rev-cancer","kind":"paper","name":"From Krebs to clinic: glutamine metabolism to cancer therapy","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 27492215 and published in Nature Reviews Cancer; the citing page links this DOI, which is how the record was matched.","summary":"The resurgence of research into cancer metabolism has recently broadened interests beyond glucose and the Warburg effect to other nutrients, including glutamine. Because oncogenic alterations of metabolism render cancer cells addicted to nutrients, pathways involved in glycolysis or glutaminolysis could be exploited for therapeutic purposes. In this Review, we provide an updated overview of glutamine metabolism and its involvement in tumorigenesis in vitro and in vivo, and explore the recent potential applications of basic science discoveries in the clinical setting.\n\nIndexed on Europe PMC as PubMed record 27492215 (DOI 10.1038/nrc.2016.71). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Cancer 2016","url":"https://doi.org/10.1038/nrc.2016.71"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27492215/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27492215"}],"tags":["europepmc-ingest"],"related":["glutamine-metabolism"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Cancer","year":2016,"doi":"10.1038/nrc.2016.71","pmid":"27492215","authors":"Altman BJ, Stine ZE, Dang CV","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-shain-nat-rev-cancer","kind":"paper","name":"From melanocytes to melanomas","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 27125352 and published in Nature Reviews Cancer; the citing page links this DOI, which is how the record was matched.","summary":"Melanomas on sun-exposed skin are heterogeneous tumours, which can be subtyped on the basis of their cumulative levels of exposure to ultraviolet (UV) radiation. A melanocytic neoplasm can also be staged by how far it has progressed, ranging from a benign neoplasm, such as a naevus, to a malignant neoplasm, such as a metastatic melanoma. Each subtype of melanoma can evolve through distinct evolutionary trajectories, passing through (or sometimes skipping over) various stages of transformation. This Review delineates several of the more common progression trajectories that occur in the patient setting and proposes models for tumour evolution that integrate genetic, histopathological, clinical and biological insights from the melanoma literature.\n\nIndexed on Europe PMC as PubMed record 27125352 (DOI 10.1038/nrc.2016.37). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Cancer 2016","url":"https://doi.org/10.1038/nrc.2016.37"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27125352/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27125352"}],"tags":["europepmc-ingest"],"related":["melanoma-signalling"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Cancer","year":2016,"doi":"10.1038/nrc.2016.37","pmid":"27125352","authors":"Shain AH, Bastian BC","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-shah-br-j-haematol","kind":"paper","name":"Front-line management of post-transplantation lymphoproliferative disorder in adult solid organ recipient patients - A British Society for Haematology Guideline","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 33877688 and published in British journal of haematology; the citing page links this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 33877688 (DOI 10.1111/bjh.17421). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Br J Haematol 2021","url":"https://doi.org/10.1111/bjh.17421"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33877688/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33877688"}],"tags":["europepmc-ingest"],"related":["post-transplant-lymphoproliferative-disorder"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"British journal of haematology","year":2021,"doi":"10.1111/bjh.17421","pmid":"33877688","authors":"Shah N, Eyre TA, Tucker D, et al.","paperType":"guideline","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-dasari-fresco-2-fruquintinib-lancet-2023","kind":"paper","name":"Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO-2)","aka":[],"tldr":"A selective VEGF receptor pill, first approved in China, repeated its effect in a global trial of 691 heavily treated patients: 7.4 against 4.8 months.","summary":"Dasari, Lonardi, Garcia-Carbonero and colleagues conducted an international randomised double-blind placebo-controlled phase 3 study at 124 hospitals and cancer centres across 14 countries in patients aged 18 or older with metastatic colorectal adenocarcinoma who had received all current standard cytotoxic and targeted therapies and had progressed on or been intolerant to trifluridine-tipiracil or regorafenib, or both. Patients were randomised 2:1 to fruquintinib 5 mg or matched placebo orally once daily on days 1 to 21 of 28-day cycles plus best supportive care, stratified by previous trifluridine-tipiracil or regorafenib, RAS status and duration of metastatic disease. The primary endpoint was overall survival.\n\nBetween August 2020 and December 2021, 691 patients were randomised; they had received a median of four previous lines and 502 (73 percent) had received more than three.","asOf":"2026-09-24","links":[{"label":"Lancet 2023","url":"https://doi.org/10.1016/S0140-6736(23)00772-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37331369/"},{"label":"Lancet 2023","url":"https://doi.org/10.1016/s0140-6736(23)00772-9"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37331369"},{"label":"ClinicalTrials.gov NCT04322539","url":"https://clinicaltrials.gov/study/NCT04322539"}],"tags":["colorectal-evidence"],"related":["paper-grothey-correct-regorafenib-lancet-2013","paper-prager-sunlight-trifluridine-tipiracil-bevacizumab-nejm-2023"],"cancers":["colorectal"],"sections":["targeted-therapy"],"technologies":["kinase-inhibitors","antiangiogenic"],"targets":["vegf"],"drugs":["fruquintinib"],"companies":["hutchmed"],"institutions":[],"pathways":[],"terms":[],"trials":["fresco-2"],"people":["eric-van-cutsem"],"bottlenecks":["b-global-access"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2023,"doi":"10.1016/S0140-6736(23)00772-9","pmid":"37331369","authors":"Dasari A, Lonardi S, Garcia-Carbonero R, et al.","paperType":"rct","findings":["Median overall survival 7.4 months (95 percent CI 6.7 to 8.2) with fruquintinib against 4.8 months (4.0 to 5.8) with placebo: hazard ratio 0.66 (0.55 to 0.80, p<0.0001).","Grade 3 or worse adverse events in 286 of 456 (63 percent) on fruquintinib against 116 of 230 (50 percent) on placebo.","Commonest grade 3 or worse fruquintinib events: hypertension 62 (14 percent), asthenia 35 (8 percent), hand-foot syndrome 29 (6 percent).","One treatment-related death in each group."],"whatItMeans":"A third refractory-line option, and the clearest example in colorectal cancer of a drug developed and approved in China going on to a global registration trial.","caveats":["Placebo-controlled in patients who had exhausted everything, so the comparison is against no active treatment.","Anti-angiogenic class toxicity, chiefly hypertension.","No biomarker selects who benefits."],"changedPractice":true,"participants":691},{"id":"paper-capivasertib-breast-hr-positive-lancet-oncol-2022","kind":"paper","name":"Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive, HER2-negative breast cancer (FAKTION): overall survival, updated progression-free survival, and expanded biomarker analysis from a randomised, phase 2 trial","aka":[],"tldr":"Phase 2 or 3 results paper on Capivasertib in HR-positive / HER2-negative breast cancer, in The Lancet Oncology (2022), one of the most cited Europe PMC records with Capivasertib in its title.","summary":"Background: Capivasertib, an AKT inhibitor, added to fulvestrant, was previously reported to improve progression-free survival in women with aromatase inhibitor-resistant oestrogen receptor (ER)-positive, HER2-negative advanced breast cancer. The benefit appeared to be independent of the phosphoinositide 3-kinase (PI3K)/AKT/phosphatase and tensin homologue (PTEN) pathway alteration status of tumours, as ascertained using assays available at the time. Here, we report updated progression-free survival and overall survival results, and a prespecified examination of the effect of PI3K/AKT/PTEN pathway alterations identified by an expanded genetic testing panel on treatment outcomes.\n\nMethods: This randomised, multicentre, double-blind, placebo-controlled, phase 2 trial recruited postmenopausal adult women aged at least 18 years with ER-positive, HER2-negative, metastatic or locally advanced inoperable breast cancer and an Eastern Cooperative Oncology Group performance status of 0-2, who had relapsed or progressed on an aromatase inhibitor, from across 19 hospitals in the UK. Participants were randomly assigned (1:1) to receive intramuscular fulvestrant 500 mg (day 1) every 28 days (plus a 500 mg loading dose on day 15 of cycle 1) with either capivasertib 400 mg or matching placebo, orally twice daily on an intermittent weekly schedule of 4 days on and 3 days off, starting on cycle 1 day 15. Treatment continued until disease progression, unacceptable toxicity, loss to follow-up, or withdrawal of consent. Treatment was allocated by an interactive web-response system using a minimisation method (with a 20% random element) and the following minimisation factors: measurable or non-measurable disease, primary or secondary aromatase inhibitor resistance, PIK3CA status, and PTEN status. The primary endpoint was progression-free survival in the intention-to-treat population. Secondary endpoints shown in this Article were overall survival and safety in the intention-to-treat population, and the effect of tumour PI3K/AKT/PTEN pathway status identified by an expanded testing panel that included next-generation sequencing assays. Recruitment is complete. The trial is registered with ClinicalTrials.gov, number NCT01992952.\n\nFindings: Between March 16, 2015, and March 6, 2018, 183 participants were screened for eligibility and 140 (77%) were randomly assigned to receive fulvestrant plus capivasertib (n=69) or fulvestrant plus placebo (n=71). Median follow-up at the data cut-off of Nov 25, 2021, was 58·5 months (IQR 45·9-64·1) for participants treated with fulvestrant plus capivasertib and 62·3 months (IQR 62·1-70·3) for fulvestrant plus placebo. Updated median progression-free survival was 10·3 months (95% CI 5·0-13·4) in the group receiving fulvestrant plus capivasertib compared with 4·8 months (3·1-7·9) for fulvestrant plus placebo (adjusted hazard ratio [HR] 0·56 [95% CI 0·38-0·81]; two-sided p=0·0023). Median overall survival in the capivasertib versus placebo groups was 29·3 months (95% CI 23·7-39·0) versus 23·4 months (18·7-32·7; adjusted HR 0·66 [95% CI 0·45-0·97]; two-sided p=0·035). The expanded biomarker panel identified an expanded pathway-altered subgroup that contained 76 participants (54% of the intention-to-treat population). Median progression-free survival in the expanded pathway-altered subgroup for participants receiving capivasertib (n=39) was 12·8 months (95% CI 6·6-18·8) compared with 4·6 months (2·8-7·9) in the placebo group (n=37; adjusted HR 0·44 [95% CI 0·26-0·72]; two-sided p=0·0014). Median overall survival for the expanded pathway-altered subgroup receiving capivasertib was 38·9 months (95% CI 23·3-50·7) compared with 20·0 months (14·8-31·4) for those receiving placebo (adjusted HR 0·46 [95% CI 0·27-0·79]; two-sided p=0·0047). By contrast, there were no statistically significant differences in progression-free or overall survival in the expanded pathway non-altered subgroup treated with capivasertib (n=30) versus placebo (n=34). One additional serious adverse event (pneumonia) in the capivasertib group had occurred subsequent to the primary analysis. One death, due to atypical pulmonary infection, was assessed as possibly related to capivasertib treatment.\n\nInterpretation: Updated FAKTION data showed that capivasertib addition to fulvestrant extends the survival of participants with aromatase inhibitor-resistant ER-positive, HER2-negative advanced breast cancer. The expanded biomarker testing suggested that capivasertib predominantly benefits patients with PI3K/AKT/PTEN pathway-altered tumours. Phase 3 data are needed to substantiate the results, including in patients with previous CDK4/6 inhibitor exposure who were not included in the FAKTION trial.\n\nFunding: AstraZeneca and Cancer Research UK.\n\nIndexed on Europe PMC as PubMed record 35671774 (DOI 10.1016/s1470-2045(22)00284-4). Its title names Capivasertib and its text names HR-positive / HER2-negative breast cancer; PubMed types it as a clinical trial report (Clinical Trial, Phase II, Research Support, Non-U.S. Gov't, research-article, Multicenter Study, Randomized Controlled Trial). It was matched automatically to the idea \"Molecular-progression switching beyond ESR1\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2022","url":"https://doi.org/10.1016/s1470-2045(22)00284-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35671774/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35671774"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2022,"doi":"10.1016/s1470-2045(22)00284-4","pmid":"35671774","authors":"Howell SJ, Casbard A, Carucci M, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Capivasertib in HR-positive / HER2-negative breast cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Capivasertib in the title and HR-positive / HER2-negative breast cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-kornauth-cancer-discov","kind":"paper","name":"Functional Precision Medicine Provides Clinical Benefit in Advanced Aggressive Hematologic Cancers and Identifies Exceptional Responders","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 34635570 and published in Cancer Discovery; the citing page links this DOI, which is how the record was matched.","summary":"Personalized medicine aims to match the right drug with the right patient by using specific features of the individual patient's tumor. However, current strategies of personalized therapy matching provide treatment opportunities for less than 10% of patients with cancer. A promising method may be drug profiling of patient biopsy specimens with single-cell resolution to directly quantify drug effects. We prospectively tested an image-based single-cell functional precision medicine (scFPM) approach to guide treatments in 143 patients with advanced aggressive hematologic cancers. Fifty-six patients (39%) were treated according to scFPM results. At a median follow-up of 23.9 months, 30 patients (54%) demonstrated a clinical benefit of more than 1.3-fold enhanced progression-free survival compared with their previous therapy. Twelve patients (40% of responders) experienced exceptional responses lasting three times longer than expected for their respective disease. We conclude that therapy matching by scFPM is clinically feasible and effective in advanced aggressive hematologic cancers. SIGNIFICANCE: This is the first precision medicine trial using a functional assay to instruct n-of-one therapies in oncology. It illustrates that for patients lacking standard therapies, high-content assay-based scFPM can have a significant value in clinical therapy guidance based on functional dependencies of each patient's cancer. See related commentary by Letai, p. 290. This article is highlighted in the In This Issue feature, p. 275.\n\nIndexed on Europe PMC as PubMed record 34635570 (DOI 10.1158/2159-8290.cd-21-0538). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer Discov 2022","url":"https://doi.org/10.1158/2159-8290.cd-21-0538"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34635570/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34635570"}],"tags":["europepmc-ingest"],"related":["functional-precision-medicine-haematology"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-discovery"],"dependsOn":[],"notes":[],"journal":"Cancer Discovery","year":2022,"doi":"10.1158/2159-8290.cd-21-0538","pmid":"34635570","authors":"Kornauth C, Pemovska T, Vladimer GI, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-furlong-lancet-respir-med-2022","kind":"paper","name":"Furmonertinib (AST2818) versus gefitinib as first-line therapy for Chinese patients with locally advanced or metastatic EGFR mutation-positive non-small-cell lung cancer (FURLONG): a multicentre, double-blind, randomised phase 3 study","aka":[],"tldr":"Published report from the FURLONG trial registered as NCT03787992, in The Lancet. Respiratory medicine (2022), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Furmonertinib (AST2818) is an irreversible, selective, third-generation EGFR tyrosine-kinase inhibitor. We aimed to investigate the efficacy and safety of furmonertinib versus the first-generation EGFR tyrosine-kinase inhibitor gefitinib as first-line treatment in patients with EGFR mutation-positive locally advanced or metastatic non-small-cell lung cancer (NSCLC).\n\nMethods: The FURLONG study is a multicentre, double-blind, randomised, phase 3 study done in 55 hospitals across mainland China. We enrolled patients who were aged 18 years or older and had histologically confirmed, locally advanced or metastatic, stage IIIB, IIIC, or IV unresectable NSCLC with EGFR exon 19 deletions or exon 21 Leu858Arg mutation on tissue biopsy confirmed by a central laboratory. Eligible patients were stratified according to EGFR mutation (exon 19 deletions or exon 21 Leu858Arg) and CNS metastases (with or without) and randomly assigned (1:1) to receive either oral furmonertinib (80 mg/day) or oral gefitinib (250 mg/day) in 21-day cycles until disease progression, the occurrence of intolerable toxicities, withdrawal of consent, or other discontinuation reasons judged by the investigators. Investigators, clinicians, participants, independent review centre (IRC) members, the sponsor, and those analysing the data were all masked to treatment allocation. The primary endpoint was IRC-assessed progression-free survival and, along with safety, was analysed in the full analysis set, which comprised all randomly assigned patients who had received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT03787992, and is ongoing for survival follow-up.\n\nFindings: Between May 30, 2019, and Dec 5, 2019, 750 patients were screened, of whom 358 were randomly assigned to receive either furmonertinib and gefitinib-matching placebo (n=178) or gefitinib and furmonertinib-matching placebo (n=180). 178 patients randomly assigned to furmonertinib and 179 patients randomly assigned to gefitinib were treated and were included in the full analysis set. Median follow-up was 21·0 months (IQR 18·0-23·5) in the furmonertinib group and 21·0 months (18·0-23·5) in the gefitinib group. Median IRC-assessed progression-free survival was 20·8 months (95% CI 17·8-23·5) in the furmonertinib group and 11·1 months (9·7-12·5) in the gefitinib group (hazard ratio 0·44, 95% CI 0·34-0·58; p<0·0001). Treatment-related adverse events of a grade 3 or more occurred in 20 (11%) of 178 patients in the furmonertinib group and in 32 (18%) of 179 patients in the gefitinib group. Treatment-related serious adverse events were reported in ten (6%) patients in the furmonertinib group and in 11 (6%) patients in the gefitinib group. Ten (6%) patients in the furmonertinib group and three (2%) patients in the gefitinib group died due to adverse events, which were all judged to be possibly unrelated to study treatment by the investigators.\n\nInterpretation: Furmonertinib showed superior efficacy compared with gefitinib as first-line therapy in Chinese patients with EGFR mutation-positive NSCLC, along with an acceptable safety profile without new signals. Furmonertinib is a new potential treatment option for this population.\n\nFunding: Shanghai Allist Pharmaceuticals and the China National Major Project for New Drug Innovation.\n\nTranslation: For the Chinese translation of the abstract see Supplementary Materials section.\n\nIndexed on Europe PMC as PubMed record 35662408 (DOI 10.1016/s2213-2600(22)00168-0). Its abstract cites the registry id NCT03787992, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Respir Med 2022","url":"https://doi.org/10.1016/s2213-2600(22)00168-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35662408/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35662408"},{"label":"ClinicalTrials.gov NCT03787992","url":"https://clinicaltrials.gov/study/NCT03787992"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["furlong"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Lancet. Respiratory medicine","year":2022,"doi":"10.1016/s2213-2600(22)00168-0","pmid":"35662408","authors":"Shi Y, Chen G, Wang X, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03787992 with the most citations, so it is the natural first reading for anyone following the FURLONG trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-hirota-kit-gist-science-1998","kind":"paper","name":"Gain-of-function mutations of c-kit in human gastrointestinal stromal tumours","aka":[],"tldr":"This discovery that gastrointestinal stromal tumours carry activating mutations in the KIT receptor, and express KIT protein, defined the disease and provided the target for imatinib three years later.","summary":"Study showing KIT expression in gastrointestinal stromal tumours, identifying gain-of-function mutations in the KIT juxtamembrane domain (exon 11) in five of six tumours analysed, and demonstrating that the mutant receptors are constitutively activated and transforming, with interstitial cells of Cajal as the likely cell of origin.","asOf":"2026-09-17","links":[{"label":"Science 1998","url":"https://doi.org/10.1126/science.279.5350.577"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/9438854/"}],"tags":[],"related":[],"cancers":["gist-kit-exon-11"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":1998,"doi":"10.1126/science.279.5350.577","pmid":"9438854","authors":"Hirota S, Isozaki K, Moriyama Y, et al.","paperType":"basic","findings":["Activating KIT juxtamembrane domain mutations in five of six GISTs.","KIT protein expression as a diagnostic marker."],"whatItMeans":"KIT immunohistochemistry and mutation testing define GIST, and the exon 11 mutations described here are the ones most sensitive to imatinib.","caveats":["Small discovery series; PDGFRA mutations in KIT-negative GIST were found later."],"changedPractice":true},{"id":"paper-galaxy-signatera-nat-med-2023","kind":"paper","name":"GALAXY: tumour DNA in blood four weeks after bowel cancer surgery predicts relapse tenfold","aka":[],"tldr":"In 1,039 Japanese patients with resected colorectal cancer, a positive Signatera test at week 4 carried a tenfold higher recurrence risk, and only ctDNA-positive patients appeared to benefit from adjuvant chemotherapy.","summary":"GALAXY is the prospective observational arm of the Japanese CIRCULATE platform. Patients with stage II-IV resectable colorectal cancer had serial tumour-informed ctDNA testing (Signatera) after surgery, with treatment at physician discretion.\n\nctDNA positivity at 4 weeks post-surgery was the strongest predictor of recurrence (HR about 10). Among ctDNA-positive patients, adjuvant chemotherapy was associated with markedly better disease-free survival (HR about 6.6 in favour of treatment), whereas ctDNA-negative patients showed no apparent benefit. Clearance of ctDNA during adjuvant therapy predicted good outcomes.\n\nThe study is the largest prospective MRD dataset in colorectal cancer and the basis for the randomised VEGA and ALTAIR trials.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1038/s41591-022-02115-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36646802/"},{"label":"Europe PMC full text (PMC9873552)","url":"https://europepmc.org/article/MED/36646802"}],"tags":[],"related":["paper-dynamic-nejm-2022","idea-ctdna-guided-adjuvant-crc","idea-tr2-ctdna-mrd-qualification","ctdna-mrd-positive"],"cancers":["colorectal","colon-cancer"],"sections":["diagnostics"],"technologies":["mrd-testing","liquid-biopsy","continuous-ctdna-monitoring","signatera"],"targets":[],"drugs":["signatera"],"companies":["natera"],"institutions":["ncc-japan"],"pathways":[],"terms":["mrd","ctdna","vaf","tumour-informed-assay"],"trials":["circulate-japan"],"people":["yoshino-takayuki"],"bottlenecks":["b-dormancy-mrd","b-biomarker-validation","b-real-world-evidence"],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2023,"doi":"10.1038/s41591-022-02115-4","pmid":"36646802","authors":"Kotani D, Oki E, Nakamura Y, et al.","paperType":"observational","findings":["ctDNA positivity at week 4 associated with recurrence: HR 10.0 (95% CI 7.7-14.0)","18-month DFS 38.4% for ctDNA-positive vs 90.5% for ctDNA-negative patients","Adjuvant chemotherapy associated with improved DFS in ctDNA-positive patients (HR 6.59, 95% CI 3.53-12.3) but not in ctDNA-negative patients","ctDNA clearance by week 24 predicted substantially better DFS than persistent positivity"],"whatItMeans":"The blood test stratifies risk far better than stage or pathology. It supports treating ctDNA-positive patients and suggests ctDNA-negative patients gain little from chemotherapy, but because treatment was not randomised the de-escalation claim needs the randomised trials that are now under way.","caveats":["Observational; treatment decisions were not randomised, so the chemotherapy benefit estimate is confounded","Short follow-up at initial publication (median about 17 months)","Japanese population and Japanese adjuvant practice; generalisability to other health systems is untested","Commercial sponsor (Natera) involvement in assay and analysis"],"changedPractice":false,"participants":1039},{"id":"paper-roa-gallbladder-cancer-primer-nat-rev-dis-primers-2022","kind":"paper","name":"Gallbladder cancer","aka":[],"tldr":"The 2022 Nature Reviews primer on gallbladder cancer: the commonest biliary cancer, mostly found by chance at gallstone surgery, driven by long-standing inflammation, curable only by surgery and badly in need of screening biomarkers and separate study.","summary":"Disease primer by authors from Chile, India, the United States and the US National Cancer Institute. Gallbladder cancer is the most common biliary tract cancer with very short survival at advanced stages; most cases are discovered incidentally after cholecystectomy for symptomatic stones, and chronic inflammation drives the disease whether or not stones are present. Omics studies have clarified inflammation-driven initiation and progression. Surgery is the only curative treatment and few cases are resectable; adjuvant therapy has low response rates. Unmet needs named: biomarkers for screening, therapy selection and prognosis; standardised nomenclature for preneoplastic lesions and specimen processing; and multidisciplinary care with neoadjuvant, adjuvant and novel systemic therapies including immunotherapy.","asOf":"2026-09-24","links":[{"label":"Nat Rev Dis Primers 2022","url":"https://doi.org/10.1038/s41572-022-00398-y"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36302789/"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nci"],"pathways":[],"terms":["incidental-gallbladder-cancer","inflammation"],"trials":[],"people":[],"bottlenecks":["b-rare-cancers","b-early-detection"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature Reviews Disease Primers","year":2022,"doi":"10.1038/s41572-022-00398-y","pmid":"36302789","authors":"Roa JC, García P, Kapoor VK, et al.","paperType":"review","findings":["Most gallbladder cancers are discovered incidentally after cholecystectomy for symptomatic gallstones.","Named unmet needs: screening, selection and prognostic biomarkers; standardised lesion nomenclature and specimen sampling."],"whatItMeans":"The best single starting point for a clinician or researcher new to the disease, written by the groups running the Chilean and Indian cohorts; its list of unmet needs is the skeleton of the ideas section on this page.","caveats":["Narrative review.","Published before the zanidatamab approvals and the TOPAZ-1 long-term update."],"changedPractice":false},{"id":"paper-cid-chile-programme-gallbladder-cancer-mortality-am-j-epidemiol-2024","kind":"paper","name":"Gallbladder cancer mortality in Chile: has the government program targeting young gallstone patients had an impact?","aka":[],"tldr":"An epidemiological analysis, with US National Cancer Institute authors, of whether Chile's preventive gallbladder surgery programme has cut deaths from gallbladder cancer.","summary":"American Journal of Epidemiology analysis by Chilean and US National Cancer Institute investigators of gallbladder cancer mortality in Chile in relation to the GES programme targeting gallstone patients aged 35 to 49. Europe PMC indexes no abstract for this article, so OnCo carries no figures from it; the two Revista Medica de Chile evaluations linked from this record supply the numbers OnCo quotes.","asOf":"2026-09-24","links":[{"label":"Am J Epidemiol 2024","url":"https://doi.org/10.1093/aje/kwae027"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38576158/"}],"tags":["gallbladder-evidence"],"related":["paper-samaniego-chile-ges-programme-evaluation-rev-med-chile-2024","paper-mardones-frenz-chile-ges-mortality-rev-med-chile-2019"],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nci"],"pathways":[],"terms":["prophylactic-cholecystectomy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"American Journal of Epidemiology","year":2024,"doi":"10.1093/aje/kwae027","pmid":"38576158","authors":"Cid V, Vargas C, Delgado I, et al.","paperType":"observational","findings":["No abstract is indexed on Europe PMC; no figures are transcribed."],"whatItMeans":"The most rigorous evaluation of the Chilean programme available; read alongside Mardones and Frenz (2019) and Samaniego and colleagues (2024).","caveats":["No abstract indexed; conclusions not transcribed here."],"changedPractice":false},{"id":"paper-samaniego-chile-ges-programme-evaluation-rev-med-chile-2024","kind":"paper","name":"Gallbladder Cancer: Is It Time to Modify the Explicit Health Guarantees (GES) Program?","aka":[],"tldr":"Chile has guaranteed gallbladder removal for people aged 35 to 49 with gallstones since 2006 to prevent gallbladder cancer; this review of official data finds deaths falling but already falling before the programme, and uptake not matching the regions where the cancer is commonest.","summary":"Retrospective analysis of official Chilean Ministry of Health and National Statistics Institute data on the GES preventive cholecystectomy programme, which since 2006 has included cholelithiasis in patients aged 35 to 49 with cholecystectomy as guaranteed treatment. Since inception 284,139 notifications had been issued to patients in that age band with gallstones, correlating with cholecystectomies performed under the programme. Standardised gallbladder cancer mortality has fallen over two decades, including before the programme began. Incidence varies across the country and high-incidence areas are not always the areas with most notifications. The authors conclude the programme should be modified to direct resources to patients in high-incidence areas with known risk factors.","asOf":"2026-09-24","links":[{"label":"Rev Med Chile 2024","url":"https://doi.org/10.4067/s0034-98872024001001028"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40052976/"},{"label":"Superintendencia de Salud: GES problem 26, preventive cholecystectomy at 35 to 49","url":"https://www.supersalud.gob.cl/difusion/665/w3-propertyvalue-1962.html"}],"tags":["gallbladder-evidence"],"related":["paper-mardones-frenz-chile-ges-mortality-rev-med-chile-2019","paper-cid-chile-programme-gallbladder-cancer-mortality-am-j-epidemiol-2024"],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["prophylactic-cholecystectomy","screening"],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-real-world-evidence"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Revista Medica de Chile","year":2024,"doi":"10.4067/s0034-98872024001001028","pmid":"40052976","authors":"Samaniego CP, de Aretxabala X, Castillo F, et al.","paperType":"observational","findings":["284,139 GES notifications issued since 2006 to patients aged 35 to 49 with gallstones.","Standardised gallbladder cancer mortality has decreased over two decades, including before the programme was implemented.","High-incidence areas are not always the areas with high notification rates."],"whatItMeans":"The only national prophylactic cholecystectomy programme in the world has run for nearly twenty years without a design that can show whether it works. Targeting by region and risk, and building in an evaluation, is the obvious next step.","caveats":["Ecological analysis of routine data; no counterfactual.","Spanish-language article; the abstract is the source used here."],"changedPractice":false},{"id":"paper-wistuba-gazdar-gallbladder-cancer-lessons-nat-rev-cancer-2004","kind":"paper","name":"Gallbladder cancer: lessons from a rare tumour","aka":[],"tldr":"A 2004 review arguing that gallbladder cancer, rare and little studied, is worth understanding because its mix of inherited risk, geography, female predominance, chronic inflammation and congenital anomalies is unusual among cancers.","summary":"Nature Reviews Cancer article stating that gallbladder cancer is a relatively rare malignancy about which knowledge is scant, and that its combination of predisposing factors (genetic predisposition, geographic distribution, female gender bias, chronic inflammation and congenital developmental abnormalities) makes it unique and informative for cancer pathogenesis generally. The authors argue that understanding how these risk factors contribute to the molecular basis of the disease is essential.","asOf":"2026-09-24","links":[{"label":"Nat Rev Cancer 2004","url":"https://doi.org/10.1038/nrc1429"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/15343276/"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-rare-cancers","b-funding-allocation"],"keyPapers":[],"journals":["nature-reviews-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Cancer","year":2004,"doi":"10.1038/nrc1429","pmid":"15343276","authors":"Wistuba II, Gazdar AF.","paperType":"review","findings":["Describes gallbladder cancer as a relatively rare malignancy about which knowledge is scant (authors' words)."],"whatItMeans":"Two decades on, the disease is still described as understudied in the 2025 immunogenomics literature; the reasons (rarity in the countries that fund research, incidental diagnosis, pooling with bile duct cancer in trials) have not changed.","caveats":["Review from 2004; molecular detail is dated.","No new data."],"changedPractice":false},{"id":"paper-gallium-obinutuzumab-first-line-follicular-lymphoma-marcus-nejm-2017","kind":"paper","name":"GALLIUM: obinutuzumab for the first-line treatment of follicular lymphoma","aka":[],"tldr":"Obinutuzumab with chemotherapy and as maintenance kept follicular lymphoma from progressing for longer than rituximab, at the cost of more serious side effects.","summary":"Open-label phase 3 trial: 1,202 patients with previously untreated follicular lymphoma were randomised to obinutuzumab or rituximab with bendamustine, CHOP or CVP, followed by antibody maintenance.\n\nAt a planned interim analysis after a median follow-up of 34.5 months, estimated three-year progression-free survival was 80.0 percent with obinutuzumab against 73.3 percent with rituximab (hazard ratio 0.66). Response rates were similar (88.5 against 86.9 percent); grade 3 to 5 adverse events (74.6 against 67.8 percent) and serious adverse events (46.1 against 39.9 percent) were more frequent with obinutuzumab, and infusion-related events were the most common adverse event.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2017","url":"https://doi.org/10.1056/NEJMoa1614598"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28976863/"}],"tags":[],"related":[],"cancers":["follicular-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["obinutuzumab","rituximab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["gallium"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2017,"doi":"10.1056/NEJMoa1614598","pmid":"28976863","authors":"Marcus R, Davies A, Ando K, et al.","paperType":"rct","findings":["Three-year progression-free survival 80.0 versus 73.3 percent; hazard ratio 0.66 (95% CI 0.51 to 0.85), p 0.001.","Overall response 88.5 versus 86.9 percent.","Grade 3 to 5 adverse events 74.6 versus 67.8 percent; deaths from adverse events 4.0 versus 3.4 percent."],"whatItMeans":"Obinutuzumab-based immunochemotherapy is a first-line option for follicular lymphoma; the choice against rituximab weighs longer progression-free survival against toxicity and cost.","caveats":["No overall survival difference; toxicity was highest with bendamustine partners.","Open-label design with investigator-assessed primary endpoint, supported by independent review."],"changedPractice":true,"participants":1202},{"id":"paper-galon-immune-contexture-colorectal-science-2006","kind":"paper","name":"Galon 2006: the type, density and location of immune cells in colorectal tumours predict outcome","aka":[],"tldr":"Counting the T cells inside a bowel cancer and at its edge predicted whether the cancer would return better than the traditional stage did, the discovery behind the Immunoscore test.","summary":"Galon and colleagues analysed immune cells in tumours from 415 patients with colorectal cancer using gene expression and tissue microarrays. A strong presence of adaptive immune cells, in particular CD3, CD8, CD45RO memory and granzyme B-positive cytotoxic T cells, in both the tumour centre and the invasive margin was associated with a much lower rate of early metastasis and longer survival, independently of and more strongly than the TNM stage. The finding led to the standardised Immunoscore, validated internationally in 2018.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1126/science.1129139"}],"tags":[],"related":["colorectal-roadmap","idea-crc-mss-immunotherapy-by-biomarker-not-by-line"],"cancers":["colorectal"],"sections":[],"technologies":["histopathology-ihc"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["tumor-microenvironment","cancer-immunity-cycle"],"terms":["tils","immune-system","prognosis","ihc"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Science","year":2006,"doi":"10.1126/science.1129139","authors":"Galon J, Costes A, Sanchez-Cabo F, et al.","paperType":"translational","findings":["Immune profiling of colorectal tumours from 415 patients by gene expression and tissue microarrays.","Tumours without signs of early metastatic invasion had higher densities of adaptive immune cells, especially memory and cytotoxic T cells.","High densities of CD3, CD8 and CD45RO cells in both the tumour centre and invasive margin predicted longer disease-free and overall survival, independently of TNM stage."],"whatItMeans":"This paper showed that the immune response to a cancer is part of its prognosis, not background noise, and it introduced the idea of the immune contexture that underlies both the Immunoscore and the biomarker work in immunotherapy.","caveats":["A single-centre cohort at the time; the Immunoscore was validated in a later international study.","Immunoscore is not yet part of routine staging in most countries."],"changedPractice":false},{"id":"paper-jin-cochrane-database-syst-rev","kind":"paper","name":"Ganoderma lucidum (Reishi mushroom) for cancer treatment","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 27045603 and published in The Cochrane database of systematic reviews; the citing page links this DOI, which is how the record was matched.","summary":"Background: Ganoderma lucidum is a natural medicine that is widely used and recommended by Asian physicians and naturopaths for its supporting effects on immune system. Laboratory research and a handful of preclinical trials have suggested that G. lucidum carries promising anticancer and immunomodulatory properties. The popularity of taking G. lucidum as an alternative medicine has been increasing in cancer patients. However, there is no systematic review that has been conducted to evaluate the actual benefits of G. lucidum in cancer treatment.\n\nObjectives: To evaluate the clinical effects of G. lucidum on long-term survival, tumour response, host immune functions and quality of life in cancer patients, as well as adverse events associated with its use.\n\nSearch methods: We searched an extensive set of databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, NIH, AMED, CBM, CNKI, CMCC and VIP Information/Chinese Scientific Journals Database was searched for randomised controlled trials (RCTs) in October 2011. Other strategies used were scanning the references of articles retrieved, handsearching of the International Journal of Medicinal Mushrooms and contact with herbal medicine experts and manufacturers of G. lucidum. For this update we updated the searches in February 2016.\n\nSelection criteria: To be eligible for being included in this review, studies had to be RCTs comparing the efficacy of G. lucidum medications to active or placebo control in patients with cancer that had been diagnosed by pathology. All types and stages of cancer were eligible for inclusion. Trials were not restricted on the basis of language.\n\nData collection and analysis: Five RCTs met the inclusion criteria and were included in this review. Two independent review authors assessed the methodological quality of individual trials. Common primary outcomes were tumour response evaluated according to the World Health Organization (WHO) criteria, immune function parameters such as natural killer (NK)-cell activity and T-lymphocyte co-receptor subsets, and quality of life measured by the Karnofsky scale score. No trial had recorded long-term survival rates. Associated adverse events were reported in one study. A meta-analysis was performed to pool available data from the primary trials. Results were gauged using relative risks (RR) and standard mean differences (SMD) for dichotomous and continuous data respectively, with a 95% confidence interval (CI).\n\nMain results: The methodological quality of primary studies was generally unsatisfying and the results were reported inadequately in many aspects. Additional information was not available from primary trialists. The meta-analysis results showed that patients who had been given G. lucidum alongside with chemo/radiotherapy were more likely to respond positively compared to chemo/radiotherapy alone (RR 1.50; 95% CI 0.90 to 2.51, P = 0.02). G. lucidum treatment alone did not demonstrate the same regression rate as that seen in combined therapy. The results for host immune function indicators suggested that G. lucidum simultaneously increases the percentage of CD3, CD4 and CD8 by 3.91% (95% CI 1.92% to 5.90%, P < 0.01), 3.05% (95% CI 1.00% to 5.11%, P < 0.01) and 2.02% (95% CI 0.21% to 3.84%, P = 0.03), respectively. In addition, leukocyte, NK-cell activity and CD4/CD8 ratio were marginally elevated. Four studies showed that patients in the G. lucidum group had relatively improved quality of life in comparison to controls. One study recorded minimal side effects, including nausea and insomnia. No significant haematological or hepatological toxicity was reported.\n\nAuthors' conclusions: Our review did not find sufficient evidence to justify the use of G. lucidum as a first-line treatment for cancer. It remains uncertain whether G. lucidum helps prolong long-term cancer survival. However, G. lucidum could be administered as an alternative adjunct to conventional treatment in consideration of its potential of enhancing tumour response and stimulating host immunity. G. lucidum was generally well tolerated by most participants with only a scattered number of minor adverse events. No major toxicity was observed across the studies. Although there were few reports of harmful effect of G. lucidum, the use of its extract should be judicious, especially after thorough consideration of cost-benefit and patient preference. Future studies should put emphasis on the improvement in methodological quality and further clinical research on the effect of G. lucidum on cancer long-term survival are needed. An update to this review will be performed every two years.\n\nIndexed on Europe PMC as PubMed record 27045603 (DOI 10.1002/14651858.cd007731.pub3). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cochrane Database Syst Rev 2016","url":"https://doi.org/10.1002/14651858.cd007731.pub3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27045603/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27045603"}],"tags":["europepmc-ingest"],"related":["medicinal-mushrooms-reishi-turkey-tail"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Cochrane database of systematic reviews","year":2016,"doi":"10.1002/14651858.cd007731.pub3","pmid":"27045603","authors":"Jin X, Ruiz Beguerie J, Sze DM, et al.","paperType":"meta-analysis","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-gap70-geriatric-assessment-lancet-2021","kind":"paper","name":"GAP70+: a geriatric assessment before chemotherapy cut serious toxicity in older adults by a fifth","aka":[],"tldr":"When oncologists received a geriatric assessment summary with management recommendations for patients aged 70 or over, grade 3-5 toxicity fell from 71% to 51% with no loss in survival.","summary":"GAP70+ was a cluster-randomised trial in 40 US community oncology practices. Patients aged 70 or over with advanced cancer and at least one impaired geriatric domain who were starting a new palliative chemotherapy or other high-risk regimen were enrolled (718 patients). Intervention practices received a geriatric assessment summary and tailored recommendations; usual-care practices received only alerts for depression and cognitive impairment.\n\nThe primary endpoint, grade 3-5 toxicity over 3 months, occurred in 51% of intervention patients versus 71% in usual care (relative risk 0.74). Oncologists in the intervention arm more often reduced dose intensity at cycle 1, and 6-month and 1-year survival did not differ. A companion trial (GAIN, JAMA Oncology 2021) found a similar toxicity reduction.\n\nThe result made geriatric assessment-guided management a guideline standard (ASCO 2023) for older adults receiving systemic therapy.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1016/S0140-6736(21)01789-X"},{"label":"ClinicalTrials.gov NCT02054741","url":"https://clinicaltrials.gov/study/NCT02054741"}],"tags":[],"related":["idea-moon-geriatric-assessment-default","idea-acc-geriatric-assessment-by-default","idea-tr1-geriatric-dose-finding-cohorts","idea-acc-upfront-reduced-dose-trials-frail"],"cancers":[],"sections":["supportive-care"],"technologies":["geriatric-assessment"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-aging-comorbidity","b-toxicity-qol","b-dose-optimisation"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2021,"doi":"10.1016/S0140-6736(21)01789-X","pmid":"34741815","authors":"Mohile SG, Mohamed MR, Xu H, et al.","paperType":"rct","findings":["Grade 3-5 toxic effects 51% vs 71% (relative risk 0.74, 95% CI 0.64-0.86)","Cycle 1 dose reduction 49% vs 35% in the intervention arm","No difference in 6-month overall survival (71% vs 74%) or 1-year survival","Falls and polypharmacy-related events were also reduced with geriatric management"],"whatItMeans":"Older patients are more likely to be harmed by standard-dose chemotherapy, and a structured assessment of function, cognition, nutrition and social support lets oncologists adjust treatment safely. Starting lower does not appear to shorten life. Most older patients still do not get such an assessment.","caveats":["Cluster randomisation at practice level with modest numbers per practice","Toxicity was the primary endpoint; quality-of-life and functional outcomes were secondary","Intervention effect depends on oncologists acting on recommendations; adherence varied","Excludes curative-intent settings, where dose reductions are riskier"],"changedPractice":true,"participants":718},{"id":"paper-garnet-dostarlimab-oaknin-jama-oncol-2020","kind":"paper","name":"GARNET: dostarlimab in mismatch repair-deficient recurrent or advanced endometrial cancer","aka":[],"tldr":"The PD-1 antibody dostarlimab shrank tumours in about four in ten women with mismatch repair-deficient endometrial cancer that had progressed after platinum chemotherapy, with most responses still ongoing after a year.","summary":"Interim analysis of the phase 1 GARNET trial's cohort of 104 patients with mismatch repair-deficient recurrent or advanced endometrial cancer treated with dostarlimab after platinum-based therapy.\n\nObjective response was 42.3 percent with complete response in 12.7 percent, and 93 percent of responses were ongoing at data cut-off; immune-related toxicity was manageable.","asOf":"2026-09-17","links":[{"label":"JAMA Oncol 2020","url":"https://doi.org/10.1001/jamaoncol.2020.4515"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33001143/"}],"tags":[],"related":[],"cancers":["endometrial-mmr-deficient"],"sections":[],"technologies":[],"targets":[],"drugs":["dostarlimab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["garnet"],"people":["ana-oaknin"],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2020,"doi":"10.1001/jamaoncol.2020.4515","pmid":"33001143","authors":"Oaknin A, Tinker AV, Gilbert L, et al.","paperType":"observational","findings":["Objective response 42.3 percent; complete response 12.7 percent.","Median duration of response not reached; 93 percent of responses ongoing."],"whatItMeans":"Dostarlimab was approved for previously treated mismatch repair-deficient endometrial cancer on these data, before moving into first-line combination in RUBY.","caveats":["Single-arm, interim data.","Response in mismatch repair-proficient disease was much lower (about 13 percent) in a parallel cohort."],"changedPractice":true,"participants":104},{"id":"paper-nct04585035-signal-transduct-target-ther-2025","kind":"paper","name":"Garsorasib, a KRAS G12C inhibitor, with or without cetuximab, an EGFR antibody, in colorectal cancer cohorts of a phase II trial in advanced solid tumors with KRAS G12C mutation","aka":[],"tldr":"Published report from the trial registered as NCT04585035, in Signal transduction and targeted therapy (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Mutations in the KRAS gene have long been implicated in the pathogenesis of colorectal cancer (CRC). KRAS G12C inhibitors overcome the \"undruggable\" challenge, enabling precision therapy. Garsorasib (D-1553), a highly potent and selective KRAS G12C inhibitor, has demonstrated promising anti-tumor activity and favorable safety profile in early clinical trials. We conducted an open-label, nonrandomized phase II trial (ClinicalTrials.gov, NCT04585035) to assess the safety and efficacy of garsorasib with or without cetuximab in KRAS G12C-mutated CRC. In the monotherapy cohort (n = 26), objective response rate (ORR) was 19.2% (95% CI, 6.6-39.4), disease control rate (DCR) was 92.3% (95% CI, 74.9-99.1), median progression-free survival (PFS) was 5.5 months (95% CI, 2.9-11.6) and median overall survival (OS) was 13.1 months (95% CI, 9.5-NE). In the combination cohort (n = 42), ORR was 45.2% (95% CI, 29.8-61.3), DCR was 92.9% (95% CI, 80.5-98.5), median PFS was 7.5 months (95% CI, 5.5-8.1), and median OS was not reached. Grade ≥3 treatment-related adverse events occurred in 5 (19.2%) and 6 (14.3%) patients in monotherapy and combination cohort, respectively. Garsorasib with or without cetuximab showed a promising efficacy and manageable safety profiles in heavily pretreated patients with KRAS G12C-mutated CRC, providing a potential new treatment approach for such population.\n\nIndexed on Europe PMC as PubMed record 40523897 (DOI 10.1038/s41392-025-02274-z). Its abstract cites the registry id NCT04585035, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Signal Transduct Target Ther 2025","url":"https://doi.org/10.1038/s41392-025-02274-z"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40523897/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40523897"},{"label":"ClinicalTrials.gov NCT04585035","url":"https://clinicaltrials.gov/study/NCT04585035"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04585035"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Signal transduction and targeted therapy","year":2025,"doi":"10.1038/s41392-025-02274-z","pmid":"40523897","authors":"Ruan DY, Wu HX, Xu Y, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04585035 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-smyth-lancet","kind":"paper","name":"Gastric cancer","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 32861308 and published in The Lancet; the citing page links this DOI, which is how the record was matched.","summary":"Gastric cancer is the fifth most common cancer and the third most common cause of cancer death globally. Risk factors for the condition include Helicobacter pylori infection, age, high salt intake, and diets low in fruit and vegetables. Gastric cancer is diagnosed histologically after endoscopic biopsy and staged using CT, endoscopic ultrasound, PET, and laparoscopy. It is a molecularly and phenotypically highly heterogeneous disease. The main treatment for early gastric cancer is endoscopic resection. Non-early operable gastric cancer is treated with surgery, which should include D2 lymphadenectomy (including lymph node stations in the perigastric mesentery and along the celiac arterial branches). Perioperative or adjuvant chemotherapy improves survival in patients with stage 1B or higher cancers. Advanced gastric cancer is treated with sequential lines of chemotherapy, starting with a platinum and fluoropyrimidine doublet in the first line; median survival is less than 1 year. Targeted therapies licensed to treat gastric cancer include trastuzumab (HER2-positive patients first line), ramucirumab (anti-angiogenic second line), and nivolumab or pembrolizumab (anti-PD-1 third line).\n\nIndexed on Europe PMC as PubMed record 32861308 (DOI 10.1016/s0140-6736(20)31288-5). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet 2020","url":"https://doi.org/10.1016/s0140-6736(20)31288-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32861308/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32861308"}],"tags":["europepmc-ingest"],"related":["gastric-cancer-signalling"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2020,"doi":"10.1016/s0140-6736(20)31288-5","pmid":"32861308","authors":"Smyth EC, Nilsson M, Grabsch HI, et al.","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-casali-ann-oncol","kind":"paper","name":"Gastrointestinal stromal tumours: ESMO-EURACAN-GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 34560242 and published in Annals of Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 34560242 (DOI 10.1016/j.annonc.2021.09.005). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Ann Oncol 2022","url":"https://doi.org/10.1016/j.annonc.2021.09.005"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34560242/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34560242"}],"tags":["europepmc-ingest"],"related":["gist"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2022,"doi":"10.1016/j.annonc.2021.09.005","pmid":"34560242","authors":"Casali PG, Blay JY, Abecassis N, et al.","paperType":"guideline","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-okane-gata6-basal-like-compass-ccr-2020","kind":"paper","name":"GATA6 expression distinguishes classical and basal-like subtypes in advanced pancreatic cancer","aka":[],"tldr":"In 195 patients treated with chemotherapy for advanced pancreatic cancer, one in five had the basal-like type; those patients responded a third as often, progressed on FOLFIRINOX four times as often and lived 5.9 rather than 9.3 months, and a simple GATA6 tissue stain picked the type out.","summary":"Within COMPASS, patients proceeding to chemotherapy for advanced pancreatic ductal adenocarcinoma had biopsies RNA-sequenced. Between December 2015 and May 2019, 195 patients (95%) had enough tissue; 39 (20%) were basal-like and 156 (80%) classical. Among 157 with response data, the overall response rate was 10% in basal-like against 33% in classical (P = 0.02); in basal-like tumours treated with modified FOLFIRINOX the progression rate was 60% against 15% (P = 0.0002). Median overall survival was 9.3 months for classical against 5.9 for basal-like (hazard ratio 0.47; P = 0.0001). GATA6 expression by RNA sequencing correlated with the classifier and in situ hybridisation predicted subtype with sensitivity 89% and specificity 83%; GATA6 was prognostic in multivariate analysis. Basal-like tumours could be identified by keratin 5, were more hypoxic and enriched for a T-cell-inflamed signature.","asOf":"2026-09-24","links":[{"label":"O'Kane et al., Clin Cancer Res 2020: GATA6 and the basal-like subtype in 195 COMPASS patients","url":"https://doi.org/10.1158/1078-0432.CCR-19-3724"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32156747/"}],"tags":[],"related":[],"cancers":["pancreatic","metastatic-pdac"],"sections":[],"technologies":["rna-seq"],"targets":[],"drugs":["folfirinox"],"companies":[],"institutions":["princess-margaret","oicr"],"pathways":["epigenetic-reprogramming"],"terms":["ihc"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2020,"doi":"10.1158/1078-0432.CCR-19-3724","pmid":"32156747","authors":"O'Kane GM, Grunwald BT, Jang GH, et al.","paperType":"translational","findings":["Basal-like 20% of 195; response 10% versus 33%; FOLFIRINOX progression 60% versus 15%.","Median overall survival 5.9 versus 9.3 months (hazard ratio 0.47).","GATA6 in situ hybridisation: sensitivity 89%, specificity 83% for the classical subtype."],"whatItMeans":"It is the number behind 'basal-like is chemoresistant' and the validation of the GATA6 stain that lets a pathology laboratory call the subtype without RNA sequencing.","caveats":["Single-programme cohort; treatment not randomised by subtype.","The T-cell-inflamed signal in basal-like tumours has not yet translated into immunotherapy benefit."],"changedPractice":false,"participants":195},{"id":"paper-majzner-nature","kind":"paper","name":"GD2-CAR T cell therapy for H3K27M-mutated diffuse midline gliomas","aka":[],"tldr":"Paper cited by one cancer page and one technology page, indexed on Europe PMC as PubMed record 35130560 and published in Nature; the citing pages link this DOI, which is how the record was matched.","summary":"Diffuse intrinsic pontine glioma (DIPG) and other H3K27M-mutated diffuse midline gliomas (DMGs) are universally lethal paediatric tumours of the central nervous system 1. We have previously shown that the disialoganglioside GD2 is highly expressed on H3K27M-mutated glioma cells and have demonstrated promising preclinical efficacy of GD2-directed chimeric antigen receptor (CAR) T cells 2, providing the rationale for a first-in-human phase I clinical trial (NCT04196413). Because CAR T cell-induced brainstem inflammation can result in obstructive hydrocephalus, increased intracranial pressure and dangerous tissue shifts, neurocritical care precautions were incorporated. Here we present the clinical experience from the first four patients with H3K27M-mutated DIPG or spinal cord DMG treated with GD2-CAR T cells at dose level 1 (1 × 10 6 GD2-CAR T cells per kg administered intravenously). Patients who exhibited clinical benefit were eligible for subsequent GD2-CAR T cell infusions administered intracerebroventricularly 3. Toxicity was largely related to the location of the tumour and was reversible with intensive supportive care. On-target, off-tumour toxicity was not observed. Three of four patients exhibited clinical and radiographic improvement. Pro-inflammatory cytokine levels were increased in the plasma and cerebrospinal fluid. Transcriptomic analyses of 65,598 single cells from CAR T cell products and cerebrospinal fluid elucidate heterogeneity in response between participants and administration routes. These early results underscore the promise of this therapeutic approach for patients with H3K27M-mutated DIPG or spinal cord DMG.\n\nIndexed on Europe PMC as PubMed record 35130560 (DOI 10.1038/s41586-022-04489-4). Matched by DOI alone: one cancer page and one technology page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2022","url":"https://doi.org/10.1038/s41586-022-04489-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35130560/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35130560"}],"tags":["europepmc-ingest"],"related":["dipg-dmg","glioma-car-t"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2022,"doi":"10.1038/s41586-022-04489-4","pmid":"35130560","authors":"Majzner RG, Ramakrishna S, Yeom KW, et al.","paperType":"basic","findings":[],"whatItMeans":"One cancer page and one technology page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-mok-ipass-gefitinib-pulmonary-adenocarcinoma-nejm-2009","kind":"paper","name":"Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma","aka":[],"tldr":"IPASS randomised 1,217 East Asian never-smokers and light former smokers between a tablet and chemotherapy. The tablet won, but only in the patients whose tumour carried an EGFR mutation; in the rest chemotherapy was better.","summary":"Mok, Wu, Thongprasert and colleagues randomised 1,217 previously untreated patients in East Asia with advanced pulmonary adenocarcinoma who were non-smokers or former light smokers to gefitinib 250 mg daily (609) or carboplatin with paclitaxel (608), with progression-free survival as the primary endpoint.\n\nIPASS is the trial that made a predictive biomarker mandatory rather than interesting. Selection was clinical (ethnicity, histology, smoking history), and the overall result was positive, but the pre-planned biomarker analysis showed the effect was carried entirely by the mutation-positive subgroup and reversed in the mutation-negative one. After IPASS, treating advanced adenocarcinoma without knowing the EGFR status became indefensible.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2009","url":"https://doi.org/10.1056/NEJMoa0810699"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19692680/"},{"label":"ClinicalTrials.gov NCT00322452","url":"https://clinicaltrials.gov/study/NCT00322452"},{"label":"N Engl J Med 2009","url":"https://doi.org/10.1056/nejmoa0810699"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/19692680"}],"tags":["lung-evidence"],"related":["paper-lynch-egfr-activating-mutations-gefitinib-nejm-2004","paper-paez-egfr-mutations-gefitinib-science-2004","paper-egfr-nsclc-n-engl-j-med-2010","paper-egfr-nsclc-lancet-oncol-2012","paper-flaura-nejm-2018","gefitinib"],"cancers":["lung-cancer","nsclc","egfr-mutant-nsclc","lung-adenocarcinoma"],"sections":["targeted-therapy","diagnostics"],"technologies":["ngs","ihc"],"targets":["egfr"],"drugs":["gefitinib","carboplatin","paclitaxel"],"companies":[],"institutions":[],"pathways":[],"terms":["driver-mutation","oncogene-addiction","histology"],"trials":[],"people":["tony-mok"],"bottlenecks":["b-biomarker-validation","b-trial-design"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2009,"doi":"10.1056/NEJMoa0810699","pmid":"19692680","authors":"Mok TS, Wu YL, Thongprasert S, et al.","paperType":"rct","findings":["Twelve-month progression-free survival 24.9 percent with gefitinib against 6.7 percent with carboplatin and paclitaxel.","Gefitinib met the primary objective of non-inferiority and also showed superiority for progression-free survival in the intention-to-treat population: hazard ratio for progression or death 0.74 (95 percent confidence interval 0.65 to 0.85).","The presence of an EGFR mutation in the tumour was a strong predictor of a better outcome with gefitinib.","Gefitinib is superior to carboplatin-paclitaxel as initial treatment for pulmonary adenocarcinoma among non-smokers or former light smokers in East Asia."],"whatItMeans":"The trial that turned EGFR testing into a standard of care rather than a research assay, and the clearest demonstration in oncology that a clinically selected population can hide two opposite treatment effects inside one positive result.","caveats":["Clinical rather than molecular entry criteria, so the trial had to rediscover the biomarker inside itself; EGFR status was available for only a subset of participants.","East Asian never-smokers and light former smokers; the mutation prevalence and therefore the overall result do not transfer to an unselected Western population.","Progression-free survival was the endpoint; crossover meant overall survival did not differ."],"changedPractice":true,"participants":1217},{"id":"paper-egfr-nsclc-n-engl-j-med-2010","kind":"paper","name":"Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR","aka":[],"tldr":"Phase 2 or 3 results paper on EGFR in Non-small-cell lung cancer, in New England Journal of Medicine (2010), one of the most cited Europe PMC records with EGFR in its title.","summary":"Background: Non-small-cell lung cancer with sensitive mutations of the epidermal growth factor receptor (EGFR) is highly responsive to EGFR tyrosine kinase inhibitors such as gefitinib, but little is known about how its efficacy and safety profile compares with that of standard chemotherapy.\n\nMethods: We randomly assigned 230 patients with metastatic, non-small-cell lung cancer and EGFR mutations who had not previously received chemotherapy to receive gefitinib or carboplatin-paclitaxel. The primary end point was progression-free survival; secondary end points included overall survival, response rate, and toxic effects.\n\nResults: In the planned interim analysis of data for the first 200 patients, progression-free survival was significantly longer in the gefitinib group than in the standard-chemotherapy group (hazard ratio for death or disease progression with gefitinib, 0.36; P<0.001), resulting in early termination of the study. The gefitinib group had a significantly longer median progression-free survival (10.8 months, vs. 5.4 months in the chemotherapy group; hazard ratio, 0.30; 95% confidence interval, 0.22 to 0.41; P<0.001), as well as a higher response rate (73.7% vs. 30.7%, P<0.001). The median overall survival was 30.5 months in the gefitinib group and 23.6 months in the chemotherapy group (P=0.31). The most common adverse events in the gefitinib group were rash (71.1%) and elevated aminotransferase levels (55.3%), and in the chemotherapy group, neutropenia (77.0%), anemia (64.6%), appetite loss (56.6%), and sensory neuropathy (54.9%). One patient receiving gefitinib died from interstitial lung disease.\n\nConclusions: First-line gefitinib for patients with advanced non-small-cell lung cancer who were selected on the basis of EGFR mutations improved progression-free survival, with acceptable toxicity, as compared with standard chemotherapy. (UMIN-CTR number, C000000376.)\n\nIndexed on Europe PMC as PubMed record 20573926 (DOI 10.1056/nejmoa0909530). Its title names EGFR and its text names Non-small-cell lung cancer; PubMed types it as a clinical trial report (Clinical Trial, Phase III, Comparative Study, Research Support, Non-U.S. Gov't, Multicenter Study, Randomized Controlled Trial). It was matched automatically to the idea \"Look for the resistant sub-population before the first dose\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2010","url":"https://doi.org/10.1056/nejmoa0909530"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20573926/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/20573926"}],"tags":["europepmc-ingest"],"related":["lung-cancer-evidence-roadmap","paper-mok-ipass-gefitinib-pulmonary-adenocarcinoma-nejm-2009"],"cancers":["lung-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2010,"doi":"10.1056/nejmoa0909530","pmid":"20573926","authors":"Maemondo M, Inoue A, Kobayashi K, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for EGFR in Non-small-cell lung cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by EGFR in the title and Non-small-cell lung cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-noronha-j-clin-oncol","kind":"paper","name":"Gefitinib Versus Gefitinib Plus Pemetrexed and Carboplatin Chemotherapy in EGFR -Mutated Lung Cancer","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 31411950 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: Standard first-line therapy for EGFR -mutant advanced non-small-cell lung cancer (NSCLC) is an epidermal growth factor receptor (EGFR)-directed oral tyrosine kinase inhibitor. Adding pemetrexed and carboplatin chemotherapy to an oral tyrosine kinase inhibitor may improve outcomes.\n\nPatients and methods: This was a phase III randomized trial in patients with advanced NSCLC harboring an EGFR -sensitizing mutation and a performance status of 0 to 2 who were planned to receive first-line palliative therapy. Random assignment was 1:1 to gefitinib 250 mg orally per day (Gef) or gefitinib 250 mg orally per day plus pemetrexed 500 mg/m 2 and carboplatin area under curve 5 intravenously every 3 weeks for four cycles, followed by maintenance pemetrexed (gefitinib plus chemotherapy [Gef+C]). The primary end point was progression-free survival (PFS); secondary end points included overall survival (OS), response rate, and toxicity.\n\nResults: Between 2016 and 2018, 350 patients were randomly assigned to Gef (n = 176) and Gef+C (n = 174). Twenty-one percent of patients had a performance status of 2, and 18% of patients had brain metastases. Median follow-up time was 17 months (range, 7 to 30 months). Radiologic response rates were 75% and 63% in the Gef+C and Gef arms, respectively ( P =.01). Estimated median PFS was significantly longer with Gef+C than Gef (16 months [95% CI, 13.5 to 18.5 months] v 8 months [95% CI, 7.0 to 9.0 months], respectively; hazard ratio for disease progression or death, 0.51 [95% CI, 0.39 to 0.66]; P <.001). Estimated median OS was significantly longer with Gef+C than Gef (not reached v 17 months [95% CI, 13.5 to 20.5 months]; hazard ratio for death, 0.45 [95% CI, 0.31 to 0.65]; P <.001). Clinically relevant grade 3 or greater toxicities occurred in 51% and 25% of patients in the Gef+C and Gef arms, respectively ( P <.001).\n\nConclusion: Adding pemetrexed and carboplatin chemotherapy to gefitinib significantly prolonged PFS and OS but increased toxicity in patients with NSCLC.\n\nIndexed on Europe PMC as PubMed record 31411950 (DOI 10.1200/jco.19.01154). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2020","url":"https://doi.org/10.1200/jco.19.01154"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31411950/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31411950"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["gefitinib-chemo-tmh"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/jco.19.01154","pmid":"31411950","authors":"Noronha V, Patil VM, Joshi A, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-zhang-gemcitabine-cisplatin-induction-nasopharyngeal-nejm-2019","kind":"paper","name":"Gemcitabine and cisplatin induction chemotherapy in nasopharyngeal carcinoma","aka":[],"tldr":"Three cycles of gemcitabine and cisplatin before chemoradiotherapy cut recurrences and improved survival in locoregionally advanced nasopharyngeal cancer, making induction chemotherapy the standard in endemic regions.","summary":"Chinese multicentre randomised phase 3 trial of 480 patients with locoregionally advanced nasopharyngeal carcinoma (stage III to IVB, excluding T3-4N0 and T3N1) comparing three cycles of induction gemcitabine and cisplatin followed by concurrent cisplatin chemoradiotherapy with chemoradiotherapy alone.\n\nThree-year recurrence-free survival was 85.3 percent with induction against 76.5 percent, and overall survival 94.6 percent against 90.3 percent, with the largest reduction in distant metastases; acute toxicity was higher during induction but late toxicity was similar.","asOf":"2026-09-18","links":[{"label":"N Engl J Med 2019","url":"https://doi.org/10.1056/NEJMoa1905287"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31150573/"}],"tags":[],"related":[],"cancers":["locoregionally-advanced-nasopharyngeal-carcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":["gemcitabine-cisplatin","cisplatin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2019,"doi":"10.1056/NEJMoa1905287","pmid":"31150573","authors":"Zhang Y, Chen L, Hu GQ, et al.","paperType":"rct","findings":["Three-year recurrence-free survival 85.3 percent with induction gemcitabine-cisplatin versus 76.5 percent with chemoradiotherapy alone.","Three-year overall survival 94.6 percent versus 90.3 percent; fewer distant metastases."],"whatItMeans":"Induction gemcitabine and cisplatin followed by chemoradiotherapy is the standard for locoregionally advanced nasopharyngeal carcinoma in endemic regions and in guidelines internationally.","caveats":["Conducted in an endemic Chinese population with non-keratinising EBV-related tumours; applicability to non-endemic disease is assumed.","Excluded the lower-risk N0 to N1 subgroups."],"changedPractice":true,"participants":480},{"id":"paper-hensley-gemcitabine-docetaxel-leiomyosarcoma-jco-2002","kind":"paper","name":"Gemcitabine and docetaxel in patients with unresectable leiomyosarcoma: results of a phase 2 trial","aka":[],"tldr":"The combination of gemcitabine and docetaxel produced responses in more than half of patients with leiomyosarcoma, most of them uterine and many previously treated with doxorubicin, establishing a widely used second regimen for the disease.","summary":"Phase 2 study of 34 patients with unresectable leiomyosarcoma (29 uterine) treated with fixed-dose-rate gemcitabine followed by docetaxel every three weeks with growth factor support.\n\nObjective response was 53 percent including three complete responses, with responses in patients previously treated with doxorubicin; median time to progression was 5.6 months and myelosuppression was the main toxicity.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2002","url":"https://doi.org/10.1200/JCO.2002.11.050"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/12065559/"}],"tags":[],"related":[],"cancers":["leiomyosarcoma"],"sections":[],"technologies":[],"targets":[],"drugs":["docetaxel","gemcitabine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2002,"doi":"10.1200/JCO.2002.11.050","pmid":"12065559","authors":"Hensley ML, Maki R, Venkatraman E, et al.","paperType":"observational","findings":["Objective response 53 percent (18 of 34).","Responses in patients with prior doxorubicin exposure."],"whatItMeans":"Gemcitabine-docetaxel is a standard first- or second-line option for leiomyosarcoma, especially uterine, and remains in use alongside doxorubicin-based regimens.","caveats":["Single-arm study; randomised trials (GeDDiS) later found gemcitabine-docetaxel no better than doxorubicin first line."],"changedPractice":true,"participants":34},{"id":"paper-seddon-lancet-oncol","kind":"paper","name":"Gemcitabine and docetaxel versus doxorubicin as first-line treatment in previously untreated advanced unresectable or metastatic soft-tissue sarcomas (GeDDiS): a randomised controlled phase 3 trial","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 28882536 and published in The Lancet Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background: For many years, first-line treatment for locally advanced or metastatic soft-tissue sarcoma has been doxorubicin. This study compared gemcitabine and docetaxel versus doxorubicin as first-line treatment for advanced or metastatic soft-tissue sarcoma.\n\nMethods: The GeDDiS trial was a randomised controlled phase 3 trial done in 24 UK hospitals and one Swiss Group for Clinical Cancer Research (SAKK) hospital. Eligible patients had histologically confirmed locally advanced or metastatic soft-tissue sarcoma of Trojani grade 2 or 3, disease progression before enrolment, and no previous chemotherapy for sarcoma or previous doxorubicin for any cancer. Patients were randomly assigned 1:1 to receive six cycles of intravenous doxorubicin 75 mg/m 2 on day 1 every 3 weeks, or intravenous gemcitabine 675 mg/m 2 on days 1 and 8 and intravenous docetaxel 75 mg/m 2 on day 8 every 3 weeks. Treatment was assigned using a minimisation algorithm incorporating a random element. Randomisation was stratified by age (≤18 years vs >18 years) and histological subtype. The primary endpoint was the proportion of patients alive and progression free at 24 weeks in the intention-to-treat population. Adherence to treatment and toxicity were analysed in the safety population, consisting of all patients who received at least one dose of their randomised treatment. The trial was registered with the European Clinical Trials (EudraCT) database (no 2009-014907-29) and with the International Standard Randomised Controlled Trial registry (ISRCTN07742377), and is now closed to patient entry.\n\nFindings: Between Dec 3, 2010, and Jan 20, 2014, 257 patients were enrolled and randomly assigned to the two treatment groups (129 to doxorubicin and 128 to gemcitabine and docetaxel). Median follow-up was 22 months (IQR 15·7-29·3). The proportion of patients alive and progression free at 24 weeks did not differ between those who received doxorubicin versus those who received gemcitabine and docetaxel (46·3% [95% CI 37·5-54·6] vs 46·4% [37·5-54·8]); median progression-free survival (23·3 weeks [95% CI 19·6-30·4] vs 23·7 weeks [18·1-20·0]; hazard ratio [HR] for progression-free survival 1·28, 95% CI 0·99-1·65, p=0·06). The most common grade 3 and 4 adverse events were neutropenia (32 [25%] of 128 patients who received doxorubicin and 25 [20%] of 126 patients who received gemcitabine and docetaxel), febrile neutropenia (26 [20%] and 15 [12%]), fatigue (eight [6%] and 17 [14%]), oral mucositis (18 [14%] and two [2%]), and pain (ten [8%] and 13 [10%]). The three most common serious adverse events, representing 111 (39%) of all 285 serious adverse events recorded, were febrile neutropenia (27 [17%] of 155 serious adverse events in patients who received doxorubicin and 15 [12%] of 130 serious adverse events in patients who received gemcitabine and docetaxel, fever (18 [12%] and 19 [15%]), and neutropenia (22 [14%] and ten [8%]). 154 (60%) of 257 patients died in the intention-to-treat population: 74 (57%) of 129 patients in the doxorubicin group and 80 (63%) of 128 in the gemcitabine and docetaxel group. No deaths were related to the treatment, but two deaths were due to a combination of disease progression and treatment.\n\nInterpretation: Doxorubicin should remain the standard first-line treatment for most patients with advanced soft-tissue sarcoma. These results provide evidence for clinicians to consider with their patients when selecting first-line treatment for locally advanced or metastatic soft-tissue sarcoma.\n\nFunding: Cancer Research UK, Sarcoma UK, and Clinical Trial Unit Kantonsspital St Gallen.\n\nIndexed on Europe PMC as PubMed record 28882536 (DOI 10.1016/s1470-2045(17)30622-8). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2017","url":"https://doi.org/10.1016/s1470-2045(17)30622-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28882536/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28882536"}],"tags":["europepmc-ingest"],"related":["uterine-sarcoma"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2017,"doi":"10.1016/s1470-2045(17)30622-8","pmid":"28882536","authors":"Seddon B, Strauss SJ, Whelan J, et al.","paperType":"rct","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-zhang-gemcitabine-cisplatin-vs-fluorouracil-cisplatin-rm-npc-lancet-2016","kind":"paper","name":"Gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma","aka":[],"tldr":"The first phase 3 trial in metastatic nasopharyngeal cancer found gemcitabine with cisplatin held the disease back for longer than the older fluorouracil-cisplatin combination, and it became the chemotherapy backbone to which immunotherapy was later added.","summary":"Chinese multicentre open-label randomised phase 3 trial of 362 patients with recurrent or metastatic nasopharyngeal carcinoma assigned to gemcitabine plus cisplatin or fluorouracil plus cisplatin for up to six cycles.\n\nMedian progression-free survival was 7.0 months with gemcitabine-cisplatin against 5.6 months (hazard ratio 0.55), with a higher response rate and a later overall survival advantage; toxicity profiles differed (myelosuppression versus mucositis).","asOf":"2026-09-18","links":[{"label":"Lancet 2016","url":"https://doi.org/10.1016/S0140-6736(16)31388-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27567279/"}],"tags":[],"related":[],"cancers":["recurrent-metastatic-nasopharyngeal-carcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":["gemcitabine-cisplatin","fluorouracil","cisplatin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2016,"doi":"10.1016/S0140-6736(16)31388-5","pmid":"27567279","authors":"Zhang L, Huang Y, Hong S, et al.","paperType":"rct","findings":["Median progression-free survival 7.0 months with gemcitabine-cisplatin versus 5.6 months with fluorouracil-cisplatin; hazard ratio 0.55.","Higher objective response rate with gemcitabine-cisplatin."],"whatItMeans":"Gemcitabine and cisplatin is the first-line chemotherapy for recurrent or metastatic nasopharyngeal carcinoma and the backbone of the toripalimab, camrelizumab and tislelizumab combinations.","caveats":["Open-label; conducted entirely in China.","Median survival remained under two years with chemotherapy alone."],"changedPractice":true,"participants":362},{"id":"paper-gap-phase2-mdacc-jama-oncol-2019","kind":"paper","name":"Gemcitabine, Cisplatin, and nab-Paclitaxel for the Treatment of Advanced Biliary Tract Cancers: A Phase 2 Clinical Trial","aka":[],"tldr":"Published report from the cisplatin and nab-paclitaxel phase 2 trial registered as NCT02392637, in JAMA Oncology (2019), chosen as the most cited paper whose own text cites the registry id.","summary":"Importance: Administration of gemcitabine-cisplatin, the current standard therapy for advanced biliary tract cancers, results in median progression-free survival and overall survival of 8.0 and 11.7 months, respectively. New treatments offering improved survival outcomes are therefore needed.\n\nObjective: To evaluate the association between progression-free survival and the addition of nanoparticle albumin-bound (nab)-paclitaxel to gemcitabine-cisplatin for the treatment of patients with advanced biliary tract cancer.\n\nDesign, setting, and participants: This open-label, single-arm, phase 2 clinical trial conducted at the University of Texas MD Anderson Cancer Center and the Mayo Clinic in Phoenix, Arizona, enrolled 62 patients with advanced biliary tract cancers between April 14, 2015, and April 24, 2017.\n\nInterventions: Patients initially received gemcitabine, 1000 mg/m2, cisplatin, 25 mg/m2, and nab-paclitaxel, 125 mg/m2, on days 1 and 8 of 21-day cycles. Owing to hematologic adverse events among the first 32 patients enrolled, these starting doses were reduced to 800, 25, and 100 mg/m2, respectively, for the remaining 28 patients.\n\nMain outcomes and measures: The primary trial end point was investigator-assessed progression-free survival in the intention-to-treat population.\n\nResults: Of 60 patients who started treatment, the mean (SD) age was 58.4 (11.0) years, 38 (63%) had intrahepatic cholangiocarcinoma, 9 (15%) had extrahepatic cholangiocarcinoma, 13 (22%) had gallbladder cancer, 47 (78%) had metastatic disease, and 13 (22%) had locally advanced disease. Median follow-up was 12.2 (95% CI, 9.4-19.4) months, and median progression-free survival was 11.8 (95% CI, 6.0 to 15.6) months. The partial response rate was 45%, and the disease control rate was 84%. Median overall survival was 19.2 months (95% CI, 13.2 months to not estimable). Patients in the safety population (n = 57) received a median of 6 (interquartile range, 3-11) cycles of treatment; 26 patients (46%) remained on their starting dose throughout the trial. Grade 3 or higher adverse events occurred in 58% of patients, and 9 patients (16%) withdrew owing to adverse events. Neutropenia was the most common grade 3 or higher adverse event, occurring in 19 patients (33%) overall. Post hoc analyses showed that treatment efficacy was not significantly associated with starting dose, tumor type, or disease status and that tolerability was improved with reduced- vs high-dose treatment.\n\nConclusions and relevance: Treatment with nab-paclitaxel plus gemcitabine-cisplatin prolonged median progression-free survival and overall survival vs those reported for historical controls treated with gemcitabine-cisplatin alone. These findings will be tested in a phase 3 randomized clinical trial.\n\nTrial registration: ClinicalTrials.gov identifier: NCT02392637.\n\nIndexed on Europe PMC as PubMed record 30998813 (DOI 10.1001/jamaoncol.2019.0270). Its abstract cites the registry id NCT02392637, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"JAMA Oncol 2019","url":"https://doi.org/10.1001/jamaoncol.2019.0270"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30998813/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30998813"},{"label":"ClinicalTrials.gov NCT02392637","url":"https://clinicaltrials.gov/study/NCT02392637"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["gap-phase2-mdacc"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2019,"doi":"10.1001/jamaoncol.2019.0270","pmid":"30998813","authors":"Shroff RT, Javle MM, Xiao L, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02392637 with the most citations, so it is the natural first reading for anyone following the cisplatin and nab-paclitaxel phase 2 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-sorlie-breast-carcinoma-subclasses-pnas-2001","kind":"paper","name":"Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications","aka":[],"tldr":"The 2001 follow-up showing that the gene-expression groups of breast cancer predict how patients fare, with the basal-like group doing worst; it made the subtypes clinical rather than descriptive.","summary":"Sørlie, Perou, Tibshirani, Aas and colleagues analysed 85 cDNA microarray experiments representing 78 cancers, three fibroadenomas and four normal breast tissues by hierarchical clustering. As reported earlier, the cancers separated into a basal epithelial-like group, an ERBB2-overexpressing group and a normal breast-like group; the luminal, oestrogen receptor-positive group divided into at least two subgroups with distinct profiles. The subtypes were robust to two gene sets (456 intrinsic clones and an outcome-correlated set). In a subcohort of locally advanced cancers treated uniformly in a prospective study, outcomes differed significantly by group, with shorter survival for the basal-like subtype and a difference between the two oestrogen receptor-positive groups.","asOf":"2026-09-24","links":[{"label":"Proc Natl Acad Sci 2001","url":"https://doi.org/10.1073/pnas.191367098"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/11553815/"}],"tags":["tnbc-evidence"],"related":["paper-perou-molecular-portraits-breast-tumours-nature-2000"],"cancers":["tnbc","breast-hr-positive","breast-her2-positive"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["pam50"],"trials":[],"people":["charles-perou"],"bottlenecks":[],"keyPapers":[],"journals":["pnas"],"dependsOn":[],"notes":[],"journal":"Proceedings of the National Academy of Sciences","year":2001,"doi":"10.1073/pnas.191367098","pmid":"11553815","authors":"Sørlie T, Perou CM, Tibshirani R, et al.","paperType":"translational","findings":["78 cancers clustered into basal-like, ERBB2-overexpressing, normal-like and at least two luminal subgroups.","Significantly different outcomes by subtype in uniformly treated locally advanced disease; basal-like had shorter survival."],"whatItMeans":"The first evidence that the basal-like group is not just biologically distinct but clinically dangerous, the observation that triple-negative outcome studies of 2007 confirmed in the clinic.","caveats":["Survival analysis on a subcohort of locally advanced disease.","Microarray platforms of the period; subtype calls were later standardised as PAM50."],"changedPractice":true,"participants":78},{"id":"paper-delattre-nature","kind":"paper","name":"Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours","aka":[],"tldr":"Paper cited by one target page, indexed on Europe PMC as PubMed record 1522903 and published in Nature; the citing page links this DOI, which is how the record was matched.","summary":"Ewing's sarcoma and related subtypes of primitive neuroectodermal tumours share a recurrent and specific t(11;22) (q24;q12) chromosome translocation, the breakpoints of which have recently been cloned. Phylogenetically conserved restriction fragments in the vicinity of EWSR1 and EWSR2, the genomic regions where the breakpoints of chromosome 22 and chromosome 11 are, respectively, have allowed identification of transcribed sequences from these regions and has indicated that a hybrid transcript might be generated by the translocation. Here we use these fragments to screen human complementary DNA libraries to show that the translocation alters the open reading frame of an expressed gene on chromosome 22 gene by substituting a sequence encoding a putative RNA-binding domain for that of the DNA-binding domain of the human homologue of murine Fli-1.\n\nIndexed on Europe PMC as PubMed record 1522903 (DOI 10.1038/359162a0). Matched by DOI alone: one target page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 1992","url":"https://doi.org/10.1038/359162a0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/1522903/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/1522903"}],"tags":["europepmc-ingest"],"related":["ewsr1-fli1"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":1992,"doi":"10.1038/359162a0","pmid":"1522903","authors":"Delattre O, Zucman J, Plougastel B, et al.","paperType":"basic","findings":[],"whatItMeans":"One target page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-minn-nature","kind":"paper","name":"Genes that mediate breast cancer metastasis to lung","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 16049480 and published in Nature; the citing page links this DOI, which is how the record was matched.","summary":"By means of in vivo selection, transcriptomic analysis, functional verification and clinical validation, here we identify a set of genes that marks and mediates breast cancer metastasis to the lungs. Some of these genes serve dual functions, providing growth advantages both in the primary tumour and in the lung microenvironment. Others contribute to aggressive growth selectively in the lung. Many encode extracellular proteins and are of previously unknown relevance to cancer metastasis.\n\nIndexed on Europe PMC as PubMed record 16049480 (DOI 10.1038/nature03799). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2005","url":"https://doi.org/10.1038/nature03799"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/16049480/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/16049480"}],"tags":["europepmc-ingest"],"related":["seed-and-soil-hypothesis"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2005,"doi":"10.1038/nature03799","pmid":"16049480","authors":"Minn AJ, Gupta GP, Siegel PM, et al.","paperType":"basic","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-vogelstein-genetic-alterations-colorectal-tumor-development-nejm-1988","kind":"paper","name":"Genetic alterations during colorectal-tumor development","aka":[],"tldr":"The 1988 study of 172 bowel tumours that showed cancer is not one mutation but a sequence of them, accumulating as a polyp grows into a cancer. It is the origin of the idea that cancer develops step by step.","summary":"Vogelstein, Fearon, Hamilton, Kern, Preisinger, Leppert, Nakamura, White, Smits and Bos looked for four genetic alterations (ras-gene mutations and allelic deletions of chromosomes 5, 17 and 18) in 172 colorectal-tumour specimens representing different stages of neoplastic development: 40 predominantly early-stage adenomas from seven patients with familial adenomatous polyposis, 40 adenomas from 33 patients without polyposis (19 without and 21 with associated foci of carcinoma), and 92 carcinomas resected from 89 patients.\n\nThe four alterations accumulated in a way that paralleled the clinical progression of the tumours, and the authors concluded that the steps to cancer often involve mutational activation of an oncogene coupled with the loss of several genes that normally suppress tumourigenesis. Fearon and Vogelstein set the model out in full two years later in Cell (the corpus holds that record as paper-fearon-cell).","asOf":"2026-09-24","links":[{"label":"N Engl J Med 1988","url":"https://doi.org/10.1056/NEJM198809013190901"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/2841597/"},{"label":"Fearon and Vogelstein: a genetic model for colorectal tumorigenesis (Cell 1990)","url":"https://doi.org/10.1016/0092-8674(90)90186-I"}],"tags":["colorectal-evidence"],"related":["paper-fearon-cell","paper-vogelstein-cancer-genome-landscapes-science-2013","paper-tcga-colorectal-comprehensive-characterization-nature-2012"],"cancers":["colorectal","colon-cancer"],"sections":["early-detection","prevention"],"technologies":["colorectal-screening"],"targets":["kras","tp53","apc","smad4"],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":["wnt","ras-mapk","colorectal-cancer-signalling","chromosomal-instability"],"terms":["driver-mutation"],"trials":[],"people":["bert-vogelstein","kenneth-kinzler","eric-fearon"],"bottlenecks":["b-early-detection","b-prevention-adoption"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":1988,"doi":"10.1056/NEJM198809013190901","pmid":"2841597","authors":"Vogelstein B, Fearon ER, Hamilton SR, et al.","paperType":"basic","findings":["ras-gene mutations in 58 percent of adenomas larger than 1 cm and 47 percent of carcinomas, but only 9 percent of adenomas under 1 cm.","Chromosome 5 sequences linked to the familial adenomatous polyposis gene were not lost in adenomas from polyposis patients but were lost in 29 to 35 percent of adenomas and carcinomas from others.","A specific region of chromosome 18 was deleted in 73 percent of carcinomas, 47 percent of advanced adenomas and only 11 to 13 percent of earlier-stage adenomas.","Chromosome 17p sequences were usually lost only in carcinomas (75 percent).","The four alterations accumulated in a fashion that paralleled clinical progression."],"whatItMeans":"Every screening programme rests on this paper: if cancer arrives through a polyp that takes years to progress, then finding and removing polyps prevents cancer rather than merely catching it early.","caveats":["Four markers in tumours collected in the 1980s; the full driver set (APC, KRAS, SMAD4, TP53, PIK3CA and the rest) came from the sequencing studies two decades later.","The sequence is typical, not obligatory: the serrated and mismatch repair-deficient routes to colorectal cancer do not follow it."],"changedPractice":true,"participants":172},{"id":"paper-lengauer-genetic-instability-colorectal-nature-1997","kind":"paper","name":"Genetic instability in colorectal cancers","aka":[],"tldr":"Colorectal cancers come in two unstable flavours: a few cannot spell-check their DNA, and most cannot divide their chromosomes evenly. This paper measured the second kind for the first time and showed it is a real, continuing defect rather than an accident.","summary":"Colorectal tumours without microsatellite instability were shown to have a striking defect in chromosome segregation, producing gains or losses in excess of 10^-2 per chromosome per generation. The instability reflected a continuing cellular defect that persisted throughout the lifetime of the tumour cell and was not simply a function of chromosome number. Microsatellite instability behaved as a recessive trait in cell fusion experiments, while chromosomal instability behaved as a dominant one. The authors concluded that persistent genetic instability may be necessary for the development of all colorectal cancers and that it arises through two distinct pathways.","asOf":"2026-09-24","links":[{"label":"Lengauer, Kinzler and Vogelstein, Nature 1997: two distinct forms of genetic instability in colorectal cancer","url":"https://doi.org/10.1038/386623a0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/9121588/"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":["chromosomal-instability","mismatch-repair-msi"],"terms":["msi","copy-number-variation-term"],"trials":[],"people":["bert-vogelstein","kenneth-kinzler"],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":1997,"doi":"10.1038/386623a0","pmid":"9121588","authors":"Lengauer C, Kinzler KW, Vogelstein B.","paperType":"basic","findings":["Chromosome gains or losses above 10^-2 per chromosome per generation in microsatellite-stable lines.","Chromosomal instability is dominant, microsatellite instability recessive, in cell fusions."],"whatItMeans":"It split colorectal cancer into the two instability classes the field still uses, and made the chromosomal class a phenotype to be explained rather than background noise.","caveats":["Cell lines, not tumours in patients.","The molecular cause of chromosomal instability is still not settled."],"changedPractice":false},{"id":"paper-duesberg-proc-natl-acad-sci-u-s-a","kind":"paper","name":"Genetic instability of cancer cells is proportional to their degree of aneuploidy","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 9811862 and published in Proceedings of the National Academy of Sciences; the citing page links this DOI, which is how the record was matched.","summary":"Genetic and phenotypic instability are hallmarks of cancer cells, but their cause is not clear. The leading hypothesis suggests that a poorly defined gene mutation generates genetic instability and that some of many subsequent mutations then cause cancer. Here we investigate the hypothesis that genetic instability of cancer cells is caused by aneuploidy, an abnormal balance of chromosomes. Because symmetrical segregation of chromosomes depends on exactly two copies of mitosis genes, aneuploidy involving chromosomes with mitosis genes will destabilize the karyotype. The hypothesis predicts that the degree of genetic instability should be proportional to the degree of aneuploidy. Thus it should be difficult, if not impossible, to maintain the particular karyotype of a highly aneuploid cancer cell on clonal propagation. This prediction was confirmed with clonal cultures of chemically transformed, aneuploid Chinese hamster embryo cells. It was found that the higher the ploidy factor of a clone, the more unstable was its karyotype. The ploidy factor is the quotient of the modal chromosome number divided by the normal number of the species. Transformed Chinese hamster embryo cells with a ploidy factor of 1.7 were estimated to change their karyotype at a rate of about 3% per generation, compared with 1.8% for cells with a ploidy factor of 0.95. Because the background noise of karyotyping is relatively high, the cells with low ploidy factor may be more stable than our method suggests. The karyotype instability of human colon cancer cell lines, recently analyzed by Lengnauer et al. [Lengnauer, C., Kinzler, K. W. & Vogelstein, B. (1997) Nature (London) 386, 623-627], also corresponds exactly to their degree of aneuploidy. We conclude that aneuploidy is sufficient to explain genetic instability and the resulting karyotypic and phenotypic heterogeneity of cancer cells, independent of gene mutation. Because aneuploidy has also been proposed to cause cancer, our hypothesis offers a common, unique mechanism of altering and simultaneously destabilizing normal cellular phenotypes.\n\nIndexed on Europe PMC as PubMed record 9811862 (DOI 10.1073/pnas.95.23.13692). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Proc Natl Acad Sci U S A 1998","url":"https://doi.org/10.1073/pnas.95.23.13692"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/9811862/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/9811862"}],"tags":["europepmc-ingest"],"related":["aneuploidy-theory-of-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["pnas"],"dependsOn":[],"notes":[],"journal":"Proceedings of the National Academy of Sciences","year":1998,"doi":"10.1073/pnas.95.23.13692","pmid":"9811862","authors":"Duesberg P, Rausch C, Rasnick D, et al.","paperType":"basic","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-grasso-immune-evasion-colorectal-cancer-discov-2018","kind":"paper","name":"Genetic mechanisms of immune evasion in colorectal cancer","aka":[],"tldr":"Even the bowel cancers that immunotherapy can cure have often already learned to hide: across 1,211 tumours, the highly mutated ones had frequently destroyed the machinery that displays their abnormal proteins to the immune system.","summary":"1,211 colorectal cancer primary tumour samples were analysed, including 179 classified as microsatellite instability-high and the completed TCGA cohort of 592. MSI-high tumours had a high rate of significantly mutated genes in immune-modulating pathways and in the antigen presentation machinery, including biallelic losses of B2M and HLA genes through copy-number alteration and copy-neutral loss of heterozygosity. WNT and beta-catenin signalling genes were significantly mutated in all subtypes, and activated WNT signalling correlated with the absence of T-cell infiltration. The authors concluded that MSI-high cancers frequently undergo immunoediting that lets them escape despite high mutational load and frequent lymphocytic infiltration, and that WNT-driven T-cell exclusion may be reversible.","asOf":"2026-09-24","links":[{"label":"Grasso et al., Cancer Discov 2018: genetic mechanisms of immune evasion in 1,211 colorectal cancers","url":"https://doi.org/10.1158/2159-8290.CD-17-1327"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29510987/"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":[],"targets":["b2m","apc","ctnnb1","mmr"],"drugs":[],"companies":[],"institutions":["dana-farber","ucsf"],"pathways":["antigen-presentation-immunoediting","immune-desert-exclusion","wnt"],"terms":["neoantigen","msi","immune-exclusion","cold-vs-hot"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-discovery"],"dependsOn":[],"notes":[],"journal":"Cancer Discovery","year":2018,"doi":"10.1158/2159-8290.CD-17-1327","pmid":"29510987","authors":"Grasso CS, Giannakis M, Wells DK, et al.","paperType":"translational","findings":["Biallelic B2M and HLA loss in MSI-high tumours through copy-number change and copy-neutral loss of heterozygosity.","WNT and beta-catenin pathway mutation in every subtype, correlated with the absence of T-cell infiltration."],"whatItMeans":"It gives a genetic account of both immunotherapy failures: why some mismatch repair deficient tumours resist, and why the microsatellite-stable majority has no T cells in it to begin with.","caveats":["Primary tumours, not samples taken at the point of checkpoint inhibitor failure.","The WNT-to-exclusion link is correlative in patients and mechanistic only in models."],"changedPractice":false,"participants":1211},{"id":"paper-schmitz-genetics-pathogenesis-dlbcl-nejm-2018","kind":"paper","name":"Genetics and pathogenesis of diffuse large B-cell lymphoma","aka":["Schmitz 2018","MCD, BN2, N1 and EZB subtypes","National Cancer Institute genetic subtypes"],"tldr":"Sequencing 574 lymphomas found four genetic patterns that recur, two of which depend on a signalling route that an existing tablet can block.","summary":"Schmitz, Staudt and colleagues studied 574 diffuse large B-cell lymphoma biopsy samples by exome and transcriptome sequencing, array copy-number analysis and targeted resequencing of 372 genes, and built an algorithm that discovers subtypes from the co-occurrence of genetic alterations rather than from expression alone.\n\nFour genetic subtypes emerged, each named for the alterations that define it: MCD, for co-occurring MYD88 L265P and CD79B mutations; BN2, for BCL6 fusions and NOTCH2 mutations; N1, for NOTCH1 mutations; and EZB, for EZH2 mutations and BCL2 translocations. They differed in gene-expression signature and in response to immunochemotherapy, with favourable survival in BN2 and EZB and inferior outcomes in MCD and N1.\n\nThe therapeutic reading is the point of the paper. MCD and BN2 tumours appear to depend on chronic active B-cell receptor signalling, which Bruton tyrosine kinase inhibitors block. That is the mechanistic argument behind the small group of patients in whom ibrutinib added to R-CHOP produced long remissions in the otherwise negative PHOENIX trial, and behind the current generation of genetics-directed trials.","asOf":"2026-10-01","links":[{"label":"New England Journal of Medicine 2018","url":"https://doi.org/10.1056/NEJMoa1801445"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29641966/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29641966"}],"tags":["lymphoma-evidence"],"related":["paper-chapuy-molecular-subtypes-dlbcl-nat-med-2018","paper-wright-lymphgen-genetic-subtypes-dlbcl-cancer-cell-2020","paper-phoenix-ibrutinib-r-chop-non-gcb-dlbcl-jco-2019","lymphoma-roadmap"],"cancers":["dlbcl","non-hodgkin-lymphoma"],"sections":["diagnostics","targeted-therapy","drug-discovery"],"technologies":["wes-wgs","ngs"],"targets":["myd88","cd79b","bcl6","notch1","notch2","ezh2","bcl2","btk"],"drugs":[],"companies":[],"institutions":["nci"],"pathways":["bcr-signalling"],"terms":["cell-of-origin"],"trials":["phoenix","arched"],"people":["louis-staudt"],"bottlenecks":["b-tumor-heterogeneity","b-biomarker-validation","b-trial-design"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2018,"doi":"10.1056/NEJMoa1801445","pmid":"29641966","authors":"Schmitz R, Wright GW, Huang DW, et al.","paperType":"basic","findings":["Four genetic subtypes of diffuse large B-cell lymphoma were identified from 574 biopsy samples: MCD (MYD88 L265P with CD79B mutations), BN2 (BCL6 fusions with NOTCH2 mutations), N1 (NOTCH1 mutations) and EZB (EZH2 mutations with BCL2 translocations).","The subtypes differed in gene-expression signature and in response to immunochemotherapy.","Survival was favourable in the BN2 and EZB subtypes and inferior in MCD and N1.","Pathway analysis suggested that MCD and BN2 lymphomas rely on chronic active B-cell receptor signalling, which is amenable to therapeutic inhibition."],"whatItMeans":"The genetic nosology that precision-medicine trials in diffuse large B-cell lymphoma now use to pick patients. It gives a mechanism, not just a label: two of the four subtypes point at a drug class that already exists.","caveats":["Published within weeks of Chapuy's five-cluster classification from a different cohort using a different algorithm; the two agree in part and disagree in part, and reconciling them took two further years.","A substantial minority of tumours fit none of the four subtypes and are left unclassified.","Outcome differences come from retrospective cohorts treated with R-CHOP, not from a trial that assigned treatment by subtype.","The B-cell receptor dependency is inferred from pathway analysis and cell-line models rather than demonstrated in patients by this paper."],"changedPractice":false,"participants":574},{"id":"paper-bielski-nat-genet","kind":"paper","name":"Genome doubling shapes the evolution and prognosis of advanced cancers","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 30013179 and published in Nature Genetics; the citing page links this DOI, which is how the record was matched.","summary":"Ploidy abnormalities are a hallmark of cancer, but their impact on the evolution and outcomes of cancers is unknown. Here, we identified whole-genome doubling (WGD) in the tumors of nearly 30% of 9,692 prospectively sequenced advanced cancer patients. WGD varied by tumor lineage and molecular subtype, and arose early in carcinogenesis after an antecedent transforming driver mutation. While associated with TP53 mutations, 46% of all WGD arose in TP53-wild-type tumors and in such cases was associated with an E2F-mediated G1 arrest defect, although neither aberration was obligate in WGD tumors. The variability of WGD across cancer types can be explained in part by cancer cell proliferation rates. WGD predicted for increased morbidity across cancer types, including KRAS-mutant colorectal cancers and estrogen receptor-positive breast cancers, independently of established clinical prognostic factors. We conclude that WGD is highly common in cancer and is a macro-evolutionary event associated with poor prognosis across cancer types.\n\nIndexed on Europe PMC as PubMed record 30013179 (DOI 10.1038/s41588-018-0165-1). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Genet 2018","url":"https://doi.org/10.1038/s41588-018-0165-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30013179/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30013179"}],"tags":["europepmc-ingest"],"related":["whole-genome-doubling"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":2018,"doi":"10.1038/s41588-018-0165-1","pmid":"30013179","authors":"Bielski CM, Zehir A, Penson AV, et al.","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-bailey-molecular-subtypes-pancreatic-nature-2016","kind":"paper","name":"Genomic analyses identify molecular subtypes of pancreatic cancer","aka":[],"tldr":"The 2016 analysis of 456 pancreatic cancers that grouped 32 recurrently mutated genes into ten pathways and defined four expression subtypes, of which the squamous type has the worst prognosis.","summary":"Bailey and colleagues of the Australian Pancreatic Cancer Genome Initiative integrated genomic analysis of 456 pancreatic ductal adenocarcinomas. Thirty-two recurrently mutated genes aggregated into ten pathways: KRAS, TGF-beta, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined four subtypes: squamous (enriched for TP53 and KDM6A mutations, TP63 network upregulation and hypermethylation of pancreatic endodermal cell-fate genes, with shorter survival), pancreatic progenitor (FOXA2/3, PDX1, MNX1), immunogenic (upregulated immune networks including acquired immune suppression) and aberrantly differentiated endocrine exocrine (ADEX; KRAS activation, exocrine and endocrine differentiation networks). The subtypes correlate with histopathology and, the authors argue, identify opportunities for therapeutic development.","asOf":"2026-09-24","links":[{"label":"Nature 2016","url":"https://doi.org/10.1038/nature16965"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26909576/"},{"label":"cBioPortal study paad_qcmg_uq_2016 (QCMG, Nature 2016; 456 samples, 383 sequenced, no copy-number profile)","url":"https://www.cbioportal.org/study/summary?id=paad_qcmg_uq_2016"}],"tags":["pancreatic-evidence"],"related":["paper-waddell-whole-genomes-pancreatic-nature-2015","paper-moffitt-virtual-microdissection-subtypes-nat-genet-2015"],"cancers":["pancreatic"],"sections":[],"technologies":["wes-wgs","rna-seq"],"targets":["kras","tp53","kdm6a","smad4","cdkn2a","rnf43","arid1a"],"drugs":[],"companies":[],"institutions":["garvan-institute","beatson-glasgow"],"pathways":["ras-mapk","tgf-beta","ddr","pancreatic-cancer-signalling","wnt","notch","swi-snf-chromatin","epigenetic-reprogramming"],"terms":["somatic-mutations-wxs-wgs"],"trials":[],"people":["owen-sansom"],"bottlenecks":["b-tumor-heterogeneity"],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2016,"doi":"10.1038/nature16965","pmid":"26909576","authors":"Bailey P, Chang DK, Nones K, et al.","paperType":"basic","findings":["456 tumours; 32 recurrently mutated genes in 10 pathways.","Four expression subtypes: squamous, pancreatic progenitor, immunogenic, ADEX.","Squamous tumours carry TP53 and KDM6A mutations and have shorter survival."],"whatItMeans":"With Moffitt's classical and basal-like split (the squamous and basal-like groups overlap) this fixed the molecular vocabulary of the disease and gave Precision-Panc and the UK's Glasgow group their trial framework.","caveats":["The ADEX and immunogenic subtypes may partly reflect normal pancreas and immune cells in the sample rather than tumour biology.","Subtype has not yet been used to choose treatment in a positive randomised trial."],"participants":456},{"id":"paper-bonilla-nat-genet","kind":"paper","name":"Genomic analysis identifies new drivers and progression pathways in skin basal cell carcinoma","aka":[],"tldr":"Paper cited by one target page, indexed on Europe PMC as PubMed record 26950094 and published in Nature Genetics; the citing page links this DOI, which is how the record was matched.","summary":"Basal cell carcinoma (BCC) of the skin is the most common malignant neoplasm in humans. BCC is primarily driven by the Sonic Hedgehog (Hh) pathway. However, its phenotypic variation remains unexplained. Our genetic profiling of 293 BCCs found the highest mutation rate in cancer (65 mutations/Mb). Eighty-five percent of the BCCs harbored mutations in Hh pathway genes (PTCH1, 73% or SMO, 20% (P = 6.6 × 10(-8)) and SUFU, 8%) and in TP53 (61%). However, 85% of the BCCs also harbored additional driver mutations in other cancer-related genes. We observed recurrent mutations in MYCN (30%), PPP6C (15%), STK19 (10%), LATS1 (8%), ERBB2 (4%), PIK3CA (2%), and NRAS, KRAS or HRAS (2%), and loss-of-function and deleterious missense mutations were present in PTPN14 (23%), RB1 (8%) and FBXW7 (5%). Consistent with the mutational profiles, N-Myc and Hippo-YAP pathway target genes were upregulated. Functional analysis of the mutations in MYCN, PTPN14 and LATS1 suggested their potential relevance in BCC tumorigenesis.\n\nIndexed on Europe PMC as PubMed record 26950094 (DOI 10.1038/ng.3525). Matched by DOI alone: one target page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Genet 2016","url":"https://doi.org/10.1038/ng.3525"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26950094/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26950094"}],"tags":["europepmc-ingest"],"related":["smoothened"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":2016,"doi":"10.1038/ng.3525","pmid":"26950094","authors":"Bonilla X, Parmentier L, King B, et al.","paperType":"observational","findings":[],"whatItMeans":"One target page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-tukachinsky-ctdna-3334-advanced-prostate-ccr-2021","kind":"paper","name":"Genomic analysis of circulating tumour DNA in 3,334 patients with advanced prostate cancer identifies targetable BRCA alterations and AR resistance mechanisms","aka":[],"tldr":"The largest blood-based study in advanced prostate cancer found detectable tumour DNA in nineteen men out of twenty, agreed with tissue on BRCA faults nine times out of ten, and found resistance changes tissue had missed.","summary":"Using plasma from 3,334 men with metastatic castration-resistant prostate cancer, including 1,674 screening samples from the TRITON2 and TRITON3 trials, the landscape of genomic alterations detectable in circulating tumour DNA was evaluated and compared with tissue-based profiling. Three thousand one hundred and twenty-nine men, 94%, had detectable circulating tumour DNA, at a median tumour fraction of 7.5%, and BRCA1 or BRCA2 was mutated in 295, 8.8%. In the concordance analysis, 72 of 837 men had BRCA1 or BRCA2 mutations detected in tissue, of which 67, 93%, were also identified in circulating tumour DNA, including 100% of the variants predicted to be germline. Circulating tumour DNA harboured some BRCA alterations not identified by tissue testing and was enriched for therapy resistance alterations as well as for possible clonal haematopoiesis mutations, for example in ATM and CHEK2. Potential androgen receptor resistance alterations were detected in 940 of 2,213 men, 42%, including amplifications, polyclonal and compound mutations, rearrangements and novel deletions in exon 8.","asOf":"2026-09-25","links":[{"label":"Tukachinsky et al., Clin Cancer Res 2021: circulating tumour DNA profiling in 3,334 men with advanced prostate cancer, including 1,674 TRITON screening samples","url":"https://doi.org/10.1158/1078-0432.CCR-20-4805"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33558422/"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["liquid-biopsy","cgp"],"targets":["brca","androgen-receptor","atm","chek2"],"drugs":[],"companies":[],"institutions":[],"pathways":["homologous-recombination-repair","ar-signaling","clonal-haematopoiesis","resistance-routes-map"],"terms":["ctdna","cfdna","liquid-biopsy","germline-vs-somatic","gbrca-mutation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2021,"doi":"10.1158/1078-0432.CCR-20-4805","pmid":"33558422","authors":"Tukachinsky H, Madison RW, Chung JH, et al.","paperType":"observational","findings":["Detectable circulating tumour DNA in 3,129 of 3,334 men, 94%, at a median tumour fraction of 7.5%.","BRCA1 or BRCA2 mutated in 295 men, 8.8%.","Ninety-three per cent concordance with tissue for BRCA mutations, including 100% of predicted germline variants.","Potential androgen receptor resistance alterations in 940 of 2,213 men, 42%.","Enrichment for possible clonal haematopoiesis mutations, notably in ATM and CHEK2."],"whatItMeans":"It established plasma profiling as a routine alternative to tissue for the BRCA question in advanced prostate cancer, with a sensible rule attached: if plasma finds nothing actionable, go back to tissue. It also documents at scale both the extra resistance information plasma gives and the clonal haematopoiesis noise that comes with it.","caveats":["Half the cohort came from trial screening, so it is enriched for men being considered for a PARP inhibitor.","One commercial assay, so the performance is that assay's.","The clonal haematopoiesis mutations were inferred rather than confirmed against a paired blood control."],"changedPractice":true,"participants":3334},{"id":"paper-zhang-lung-cancer-never-smokers-nat-genet-2021","kind":"paper","name":"Genomic and evolutionary classification of lung cancer in never smokers","aka":[],"tldr":"The Sherlock-Lung study sequenced 232 lung cancers from people who never smoked and found three distinct types, none of them carrying the tobacco damage signature. One type appears to begin decades before it is diagnosed.","summary":"Zhang, Joubert, Ansari-Pour and colleagues, with Landi as senior author, performed high-coverage whole-genome sequencing of 232 lung cancers in never smokers and defined three subtypes by copy-number aberration, named piano, mezzo-forte and forte.\n\nThe dominant piano subtype is rare in smokers' lung cancer: low mutational burden, high intratumour heterogeneity, long telomeres, frequent KRAS mutations, stem cell-like properties and slow growth, with driver progenitor cells datable to many years before diagnosis. Mezzo-forte carries specific amplifications and EGFR mutations; forte is defined by whole-genome doubling. No strong tobacco smoking signatures were detected, even in cases with secondhand smoke exposure.","asOf":"2026-09-25","links":[{"label":"Nat Genet 2021","url":"https://doi.org/10.1038/s41588-021-00920-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34493867/"},{"label":"Sherlock-Lung study (NCI)","url":"https://dceg.cancer.gov/research/cancer-types/lung/sherlock-lung-study"},{"label":"cBioPortal study lung_nci_2022 (Sherlock-Lung, NCI, Nat Genet 2021; 232 whole genomes of lung cancer in never smokers)","url":"https://www.cbioportal.org/study/summary?id=lung_nci_2022"}],"tags":["lung-evidence"],"related":["paper-hill-lung-adenocarcinoma-air-pollutants-nature-2023","paper-tracerx-100-nejm-2017"],"cancers":["lung-cancer","nsclc","lung-adenocarcinoma"],"sections":["early-detection","diagnostics"],"technologies":["wes-wgs","low-dose-ct-screening"],"targets":["egfr","kras","tp53","alk","her2","met"],"drugs":[],"companies":[],"institutions":["nci"],"pathways":["mutagenesis-signatures","chromosomal-instability","clonal-evolution","rtk-activation","field-cancerisation"],"terms":["clonal-evolution","driver-mutation","mutational-signature","tmb","copy-number-variation-term"],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-tumor-heterogeneity","b-rare-cancers"],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":2021,"doi":"10.1038/s41588-021-00920-0","pmid":"34493867","authors":"Zhang T, Joubert P, Ansari-Pour N, et al.","paperType":"basic","findings":["Three subtypes defined by copy-number aberration across 232 whole genomes: piano, mezzo-forte and forte.","The piano subtype features somatic UBA1 mutations, germline AR variants, stem cell-like properties, low mutational burden, high intratumour heterogeneity, long telomeres and frequent KRAS mutations.","Mezzo-forte is characterised by specific amplifications and EGFR mutations; forte by whole-genome doubling.","No strong tobacco smoking signatures were detected, even in cases with exposure to secondhand tobacco smoke.","Five genomic alterations independently doubled mortality; genes in the receptor tyrosine kinase-Ras pathway had distinct impacts on survival."],"whatItMeans":"Lung cancer in never-smokers is not smokers' lung cancer with the smoking removed; it is a different set of diseases with a different clock. The slow-growing piano subtype in particular is the argument that a screening test aimed at never-smokers would need to look for something other than what low-dose computed tomography was built to find.","caveats":["232 genomes, largely from tissue banks, with the referral patterns that implies; subtype frequencies are not population estimates.","Subtypes are defined by copy-number structure and have no prospective treatment implication yet.","Mutational signature analysis cannot exclude every unrecorded tobacco or environmental exposure."],"changedPractice":false,"participants":232},{"id":"paper-jiang-fuscc-tnbc-landscape-cancer-cell-2019","kind":"paper","name":"Genomic and transcriptomic landscape of triple-negative breast cancers: subtypes and treatment strategies","aka":[],"tldr":"The largest Chinese triple-negative cohort, 465 patients from Fudan, carried more PIK3CA mutations than American tumours and sorted into four subtypes, with the luminal androgen receptor type showing HER2 mutations and CDKN2A loss.","summary":"Clinical, genomic and transcriptomic data of 465 primary TNBCs were analysed. PIK3CA mutations and copy-number gains of chromosome 22q11 were more frequent in the Chinese cohort than in The Cancer Genome Atlas. TNBCs were classified into four transcriptome-based subtypes: luminal androgen receptor (LAR), immunomodulatory, basal-like immune-suppressed and mesenchymal-like, with putative therapeutic targets or biomarkers identified in each. The LAR subtype showed more ERBB2 somatic mutations, infrequent mutational signature 3 and frequent CDKN2A loss.","asOf":"2026-09-24","links":[{"label":"Jiang et al., Cancer Cell 2019: genomic and transcriptomic landscape of 465 Chinese TNBCs (FUSCC)","url":"https://doi.org/10.1016/j.ccell.2019.02.001"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30853353/"}],"tags":[],"related":[],"cancers":["tnbc"],"sections":[],"technologies":[],"targets":["pik3ca","her2","cdkn2a","androgen-receptor"],"drugs":[],"companies":[],"institutions":["zhongshan-hospital-fudan"],"pathways":[],"terms":["mutational-signature"],"trials":[],"people":["jiang-yi-zhou","shao-zhi-ming"],"bottlenecks":[],"keyPapers":[],"journals":["cancer-cell"],"dependsOn":[],"notes":[],"journal":"Cancer Cell","year":2019,"doi":"10.1016/j.ccell.2019.02.001","pmid":"30853353","authors":"Jiang YZ, Ma D, Suo C, et al.","paperType":"translational","findings":["PIK3CA mutations and 22q11 gains more frequent than in TCGA.","Four subtypes: LAR, immunomodulatory, basal-like immune-suppressed, mesenchymal-like.","LAR: more ERBB2 mutations, infrequent signature 3, frequent CDKN2A loss."],"whatItMeans":"The FUSCC cohort is the East Asian reference and the basis of the FUTURE subtype-guided umbrella trial; its LAR findings point to CDK4/6 and HER2-mutant strategies rather than PARP inhibitors for that subtype.","caveats":["Single-institution Chinese cohort; subtype frequencies are not in the abstract and are not quoted here.","Comparison with TCGA mixes sequencing platforms."],"changedPractice":false,"participants":465},{"id":"paper-rodon-nat-med","kind":"paper","name":"Genomic and transcriptomic profiling expands precision cancer medicine: the WINTHER trial","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 31011205 and published in Nature Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Precision medicine focuses on DNA abnormalities, but not all tumors have tractable genomic alterations. The WINTHER trial ( NCT01856296) navigated patients to therapy on the basis of fresh biopsy-derived DNA sequencing (arm A; 236 gene panel) or RNA expression (arm B; comparing tumor to normal). The clinical management committee (investigators from five countries) recommended therapies, prioritizing genomic matches; physicians determined the therapy given. Matching scores were calculated post-hoc for each patient, according to drugs received: for DNA, the number of alterations matched divided by the total alteration number; for RNA, expression-matched drug ranks. Overall, 303 patients consented; 107 (35%; 69 in arm A and 38 in arm B) were evaluable for therapy. The median number of previous therapies was three. The most common diagnoses were colon, head and neck, and lung cancers. Among the 107 patients, the rate of stable disease ≥6 months and partial or complete response was 26.2% (arm A: 23.2%; arm B: 31.6% (P = 0.37)). The patient proportion with WINTHER versus previous therapy progression-free survival ratio of >1.5 was 22.4%, which did not meet the pre-specified primary end point. Fewer previous therapies, better performance status and higher matching score correlated with longer progression-free survival (all P < 0.05, multivariate). Our study shows that genomic and transcriptomic profiling are both useful for improving therapy recommendations and patient outcome, and expands personalized cancer treatment.\n\nIndexed on Europe PMC as PubMed record 31011205 (DOI 10.1038/s41591-019-0424-4). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Med 2019","url":"https://doi.org/10.1038/s41591-019-0424-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31011205/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31011205"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["winther"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2019,"doi":"10.1038/s41591-019-0424-4","pmid":"31011205","authors":"Rodon J, Soria JC, Berger R, et al.","paperType":"observational","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-wardell-biliary-drivers-germline-j-hepatol-2018","kind":"paper","name":"Genomic characterization of biliary tract cancers identifies driver genes and predisposing mutations","aka":[],"tldr":"Sequencing 412 Japanese and Italian biliary cancers, including 66 gallbladder and cystic duct tumours, found 32 driver genes and, unexpectedly, an inherited cancer-predisposing mutation in about one in nine patients.","summary":"412 biliary tract cancer samples from Japanese and Italian populations were analysed, 107 by whole-exome sequencing, 39 by whole-genome sequencing and 266 by targeted sequencing: 136 intrahepatic, 101 distal and 109 perihilar cholangiocarcinomas and 66 gallbladder or cystic duct cancers. Thirty-two significantly and commonly mutated genes were identified, including TP53, KRAS, SMAD4, NF1, ARID1A, PBRM1 and ATR, some of which negatively affected prognosis, and a novel deletion of MUC17 at 7q22.1 affected prognosis.\n\nCell-of-origin predictions using whole-genome and epigenetic features suggested a hepatocyte origin for hepatitis-related intrahepatic cholangiocarcinoma. Deleterious germline mutations of cancer-predisposing genes such as BRCA1, BRCA2, RAD51D, MLH1 or MSH2 were detected in 11% (16 of 146) of patients.","asOf":"2026-09-24","links":[{"label":"Wardell et al., J Hepatol 2018: genomic characterisation of 412 biliary tract cancers","url":"https://doi.org/10.1016/j.jhep.2018.01.009"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29360550/"}],"tags":[],"related":[],"cancers":["gallbladder","cholangiocarcinoma","biliary-tract-cancer"],"sections":[],"technologies":[],"targets":["brca","rad51d","mlh1","msh2","smad4","arid1a","nf1","atr"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["lynch-syndrome","hrd"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of Hepatology","year":2018,"doi":"10.1016/j.jhep.2018.01.009","pmid":"29360550","authors":"Wardell CP, Fujita M, Yamada T, et al.","paperType":"translational","findings":["32 significantly mutated genes including TP53, KRAS, SMAD4, NF1, ARID1A, PBRM1 and ATR.","Deleterious germline variants in BRCA1, BRCA2, RAD51D, MLH1 or MSH2 in 11% (16 of 146) of patients.","A MUC17 deletion at 7q22.1 affected prognosis."],"whatItMeans":"The germline finding is the practical lesson: a meaningful minority of biliary cancer patients carry inherited repair-gene mutations that matter for PARP inhibitor eligibility and for their relatives, which argues for germline testing alongside tumour sequencing.","caveats":["Gallbladder cancers were 66 of 412 and not always reported separately.","Germline analysis covered 146 of the patients."],"changedPractice":false,"participants":412},{"id":"paper-lin-gallbladder-neoplasia-carcinoma-evolution-nat-commun-2021","kind":"paper","name":"Genomic characterization of co-existing neoplasia and carcinoma lesions reveals distinct evolutionary paths of gallbladder cancer","aka":[],"tldr":"Sequencing benign, precancerous and cancerous patches from the same gallbladders showed two ways cancer arises: the textbook stepwise route through adenoma and dysplasia, and an early split in which the cancer evolves on its own after heavy chromosome loss.","summary":"Whole-exome sequencing was performed on co-existing low-grade biliary intraepithelial neoplasia (adenoma), high-grade BilIN and carcinoma lesions, and normal tissues, from the same patients. Ageing was identified as a major factor contributing to accumulated mutations, and CTNNB1 mutations played a critical role in these tumours.\n\nTwo distinct carcinoma evolutionary paths were revealed: carcinoma can either diverge earlier and evolve more independently, or form through the classic adenoma or dysplasia to carcinoma sequence. Extensive loss of heterozygosity and mutation events in the initial stage tended to result in a cancerous niche, leading to the subsequent BilIN-independent path.","asOf":"2026-09-24","links":[{"label":"Lin et al., Nat Commun 2021: co-existing neoplasia and carcinoma lesions of the gallbladder","url":"https://doi.org/10.1038/s41467-021-25012-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34362903/"}],"tags":[],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":["ctnnb1"],"drugs":[],"companies":[],"institutions":[],"pathways":["wnt"],"terms":["metaplasia-dysplasia-carcinoma-sequence","dysplasia"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-communications"],"dependsOn":[],"notes":[],"journal":"Nature Communications","year":2021,"doi":"10.1038/s41467-021-25012-9","pmid":"34362903","authors":"Lin J, Peng X, Dong K, et al.","paperType":"translational","findings":["CTNNB1 mutation was a critical event in co-existing neoplasia and carcinoma; ageing drove mutation accumulation.","Two evolutionary paths: the classic adenoma or dysplasia to carcinoma sequence, and early divergence with independent evolution.","Extensive early loss of heterozygosity created a cancerous niche for the BilIN-independent path."],"whatItMeans":"Molecular confirmation that the visible precursor is not always the parent of the cancer beside it, which tempers hopes that finding and removing dysplasia catches every tumour, and puts Wnt signalling through CTNNB1 at the start of the raised route.","caveats":["Small number of patients with multi-region sampling; the abstract does not state n.","Chinese cohort."],"changedPractice":false},{"id":"paper-noe-cyst-malignant-progression-genomics-nat-commun-2020","kind":"paper","name":"Genomic characterization of malignant progression in neoplastic pancreatic cysts","aka":[],"tldr":"Sequencing 148 samples from cysts and the small cancers beside them established that both IPMNs and mucinous cystic neoplasms are true precursors, and that SMAD4 and TGFBR2 mutations mark the step into invasion, with about three years between high-grade dysplasia and cancer.","summary":"148 samples from IPMNs, mucinous cystic neoplasms and small associated invasive carcinomas from 18 patients were analysed by whole-exome or targeted sequencing. Evolutionary analyses established both IPMNs and MCNs as direct precursors to pancreatic cancer. Mutations in SMAD4 and TGFBR2 were frequently restricted to the invasive carcinoma while RNF43 alterations were largely in the non-invasive lesions. Genomic analyses suggested an average window of over three years between the development of high-grade dysplasia and pancreatic cancer.","asOf":"2026-09-24","links":[{"label":"Noe et al., Nat Commun 2020: genomic progression in 148 samples from IPMNs, MCNs and associated cancers","url":"https://doi.org/10.1038/s41467-020-17917-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32796935/"}],"tags":[],"related":[],"cancers":["pancreatic","ipmn-cystic-precursors"],"sections":[],"technologies":["wes-wgs","pancreatic-surveillance"],"targets":["smad4","tgfbr2","rnf43"],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":["tgf-beta","wnt","clonal-evolution"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-communications"],"dependsOn":[],"notes":[],"journal":"Nature Communications","year":2020,"doi":"10.1038/s41467-020-17917-8","pmid":"32796935","authors":"Noe M, Niknafs N, Fischer CG, et al.","paperType":"translational","findings":["IPMNs and MCNs are direct precursors of invasive cancer.","SMAD4 and TGFBR2 mutations mark the invasive step; RNF43 the non-invasive lesion.","Average window over three years from high-grade dysplasia to cancer."],"whatItMeans":"It gives surveillance a target and a timetable: catch high-grade dysplasia and there are about three years before invasion, and TGF-beta pathway loss is the event to detect.","caveats":["Eighteen patients.","Timing estimated from molecular clocks, not observed."],"changedPractice":false,"participants":18},{"id":"paper-bertucci-metastatic-breast-genomics-nature-2019","kind":"paper","name":"Genomic characterization of metastatic breast cancers","aka":[],"tldr":"Sequencing 617 metastatic breast cancers showed they carry more mutations and more clonal diversity than early tumours, and that metastatic triple-negative cancers have somatic loss of both copies of a homologous recombination gene in 7% against 2% of early ones.","summary":"The landscape of somatic alterations was investigated in 617 metastatic breast cancers. Nine driver genes (TP53, ESR1, GATA3, KMT2C, NCOR1, AKT1, NF1, RIC8A, RB1) were more frequently mutated in hormone receptor-positive, HER2-negative metastatic cancers (381) than in early cancers from TCGA, with 18 enriched amplicons and increased mutational signatures S2, S3, S10, S13 and S17; TP53, RB1 and NF1 mutations and S10, S13 and S17 marked poor outcome. Metastatic TNBCs showed an increased frequency of somatic biallelic loss-of-function mutations in homologous recombination DNA repair genes compared with early TNBC (7% versus 2%). Metastatic cancers showed increased mutational burden and clonal diversity.","asOf":"2026-09-24","links":[{"label":"Bertucci et al., Nature 2019: genomic characterisation of 617 metastatic breast cancers","url":"https://doi.org/10.1038/s41586-019-1056-z"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31118521/"}],"tags":[],"related":[],"cancers":["tnbc","tnbc-metastatic","breast-hr-positive"],"sections":[],"technologies":[],"targets":["brca","tp53","rb1","nf1"],"drugs":[],"companies":[],"institutions":[],"pathways":["homologous-recombination-repair","clonal-evolution"],"terms":["tmb"],"trials":[],"people":["fabrice-andre"],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2019,"doi":"10.1038/s41586-019-1056-z","pmid":"31118521","authors":"Bertucci F, Ng CKY, Patsouris A, et al.","paperType":"translational","findings":["Metastatic TNBC: somatic biallelic homologous recombination gene loss 7% versus 2% in early TNBC.","Metastatic tumours carry higher mutational burden and clonal diversity than early tumours.","TP53, RB1 and NF1 mutations and signatures S10, S13, S17 mark poor outcome in HR-positive metastatic disease."],"whatItMeans":"Re-biopsy and re-sequencing at relapse can find repair defects and a higher mutation burden that the primary did not show, which matters for PARP inhibitor and immunotherapy eligibility in metastatic TNBC.","caveats":["French SAFIR and MOSCATO programmes; patients heavily pretreated.","The TNBC subset was small relative to the hormone receptor-positive group."],"changedPractice":false,"participants":617},{"id":"paper-abida-genomic-correlates-outcome-mcrpc-pnas-2019","kind":"paper","name":"Genomic correlates of clinical outcome in advanced prostate cancer","aka":[],"tldr":"Linking the genetics of 429 men with advanced prostate cancer to how long they lived showed that only one gene, RB1, predicted a worse outcome once everything else was accounted for.","summary":"Comprehensive genomic and transcriptomic analysis of 429 patients with metastatic castration-resistant prostate cancer was linked with longitudinal clinical outcomes, integrating whole-exome, transcriptome and histological analysis. For the 128 patients treated with a first-line next-generation androgen receptor signalling inhibitor, abiraterone or enzalutamide, the association of 18 recurrent DNA- and RNA-based alterations with clinical outcome was examined, including AR variant expression, AR transcriptional output and neuroendocrine expression signatures. Of these, only RB1 alteration was significantly associated with shorter survival, whereas alterations in RB1, AR and TP53 were each associated with a shorter time on treatment with a receptor signalling inhibitor.","asOf":"2026-09-25","links":[{"label":"Abida et al., PNAS 2019: genomic correlates of clinical outcome in 429 patients with metastatic castration-resistant prostate cancer (SU2C/PCF)","url":"https://doi.org/10.1073/pnas.1902651116"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31061129/"},{"label":"cBioPortal study prad_su2c_2019 (SU2C/PCF Dream Team, PNAS 2019; 444 metastatic castration-resistant samples from 429 patients, whole exome)","url":"https://www.cbioportal.org/study/summary?id=prad_su2c_2019"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["wes-wgs","rna-seq"],"targets":["rb1","androgen-receptor","tp53"],"drugs":[],"companies":[],"institutions":[],"pathways":["ar-signaling","p53-cell-cycle","lineage-plasticity-neuroendocrine"],"terms":["castration-resistance","resistance","driver-mutation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["pnas"],"dependsOn":[],"notes":[],"journal":"Proceedings of the National Academy of Sciences","year":2019,"doi":"10.1073/pnas.1902651116","pmid":"31061129","authors":"Abida W, Cyrta J, Heller G, et al.","paperType":"observational","findings":["Only RB1 alteration was significantly associated with poor overall survival among 18 candidate markers.","RB1, AR and TP53 alterations each associated with shorter time on a first receptor signalling inhibitor.","A community resource pairing metastatic genomics with histology and longitudinal outcomes."],"whatItMeans":"It is the most disciplined outcome analysis in this disease and its result is deflationary in a useful way: most of the alterations people quote as prognostic do not survive adjustment, and the one that does, RB1, is also the one that marks the route to neuroendocrine transformation.","caveats":["Observational and not randomised, so the associations are prognostic rather than predictive.","One hundred and twenty-eight men in the treatment-outcome subset.","Academic referral centres, so the cohort is younger and fitter than the disease as a whole."],"changedPractice":false,"participants":429},{"id":"paper-giannakis-genomic-correlates-immune-colorectal-cell-rep-2016","kind":"paper","name":"Genomic correlates of immune-cell infiltrates in colorectal carcinoma","aka":[],"tldr":"Sequencing 619 bowel cancers collected prospectively in two long-running health studies found four new recurrently mutated genes and showed that the tumours making the most abnormal proteins attract the most immune cells and their owners live longer, even among tumours with an intact DNA spell-checker.","summary":"Whole-exome sequencing of 619 incident colorectal cancers from prospective cohorts was integrated with tumour immunity, pathology and survival data. Recurrently mutated genes not previously appreciated in the disease were identified, including BCL9L, RBM10, CTCF and KLF5. Higher neoantigen load was positively associated with overall lymphocytic infiltration, tumour-infiltrating lymphocytes, memory T cells and colorectal-cancer-specific survival, and the association with tumour-infiltrating lymphocytes was evident even within microsatellite-stable tumours. Mutations in HLA genes and other components of the antigen-processing machinery were positively selected in lymphocyte-rich tumours.\n\nDeposited as coadread_dfci_2016 on cBioPortal (619 exomes; MSI-high 91 of 529 assessable, CIMP-high 95 of 500).","asOf":"2026-09-24","links":[{"label":"Giannakis et al., Cell Reports 2016: exomes of 619 incident colorectal cancers with immune, pathology and survival data","url":"https://doi.org/10.1016/j.celrep.2016.03.075"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27149842/"},{"label":"cBioPortal study coadread_dfci_2016 (DFCI, Cell Reports 2016; 619 exomes from the Nurses' Health Study and Health Professionals Follow-up Study, no copy-number profile)","url":"https://www.cbioportal.org/study/summary?id=coadread_dfci_2016"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["wes-wgs"],"targets":["b2m","braf","mmr"],"drugs":[],"companies":[],"institutions":["dana-farber","broad-institute"],"pathways":["cancer-immunity-cycle","antigen-presentation-immunoediting"],"terms":["neoantigen","msi","tmb"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Cell Reports","year":2016,"doi":"10.1016/j.celrep.2016.03.075","pmid":"27149842","authors":"Giannakis M, Mu XJ, Shukla SA, et al.","paperType":"observational","findings":["New recurrently mutated genes: BCL9L (46 of 619), RBM10, CTCF, KLF5.","Neoantigen load associated with lymphocytic infiltration and cancer-specific survival, including within microsatellite-stable tumours.","Positive selection on HLA and antigen-processing genes in lymphocyte-rich tumours."],"whatItMeans":"It is the argument that immune biology matters across the whole disease rather than only in the mismatch repair deficient sixth, and the reason microsatellite-stable tumours with high neoantigen load are still being pursued for immunotherapy.","caveats":["Prospective cohorts of health professionals; not a random population sample.","Neoantigen prediction depends on the algorithm.","Exome only, so fusions and copy number are not covered."],"changedPractice":false,"participants":619},{"id":"paper-quigley-structural-variation-mcrpc-cell-2018","kind":"paper","name":"Genomic hallmarks and structural variation in metastatic prostate cancer","aka":[],"tldr":"Reading 101 advanced prostate cancers by whole genome rather than by gene panel found that four out of five had amplified a stretch of DNA that switches the androgen receptor on, sitting more than half a million letters away from the gene itself, where no ordinary test would look.","summary":"Integrative deep whole-genome and whole-transcriptome analysis of 101 castration-resistant prostate cancer metastases, at 109-fold tumour and 38-fold normal coverage, identified structural variants altering critical regulators that exome approaches cannot detect. Amplification of an intergenic enhancer region 624 kb upstream of the androgen receptor was present in 81% of patients and correlated with increased receptor expression. Tandem duplication hotspots also occurred near MYC, in long non-coding RNAs associated with post-translational MYC regulation. Classes of structural variation were linked to distinct DNA repair deficiencies: CDK12 mutation with tandem duplications, TP53 inactivation with inverted rearrangements and chromothripsis, and BRCA2 inactivation with deletions.","asOf":"2026-09-25","links":[{"label":"Quigley et al., Cell 2018: genomic hallmarks and structural variation in 101 metastatic castration-resistant prostate cancers (deep whole genomes)","url":"https://doi.org/10.1016/j.cell.2018.06.039"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30033370/"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["wes-wgs","rna-seq"],"targets":["androgen-receptor","cdk12","tp53","brca"],"drugs":[],"companies":[],"institutions":[],"pathways":["ar-signaling","chromosomal-instability","homologous-recombination-repair","mutagenesis-signatures"],"terms":["gene-amplification","copy-number-variation-term","somatic-mutations-wxs-wgs","castration-resistance"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Cell","year":2018,"doi":"10.1016/j.cell.2018.06.039","pmid":"30033370","authors":"Quigley DA, Dang HX, Zhao SG, et al.","paperType":"basic","findings":["An enhancer 624 kb upstream of AR amplified in 81% of 101 metastatic castration-resistant cancers, correlating with receptor expression.","Tandem duplication hotspots near MYC in long non-coding RNAs that regulate MYC after translation.","CDK12 mutation associated with tandem duplications, TP53 inactivation with inverted rearrangements and chromothripsis, BRCA2 inactivation with deletions."],"whatItMeans":"It shows that the commonest driver event in advanced prostate cancer is invisible to the panels used to test for it, and that the shape of the structural damage in a genome tells you which repair pathway failed, which is information a mutation list does not carry.","caveats":["A hundred and one metastases from men with heavily treated disease, so it describes late disease rather than the whole spectrum.","Deep whole-genome sequencing of metastases is not available outside research.","Enhancer amplification is not reported by any clinical assay, so the finding cannot yet be acted on."],"changedPractice":false,"participants":101},{"id":"paper-chen-east-asian-lung-adenocarcinoma-nat-genet-2020","kind":"paper","name":"Genomic landscape of lung adenocarcinoma in East Asians","aka":[],"tldr":"Sequencing 305 lung adenocarcinomas from East Asian patients showed that the same cancer in a different population has a calmer genome, far more of the one mutation that has a good pill, and an immune-rich subgroup that nobody had described.","summary":"A genomic and transcriptomic dataset of 305 lung adenocarcinomas from individuals of East Asian ancestry was assembled and compared with European-ancestry cohorts. East Asian tumours had more stable genomes, with fewer mutations and fewer copy-number alterations, and the difference was much stronger in smokers than in non-smokers. Transcriptomic clustering identified an East Asian-specific subgroup with a less complex genomic profile and upregulated immune-related genes, raising the possibility of immunotherapy-based approaches. Integrative analysis across clinical and molecular features showed the importance of molecular phenotypes in prognostic stratification, and prediction accuracy was better in the East Asian cohort than in the European-ancestry one, potentially because of the simpler genomic architecture.","asOf":"2026-09-25","links":[{"label":"Chen et al., Nat Genet 2020: the genomic landscape of lung adenocarcinoma in 305 East Asians (OncoSG)","url":"https://doi.org/10.1038/s41588-019-0569-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32015526/"},{"label":"cBioPortal study luad_oncosg_2020 (OncoSG, Nat Genet 2020; 305 East Asian lung adenocarcinomas, 302 sequenced)","url":"https://www.cbioportal.org/study/summary?id=luad_oncosg_2020"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":["wes-wgs","rna-seq"],"targets":["egfr","kras","tp53","stk11","keap1","her2"],"drugs":[],"companies":[],"institutions":["nccs"],"pathways":["nsclc-signalling","rtk-activation","mutagenesis-signatures"],"terms":["driver-mutation","egfr-mutation-subtypes","copy-number-variation-term"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":2020,"doi":"10.1038/s41588-019-0569-6","pmid":"32015526","authors":"Chen J, Yang H, Teo ASM, et al.","paperType":"basic","findings":["East Asian lung adenocarcinomas carry fewer mutations and fewer copy-number alterations than European-ancestry tumours.","The ancestry difference is much larger among smokers.","A new East Asian subgroup with a simple genome and high immune gene expression.","EGFR is mutated in 143 of 302 sequenced tumours, 47.4%, against 12.4% in the TCGA series."],"whatItMeans":"It shows that the driver frequencies quoted in Western guidelines are population statistics rather than facts about the disease, which matters for how many patients anywhere are expected to benefit from a given medicine.","caveats":["A single-country cohort, so East Asian is a coarse label for several populations.","Smoking history is self-reported.","Prognostic models built on one ancestry have not been validated prospectively in another."],"changedPractice":false,"participants":305},{"id":"paper-park-hrd-pancreatic-platinum-ccr-2020","kind":"paper","name":"Genomic methods identify homologous recombination deficiency in pancreas adenocarcinoma and optimize treatment selection","aka":[],"tldr":"In 262 patients with advanced pancreatic cancer, the 19% with a broken homologous recombination gene did much better on first-line platinum chemotherapy than others, and the benefit was concentrated in BRCA1, BRCA2 and PALB2 and in tumours that had lost both copies.","summary":"Progression-free and overall survival were evaluated in advanced pancreatic ductal adenocarcinoma patients with both germline and somatic targeted sequencing. Homologous recombination mutations (17 genes) were grouped as germline versus somatic, core (BRCA1, BRCA2, PALB2) versus non-core, and monoallelic versus biallelic; genomic instability was compared by large-scale state transitions, signature 3 and tumour mutation burden. Among 262 patients, 50 (19%) had deficiency (15% germline, 4% somatic). Median overall and progression-free survival were 15.5 and 7 months. Deficient patients had improved progression-free survival on first-line platinum (hazard ratio 0.44) but not non-platinum. Biallelic (11%) and core (12%) mutations had higher genomic instability and greater platinum benefit.","asOf":"2026-09-24","links":[{"label":"Park et al., Clin Cancer Res 2020: homologous recombination deficiency in 262 advanced patients and first-line platinum","url":"https://doi.org/10.1158/1078-0432.CCR-20-0418"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32444418/"}],"tags":[],"related":["hrd-positive","brca-somatic","brca-germline"],"cancers":["pancreatic","brca-palb2-pdac","metastatic-pdac"],"sections":[],"technologies":["hrd-testing"],"targets":["brca","palb2","atm"],"drugs":["folfirinox","gemcitabine-cisplatin"],"companies":[],"institutions":["mskcc"],"pathways":["homologous-recombination-repair"],"terms":["hrd","germline-vs-somatic","mutational-signature"],"trials":[],"people":["eileen-oreilly","vinod-balachandran"],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2020,"doi":"10.1158/1078-0432.CCR-20-0418","pmid":"32444418","authors":"Park W, Chen J, Chou JF, et al.","paperType":"observational","findings":["Homologous recombination gene mutation in 19%: germline 15%, somatic 4%; biallelic 11%, core 12%.","First-line platinum progression-free survival hazard ratio 0.44 in the deficient group; no benefit from non-platinum.","Core and biallelic mutations carry the higher genomic instability and the larger benefit."],"whatItMeans":"It defines who a homologous recombination result should send to platinum: core-gene and biallelic carriers, germline or somatic, rather than any repair-gene variant.","caveats":["Retrospective single-centre series; treatment not randomised.","Non-core genes such as ATM showed little benefit but small numbers."],"changedPractice":false,"participants":262},{"id":"paper-suryavanshi-indian-gallbladder-genomics-jco-go-2025","kind":"paper","name":"Genomic profiling of Indian gallbladder carcinoma: mutational insights in a high-incidence population","aka":[],"tldr":"The largest Indian series, 376 patients sequenced at three centres, found the disease strikes a decade earlier than elsewhere, with TP53 and HER2 the leading changes and immunotherapy markers rare.","summary":"376 patients with gallbladder carcinoma (339 tissue and 37 plasma cell-free DNA samples) from three Indian institutions (2022 to 2024) were analysed with clinically validated next-generation sequencing panels and compared with Western, Asian and multi-ethnic cohorts curated from cBioPortal. The disease was more frequent in women (1.5 to 1) and diagnosed nearly a decade earlier than in international cohorts (median age 54).\n\nTP53 (54%) and ERBB2 (15%; approximately 8% amplification, with S310F/Y hotspot predominance) were the most common alterations, followed by CDKN2A (9%), KRAS (7%) and SMAD4 (7%). Microsatellite instability-high (0.6%, 2 of 170 tested) and tumour mutational burden-high (1.3%, 1 of 79 tested) were rare. Indian patients had significantly lower ARID1A, SMAD4 and CDKN2A alteration rates than Western and Asian cohorts (all P < 0.001). Of 37 cfDNA patients, 13 showed no variants, but detected alterations qualitatively mirrored tissue.","asOf":"2026-09-24","links":[{"label":"Suryavanshi et al., JCO Glob Oncol 2025: genomic profiling of 376 Indian gallbladder carcinomas","url":"https://doi.org/10.1200/go-25-00332"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41418080/"}],"tags":[],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":["tp53","her2","cdkn2a","kras","smad4","arid1a","mmr"],"drugs":[],"companies":[],"institutions":["tata-memorial"],"pathways":[],"terms":["msi","tmb","ctdna"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"JCO Global Oncology","year":2025,"doi":"10.1200/go-25-00332","pmid":"41418080","authors":"Suryavanshi M, Ostwal V, Javle MM, et al.","paperType":"observational","findings":["TP53 54%, ERBB2 15% (about 8% amplification; S310F/Y hotspot), CDKN2A 9%, KRAS 7%, SMAD4 7%.","MSI-high 0.6% (2 of 170) and TMB-high 1.3% (1 of 79).","ARID1A, SMAD4 and CDKN2A significantly less altered than in Western and Asian cohorts; median age at diagnosis 54."],"whatItMeans":"HER2 is as frequent in India as in the West, so HER2 testing pays off in the highest-incidence population, while tumour-agnostic immunotherapy markers will rarely apply. The paper also shows plasma testing is feasible where tissue is scarce.","caveats":["Heterogeneous panels across three institutions introduce variability in frequency estimates, as the authors state.","Retrospective series of patients who reached sequencing."],"changedPractice":false,"participants":376},{"id":"paper-nakamura-biliary-genomic-spectra-nat-genet-2015","kind":"paper","name":"Genomic spectra of biliary tract cancer","aka":[],"tldr":"Sequencing 260 Japanese bile duct and gallbladder cancers showed that the three sites carry different mutations, that nearly 40% have a targetable change, and that gallbladder and extrahepatic tumours carry a heavier APOBEC mutation signature.","summary":"260 biliary tract cancers, including intrahepatic and extrahepatic cholangiocarcinoma and gallbladder cancer, were molecularly characterised. Gradient spectra of mutational signatures with a higher burden of the APOBEC-associated signature were observed in gallbladder cancer and extrahepatic cholangiocarcinoma. Thirty-two significantly altered genes, including ELF3, were identified, and nearly 40% of cases harboured targetable genetic alterations.\n\nGene fusions involving FGFR2 and PRKACA or PRKACB preferentially occurred in intrahepatic and extrahepatic cholangiocarcinoma respectively. The subgroup with the shortest survival had significant enrichment of hypermutated tumours and a characteristic elevation in the expression of immune checkpoint molecules.","asOf":"2026-09-24","links":[{"label":"Nakamura et al., Nat Genet 2015: genomic spectra of 260 biliary tract cancers","url":"https://doi.org/10.1038/ng.3375"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26258846/"}],"tags":[],"related":[],"cancers":["gallbladder","cholangiocarcinoma","biliary-tract-cancer"],"sections":[],"technologies":[],"targets":["elf3","fgfr2","her2"],"drugs":[],"companies":[],"institutions":["ncc-japan"],"pathways":[],"terms":["mutational-signature","gene-fusion"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":2015,"doi":"10.1038/ng.3375","pmid":"26258846","authors":"Nakamura H, Arai Y, Totoki Y, et al.","paperType":"translational","findings":["32 significantly altered genes, including ELF3; nearly 40% of cases had a targetable alteration.","APOBEC mutational signature heaviest in gallbladder cancer and extrahepatic cholangiocarcinoma.","FGFR2 fusions occurred preferentially in intrahepatic cholangiocarcinoma, PRKACA/PRKACB fusions in extrahepatic tumours."],"whatItMeans":"The paper that separated the biliary tree into molecular subtypes: FGFR2 and IDH belong to the intrahepatic ducts, while gallbladder cancer carries HER2, ELF3 and an APOBEC signature. Its hypermutated, checkpoint-high poor-prognosis group foreshadowed immunotherapy.","caveats":["Japanese cohort; gallbladder cancers were a minority of the 260.","Targetable was defined by the 2015 drug landscape."],"changedPractice":false,"participants":260},{"id":"paper-mateo-genomics-lethal-prostate-diagnosis-castration-resistance-jci-2020","kind":"paper","name":"Genomics of lethal prostate cancer at diagnosis and castration resistance","aka":[],"tldr":"Sequencing the original diagnostic biopsies of men who later died of prostate cancer showed the dangerous changes were already there at the start, years before the disease became resistant.","summary":"Genomic aberrations were studied in primary prostate cancer diagnostic biopsies from men who went on to develop metastatic castration-resistant prostate cancer, with matching same-patient diagnostic and castration-resistant biopsies for a subset. Four hundred and seventy treatment-naive diagnostic biopsies were profiled by targeted and low-pass whole-genome sequencing, with 61 matched castration-resistant biopsies. TP53 was altered in 27% and PTEN in 12%, with DNA damage repair gene defects in BRCA2 at 7%, CDK12 at 5% and ATM at 4%. TP53, BRCA2 and CDK12 mutations were markedly more common than in the TCGA primary cohort. Men whose primary tumour carried RB1 loss had a worse prognosis. Among the 61 men with matched biopsies, differences were identified in AR, TP53, RB1 and PI3K or AKT mutational status between the two time points.","asOf":"2026-09-25","links":[{"label":"Mateo et al., J Clin Invest 2020: genomics of 470 diagnostic biopsies from men who went on to develop metastatic castration-resistant disease, with 61 matched later biopsies","url":"https://doi.org/10.1172/JCI132031"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31874108/"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["cgp","wes-wgs"],"targets":["tp53","pten","brca","cdk12","atm","rb1","androgen-receptor"],"drugs":[],"companies":[],"institutions":[],"pathways":["homologous-recombination-repair","p53-cell-cycle","ar-signaling","pi3k-akt-mtor","clonal-evolution"],"terms":["biopsy","castration-resistance","driver-mutation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jci"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Investigation","year":2020,"doi":"10.1172/JCI132031","pmid":"31874108","authors":"Mateo J, Seed G, Bertan C, et al.","paperType":"observational","findings":["TP53 altered in 27% and PTEN in 12% of diagnostic biopsies from men who later developed castration-resistant disease.","BRCA2 7%, CDK12 5% and ATM 4% at diagnosis, similar to the prevalence in castration-resistant disease.","RB1 loss in the primary tumour associated with worse prognosis.","AR, TP53, RB1 and PI3K/AKT status differed between paired diagnostic and castration-resistant samples."],"whatItMeans":"It splits the alterations into two groups with different practical meanings. The repair defects are present at diagnosis at close to their castration-resistant prevalence, so testing early is worthwhile; AR, TP53 and RB1 changes accumulate later, so a diagnostic sample does not answer questions about the disease in front of you at relapse.","caveats":["Selected by outcome: these are the primaries of men who went on to die of the disease, so the prevalences are not those of prostate cancer generally.","Targeted and low-pass sequencing on archival diagnostic biopsies, which are small and often decades old.","Sixty-one matched pairs is a small number on which to describe evolution."],"changedPractice":false,"participants":470},{"id":"paper-aung-compass-early-results-ccr-2018","kind":"paper","name":"Genomics-driven precision medicine for advanced pancreatic cancer: early results from the COMPASS trial","aka":[],"tldr":"COMPASS showed that a fresh biopsy of advanced pancreatic cancer can be whole-genome and RNA sequenced fast enough to report before the first scan, and that classical-subtype tumours responded to first-line chemotherapy far better than basal-like ones.","summary":"Patients with advanced pancreatic ductal adenocarcinoma were prospectively recruited before first-line combination chemotherapy; fresh image-guided core biopsies underwent laser capture microdissection, whole-genome and RNA sequencing. Sixty-three patients were biopsied between December 2015 and June 2017; sequencing succeeded in 62 (98%) and 60 (95%), with results reported at a median of 35 days, meeting the feasibility endpoint. Objective responses to first-line chemotherapy were significantly better in the classical RNA subtype than the basal-like (P = 0.004), with the best progression-free survival in classical tumours on modified FOLFIRINOX. GATA6 expression by RNA in situ hybridisation was a robust surrogate for the subtypes. Potentially actionable alterations were found in 30%.","asOf":"2026-09-24","links":[{"label":"Aung et al., Clin Cancer Res 2018: COMPASS, real-time whole-genome and RNA sequencing of 63 advanced patients","url":"https://doi.org/10.1158/1078-0432.CCR-17-2994"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29288237/"}],"tags":[],"related":[],"cancers":["pancreatic","metastatic-pdac"],"sections":[],"technologies":["wes-wgs","rna-seq"],"targets":[],"drugs":["folfirinox"],"companies":[],"institutions":["princess-margaret","oicr"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2018,"doi":"10.1158/1078-0432.CCR-17-2994","pmid":"29288237","authors":"Aung KL, Fischer SE, Denroche RE, et al.","paperType":"translational","findings":["Whole-genome and RNA sequencing feasible from biopsies within a median 35 days.","Response to first-line chemotherapy better in classical than basal-like tumours (P = 0.004).","GATA6 in situ hybridisation as a subtype surrogate; actionable alterations in 30%."],"whatItMeans":"COMPASS is the prospective evidence that transcriptional subtype predicts chemotherapy response, and it produced the practical GATA6 test that trials now use to stratify.","caveats":["63 patients; chemotherapy was not assigned by subtype.","Subtype calls require enough tumour cellularity."],"changedPractice":false,"participants":63},{"id":"paper-sequist-genotypic-histological-evolution-egfr-resistance-sci-transl-med-2011","kind":"paper","name":"Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors","aka":[],"tldr":"37 patients were re-biopsied when their EGFR drug stopped working. Some had the expected resistance mutation; five had turned into small-cell lung cancer. In three, the resistance disappeared when the drug was stopped.","summary":"Sequist, Waltman, Dias-Santagata and colleagues, with Engelman as senior author, performed systematic genetic and histological analysis of tumour biopsies from 37 patients with drug-resistant EGFR-mutant non-small-cell lung cancers.\n\nThree findings in one paper remade how resistance is thought about. Resistance is heterogeneous in mechanism; it can be histological rather than genetic, with 14 percent of tumours transforming into small-cell lung cancer; and it can be reversible, with resistance mechanisms lost when the selective pressure is removed, so that a patient can respond again to a drug they had already failed.","asOf":"2026-09-25","links":[{"label":"Sci Transl Med 2011","url":"https://doi.org/10.1126/scitranslmed.3002003"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21430269/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/21430269"}],"tags":["lung-evidence"],"related":["paper-kobayashi-egfr-t790m-gefitinib-resistance-nejm-2005","paper-tracerx-100-nejm-2017","paper-rudin-sclc-molecular-subtypes-nat-rev-cancer-2019","egfr-t790m","met-amplification-readout","histologic-transformation","met-amplification"],"cancers":["lung-cancer","nsclc","egfr-mutant-nsclc","sclc"],"sections":["targeted-therapy","diagnostics"],"technologies":["ngs"],"targets":["egfr","met","rb1","tp53"],"drugs":["gefitinib","erlotinib","osimertinib"],"companies":[],"institutions":["mgh"],"pathways":["pi3k-akt-mtor","resistance-routes-map","lineage-plasticity-neuroendocrine","clonal-evolution"],"terms":["resistance","histology","clonal-evolution","histologic-transformation","biopsy"],"trials":[],"people":["lecia-sequist"],"bottlenecks":["b-resistance","b-tumor-heterogeneity","b-preclinical-models"],"keyPapers":[],"journals":["science-translational-medicine"],"dependsOn":[],"notes":[],"journal":"Science Translational Medicine","year":2011,"doi":"10.1126/scitranslmed.3002003","pmid":"21430269","authors":"Sequist LV, Waltman BA, Dias-Santagata D, et al.","paperType":"translational","findings":["All drug-resistant tumours retained their original activating EGFR mutations.","Known resistance mechanisms were found in some: the EGFR T790M mutation or MET gene amplification.","Unexpected changes included EGFR amplification and PIK3CA mutations","Five resistant tumours (14 percent) transformed from non-small-cell into small-cell lung cancer and were sensitive to standard small-cell treatments.","In three patients, serial biopsies showed genetic resistance mechanisms were lost without continued selective pressure, and those cancers responded again to EGFR inhibitors."],"whatItMeans":"The case for re-biopsy at progression, for treating resistance as a diagnosis rather than an endpoint, and for the idea of a drug holiday. It is also the origin of resistance-directed sequencing: what you give next should depend on what the tumour became.","caveats":["37 patients from one centre, biopsied when it was feasible, which selects for accessible disease.","Mechanisms were assigned from single-site biopsies, so heterogeneity between lesions in the same patient is invisible.","Reversibility was seen in three patients and has never been tested prospectively as a treatment strategy."],"changedPractice":true,"participants":37},{"id":"paper-ettrich-cholangiocarcinoma-ctdna-genotyping-sci-rep-2019","kind":"paper","name":"Genotyping of circulating tumor DNA in cholangiocarcinoma reveals diagnostic and prognostic information","aka":[],"tldr":"Comparing tumour tissue with blood in bile duct cancer patients, three quarters of mutations were found in both, rising to over nine in ten for tumours inside the liver, and the amount of tumour DNA in blood tracked tumour burden and outcome.","summary":"Tumour tissue and corresponding circulating tumour DNA samples were collected from patients with cholangiocarcinoma before and during chemotherapy and deep-sequenced for 15 genes frequently mutated in the disease; a set of ctDNA samples was also sequenced with a 710-gene panel to identify progression signatures.\n\nBlood to tissue concordance was 74% overall and 92% for intrahepatic tumours. Variant allele frequency in ctDNA correlated with tumour load and, in intrahepatic disease, with progression-free survival. 63% of therapy-naive patients had their mutational profile change during chemotherapy, and 76 potential progression driver genes were identified among 710 candidates.","asOf":"2026-09-24","links":[{"label":"Ettrich et al., Sci Rep 2019: ctDNA genotyping in cholangiocarcinoma","url":"https://doi.org/10.1038/s41598-019-49860-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31519967/"}],"tags":[],"related":[],"cancers":["cholangiocarcinoma","gallbladder"],"sections":[],"technologies":["liquid-biopsy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ctdna"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Scientific Reports","year":2019,"doi":"10.1038/s41598-019-49860-0","pmid":"31519967","authors":"Ettrich TJ, Schwerdel D, Dolnik A, et al.","paperType":"translational","findings":["Blood to tissue concordance 74% overall and 92% for intrahepatic cholangiocarcinoma.","ctDNA variant allele frequency correlated with tumour load and with progression-free survival in intrahepatic disease.","63% of therapy-naive patients changed mutational profile during chemotherapy."],"whatItMeans":"The concordance figures are the reference for how well plasma stands in for tissue in biliary cancer, and the profile changes on chemotherapy are the argument for re-testing at progression rather than treating on the diagnostic panel alone.","caveats":["Cholangiocarcinoma only, small cohort (n not stated in the abstract).","15-gene panel for concordance; gallbladder cancer was not studied."],"changedPractice":false},{"id":"paper-diaz-gay-colibactin-geographic-age-mutational-processes-nature-2025","kind":"paper","name":"Geographic and age variations in mutational processes in colorectal cancer","aka":[],"tldr":"Reading 981 bowel cancer genomes from 11 countries found that the fingerprint of colibactin, a DNA-damaging toxin made by some gut bacteria, is more than three times as common in people diagnosed under 40 as over 70, and is stamped on the tumour early in life. It is the strongest lead yet on why bowel cancer is rising in young adults.","summary":"Díaz-Gay, Dos Santos, Moody and colleagues examined 981 colorectal cancer genomes from 11 countries to ask whether mutational processes contribute to geographic and age-related differences in incidence. No major differences were found in microsatellite-unstable cancers, but variations in mutation burden and signatures were observed in the 802 microsatellite-stable cases.\n\nMultiple signatures, most with unknown aetiologies, varied in prevalence across Argentina, Brazil, Colombia, Russia and Thailand, indicating geographically diverse levels of mutagenic exposure. Signatures SBS88 and ID18, caused by the bacteria-produced mutagen colibactin, had higher mutation loads in countries with higher colorectal cancer incidence rates, were enriched in early-onset cancers and were imprinted early during tumour development. Colibactin exposure was further linked to APC driver mutations.","asOf":"2026-09-24","links":[{"label":"Nature 2025","url":"https://doi.org/10.1038/s41586-025-09025-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40267983/"},{"label":"Europe PMC full text (PMC12221974)","url":"https://europepmc.org/article/MED/40267983"}],"tags":["colorectal-evidence"],"related":["paper-siegel-colorectal-incidence-birth-cohort-jnci-2017","paper-vuik-early-onset-colorectal-europe-gut-2019"],"cancers":["colorectal","early-onset-colorectal"],"sections":["prevention"],"technologies":["wes-wgs"],"targets":["apc"],"drugs":[],"companies":[],"institutions":["iarc"],"pathways":["microbiome-tumour"],"terms":["gut-microbiome-diversity"],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-prevention-adoption","b-metastasis-biology"],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2025,"doi":"10.1038/s41586-025-09025-8","pmid":"40267983","authors":"Díaz-Gay M, Dos Santos W, Moody S, et al.","paperType":"basic","findings":["981 genomes from 11 countries; 802 microsatellite-stable cases carried the geographic and age variation.","Colibactin signatures SBS88 and ID18 were 3.3 times more common in people diagnosed before 40 than in those over 70.","SBS88 and ID18 mutation loads were higher in countries with higher colorectal cancer incidence.","ID18 was responsible for about 25 percent of APC driver insertions and deletions in colibactin-positive cases.","The colibactin signatures were imprinted early during colorectal cancer development."],"whatItMeans":"If a childhood exposure to colibactin-producing Escherichia coli writes APC mutations into the colon decades before a tumour appears, then the rise in early-onset bowel cancer may be preventable by something done in childhood rather than by screening alone.","caveats":["Association, not causation: the signature records exposure at some point, and no trial has shown that removing colibactin-producing bacteria lowers risk.","981 genomes across 11 countries is a thin sample per country, and the countries were not chosen to be representative.","Most of the geographically variable signatures still have no known cause."],"participants":981},{"id":"paper-garate-calderon-gallbladder-cancer-worldwide-exome-ebiomedicine-2026","kind":"paper","name":"Geographic and genetic diversity in gallbladder cancer mutation profiles: insights from a worldwide exome analysis","aka":[],"tldr":"Sequencing 262 gallbladder tumours from Chile, China, India, Japan and South Korea showed that the mutations differ by country and ancestry, with Chinese tumours carrying the most mutations and Chilean the fewest.","summary":"Whole-exome sequencing of 262 gallbladder cancer tumour-normal pairs from Chilean, Chinese, Indian, Japanese and South Korean patients, analysed with a unified pipeline for gene mutations and mutational signatures, with individual ancestry proportions estimated and related to genomic profiles. Tumour mutation burden was highest in China and lowest in Chile. The authors conclude that gallbladder cancer shows marked geographic and genetic heterogeneity in mutation profiles with implications for prevention and targeted therapy in high-incidence regions. Funded by the EU Horizon 2020 programme (grant 825741).","asOf":"2026-09-24","links":[{"label":"EBioMedicine 2026","url":"https://doi.org/10.1016/j.ebiom.2026.106305"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42167123/"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":["cgp"],"targets":["tp53","her2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ngs"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"EBioMedicine","year":2026,"doi":"10.1016/j.ebiom.2026.106305","pmid":"42167123","authors":"Gárate-Calderón V, Kumar R, Marcelain K, et al.","paperType":"translational","findings":["262 tumour-normal exome pairs from five countries; tumour mutation burden highest in China and lowest in Chile.","Mutation profiles vary with geography and genetic ancestry."],"whatItMeans":"Targeted therapy prevalence estimates from one country may not hold in another, so a UK cohort, with its own ancestry mix, would need its own molecular survey before assuming HER2 or other rates from Asian or Latin American series.","caveats":["Cohort sizes per country are modest and recruited from referral centres.","Abstract figures beyond the mutation burden comparison are not indexed."],"changedPractice":false,"participants":262},{"id":"paper-gerlinger-intratumour-heterogeneity-nejm-2012","kind":"paper","name":"Gerlinger: a single biopsy misses most of the mutations in a kidney tumour","aka":[],"tldr":"Sequencing multiple regions of four kidney cancers and their metastases showed that around two-thirds of mutations were not shared across the whole tumour, that good- and poor-prognosis gene signatures coexisted in the same tumour, and that different regions had independently hit the same genes.","summary":"Swanton's group performed exome sequencing, chromosome aberration analysis and ploidy profiling on multiple spatially separated samples from primary clear-cell renal carcinomas and associated metastases in four patients, reconstructing phylogenetic trees for each tumour.\n\nBranched rather than linear evolution was the rule: 63-69% of all somatic mutations in the index case were not detectable in every region. Prognostic gene expression signatures classified different regions of the same tumour as favourable or unfavourable. Convergent evolution was seen, with distinct inactivating mutations in SETD2, KDM5C and PTEN arising in different regions, indicating strong selection on those pathways.\n\nThe paper made intratumour heterogeneity a central problem for biomarkers, drug resistance and trial design, and led directly to the TRACERx programme.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1056/NEJMoa1113205"}],"tags":[],"related":["paper-tracerx-100-nejm-2017","idea-bio1-ctdna-clone-report"],"cancers":["rcc"],"sections":["diagnostics"],"technologies":["wes-wgs","liquid-biopsy"],"targets":[],"drugs":[],"companies":[],"institutions":["cruk","francis-crick"],"pathways":["clonal-evolution"],"terms":["resistance","vaf"],"trials":[],"people":["charles-swanton"],"bottlenecks":["b-tumor-heterogeneity","b-resistance","b-biomarker-validation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2012,"doi":"10.1056/NEJMoa1113205","pmid":"22397650","authors":"Gerlinger M, Rowan AJ, Horswell S, et al.","paperType":"translational","findings":["63-69% of somatic mutations in the index tumour were not present in every region sampled","A single biopsy captured only a minority of the tumour's mutational landscape","Good- and poor-prognosis expression signatures were found in different regions of the same tumour","Convergent evolution: distinct loss-of-function mutations in SETD2, KDM5C and PTEN in separate regions of the same tumour"],"whatItMeans":"A single biopsy is an incomplete picture of a patient's cancer. Truncal mutations shared by all cells (in kidney cancer, VHL) are the most reliable drug targets, whereas mutations in only some branches predict resistance. This is why liquid biopsy and multi-region sampling matter.","caveats":["Four patients; the extent of heterogeneity varies across cancer types","Clear-cell renal carcinoma may be unusually heterogeneous","Exome sequencing depth of the time limited detection of low-frequency subclones","Clinical consequences (whether targeting truncal alterations improves outcomes) were not tested"],"changedPractice":false,"participants":4},{"id":"paper-sharma-tnbc-registry-germline-brca-bcrt-2014","kind":"paper","name":"Germline BRCA mutation evaluation in a prospective triple-negative breast cancer registry: implications for hereditary breast and/or ovarian cancer syndrome testing","aka":[],"tldr":"Every one of 207 women with triple-negative breast cancer in a Kansas registry was tested for BRCA mutations: 15.4% carried one, and the guideline rule of testing all TNBC patients aged 60 or under found every carrier.","summary":"Stage I to IV TNBC patients enrolled in a prospective registry at academic and community practices between 2011 and 2013 (207; 80% Caucasian, 14% African American, 1% Ashkenazi) all underwent BRCA1/2 testing. Deleterious mutations were found in 15.4% (BRCA1 11.1%, BRCA2 4.3%). Prevalence was 31.6% with and 6.1% without a significant family history, and 27.6% at 50 or under, 11.4% at 51 to 60 and 4.9% at 61 or over. Using family history or age 50 or under alone would have missed 25% and 34% of carriers; the NCCN criteria of the time (all TNBC at 60 or under) identified 18.3% (32 of 175) and no carrier among the 32 patients outside them.","asOf":"2026-09-24","links":[{"label":"Sharma et al., Breast Cancer Res Treat 2014: germline BRCA in a prospective registry of 207 TNBC patients","url":"https://doi.org/10.1007/s10549-014-2980-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24807107/"}],"tags":[],"related":[],"cancers":["tnbc"],"sections":[],"technologies":["germline-testing"],"targets":["brca"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["gbrca-mutation"],"trials":[],"people":["priyanka-sharma"],"bottlenecks":[],"keyPapers":[],"journals":["breast-cancer-research-and-treatment"],"dependsOn":[],"notes":[],"journal":"Breast Cancer Research and Treatment","year":2014,"doi":"10.1007/s10549-014-2980-0","pmid":"24807107","authors":"Sharma P, Klemp JR, Kimler BF, et al.","paperType":"observational","findings":["Germline BRCA in 15.4%: BRCA1 11.1%, BRCA2 4.3%.","Prevalence by age: 27.6% at 50 or under, 11.4% at 51 to 60, 4.9% at 61 or over.","Age or family history alone missed a quarter to a third of carriers."],"whatItMeans":"The registry showed that age and family-history filters leak carriers, the argument that carried testing criteria from 'under 60' towards every TNBC diagnosis.","caveats":["207 patients, mostly of European ancestry.","Tested with the criteria of 2013; later guidelines broadened."],"changedPractice":false,"participants":207},{"id":"paper-castro-germline-brca-prostate-outcomes-jco-2013","kind":"paper","name":"Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis and poor survival outcomes in prostate cancer","aka":[],"tldr":"Comparing 79 men who inherited a BRCA fault with 1,940 who did not showed the carriers' cancers were higher grade, more often spread at diagnosis, and shortened life by years.","summary":"The tumour features and outcomes of 2,019 men with prostate cancer were analysed, 18 BRCA1 carriers, 61 BRCA2 carriers and 1,940 non-carriers. Prostate cancers in germline BRCA1 or BRCA2 carriers were more often Gleason 8 or higher, T3 or T4 stage, node-positive and metastatic at diagnosis. Cause-specific survival was significantly longer in non-carriers, 15.7 against 8.6 years, with a multivariable hazard ratio of 1.8. For localised disease at presentation, five-year cause-specific survival was 96% in non-carriers against 82% in carriers and five-year metastasis-free survival 93% against 77%. Subgroup analyses confirmed the poor outcomes in BRCA2 carriers, while the role of BRCA1 could not be defined because of the limited size of that subgroup.","asOf":"2026-09-25","links":[{"label":"Castro et al., J Clin Oncol 2013: germline BRCA1 and BRCA2 mutations and outcome in 2,019 men with prostate cancer","url":"https://doi.org/10.1200/JCO.2012.43.1882"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23569316/"}],"tags":[],"related":[],"cancers":["prostate"],"sections":[],"technologies":["germline-testing"],"targets":["brca"],"drugs":[],"companies":[],"institutions":[],"pathways":["homologous-recombination-repair","ddr"],"terms":["germline-vs-somatic","gbrca-mutation","gleason-grade-group","hrd"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2013,"doi":"10.1200/JCO.2012.43.1882","pmid":"23569316","authors":"Castro E, Goh C, Olmos D, et al.","paperType":"observational","findings":["Carriers more often Gleason 8 or above, T3/T4, node-positive and metastatic at diagnosis.","Cause-specific survival 15.7 years in non-carriers against 8.6 years in carriers, hazard ratio 1.8.","Five-year cause-specific survival in localised disease 96% against 82%, metastasis-free survival 93% against 77%.","The effect was confirmed for BRCA2; BRCA1 could not be resolved with 18 carriers."],"whatItMeans":"It established that an inherited BRCA2 mutation changes the disease and not only the treatment options, which is why a carrier's localised disease is generally treated more intensively and watched more closely rather than put on surveillance.","caveats":["These are cohort figures and not a personal prognosis.","Predates PARP inhibitors, hormone intensification in castration-sensitive disease and PSMA PET staging, all of which change outcomes.","Carriers were identified through family-cancer programmes, which selects for stronger family histories."],"changedPractice":true,"participants":2019},{"id":"paper-foulkes-brca1-basal-phenotype-jnci-2003","kind":"paper","name":"Germline BRCA1 mutations and a basal epithelial phenotype in breast cancer","aka":[],"tldr":"A 2003 study using an ordinary pathology stain, cytokeratin 5/6, to show that breast cancers in women with an inherited BRCA1 fault are nine times more likely to have the basal pattern; it brought the basal-like idea from the microarray to the pathology bench.","summary":"Foulkes, Stefansson, Chappuis, Bégin and colleagues tested whether BRCA1-related breast cancers are more likely than non-BRCA1/2 cancers to express a basal epithelial phenotype, found in at most 15 percent of invasive breast cancers and associated with oestrogen receptor- and HER2-negative tumours. Among 292 specimens previously analysed for oestrogen receptor, HER2, p53 and germline BRCA1 and BRCA2 mutations, 76 were negative for both receptors; of 72 with sufficient material, 40 expressed cytokeratin 5 and/or 6. Cytokeratin 5/6 expression was significantly associated with BRCA1-related cancer (odds ratio 9.0, 95 percent confidence interval 1.9 to 43; p=0.002).","asOf":"2026-09-24","links":[{"label":"J Natl Cancer Inst 2003","url":"https://doi.org/10.1093/jnci/djg050"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/14519755/"}],"tags":["tnbc-evidence"],"related":["paper-sorlie-repeated-observation-subtypes-brca1-basal-pnas-2003","paper-carey-race-breast-cancer-subtypes-cbcs-jama-2006"],"cancers":["tnbc"],"sections":[],"technologies":[],"targets":["brca"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ihc","germline-testing"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jnci"],"dependsOn":[],"notes":[],"journal":"Journal of the National Cancer Institute","year":2003,"doi":"10.1093/jnci/djg050","pmid":"14519755","authors":"Foulkes WD, Stefansson IM, Chappuis PO, et al.","paperType":"translational","findings":["Among 72 oestrogen receptor- and HER2-negative tumours, cytokeratin 5/6 expression was associated with germline BRCA1 mutation: odds ratio 9.0 (95 percent CI 1.9 to 43), p=0.002."],"whatItMeans":"Confirmed the BRCA1 to basal link with a stain any laboratory could run, which is how the basal-like concept reached clinical pathology and how the Carolina Breast Cancer Study defined its subtypes three years later.","caveats":["Small numbers and a wide confidence interval.","Cytokeratin 5/6 is a surrogate; the immunohistochemical definition of basal-like was never standardised."],"changedPractice":false,"participants":292},{"id":"paper-taylor-germline-brca2-evolutionary-trajectories-nat-commun-2017","kind":"paper","name":"Germline BRCA2 mutations drive prostate cancers with distinct evolutionary trajectories","aka":[],"tldr":"Reading the whole genomes of localised prostate cancers from 14 men who had inherited a BRCA2 fault found tumours that already looked like advanced disease while still confined to the prostate.","summary":"The genomes and methylomes of localised prostate cancer from 14 carriers of deleterious germline BRCA2 mutations were profiled. BRCA2-mutant prostate cancers showed increased genomic instability and a mutational profile that more closely resembled metastatic than localised disease. They showed genomic and epigenomic dysregulation of the MED12L and MED12 axis, which is frequently dysregulated in metastatic castration-resistant prostate cancer, and this dysregulation was enriched in BRCA2-mutant tumours containing intraductal carcinoma. Microdissection and sequencing of intraductal carcinoma and the juxtaposed adjacent non-intraductal invasive carcinoma in 10 patients demonstrated a common ancestor to both histopathologies.","asOf":"2026-09-25","links":[{"label":"Taylor et al., Nat Commun 2017: genomes and methylomes of localised prostate cancer from 14 germline BRCA2 carriers, with microdissection of intraductal carcinoma","url":"https://doi.org/10.1038/ncomms13671"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28067867/"}],"tags":[],"related":[],"cancers":["prostate"],"sections":[],"technologies":["wes-wgs"],"targets":["brca"],"drugs":[],"companies":[],"institutions":[],"pathways":["homologous-recombination-repair","chromosomal-instability","clonal-evolution"],"terms":["germline-vs-somatic","gbrca-mutation","hrd","intraductal-carcinoma-prostate"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-communications"],"dependsOn":[],"notes":[],"journal":"Nature Communications","year":2017,"doi":"10.1038/ncomms13671","pmid":"28067867","authors":"Taylor RA, Fraser M, Livingstone J, et al.","paperType":"basic","findings":["Localised BRCA2-mutant prostate cancers showed greater genomic instability and a metastatic-like mutational profile.","Dysregulation of the MED12L and MED12 axis, enriched in tumours containing intraductal carcinoma.","Intraductal carcinoma and the adjacent invasive carcinoma share a common ancestor on microdissection of 10 cases."],"whatItMeans":"It supplies the biological reason for treating a BRCA2 carrier's localised disease aggressively rather than watching it, and it settles a long-standing pathology question by showing that intraductal carcinoma and the adjacent invasive tumour are the same clone rather than two separate processes.","caveats":["Fourteen genomes, so gene-level claims rest on very small numbers.","Localised disease from carriers identified through genetics services.","MED12L has no therapeutic consequence."],"changedPractice":false,"participants":14},{"id":"paper-yurgelun-germline-second-hits-resected-pancreatic-genet-med-2019","kind":"paper","name":"Germline cancer susceptibility gene variants, somatic second hits, and survival outcomes in patients with resected pancreatic cancer","aka":[],"tldr":"Nearly one in ten of 289 unselected patients with resected pancreatic cancer carried an inherited cancer-gene variant, but the tumour had lost the second copy in fewer than half, which matters for whether PARP inhibitors will work.","summary":"Germline and somatic DNA from 289 patients with resected pancreatic ductal adenocarcinoma, ascertained without preselection, were analysed on a customised panel. 28 of 289 (9.7%) carried pathogenic or likely pathogenic germline variants: 21 (7.3%) in double-strand DNA damage repair genes (3 BRCA1, 4 BRCA2, 14 in ATM, BRIP1, CHEK2, NBN, PALB2, RAD50 or RAD51C), 3 Lynch syndrome and 4 other (APC p.I1307K, CDKN2A, TP53). Somatic sequencing and immunohistochemistry found second hits in 12 of 27 (44.4%). Carriers of double-strand repair variants had superior overall survival (hazard ratio 0.54).","asOf":"2026-09-24","links":[{"label":"Yurgelun et al., Genet Med 2019: germline variants and somatic second hits in 289 resected cancers","url":"https://doi.org/10.1038/s41436-018-0009-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29961768/"}],"tags":[],"related":["brca-germline","brca-somatic"],"cancers":["pancreatic","resectable-pdac","brca-palb2-pdac"],"sections":[],"technologies":["germline-testing"],"targets":["brca","atm","palb2","cdkn2a"],"drugs":[],"companies":[],"institutions":["dana-farber"],"pathways":[],"terms":["germline-vs-somatic"],"trials":[],"people":["andrew-aguirre"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Genetics in Medicine","year":2019,"doi":"10.1038/s41436-018-0009-5","pmid":"29961768","authors":"Yurgelun MB, Chittenden AB, Morales-Oyarvide V, et al.","paperType":"observational","findings":["Germline variants in 9.7%; double-strand repair genes 7.3%.","Somatic second hit in 12 of 27 carriers, 44.4%.","Repair-gene carriers: overall survival hazard ratio 0.54."],"whatItMeans":"A germline result is not the whole story: without loss of the second allele the tumour may not be repair-deficient, which is why tumour sequencing and, in trials, HRD signatures are read alongside.","caveats":["Resected patients; survival advantage may reflect platinum exposure.","Second-hit assessment on a panel misses epigenetic silencing."],"changedPractice":false,"participants":289},{"id":"paper-hahnen-geparsixto-germline-brca-jama-oncol-2017","kind":"paper","name":"Germline mutation status, pathological complete response, and disease-free survival in triple-negative breast cancer: secondary analysis of the GeparSixto randomized clinical trial","aka":[],"tldr":"In GeparSixto, 17% of triple-negative patients carried a germline BRCA1 or BRCA2 mutation; they responded well to chemotherapy whether or not carboplatin was added, while it was the non-carriers whose complete response rate rose from 36% to 55% with carboplatin.","summary":"Archived DNA from 291 of 315 TNBC patients in GeparSixto (NCT01426880) was analysed for germline mutations in BRCA1, BRCA2 and 16 other predisposition genes. Pathological complete response (ypT0/is ypN0) was 56.8% with carboplatin and 41.4% without (OR 1.87). Pathogenic BRCA1/2 germline mutations were present in 50 patients (17.2%). Without carboplatin, pCR was 66.7% in carriers versus 36.4% in non-carriers (OR 3.50); carboplatin did not raise the carriers' rate further (65.4%) but raised non-carriers' from 36.4% to 55% (OR 2.14), and non-carriers gained disease-free survival with carboplatin (85.3% versus 73.5%; HR 0.53).","asOf":"2026-09-24","links":[{"label":"Hahnen et al., JAMA Oncol 2017: germline status and response in 291 GeparSixto TNBC patients","url":"https://doi.org/10.1001/jamaoncol.2017.1007"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28715532/"}],"tags":[],"related":[],"cancers":["tnbc","tnbc-early"],"sections":[],"technologies":[],"targets":["brca"],"drugs":["carboplatin"],"companies":["gbg"],"institutions":[],"pathways":[],"terms":["gbrca-mutation","pcr"],"trials":["geparsixto"],"people":["sibylle-loibl","carsten-denkert","rita-schmutzler"],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2017,"doi":"10.1001/jamaoncol.2017.1007","pmid":"28715532","authors":"Hahnen E, Lederer B, Hauke J, et al.","paperType":"rct","findings":["Germline BRCA1/2 in 50 of 291 TNBC patients, 17.2%.","Carriers: pCR 66.7% without and 65.4% with carboplatin; non-carriers: 36.4% rising to 55%.","Non-carriers gained disease-free survival with carboplatin (HR 0.53)."],"whatItMeans":"Germline status changes the reading of the platinum question: in early TNBC the carboplatin benefit was seen in non-carriers, so a BRCA result argues for testing everyone rather than reserving platinum for carriers.","caveats":["Secondary analysis of a non-standard regimen with bevacizumab and liposomal doxorubicin.","Small carrier subgroups (24 and 26 patients)."],"changedPractice":false,"participants":291},{"id":"paper-palles-germline-pole-pold1-proofreading-nat-genet-2013","kind":"paper","name":"Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas","aka":[],"tldr":"Some families with many bowel polyps and early cancers have an inherited fault in the part of the copying machinery that checks its own work. The tumours end up with enormous numbers of mutations but normal-looking repeat sequences.","summary":"Whole-genome sequencing, supplemented by linkage and association analysis, identified specific heterozygous POLE or POLD1 germline variants in several multiple-adenoma and early-onset colorectal cancer cases but in no controls. The susceptibility variants, POLE p.Leu424Val and POLD1 p.Ser478Asn, have high penetrance, and POLD1 mutation was also associated with endometrial cancer predisposition. Both map to equivalent sites in the proofreading (exonuclease) domain of DNA polymerases epsilon and delta and are predicted to prevent correction of mispaired bases inserted during replication. Tumours from carriers were microsatellite stable but accumulated base substitutions, as confirmed by yeast functional assays; the authors noted that the hypermutant, microsatellite-stable colorectal cancers described shortly before were likely caused by somatic exonuclease-domain POLE mutations.","asOf":"2026-09-24","links":[{"label":"Palles et al., Nat Genet 2013: germline POLE and POLD1 proofreading-domain mutations predispose to colorectal adenomas and carcinomas","url":"https://doi.org/10.1038/ng.2503"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23263490/"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["germline-testing","wes-wgs"],"targets":["pole","pold1"],"drugs":[],"companies":[],"institutions":["oxford-cancer"],"pathways":["replication-stress","ddr"],"terms":["pole-ultramutation","hereditary-cancer-syndromes","germline-vs-somatic","tmb"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":2013,"doi":"10.1038/ng.2503","pmid":"23263490","authors":"Palles C, Cazier JB, Howarth KM, et al.","paperType":"translational","findings":["Germline POLE p.Leu424Val and POLD1 p.Ser478Asn are high-penetrance colorectal predisposition variants.","Carrier tumours are microsatellite stable but accumulate base substitutions.","POLD1 also predisposes to endometrial cancer."],"whatItMeans":"POLE and POLD1 are now on polyposis and colorectal germline panels, and the paper explains why a patient with many adenomas and an entirely normal mismatch repair panel still needs sequencing.","caveats":["Rare; most multiple-adenoma families still have no explanation.","Penetrance estimates come from selected families."],"changedPractice":true},{"id":"paper-neumann-germline-mutations-nonsyndromic-pheochromocytoma-nejm-2002","kind":"paper","name":"Germline mutations in nonsyndromic pheochromocytoma","aka":[],"tldr":"One in four patients with an apparently sporadic adrenaline-producing tumour turned out to carry an inherited mutation in one of four genes, showing that pheochromocytoma is the most heritable of all tumours and that everyone with one should be offered genetic testing.","summary":"Study of 271 patients with pheochromocytoma or paraganglioma and no family history or syndromic features, from the Freiburg-Warsaw-Columbus registry, tested for germline mutations in VHL, RET, SDHD and SDHB.\n\nMutations were found in 66 patients (24 percent), most often in VHL and SDHB, and were associated with younger age, multifocal and extra-adrenal tumours. The finding transformed pheochromocytoma from a tumour with 10 percent heritability to one where germline testing is recommended for every patient.","asOf":"2026-09-18","links":[{"label":"N Engl J Med 2002","url":"https://doi.org/10.1056/NEJMoa020152"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/12000816/"}],"tags":[],"related":[],"cancers":["hereditary-ppgl"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2002,"doi":"10.1056/NEJMoa020152","pmid":"12000816","authors":"Neumann HP, Bausch B, McWhinney SR, et al.","paperType":"translational","findings":["Germline mutations in VHL, RET, SDHD or SDHB in 66 of 271 (24 percent) apparently sporadic cases.","Mutation carriers were younger and more often had multifocal or extra-adrenal tumours."],"whatItMeans":"Every patient with a pheochromocytoma or paraganglioma is now offered germline testing, which directs surveillance of the patient and relatives and, with SDHB, warns of metastatic risk.","caveats":["Only four genes were tested; more than a dozen susceptibility genes are now known, raising the heritable fraction to about 40 percent.","Registry population may over-represent younger patients."],"changedPractice":true,"participants":271},{"id":"paper-bedrosian-asco-sso-germline-testing-breast-jco-2024","kind":"paper","name":"Germline testing in patients with breast cancer: ASCO-Society of Surgical Oncology guideline","aka":[],"tldr":"The 2024 American guideline says every woman diagnosed with breast cancer at 65 or under should be offered BRCA1/2 testing, as should anyone who might be treated with a PARP inhibitor, whatever her family history.","summary":"An ASCO-SSO panel developed recommendations from a systematic review (47 articles on testing, 18 on counselling) and formal consensus. BRCA1/2 testing should be offered to all newly diagnosed patients at 65 or under and to selected older patients based on personal or family history, ancestry or PARP inhibitor eligibility; to all patients with recurrent breast cancer who are PARP inhibitor candidates regardless of family history; to women with a second primary in either breast; and to previously treated patients diagnosed at 65 or under. Testing beyond BRCA1/2 for high-penetrance genes should follow supportive family history, and moderate-penetrance testing may be offered to inform risk. Variants of uncertain significance should not change management.","asOf":"2026-09-24","links":[{"label":"Bedrosian et al., J Clin Oncol 2024: ASCO-SSO guideline on germline testing in breast cancer","url":"https://doi.org/10.1200/JCO.23.02225"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38175972/"},{"label":"ASCO breast cancer guidelines","url":"https://ascopubs.org/topics/asco-guidelines/breast-cancer"}],"tags":[],"related":[],"cancers":["tnbc","breast-cancer"],"sections":[],"technologies":["germline-testing"],"targets":["brca"],"drugs":["olaparib","talazoparib"],"companies":[],"institutions":[],"pathways":[],"terms":["gbrca-mutation","vus","germline-vs-somatic"],"trials":[],"people":["giuseppe-curigliano"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2024,"doi":"10.1200/JCO.23.02225","pmid":"38175972","authors":"Bedrosian I, Somerfield MR, Achatz MI, et al.","paperType":"guideline","findings":["BRCA1/2 testing for all patients diagnosed at 65 or under, and for any PARP inhibitor candidate.","Testing for a second primary breast cancer and for previously treated patients diagnosed at 65 or under.","Variants of uncertain significance should not alter management."],"whatItMeans":"For TNBC, which is diagnosed young and is the PARP inhibitor-eligible subtype, the guideline makes germline testing part of the diagnostic workup rather than a referral decision.","caveats":["United States guideline; NHS eligibility runs through the National Genomic Test Directory R208 criteria.","Population testing beyond age 65 was not endorsed."],"changedPractice":true},{"id":"paper-getug-13-marker-guided-dose-dense-chemotherapy-fizazi-lancet-oncol-2014","kind":"paper","name":"GETUG 13: personalised chemotherapy based on tumour marker decline in poor-prognosis germ cell tumours","aka":[],"tldr":"Men with poor-prognosis testicular cancer whose tumour markers fell too slowly after one cycle of BEP did better when their chemotherapy was intensified, with fewer needing high-dose salvage treatment.","summary":"Phase 3 multicentre randomised trial: of 263 patients with poor-prognosis non-seminomatous germ cell tumours, 203 with an unfavourable marker decline after one BEP cycle were randomised to continue BEP (98) or switch to dose-dense chemotherapy (105); 51 with a favourable decline continued BEP.\n\nThree-year progression-free survival was 59 percent with dose-dense chemotherapy against 48 percent with BEP (hazard ratio 0.66, p 0.05) and 70 percent in the favourable group. More grade 3 to 4 neurotoxicity and haematotoxicity occurred with intensification, with no difference in toxic deaths; salvage high-dose chemotherapy was needed in 6 against 16 percent.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2014","url":"https://doi.org/10.1016/S1470-2045(14)70490-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25456363/"}],"tags":[],"related":[],"cancers":["non-seminoma","testicular"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["getug-13"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2014,"doi":"10.1016/S1470-2045(14)70490-5","pmid":"25456363","authors":"Fizazi K, Pagliaro L, Laplanche A, et al.","paperType":"rct","findings":["Three-year progression-free survival 59 percent (95% CI 49 to 68) versus 48 percent (38 to 59); hazard ratio 0.66 (0.44 to 1.00), p 0.05.","Favourable marker decline group: three-year progression-free survival 70 percent (57 to 81).","Salvage high-dose chemotherapy 6 versus 16 percent; grade 3 to 4 neurotoxicity 7 versus 1 percent."],"whatItMeans":"Early tumour marker decline should guide treatment intensification in poor-prognosis germ cell tumours, which is now standard in expert centres.","caveats":["Borderline statistical significance; the dose-dense regimen is complex and toxic and belongs in high-volume centres."],"changedPractice":true,"participants":263},{"id":"paper-gravis-getug-afu-15-docetaxel-lancet-oncol-2013","kind":"paper","name":"GETUG-AFU 15: androgen deprivation alone or with docetaxel in non-castrate metastatic prostate cancer","aka":["GETUG-AFU 15","GETUG 15","Gravis 2013 docetaxel hormone-sensitive"],"tldr":"The first trial to give chemotherapy at the same time as hormone therapy in newly diagnosed metastatic prostate cancer. It found no survival benefit and concluded against the approach, two years before two larger trials found the opposite.","summary":"Gwenaelle Gravis and the French GETUG-AFU group randomised 385 men with metastatic non-castrate prostate cancer to androgen deprivation alone or with up to nine cycles of docetaxel, between 2004 and 2008. Median follow-up was 50 months and the primary endpoint was overall survival.\n\nThe trial is in this roadmap because of what happened next. Its conclusion, printed in the abstract, was that docetaxel should not be used as part of first-line treatment. CHAARTED in 2015 and STAMPEDE in 2016 then reported the opposite, in larger populations with more high-volume disease, and the STOpCaP meta-analysis in 2016 resolved the three by pooling them. GETUG-AFU 15 is the clearest case in prostate cancer of a trial that was underpowered for the population in which the effect actually lives, and it is why the volume-of-disease subgroup became part of how the field thinks.","asOf":"2026-09-25","links":[{"label":"Lancet Oncol 2013","url":"https://doi.org/10.1016/s1470-2045(12)70560-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23306100/"},{"label":"ClinicalTrials.gov NCT00104715","url":"https://clinicaltrials.gov/study/NCT00104715"}],"tags":["prostate-evidence"],"related":["paper-chaarted-nejm-2015","paper-stampede-lancet-2016","paper-vale-stopcap-docetaxel-bisphosphonates-lancet-oncol-2016","prostate-roadmap"],"cancers":["prostate","prostate-mhspc"],"sections":["chemotherapy","hormonal"],"technologies":[],"targets":[],"drugs":["docetaxel"],"companies":[],"institutions":[],"pathways":[],"terms":["adt","hazard-ratio"],"trials":[],"people":["karim-fizazi"],"bottlenecks":["b-trial-design","b-negative-results","b-trial-enrolment"],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2013,"doi":"10.1016/s1470-2045(12)70560-0","pmid":"23306100","authors":"Gravis G, Fizazi K, Joly F, et al.","paperType":"rct","findings":["Median overall survival 58.9 months (95 percent confidence interval 50.8 to 69.1) with androgen deprivation plus docetaxel against 54.2 months (42.2 to not reached) with androgen deprivation alone; hazard ratio 1.01 (0.75 to 1.36).","72 serious adverse events in the docetaxel group, most frequently neutropenia in 40 patients (21 percent) and febrile neutropenia in 6 (3 percent).","Four treatment-related deaths occurred in the docetaxel group, two of them neutropenia-related, after which the data monitoring committee recommended granulocyte colony-stimulating factor; no further treatment-related deaths followed.","No serious adverse events were reported in the androgen deprivation alone group.","The published interpretation was that docetaxel should not be used as part of first-line treatment for non-castrate metastatic prostate cancer."],"whatItMeans":"A negative trial that was later overturned, and a standing argument for pooling individual trials rather than acting on the first one to report. It is also the reason the distinction between high-volume and low-volume metastatic disease is written into guidelines.","caveats":["385 patients, which is small for an overall survival endpoint in a disease with a median survival near five years.","Enrolment ran from 2004 to 2008, before prostate-specific membrane antigen imaging, so disease volume was classified on bone scan and computed tomography.","The trial included a higher proportion of low-volume disease than CHAARTED, which is the most likely explanation for the difference in result."],"changedPractice":true,"participants":385},{"id":"paper-ghsg-hd10-reduced-intensity-early-hodgkin-nejm-2010","kind":"paper","name":"GHSG HD10: reduced treatment intensity in early-stage favourable Hodgkin lymphoma","aka":[],"tldr":"Two cycles of ABVD chemotherapy and a lower radiotherapy dose cured early favourable Hodgkin lymphoma as well as four cycles and a higher dose, so patients could be given less treatment and fewer late effects.","summary":"German Hodgkin Study Group randomised 2 by 2 trial of 1,370 patients with early-stage favourable Hodgkin lymphoma comparing four with two cycles of ABVD and involved-field radiotherapy of 30 Gy with 20 Gy.\n\nFive-year freedom from treatment failure and overall survival were about 93 percent and 97 percent with no differences between arms, while toxicity was lower with the reduced treatment. Two cycles of ABVD followed by 20 Gy became a standard for early favourable disease.","asOf":"2026-09-18","links":[{"label":"N Engl J Med 2010","url":"https://doi.org/10.1056/NEJMoa1000067"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20818855/"}],"tags":[],"related":["lymphoma-roadmap","hd10","paper-ghsg-hd16-pet-guided-early-favourable-hodgkin-jco-2019"],"cancers":["early-stage-classical-hodgkin-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["doxorubicin","vinblastine","dacarbazine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["hd10"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2010,"doi":"10.1056/NEJMoa1000067","pmid":"20818855","authors":"Engert A, Plütschow A, Eich HT, et al.","paperType":"rct","findings":["Five-year freedom from treatment failure about 93 percent and overall survival about 97 percent, with no difference between two and four cycles of ABVD or between 20 and 30 Gy.","Fewer acute adverse events with the reduced-intensity arm."],"whatItMeans":"Patients with early favourable Hodgkin lymphoma are cured with two cycles of ABVD and 20 Gy of involved-site radiotherapy; later trials tested whether PET can spare radiotherapy altogether.","caveats":["Applies only to the GHSG favourable group (no bulk, few nodal areas, normal sedimentation rate, no extranodal disease).","Predates PET-guided therapy."],"changedPractice":true,"participants":1370},{"id":"paper-ghsg-hd21-brecadd-vs-ebeacopp-advanced-hodgkin-lancet-2024","kind":"paper","name":"GHSG HD21: PET-guided BrECADD versus escalated BEACOPP in advanced-stage classical Hodgkin lymphoma","aka":[],"tldr":"A new regimen built around brentuximab vedotin cured more patients with advanced Hodgkin lymphoma than the intensive BEACOPP standard, and did so with less toxicity, including less damage to fertility.","summary":"International randomised phase 3 trial of 1,500 patients with newly diagnosed advanced-stage classical Hodgkin lymphoma comparing PET-guided BrECADD (brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine and dexamethasone) with PET-guided escalated BEACOPP, four or six cycles depending on interim PET.\n\nFour-year progression-free survival was 94.3 percent with BrECADD against 90.9 percent with escalated BEACOPP, and treatment-related morbidity was lower (about 42 versus 59 percent), with faster recovery of gonadal function. BrECADD is now the GHSG standard for advanced disease.","asOf":"2026-09-18","links":[{"label":"Lancet 2024","url":"https://doi.org/10.1016/S0140-6736(24)01315-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38971175/"}],"tags":[],"related":["lymphoma-roadmap","paper-ghsg-hd18-pet-guided-escalated-beacopp-lancet-2017"],"cancers":["advanced-stage-classical-hodgkin-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["brentuximab-vedotin","doxorubicin","dacarbazine","etoposide","cyclophosphamide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["hd21"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2024,"doi":"10.1016/S0140-6736(24)01315-1","pmid":"38971175","authors":"Borchmann P, Ferdinandus J, Schneider G, et al.","paperType":"rct","findings":["Four-year progression-free survival 94.3 percent with BrECADD versus 90.9 percent with escalated BEACOPP.","Treatment-related morbidity about 42 versus 59 percent, with better recovery of gonadal function."],"whatItMeans":"For fit younger patients treated in the intensive German tradition, BrECADD replaces escalated BEACOPP; how it compares with nivolumab-AVD from S1826 is the open question.","caveats":["Patients were mostly under 60 and fit enough for intensive therapy.","Follow-up for late effects such as second cancers is still short."],"changedPractice":true,"participants":1500},{"id":"paper-ryan-support-care-cancer","kind":"paper","name":"Ginger (Zingiber officinale) reduces acute chemotherapy-induced nausea: a URCC CCOP study of 576 patients","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 21818642 and published in Supportive care in cancer; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: Despite the widespread use of antiemetics, nausea continues to be reported by over 70% of patients receiving chemotherapy.\n\nMethods: In this double blind, multicenter trial, we randomly assigned 744 cancer patients to four arms: 1) placebo, 2) 0.5 g ginger, 3) 1.0 g ginger, or 4) 1.5 g ginger. Nausea occurrence and severity were assessed at a baseline cycle and the two following cycles during which patients were taking their assigned study medication. All patients received a 5-HT(3) receptor antagonist antiemetic on Day 1 of all cycles. Patients took three capsules of ginger (250 mg) or placebo twice daily for 6 days starting 3 days before the first day of chemotherapy. Patients reported the severity of nausea on a 7-point rating scale (\"1\" = \"Not at all Nauseated\" and \"7\" = \"Extremely Nauseated\") for Days 1-4 of each cycle. The primary outcomes were to determine the dose and efficacy of ginger at reducing the severity of chemotherapy-induced nausea on Day 1 of chemotherapy.\n\nResults: A total of 576 patients were included in final analysis (91% female, mean age = 53). Mixed model analyses demonstrated that all doses of ginger significantly reduced acute nausea severity compared to placebo on Day 1 of chemotherapy (p = 0.003). The largest reduction in nausea intensity occurred with 0.5 g and 1.0 g of ginger (p = 0.017 and p = 0.036, respectively). Anticipatory nausea was a key factor in acute chemotherapy-induced nausea (p < 0.0001).\n\nConclusions: Ginger supplementation at a daily dose of 0.5 g-1.0 g significantly aids in reduction of the severity of acute chemotherapy-induced nausea in adult cancer patients.\n\nIndexed on Europe PMC as PubMed record 21818642 (DOI 10.1007/s00520-011-1236-3). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Support Care Cancer 2012","url":"https://doi.org/10.1007/s00520-011-1236-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21818642/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/21818642"}],"tags":["europepmc-ingest"],"related":["ginger-nausea"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["supportive-care-in-cancer"],"dependsOn":[],"notes":[],"journal":"Supportive care in cancer","year":2012,"doi":"10.1007/s00520-011-1236-3","pmid":"21818642","authors":"Ryan JL, Heckler CE, Roscoe JA, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nct04576455-j-clin-oncol-2024","kind":"paper","name":"Giredestrant for Estrogen Receptor-Positive, HER2-Negative, Previously Treated Advanced Breast Cancer: Results From the Randomized, Phase II acelERA Breast Cancer Study","aka":[],"tldr":"Published report from the trial registered as NCT04576455, in Journal of Clinical Oncology (2024), chosen as the most cited paper whose own text cites the registry id.","summary":"Purpose: To compare giredestrant and physician's choice of endocrine monotherapy (PCET) for estrogen receptor-positive, HER2-negative, advanced breast cancer (BC) in the phase II acelERA BC study (ClinicalTrials.gov identifier: NCT04576455).\n\nMethods: Post-/pre-/perimenopausal women, or men, age 18 years or older with measurable disease/evaluable bone lesions, whose disease progressed after 1-2 lines of systemic therapy (≤1 targeted, ≤1 chemotherapy regimen, prior fulvestrant allowed) were randomly assigned 1:1 to giredestrant (30 mg oral once daily) or fulvestrant/aromatase inhibitor per local guidelines (+luteinizing hormone-releasing hormone agonist in pre-/perimenopausal women, and men) until disease progression/unacceptable toxicity. Stratification was by visceral versus nonvisceral disease, prior cyclin-dependent kinase 4/6 inhibitor, and prior fulvestrant. The primary end point was investigator-assessed progression-free survival (INV-PFS).\n\nResults: At clinical cutoff (February 18, 2022; median follow-up: 7.9 months; N = 303), the INV-PFS hazard ratio (HR) was 0.81 (95% CI, 0.60 to 1.10; P =.1757). In the prespecified secondary end point analysis of INV-PFS by ESR1 mutation (m) status in circulating tumor DNA-evaluable patients (n = 232), the HR in patients with a detectable ESR1 m (n = 90) was 0.60 (95% CI, 0.35 to 1.03) versus 0.88 (95% CI, 0.54 to 1.42) in patients with no ESR1 m detected (n = 142). Related grade 3-4 adverse events (AEs), serious AEs, and discontinuations due to AEs were balanced across arms.\n\nConclusion: Although the acelERA BC study did not reach statistical significance for its primary INV-PFS end point, there was a consistent treatment effect with giredestrant across most key subgroups and a trend toward favorable benefit among patients with ESR1 -mutated tumors. Giredestrant was well tolerated, with a safety profile comparable to PCET and consistent with known endocrine therapy risks. Overall, these data support the continued investigation of giredestrant in other studies.\n\nIndexed on Europe PMC as PubMed record 38537155 (DOI 10.1200/jco.23.01500). Its abstract cites the registry id NCT04576455, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2024","url":"https://doi.org/10.1200/jco.23.01500"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38537155/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38537155"},{"label":"ClinicalTrials.gov NCT04576455","url":"https://clinicaltrials.gov/study/NCT04576455"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04576455"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2024,"doi":"10.1200/jco.23.01500","pmid":"38537155","authors":"Martín M, Lim E, Chavez-MacGregor M, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04576455 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-nct05009329-nat-med-2025","kind":"paper","name":"Glecirasib in KRAS G12C -mutated nonsmall-cell lung cancer: a phase 2b trial","aka":[],"tldr":"Published report from the trial registered as NCT05009329, in Nature Medicine (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Glecirasib (JAB-21822) is a new covalent oral KRAS-G12C inhibitor. This multicenter, single-arm phase 2b study assessed the efficacy and safety of glecirasib administered orally at 800 mg daily in patients with locally advanced or metastatic KRAS G12C -mutated nonsmall-cell lung cancer. The primary endpoint was the objective response rate (ORR) assessed by an independent review committee (IRC). Between 15 September 2022 and 28 September 2023, 119 patients with a median age of 62 years were enrolled. at the data cut-off date on 28 March 2024, the ORR assessed by IRC was 47.9% (56/117; 95% confidence interval: 38.5-57.3%). The incidence of treatment-related adverse events (TRAEs) of any grade was 97.5% (116/119). The incidence of grades 3 and 4 TRAEs was 38.7% (46/119). A total of 5.0% (6/119) of patients discontinued the treatment due to TRAEs. No treatment-related deaths occurred. Glecirasib exhibited promising clinical efficacy and manageable safety profiles in these patient populations. ClinicalTrials.gov identifier: NCT05009329.\n\nIndexed on Europe PMC as PubMed record 39762419 (DOI 10.1038/s41591-024-03401-z). Its abstract cites the registry id NCT05009329, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Nat Med 2025","url":"https://doi.org/10.1038/s41591-024-03401-z"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39762419/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39762419"},{"label":"ClinicalTrials.gov NCT05009329","url":"https://clinicaltrials.gov/study/NCT05009329"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05009329"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2025,"doi":"10.1038/s41591-024-03401-z","pmid":"39762419","authors":"Shi Y, Fang J, Xing L, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05009329 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-nct05288205-lancet-respir-med-2026","kind":"paper","name":"Glecirasib plus sitneprotafib in patients with KRAS G12C -mutated non-small-cell lung cancer in China: an open-label, multicentre, single-arm, phase 1/2a trial","aka":[],"tldr":"Published report from the Phase 1 trial registered as NCT05288205, in The Lancet. Respiratory medicine (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Monotherapy with KRAS G12C (ie, KRAS Gly12Cys) inhibitors has emerged as a mainstream treatment for patients with KRAS G12C -mutated non-small-cell lung cancer (NSCLC). Synergistic effects have been observed with the combination of a KRAS G12C inhibitor and a SHP2 inhibitor in multiple xenograft models. We aimed to evaluate the safety and efficacy of the KRAS G12C inhibitor glecirasib combined with the SHP2 inhibitor sitneprotafib (JAB-3312; Jacobio Pharmaceuticals, Beijing, China) in patients with KRAS G12C -mutated solid tumours.\n\nMethods: We conducted an open-label, multicentre, single-arm, phase 1/2a trial at 26 hospitals across China. Patients (aged ≥18 years) with locally advanced or metastatic solid tumours harbouring a KRAS G12C mutation, an Eastern Cooperative Oncology Group performance status score of 0-1, and measurable disease according to Response Evaluation Criteria in Solid Tumours (RECIST; version 1.1) were eligible for inclusion in both phases. Patients received oral glecirasib (400 mg or 800 mg once daily) in combination with oral sitneprotafib (2 mg or 3 mg once daily) in seven cohorts evaluating various dose levels and schedules of the two drugs. In phase 1, the primary endpoint was safety assessed by investigators according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0) from first treatment dose to 30 days after the last dose of both agents. In phase 2a, the primary endpoint was objective response rate (ORR) between baseline and disease progression or initiation of anticancer therapy, whichever occurred first, based on the comprehensive assessment of all tumour evaluations by investigators following RECIST (version 1.1). All patients who received at least one dose of combination therapy were included in the safety and efficacy analyses. This trial is registered with ClinicalTrials.gov (NCT05288205) and is currently recruiting.\n\nFindings: Between May 7, 2022, and Aug 20, 2024, a total of 194 patients with advanced solid tumours were enrolled, of whom 171 (88%) had NSCLC (50 [29%] in phase 1 and 121 [71%] in phase 2a). Median participant age was 65 years (IQR 59-70); 140 (82%) were men and 31 (18%) were women. At data cutoff on Aug 20, 2024, the median follow-up duration was 14·5 months (IQR 11·9-17·1), and 106 (62%) patients had discontinued treatment. Phase 1 concluded with one dose-limiting toxicity (DLT; grade 3 pneumonitis) at the highest dose level (glecirasib 800 mg plus sitneprotafib 3 mg once daily, 1 week on and 1 week off); no DLTs were observed at other dose levels. Across phase 1 and 2a, 167 patients (98%) had at least one treatment-related adverse event, which were grade 3-4 in 78 (46%) patients. The most common treatment-related adverse events (occurring in ≥20% of all 171 patients) were anaemia (105 [61%]), hypertriglyceridaemia (103 [60%]), increased aspartate aminotransferase (95 [56%]), increased alanine aminotransferase (83 [49%]), increased blood bilirubin (78 [46%]), oedema (62 [36%]), increased blood creatine phosphokinase (60 [35%]), neutropenia (54 [32%]), decreased white blood cell count (50 [29%]), and increased bodyweight (44 [26%]). Three (2%) patients discontinued glecirasib and sitneprotafib due to treatment-related adverse events. No grade 5 treatment-related adverse event was reported. The ORR was 71% (72 patients [95% CI 61-79]) in the subgroup of 102 patients with previously untreated NSCLC; 49% (19 patients [32-65]) in the 39 patients previously treated with systemic therapy but naive to KRAS G12C inhibitors; and 10% (three patients [2-27]) in the 30 patients previously treated with KRAS G12C inhibitor therapy.\n\nInterpretation: Glecirasib combined with sitneprotafib showed promising efficacy and manageable safety in patients with advanced KRAS G12C -mutated NSCLC, particularly among those who had not received previous treatment. These findings support the evaluation of this combination in a phase 3 trial comparing this chemotherapy-free regimen to current standard of care in this patient group.\n\nFunding: Jacobio Pharmaceuticals.\n\nTranslation: For the Chinese translation of the abstract see Supplementary Materials section.\n\nIndexed on Europe PMC as PubMed record 41325755 (DOI 10.1016/s2213-2600(25)00258-9). Its abstract cites the registry id NCT05288205, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Respir Med 2026","url":"https://doi.org/10.1016/s2213-2600(25)00258-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41325755/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41325755"},{"label":"ClinicalTrials.gov NCT05288205","url":"https://clinicaltrials.gov/study/NCT05288205"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05288205"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Lancet. Respiratory medicine","year":2026,"doi":"10.1016/s2213-2600(25)00258-9","pmid":"41325755","authors":"Zhong J, Zhao J, Duan J, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05288205 with the most citations, so it is the natural first reading for anyone following the Phase 1 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-andrew-lassman-neuro-oncol-2020","kind":"paper","name":"Glioblastoma in adults: a Society for Neuro-Oncology (SNO) and European Society of Neuro-Oncology (EANO) consensus review on current management and future directions","aka":[],"tldr":"Paper by Andrew B. Lassman indexed on Europe PMC as PubMed record 32328653, in Neuro-Oncology (2020), one of the most cited records naming an author with this name at Herbert Irving Comprehensive Cancer Center, Columbia University.","summary":"Glioblastomas are the most common form of malignant primary brain tumor and an important cause of morbidity and mortality. In recent years there have been important advances in understanding the molecular pathogenesis and biology of these tumors, but this has not translated into significantly improved outcomes for patients. In this consensus review from the Society for Neuro-Oncology (SNO) and the European Association of Neuro-Oncology (EANO), the current management of isocitrate dehydrogenase wildtype (IDHwt) glioblastomas will be discussed. In addition, novel therapies such as targeted molecular therapies, agents targeting DNA damage response and metabolism, immunotherapies, and viral therapies will be reviewed, as well as the current challenges and future directions for research.\n\nIndexed on Europe PMC as PubMed record 32328653 (DOI 10.1093/neuonc/noaa106). Its author list gives \"Lassman AB\" with the affiliation \"Department of Neurology and Herbert Irving Comprehensive Cancer Center, NewYork-Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, USA\", which names Herbert Irving Comprehensive Cancer Center, Columbia University; that is how the record was matched to Andrew B. Lassman, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Neuro Oncol 2020","url":"https://doi.org/10.1093/neuonc/noaa106"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32328653/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32328653"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["andrew-lassman"],"bottlenecks":[],"keyPapers":[],"journals":["neuro-oncology"],"dependsOn":[],"notes":[],"journal":"Neuro-Oncology","year":2020,"doi":"10.1093/neuonc/noaa106","pmid":"32328653","authors":"Wen PY, Weller M, Lee EQ, et al.","paperType":"review","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Andrew B. Lassman at Herbert Irving Comprehensive Cancer Center, Columbia University, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-kamath-neurosurgery","kind":"paper","name":"Glioblastoma Treated With Magnetic Resonance Imaging-Guided Laser Interstitial Thermal Therapy: Safety, Efficacy, and Outcomes","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 30137606 and published in Neurosurgery; the citing page links this DOI, which is how the record was matched.","summary":"Background: Despite the multitude of available treatments, glioblastoma (GBM) remains an aggressive and uniformly fatal tumor. Laser interstitial thermal therapy (LITT) is a novel, minimally invasive treatment that holds promise for treating patients with GBM who are not candidates for traditional open craniotomy. However, due to the recent introduction of LITT into clinical practice, large series that evaluate safety and long-term outcomes after LITT are lacking.\n\nObjective: To present our institution's series of over 50 GBM patients treated with LITT, with regard to safety, efficacy, and outcomes.\n\nMethods: We performed a retrospective descriptive study of patients with histologically proven GBM who underwent LITT. Data collected included demographics, tumor location and volume, tumor genetic markers, treatment volume, perioperative complications, and long-term follow-up data.\n\nResults: We performed 58 LITT treatments for GBM in 54 patients over 5.5 yr. Forty-one were recurrent tumors while 17 were frontline treatments. Forty GBMs were lobar in location, while 18 were in deep structures (thalamus, insula, corpus callosum). Average tumor volume was 12.5 ± 13.4 cm3. Average percentage of tumor treated with the yellow thermal damage threshold (TDT) line (dose equivalent of 43°C for 2 min) was 93.3% ± 10.6%, and with the blue TDT line (dose equivalent of 43°C for 10 min) was 88.0% ± 14.2%. There were 7 perioperative complications (12%) and 2 mortalities (3.4%). Median overall survival after LITT for the total cohort was 11.5 mo, and median progression-free survival 6.6 mo.\n\nConclusion: LITT appears to be a safe and effective treatment for GBM in properly selected patients.\n\nIndexed on Europe PMC as PubMed record 30137606 (DOI 10.1093/neuros/nyy375). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Neurosurgery 2019","url":"https://doi.org/10.1093/neuros/nyy375"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30137606/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30137606"}],"tags":["europepmc-ingest"],"related":["litt"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Neurosurgery","year":2019,"doi":"10.1093/neuros/nyy375","pmid":"30137606","authors":"Kamath AA, Friedman DD, Akbari SHA, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-weller-nat-rev-dis-primers","kind":"paper","name":"Glioma","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 27188790 and published in Nature reviews. Disease primers; the citing page links this DOI, which is how the record was matched.","summary":"Gliomas are primary brain tumours that are thought to derive from neuroglial stem or progenitor cells. On the basis of their histological appearance, they have been traditionally classified as astrocytic, oligodendroglial or ependymal tumours and assigned WHO grades I-IV, which indicate different degrees of malignancy. Tremendous progress in genomic, transcriptomic and epigenetic profiling has resulted in new concepts of classifying and treating gliomas. Diffusely infiltrating gliomas in adults are now separated into three overarching tumour groups with distinct natural histories, responses to treatment and outcomes: isocitrate dehydrogenase (IDH)-mutant, 1p/19q co-deleted tumours with mostly oligodendroglial morphology that are associated with the best prognosis; IDH-mutant, 1p/19q non-co-deleted tumours with mostly astrocytic histology that are associated with intermediate outcome; and IDH wild-type, mostly higher WHO grade (III or IV) tumours that are associated with poor prognosis. Gliomas in children are molecularly distinct from those in adults, the majority being WHO grade I pilocytic astrocytomas characterized by circumscribed growth, favourable prognosis and frequent BRAF gene fusions or mutations. Ependymal tumours can be molecularly subdivided into distinct epigenetic subgroups according to location and prognosis. Although surgery, radiotherapy and alkylating agent chemotherapy are still the mainstay of treatment, individually tailored strategies based on tumour-intrinsic dominant signalling pathways and antigenic tumour profiles may ultimately improve outcome. For an illustrated summary of this Primer, visit: http://go.nature.com/TXY7Ri.\n\nIndexed on Europe PMC as PubMed record 27188790 (DOI 10.1038/nrdp.2015.17). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Dis Primers 2015","url":"https://doi.org/10.1038/nrdp.2015.17"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27188790/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27188790"}],"tags":["europepmc-ingest"],"related":["glioma-signalling"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature reviews. Disease primers","year":2015,"doi":"10.1038/nrdp.2015.17","pmid":"27188790","authors":"Weller M, Wick W, Aldape K, et al.","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-sullivan-lancet-oncol","kind":"paper","name":"Global cancer surgery: delivering safe, affordable, and timely cancer surgery","aka":[],"tldr":"Paper cited by two bottleneck pages and 13 idea pages, indexed on Europe PMC as PubMed record 26427363 and published in The Lancet Oncology; the citing pages link this DOI, which is how the record was matched.","summary":"Surgery is essential for global cancer care in all resource settings. Of the 15.2 million new cases of cancer in 2015, over 80% of cases will need surgery, some several times. By 2030, we estimate that annually 45 million surgical procedures will be needed worldwide. Yet, less than 25% of patients with cancer worldwide actually get safe, affordable, or timely surgery. This Commission on global cancer surgery, building on Global Surgery 2030, has examined the state of global cancer surgery through an analysis of the burden of surgical disease and breadth of cancer surgery, economics and financing, factors for strengthening surgical systems for cancer with multiple-country studies, the research agenda, and the political factors that frame policy making in this area. We found wide equity and economic gaps in global cancer surgery. Many patients throughout the world do not have access to cancer surgery, and the failure to train more cancer surgeons and strengthen systems could result in as much as US $6.2 trillion in lost cumulative gross domestic product by 2030. Many of the key adjunct treatment modalities for cancer surgery--e.g., pathology and imaging--are also inadequate. Our analysis identified substantial issues, but also highlights solutions and innovations. Issues of access, a paucity of investment in public surgical systems, low investment in research, and training and education gaps are remarkably widespread. Solutions include better regulated public systems, international partnerships, super-centralisation of surgical services, novel surgical clinical trials, and new approaches to improve quality and scale up cancer surgical systems through education and training. Our key messages are directed at many global stakeholders, but the central message is that to deliver safe, affordable, and timely cancer surgery to all, surgery must be at the heart of global and national cancer control planning.\n\nIndexed on Europe PMC as PubMed record 26427363 (DOI 10.1016/s1470-2045(15)00223-5). Matched by DOI alone: two bottleneck pages and 13 idea pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2015","url":"https://doi.org/10.1016/s1470-2045(15)00223-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26427363/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26427363"}],"tags":["europepmc-ingest"],"related":["b-global-access","b-surgery-radiation-innovation","idea-fund-organ-preservation-programme","idea-fund-rt-io-platform","idea-fund-intraoperative-imaging-trials","idea-fund-surgical-video-registry","idea-fund-surgical-ai-robotics-evaluation","idea-moon-compact-flash-proton","idea-fund-adaptive-radiotherapy-evidence","idea-fund-ablation-versus-surgery-trials","idea-fund-course-based-radiotherapy-payment","idea-fund-omission-deescalation-trials","idea-fund-technique-innovation-prize","idea-moon-image-guided-surgery-everywhere","idea-fund-rt-planning-ai-capacity"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2015,"doi":"10.1016/s1470-2045(15)00223-5","pmid":"26427363","authors":"Sullivan R, Alatise OI, Anderson BO, et al.","paperType":"review","findings":[],"whatItMeans":"Two bottleneck pages and 13 idea pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-global-retinoblastoma-study-jama-oncol","kind":"paper","name":"Global Retinoblastoma Presentation and Analysis by National Income Level","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 32105305 and published in JAMA Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale.\n\nObjectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis.\n\nDesign, setting, and participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017.\n\nMain outcomes and measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis.\n\nResults: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]).\n\nConclusions and relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs.\n\nIndexed on Europe PMC as PubMed record 32105305 (DOI 10.1001/jamaoncol.2019.6716). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA Oncol 2020","url":"https://doi.org/10.1001/jamaoncol.2019.6716"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32105305/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32105305"}],"tags":["europepmc-ingest"],"related":["retinoblastoma"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2020,"doi":"10.1001/jamaoncol.2019.6716","pmid":"32105305","authors":"Global Retinoblastoma Study Group, Fabian ID, Abdallah E, et al.","paperType":"observational","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-glofitamab-dlbcl-n-engl-j-med-2022","kind":"paper","name":"Glofitamab for Relapsed or Refractory Diffuse Large B-Cell Lymphoma","aka":[],"tldr":"Phase 2 or 3 results paper on Glofitamab in Diffuse large B-cell lymphoma, in New England Journal of Medicine (2022), one of the most cited Europe PMC records with Glofitamab in its title.","summary":"Background: The prognosis for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) is poor. Glofitamab is a bispecific antibody that recruits T cells to tumor cells.\n\nMethods: In the phase 2 part of a phase 1-2 study, we enrolled patients with relapsed or refractory DLBCL who had received at least two lines of therapy previously. Patients received pretreatment with obinutuzumab to mitigate cytokine release syndrome, followed by fixed-duration glofitamab monotherapy (12 cycles total). The primary end point was complete response according to assessment by an independent review committee. Key secondary end points included duration of response, survival, and safety.\n\nResults: Of the 155 patients who were enrolled, 154 received at least one dose of any study treatment (obinutuzumab or glofitamab). At a median follow-up of 12.6 months, 39% (95% confidence interval [CI], 32 to 48) of the patients had a complete response according to independent review. Results were consistent among the 52 patients who had previously received chimeric antigen receptor T-cell therapy (35% of whom had a complete response). The median time to a complete response was 42 days (95% CI, 42 to 44). The majority (78%) of complete responses were ongoing at 12 months. The 12-month progression-free survival was 37% (95% CI, 28 to 46). Discontinuation of glofitamab due to adverse events occurred in 9% of the patients. The most common adverse event was cytokine release syndrome (in 63% of the patients). Adverse events of grade 3 or higher occurred in 62% of the patients, with grade 3 or higher cytokine release syndrome in 4% and grade 3 or higher neurologic events in 3%.\n\nConclusions: Glofitamab therapy was effective for DLBCL. More than half the patients had an adverse event of grade 3 or 4. (Funded by F. Hoffmann-La Roche; ClinicalTrials.gov number, NCT03075696.).\n\nIndexed on Europe PMC as PubMed record 36507690 (DOI 10.1056/nejmoa2206913). Its title names Glofitamab and its text names Diffuse large B-cell lymphoma; PubMed types it as a clinical trial report (Clinical Trial, Phase II, Research Support, Non-U.S. Gov't). It was matched automatically to the idea \"Head-to-head bispecific vs CAR-T in second-line LBCL\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2022","url":"https://doi.org/10.1056/nejmoa2206913"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36507690/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36507690"},{"label":"ClinicalTrials.gov NCT03075696","url":"https://clinicaltrials.gov/study/NCT03075696"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct03075696"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/nejmoa2206913","pmid":"36507690","authors":"Dickinson MJ, Carlo-Stella C, Morschhauser F, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Glofitamab in Diffuse large B-cell lymphoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Glofitamab in the title and Diffuse large B-cell lymphoma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-glofitamab-dlbcl-lancet-2024","kind":"paper","name":"Glofitamab plus gemcitabine and oxaliplatin (GemOx) versus rituximab-GemOx for relapsed or refractory diffuse large B-cell lymphoma (STARGLO): a global phase 3, randomised, open-label trial","aka":[],"tldr":"Phase 2 or 3 results paper on Glofitamab in Diffuse large B-cell lymphoma, in The Lancet (2024), one of the most cited Europe PMC records with Glofitamab in its title.","summary":"Background: Glofitamab monotherapy induces durable remission in patients with relapsed or refractory diffuse large B-cell lymphoma after two or more previous therapies, but has not previously been assessed as a second-line therapy. We investigated the efficacy and safety of glofitamab plus gemcitabine-oxaliplatin (Glofit-GemOx) versus rituximab (R)-GemOx in patients with relapsed or refractory diffuse large B-cell lymphoma.\n\nMethods: The phase 3, randomised, open-label STARGLO trial was done at 62 centres in 13 countries in Asia and Australia, Europe, and North America. We recruited transplant-ineligible patients (aged ≥18 years) with histologically confirmed relapsed or refractory diffuse large B-cell lymphoma after one or more previous therapies. Patients were randomly assigned in permuted blocks (block size of six) via an interactive voice or web response system (2:1; stratified by 1 vs ≥2 previous lines of therapy and relapsed vs refractory status) to Glofit-GemOx (intravenous gemcitabine 1000 mg/m 2 and oxaliplatin 100 mg/m 2 plus glofitamab step-up dosing to 30 mg; for a total of eight cycles, plus four additional cycles of glofitamab monotherapy) or R-GemOx (intravenous gemcitabine 1000 mg/m 2 and oxaliplatin 100 mg/m 2 plus rituximab 375 mg/m 2; for a total of eight cycles). The trial independent review committee, which evaluated all response-based endpoints, was masked to treatment assignment. The primary endpoint was overall survival. Efficacy analyses were by intention to treat in all randomly assigned patients. We present results from both the primary analysis (cutoff: March 29, 2023) and updated analysis after all patients had completed study therapy (cutoff: Feb 16, 2024). Safety analyses included all patients who received any study treatment. This study is registered with ClinicalTrials.gov, NCT04408638, and is ongoing (closed to recruitment).\n\nFindings: From Feb 23, 2021, to March 14, 2023, 274 patients were enrolled and randomly assigned to receive Glofit-GemOx (n=183) or R-GemOx (n=91). 158 (58%) patients were male and 116 (42%) were female; median age was 68 years (IQR 58-74). At the primary analysis after a median follow-up of 11·3 months (95% CI 9·6-12·7), overall survival was significantly improved with Glofit-GemOx versus R-GemOx (median not estimable [NE; 95% CI 13·8 months-NE] vs 9·0 months [7·3-14·4]; hazard ratio [HR] 0·59 [95% CI 0·40-0·89]; p=0·011). At the updated analysis after a median follow-up of 20·7 months (19·9-23·3), a consistent improvement in overall survival was observed with Glofit-GemOx versus R-GemOx (median 25·5 months [18·3-NE] vs 12·9 months [7·9-18·5]; HR 0·62 [0·43-0·88]). In the safety sets, 180 (100%) patients in the Glofit-GemOx group and 84 (96%) of 88 patients in the R-GemOx group had at least one adverse event during the study period. Cytokine release syndrome occurred in 76 (44%) of 172 glofitamab-exposed patients and was predominantly low grade. Deaths related to glofitamab or rituximab occurred in five (3%) patients in the Glofit-GemOx group and in one (1%) patient in the R-GemOx group.\n\nInterpretation: Glofit-GemOx had a significant overall survival benefit compared with R-GemOx, supporting its use in transplant-ineligible patients with relapsed or refractory diffuse large B-cell lymphoma after one or more previous lines of therapy.\n\nFunding: F Hoffmann-La Roche.\n\nIndexed on Europe PMC as PubMed record 39550172 (DOI 10.1016/s0140-6736(24)01774-4). Its title names Glofitamab and its text names Diffuse large B-cell lymphoma; PubMed types it as a clinical trial report (Clinical Trial, Phase III, Comparative Study, Research Support, Non-U.S. Gov't, Multicenter Study, Randomized Controlled Trial). It was matched automatically to the idea \"Head-to-head bispecific vs CAR-T in second-line LBCL\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet 2024","url":"https://doi.org/10.1016/s0140-6736(24)01774-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39550172/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39550172"},{"label":"ClinicalTrials.gov NCT04408638","url":"https://clinicaltrials.gov/study/NCT04408638"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["starglo"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2024,"doi":"10.1016/s0140-6736(24)01774-4","pmid":"39550172","authors":"Abramson JS, Ku M, Hertzberg M, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Glofitamab in Diffuse large B-cell lymphoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Glofitamab in the title and Diffuse large B-cell lymphoma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-glow-zolbetuximab-nat-med-2023","kind":"paper","name":"GLOW: zolbetuximab plus CAPOX in claudin 18.2-positive, HER2-negative gastric or gastro-oesophageal junction adenocarcinoma","aka":[],"tldr":"Adding the claudin 18.2 antibody zolbetuximab to CAPOX chemotherapy lengthened survival in claudin 18.2-positive advanced gastric cancer, confirming the SPOTLIGHT result with a different chemotherapy backbone.","summary":"Phase 3 placebo-controlled trial of 507 patients with untreated claudin 18.2-positive (75 percent or more of tumour cells), HER2-negative locally advanced or metastatic gastric or junctional adenocarcinoma randomised to zolbetuximab or placebo with capecitabine and oxaliplatin.\n\nMedian progression-free survival was 8.21 versus 6.80 months (hazard ratio 0.687) and median overall survival 14.39 versus 12.16 months (hazard ratio 0.771); nausea and vomiting were the characteristic added toxicities.","asOf":"2026-09-17","links":[{"label":"Nat Med 2023","url":"https://doi.org/10.1038/s41591-023-02465-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37524953/"}],"tags":[],"related":[],"cancers":["gastric-cldn18-2-positive"],"sections":[],"technologies":[],"targets":[],"drugs":["zolbetuximab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["manish-shah"],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2023,"doi":"10.1038/s41591-023-02465-7","pmid":"37524953","authors":"Shah MA, Shitara K, Ajani JA, et al.","paperType":"rct","findings":["Median overall survival 14.39 vs 12.16 months; hazard ratio 0.771.","Median progression-free survival 8.21 vs 6.80 months."],"whatItMeans":"Zolbetuximab with either FOLFOX or CAPOX is a first-line standard for claudin 18.2-positive, HER2-negative gastric cancer, making claudin 18.2 testing routine.","caveats":["About 38 percent of screened patients were claudin 18.2-positive.","Nausea and vomiting in the first cycles lead to some discontinuation."],"changedPractice":true,"participants":507},{"id":"paper-venkataramani-nature","kind":"paper","name":"Glutamatergic synaptic input to glioma cells drives brain tumour progression","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 31534219 and published in Nature; the citing page links this DOI, which is how the record was matched.","summary":"A network of communicating tumour cells that is connected by tumour microtubes mediates the progression of incurable gliomas. Moreover, neuronal activity can foster malignant behaviour of glioma cells by non-synaptic paracrine and autocrine mechanisms. Here we report a direct communication channel between neurons and glioma cells in different disease models and human tumours: functional bona fide chemical synapses between presynaptic neurons and postsynaptic glioma cells. These neurogliomal synapses show a typical synaptic ultrastructure, are located on tumour microtubes, and produce postsynaptic currents that are mediated by glutamate receptors of the AMPA subtype. Neuronal activity including epileptic conditions generates synchronised calcium transients in tumour-microtube-connected glioma networks. Glioma-cell-specific genetic perturbation of AMPA receptors reduces calcium-related invasiveness of tumour-microtube-positive tumour cells and glioma growth. Invasion and growth are also reduced by anaesthesia and the AMPA receptor antagonist perampanel, respectively. These findings reveal a biologically relevant direct synaptic communication between neurons and glioma cells with potential clinical implications.\n\nIndexed on Europe PMC as PubMed record 31534219 (DOI 10.1038/s41586-019-1564-x). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2019","url":"https://doi.org/10.1038/s41586-019-1564-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31534219/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31534219"}],"tags":["europepmc-ingest"],"related":["bioelectric-theory-of-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2019,"doi":"10.1038/s41586-019-1564-x","pmid":"31534219","authors":"Venkataramani V, Tanev DI, Strahle C, et al.","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-rose-cisplatin-chemoradiation-cervical-nejm-1999","kind":"paper","name":"GOG 120: concurrent cisplatin-based chemotherapy with radiotherapy for locally advanced cervical cancer","aka":[],"tldr":"Giving cisplatin during pelvic radiotherapy nearly halved the risk of death compared with radiotherapy with hydroxyurea in locally advanced cervical cancer, establishing weekly cisplatin chemoradiation as the worldwide standard.","summary":"Phase 3 trial of 526 women with stage IIB to IVA cervical cancer randomised to radiotherapy with weekly cisplatin, with cisplatin plus fluorouracil and hydroxyurea, or with hydroxyurea alone.\n\nBoth cisplatin arms improved progression-free and overall survival compared with hydroxyurea (relative risk of death 0.61 and 0.58), and weekly cisplatin was the least toxic, becoming the standard regimen.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 1999","url":"https://doi.org/10.1056/NEJM199904153401502"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/10202165/"}],"tags":[],"related":[],"cancers":["locally-advanced-cervical-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["cisplatin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":1999,"doi":"10.1056/NEJM199904153401502","pmid":"10202165","authors":"Rose PG, Bundy BN, Watkins EB, et al.","paperType":"rct","findings":["Relative risk of death 0.61 with weekly cisplatin vs hydroxyurea.","Four-year progression-free survival about 65 percent with cisplatin vs 47 percent with hydroxyurea."],"whatItMeans":"Weekly cisplatin with external beam radiotherapy and brachytherapy remains the backbone of curative treatment for locally advanced cervical cancer; INTERLACE and KEYNOTE-A18 build on it.","caveats":["The comparator (hydroxyurea) is not a no-chemotherapy control.","Brachytherapy technique has since advanced."],"changedPractice":true,"participants":526},{"id":"paper-gog-174-methotrexate-vs-dactinomycin-low-risk-gtn-jco-2011","kind":"paper","name":"GOG 174: weekly methotrexate or pulsed dactinomycin for low-risk gestational trophoblastic neoplasia","aka":[],"tldr":"In the only large randomised comparison of the two standard single drugs for low-risk GTN, dactinomycin given once a fortnight cured more women than weekly methotrexate, though both were followed by successful rescue in almost everyone.","summary":"Gynecologic Oncology Group randomised phase 3 trial of 216 eligible women with low-risk gestational trophoblastic neoplasia (WHO score 0 to 6) assigned to weekly intramuscular methotrexate 30 mg/m2 or pulsed intravenous dactinomycin 1.25 mg/m2 every two weeks.\n\nComplete response occurred in 70 percent with dactinomycin against 53 percent with methotrexate; women with a score of 5 to 6 or with choriocarcinoma did poorly with either drug. Nearly all women who failed were cured with subsequent therapy.","asOf":"2026-09-18","links":[{"label":"J Clin Oncol 2011","url":"https://doi.org/10.1200/JCO.2010.30.4386"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21263100/"}],"tags":[],"related":[],"cancers":["low-risk-gtn"],"sections":[],"technologies":[],"targets":[],"drugs":["methotrexate","dactinomycin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2011,"doi":"10.1200/JCO.2010.30.4386","pmid":"21263100","authors":"Osborne RJ, Filiaci V, Schink JC, et al.","paperType":"rct","findings":["Complete response 70 percent with pulsed dactinomycin versus 53 percent with weekly methotrexate.","Response rates were low with either drug in women with WHO scores of 5 to 6 or with choriocarcinoma."],"whatItMeans":"Pulsed dactinomycin is at least as good as weekly methotrexate for low-risk GTN, but many centres still prefer the multi-day methotrexate-folinic acid schedule, which was not tested here; overall cure approaches 100 percent whichever drug comes first.","caveats":["The weekly methotrexate schedule tested is less effective than the eight-day methotrexate-folinic acid regimen used in Europe.","Dactinomycin causes more nausea and alopecia."],"changedPractice":true,"participants":216},{"id":"paper-gog-240-bevacizumab-cervical-nejm-2014","kind":"paper","name":"GOG 240: bevacizumab added to chemotherapy for advanced cervical cancer","aka":[],"tldr":"Adding the anti-angiogenic antibody bevacizumab to chemotherapy lengthened survival by almost four months in recurrent or metastatic cervical cancer, the first targeted drug to improve survival in a gynaecological cancer.","summary":"Phase 3 factorial trial of 452 patients with recurrent, persistent or metastatic cervical cancer randomised to cisplatin-paclitaxel or topotecan-paclitaxel, with or without bevacizumab.\n\nMedian overall survival was 17.0 versus 13.3 months with bevacizumab (hazard ratio 0.71) and response 48 versus 36 percent; topotecan-paclitaxel was not superior to cisplatin-paclitaxel. Fistula occurred in about 6 percent of bevacizumab patients, mostly after prior radiotherapy.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2014","url":"https://doi.org/10.1056/NEJMoa1309748"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24552320/"}],"tags":[],"related":[],"cancers":["recurrent-metastatic-cervical-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["bevacizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["krishnansu-tewari"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2014,"doi":"10.1056/NEJMoa1309748","pmid":"24552320","authors":"Tewari KS, Sill MW, Long HJ, et al.","paperType":"rct","findings":["Median overall survival 17.0 vs 13.3 months; hazard ratio 0.71.","Objective response 48 percent vs 36 percent."],"whatItMeans":"Platinum-paclitaxel with bevacizumab became the first-line standard for advanced cervical cancer and remains the backbone to which pembrolizumab is added.","caveats":["Gastrointestinal and genitourinary fistulas in irradiated patients.","Hypertension and thromboembolism increased."],"changedPractice":true,"participants":452},{"id":"paper-gog-281-trametinib-lgsoc-gershenson-lancet-2022","kind":"paper","name":"GOG 281/LOGS: trametinib versus standard of care in recurrent low-grade serous ovarian cancer","aka":[],"tldr":"The MEK inhibitor trametinib more than doubled the time to progression compared with chemotherapy or hormone therapy in recurrent low-grade serous ovarian cancer, the first positive randomised trial in this slow-growing, chemotherapy-resistant disease.","summary":"Phase 2/3 trial of 260 patients with recurrent low-grade serous carcinoma of the ovary or peritoneum randomised to trametinib or investigator's choice of letrozole, tamoxifen, weekly paclitaxel, pegylated liposomal doxorubicin or topotecan.\n\nMedian progression-free survival was 13.0 versus 7.2 months (hazard ratio 0.48) and response 26 versus 6 percent; skin rash, anaemia and hypertension were common with trametinib.","asOf":"2026-09-17","links":[{"label":"Lancet 2022","url":"https://doi.org/10.1016/S0140-6736(21)02175-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35123694/"}],"tags":[],"related":[],"cancers":["low-grade-serous-ovarian-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["trametinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["david-gershenson"],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2022,"doi":"10.1016/S0140-6736(21)02175-9","pmid":"35123694","authors":"Gershenson DM, Miller A, Brady WE, et al.","paperType":"rct","findings":["Median progression-free survival 13.0 vs 7.2 months; hazard ratio 0.48.","Objective response 26 percent vs 6 percent."],"whatItMeans":"MEK inhibition is a standard option for recurrent low-grade serous ovarian cancer, and the trial validated the MAPK pathway as the disease's therapeutic target, now extended by avutometinib-defactinib.","caveats":["Open-label; overall survival not significantly different with crossover.","Toxicity led to dose reductions in many patients."],"changedPractice":true,"participants":260},{"id":"paper-gog-0261-carcinosarcoma-powell-jco-2022","kind":"paper","name":"GOG-0261: paclitaxel-carboplatin versus paclitaxel-ifosfamide in uterine carcinosarcoma","aka":[],"tldr":"For uterine carcinosarcoma, the standard breast and ovarian regimen carboplatin-paclitaxel was as effective as the older, more toxic paclitaxel-ifosfamide combination, simplifying treatment of this rare aggressive cancer.","summary":"Phase 3 non-inferiority trial of 536 patients with stage I to IV, persistent or recurrent uterine carcinosarcoma (with a small ovarian carcinosarcoma cohort) randomised to paclitaxel-carboplatin or paclitaxel-ifosfamide.\n\nMedian overall survival was 37 versus 29 months (hazard ratio 0.87, non-inferior) and progression-free survival 16 versus 12 months, with more haematological toxicity but less confusion and genitourinary toxicity with carboplatin.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2022","url":"https://doi.org/10.1200/JCO.21.02050"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35007153/"}],"tags":[],"related":[],"cancers":["uterine-carcinosarcoma"],"sections":[],"technologies":[],"targets":[],"drugs":["carboplatin","ifosfamide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2022,"doi":"10.1200/JCO.21.02050","pmid":"35007153","authors":"Powell MA, Filiaci VL, Hensley ML, et al.","paperType":"rct","findings":["Median overall survival 37 vs 29 months; hazard ratio 0.87 (non-inferior).","Median progression-free survival 16 vs 12 months."],"whatItMeans":"Carboplatin-paclitaxel is the chemotherapy standard for uterine carcinosarcoma in all stages, now combined with dostarlimab in advanced disease following RUBY, which included carcinosarcoma.","caveats":["Non-inferiority design; the trend favouring carboplatin was not tested for superiority.","Adjuvant radiotherapy was not standardised."],"changedPractice":true,"participants":536},{"id":"paper-nct05671510-nat-med-2026","kind":"paper","name":"Gotistobart or docetaxel in metastatic squamous non-small cell lung cancer: stage 1 of the randomized phase 3 PRESERVE-003 trial","aka":[],"tldr":"Published report from the PD-L1 Inhibitors trial registered as NCT05671510, in Nature Medicine (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"PRESERVE-003 is a two-stage phase 3 trial evaluating gotistobart (BNT316/ONC-392), a novel pH-sensitive anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) antibody that selectively depletes regulatory T cells within the tumor microenvironment, in patients with metastatic squamous non-small cell lung cancer (sqNSCLC) without actionable genomic alterations who progressed on programmed cell death protein/programmed death ligand 1 inhibitor/platinum-based chemotherapy-a population with a poor prognosis. Here we report on stage 1, which aimed to confirm the dose and assess the preliminary efficacy (primary outcome: overall survival; secondary outcomes: progression‑free survival, objective response rate and duration of response) and safety of gotistobart compared to docetaxel. Patients with sqNSCLC were randomized (1:1) to gotistobart (6 mg kg -1 with two 10 mg kg -1 loading doses every 3 weeks (N = 45)) or docetaxel (75 mg m - 2 every 3 weeks (N = 42)). After a median follow-up of 14.5 months, median overall survival was not reached with gotistobart (95% confidence interval (CI) 9.3 to not evaluable) versus 10.0 months (95% CI 6.2 to 11.9 months) with docetaxel (hazard ratio 0.46, 95% CI 0.25 to 0.84, nominal two-sided P = 0.0102). Safety was manageable, with grade ≥3 treatment-related adverse events in 42% and 49% of patients receiving gotistobart and docetaxel, respectively. Stage 1 results suggest that gotistobart monotherapy can provide clinically meaningful benefit for patients with programmed cell death protein/programmed death ligand 1-resistant and chemotherapy-resistant metastatic sqNSCLC. ClinicalTrials.gov identifier: NCT05671510.\n\nIndexed on Europe PMC as PubMed record 41896648 (DOI 10.1038/s41591-026-04323-8). Its abstract cites the registry id NCT05671510, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Nat Med 2026","url":"https://doi.org/10.1038/s41591-026-04323-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41896648/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41896648"},{"label":"ClinicalTrials.gov NCT05671510","url":"https://clinicaltrials.gov/study/NCT05671510"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05671510"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2026,"doi":"10.1038/s41591-026-04323-8","pmid":"41896648","authors":"Cho BC, Balaraman R, Chen HJ, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05671510 with the most citations, so it is the natural first reading for anyone following the PD-L1 Inhibitors trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-graall-2005-huguet-jco-2018","kind":"paper","name":"GRAALL-2005: randomised hyperfractionated cyclophosphamide in a paediatric-inspired adult ALL protocol","aka":[],"tldr":"Treating adults up to 59 with a children's-style leukaemia protocol produced remission in nine out of ten and five-year survival near 60 percent, but intensifying cyclophosphamide added nothing and patients aged 55 and over tolerated the treatment poorly.","summary":"Report of the randomised GRAALL-2005 trial: 787 evaluable adults with newly diagnosed Philadelphia-negative acute lymphoblastic leukaemia (525 B-lineage, 262 T-lineage; median age 36) were randomised to standard-dose or hyperfractionated cyclophosphamide during induction and late intensification of a paediatric-inspired protocol.\n\nThe complete remission rate was 91.9 percent; five-year event-free survival was 52.2 percent and overall survival 58.5 percent. Hyperfractionated cyclophosphamide did not improve remission or survival. Age continuously worsened outcomes, with 55 years the best cut-off (five-year event-free survival 55.7 percent under 55 against 25.8 percent at 55 and over).","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2018","url":"https://doi.org/10.1200/JCO.2017.76.8192"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29863974/"}],"tags":[],"related":[],"cancers":["all-leukemia"],"sections":[],"technologies":[],"targets":[],"drugs":["cyclophosphamide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["graall-2005"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2018,"doi":"10.1200/JCO.2017.76.8192","pmid":"29863974","authors":"Huguet F, Chevret S, Leguay T, et al.","paperType":"rct","findings":["Complete remission 91.9 percent; five-year event-free survival 52.2 percent (95% CI 48.5 to 55.7) and overall survival 58.5 percent.","Hyperfractionated cyclophosphamide did not increase remission or prolong event-free or overall survival.","Five-year event-free survival 55.7 percent under age 55 versus 25.8 percent at 55 and over (hazard ratio 2.16, p < 0.001)."],"whatItMeans":"Paediatric-inspired protocols are the reference for younger adults with ALL, but their intensity is not tolerated from about age 55, which is where reduced-intensity and antibody-based approaches take over.","caveats":["Patients aged 55 and over, who tolerated the protocol worst, were the only group in which hyperfractionated cyclophosphamide appeared to help."],"changedPractice":false,"participants":787},{"id":"paper-filippini-cochrane-database-syst-rev","kind":"paper","name":"Green tea (Camellia sinensis) for the prevention of cancer","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 32118296 and published in The Cochrane database of systematic reviews; the citing page links this DOI, which is how the record was matched.","summary":"Background: This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (2009, Issue 3).Tea is one of the most commonly consumed beverages worldwide. Teas from the plant Camellia sinensis can be grouped into green, black and oolong tea, and drinking habits vary cross-culturally. C sinensis contains polyphenols, one subgroup being catechins. Catechins are powerful antioxidants, and laboratory studies have suggested that these compounds may inhibit cancer cell proliferation. Some experimental and nonexperimental epidemiological studies have suggested that green tea may have cancer-preventative effects.\n\nObjectives: To assess possible associations between green tea consumption and the risk of cancer incidence and mortality as primary outcomes, and safety data and quality of life as secondary outcomes.\n\nSearch methods: We searched eligible studies up to January 2019 in CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and reference lists of previous reviews and included studies.\n\nSelection criteria: We included all epidemiological studies, experimental (i.e. randomised controlled trials (RCTs)) and nonexperimental (non-randomised studies, i.e. observational studies with both cohort and case-control design) that investigated the association of green tea consumption with cancer risk or quality of life, or both.\n\nData collection and analysis: Two or more review authors independently applied the study criteria, extracted data and assessed methodological quality of studies. We summarised the results according to diagnosis of cancer type.\n\nMain results: In this review update, we included in total 142 completed studies (11 experimental and 131 nonexperimental) and two ongoing studies. This is an additional 10 experimental and 85 nonexperimental studies from those included in the previous version of the review. Eleven experimental studies allocated a total of 1795 participants to either green tea extract or placebo, all demonstrating an overall high methodological quality based on 'Risk of bias' assessment. For incident prostate cancer, the summary risk ratio (RR) in the green tea-supplemented participants was 0.50 (95% confidence interval (CI) 0.18 to 1.36), based on three studies and involving 201 participants (low-certainty evidence). The summary RR for gynaecological cancer was 1.50 (95% CI 0.41 to 5.48; 2 studies, 1157 participants; low-certainty evidence). No evidence of effect of non-melanoma skin cancer emerged (summary RR 1.00, 95% CI 0.06 to 15.92; 1 study, 1075 participants; low-certainty evidence). In addition, adverse effects of green tea extract intake were reported, including gastrointestinal disorders, elevation of liver enzymes, and, more rarely, insomnia, raised blood pressure and skin/subcutaneous reactions. Consumption of green tea extracts induced a slight improvement in quality of life, compared with placebo, based on three experimental studies. In nonexperimental studies, we included over 1,100,000 participants from 46 cohort studies and 85 case-control studies, which were on average of intermediate to high methodological quality based on Newcastle-Ottawa Scale 'Risk of bias' assessment. When comparing the highest intake of green tea with the lowest, we found a lower overall cancer incidence (summary RR 0.83, 95% CI 0.65 to 1.07), based on three studies, involving 52,479 participants (low-certainty evidence). Conversely, we found no association between green tea consumption and cancer-related mortality (summary RR 0.99, 95% CI 0.91 to 1.07), based on eight studies and 504,366 participants (low-certainty evidence). For most of the site-specific cancers we observed a decreased RR in the highest category of green tea consumption compared with the lowest one. After stratifying the analysis according to study design, we found strongly conflicting results for some cancer sites: oesophageal, prostate and urinary tract cancer, and leukaemia showed an increased RR in cohort studies and a decreased RR or no difference in case-control studies.\n\nAuthors' conclusions: Overall, findings from experimental and nonexperimental epidemiological studies yielded inconsistent results, thus providing limited evidence for the beneficial effect of green tea consumption on the overall risk of cancer or on specific cancer sites. Some evidence of a beneficial effect of green tea at some cancer sites emerged from the RCTs and from case-control studies, but their methodological limitations, such as the low number and size of the studies, and the inconsistencies with the results of cohort studies, limit the interpretability of the RR estimates. The studies also indicated the occurrence of several side effects associated with high intakes of green tea. In addition, the majority of included studies were carried out in Asian populations characterised by a high intake of green tea, thus limiting the generalisability of the findings to other populations. Well conducted and adequately powered RCTs would be needed to draw conclusions on the possible beneficial effects of green tea consumption on cancer risk.\n\nIndexed on Europe PMC as PubMed record 32118296 (DOI 10.1002/14651858.cd005004.pub3). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cochrane Database Syst Rev 2020","url":"https://doi.org/10.1002/14651858.cd005004.pub3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32118296/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32118296"}],"tags":["europepmc-ingest"],"related":["green-tea-egcg"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Cochrane database of systematic reviews","year":2020,"doi":"10.1002/14651858.cd005004.pub3","pmid":"32118296","authors":"Filippini T, Malavolti M, Borrelli F, et al.","paperType":"meta-analysis","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-grid-regorafenib-gist-lancet-2013","kind":"paper","name":"GRID: regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib","aka":[],"tldr":"Regorafenib delayed progression by almost four months compared with placebo in gastrointestinal stromal tumours resistant to both imatinib and sunitinib, giving patients a third line of targeted therapy.","summary":"Phase 3 placebo-controlled trial of 199 patients with metastatic or unresectable GIST after failure of imatinib and sunitinib randomised 2:1 to regorafenib 160 mg daily (three weeks on, one off) or placebo with crossover at progression.\n\nMedian progression-free survival was 4.8 versus 0.9 months (hazard ratio 0.27) with disease control in 53 versus 9 percent; hypertension, hand-foot skin reaction and diarrhoea were the main toxicities.","asOf":"2026-09-17","links":[{"label":"Lancet 2013","url":"https://doi.org/10.1016/S0140-6736(12)61857-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23177515/"}],"tags":[],"related":[],"cancers":["gist-imatinib-resistant"],"sections":[],"technologies":[],"targets":[],"drugs":["imatinib","regorafenib","sunitinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["grid"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2013,"doi":"10.1016/S0140-6736(12)61857-1","pmid":"23177515","authors":"Demetri GD, Reichardt P, Kang YK, et al.","paperType":"rct","findings":["Median progression-free survival 4.8 vs 0.9 months; hazard ratio 0.27.","Disease control rate 52.6 percent vs 9.1 percent."],"whatItMeans":"Regorafenib is the standard third-line treatment for GIST after imatinib and sunitinib.","caveats":["No overall survival benefit because of crossover.","Dose reductions needed in most patients."],"changedPractice":true,"participants":199},{"id":"paper-grivennikov-immunity-inflammation-cancer-cell-2010","kind":"paper","name":"Grivennikov, Greten and Karin 2010: immunity, inflammation and cancer","aka":[],"tldr":"The review that laid out how inflammation contributes at every stage of cancer, from the DNA damage that starts it to the signals that help it grow and spread, and named the molecular switches, such as NF-kB and STAT3, that connect immune cells to tumour cells.","summary":"Grivennikov, Greten and Karin reviewed the roles of inflammation in tumour initiation, promotion, progression and metastasis. Chronic inflammation from infection, autoimmunity or environmental irritants produces reactive oxygen species and cytokines that damage DNA and stimulate proliferation; tumour-promoting inflammation acts through transcription factors NF-kB and STAT3 and cytokines such as IL-6, TNF and IL-1; and inflammation also supports angiogenesis and metastasis while suppressing anti-tumour immunity. They noted that a substantial share of cancers, on some estimates up to a fifth, is linked to chronic infection or inflammation.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1016/j.cell.2010.01.025"}],"tags":[],"related":["paper-coussens-werb-inflammation-cancer-nature-2002"],"cancers":[],"sections":[],"technologies":["aspirin-cancer-prevention"],"targets":["il6"],"drugs":[],"companies":[],"institutions":["uct-frankfurt","ucsd-moores"],"pathways":["inflammation-nfkb","jak-stat"],"terms":["inflammation","tumor-promoting-inflammation"],"trials":[],"people":["florian-greten"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Cell","year":2010,"doi":"10.1016/j.cell.2010.01.025","authors":"Grivennikov SI, Greten FR, Karin M.","paperType":"review","findings":["Inflammation contributes to initiation through DNA damage and to promotion through NF-kB and STAT3 signalling driven by cytokines such as IL-6 and TNF.","Tumour-associated inflammation also supports angiogenesis and metastasis and dampens adaptive anti-tumour immunity.","Chronic infection and inflammation are estimated to underlie up to about a fifth of cancers."],"whatItMeans":"This paper is the molecular sequel to the 2002 inflammation and cancer review and the basis for IL-6, JAK-STAT and NF-kB directed strategies in cancer as well as for aspirin and other anti-inflammatory prevention trials.","caveats":["A review synthesising mostly mouse genetic evidence.","Anti-inflammatory approaches have shown clearer benefit in prevention than in treating established cancers."],"changedPractice":false},{"id":"paper-groinss-v-ii-radiotherapy-vulvar-micrometastases-jco-2021","kind":"paper","name":"GROINSS-V II: radiotherapy versus inguinofemoral lymphadenectomy for vulvar cancer with sentinel node micrometastases","aka":[],"tldr":"When the sentinel node in the groin held only a tiny deposit of vulvar cancer, radiotherapy to the groin was a safe alternative to removing all the nodes; when the deposit was larger, radiotherapy alone was not enough.","summary":"Prospective multicentre phase 2 study of 1,535 women with early vulvar squamous cell carcinoma who had a sentinel node procedure; those with a positive node received inguinofemoral radiotherapy (50 Gy) instead of lymphadenectomy.\n\nAmong women with micrometastases (2 mm or less), the isolated groin recurrence rate at two years was about 1.6 percent with radiotherapy. Among those with macrometastases (over 2 mm), recurrence with radiotherapy alone was unacceptably high (about 22 percent), a stopping rule was triggered and lymphadenectomy was reinstated for that group.","asOf":"2026-09-18","links":[{"label":"J Clin Oncol 2021","url":"https://doi.org/10.1200/JCO.21.00006"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34432481/"}],"tags":[],"related":[],"cancers":["hpv-associated-vulvar-cancer","hpv-independent-vulvar-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2021,"doi":"10.1200/JCO.21.00006","pmid":"34432481","authors":"Oonk MHM, Slomovitz B, Baldwin PJW, et al.","paperType":"observational","findings":["Isolated groin recurrence at two years about 1.6 percent after radiotherapy for sentinel node micrometastases of 2 mm or less.","About 22 percent groin recurrence with radiotherapy alone for macrometastases over 2 mm, so lymphadenectomy remains the standard for those women."],"whatItMeans":"The size of the deposit in the sentinel node now decides treatment: radiotherapy for micrometastases, full groin dissection (with or without chemoradiotherapy) for macrometastases.","caveats":["Not randomised; the comparison is with historical outcomes after lymphadenectomy.","Long-term lymphoedema and other late effects of groin radiotherapy are still being followed."],"changedPractice":true,"participants":1535},{"id":"paper-groinss-v-sentinel-node-vulvar-cancer-jco-2008","kind":"paper","name":"GROINSS-V: sentinel node dissection is safe in early-stage vulvar cancer","aka":[],"tldr":"Removing only the first draining lymph node in the groin, and leaving the rest when it was clear, was safe for women with small vulvar cancers: very few groins relapsed and the swelling and wound problems of full groin surgery were largely avoided.","summary":"Prospective multicentre observational study of 403 women with unifocal vulvar squamous cell carcinoma under 4 cm and clinically negative groins who had sentinel node detection with radiotracer and blue dye; inguinofemoral lymphadenectomy was omitted when the sentinel node was negative.\n\nGroin recurrence occurred in 2.3 percent of women with a negative sentinel node, three-year survival was 97 percent, and wound breakdown, infection and lymphoedema were far less common than after full lymphadenectomy. The procedure became the standard for early vulvar cancer.","asOf":"2026-09-18","links":[{"label":"J Clin Oncol 2008","url":"https://doi.org/10.1200/JCO.2007.14.0566"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/18281661/"}],"tags":[],"related":[],"cancers":["hpv-associated-vulvar-cancer","hpv-independent-vulvar-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2008,"doi":"10.1200/JCO.2007.14.0566","pmid":"18281661","authors":"Van der Zee AG, Oonk MH, De Hullu JA, et al.","paperType":"observational","findings":["Groin recurrence in 2.3 percent of sentinel-node-negative women; three-year disease-specific survival 97 percent.","Short-term wound complications and lymphoedema much less frequent than after inguinofemoral lymphadenectomy."],"whatItMeans":"Women with small, unifocal vulvar cancers and clinically negative groins can be staged with a sentinel node procedure and spared full groin dissection when the node is clear.","caveats":["Applies only to unifocal tumours under 4 cm with clinically negative groins, in centres experienced in the technique.","Not randomised against lymphadenectomy."],"changedPractice":true,"participants":403},{"id":"paper-nct04270591-eclinicalmedicine-2023","kind":"paper","name":"Gumarontinib in patients with non-small-cell lung cancer harbouring MET exon 14 skipping mutations: a multicentre, single-arm, open-label, phase 1b/2 trial","aka":[],"tldr":"Published report from the trial registered as NCT04270591, in EClinicalMedicine (2023), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Approximately 3-4% of patients with non-small-cell lung cancer (NSCLC) have MET exon 14 ( MET ex14) skipping mutations. We report primary results from the phase 2 stage of a phase 1b/2 study of gumarontinib, a selective, potent, oral MET inhibitor, in patients with MET ex14 skipping mutation-positive ( MET ex14-positive) NSCLC.\n\nMethods: The single-arm, multicentre, open-label, phase 2 stage of the GLORY study was conducted at 42 centres across China and Japan. Adults with locally advanced or metastatic MET ex14-positive NSCLC received oral gumarontinib 300 mg once daily in continuous 21-day cycles until disease progression, intolerable toxicity, or withdrawal of consent. Eligible patients had failed one or two prior lines of therapy (not including a MET inhibitor), were ineligible for/refused chemotherapy, and had no genetic alterations targetable with standard therapies. The primary endpoint was objective response rate in patients with a valid baseline tumour assessment, by blinded independent review. The study was registered at ClinicalTrials.gov (NCT04270591).\n\nFindings: Between Aug 2, 2019 and Apr 28, 2021, 84 patients were enrolled and received gumarontinib (median follow-up 13.5 months [IQR 8.7-17.1]), at data cut-off (Apr 28, 2022) five patients whose MET ex14 status could not be confirmed by a central laboratory were excluded from the efficacy analysis. The objective response rate was 66% (95% CI 54-76) overall (n = 79), 71% (95% CI 55-83) in treatment-naïve patients (n = 44), and 60% (95% CI 42-76) in previously-treated patients (n = 35). The most common treatment-related adverse events (any grade) were oedema (67/84 patients, 80%) and hypoalbuminuria (32/84, 38%). Grade ≥3 treatment-emergent adverse events occurred in 45 (54%) patients. Treatment-related adverse events leading to permanent discontinuation occurred in 8% (7/84) of patients.\n\nInterpretation: Gumarontinib monotherapy had durable antitumour activity with manageable toxicity in patients with locally advanced or metastatic MET ex14-positive NSCLC when used in first line or later.\n\nFunding: Haihe Biopharma Co., Ltd. Supported in part by grants from the National Science and Technology Major Project of China for \"Clinical Research of Gumarontinib, a highly selective MET inhibitor\" (2018ZX09711002-011-003); the National Natural Science Foundation of China (82030045 to S.L. and 82172633 to YF.Y); Shanghai Municipal Science & Technology Commission Research Project (19411950500 to S.L.); Shanghai Shenkang Action Plan (16CR3005A to S.L.) and Shanghai Chest Hospital Project of Collaborative Innovation (YJXT20190105 to S.L.).\n\nIndexed on Europe PMC as PubMed record 37096188 (DOI 10.1016/j.eclinm.2023.101952). Its abstract cites the registry id NCT04270591, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"EClinicalMedicine 2023","url":"https://doi.org/10.1016/j.eclinm.2023.101952"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37096188/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37096188"},{"label":"ClinicalTrials.gov NCT04270591","url":"https://clinicaltrials.gov/study/NCT04270591"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04270591"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"EClinicalMedicine","year":2023,"doi":"10.1016/j.eclinm.2023.101952","pmid":"37096188","authors":"Yu Y, Zhou J, Li X, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04270591 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-freites-martinez-j-am-acad-dermatol","kind":"paper","name":"Hair disorders in cancer survivors","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 29660423 and published in Journal of the American Academy of Dermatology; the citing page links this DOI, which is how the record was matched.","summary":"With increasing survival rates across all cancers, survivors represent a growing population that is frequently affected by persistent or permanent hair growth disorders as a result of systemic therapies, radiotherapy, surgical procedures, and therapeutic transplants. These hair disorders include persistent chemotherapy-induced alopecia, persistent radiotherapy-induced alopecia, endocrine therapy-induced alopecia and hirsutism, postsurgery alopecia and localized hypertrichosis, and persistent stem cell transplantation and targeted therapy-induced alopecia. The information contained in this continuing medical education series should facilitate a better understanding on hair disorders in cancer survivors so that adequate support and therapies may be provided.\n\nIndexed on Europe PMC as PubMed record 29660423 (DOI 10.1016/j.jaad.2018.03.056). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Am Acad Dermatol 2019","url":"https://doi.org/10.1016/j.jaad.2018.03.056"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29660423/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29660423"}],"tags":["europepmc-ingest"],"related":["minoxidil-chemotherapy-alopecia"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of the American Academy of Dermatology","year":2019,"doi":"10.1016/j.jaad.2018.03.056","pmid":"29660423","authors":"Freites-Martinez A, Shapiro J, van den Hurk C, et al.","paperType":"review","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-hallmarks-new-dimensions-cancer-discov-2022","kind":"paper","name":"Hallmarks of Cancer 2022: adding phenotypic plasticity, epigenetic reprogramming, microbiomes and senescent cells","aka":[],"tldr":"The third hallmarks paper proposed two new hallmarks (unlocking phenotypic plasticity, senescent cells) and two new enabling characteristics (non-mutational epigenetic reprogramming, polymorphic microbiomes), bringing the framework to fourteen elements.","summary":"Twenty-two years after the original, Douglas Hanahan reviewed developments that the 2000 and 2011 frameworks did not accommodate. He proposed unlocking phenotypic plasticity (dedifferentiation, blocked differentiation and transdifferentiation, as in neuroendocrine transformation of prostate and lung cancers) as a hallmark, and senescent cells as a distinct cell type contributing to tumour progression.\n\nHe added non-mutational epigenetic reprogramming and polymorphic microbiomes as enabling characteristics: mechanisms by which cells acquire hallmark capabilities without new mutations, and ways in which microbial communities in gut and tumour modulate cancer risk, progression and therapy response.\n\nThe paper reflects how much lineage plasticity, epigenetics and the microbiome now feature in drug development, including for resistance to targeted therapy and immunotherapy.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1158/2159-8290.CD-21-1059"}],"tags":[],"related":["paper-hallmarks-of-cancer-cell-2000","unlocking-phenotypic-plasticity","nonmutational-epigenetic-reprogramming","polymorphic-microbiomes","senescent-cells"],"cancers":[],"sections":["drug-discovery","epigenetics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["epigenetic-reprogramming","senescence","microbiome-tumour","cancer-stem-cells-plasticity"],"terms":["hallmarks-of-cancer"],"trials":[],"people":[],"bottlenecks":["b-resistance","b-knowledge-diffusion"],"keyPapers":[],"journals":["cancer-discovery"],"dependsOn":[],"notes":[],"journal":"Cancer Discovery","year":2022,"doi":"10.1158/2159-8290.CD-21-1059","pmid":"35022204","authors":"Hanahan D","paperType":"review","findings":["New hallmark: unlocking phenotypic plasticity (dedifferentiation, blocked differentiation, transdifferentiation)","New hallmark: senescent cells, whose secretory phenotype can promote proliferation, invasion and immune suppression","New enabling characteristic: non-mutational epigenetic reprogramming, including microenvironment-driven states","New enabling characteristic: polymorphic microbiomes affecting carcinogenesis and therapy response","Reaffirmed the 2011 set of eight hallmarks and two enabling characteristics"],"whatItMeans":"Cancer is now understood to change its identity and behaviour without new mutations, to be shaped by bacteria inside and around it, and to be helped along by ageing cells. This explains why some tumours escape targeted drugs by changing cell type and why gut bacteria affect immunotherapy response.","caveats":["Single-author perspective; some proposed additions remain contested as hallmarks rather than mechanisms","Evidence for microbiome causality in human tumours is uneven and confounded","Senolytic therapy in cancer is early and unproven","The framework has grown to 14 elements, reducing the parsimony that made the original influential"],"changedPractice":false},{"id":"paper-saxena-mol-cell","kind":"paper","name":"Hallmarks of DNA replication stress","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 35714587 and published in Molecular cell; the citing page links this DOI, which is how the record was matched.","summary":"Faithful DNA replication is critical for the maintenance of genomic integrity. Although DNA replication machinery is highly accurate, the process of DNA replication is constantly challenged by DNA damage and other intrinsic and extrinsic stresses throughout the genome. A variety of cellular stresses interfering with DNA replication, which are collectively termed replication stress, pose a threat to genomic stability in both normal and cancer cells. To cope with replication stress and maintain genomic stability, cells have evolved a complex network of cellular responses to alleviate and tolerate replication problems. This review will focus on the major sources of replication stress, the impacts of replication stress in cells, and the assays to detect replication stress, offering an overview of the hallmarks of DNA replication stress.\n\nIndexed on Europe PMC as PubMed record 35714587 (DOI 10.1016/j.molcel.2022.05.004). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Mol Cell 2022","url":"https://doi.org/10.1016/j.molcel.2022.05.004"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35714587/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35714587"}],"tags":["europepmc-ingest"],"related":["replication-stress"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Molecular cell","year":2022,"doi":"10.1016/j.molcel.2022.05.004","pmid":"35714587","authors":"Saxena S, Zou L","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-huang-bone-marrow-transplant","kind":"paper","name":"Haploidentical hematopoietic stem cell transplantation without in vitro T-cell depletion for the treatment of hematological malignancies","aka":[],"tldr":"Paper cited by one institution page, indexed on Europe PMC as PubMed record 16883312 and published in Bone marrow transplantation; the citing page links this DOI, which is how the record was matched.","summary":"Many patients who require allogeneic hematopoietic stem cell transplantation (allo-HSCT) lack a human leukocyte antigen (HLA)-matched donor. Here, we report a protocol for haploidentical allo-HSCT that combines granulocyte-colony stimulating factor primed bone marrow (G-BM) and peripheral blood stem cells (PBSC) without in vitro T-cell depletion (TCD). In this study, 171 patients, including 86 in high-risk group, underwent transplantation from haploidentical family donors. All patients achieved sustained, full donor chimerism. One hundred and eleven patients were alive in remission at a median of 682 (253-1502) days. The cumulative incidence of grade III-IV acute graft-versus-host disease (GVHD) was 23% and that of extensive chronic GVHD, 47%; these were not influenced by HLA disparity. Patients younger than 15 years had less grade III-IV acute GVHD than older patients (P=0.044). The 2-year probability of relapse was 12% for standard-risk disease and 39% for high-risk disease. The 2-year probability of leukemia-free survival (LFS) was 68% for standard-risk patients and 42% for high-risk patients (P=0.0009). Grade III-IV acute GVHD was associated with better LFS (P=0.0017). The results require confirmation and show that G-BM combined with PBSC from haploidentical family donors, without in vitro TCD, may be used as a good source of stem cells for allo-HSCT.\n\nIndexed on Europe PMC as PubMed record 16883312 (DOI 10.1038/sj.bmt.1705445). Matched by DOI alone: one institution page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Bone Marrow Transplant 2006","url":"https://doi.org/10.1038/sj.bmt.1705445"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/16883312/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/16883312"}],"tags":["europepmc-ingest"],"related":["pku-peoples-hospital"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Bone marrow transplantation","year":2006,"doi":"10.1038/sj.bmt.1705445","pmid":"16883312","authors":"Huang XJ, Liu DH, Liu KY, et al.","paperType":"observational","findings":[],"whatItMeans":"One institution page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-harmoni-2-lancet-2025","kind":"paper","name":"HARMONi-2: ivonescimab, a PD-1 x VEGF bispecific, beats pembrolizumab head-to-head in PD-L1-positive lung cancer","aka":[],"tldr":"In the first randomised trial to beat pembrolizumab directly, a single antibody that blocks both PD-1 and VEGF nearly doubled the time to progression in PD-L1-positive lung cancer, though survival data were still immature.","summary":"Double-blind phase 3 trial conducted in China of 398 patients with untreated, PD-L1-positive (TPS 1% or more) advanced NSCLC without EGFR or ALK alterations, randomised to ivonescimab or pembrolizumab monotherapy. Primary endpoint was PFS by blinded review.\n\nMedian PFS was 11.1 vs 5.8 months (HR 0.51), with benefit in squamous and non-squamous histology and in PD-L1 1-49% and 50% or more. Overall survival was immature at publication and a later interim analysis did not reach statistical significance. It is the first time any agent has beaten pembrolizumab head-to-head in lung cancer and it revived interest in PD-(L)1 x VEGF bispecifics, with several Western companies licensing similar molecules.","asOf":"2026-09-08","links":[{"label":"PubMed search: HARMONi-2 ivonescimab Lancet","url":"https://pubmed.ncbi.nlm.nih.gov/?term=HARMONi-2+ivonescimab+pembrolizumab+Lancet"},{"label":"ClinicalTrials.gov NCT05499390","url":"https://clinicaltrials.gov/study/NCT05499390"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":["bispecific-antibody","checkpoint-inhibitor","antiangiogenic"],"targets":["pd1","vegf"],"drugs":["ivonescimab","pembrolizumab"],"companies":["akeso","summit-therapeutics","merck"],"institutions":[],"pathways":[],"terms":["pfs","os","first-line"],"trials":[],"people":["zhou-caicun"],"bottlenecks":["b-immunotherapy-response","b-trial-diversity","b-regulatory-fragmentation"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2025,"doi":"10.1016/S0140-6736(24)02722-3","pmid":"40057343","authors":"Zhou C, Chen J, Wu L, et al.","paperType":"rct","findings":["Median PFS 11.1 vs 5.8 months; HR 0.51 (95% CI 0.38-0.69).","Objective response 50.0% vs 38.5%.","Benefit seen in PD-L1 TPS 1-49% (HR 0.54) and 50% or more (HR 0.46), and in squamous (HR 0.48) and non-squamous (HR 0.54) tumours.","Grade 3 or higher treatment-related adverse events 29.4% vs 15.6%, largely VEGF-related (proteinuria, hypertension) with no excess of severe bleeding in squamous tumours.","Overall survival immature at primary analysis; a subsequent interim OS analysis showed a hazard ratio below 1 that was not statistically significant."],"whatItMeans":"For the first time a new drug has beaten pembrolizumab, the global first-line standard, in a randomised lung cancer trial, and it did so by combining checkpoint blockade with anti-angiogenesis in one molecule. For patients outside China nothing changes yet: the drug is not approved in the West, the trial was single-country, and survival benefit has not been shown. If confirmed in the global HARMONi-3 and HARMONi-7 trials, PD-1 x VEGF bispecifics could replace PD-1 antibodies as the immunotherapy backbone.","caveats":["Single-country (China) trial; generalisability to other populations is untested.","Progression-free survival only; overall survival has not reached significance, and pembrolizumab's own benefit is defined by OS.","Comparator was pembrolizumab monotherapy, whereas many PD-L1 1-49% patients would receive chemo-immunotherapy.","VEGF-class toxicities and the cost of a novel bispecific are additional considerations."],"changedPractice":false,"participants":398},{"id":"paper-plotkin-bevacizumab-nf2-nejm-2009","kind":"paper","name":"Hearing improvement after bevacizumab in patients with neurofibromatosis type 2","aka":[],"tldr":"In a small series of people with NF2 and progressive vestibular schwannomas, the anti-VEGF antibody bevacizumab shrank the tumours in most and, remarkably, improved hearing in more than half, opening the first drug treatment for these tumours.","summary":"Retrospective series of 10 patients with neurofibromatosis type 2 and progressive vestibular schwannomas treated with bevacizumab after showing VEGF expression in tumour specimens.\n\nTumour shrinkage occurred in nine of ten patients (volumetric response of 20 percent or more in six), and hearing improved in four of seven evaluable patients, with responses maintained over months of treatment.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2009","url":"https://doi.org/10.1056/NEJMoa0902579"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19587327/"}],"tags":[],"related":[],"cancers":["vestibular-schwannoma"],"sections":[],"technologies":[],"targets":[],"drugs":["bevacizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["scott-plotkin"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2009,"doi":"10.1056/NEJMoa0902579","pmid":"19587327","authors":"Plotkin SR, Stemmer-Rachamimov AO, Barker FG, et al.","paperType":"observational","findings":["Volumetric tumour response in six of ten patients.","Hearing improvement in four of seven evaluable patients."],"whatItMeans":"Bevacizumab is used off label for NF2-related schwannomatosis with growing tumours or declining hearing, supported by later phase 2 trials, and the study opened the search for medical therapy of schwannoma.","caveats":["Ten patients, retrospective, no control.","Responses are not permanent and treatment must continue; hypertension and proteinuria limit long-term use."],"changedPractice":true,"participants":10},{"id":"paper-heining-nrg1-fusions-kras-wild-type-pancreatic-cancer-discov-2018","kind":"paper","name":"Heining 2018: NRG1 fusions in KRAS wild-type pancreatic cancer","aka":[],"tldr":"Whole-genome and RNA sequencing of pancreatic cancers in younger patients found that most of the tumours without a KRAS mutation instead carried a fusion of the NRG1 gene, and two patients given a HER-family blocker responded. It established NRG1 fusions as the driver to look for in KRAS wild-type pancreatic cancer.","summary":"Report from the German NCT/DKTK MASTER precision oncology programme on whole-genome and transcriptome sequencing of pancreatic ductal adenocarcinomas from young patients (50 or under). Among the tumours without a KRAS mutation, most harboured an NRG1 gene fusion, whereas no KRAS-mutant tumour did.\n\nTwo patients with NRG1 fusion-positive tumours treated with the ERBB inhibitor afatinib had clinical and radiological responses, providing the first evidence that these fusions are actionable in pancreatic cancer and that RNA-level analysis is needed to find them.","asOf":"2026-09-21","links":[{"label":"Cancer Discov 2018","url":"https://doi.org/10.1158/2159-8290.CD-18-0036"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29802158/"}],"tags":[],"related":["kras-g12d"],"cancers":["kras-wild-type-pdac","pancreatic"],"sections":[],"technologies":["wes-wgs","rna-seq"],"targets":["nrg1","kras","her3"],"drugs":["afatinib"],"companies":[],"institutions":["dkfz","heidelberg-nct"],"pathways":["rtk-activation","ras-mapk"],"terms":["wild-type"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-discovery"],"dependsOn":[],"notes":[],"journal":"Cancer Discovery","year":2018,"doi":"10.1158/2159-8290.CD-18-0036","pmid":"29802158","authors":"Heining C, Horak P, Uhrig S, et al.","paperType":"translational","findings":["NRG1 fusions were found in most KRAS wild-type pancreatic cancers in a young-onset cohort and in none of the KRAS-mutant tumours.","Two patients with NRG1 fusion-positive tumours responded to afatinib."],"whatItMeans":"KRAS wild-type status should trigger fusion testing, ideally by RNA sequencing, because NRG1 fusions can be targeted by HER-family inhibitors and now by zenocutuzumab.","caveats":["A small, young-onset cohort; the frequency of NRG1 fusions in unselected KRAS wild-type disease is lower.","Afatinib responses were anecdotal and often short."],"changedPractice":true},{"id":"paper-llovet-nat-rev-dis-primers","kind":"paper","name":"Hepatocellular carcinoma","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 33479224 and published in Nature reviews. Disease primers; the citing page links this DOI, which is how the record was matched.","summary":"Liver cancer remains a global health challenge, with an estimated incidence of >1 million cases by 2025. Hepatocellular carcinoma (HCC) is the most common form of liver cancer and accounts for ~90% of cases. Infection by hepatitis B virus and hepatitis C virus are the main risk factors for HCC development, although non-alcoholic steatohepatitis associated with metabolic syndrome or diabetes mellitus is becoming a more frequent risk factor in the West. Moreover, non-alcoholic steatohepatitis-associated HCC has a unique molecular pathogenesis. Approximately 25% of all HCCs present with potentially actionable mutations, which are yet to be translated into the clinical practice. Diagnosis based upon non-invasive criteria is currently challenged by the need for molecular information that requires tissue or liquid biopsies. The current major advancements have impacted the management of patients with advanced HCC. Six systemic therapies have been approved based on phase III trials (atezolizumab plus bevacizumab, sorafenib, lenvatinib, regorafenib, cabozantinib and ramucirumab) and three additional therapies have obtained accelerated FDA approval owing to evidence of efficacy. New trials are exploring combination therapies, including checkpoint inhibitors and tyrosine kinase inhibitors or anti-VEGF therapies, or even combinations of two immunotherapy regimens. The outcomes of these trials are expected to change the landscape of HCC management at all evolutionary stages.\n\nIndexed on Europe PMC as PubMed record 33479224 (DOI 10.1038/s41572-020-00240-3). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Dis Primers 2021","url":"https://doi.org/10.1038/s41572-020-00240-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33479224/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33479224"}],"tags":["europepmc-ingest"],"related":["hepatocellular-carcinoma-signalling"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature reviews. Disease primers","year":2021,"doi":"10.1038/s41572-020-00240-3","pmid":"33479224","authors":"Llovet JM, Kelley RK, Villanueva A, et al.","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-richman-her2-amplification-quasar-focus-piccolo-j-pathol-2016","kind":"paper","name":"HER2 overexpression and amplification as a potential therapeutic target in colorectal cancer: analysis of 3256 patients enrolled in the QUASAR, FOCUS and PICCOLO colorectal cancer trials","aka":[],"tldr":"Staining more than three thousand tumours from three British trials put a number on how often bowel cancer is HER2-driven: about 1% at stage II-III and 2% at stage IV, rising to 5% in the tumours with no RAS or BRAF mutation.","summary":"HER2 amplification and overexpression were assessed in stage II-III and stage IV colorectal cancer patients, with the relationship to KRAS and BRAF status and outcome. Pathological material came from 1,914 patients in the QUASAR stage II-III trial and 1,342 patients in the FOCUS and PICCOLO stage IV trials, with tissue microarrays for HER2 immunohistochemistry, fluorescence in situ hybridisation and copy number for amplification, and pyrosequencing for KRAS and BRAF. HER2 protein overexpression was seen in 29 of 1,342 (2.2%) stage IV and 25 of 1,914 (1.3%) stage II-III tumours. Of the overexpressing cases, 27 of 28 stage IV and 20 of 24 stage II-III were amplified by fluorescence in situ hybridisation, and 41 of 47 showed copy number gains. Overexpression was associated with KRAS and BRAF wild-type status at all stages: 5.2% against 1.0% in stage IV and 2.1% against 0.2% in stage II-III. HER2 status was not associated with overall or progression-free survival, and at stage II-III there was no correlation with response to fluorouracil.","asOf":"2026-09-24","links":[{"label":"Richman et al., J Pathol 2016: HER2 amplification in 3,256 patients from QUASAR, FOCUS and PICCOLO","url":"https://doi.org/10.1002/path.4679"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26690310/"}],"tags":[],"related":["her2-ish-amplified","her2-ihc-3-plus"],"cancers":["colorectal"],"sections":[],"technologies":["histopathology-ihc","cytogenetics-fish"],"targets":["her2","kras","braf"],"drugs":[],"companies":[],"institutions":["leeds-cancer-centre"],"pathways":[],"terms":["ihc","fish","wild-type"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"Journal of Pathology","year":2016,"doi":"10.1002/path.4679","pmid":"26690310","authors":"Richman SD, Southward K, Chambers P, et al.","paperType":"observational","findings":["HER2 overexpression in 2.2% of stage IV and 1.3% of stage II-III patients.","5.2% of KRAS and BRAF wild-type stage IV tumours against 1.0% of mutant ones.","Overexpression almost always confirmed as amplification (27 of 28 stage IV cases)."],"whatItMeans":"It fixes the population size for HER2-directed therapy, shows the enrichment in wild-type disease that makes reflex HER2 testing worthwhile there, and establishes that HER2 is not itself prognostic in this cancer.","caveats":["Tissue microarrays can miss heterogeneous expression.","Predates the colorectal-specific HERACLES scoring criteria.","Trial populations rather than a consecutive series."],"changedPractice":false,"participants":3256},{"id":"paper-angerilli-her2-ihc-cish-biliary-hum-pathol-2026","kind":"paper","name":"HER2 status in extrahepatic cholangiocarcinoma and gallbladder carcinoma: concordance between immunohistochemistry and chromogenic in situ hybridization in 140 cases","aka":[],"tldr":"In 140 resected bile duct and gallbladder cancers scored by the rules used in the zanidatamab trial, about one in ten was HER2-positive; every strongly stained tumour had extra gene copies, some weakly stained ones did too, and staining was often patchy.","summary":"HER2 status was evaluated in 140 consecutive surgically resected biliary tract cancers collected between 2020 and 2025 (87 extrahepatic cholangiocarcinomas and 53 gallbladder carcinomas) using immunohistochemistry and dual chromogenic in situ hybridisation. HER2 expression was scored by gastric cancer criteria and positivity was defined by HERIZON-BTC-01 criteria; selected cases were also analysed with a combined IHC-DISH approach.\n\nHER2 expression was 0 in 72.9%, 1+ in 12.1%, 2+ in 8.6% and 3+ in 6.4% of cases. HER2 positivity was 9.2% in extrahepatic cholangiocarcinoma and 9.4% in gallbladder carcinoma. ERBB2 amplification was consistently identified in all IHC 3+ tumours and in a subset of IHC 2+ and, rarely, 1+ cases; the mean ERBB2/CEP17 ratio was 6.2 in 3+ tumours versus 3.9 in amplified 2+ or 1+ tumours (P = 0.001). Combined analysis confirmed that overexpression and amplification sat in the same tumour cells, and HER2 expression frequently showed intratumoral heterogeneity, often involving less than 50% of tumour cells.","asOf":"2026-09-24","links":[{"label":"Angerilli et al., Hum Pathol 2026: HER2 IHC and chromogenic ISH concordance in 140 biliary cancers","url":"https://doi.org/10.1016/j.humpath.2026.106234"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42595189/"}],"tags":[],"related":[],"cancers":["gallbladder","extrahepatic-cholangiocarcinoma","cholangiocarcinoma"],"sections":[],"technologies":[],"targets":["her2"],"drugs":["zanidatamab"],"companies":[],"institutions":[],"pathways":[],"terms":["ihc","fish","her2-testing-in-biliary-cancer","her2-positive"],"trials":["herizon-btc-01"],"people":[],"bottlenecks":["b-biomarker-validation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Human Pathology","year":2026,"doi":"10.1016/j.humpath.2026.106234","pmid":"42595189","authors":"Angerilli V, Gasparello J, Niero M, et al.","paperType":"observational","findings":["IHC 0 in 72.9%, 1+ in 12.1%, 2+ in 8.6%, 3+ in 6.4%; HER2-positive 9.4% of gallbladder and 9.2% of extrahepatic tumours.","All IHC 3+ tumours were amplified; mean ERBB2/CEP17 ratio 6.2 in 3+ versus 3.9 in amplified 2+ or 1+ tumours.","Heterogeneous staining, often under 50% of tumour cells."],"whatItMeans":"A direct check of the HERIZON-BTC-01 testing algorithm in routine pathology: IHC 3+ can stand alone, 2+ needs ISH, and the low-level amplification in weakly stained tumours is the group where HER2 drugs are least likely to help.","caveats":["Resected Italian cases; advanced disease may differ.","Chromogenic rather than fluorescent ISH; consecutive but single-region series."],"changedPractice":false,"participants":140},{"id":"paper-galdy-her2-biliary-tract-meta-analysis-cancer-metastasis-rev-2017","kind":"paper","name":"HER2/HER3 pathway in biliary tract malignancies; systematic review and meta-analysis: a potential therapeutic target?","aka":[],"tldr":"Pooling 40 studies, about one in five bile duct and gallbladder cancers outside the liver over-express HER2, against fewer than one in twenty inside the liver, which is why HER2 drugs matter most for gallbladder cancer.","summary":"Systematic review and meta-analysis from Manchester of HER2 and HER3 overexpression (immunohistochemistry) and amplification (in situ hybridisation) in biliary tract cancers; 40 of 440 screened studies qualified. Overall HER2 expression was 26.5 percent (95 percent CI 18.9 to 34.1). In 27 high-quality studies (moderate or strong staining), extrahepatic biliary cancers showed 19.9 percent (12.8 to 27.1) overexpression against 4.8 percent (0 to 14.5) for intrahepatic cholangiocarcinoma (p=0.0049). Amplification was 57.6 percent in patients selected by overexpression and 17.9 percent unselected. HER3 overexpression was 27.9 percent.","asOf":"2026-09-24","links":[{"label":"Cancer Metastasis Rev 2017","url":"https://doi.org/10.1007/s10555-016-9645-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27981460/"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder","extrahepatic-cholangiocarcinoma","biliary-tract-cancer"],"sections":[],"technologies":[],"targets":["her2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["her2-positive","ihc","fish"],"trials":[],"people":["angela-lamarca","juan-valle"],"bottlenecks":["b-biomarker-validation"],"keyPapers":[],"journals":["cancer-metastasis-reviews"],"dependsOn":[],"notes":[],"journal":"Cancer Metastasis Reviews","year":2017,"doi":"10.1007/s10555-016-9645-x","pmid":"27981460","authors":"Galdy S, Lamarca A, McNamara MG, et al.","paperType":"meta-analysis","findings":["HER2 overexpression 19.9 percent (95 percent CI 12.8 to 27.1) in extrahepatic biliary cancers vs 4.8 percent (0 to 14.5) in intrahepatic cholangiocarcinoma in high-quality studies.","Amplification 57.6 percent among overexpressors vs 17.9 percent unselected.","HER3 overexpression 27.9 percent."],"whatItMeans":"The prevalence estimate that made HER2 the first gallbladder-relevant target; it argues for testing every advanced gallbladder cancer, since one in five may qualify for zanidatamab or trastuzumab deruxtecan.","caveats":["Scoring criteria varied across studies; the 26.5 percent overall figure includes weak staining.","Gallbladder cancer is pooled with extrahepatic cholangiocarcinoma."],"changedPractice":false},{"id":"paper-her2climb-brain-lin-jco-2020","kind":"paper","name":"HER2CLIMB brain metastases analysis: intracranial efficacy and survival with tucatinib","aka":[],"tldr":"Among the HER2CLIMB patients with brain metastases, tucatinib doubled the intracranial response rate, cut the risk of intracranial progression or death by about two thirds and lengthened survival.","summary":"Exploratory analysis of the 291 HER2CLIMB patients with brain metastases at baseline, including 174 with active lesions.\n\nRisk of intracranial progression or death was reduced by 68 percent with tucatinib, median central nervous system progression-free survival was 9.9 versus 4.2 months, intracranial response was 47.3 versus 20.0 percent, and median overall survival was 18.1 versus 12.0 months.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2020","url":"https://doi.org/10.1200/JCO.20.00775"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32468955/"}],"tags":[],"related":[],"cancers":["her2-positive-breast-brain-metastases"],"sections":[],"technologies":[],"targets":[],"drugs":["capecitabine","trastuzumab","tucatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["her2climb"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/JCO.20.00775","pmid":"32468955","authors":"Lin NU, Borges V, Anders C, et al.","paperType":"rct","findings":["Intracranial objective response 47.3 percent vs 20.0 percent.","Median central nervous system progression-free survival 9.9 vs 4.2 months; median overall survival 18.1 vs 12.0 months."],"whatItMeans":"This analysis is the evidence base for treating active HER2-positive brain metastases with a systemic regimen, sometimes deferring radiotherapy, and for tucatinib's brain-specific labelling.","caveats":["Exploratory subgroup analysis, though prespecified.","Local therapy was permitted at isolated brain progression, which complicates interpretation."],"changedPractice":true,"participants":291},{"id":"paper-her2climb-05-j-clin-oncol-2026","kind":"paper","name":"HER2CLIMB-05: A Phase III Study of Tucatinib Versus Placebo in Combination With Trastuzumab and Pertuzumab as First-Line Maintenance Therapy for HER2+ Metastatic Breast Cancer","aka":[],"tldr":"Published report from the HER2CLIMB-05 trial registered as NCT05132582, in Journal of Clinical Oncology (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Purpose: The HER2CLIMB-05 study (ClinicalTrials.gov identifier: NCT05132582) is investigating the efficacy and safety of adding tucatinib to trastuzumab and pertuzumab as first-line (1L) maintenance therapy in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC).\n\nMethods: Patients with centrally confirmed HER2+ MBC without evidence of progression post induction therapy and no or asymptomatic brain metastases (BM) were enrolled. Patients were randomly assigned 1:1 to tucatinib (300 mg) or placebo twice a day combined with trastuzumab/pertuzumab. The primary end point is investigator-assessed progression-free survival (PFS); secondary end points include overall survival (OS), PFS per blinded independent central review, CNS-PFS, and safety.\n\nResults: Between March 2022 and July 2024, 654 patients were randomly assigned to tucatinib (n = 326) and placebo (n = 328) arms. All patients were female (median age, 54 years), 69.3% had de novo MBC, 52.6% were hormone receptor-positive, and 12.4% had presence/history of baseline BM. In this primary analysis, PFS was statistically significantly improved with addition of tucatinib versus placebo (hazard ratio, 0.641 [95% CI, 0.514 to 0.799]; P <.0001; median PFS: 24.9 v 16.3 months); a PFS benefit was seen regardless of the presence/absence of BM or hormone receptor status. OS data remain immature. The most common treatment-emergent adverse events (TEAEs) in the tucatinib arm were diarrhea (72.7%), nausea (33.1%), and elevated liver enzymes (ALT: 28.2%; AST: 25.8%), of which 6.1%, 0.9%, 13.5%, and 7.1%, respectively, were grade ≥3. In the tucatinib arm, 13.5% discontinued tucatinib because of TEAEs.\n\nConclusion: Tucatinib addition to trastuzumab and pertuzumab demonstrated improvement in PFS with no new safety signals identified and may be an option for 1L maintenance therapy in patients with HER2+ MBC.\n\nIndexed on Europe PMC as PubMed record 41369677 (DOI 10.1200/jco-25-02600). Its abstract cites the registry id NCT05132582, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2026","url":"https://doi.org/10.1200/jco-25-02600"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41369677/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41369677"},{"label":"ClinicalTrials.gov NCT05132582","url":"https://clinicaltrials.gov/study/NCT05132582"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["her2climb-05"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2026,"doi":"10.1200/jco-25-02600","pmid":"41369677","authors":"Dieras V, Curigliano G, Martin M, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05132582 with the most citations, so it is the natural first reading for anyone following the HER2CLIMB-05 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-her2climb-nejm-2020","kind":"paper","name":"HER2CLIMB: tucatinib with trastuzumab and capecitabine for HER2-positive metastatic breast cancer, including brain metastases","aka":[],"tldr":"Adding the brain-penetrant HER2 pill tucatinib to trastuzumab and capecitabine lengthened survival in heavily pretreated HER2-positive metastatic breast cancer, and uniquely the trial included patients with active brain metastases, who also benefited.","summary":"Phase 3 placebo-controlled trial of 612 patients with HER2-positive metastatic breast cancer previously treated with trastuzumab, pertuzumab and T-DM1, randomised 2:1 to tucatinib or placebo with trastuzumab and capecitabine; nearly half had brain metastases, including untreated or progressing lesions.\n\nOverall survival at two years was 44.9 percent with tucatinib against 26.6 percent with placebo (hazard ratio 0.66); progression-free survival among patients with brain metastases at one year was 24.9 versus 0 percent.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2020","url":"https://doi.org/10.1056/NEJMoa1914609"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31825569/"}],"tags":[],"related":[],"cancers":["her2-positive-breast-brain-metastases"],"sections":[],"technologies":[],"targets":[],"drugs":["capecitabine","trastuzumab","tucatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["her2climb"],"people":["rashmi-murthy"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2020,"doi":"10.1056/NEJMoa1914609","pmid":"31825569","authors":"Murthy RK, Loi S, Okines A, et al.","paperType":"rct","findings":["Two-year overall survival 44.9 percent vs 26.6 percent; hazard ratio for death 0.66.","One-year progression-free survival in patients with brain metastases 24.9 percent vs 0 percent."],"whatItMeans":"Tucatinib-based therapy is the standard for HER2-positive disease with active brain metastases and a standard later-line option overall; it was the first trial to enrol progressing brain metastases and show a systemic drug helps them.","caveats":["Diarrhoea and liver enzyme rises were more frequent with tucatinib.","Trial predates trastuzumab deruxtecan as second-line standard."],"changedPractice":true,"participants":612},{"id":"paper-ligtenberg-epcam-deletion-msh2-silencing-nat-genet-2009","kind":"paper","name":"Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3' exons of TACSTD1","aka":[],"tldr":"Some families with inherited bowel cancer have no mutation in any repair gene. The fault is in the neighbouring gene: losing its end makes it run on into the repair gene and chemically silence it, but only in the tissues where the neighbour is switched on.","summary":"Patients from Dutch and Chinese families with MSH2-deficient tumours were found to carry heterozygous germline deletions of the last exons of TACSTD1 (EPCAM), the gene directly upstream of MSH2. Because of these deletions, transcription of TACSTD1 extends into MSH2. The MSH2 promoter in cis with the deletion was methylated in EpCAM-positive but not in EpCAM-negative normal tissues, showing a correlation between activity of the mutated TACSTD1 allele and epigenetic inactivation of the corresponding MSH2 allele. The authors proposed gene silencing by transcriptional read-through of a neighbouring gene as a general mutational mechanism, producing generalised or mosaic epigenetic inactivation depending on the neighbour's expression pattern.","asOf":"2026-09-24","links":[{"label":"Ligtenberg et al., Nat Genet 2009: EPCAM (TACSTD1) 3' deletions silence MSH2 in Lynch syndrome","url":"https://doi.org/10.1038/ng.283"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19098912/"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["germline-testing"],"targets":["msh2","epcam","mmr"],"drugs":[],"companies":[],"institutions":["radboudumc"],"pathways":["mismatch-repair-msi","epigenetic-reprogramming"],"terms":["lynch-syndrome","hereditary-cancer-syndromes","germline-vs-somatic"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":2009,"doi":"10.1038/ng.283","pmid":"19098912","authors":"Ligtenberg MJ, Kuiper RP, Chan TL, et al.","paperType":"basic","findings":["3' EPCAM (TACSTD1) deletions cause tissue-specific MSH2 promoter methylation in cis.","A new class of Lynch syndrome with no mismatch repair gene mutation."],"whatItMeans":"EPCAM deletion testing is now part of Lynch syndrome panels, and it explains the MSH2-deficient tumours in families where sequencing of the four repair genes comes back clean.","caveats":["Rare: a small percentage of Lynch syndrome.","Copy-number analysis, not sequencing, is needed to find it."],"changedPractice":true},{"id":"paper-nct04619004-j-clin-oncol-2023","kind":"paper","name":"HERTHENA-Lung01, a Phase II Trial of Patritumab Deruxtecan (HER3-DXd) in Epidermal Growth Factor Receptor-Mutated Non-Small-Cell Lung Cancer After Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and Platinum-Based Chemotherapy","aka":[],"tldr":"Published report from the HERTHENA-Lung01 trial registered as NCT04619004, in Journal of Clinical Oncology (2023), chosen as the most cited paper whose own text cites the registry id.","summary":"Purpose: Patritumab deruxtecan, or HER3-DXd, is an antibody-drug conjugate consisting of a fully human monoclonal antibody to human epidermal growth factor receptor 3 (HER3) attached to a topoisomerase I inhibitor payload via a stable tetrapeptide-based cleavable linker. We assessed the efficacy and safety of HER3-DXd in patients with epidermal growth factor receptor ( EGFR)-mutated non-small-cell lung cancer (NSCLC).\n\nMethods: This phase II study (ClinicalTrials.gov identifier: NCT04619004) was designed to evaluate HER3-DXd in patients with advanced EGFR- mutated NSCLC previously treated with EGFR tyrosine kinase inhibitor (TKI) therapy and platinum-based chemotherapy (PBC). Patients received HER3-DXd 5.6 mg/kg intravenously once every 3 weeks or an uptitration regimen (3.2 → 4.8 → 6.4 mg/kg). The primary end point was confirmed objective response rate (ORR; RECIST 1.1) by blinded independent central review (BICR), with a null hypothesis of 26.4% on the basis of historical data.\n\nResults: Enrollment into the uptitration arm closed early on the basis of a prespecified benefit-risk assessment of data from the phase I U31402-A-U102 trial. In total, 225 patients received HER3-DXd 5.6 mg/kg once every 3 weeks. at May 18, 2023, median study duration was 18.9 (range, 14.9-27.5) months. Confirmed ORR by BICR was 29.8% (95% CI, 23.9 to 36.2); median duration of response, 6.4 months; median progression-free survival, 5.5 months; and median overall survival, 11.9 months. The subgroup of patients with previous osimertinib and PBC had similar outcomes. Efficacy was observed across a broad range of pretreatment tumor HER3 membrane expression levels and across diverse mechanisms of EGFR TKI resistance. In patients with nonirradiated brain metastases at baseline (n = 30), the confirmed CNS ORR by BICR per CNS RECIST was 33.3% (95% CI, 17.3 to 52.8). The safety profile (National Cancer Institute Common Terminology Criteria for Adverse Events v5.0) was manageable and tolerable, consistent with previous observations.\n\nConclusion: After tumor progression with EGFR TKI therapy and PBC in patients with EGFR -mutated NSCLC, HER3-DXd once every 3 weeks demonstrated clinically meaningful efficacy with durable responses, including in CNS metastases. A phase III trial in EGFR- mutated NSCLC after progression on an EGFR TKI is ongoing (HERTHENA-Lung02; ClinicalTrials.gov identifier: NCT05338970).\n\nIndexed on Europe PMC as PubMed record 37689979 (DOI 10.1200/jco.23.01476). Its abstract cites the registry id NCT04619004, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2023","url":"https://doi.org/10.1200/jco.23.01476"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37689979/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37689979"},{"label":"ClinicalTrials.gov NCT04619004","url":"https://clinicaltrials.gov/study/NCT04619004"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04619004"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2023,"doi":"10.1200/jco.23.01476","pmid":"37689979","authors":"Yu HA, Goto Y, Hayashi H, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04619004 with the most citations, so it is the natural first reading for anyone following the HERTHENA-Lung01 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","The abstract cites more than one registry id (NCT04619004, NCT05338970); it was kept because the trial's acronym appears in the title."]},{"id":"paper-hietanen-rigvir-echovirus-viruses-2022","kind":"paper","name":"Hietanen 2022: the marketed oncolytic virus Rigvir was no more oncolytic than any other echovirus isolate","aka":[],"tldr":"A virus sold for years as a cancer treatment in Latvia was sequenced and tested against ordinary strains of the same virus, and it killed cancer cells no better, and infected healthy cells too.","summary":"Rigvir was a cell-adapted enterovirus derived from an echovirus 7 isolate, registered in Latvia and promoted internationally as an oncolytic virotherapy, particularly for melanoma. Hietanen and colleagues sequenced Rigvir and five other echovirus 7 isolates, analysed the genomes, and ran cell infectivity assays on eight cell lines including both cancer and non-cancer lines.\n\nPhylogenetically Rigvir sat in its own clade at the root, most distant from the other isolates, and carried nine unique capsid mutations, six of them at surface-exposed residues, one at the contact interface with decay-accelerating factor. Functionally, the infectivity assays showed no discernible difference in oncolytic effect between Rigvir, the Wallace prototype and four other echovirus 7 isolates, and Rigvir also infected non-cancer cell lines. The authors conclude that the claim of Rigvir being an effective treatment against multiple cancers is not warranted by the evidence presented, and that neither the bioinformatics nor the cell work reveals a mechanism.","asOf":"2026-09-25","links":[{"label":"Viruses 2022","url":"https://doi.org/10.3390/v14030525"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35336934/"},{"label":"Authors' reply to the manufacturer's comment","url":"https://doi.org/10.3390/v14092078"}],"tags":[],"related":[],"cancers":["melanoma"],"sections":["immunotherapy"],"technologies":["oncolytic-virus"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Viruses","year":2022,"doi":"10.3390/v14030525","pmid":"35336934","authors":"Hietanen E, Koivu MKA, Susi P","paperType":"basic","findings":["Rigvir showed no discernible difference in oncolytic effect from the Wallace prototype or four other echovirus 7 isolates across eight cell lines.","Rigvir infected non-cancer cell lines as well as cancer lines, contradicting the claim that it is oncotropic.","Phylogenetic analysis placed Rigvir in its own clade at the root of the tree, most distant from the other echovirus 7 isolates studied.","Nine unique capsid mutations were found, six at surface-exposed residues, one at the contact interface with decay-accelerating factor.","No mechanism for the claimed oncolytic and oncotropic behaviour emerged from either the sequence analysis or the infectivity work."],"whatItMeans":"Rigvir is the field's clearest case of a product sold far ahead of its evidence: a national registration, international marketing to patients, and no randomised trial. This is the laboratory work that should have been done first. It is here because a field that produces striking single cases attracts exactly this, and readers deserve to know that an approval somewhere in the world is not the same as evidence.","caveats":["Cell culture work, which cannot by itself disprove a clinical effect; the point is that no adequate clinical evidence exists either.","The manufacturer disputed the findings in a published comment, to which the authors replied; both exchanges are in the same journal.","Rigvir is not a genetically engineered oncolytic virus and does not represent the mainstream of the field."]},{"id":"paper-mindact-ann-oncol-2014","kind":"paper","name":"High concordance of protein (by IHC), gene (by FISH; HER2 only), and microarray readout (by TargetPrint) of ER, PgR, and HER2: results from the EORTC 10041/BIG 03-04 MINDACT trial","aka":[],"tldr":"Published report from the MINDACT trial registered as NCT00433589, in Annals of Oncology (2014), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: To investigate the correlation of TargetPrint with local and central immunohistochemistry/fluorescence in situ hybridization assessment of estrogen (ER), progesterone (PgR), and human epidermal growth factor receptor 2 (HER2) in the first 800 patients enrolled in the MINDACT trial.\n\nPatients and methods: Data from local (N = 800) and central (N = 626) assessments of receptor status were collected and compared with TargetPrint results.\n\nResults: For ER, the positive agreement (the percentage of central pathology positive assessments that were also TargetPrint/local laboratory positive) for TargetPrint in comparison to centralized assessment was 98% with a negative agreement (the percentage of central pathology negative assessments that were also TargetPrint/local laboratory negative) of 96%. For PgR, the positive agreement was 83% with a negative agreement of 92%. For HER2, the positive agreement was 75% with a negative agreement of 99%. Even though the local assessment showed higher positive agreement for PgR (89%) and higher positive agreement for HER2 (85%), the range of discordant local versus central assessments were as high as 6.7% for ER, 12.9% for PgR, and 4.3% for HER2.\n\nConclusion: TargetPrint and local assessment of ER, PgR, and HER2 show high concordance with central assessment in the first 800 MINDACT patients. However, there are concerns about the higher discordance rates for some local sites. TargetPrint can improve the reliability of hormone receptor and HER2 testing for those centers with a lower rate of concordance with the reference laboratory, with the limitation of a positive agreement of 75% for HER2. TargetPrint consequently has important implications for treatment decisions in clinical practice and is a reliable alternative to local assessment for ER.\n\nClinical trials number: NCT00433589.\n\nIndexed on Europe PMC as PubMed record 24667714 (DOI 10.1093/annonc/mdu026). Its abstract cites the registry id NCT00433589, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2014","url":"https://doi.org/10.1093/annonc/mdu026"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24667714/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/24667714"},{"label":"ClinicalTrials.gov NCT00433589","url":"https://clinicaltrials.gov/study/NCT00433589"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["mindact"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2014,"doi":"10.1093/annonc/mdu026","pmid":"24667714","authors":"Viale G, Slaets L, Bogaerts J, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT00433589 with the most citations, so it is the natural first reading for anyone following the MINDACT trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-moertel-n-engl-j-med","kind":"paper","name":"High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy. A randomized double-blind comparison","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 3880867 and published in New England Journal of Medicine; the citing page links this DOI, which is how the record was matched.","summary":"It has been claimed that high-dose vitamin C is beneficial in the treatment of patients with advanced cancer, especially patients who have had no prior chemotherapy. In a double-blind study 100 patients with advanced colorectal cancer were randomly assigned to treatment with either high-dose vitamin C (10 g daily) or placebo. Overall, these patients were in very good general condition, with minimal symptoms. None had received any previous treatment with cytotoxic drugs. Vitamin C therapy showed no advantage over placebo therapy with regard to either the interval between the beginning of treatment and disease progression or patient survival. Among patients with measurable disease, none had objective improvement. On the basis of this and our previous randomized study, it can be concluded that high-dose vitamin C therapy is not effective against advanced malignant disease regardless of whether the patient has had any prior chemotherapy.\n\nIndexed on Europe PMC as PubMed record 3880867 (DOI 10.1056/nejm198501173120301). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 1985","url":"https://doi.org/10.1056/nejm198501173120301"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/3880867/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/3880867"}],"tags":["europepmc-ingest"],"related":["high-dose-vitamin-c"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":1985,"doi":"10.1056/nejm198501173120301","pmid":"3880867","authors":"Moertel CG, Fleming TR, Creagan ET, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-himalaya-nejm-evidence-2022","kind":"paper","name":"HIMALAYA: tremelimumab plus durvalumab in unresectable hepatocellular carcinoma","aka":[],"tldr":"A single priming dose of the CTLA-4 antibody tremelimumab followed by durvalumab lengthened survival compared with sorafenib in advanced liver cancer without the bleeding risk of bevacizumab, giving a second first-line immunotherapy standard.","summary":"Phase 3 trial of 1,171 patients with unresectable hepatocellular carcinoma and no prior systemic therapy randomised to STRIDE (single tremelimumab plus regular durvalumab), durvalumab alone or sorafenib.\n\nMedian overall survival was 16.4 months with STRIDE against 13.8 months with sorafenib (hazard ratio 0.78), with three-year survival of 30.7 versus 20.2 percent and durvalumab monotherapy non-inferior to sorafenib; grade 3 to 4 treatment-related adverse events were 25.8 versus 36.9 percent.","asOf":"2026-09-17","links":[{"label":"NEJM Evid 2022","url":"https://doi.org/10.1056/EVIDoa2100070"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38319892/"}],"tags":[],"related":[],"cancers":["hcc-advanced","hcc-intermediate"],"sections":[],"technologies":[],"targets":[],"drugs":["durvalumab","tremelimumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["himalaya"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm-evidence"],"dependsOn":[],"notes":[],"journal":"NEJM Evidence","year":2022,"doi":"10.1056/EVIDoa2100070","pmid":"38319892","authors":"Abou-Alfa GK, Lau G, Kudo M, et al.","paperType":"rct","findings":["Median overall survival 16.4 vs 13.8 months; hazard ratio 0.78.","Three-year overall survival 30.7 percent vs 20.2 percent."],"whatItMeans":"Durvalumab-tremelimumab is a first-line standard for advanced hepatocellular carcinoma, particularly for patients with varices or bleeding risk in whom atezolizumab-bevacizumab is unsuitable.","caveats":["Progression-free survival was not improved, reflecting a subset of long-term responders.","Excluded main portal vein thrombosis."],"changedPractice":true,"participants":1171},{"id":"paper-jacques-grill-acta-neuropathol-2015","kind":"paper","name":"Histone H3F3A and HIST1H3B K27M mutations define two subgroups of diffuse intrinsic pontine gliomas with different prognosis and phenotypes","aka":[],"tldr":"Paper by Jacques Grill indexed on Europe PMC as PubMed record 26399631, in Acta neuropathologica (2015), one of the most cited records naming an author with this name at Gustave Roussy.","summary":"Diffuse intrinsic pontine glioma (DIPG) is the most severe paediatric solid tumour, with no significant therapeutic progress made in the past 50 years. Recent studies suggest that diffuse midline glioma, H3-K27M mutant, may comprise more than one biological entity. The aim of the study was to determine the clinical and biological variables that most impact their prognosis. Ninety-one patients with classically defined DIPG underwent a systematic stereotactic biopsy and were included in this observational retrospective study. Histone H3 genes mutations were assessed by immunochemistry and direct sequencing, whilst global gene expression profiling and chromosomal imbalances were determined by microarrays. A full description of the MRI findings at diagnosis and at relapse was integrated with the molecular profiling data and clinical outcome. All DIPG but one were found to harbour either a somatic H3-K27M mutation and/or loss of H3K27 trimethylation. We also discovered a novel K27M mutation in HIST2H3C, and a lysine-to-isoleucine substitution (K27I) in H3F3A, also creating a loss of trimethylation. Patients with tumours harbouring a K27M mutation in H3.3 (H3F3A) did not respond clinically to radiotherapy as well, relapsed significantly earlier and exhibited more metastatic recurrences than those in H3.1 (HIST1H3B/C). H3.3-K27M-mutated DIPG have a proneural/oligodendroglial phenotype and a pro-metastatic gene expression signature with PDGFRA activation, while H3.1-K27M-mutated tumours exhibit a mesenchymal/astrocytic phenotype and a pro-angiogenic/hypoxic signature supported by expression profiling and radiological findings. H3K27 alterations appear as the founding event in DIPG and the mutations in the two main histone H3 variants drive two distinct oncogenic programmes with potential specific therapeutic targets.\n\nIndexed on Europe PMC as PubMed record 26399631 (DOI 10.1007/s00401-015-1478-0). Its author list gives \"Grill J\" with the affiliation \"UMR8203 \"Vectorologie et Thérapeutiques Anticancéreuses\", CNRS, Gustave Roussy, Univ. Paris-Sud, Université Paris-Saclay, 94805, Villejuif, France. jacques.grill@gustaveroussy.fr\", which names Gustave Roussy; that is how the record was matched to Jacques Grill, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Acta Neuropathol 2015","url":"https://doi.org/10.1007/s00401-015-1478-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26399631/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26399631"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["jacques-grill"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Acta neuropathologica","year":2015,"doi":"10.1007/s00401-015-1478-0","pmid":"26399631","authors":"Castel D, Philippe C, Calmon R, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Jacques Grill at Gustave Roussy, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-ezh2-ovarian-mol-cancer-ther-2018","kind":"paper","name":"Histone Methyltransferase EZH2: A Therapeutic Target for Ovarian Cancer","aka":[],"tldr":"Review on EZH2 in Ovarian cancer, in Molecular Cancer Therapeutics (2018), one of the most cited Europe PMC records with EZH2 in its title.","summary":"Ovarian cancer is the fifth leading cause of cancer-related deaths in females in the United States. There were an estimated 22,440 new cases and 14,080 deaths due to ovarian cancer in 2017. Most patients present with advanced-stage disease, revealing the urgent need for new therapeutic strategies targeting pathways of tumorigenesis and chemotherapy resistance. While multiple genomic changes contribute to the progression of this aggressive disease, it has become increasingly evident that epigenetic events play a pivotal role in ovarian cancer development. One of the well-studied epigenetic modifiers, the histone methyltransferase EZH2, is a member of polycomb repressive complex 2 (PRC2) and is commonly involved in transcriptional repression. EZH2 is the enzymatic catalytic subunit of the PRC2 complex that can alter gene expression by trimethylating lysine 27 on histone 3 (H3K27). In ovarian cancer, EZH2 is commonly overexpressed and therefore potentially serves as an effective therapeutic target. Multiple small-molecule inhibitors are being developed to target EZH2, which are now in clinical trials. Thus, in this review, we highlight the progress made in EZH2-related research in ovarian cancer and discuss the potential utility of targeting EZH2 with available small-molecule inhibitors for ovarian cancer. Mol Cancer Ther; 17(3); 591-602. ©2018 AACR.\n\nIndexed on Europe PMC as PubMed record 29726819 (DOI 10.1158/1535-7163.mct-17-0437). Its title names EZH2 and its text names Ovarian cancer; PubMed types it as a review (Research Support, Non-U.S. Gov't, research-article, Review, Research Support, N.I.H., Extramural). It was matched automatically to the idea \"Group trials by broken mechanism, not by organ or single mutation\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Mol Cancer Ther 2018","url":"https://doi.org/10.1158/1535-7163.mct-17-0437"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29726819/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29726819"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["molecular-cancer-therapeutics"],"dependsOn":[],"notes":[],"journal":"Molecular Cancer Therapeutics","year":2018,"doi":"10.1158/1535-7163.mct-17-0437","pmid":"29726819","authors":"Jones BA, Varambally S, Arend RC","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for EZH2 in Ovarian cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by EZH2 in the title and Ovarian cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-hodi-ipilimumab-melanoma-nejm-2010","kind":"paper","name":"Hodi 2010: ipilimumab, the first checkpoint inhibitor, extends survival in metastatic melanoma","aka":[],"tldr":"Blocking the immune brake CTLA-4 was the first treatment ever to prolong life in metastatic melanoma, with about one in five patients alive at two years and a new class of autoimmune side effects.","summary":"This phase 3 trial randomised 676 patients with previously treated, HLA-A*0201-positive metastatic melanoma in a 3:1:1 ratio to ipilimumab plus a gp100 peptide vaccine, ipilimumab alone, or gp100 alone. The primary endpoint was overall survival. Median OS was 10.0 months with ipilimumab plus gp100 and 10.1 months with ipilimumab alone versus 6.4 months with gp100 (hazard ratios 0.68 and 0.66), with survival curves showing a durable tail. Grade 3-4 immune-related adverse events occurred in 10-15% of ipilimumab-treated patients, and 14 deaths were related to study drugs, 7 from immune-related events. It led to FDA approval in March 2011 and validated James Allison's checkpoint-blockade hypothesis in humans.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa1003466"},{"label":"ClinicalTrials.gov NCT00094653","url":"https://clinicaltrials.gov/study/NCT00094653"}],"tags":[],"related":["paper-topalian-anti-pd1-nejm-2012","paper-checkmate-067-10-year-nejm-2025"],"cancers":["melanoma"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["ctla4"],"drugs":["ipilimumab"],"companies":["bms"],"institutions":["dana-farber"],"pathways":[],"terms":["irae","os"],"trials":[],"people":["f-stephen-hodi","james-allison","padmanee-sharma"],"bottlenecks":["b-immunotherapy-response","b-toxicity-qol"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2010,"doi":"10.1056/NEJMoa1003466","authors":"Hodi FS, O'Day SJ, McDermott DF, et al.","paperType":"rct","findings":["676 previously treated metastatic melanoma patients; ipilimumab + gp100, ipilimumab alone, or gp100 alone (3:1:1).","Median OS 10.0 and 10.1 months with ipilimumab arms vs 6.4 months with gp100; hazard ratios 0.68 and 0.66.","Response rates were low (about 11% for ipilimumab alone) yet survival improved, showing a disconnect between shrinkage and benefit.","Grade 3-4 immune-related adverse events 10-15% with ipilimumab; 7 deaths from immune-related events.","A plateau in the survival curve suggested long-term survivors, later confirmed at about 20% alive at 3 years in pooled analyses."],"whatItMeans":"This paper launched the immunotherapy era. It was the first randomised evidence that taking a brake off the immune system could extend life in a solid cancer, and it introduced clinicians to immune-related adverse events and to responses that arrive late or after apparent progression. Ipilimumab alone has since been superseded by PD-1 antibodies and combinations, but every checkpoint programme traces back to this result.","caveats":["Comparator was a peptide vaccine, not an active therapy, and was itself of uncertain effect.","Restricted to HLA-A*0201-positive patients because of the vaccine.","Response rate was low; benefit concentrated in a minority with durable responses.","Toxicity was substantial and management was still being learned."],"changedPractice":true,"participants":676},{"id":"paper-hollstein-p53-mutations-science-1991","kind":"paper","name":"Hollstein 1991: p53 mutations in human cancers","aka":[],"tldr":"The survey that showed p53 is the most commonly altered gene in human cancer and that the pattern of its mutations differs by cancer type and by cause, such as tobacco smoke in lung cancer and a dietary toxin in liver cancer.","summary":"Hollstein, Sidransky, Vogelstein and Harris compiled the p53 mutations reported across human tumours and showed that they occurred in a wide range of cancers, clustered in the evolutionarily conserved regions of the gene, and mostly changed single amino acids rather than truncating the protein. The spectrum of mutations varied by tumour type and exposure: G to T changes typical of tobacco carcinogens in lung cancer and a specific codon 249 change in liver cancers from regions with aflatoxin exposure. The paper established p53 mutation as a molecular record of carcinogen exposure.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1126/science.1905840"}],"tags":[],"related":[],"cancers":["nsclc","hcc","colorectal"],"sections":[],"technologies":[],"targets":["tp53"],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":[],"terms":["tp53-mutated","tumour-suppressor-gene","mutational-signature"],"trials":[],"people":["bert-vogelstein"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Science","year":1991,"doi":"10.1126/science.1905840","authors":"Hollstein M, Sidransky D, Vogelstein B, Harris CC.","paperType":"review","findings":["p53 mutations were found across a wide range of human cancers, making it the most frequently mutated gene known.","Mutations clustered in four conserved regions of the gene and were mostly missense changes.","Mutation spectra differed by cancer and exposure, including tobacco-associated changes in lung cancer and a codon 249 hotspot in aflatoxin-related liver cancer."],"whatItMeans":"This paper is why TP53 status is reported in almost every tumour genome and why mutational signatures can point to causes. Its idea that mutation patterns record exposures grew into the mutational signature field, and TP53 mutation remains a marker of shorter survival and a drug target still being pursued.","caveats":["A compilation of early sequencing studies with uneven coverage across cancers.","The functional consequences of different p53 mutations were still largely unknown."],"changedPractice":false},{"id":"paper-kassab-cochrane-database-syst-rev","kind":"paper","name":"Homeopathic medicines for adverse effects of cancer treatments","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 19370613 and published in The Cochrane database of systematic reviews; the citing page links this DOI, which is how the record was matched.","summary":"Background: Homeopathic medicines are used by patients with cancer, often alongside conventional treatment. Cancer treatments can cause considerable morbidity and one of the reasons patients use homeopathic medicines is to help with adverse effects.\n\nObjectives: Evaluate effectiveness and safety of homeopathic medicines used to prevent or treat adverse effects of cancer treatments.\n\nSearch strategy: The following were searched up to November 2008: Cochrane PaPaS Trials Register; Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; CINAHL; BNI; CancerLIT; AMED; CISCOM; Hom-Inform; SIGLE; National Research Register; Zetoc; www.controlled-trials.com; http://clinicaltrials.gov; Liga Medicorum Homeopathica Internationalis (LMHI, Liga) conference proceedings; reference lists of relevant studies were checked; and homeopathic manufacturers, leading researchers and practitioners were contacted.\n\nSelection criteria: Randomised controlled trials (RCTs) of homeopathic medicines in participants with a clinical or histological diagnosis of cancer where the intervention was aimed at preventing or treating symptoms associated with cancer treatments. All age groups, and all stages of disease were included.\n\nData collection and analysis: Two review authors independently assessed studies for inclusion and two review authors extracted data. Three review authors independently assessed trial quality using the Delphi List and the Cochrane Collaboration's tool for assessing risk of bias. Disagreements were resolved by consensus. Where available, data were extracted for analysis.\n\nMain results: Eight controlled trials (seven placebo controlled and one trial against an active treatment) with a total of 664 participants met the inclusion criteria. Three studied adverse effects of radiotherapy, three studied adverse effects of chemotherapy and two studied menopausal symptoms associated with breast cancer treatment.Two studies with low risk of bias demonstrated benefit: one with 254 participants demonstrated superiority of topical calendula over trolamine (a topical agent not containing corticosteroids) for prevention of radiotherapy-induced dermatitis, and another with 32 participants demonstrated superiority of Traumeel S (a proprietary complex homeopathic medicine) over placebo as a mouthwash for chemotherapy-induced stomatitis. Two other studies reported positive results, although the risk of bias was unclear, and four further studies reported negative results.No serious adverse effects or interactions were reported attributable to the homeopathic medicines used.\n\nAuthors' conclusions: This review found preliminary data in support of the efficacy of topical calendula for prophylaxis of acute dermatitis during radiotherapy and Traumeel S mouthwash in the treatment of chemotherapy-induced stomatitis. These trials need replicating. There is no convincing evidence for the efficacy of homeopathic medicines for other adverse effects of cancer treatments. Further research is required.\n\nIndexed on Europe PMC as PubMed record 19370613 (DOI 10.1002/14651858.cd004845.pub2). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cochrane Database Syst Rev 2009","url":"https://doi.org/10.1002/14651858.cd004845.pub2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19370613/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/19370613"}],"tags":["europepmc-ingest"],"related":["homeopathy-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Cochrane database of systematic reviews","year":2009,"doi":"10.1002/14651858.cd004845.pub2","pmid":"19370613","authors":"Kassab S, Cummings M, Berkovitz S, et al.","paperType":"meta-analysis","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-telli-hrd-score-platinum-tnbc-ccr-2016","kind":"paper","name":"Homologous recombination deficiency (HRD) score predicts response to platinum-containing neoadjuvant chemotherapy in patients with triple-negative breast cancer","aka":[],"tldr":"A genome-scar score built from three measures of chromosomal damage, with 42 as the cut-off, picked out triple-negative tumours that melted away on platinum chemotherapy before surgery, including tumours without a BRCA mutation.","summary":"A combined HRD score, the unweighted sum of loss of heterozygosity, telomeric allelic imbalance and large-scale state transition scores, was assessed in three neoadjuvant TNBC trials of platinum-containing therapy, with HR deficiency defined as HRD score 42 or more or BRCA1/2 mutation. In the platinum, gemcitabine and iniparib trial HR deficiency predicted residual cancer burden 0/I and pathological complete response (OR 4.96 and 6.52), remaining significant after clinical adjustment (OR 5.86); in two cisplatin trials it predicted RCB 0/I and pCR (OR 10.18 and 17.00; multivariable OR 12.08). Among BRCA1/2 non-mutated tumours response was higher with high HRD scores.","asOf":"2026-09-24","links":[{"label":"Telli et al., Clin Cancer Res 2016: HRD score predicts platinum response in three neoadjuvant TNBC trials","url":"https://doi.org/10.1158/1078-0432.CCR-15-2477"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26957554/"}],"tags":[],"related":[],"cancers":["tnbc","tnbc-early"],"sections":[],"technologies":["hrd-testing","hrd-genomic-scar-scores","platinum"],"targets":["brca"],"drugs":["cisplatin","carboplatin","mychoice-cdx"],"companies":["myriad-genetics"],"institutions":[],"pathways":[],"terms":["hrd","rcb","pcr"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2016,"doi":"10.1158/1078-0432.CCR-15-2477","pmid":"26957554","authors":"Telli ML, Timms KM, Reid J, et al.","paperType":"translational","findings":["HR deficiency (HRD score 42 or more or BRCA1/2 mutation) predicted RCB 0/I and pCR in three platinum trials (OR 4.96 to 17.00).","The association held in BRCA1/2 wild-type tumours with high scores.","The 42 threshold later became the myChoice CDx cut-off in ovarian cancer."],"whatItMeans":"This paper set the HRD score threshold the myChoice assay still uses and showed that genomic scars extend platinum sensitivity beyond BRCA carriers in early TNBC, though the TNT trial later found the same score did not predict carboplatin benefit in advanced disease.","caveats":["Three small single-arm or phase 2 trials; response, not survival, endpoints.","Predictive of platinum response, not of benefit over non-platinum chemotherapy."],"changedPractice":false},{"id":"paper-gershenson-hormonal-maintenance-lgsoc-jco-2017","kind":"paper","name":"Hormonal maintenance therapy for women with low-grade serous cancer of the ovary or peritoneum","aka":[],"tldr":"In this retrospective study, women who took an aromatase inhibitor or other hormonal therapy after first-line surgery and chemotherapy for low-grade serous ovarian cancer had a median progression-free survival of over five years compared with about two years with observation.","summary":"Retrospective analysis of 203 women with stage II to IV low-grade serous carcinoma treated with primary surgery and platinum-based chemotherapy, comparing those who received hormonal maintenance therapy (mostly letrozole) with those observed.\n\nMedian progression-free survival was 64.9 months with hormonal maintenance against 26.4 months with observation, with the benefit maintained in women without residual disease and in a multivariable analysis.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2017","url":"https://doi.org/10.1200/JCO.2016.71.0632"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28221866/"}],"tags":[],"related":[],"cancers":["low-grade-serous-ovarian-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["david-gershenson"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2017,"doi":"10.1200/JCO.2016.71.0632","pmid":"28221866","authors":"Gershenson DM, Bodurka DC, Coleman RL, et al.","paperType":"observational","findings":["Median progression-free survival 64.9 vs 26.4 months.","Benefit maintained in patients with no gross residual disease."],"whatItMeans":"Letrozole maintenance after first-line therapy is now common practice and guideline-supported for low-grade serous ovarian cancer, and the randomised NRG-GY019 trial is testing letrozole alone.","caveats":["Retrospective single-institution study with selection bias.","No overall survival difference."],"changedPractice":true,"participants":203},{"id":"paper-birkmeyer-n-engl-j-med","kind":"paper","name":"Hospital volume and surgical mortality in the United States","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 11948273 and published in New England Journal of Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Background: Although numerous studies suggest that there is an inverse relation between hospital volume of surgical procedures and surgical mortality, the relative importance of hospital volume in various surgical procedures is disputed.\n\nMethods: Using information from the national Medicare claims data base and the Nationwide Inpatient Sample, we examined the mortality associated with six different types of cardiovascular procedures and eight types of major cancer resections between 1994 and 1999 (total number of procedures, 2.5 million). Regression techniques were used to describe relations between hospital volume (total number of procedures performed per year) and mortality (in-hospital or within 30 days), with adjustment for characteristics of the patients.\n\nResults: Mortality decreased as volume increased for all 14 types of procedures, but the relative importance of volume varied markedly according to the type of procedure. Absolute differences in adjusted mortality rates between very-low-volume hospitals and very-high-volume hospitals ranged from over 12 percent (for pancreatic resection, 16.3 percent vs. 3.8 percent) to only 0.2 percent (for carotid endarterectomy, 1.7 percent vs. 1.5 percent). The absolute differences in adjusted mortality rates between very-low-volume hospitals and very-high-volume hospitals were greater than 5 percent for esophagectomy and pneumonectomy, 2 to 5 percent for gastrectomy, cystectomy, repair of a nonruptured abdominal aneurysm, and replacement of an aortic or mitral valve, and less than 2 percent for coronary-artery bypass grafting, lower-extremity bypass, colectomy, lobectomy, and nephrectomy.\n\nConclusions: In the absence of other information about the quality of surgery at the hospitals near them, Medicare patients undergoing selected cardiovascular or cancer procedures can significantly reduce their risk of operative death by selecting a high-volume hospital.\n\nIndexed on Europe PMC as PubMed record 11948273 (DOI 10.1056/nejmsa012337). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2002","url":"https://doi.org/10.1056/nejmsa012337"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/11948273/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/11948273"}],"tags":["europepmc-ingest"],"related":["centralisation"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2002,"doi":"10.1056/nejmsa012337","pmid":"11948273","authors":"Birkmeyer JD, Siewers AE, Finlayson EV, et al.","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-patkar-tata-memorial-gallbladder-cancer-registry-cancer-epidemiol-2025","kind":"paper","name":"Hospital-based gallbladder cancer registry from a high-volume referral cancer centre in India: Insights into epidemiology and roadmap for enhancing cancer care","aka":[],"tldr":"Of nearly 2,000 people with gallbladder cancer seen at Mumbai's Tata Memorial in four years, six in ten already had spread when they arrived and only one in six could be offered treatment aimed at cure.","summary":"Prospective hospital registry of all patients presenting with presumed gallbladder cancer to Tata Memorial Hospital from January 2019 to December 2022: 1,950 patients, of whom 1,441 (73.9 percent) came from the Gangetic belt and a further 209 (10.7 percent) were migrants from it (84.6 percent together); over 55 percent were from lower socioeconomic classes. At presentation 60 percent had metastatic disease; 318 (16.3 percent) were eligible for curative-intent therapy and 132 (6.8 percent) did not complete planned treatment, with dropout linked to male sex and unemployment. After a median follow-up of 38.2 months, median overall survival was 58.2 months for early-stage and 4.2 months for metastatic disease.","asOf":"2026-09-24","links":[{"label":"Cancer Epidemiol 2025","url":"https://doi.org/10.1016/j.canep.2025.102958"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41237686/"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["tata-memorial"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-global-access","b-early-detection"],"keyPapers":[],"journals":["cancer-epidemiology"],"dependsOn":[],"notes":[],"journal":"Cancer Epidemiology","year":2025,"doi":"10.1016/j.canep.2025.102958","pmid":"41237686","authors":"Patkar S, Shah TM, Varty G, et al.","paperType":"real-world","findings":["1,950 patients in four years; 84.6 percent from or migrated from the Gangetic belt.","60 percent metastatic at presentation; 16.3 percent eligible for curative-intent treatment; 6.8 percent did not complete treatment.","Median overall survival 58.2 months early-stage vs 4.2 months metastatic."],"whatItMeans":"The clearest statement of where the burden falls and why late presentation, not drug choice, decides most outcomes in high-incidence regions; it is also the home of the POLCAGB trial.","caveats":["Single referral centre; patients who never reach a cancer centre are not counted.","Stage distribution reflects referral patterns."],"changedPractice":false,"participants":1950},{"id":"paper-anthony-nichols-nat-genet-2014","kind":"paper","name":"Hotspot activating PRKD1 somatic mutations in polymorphous low-grade adenocarcinomas of the salivary glands","aka":[],"tldr":"Paper by Anthony C. Nichols indexed on Europe PMC as PubMed record 25240283, in Nature Genetics (2014), one of the most cited records naming an author with this name at Verspeeten Family Cancer Centre, London Health Sciences Centre.","summary":"Polymorphous low-grade adenocarcinoma (PLGA) is the second most frequent type of malignant tumor of the minor salivary glands. We identified PRKD1 hotspot mutations encoding p.Glu710Asp in 72.9% of PLGAs but not in other salivary gland tumors. Functional studies demonstrated that this kinase-activating alteration likely constitutes a driver of PLGA.\n\nIndexed on Europe PMC as PubMed record 25240283 (DOI 10.1038/ng.3096). Its author list gives \"Nichols AC\" with the affiliation \"Western University, London, Ontario, Canada\", which names Verspeeten Family Cancer Centre, London Health Sciences Centre; that is how the record was matched to Anthony C. Nichols, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Genet 2014","url":"https://doi.org/10.1038/ng.3096"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25240283/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25240283"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["anthony-nichols"],"bottlenecks":[],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":2014,"doi":"10.1038/ng.3096","pmid":"25240283","authors":"Weinreb I, Piscuoglio S, Martelotto LG, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Anthony C. Nichols at Verspeeten Family Cancer Centre, London Health Sciences Centre, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-cd19-multiple-myeloma-blood-2020","kind":"paper","name":"How I prevent infections in patients receiving CD19-targeted chimeric antigen receptor T cells for B-cell malignancies","aka":[],"tldr":"Review on CD19 in Multiple myeloma, in Blood (2020), one of the most cited Europe PMC records with CD19 in its title.","summary":"Adoptive immunotherapy using B-cell-targeted chimeric antigen receptor (CAR)-modified T cells to treat hematologic malignancies is transforming cancer care for patients with refractory or relapsed diseases. Recent and anticipated regulatory approval for products targeting acute lymphoblastic leukemia, lymphomas, and multiple myeloma have led to global implementation of these novel treatments. The rapidity of commercial utilization of CAR-T-cell therapy has created a largely unexplored gap in patient supportive-care approaches. Such approaches are critical in these complex patients given their high net state of immunosuppression prior to CAR-T-cell infusion coupled with unique acute and persistent insults to their immune function after CAR-T-cell infusion. In this \"How I Treat\" article, we focus on key questions that arise during 3 phases of management for patients receiving CD19-targeted CAR-T cells: pre CAR-T-cell infusion, immediate post CAR-T-cell infusion, and long-term follow-up. A longitudinal patient case is presented for each phase to highlight fundamental issues including infectious diseases screening, antimicrobial prophylaxis, immunoglobulin supplementation, risk factors for infection, and vaccination. We hope this discussion will provide a framework for institutions and health care providers to formulate their own approach to preventing infections in light of the paucity of data specific to this treatment modality.\n\nIndexed on Europe PMC as PubMed record 32582924 (DOI 10.1182/blood.2019004000). Its title names CD19 and its text names Multiple myeloma; PubMed types it as a review (review-article, Review, Research Support, N.I.H., Extramural). It was matched automatically to the idea \"In vivo CAR-T manufactured and priced like a generic biologic\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Blood 2020","url":"https://doi.org/10.1182/blood.2019004000"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32582924/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32582924"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["blood"],"dependsOn":[],"notes":[],"journal":"Blood","year":2020,"doi":"10.1182/blood.2019004000","pmid":"32582924","authors":"Hill JA, Seo SK","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for CD19 in Multiple myeloma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by CD19 in the title and Multiple myeloma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-wu-nat-med","kind":"paper","name":"How medical AI devices are evaluated: limitations and recommendations from an analysis of FDA approvals","aka":[],"tldr":"Paper cited by one bottleneck page and 22 idea pages, indexed on Europe PMC as PubMed record 33820998 and published in Nature Medicine; the citing pages link this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 33820998 (DOI 10.1038/s41591-021-01312-x). Matched by DOI alone: one bottleneck page and 22 idea pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Med 2021","url":"https://doi.org/10.1038/s41591-021-01312-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33820998/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33820998"}],"tags":["europepmc-ingest"],"related":["b-ai-validation","idea-data-ai-liability-safe-harbour","idea-data-silent-trial-before-deployment","idea-data-neutral-ai-evaluator","idea-data-precompetitive-cancer-foundation-model","idea-data-llm-documentation-rct-oncology","idea-data-ai-vs-tumour-board-rct","idea-data-ai-pathology-evaluation-standard","idea-data-drift-monitoring-standard","idea-moon-continuous-ai-validation-registry","idea-data-digital-twin-predict-then-observe","idea-data-ai-audit-trail-in-ehr","idea-data-multisite-validation-precondition","idea-data-in-silico-trials-calibrated","idea-data-ai-post-market-performance-reporting","idea-data-subgroup-performance-reporting-mandate","idea-data-patient-facing-model-cards","idea-data-ai-reimbursement-tied-to-outcomes","idea-data-open-weights-for-public-funded-ai","idea-data-ai-red-team-programme","idea-data-ai-screening-endpoints","idea-data-ai-decommissioning-rules","idea-moon-validated-digital-twins"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2021,"doi":"10.1038/s41591-021-01312-x","pmid":"33820998","authors":"Wu E, Wu K, Daneshjou R, et al.","paperType":"observational","findings":[],"whatItMeans":"One bottleneck page and 22 idea pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nct05128487-cell-rep-med-2026","kind":"paper","name":"HPK1 inhibitor NDI-101150 as monotherapy and in combination with pembrolizumab in patients with advanced solid tumors: Phase 1/2 trial results","aka":[],"tldr":"Published report from the trial registered as NCT05128487, in Cell reports. Medicine (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Hematopoietic progenitor kinase 1 (HPK1) induces potent anti-tumor immunity in preclinical models by activating and recruiting T cells, B cells, and dendritic cells into the tumor microenvironment (TME). Here, we evaluate NDI-101150, a potent, selective HPK1 inhibitor, in a phase 1/2 trial as a monotherapy or in combination with pembrolizumab in patients with advanced solid tumors. The monotherapy maximum tolerated dose (MTD) is 150 mg once daily, and doses tested up to 100 mg once daily are combinable with pembrolizumab without reaching an MTD. In clear cell renal cell carcinoma, the investigator-assessed overall response rate with monotherapy treatment is 13.6%, including one complete response and two partial responses, with a clinical benefit rate of 27.3% and a disease control rate of 54.5%. Pharmacodynamic analyses show pharmacodynamic biomarker phospho-SLP76 inhibition and increased activated CD8 + T cells and dendritic cells in the TME, supporting continued development (clinical registration number NCT05128487).\n\nIndexed on Europe PMC as PubMed record 42097144 (DOI 10.1016/j.xcrm.2026.102789). Its abstract cites the registry id NCT05128487, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Cell Rep Med 2026","url":"https://doi.org/10.1016/j.xcrm.2026.102789"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42097144/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42097144"},{"label":"ClinicalTrials.gov NCT05128487","url":"https://clinicaltrials.gov/study/NCT05128487"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05128487"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Cell reports. Medicine","year":2026,"doi":"10.1016/j.xcrm.2026.102789","pmid":"42097144","authors":"Braun DA, Noel MS, Moy RH, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05128487 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-sankaranarayanan-hpv-screening-nejm-2009","kind":"paper","name":"HPV screening for cervical cancer in rural India (Osmanabad)","aka":[],"tldr":"In 131,746 rural Indian women, a single round of HPV testing roughly halved deaths from cervical cancer within eight years, while Pap smears and visual inspection did not.","summary":"Cluster-randomised trial in 52 villages of Osmanabad district, Maharashtra, comparing one round of HPV DNA testing, cytology, visual inspection with acetic acid and usual care in women aged 30 to 59. In the HPV arm there were 39 advanced cancers versus 82 in controls (hazard ratio 0.47; 95% CI 0.32-0.69) and 34 deaths versus 64 (hazard ratio 0.52; 95% CI 0.33-0.83); the cytology and visual inspection arms showed no significant reduction. Adverse events occurred in 0.1% of screened women.","asOf":"2026-09-10","links":[{"label":"NEJM 2009","url":"https://doi.org/10.1056/NEJMoa0808516"}],"tags":[],"related":[],"cancers":["cervical"],"sections":[],"technologies":["hpv-testing"],"targets":[],"drugs":[],"companies":[],"institutions":["iarc","tata-memorial"],"pathways":[],"terms":[],"trials":["osmanabad-hpv-screening"],"people":["sankaranarayanan-rengaswamy","shastri-surendra"],"bottlenecks":["b-early-detection","b-prevention-adoption"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2009,"doi":"10.1056/NEJMoa0808516","authors":"Sankaranarayanan R, Nene BM, Shastri SS, et al.","paperType":"rct","findings":["Cervical cancer deaths: 34 with HPV testing versus 64 with usual care; hazard ratio 0.52.","Advanced cervical cancers: 39 versus 82; hazard ratio 0.47.","Neither cytology nor visual inspection with acetic acid significantly reduced advanced cancers or deaths in this trial.","Total cervical cancers detected were similar (127 versus 118), so the gain came from earlier stage and treatment."],"whatItMeans":"HPV DNA testing is the screening test that saves lives in low-resource settings, even when done once. The result underpins WHO's HPV-first screening guidance and India's operational guidelines, and gives the rationale for self-sampled HPV tests as the route to cervical cancer elimination.","caveats":["One round of screening with eight years of follow-up; long-term programme effects were not measured.","The visual inspection arm's null result differs from the later Mumbai trial, which used repeated rounds and health workers with intensive training.","Treatment access after a positive test was provided by the trial, which programmes must replicate."],"changedPractice":true,"participants":131746},{"id":"paper-hr-nbl1-busulfan-melphalan-ladenstein-lancet-oncol-2017","kind":"paper","name":"HR-NBL1/SIOPEN: busulfan-melphalan versus carboplatin-etoposide-melphalan high-dose chemotherapy for high-risk neuroblastoma","aka":[],"tldr":"Busulfan and melphalan as the high-dose conditioning before stem cell rescue gave better event-free survival and less severe toxicity than the carboplatin-etoposide-melphalan regimen in high-risk neuroblastoma, becoming Europe's standard.","summary":"Phase 3 trial within the European HR-NBL1 study randomising 598 children with high-risk neuroblastoma after rapid COJEC induction to busulfan-melphalan or carboplatin-etoposide-melphalan (CEM) high-dose chemotherapy with autologous stem cell rescue.\n\nThree-year event-free survival was 50 versus 38 percent (hazard ratio about 0.7), overall survival 60 versus 48 percent, and severe toxicity and toxic deaths were fewer with busulfan-melphalan.","asOf":"2026-09-17","links":[{"label":"Lancet Oncol 2017","url":"https://doi.org/10.1016/S1470-2045(17)30070-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28259608/"}],"tags":[],"related":[],"cancers":["neuroblastoma-high-risk"],"sections":[],"technologies":[],"targets":[],"drugs":["busulfan","carboplatin","etoposide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["hr-nbl1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2017,"doi":"10.1016/S1470-2045(17)30070-0","pmid":"28259608","authors":"Ladenstein R, Pötschger U, Pearson ADJ, et al.","paperType":"rct","findings":["Three-year event-free survival 50 percent vs 38 percent.","Severe acute toxicity 4 percent vs 10 percent."],"whatItMeans":"Busulfan-melphalan is the standard single high-dose regimen for high-risk neuroblastoma in Europe and many other regions; North America uses tandem transplant.","caveats":["Randomisation occurred after induction, so early failures are excluded.","Veno-occlusive disease is the characteristic busulfan toxicity."],"changedPractice":true,"participants":598},{"id":"paper-davies-nat-med","kind":"paper","name":"HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 28288110 and published in Nature Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Approximately 1-5% of breast cancers are attributed to inherited mutations in BRCA1 or BRCA2 and are selectively sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors. In other cancer types, germline and/or somatic mutations in BRCA1 and/or BRCA2 (BRCA1/BRCA2) also confer selective sensitivity to PARP inhibitors. Thus, assays to detect BRCA1/BRCA2-deficient tumors have been sought. Recently, somatic substitution, insertion/deletion and rearrangement patterns, or 'mutational signatures', were associated with BRCA1/BRCA2 dysfunction. Herein we used a lasso logistic regression model to identify six distinguishing mutational signatures predictive of BRCA1/BRCA2 deficiency. A weighted model called HRDetect was developed to accurately detect BRCA1/BRCA2-deficient samples. HRDetect identifies BRCA1/BRCA2-deficient tumors with 98.7% sensitivity (area under the curve (AUC) = 0.98). Application of this model in a cohort of 560 individuals with breast cancer, of whom 22 were known to carry a germline BRCA1 or BRCA2 mutation, allowed us to identify an additional 22 tumors with somatic loss of BRCA1 or BRCA2 and 47 tumors with functional BRCA1/BRCA2 deficiency where no mutation was detected. We validated HRDetect on independent cohorts of breast, ovarian and pancreatic cancers and demonstrated its efficacy in alternative sequencing strategies. Integrating all of the classes of mutational signatures thus reveals a larger proportion of individuals with breast cancer harboring BRCA1/BRCA2 deficiency (up to 22%) than hitherto appreciated (∼1-5%) who could have selective therapeutic sensitivity to PARP inhibition.\n\nIndexed on Europe PMC as PubMed record 28288110 (DOI 10.1038/nm.4292). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Med 2017","url":"https://doi.org/10.1038/nm.4292"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28288110/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28288110"}],"tags":["europepmc-ingest"],"related":["hrd-genomic-scar-scores","hrd-positive","brca-somatic"],"cancers":["tnbc","breast-cancer"],"sections":[],"technologies":["hrd-testing","wes-wgs"],"targets":["brca"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["hrd","mutational-signature"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2017,"doi":"10.1038/nm.4292","pmid":"28288110","authors":"Davies H, Glodzik D, Morganella S, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nct05435248-j-transl-med-2025","kind":"paper","name":"HS-10375, a selective EGFR C797S tyrosine kinase inhibitor, in advanced non-small cell lung cancer","aka":[],"tldr":"Published report from the Phase 1 trial registered as NCT05435248, in Journal of translational medicine (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: The C797S mutation is one of the most common mechanisms of acquired resistance to third generation EGFR TKIs, yet no approved therapies have been available to target it. Here we developed a novel selective EGFR C797S inhibitor, HS-10375, and report the results of pre-clinical research and the first-in-human phase 1 trial.\n\nMethods: Ba/F3 cell lines and patient-derived cells expressing mutant EGFR were used to test the selectively inhibitory potency of HS-10375 in vitro, and cell line-derived xenograft animal models were used to evaluate the anticancer efficacy of HS-10375 in vivo. In the phase 1 trial, HS-10375 was administered orally at six dose levels (10-240 mg) daily (QD) in 21-day cycles, following a rule-based, rolling six design. The primary objectives were the safety, tolerability and maximum tolerated dose (MTD). The secondary objectives included PK parameters and anti-tumor activity.\n\nResults: HS-10375 showed more potent activity in inhibiting EGFR phosphorylation compared to 1st to 3rd generation EGFR TKIs in C797S triple-mutant cell lines. HS-10375 also exhibited comparable inhibitory activity to 1st- and 2nd- generation EGFR TKIs and superior activity to 3rd-generation EGFR TKIs in C797S double-mutant cell lines. Furthermore, cells harboring EGFR double or triple C797S mutation underwent remarkable apoptosis upon HS-10375 treatment. HS-10375 effectively inhibited tumor growth in C797S triple-mutant mouse models. In the first-in-human trial, 28 patients with advanced or metastatic non-small cell lung cancers who harbored EGFR mutation and who had experienced treatment failure with EGFR TKI treatment received at least one dose of HS-10375. Dose-limiting toxicities were observed in 2 patients at 240 mg QD, and MTD was reached at HS-10375 150 mg QD. The most common treatment-related adverse events were vomit (37.0%), loss of appetite (33.3%), and elevated AST (33.3%). One patient with EGFR mutations showed tumor shrinkage after progression on five-line treatment including gefitinib, almonertinib, chemotherapy, immunotherapy, and EGFRxHER3 antibody-drug conjugate.\n\nConclusions: HS-10375 demonstrated potent and mutant-selective activity against the EGFR C797S mutation in preclinical results, and showed an acceptable safety profile and objective response in a first-in-human phase 1 trial. Trial registration This trial is registered on China Drug Trials (CTR20220045), and ClinicalTrials.gov (NCT05435248).\n\nIndexed on Europe PMC as PubMed record 40468352 (DOI 10.1186/s12967-025-06613-0). Its abstract cites the registry id NCT05435248, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Transl Med 2025","url":"https://doi.org/10.1186/s12967-025-06613-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40468352/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40468352"},{"label":"ClinicalTrials.gov NCT05435248","url":"https://clinicaltrials.gov/study/NCT05435248"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05435248"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of translational medicine","year":2025,"doi":"10.1186/s12967-025-06613-0","pmid":"40468352","authors":"Zhan J, Xue J, Wu L, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05435248 with the most citations, so it is the natural first reading for anyone following the Phase 1 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-hu-mismatch-repair-deficiency-pancreatic-adenocarcinoma-ccr-2018","kind":"paper","name":"Hu 2018: evaluating mismatch repair deficiency in pancreatic adenocarcinoma, challenges and recommendations","aka":[],"tldr":"Of more than 800 pancreatic cancers sequenced at one centre, under one in a hundred were mismatch repair deficient, most in people with Lynch syndrome, and several responded to immunotherapy. The paper set out how to test for the abnormality reliably in a cancer where standard tests often mislead.","summary":"Analysis of 833 pancreatic ductal adenocarcinomas sequenced with the MSK-IMPACT panel at Memorial Sloan Kettering, using MSIsensor scoring with immunohistochemistry and germline testing to identify mismatch repair deficiency. Deficiency was found in about 0.8 percent of tumours, most of them in patients with Lynch syndrome, and several treated with anti-PD-1 therapy had durable responses.\n\nThe authors show that low tumour cellularity and the desmoplastic stroma of pancreatic cancer make PCR-based microsatellite instability testing unreliable and recommend immunohistochemistry or sequencing-based assays with germline follow-up.","asOf":"2026-09-21","links":[{"label":"Clin Cancer Res 2018","url":"https://doi.org/10.1158/1078-0432.CCR-17-3099"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29367431/"}],"tags":[],"related":["msi-high","dmmr-ihc"],"cancers":["msi-high-pdac","pancreatic"],"sections":[],"technologies":["msi-mmr-testing","germline-testing"],"targets":["mmr","mlh1","msh2","msh6","pms2"],"drugs":["pembrolizumab"],"companies":[],"institutions":["mskcc"],"pathways":["mismatch-repair-msi"],"terms":["msi","lynch-syndrome","ngs"],"trials":[],"people":["eileen-oreilly"],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2018,"doi":"10.1158/1078-0432.CCR-17-3099","pmid":"29367431","authors":"Hu ZI, Shia J, Stadler ZK, et al.","paperType":"observational","findings":["Mismatch repair deficiency in about 0.8 percent of 833 pancreatic adenocarcinomas, most in Lynch syndrome carriers.","Durable responses to PD-1 blockade in treated deficient cases.","PCR-based MSI testing under-performs in pancreatic cancer; immunohistochemistry or sequencing is recommended."],"whatItMeans":"Guidelines recommending universal mismatch repair testing in pancreatic cancer, by immunohistochemistry or sequencing rather than PCR alone, rest on this and similar series.","caveats":["Single-centre series with a small number of deficient cases.","Frequency estimates vary between 0.5 and 2 percent across cohorts depending on the assay."],"changedPractice":true,"participants":833},{"id":"paper-huggins-hodges-castration-serum-phosphatases-prostate-1941","kind":"paper","name":"Huggins and Hodges 1941: the effect of castration, of oestrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate","aka":["Studies on prostatic cancer. I.","Huggins and Hodges 1941","Huggins 1941 castration prostate cancer"],"tldr":"In 1941 two Chicago surgeons showed that removing a man's testicles, or giving him oestrogen, made advanced prostate cancer shrink and his blood chemistry improve, and that giving testosterone made it worse. It was the first time any cancer in any organ had been made to regress by a drug or a hormone.","summary":"Charles Huggins and Clarence Hodges published the first of the Studies on Prostatic Cancer in Cancer Research in 1941. They measured serum acid and alkaline phosphatase in men with metastatic carcinoma of the prostate, then castrated them or gave them oestrogen, and watched the phosphatases fall and the men improve; injecting androgen sent the disease the other way.\n\nThe experiment did two things at once. It established that a human cancer can depend on a circulating hormone for its growth, which is the founding observation of systemic cancer therapy, and it gave that cancer a blood measurement that tracked it, which is the founding observation of the tumour marker. Everything on this page that suppresses, blocks or manipulates androgen descends from it, and so does the whole idea that a cancer has a dependency you can withdraw. Huggins shared the 1966 Nobel Prize in Physiology or Medicine for the work.\n\nEurope PMC indexes no abstract for the 1941 article, so OnCo carries no figures from it. The article was reprinted as a landmark in CA: A Cancer Journal for Clinicians in 1972, which is the copy Europe PMC holds (PMID 4625049, DOI 10.3322/canjclin.22.4.232).","asOf":"2026-09-25","links":[{"label":"CA Cancer J Clin 1972 reprint of the 1941 article","url":"https://doi.org/10.3322/canjclin.22.4.232"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/4625049/"},{"label":"Nobel Prize in Physiology or Medicine 1966: Charles B. Huggins","url":"https://www.nobelprize.org/prizes/medicine/1966/huggins/facts/"},{"label":"Cancer Research commentary on Huggins and Hodges (Nelson, 2016)","url":"https://europepmc.org/article/MED/26773095"}],"tags":["prostate-evidence"],"related":["hormonal-therapy-roadmap","prostate-roadmap","paper-visakorpi-androgen-receptor-amplification-nat-genet-1995"],"cancers":["prostate","prostate-mhspc","prostate-mcrpc"],"sections":["hormonal"],"technologies":[],"targets":["androgen-receptor"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["adt","castration-resistance"],"trials":[],"people":[],"bottlenecks":["b-resistance","b-undruggable-targets"],"keyPapers":[],"journals":["cancer-research"],"dependsOn":[],"notes":[],"journal":"Cancer Research","year":1941,"authors":"Huggins C, Hodges CV.","paperType":"translational","findings":["No abstract is indexed on Europe PMC; the design (serum acid and alkaline phosphatase measured in men with metastatic carcinoma of the prostate before and after castration, oestrogen and androgen injection) is read from the article itself and from the 1972 reprint."],"whatItMeans":"The origin of hormone therapy for cancer, and the reason prostate cancer is treated by taking something away rather than adding a cytotoxic drug. More than eighty years later, every man who starts androgen deprivation is having this experiment repeated on him, and the disease is still defined by whether it has stopped responding to it.","caveats":["A small uncontrolled surgical series from 1941, reported before randomised trials existed; the size of the benefit and its duration were established later.","Serum phosphatase was the marker of the day and is not the marker now; the modern equivalent, prostate-specific antigen, was not described until 1987 (paper-stamey-psa-serum-marker-nejm-1987).","High-dose oestrogen, the other arm of the original observation, was abandoned for cardiovascular harm rather than for lack of anticancer effect; that harm is the reason luteinising hormone-releasing hormone agonists replaced it."],"changedPractice":true},{"id":"paper-bonnet-nat-med","kind":"paper","name":"Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 9212098 and published in Nature Medicine; the citing page links this DOI, which is how the record was matched.","summary":"On the subject of acute myeloid leukemia (AML), there is little consensus about the target cell within the hematopoietic stem cell hierarchy that is susceptible to leukemic transformation, or about the mechanism that underlies the phenotypic, genotypic and clinical heterogeneity. Here we demonstrate that the cell capable of initiating human AML in non-obese diabetic mice with severe combined immunodeficiency disease (NOD/SCID mice) - termed the SCID leukemia-initiating cell, or SL-IC - possesses the differentiative and proliferative capacities and the potential for self-renewal expected of a leukemic stem cell. The SL-ICs from all subtypes of AML analyzed, regardless of the heterogeneity in maturation characteristics of the leukemic blasts, were exclusively CD34++ CD38-, similar to the cell-surface phenotype of normal SCID-repopulating cells, suggesting that normal primitive cells, rather than committed progenitor cells, are the target for leukemic transformation. The SL-ICs were able to differentiate in vivo into leukemic blasts, indicating that the leukemic clone is organized as a hierarchy.\n\nIndexed on Europe PMC as PubMed record 9212098 (DOI 10.1038/nm0797-730). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Med 1997","url":"https://doi.org/10.1038/nm0797-730"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/9212098/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/9212098"}],"tags":["europepmc-ingest"],"related":["cancer-stem-cell-theory"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":1997,"doi":"10.1038/nm0797-730","pmid":"9212098","authors":"Bonnet D, Dick JE","paperType":"basic","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-pd-l1-urothelial-trends-mol-med-2015","kind":"paper","name":"Human cancer immunotherapy with antibodies to the PD-1 and PD-L1 pathway","aka":[],"tldr":"Review on PD-L1 in Bladder & urothelial cancer, in Trends in molecular medicine (2015), one of the most cited Europe PMC records with PD-L1 in its title.","summary":"The programmed death 1 (PD-1) receptor and its ligands programmed death ligand 1 (PD-L1) and PD-L2, members of the CD28 and B7 families, play critical roles in T cell coinhibition and exhaustion. Overexpression of PD-L1 and PD-1 on tumor cells and tumor-infiltrating lymphocytes, respectively, correlates with poor disease outcome in some human cancers. Monoclonal antibodies (mAbs) blockading the PD-1/PD-L1 pathway have been developed for cancer immunotherapy via enhancing T cell functions. Clinical trials with mAbs to PD-1 and PD-L1 have shown impressive response rates in patients, particularly for melanoma, non-small-cell lung cancer (NSCLC), renal cell carcinoma (RCC), and bladder cancer. Further studies are needed to dissect the mechanisms of variable response rate, to identify biomarkers for clinical response, to develop small-molecule inhibitors, and to combine these treatments with other therapies.\n\nIndexed on Europe PMC as PubMed record 25440090 (DOI 10.1016/j.molmed.2014.10.009). Its title names PD-L1 and its text names Bladder & urothelial cancer; PubMed types it as a review (Research Support, Non-U.S. Gov't, research-article, Review, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural). It was matched automatically to the idea \"Anchor a TGF-beta trap in the tumour stroma so it cannot act everywhere\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Trends Mol Med 2015","url":"https://doi.org/10.1016/j.molmed.2014.10.009"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25440090/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25440090"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Trends in molecular medicine","year":2015,"doi":"10.1016/j.molmed.2014.10.009","pmid":"25440090","authors":"Ohaegbulam KC, Assal A, Lazar-Molnar E, et al.","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for PD-L1 in Bladder & urothelial cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by PD-L1 in the title and Bladder & urothelial cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-klichinsky-nat-biotechnol","kind":"paper","name":"Human chimeric antigen receptor macrophages for cancer immunotherapy","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 32361713 and published in Nature Biotechnology; the citing page links this DOI, which is how the record was matched.","summary":"Chimeric antigen receptor (CAR) T cell therapy has shown promise in hematologic malignancies, but its application to solid tumors has been challenging 1-4. Given the unique effector functions of macrophages and their capacity to penetrate tumors 5, we genetically engineered human macrophages with CARs to direct their phagocytic activity against tumors. We found that a chimeric adenoviral vector overcame the inherent resistance of primary human macrophages to genetic manipulation and imparted a sustained pro-inflammatory (M1) phenotype. CAR macrophages (CAR-Ms) demonstrated antigen-specific phagocytosis and tumor clearance in vitro. In two solid tumor xenograft mouse models, a single infusion of human CAR-Ms decreased tumor burden and prolonged overall survival. Characterization of CAR-M activity showed that CAR-Ms expressed pro-inflammatory cytokines and chemokines, converted bystander M2 macrophages to M1, upregulated antigen presentation machinery, recruited and presented antigen to T cells and resisted the effects of immunosuppressive cytokines. In humanized mouse models, CAR-Ms were further shown to induce a pro-inflammatory tumor microenvironment and boost anti-tumor T cell activity.\n\nIndexed on Europe PMC as PubMed record 32361713 (DOI 10.1038/s41587-020-0462-y). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Biotechnol 2020","url":"https://doi.org/10.1038/s41587-020-0462-y"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32361713/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32361713"}],"tags":["europepmc-ingest"],"related":["car-nk-macrophage"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-biotechnology"],"dependsOn":[],"notes":[],"journal":"Nature Biotechnology","year":2020,"doi":"10.1038/s41587-020-0462-y","pmid":"32361713","authors":"Klichinsky M, Ruella M, Shestova O, et al.","paperType":"basic","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-wolff-j-clin-oncol-2018","kind":"paper","name":"Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 29846122 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose To update key recommendations of the American Society of Clinical Oncology/College of American Pathologists human epidermal growth factor receptor 2 (HER2) testing in breast cancer guideline. Methods Based on the signals approach, an Expert Panel reviewed published literature and research survey results on the observed frequency of less common in situ hybridization (ISH) patterns to update the recommendations. Recommendations Two recommendations addressed via correspondence in 2015 are included. First, immunohistochemistry (IHC) 2+ is defined as invasive breast cancer with weak to moderate complete membrane staining observed in > 10% of tumor cells. Second, if the initial HER2 test result in a core needle biopsy specimen of a primary breast cancer is negative, a new HER2 test may (not \"must\") be ordered on the excision specimen based on specific clinical criteria. The HER2 testing algorithm for breast cancer is updated to address the recommended work-up for less common clinical scenarios (approximately 5% of cases) observed when using a dual-probe ISH assay. These scenarios are described as ISH group 2 ( HER2/chromosome enumeration probe 17 [CEP17] ratio ≥ 2.0; average HER2 copy number < 4.0 signals per cell), ISH group 3 ( HER2/CEP17 ratio < 2.0; average HER2 copy number ≥ 6.0 signals per cell), and ISH group 4 ( HER2/CEP17 ratio < 2.0; average HER2 copy number ≥ 4.0 and < 6.0 signals per cell). The diagnostic approach includes more rigorous interpretation criteria for ISH and requires concomitant IHC review for dual-probe ISH groups 2 to 4 to arrive at the most accurate HER2 status designation (positive or negative) based on combined interpretation of the ISH and IHC assays. The Expert Panel recommends that laboratories using single-probe ISH assays include concomitant IHC review as part of the interpretation of all single-probe ISH assay results. Find additional information at www.asco.org/breast-cancer-guidelines.\n\nIndexed on Europe PMC as PubMed record 29846122 (DOI 10.1200/jco.2018.77.8738). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2018","url":"https://doi.org/10.1200/jco.2018.77.8738"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29846122/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29846122"}],"tags":["europepmc-ingest"],"related":["preanalytics-sample-stabilisation"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2018,"doi":"10.1200/jco.2018.77.8738","pmid":"29846122","authors":"Wolff AC, Hammond MEH, Allison KH, et al.","paperType":"guideline","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-wolff-j-clin-oncol","kind":"paper","name":"Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: ASCO-College of American Pathologists Guideline Update","aka":[],"tldr":"Paper cited by one treatment page, indexed on Europe PMC as PubMed record 37284804 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: To update ASCO-College of American Pathologists (CAP) recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer. The Panel is aware that a new generation of antibody-drug conjugates (ADCs) targeting the HER2 protein is active against breast cancers that lack protein overexpression or gene amplification.\n\nMethods: An Update Panel conducted a systematic literature review to identify signals for updating recommendations.\n\nResults: The search identified 173 abstracts. Of five potential publications reviewed, none constituted a signal for revising existing recommendations.\n\nRecommendations: The 2018 ASCO-CAP recommendations for HER2 testing are affirmed.\n\nDiscussion: HER2 testing guidelines have focused on identifying HER2 protein overexpression or gene amplification in breast cancer to identify patients for therapies that disrupt HER2 signaling. This update acknowledges a new indication for trastuzumab deruxtecan when HER2 is not overexpressed or amplified but is immunohistochemistry (IHC) 1+ or 2+ without amplification by in situ hybridization. Clinical trial data on tumors that tested IHC 0 are limited (excluded from DESTINY-Breast04), and evidence is lacking that these cancers behave differently or do not respond similarly to newer HER2 ADCs. Although current data do not support a new IHC 0 versus 1+ prognostic or predictive threshold for response to trastuzumab deruxtecan, this threshold is now relevant because of the trial entry criteria that supported its new regulatory approval. Therefore, while it is premature to create new result categories of HER2 expression (eg, HER2-Low, HER2-Ultra-Low), best practices to distinguish IHC 0 from 1+ are now clinically relevant. This Update affirms prior HER2 reporting recommendations and offers a new HER2 testing reporting comment to highlight the current relevance of IHC 0 versus 1+ results and best practice recommendations to distinguish these often subtle differences.Additional information is available at www.asco.org/breast-cancer-guidelines.\n\nIndexed on Europe PMC as PubMed record 37284804 (DOI 10.1200/jco.22.02864). Matched by DOI alone: one treatment page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2023","url":"https://doi.org/10.1200/jco.22.02864"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37284804/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37284804"}],"tags":["europepmc-ingest"],"related":["her2-testing-assays"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2023,"doi":"10.1200/jco.22.02864","pmid":"37284804","authors":"Wolff AC, Somerfield MR, Dowsett M, et al.","paperType":"review","findings":[],"whatItMeans":"One treatment page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-ang-hpv-oropharyngeal-nejm-2010","kind":"paper","name":"Human papillomavirus and survival of patients with oropharyngeal cancer (RTOG 0129)","aka":[],"tldr":"Analysing a large chemoradiation trial showed that HPV-positive oropharyngeal cancers have a far better prognosis than HPV-negative ones, with three-year survival of 82 versus 57 percent, and that smoking history further modifies risk.","summary":"Retrospective analysis of 323 patients with stage III to IV oropharyngeal cancer treated with cisplatin chemoradiation in RTOG 0129, stratified by tumour HPV status determined by in situ hybridisation and p16 immunohistochemistry.\n\nHPV-positive tumours (63.8 percent) had three-year overall survival of 82.4 versus 57.1 percent (hazard ratio for death 0.42 after adjustment), and a recursive partitioning model combining HPV status, pack-years of smoking, T stage and N stage defined low, intermediate and high-risk groups.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2010","url":"https://doi.org/10.1056/NEJMoa0912217"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20530316/"}],"tags":[],"related":[],"cancers":["hpv-positive-oropharyngeal-cancer","oropharyngeal-cancer","hpv-negative-head-and-neck-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2010,"doi":"10.1056/NEJMoa0912217","pmid":"20530316","authors":"Ang KK, Harris J, Wheeler R, et al.","paperType":"observational","findings":["Three-year overall survival 82.4 percent HPV-positive vs 57.1 percent HPV-negative.","Smoking of more than 10 pack-years shifted HPV-positive patients into intermediate risk."],"whatItMeans":"HPV-positive oropharyngeal cancer is now staged and studied separately, and this risk model underlies de-escalation trials and the eighth-edition staging system.","caveats":["Retrospective analysis of a single trial population treated with chemoradiation."],"changedPractice":true,"participants":323},{"id":"paper-shelley-hwang-cancer-cell-2019","kind":"paper","name":"Human Tumor-Associated Macrophage and Monocyte Transcriptional Landscapes Reveal Cancer-Specific Reprogramming, Biomarkers, and Therapeutic Targets","aka":[],"tldr":"Paper by E. Shelley Hwang indexed on Europe PMC as PubMed record 30930117, in Cancer Cell (2019), one of the most cited records naming an author with this name at Duke Cancer Institute.","summary":"The roles of tumor-associated macrophages (TAMs) and circulating monocytes in human cancer are poorly understood. Here, we show that monocyte subpopulation distribution and transcriptomes are significantly altered by the presence of endometrial and breast cancer. Furthermore, TAMs from endometrial and breast cancers are transcriptionally distinct from monocytes and their respective tissue-resident macrophages. We identified a breast TAM signature that is highly enriched in aggressive breast cancer subtypes and associated with shorter disease-specific survival. We also identified an auto-regulatory loop between TAMs and cancer cells driven by tumor necrosis factor alpha involving SIGLEC1 and CCL8, which is self-reinforcing through the production of CSF1. Together these data provide direct evidence that monocyte and macrophage transcriptional landscapes are perturbed by cancer, reflecting patient outcomes.\n\nIndexed on Europe PMC as PubMed record 30930117 (DOI 10.1016/j.ccell.2019.02.009). Its author list gives \"Hwang ES\" with the affiliation \"Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA\", which names Duke Cancer Institute; that is how the record was matched to E. Shelley Hwang, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer Cell 2019","url":"https://doi.org/10.1016/j.ccell.2019.02.009"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30930117/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30930117"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["shelley-hwang"],"bottlenecks":[],"keyPapers":[],"journals":["cancer-cell"],"dependsOn":[],"notes":[],"journal":"Cancer Cell","year":2019,"doi":"10.1016/j.ccell.2019.02.009","pmid":"30930117","authors":"Cassetta L, Fragkogianni S, Sims AH, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for E. Shelley Hwang at Duke Cancer Institute, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-mesri-cell-host-microbe","kind":"paper","name":"Human viral oncogenesis: a cancer hallmarks analysis","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 24629334 and published in Cell host & microbe; the citing page links this DOI, which is how the record was matched.","summary":"Approximately 12% of all human cancers are caused by oncoviruses. Human viral oncogenesis is complex, and only a small percentage of the infected individuals develop cancer, often many years to decades after the initial infection. This reflects the multistep nature of viral oncogenesis, host genetic variability, and the fact that viruses contribute to only a portion of the oncogenic events. In this review, the Hallmarks of Cancer framework of Hanahan and Weinberg (2000 and 2011) is used to dissect the viral, host, and environmental cofactors that contribute to the biology of multistep oncogenesis mediated by established human oncoviruses. The viruses discussed include Epstein-Barr virus (EBV), high-risk human papillomaviruses (HPVs), hepatitis B and C viruses (HBV and HCV, respectively), human T cell lymphotropic virus-1 (HTLV-1), and Kaposi's sarcoma herpesvirus (KSHV).\n\nIndexed on Europe PMC as PubMed record 24629334 (DOI 10.1016/j.chom.2014.02.011). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cell Host Microbe 2014","url":"https://doi.org/10.1016/j.chom.2014.02.011"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24629334/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/24629334"}],"tags":["europepmc-ingest"],"related":["oncogenic-viruses"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Cell host & microbe","year":2014,"doi":"10.1016/j.chom.2014.02.011","pmid":"24629334","authors":"Mesri EA, Feitelson MA, Munger K","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-cardillo-clin-cancer-res","kind":"paper","name":"Humanized anti-Trop-2 IgG-SN-38 conjugate for effective treatment of diverse epithelial cancers: preclinical studies in human cancer xenograft models and monkeys","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 21372224 and published in Clinical Cancer Research; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: Evaluate the efficacy of an SN-38-anti-Trop-2 antibody-drug conjugate (ADC) against several human solid tumor types, and to assess its tolerability in mice and monkeys, the latter with tissue cross-reactivity to hRS7 similar to humans.\n\nExperimental design: Two SN-38 derivatives, CL2-SN-38 and CL2A-SN-38, were conjugated to the anti-Trop-2-humanized antibody, hRS7. The immunoconjugates were characterized in vitro for stability, binding, and cytotoxicity. Efficacy was tested in five different human solid tumor-xenograft models that expressed Trop-2 antigen. Toxicity was assessed in mice and in Cynomolgus monkeys.\n\nResults: The hRS7 conjugates of the two SN-38 derivatives were equivalent in drug substitution (∼ 6), cell binding (K(d) ∼ 1.2 nmol/L), cytotoxicity (IC(50) ∼ 2.2 nmol/L), and serum stability in vitro (t/(½) ∼ 20 hours). Exposure of cells to the ADC demonstrated signaling pathways leading to PARP cleavage, but differences versus free SN-38 in p53 and p21 upregulation were noted. Significant antitumor effects were produced by hRS7-SN-38 at nontoxic doses in mice bearing Calu-3 (P ≤ 0.05), Capan-1 (P < 0.018), BxPC-3 (P < 0.005), and COLO 205 tumors (P < 0.033) when compared to nontargeting control ADCs. Mice tolerated a dose of 2 × 12 mg/kg (SN-38 equivalents) with only short-lived elevations in ALT and AST liver enzyme levels. Cynomolgus monkeys infused with 2 × 0.96 mg/kg exhibited only transient decreases in blood counts, although, importantly, the values did not fall below normal ranges.\n\nConclusions: The anti-Trop-2 hRS7-CL2A-SN-38 ADC provides significant and specific antitumor effects against a range of human solid tumor types. It is well tolerated in monkeys, with tissue Trop-2 expression similar to humans, at clinically relevant doses, and warrants clinical investigation.\n\nIndexed on Europe PMC as PubMed record 21372224 (DOI 10.1158/1078-0432.ccr-10-2939). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Clin Cancer Res 2011","url":"https://doi.org/10.1158/1078-0432.ccr-10-2939"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21372224/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/21372224"}],"tags":["europepmc-ingest"],"related":["cl2a"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2011,"doi":"10.1158/1078-0432.ccr-10-2939","pmid":"21372224","authors":"Cardillo TM, Govindan SV, Sharkey RM, et al.","paperType":"basic","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-hurwitz-bevacizumab-crc-nejm-2004","kind":"paper","name":"Hurwitz 2004: bevacizumab with chemotherapy for metastatic colorectal cancer, the first anti-angiogenic drug to extend life","aka":[],"tldr":"Adding the VEGF antibody bevacizumab to irinotecan-based chemotherapy prolonged survival in first-line metastatic colorectal cancer, the first time blocking a tumour's blood supply had been shown to help patients.","summary":"This phase 3 trial randomised 813 patients with untreated metastatic colorectal cancer to irinotecan, fluorouracil and leucovorin (IFL) plus bevacizumab or IFL plus placebo. Bevacizumab improved overall survival, progression-free survival and response rate. Grade 3 hypertension was more common with bevacizumab but manageable, and gastrointestinal perforation appeared as a rare but serious class effect. The trial led to the first approval of an anti-angiogenic drug and validated Judah Folkman's decades-old hypothesis that tumours depend on new blood vessels.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa032691"}],"tags":[],"related":["colorectal-roadmap","paper-van-cutsem-crystal-cetuximab-folfiri-nejm-2009"],"cancers":["colorectal"],"sections":[],"technologies":[],"targets":["vegf"],"drugs":["bevacizumab","irinotecan","fluorouracil"],"companies":["roche-genentech"],"institutions":[],"pathways":[],"terms":["os","pfs"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2004,"doi":"10.1056/NEJMoa032691","authors":"Hurwitz H, Fehrenbacher L, Novotny W, et al.","paperType":"rct","findings":["813 patients with untreated metastatic colorectal cancer; IFL plus bevacizumab or placebo.","Median overall survival 20.3 vs 15.6 months, hazard ratio 0.66.","Median progression-free survival 10.6 vs 6.2 months, hazard ratio 0.54; response rate 44.8% vs 34.8%.","Grade 3 hypertension 11.0% vs 2.3%; gastrointestinal perforation in 1.5% of bevacizumab patients."],"whatItMeans":"This trial opened anti-angiogenic therapy as a class, and bevacizumab went on to approvals in lung, kidney, ovarian, cervical and brain cancers. It also set the pattern of modest but real survival gains from adding a biologic to chemotherapy, and introduced hypertension, proteinuria and perforation as the signature side effects clinicians now monitor.","caveats":["IFL is no longer a standard backbone; FOLFOX and FOLFIRI replaced it.","Benefit in later trials was smaller and no predictive biomarker for bevacizumab has emerged.","Placebo-controlled but with an active chemotherapy backbone in both arms."],"changedPractice":true,"participants":813},{"id":"paper-bennett-cochrane-database-syst-rev","kind":"paper","name":"Hyperbaric oxygen therapy for late radiation tissue injury","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 27123955 and published in The Cochrane database of systematic reviews; the citing page links this DOI, which is how the record was matched.","summary":"Background: Cancer is a significant global health problem. Radiotherapy is a treatment for many cancers and about 50% of people having radiotherapy will be long-term survivors. Some will experience late radiation tissue injury (LRTI) developing months or years later. Hyperbaric oxygen therapy (HBOT) has been suggested as a treatment for LRTI based upon the ability to improve the blood supply to these tissues. It is postulated that HBOT may result in both healing of tissues and the prevention of problems following surgery.\n\nObjectives: To assess the benefits and harms of HBOT for treating or preventing LRTI.\n\nSearch methods: We updated the searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 11), MEDLINE, EMBASE, DORCTIHM and reference lists of articles in December 2015. We also searched for ongoing trials at clinicaltrials.gov.\n\nSelection criteria: Randomised controlled trials (RCTs) comparing the effect of HBOT versus no HBOT on LRTI prevention or healing.\n\nData collection and analysis: Three review authors independently evaluated the quality of the relevant trials using the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions and extracted the data from the included trials.\n\nMain results: Fourteen trials contributed to this review (753 participants). There was some moderate quality evidence that HBOT was more likely to achieve mucosal coverage with osteoradionecrosis (ORN) (risk ratio (RR) 1.3; 95% confidence interval (CI) 1.1 to 1.6, P value = 0.003, number needed to treat for an additional beneficial outcome (NNTB) 5; 246 participants, 3 studies). There was also moderate quality evidence of a significantly improved chance of wound breakdown without HBOT following operative treatment for ORN (RR 4.2; 95% CI 1.1 to 16.8, P value = 0.04, NNTB 4; 264 participants, 2 studies). From single studies there was a significantly increased chance of improvement or cure following HBOT for radiation proctitis (RR 1.72; 95% CI 1.0 to 2.9, P value = 0.04, NNTB 5), and following both surgical flaps (RR 8.7; 95% CI 2.7 to 27.5, P value = 0.0002, NNTB 4) and hemimandibulectomy (RR 1.4; 95% CI 1.1 to 1.8, P value = 0.001, NNTB 5). There was also a significantly improved probability of healing irradiated tooth sockets following dental extraction (RR 1.4; 95% CI 1.1 to 1.7, P value = 0.009, NNTB 4).There was no evidence of benefit in clinical outcomes with established radiation injury to neural tissue, and no randomised data reported on the use of HBOT to treat other manifestations of LRTI. These trials did not report adverse events.\n\nAuthors' conclusions: These small trials suggest that for people with LRTI affecting tissues of the head, neck, anus and rectum, HBOT is associated with improved outcome. HBOT also appears to reduce the chance of ORN following tooth extraction in an irradiated field. There was no such evidence of any important clinical effect on neurological tissues. The application of HBOT to selected participants and tissues may be justified. Further research is required to establish the optimum participant selection and timing of any therapy. An economic evaluation should be undertaken.\n\nIndexed on Europe PMC as PubMed record 27123955 (DOI 10.1002/14651858.cd005005.pub4). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cochrane Database Syst Rev 2016","url":"https://doi.org/10.1002/14651858.cd005005.pub4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27123955/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27123955"}],"tags":["europepmc-ingest"],"related":["hyperbaric-oxygen-radiation-injury"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Cochrane database of systematic reviews","year":2016,"doi":"10.1002/14651858.cd005005.pub4","pmid":"27123955","authors":"Bennett MH, Feldmeier J, Hampson NB, et al.","paperType":"meta-analysis","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-murray-brunt-lancet","kind":"paper","name":"Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-Forward): 5-year efficacy and late normal tissue effects results from a multicentre, non-inferiority, randomised, phase 3 trial","aka":[],"tldr":"Paper cited by one trial page, one roadmap page and one idea page, indexed on Europe PMC as PubMed record 32580883 and published in The Lancet; the citing pages link this DOI, which is how the record was matched.","summary":"Background: We aimed to identify a five-fraction schedule of adjuvant radiotherapy (radiation therapy) delivered in 1 week that is non-inferior in terms of local cancer control and is as safe as an international standard 15-fraction regimen after primary surgery for early breast cancer. Here, we present 5-year results of the FAST-Forward trial.\n\nMethods: FAST-Forward is a multicentre, phase 3, randomised, non-inferiority trial done at 97 hospitals (47 radiotherapy centres and 50 referring hospitals) in the UK. Patients aged at least 18 years with invasive carcinoma of the breast (pT1-3, pN0-1, M0) after breast conservation surgery or mastectomy were eligible. We randomly allocated patients to either 40 Gy in 15 fractions (over 3 weeks), 27 Gy in five fractions (over 1 week), or 26 Gy in five fractions (over 1 week) to the whole breast or chest wall. Allocation was not masked because of the nature of the intervention. The primary endpoint was ipsilateral breast tumour relapse; assuming a 2% 5-year incidence for 40 Gy, non-inferiority was predefined as ≤1·6% excess for five-fraction schedules (critical hazard ratio [HR] of 1·81). Normal tissue effects were assessed by clinicians, patients, and from photographs. This trial is registered at isrctn.com, ISRCTN19906132.\n\nFindings: Between Nov 24, 2011, and June 19, 2014, we recruited and obtained consent from 4096 patients from 97 UK centres, of whom 1361 were assigned to the 40 Gy schedule, 1367 to the 27 Gy schedule, and 1368 to the 26 Gy schedule. At a median follow-up of 71·5 months (IQR 71·3 to 71·7), the primary endpoint event occurred in 79 patients (31 in the 40 Gy group, 27 in the 27 Gy group, and 21 in the 26 Gy group); HRs versus 40 Gy in 15 fractions were 0·86 (95% CI 0·51 to 1·44) for 27 Gy in five fractions and 0·67 (0·38 to 1·16) for 26 Gy in five fractions. 5-year incidence of ipsilateral breast tumour relapse after 40 Gy was 2·1% (1·4 to 3·1); estimated absolute differences versus 40 Gy in 15 fractions were -0·3% (-1·0 to 0·9) for 27 Gy in five fractions (probability of incorrectly accepting an inferior five-fraction schedule: p=0·0022 vs 40 Gy in 15 fractions) and -0·7% (-1·3 to 0·3) for 26 Gy in five fractions (p=0·00019 vs 40 Gy in 15 fractions). At 5 years, any moderate or marked clinician-assessed normal tissue effects in the breast or chest wall was reported for 98 of 986 (9·9%) 40 Gy patients, 155 (15·4%) of 1005 27 Gy patients, and 121 of 1020 (11·9%) 26 Gy patients. Across all clinician assessments from 1-5 years, odds ratios versus 40 Gy in 15 fractions were 1·55 (95% CI 1·32 to 1·83, p<0·0001) for 27 Gy in five fractions and 1·12 (0·94 to 1·34, p=0·20) for 26 Gy in five fractions. Patient and photographic assessments showed higher normal tissue effect risk for 27 Gy versus 40 Gy but not for 26 Gy versus 40 Gy.\n\nInterpretation: 26 Gy in five fractions over 1 week is non-inferior to the standard of 40 Gy in 15 fractions over 3 weeks for local tumour control, and is as safe in terms of normal tissue effects up to 5 years for patients prescribed adjuvant local radiotherapy after primary surgery for early-stage breast cancer.\n\nFunding: National Institute for Health Research Health Technology Assessment Programme.\n\nIndexed on Europe PMC as PubMed record 32580883 (DOI 10.1016/s0140-6736(20)30932-6). Matched by DOI alone: one trial page, one roadmap page and one idea page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet 2020","url":"https://doi.org/10.1016/s0140-6736(20)30932-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32580883/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32580883"}],"tags":["europepmc-ingest"],"related":["radiation-roadmap","idea-cost-hypofractionation-payment"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["fast-forward"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2020,"doi":"10.1016/s0140-6736(20)30932-6","pmid":"32580883","authors":"Murray Brunt A, Haviland JS, Wheatley DA, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page, one roadmap page and one idea page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-feinberg-nature","kind":"paper","name":"Hypomethylation distinguishes genes of some human cancers from their normal counterparts","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 6185846 and published in Nature; the citing page links this DOI, which is how the record was matched.","summary":"It has been suggested that cancer represents an alteration in DNA, heritable by progeny cells, that leads to abnormally regulated expression of normal cellular genes; DNA alterations such as mutations, rearrangements and changes in methylation have been proposed to have such a role. Because of increasing evidence that DNA methylation is important in gene expression (for review see refs 7, 9-11), several investigators have studied DNA methylation in animal tumours, transformed cells and leukaemia cells in culture. The results of these studies have varied; depending on the techniques and systems used, an increase, decrease, or no change in the degree of methylation has been reported. To our knowledge, however, primary human tumour tissues have not been used in such studies. We have now examined DNA methylation in human cancer with three considerations in mind: (1) the methylation pattern of specific genes, rather than total levels of methylation, was determined; (2) human cancers and adjacent analogous normal tissues, unconditioned by culture media, were analysed; and (3) the cancers were taken from patients who had received neither radiation nor chemotherapy. In four of five patients studied, representing two histological types of cancer, substantial hypomethylation was found in genes of cancer cells compared with their normal counterparts. This hypomethylation was progressive in a metastasis from one of the patients.\n\nIndexed on Europe PMC as PubMed record 6185846 (DOI 10.1038/301089a0). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 1983","url":"https://doi.org/10.1038/301089a0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/6185846/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/6185846"}],"tags":["europepmc-ingest"],"related":["epigenetic-progenitor-theory"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":1983,"doi":"10.1038/301089a0","pmid":"6185846","authors":"Feinberg AP, Vogelstein B","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-body-fatness-iarc-nejm-2016","kind":"paper","name":"IARC verdict: excess body fat causes 13 cancers","aka":[],"tldr":"An IARC working group reviewed over 1,000 studies and concluded there is sufficient evidence that absence of excess body fat lowers the risk of 13 cancers, up from 5 in the 2002 evaluation.","summary":"The International Agency for Research on Cancer convened a working group in 2016 to re-evaluate body fatness and cancer for the IARC Handbooks of Cancer Prevention, reviewing more than 1,000 epidemiological studies, mostly cohort studies, plus mechanistic evidence on insulin, sex hormones and inflammation.\n\nSufficient evidence of a cancer-preventive effect of avoiding excess body fat was found for cancers of the oesophagus (adenocarcinoma), gastric cardia, colon and rectum, liver, gallbladder, pancreas, breast (postmenopausal), corpus uteri, ovary, kidney (renal cell), meningioma, thyroid and multiple myeloma. Relative risks rose with BMI, ranging from about 1.1 per 5 BMI units for postmenopausal breast cancer to around 7 for endometrial cancer at BMI 40 or above.\n\nThe paper reframed obesity as a leading modifiable cancer cause after tobacco.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1056/NEJMsr1606602"},{"label":"IARC Handbooks Volume 16","url":"https://publications.iarc.who.int/570"}],"tags":[],"related":["idea-prev-glp1-cancer-prevention-rct","idea-fund-prevention-moonshot"],"cancers":["colorectal","endometrial","esophageal","hcc","pancreatic","rcc","breast-hr-positive","multiple-myeloma","thyroid","ovarian","gastric"],"sections":["prevention","nutrition-lifestyle"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["iarc"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-funding-allocation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2016,"doi":"10.1056/NEJMsr1606602","pmid":"27557308","authors":"Lauby-Secretan B, Scoccianti C, Loomis D, Grosse Y, Bianchini F, Straif K (IARC Handbook Working Group)","paperType":"review","findings":["Thirteen cancers with sufficient evidence, up from five (colon, oesophagus, kidney, breast, endometrium) in 2002","Strongest associations: endometrial cancer (RR about 7.1 for BMI 40 or more) and oesophageal adenocarcinoma (RR 4.8)","Colorectal cancer RR 1.3 and postmenopausal breast cancer RR 1.1 for the highest BMI category studied","Evidence in children and young adults suggests early-life body fatness raises adult cancer risk"],"whatItMeans":"Maintaining a healthy weight is now established cancer prevention for over a dozen cancer types. For clinicians and policymakers, obesity belongs alongside tobacco and alcohol in prevention strategy. Whether intentional weight loss in adulthood reverses risk is still being studied, including in trials of GLP-1 drugs.","caveats":["Evidence is observational; residual confounding (diet, activity, socioeconomic status) cannot be excluded","BMI is a crude measure of body fat; central adiposity may matter more","Whether losing weight lowers risk is inferred, mainly from bariatric surgery cohorts","Relative risks for several cancers are modest even though population-attributable fractions are large"],"changedPractice":true},{"id":"paper-ibis-i-tamoxifen-lancet-oncol-2015","kind":"paper","name":"IBIS-I: five years of tamoxifen keeps preventing breast cancer for at least 20 years","aka":[],"tldr":"In women at increased risk, 5 years of tamoxifen reduced breast cancer by 29% over a median 16 years of follow-up, with the benefit continuing long after the pills stopped, but no reduction in breast cancer deaths.","summary":"IBIS-I randomised 7,154 women aged 35-70 at increased risk of breast cancer to tamoxifen 20 mg daily or placebo for 5 years. This long-term analysis had a median follow-up of 16 years.\n\nBreast cancer (invasive plus ductal carcinoma in situ) occurred in 251 tamoxifen-arm and 350 placebo-arm women (HR 0.71). The reduction was similar in the first 10 years and after 10 years, showing a carry-over effect. Oestrogen-receptor-positive invasive cancer fell by a third; ER-negative cancer was unaffected. There was no difference in breast cancer mortality. Endometrial cancer and thromboembolic events were increased mainly during active treatment.\n\nWith the earlier NSABP P-1 trial (49% reduction at 5 years), IBIS-I is the basis for guideline recommendations of tamoxifen for risk reduction.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1016/S1470-2045(14)71171-4"},{"label":"NSABP P-1 (Fisher 1998)","url":"https://doi.org/10.1093/jnci/90.18.1371"}],"tags":[],"related":["idea-prev-low-dose-tamoxifen-uptake","idea-prev-chemoprevention-master-protocol"],"cancers":["breast-hr-positive"],"sections":["prevention","hormonal"],"technologies":["chemoprevention","endocrine-therapy"],"targets":["estrogen-receptor"],"drugs":["tamoxifen"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-hereditary-risk","b-toxicity-qol"],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"Lancet Oncology","year":2015,"doi":"10.1016/S1470-2045(14)71171-4","pmid":"25497694","authors":"Cuzick J, Sestak I, Cawthorn S, et al.","paperType":"rct","findings":["Breast cancer HR 0.71 (95% CI 0.60-0.83) over median 16 years; 251 vs 350 cases","ER-positive invasive breast cancer HR 0.66; no effect on ER-negative disease","Benefit continued beyond 10 years after randomisation (HR 0.69 for years 10 and later)","No significant difference in breast cancer deaths (31 vs 26) or all-cause mortality","Endometrial cancer was increased during the 5 treatment years but not afterwards"],"whatItMeans":"For women at raised risk, a 5-year course of tamoxifen offers long-lasting protection against the commonest kind of breast cancer. Uptake is low because of side effects and fear of rare serious harms; low-dose tamoxifen (TAM-01) is now being tested to improve the balance. It has not been shown to save lives.","caveats":["No mortality benefit despite fewer cancers, partly because ER-positive cancers are highly treatable","Only about 10% of eligible women in most countries accept preventive tamoxifen","Increased endometrial cancer and venous thromboembolism during treatment, concentrated in postmenopausal women","Risk assessment relied on family history criteria of the 1990s rather than modern risk models"],"changedPractice":true,"participants":7154},{"id":"paper-enrich-ibrutinib-rituximab-mantle-cell-lancet-2025","kind":"paper","name":"Ibrutinib and rituximab versus immunochemotherapy in patients with previously untreated mantle cell lymphoma (ENRICH): a randomised, open-label, phase 2/3 superiority trial","aka":["ENRICH","Lewis 2025"],"tldr":"The first trial to show that a chemotherapy-free first-line combination beats immunochemotherapy in older people with mantle cell lymphoma.","summary":"A randomised, open-label, phase 2/3 superiority trial at 66 sites in the United Kingdom, Sweden, Norway, Finland and Denmark. Patients aged 60 or over with untreated mantle-cell lymphoma, Ann Arbor stage II to IV and performance status 0 to 2, were randomised 1 to 1, stratified by the investigator's pre-chosen immunochemotherapy, between that immunochemotherapy with rituximab and ibrutinib 560 mg daily with six to eight cycles of rituximab on the matched schedule. All responders received rituximab maintenance every eight weeks for two years; the ibrutinib group continued ibrutinib until progression or unacceptable toxicity. The trial was registered with EudraCT as 2015-000832-13.\n\nBetween 15 February 2016 and 30 June 2021, 397 patients were randomised, 198 to control and 199 to intervention; 107 (27 per cent) were pre-allocated to R-CHOP and 290 (73 per cent) to rituximab-bendamustine. Median age was 74 in both groups, and 296 patients (75 per cent) were male. At a median follow-up of 47.9 months the adjusted hazard ratio for progression-free survival was 0.69 (95 per cent confidence interval 0.52 to 0.90, p = 0.0034). Grade 3 or above adverse events were reported by 67 per cent of the ibrutinib-rituximab group and 70 per cent of the immunochemotherapy group.","asOf":"2026-10-01","links":[{"label":"Lancet 2025","url":"https://doi.org/10.1016/S0140-6736(25)01432-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41052510/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41052510"}],"tags":["lymphoma-evidence"],"related":["lymphoma-roadmap"],"cancers":["mantle-cell-lymphoma","non-hodgkin-lymphoma"],"sections":["targeted-therapy","chemotherapy"],"technologies":[],"targets":["btk","cd20","ccnd1"],"drugs":["ibrutinib","rituximab","bendamustine","cyclophosphamide","doxorubicin","vincristine","prednisone"],"companies":[],"institutions":["cruk"],"pathways":["bcr-signalling"],"terms":["r-chop","maintenance-therapy"],"trials":["enrich","shine"],"people":[],"bottlenecks":["b-aging-comorbidity","b-toxicity-qol","b-trial-diversity"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"Lancet","year":2025,"doi":"10.1016/S0140-6736(25)01432-1","pmid":"41052510","authors":"Lewis DJ, Jerkeman M, Sorrell L, et al.","paperType":"rct","findings":["The adjusted hazard ratio for progression-free survival with ibrutinib-rituximab against immunochemotherapy was 0.69 (95 per cent confidence interval 0.52 to 0.90, p = 0.0034).","Against the pre-randomisation choice of R-CHOP the hazard ratio was 0.37 (0.22 to 0.62); against bendamustine-rituximab it was 0.91 (0.66 to 1.25).","Grade 3 or above adverse events were reported by 67 per cent of the ibrutinib-rituximab group and 70 per cent of the immunochemotherapy group.","Median age was 74 years in both groups; 296 patients (75 per cent) were male and 101 (25 per cent) female, and ethnicity data were not collected.","The trial was registered with EudraCT (2015-000832-13) and has no ClinicalTrials.gov record."],"whatItMeans":"The authors' conclusion is that ibrutinib-rituximab should be considered a new standard-of-care option for first-line treatment of older patients with mantle-cell lymphoma. The subgroup split means it is clearly better than R-CHOP and roughly equivalent to bendamustine-rituximab.","caveats":["Open-label, with progression-free survival assessed by investigators.","The overall superiority result is driven by the R-CHOP stratum, which was only 27 per cent of the trial; against the more commonly used bendamustine-rituximab the confidence interval crosses 1.","Ethnicity data were not collected, and three-quarters of participants were male, which reflects the disease but limits what can be said about other groups.","No overall survival result is reported at this analysis."],"changedPractice":true,"participants":397},{"id":"paper-jan-burger-n-engl-j-med-2015","kind":"paper","name":"Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia","aka":[],"tldr":"Paper by Jan A. Burger indexed on Europe PMC as PubMed record 26639149, in New England Journal of Medicine (2015), one of the most cited records naming an author with this name at MD Anderson Cancer Center.","summary":"Background: Chronic lymphocytic leukemia (CLL) primarily affects older persons who often have coexisting conditions in addition to disease-related immunosuppression and myelosuppression. We conducted an international, open-label, randomized phase 3 trial to compare two oral agents, ibrutinib and chlorambucil, in previously untreated older patients with CLL or small lymphocytic lymphoma.\n\nMethods: We randomly assigned 269 previously untreated patients who were 65 years of age or older and had CLL or small lymphocytic lymphoma to receive ibrutinib or chlorambucil. The primary end point was progression-free survival as assessed by an independent review committee.\n\nResults: The median age of the patients was 73 years. During a median follow-up period of 18.4 months, ibrutinib resulted in significantly longer progression-free survival than did chlorambucil (median, not reached vs. 18.9 months), with a risk of progression or death that was 84% lower with ibrutinib than that with chlorambucil (hazard ratio, 0.16; P<0.001). Ibrutinib significantly prolonged overall survival; the estimated survival rate at 24 months was 98% with ibrutinib versus 85% with chlorambucil, with a relative risk of death that was 84% lower in the ibrutinib group than in the chlorambucil group (hazard ratio, 0.16; P=0.001). The overall response rate was higher with ibrutinib than with chlorambucil (86% vs. 35%, P<0.001). The rates of sustained increases from baseline values in the hemoglobin and platelet levels were higher with ibrutinib. Adverse events of any grade that occurred in at least 20% of the patients receiving ibrutinib included diarrhea, fatigue, cough, and nausea; adverse events occurring in at least 20% of those receiving chlorambucil included nausea, fatigue, neutropenia, anemia, and vomiting. In the ibrutinib group, four patients had a grade 3 hemorrhage and one had a grade 4 hemorrhage. A total of 87% of the patients in the ibrutinib group are continuing to take ibrutinib.\n\nConclusions: Ibrutinib was superior to chlorambucil in previously untreated patients with CLL or small lymphocytic lymphoma, as assessed by progression-free survival, overall survival, response rate, and improvement in hematologic variables. (Funded by Pharmacyclics and others; RESONATE-2 ClinicalTrials.gov number, NCT01722487.).\n\nIndexed on Europe PMC as PubMed record 26639149 (DOI 10.1056/nejmoa1509388). Its author list gives \"Burger JA\" with the affiliation \"From the University of Texas MD Anderson Cancer Center, Houston (J.A.B.); Azienda Ospedaliera Niguarda Cà Granda (A.T.) and Università Vita-Salute San Raffaele and IRCCS Istituto Scientifico San Raffaele (P.G.), Milan, and the Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara (G.G.) - all in Italy; Wilmot Cancer Institute, University of Rochester, Rochester, NY (P.M.B.); Medical University of Lodz and Copernicus Memorial Hospital, Lodz (T.R.), the Department of Cancer Prevention, School of Public Health, Medical University of Silesia, Katowice (S.G.), and the Department of Hematology, University Clinical Center of Medical University of Gdansk, Gdansk (A.H.) - all in Poland; Tom Baker Cancer Centre, Calgary, AB, Canada (C.O.); Rabin Medical Center, Beilinson Hospital and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (O.B.), and Hadassah University Hospital, Hebrew University Medical School, Jerusalem (A.P.) - both in Israel; Leeds Teaching Hospitals, St. James Institute of Oncology, Leeds (P.H.), Kings College Hospital, London (S.D.), Royal Bournemouth Hospital, Bournemouth (H.M.), and University of Oxford, Oxford (A.S.) - all in the United Kingdom; Washington University School of Medicine, St. Louis (N.L.B.); Jiangsu Province Hospital, Nanjing, China (J.L.); North Shore Hospital, Auckland, New Zealand (D. Simpson); Stanford University School of Medicine, Stanford (S.C.), City of Hope National Medical Center, Duarte (T.S.), Pharmacyclics, Sunnyvale (D. Suri, M.C., F.C., L.S., D.F.J.), and Moores Cancer Center, University of California, San Diego, San Diego (T.J.K.) - all in California; St. Vincent's Hospital, University of Melbourne (H.Q.), and Peter MacCallum Cancer Centre and St. Vincent's Hospital (C.S.T.), Melbourne, VIC, Australia; Institute of Blood Pathology and Transfusion Medicine, National Academy of Medical Sciences of Ukraine, Lviv, Ukraine (Z.M.); Norton Cancer Institute, Louisville, KY (D.A.S.);\", which names MD Anderson Cancer Center; that is how the record was matched to Jan A. Burger, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2015","url":"https://doi.org/10.1056/nejmoa1509388"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26639149/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26639149"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["jan-burger"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2015,"doi":"10.1056/nejmoa1509388","pmid":"26639149","authors":"Burger JA, Tedeschi A, Barr PM, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Jan A. Burger at MD Anderson Cancer Center, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-shine-ibrutinib-bendamustine-rituximab-mantle-cell-nejm-2022","kind":"paper","name":"Ibrutinib plus bendamustine and rituximab in untreated mantle-cell lymphoma","aka":["SHINE","Wang 2022"],"tldr":"Adding a targeted tablet to first-line chemotherapy gave older people with mantle cell lymphoma about two and a half more years before relapse, without helping them live longer.","summary":"A randomised trial in patients aged 65 or over with untreated mantle-cell lymphoma. 523 patients received ibrutinib 560 mg orally once daily until progression or unacceptable toxicity (261) or placebo (262), plus six cycles of bendamustine 90 mg per square metre and rituximab 375 mg per square metre. Responders received rituximab maintenance every eight weeks for up to twelve additional doses. The primary endpoint was investigator-assessed progression-free survival.\n\nAt a median follow-up of 84.7 months, median progression-free survival was 80.6 months with ibrutinib against 52.9 months with placebo (hazard ratio for progression or death 0.75, 95 per cent confidence interval 0.59 to 0.96, p = 0.01). Complete response occurred in 65.5 against 57.6 per cent (p = 0.06). Overall survival was similar in the two groups. Grade 3 or 4 adverse events during treatment occurred in 81.5 against 77.3 per cent.","asOf":"2026-10-01","links":[{"label":"New England Journal of Medicine 2022","url":"https://doi.org/10.1056/NEJMoa2201817"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35657079/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35657079"}],"tags":["lymphoma-evidence"],"related":["lymphoma-roadmap"],"cancers":["mantle-cell-lymphoma","non-hodgkin-lymphoma"],"sections":["targeted-therapy","chemotherapy"],"technologies":[],"targets":["btk","cd20","ccnd1"],"drugs":["ibrutinib","bendamustine","rituximab"],"companies":["johnson-johnson"],"institutions":[],"pathways":["bcr-signalling"],"terms":["maintenance-therapy"],"trials":["shine","enrich","nct02972840"],"people":["michael-wang","martin-dreyling"],"bottlenecks":["b-aging-comorbidity","b-toxicity-qol"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/NEJMoa2201817","pmid":"35657079","authors":"Wang ML, Jurczak W, Jerkeman M, et al.","paperType":"rct","findings":["Median progression-free survival was 80.6 months with ibrutinib against 52.9 months with placebo (hazard ratio 0.75, 95 per cent confidence interval 0.59 to 0.96, p = 0.01).","Complete response occurred in 65.5 per cent with ibrutinib against 57.6 per cent with placebo (p = 0.06).","Overall survival was similar in the two groups.","Grade 3 or 4 adverse events during treatment occurred in 81.5 per cent with ibrutinib against 77.3 per cent with placebo.","Median follow-up was 84.7 months."],"whatItMeans":"Twenty-eight extra months of progression-free survival, with no survival gain and a high rate of severe adverse events in both arms. It set up the two trials that followed: ECHO, which substituted a more selective inhibitor, and ENRICH, which removed the chemotherapy.","caveats":["Progression-free survival without an overall survival benefit, in a population whose median age is over 70 and who have competing causes of death.","Continuous ibrutinib until progression means indefinite treatment, with the cardiac and bleeding risks that carries in this age group.","Investigator-assessed primary endpoint in a placebo-controlled trial, which is standard but less robust than central review."],"changedPractice":true,"participants":523},{"id":"paper-shi-lancet-oncol","kind":"paper","name":"Icotinib versus gefitinib in previously treated advanced non-small-cell lung cancer (ICOGEN): a randomised, double-blind phase 3 non-inferiority trial","aka":[],"tldr":"Paper cited by one treatment page, indexed on Europe PMC as PubMed record 23948351 and published in The Lancet Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background: Icotinib, an oral EGFR tyrosine kinase inhibitor, had shown antitumour activity and favourable toxicity in early-phase clinical trials. We aimed to investigate whether icotinib is non-inferior to gefitinib in patients with non-small-cell lung cancer.\n\nMethods: In this randomised, double-blind, phase 3 non-inferiority trial we enrolled patients with advanced non-small-cell lung cancer from 27 sites in China. Eligible patients were those aged 18-75 years who had not responded to one or more platinum-based chemotherapy regimen. Patients were randomly assigned (1:1), using minimisation methods, to receive icotinib (125 mg, three times per day) or gefitinib (250 mg, once per day) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, analysed in the full analysis set. We analysed EGFR status if tissue samples were available. All investigators, clinicians, and participants were masked to patient distribution. The non-inferiority margin was 1·14; non-inferiority would be established if the upper limit of the 95% CI for the hazard ratio (HR) of gefitinib versus icotinib was less than this margin. This study is registered with ClinicalTrials.gov, number NCT01040780, and the Chinese Clinical Trial Registry, number ChiCTR-TRC-09000506.\n\nFindings: 400 eligible patients were enrolled between Feb 26, 2009, and Nov 13, 2009; one patient was enrolled by mistake and removed from the study, 200 were assigned to icotinib and 199 to gefitinib. 395 patients were included in the full analysis set (icotinib, n=199; gefitinib, n=196). Icotinib was non-inferior to gefitinib in terms of progression-free survival (HR 0·84, 95% CI 0·67-1·05; median progression-free survival 4·6 months [95% CI 3·5-6·3] vs 3·4 months [2·3-3·8]; p=0·13). The most common adverse events were rash (81 [41%] of 200 patients in the icotinib group vs 98 [49%] of 199 patients in the gefitinib group) and diarrhoea (43 [22%] vs 58 [29%]). Patients given icotinib had less drug-related adverse events than did those given gefitinib (121 [61%] vs 140 [70%]; p=0·046), especially drug-related diarrhoea (37 [19%] vs 55 [28%]; p=0·033).\n\nInterpretation: Icotinib could be a new treatment option for pretreated patients with advanced non-small-cell lung cancer.\n\nIndexed on Europe PMC as PubMed record 23948351 (DOI 10.1016/s1470-2045(13)70355-3). Matched by DOI alone: one treatment page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2013","url":"https://doi.org/10.1016/s1470-2045(13)70355-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23948351/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/23948351"}],"tags":["europepmc-ingest"],"related":["icotinib"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2013,"doi":"10.1016/s1470-2045(13)70355-3","pmid":"23948351","authors":"Shi Y, Zhang L, Liu X, et al.","paperType":"rct","findings":[],"whatItMeans":"One treatment page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-lehmann-tnbc-subtypes-jci-2011","kind":"paper","name":"Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies","aka":[],"tldr":"The 2011 Vanderbilt analysis of 587 triple-negative tumours that split the disease into six molecular groups, two basal-like, an immune group, two mesenchymal groups and a luminal androgen receptor group, and matched each to cell lines and candidate drugs.","summary":"Lehmann, Bauer, Chen, Sanders and colleagues analysed gene expression from 21 breast cancer data sets, identified 587 triple-negative cases and by cluster analysis defined six subtypes with distinct expression and ontologies: basal-like 1 and 2 (BL1, BL2), immunomodulatory (IM), mesenchymal (M), mesenchymal stem-like (MSL) and luminal androgen receptor (LAR). Cell line models representing each subtype were identified and their predicted driver pathways targeted pharmacologically. BL1 and BL2 had higher expression of cell cycle and DNA damage response genes and their cell lines responded preferentially to cisplatin; M and MSL were enriched for epithelial-mesenchymal transition and growth factor pathways and responded to a PI3K/mTOR inhibitor (NVP-BEZ235) and dasatinib; LAR, associated with decreased relapse-free survival, was driven by androgen receptor signalling and its cell lines were uniquely sensitive to bicalutamide.","asOf":"2026-09-24","links":[{"label":"J Clin Invest 2011","url":"https://doi.org/10.1172/JCI45014"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21633166/"}],"tags":["tnbc-evidence"],"related":["paper-lehmann-tnbctype-4-refinement-plos-one-2016","paper-burstein-tnbc-genomic-subtypes-ccr-2015"],"cancers":["tnbc"],"sections":[],"technologies":["rna-seq","platinum"],"targets":["androgen-receptor","egfr"],"drugs":[],"companies":[],"institutions":["vanderbilt-ingram"],"pathways":["ddr","emt","pi3k-akt-mtor","ar-signaling"],"terms":[],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity"],"keyPapers":[],"journals":["jci"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Investigation","year":2011,"doi":"10.1172/JCI45014","pmid":"21633166","authors":"Lehmann BD, Bauer JA, Chen X, et al.","paperType":"translational","findings":["Six subtypes from 587 triple-negative cases across 21 data sets: BL1, BL2, IM, M, MSL, LAR.","BL1 and BL2 cell lines preferentially sensitive to cisplatin; M and MSL to PI3K/mTOR and abl/src inhibition; LAR to bicalutamide."],"whatItMeans":"The vocabulary used on the triple-negative page (basal-like 1 and 2, mesenchymal, luminal androgen receptor, immunomodulatory) comes from this paper; it made triple-negative breast cancer several diseases with several possible drugs rather than one disease with none.","caveats":["Subtypes derived from bulk expression; the 2016 refinement showed two of the six came from infiltrating immune and stromal cells.","Drug sensitivities are cell line results; no subtype-directed therapy has yet succeeded in a phase 3 trial."],"changedPractice":true,"participants":587},{"id":"paper-moreira-lynch-syndrome-identification-jama-2012","kind":"paper","name":"Identification of Lynch syndrome among patients with colorectal cancer","aka":[],"tldr":"Pooling four large studies, over 10,000 people with bowel cancer, showed that testing every tumour finds every case of the commonest inherited bowel cancer syndrome, while the clinical rules then in use missed about one in eight.","summary":"A pooled analysis of four cohorts of newly diagnosed colorectal cancer probands recruited between 1994 and 2010 (10,206 patients) examined personal, tumour-related and family characteristics alongside microsatellite instability, mismatch repair immunostaining and germline mutational status. Of 10,206 informative, unrelated probands, 312 (3.1%) were mismatch repair gene mutation carriers. In the population-based cohorts, universal tumour testing had sensitivity 100% and specificity 93.0%, against 87.8% sensitivity for the Bethesda guidelines, 85.4% for the Jerusalem recommendations and 95.1% for a selective strategy based on testing everyone diagnosed at 70 or younger plus older patients meeting the Bethesda guidelines. The selective strategy missed 4.9% of cases but required 34.8% fewer tumour tests and 28.6% fewer germline analyses.","asOf":"2026-09-24","links":[{"label":"Moreira et al., JAMA 2012: identification of Lynch syndrome among 10,206 colorectal cancer probands","url":"https://doi.org/10.1001/jama.2012.13088"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23073952/"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["msi-mmr-testing","germline-testing","histopathology-ihc"],"targets":["mmr","mlh1","msh2","msh6","pms2"],"drugs":[],"companies":[],"institutions":["hospital-clinic-barcelona","mayo-clinic","helsinki-hus"],"pathways":["mismatch-repair-msi"],"terms":["lynch-syndrome","msi","hereditary-cancer-syndromes","ihc"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2012,"doi":"10.1001/jama.2012.13088","pmid":"23073952","authors":"Moreira L, Balaguer F, Lindor N, et al.","paperType":"meta-analysis","findings":["312 of 10,206 probands (3.1%) carried a mismatch repair gene mutation.","Universal tumour testing: sensitivity 100%, specificity 93.0%.","Bethesda guidelines: sensitivity 87.8%; Jerusalem recommendations 85.4%."],"whatItMeans":"It is the evidence behind universal mismatch repair testing of every colorectal cancer, which is now standard in most guidelines and which, as a by-product, identifies everyone eligible for immunotherapy.","caveats":["Pooled cohorts with differing ascertainment.","Universal testing costs more and finds variants of uncertain significance.","Germline analysis was not performed in every mismatch repair deficient case."],"changedPractice":true,"participants":10206},{"id":"paper-clark-syt-ssx-synovial-sarcoma-nat-genet-1994","kind":"paper","name":"Identification of SYT and SSX, the genes fused by the t(X;18) translocation in synovial sarcoma","aka":[],"tldr":"This study cloned the SYT-SSX (SS18-SSX) gene fusion produced by the chromosome translocation found in essentially every synovial sarcoma, giving the tumour a defining molecular marker and the basis for later targeted and immune therapies.","summary":"Molecular cloning of the t(X;18)(p11.2;q11.2) translocation breakpoint in synovial sarcoma, identifying the SYT gene on chromosome 18 fused to the SSX genes on the X chromosome and characterising the resulting fusion transcripts.","asOf":"2026-09-17","links":[{"label":"Nat Genet 1994","url":"https://doi.org/10.1038/ng0894-502"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/7951320/"}],"tags":[],"related":[],"cancers":["synovial-sarcoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":1994,"doi":"10.1038/ng0894-502","pmid":"7951320","authors":"Clark J, Rocques PJ, Crew AJ, et al.","paperType":"basic","findings":["SYT-SSX fusion identified as the product of t(X;18) in synovial sarcoma."],"whatItMeans":"SS18-SSX fusion testing confirms the diagnosis of synovial sarcoma, and the fusion's disruption of the BAF chromatin remodelling complex underlies experimental therapies such as BRD9 degraders; the tumour's MAGE-A4 and NY-ESO-1 expression enabled T-cell receptor therapy.","caveats":["Discovery paper; clinical translation came decades later."],"changedPractice":true},{"id":"paper-singhi-alk-rearrangements-pancreatic-jnccn-2017","kind":"paper","name":"Identification of targetable ALK rearrangements in pancreatic ductal adenocarcinoma","aka":[],"tldr":"Screening 3,170 pancreatic cancers found five with an ALK gene fusion, all in patients under 50 and none with a KRAS mutation, and three of four treated with ALK inhibitors benefited.","summary":"Comprehensive genomic profiling of 3,170 pancreatic ductal adenocarcinomas identified 5 cases (0.16%) with an ALK fusion: exon 6 EML4-exon 20 ALK (3), exon 13 EML4-exon 20 ALK (1) and exon 3 STRN-exon 20 ALK (1). Activating KRAS mutations were absent in all 5, who were under 50; among patients under 50, ALK translocations were 1.3% of cancers. Four of 5 were treated with an ALK inhibitor and 3 showed stable disease, radiographic response and/or CA 19-9 normalisation.","asOf":"2026-09-24","links":[{"label":"Singhi et al., JNCCN 2017: ALK rearrangements in 5 of 3,170 pancreatic ductal adenocarcinomas","url":"https://doi.org/10.6004/jnccn.2017.0058"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28476735/"}],"tags":[],"related":["alk-fusion"],"cancers":["pancreatic","kras-wild-type-pdac"],"sections":[],"technologies":[],"targets":["alk"],"drugs":["crizotinib","alectinib"],"companies":[],"institutions":["upmc-hillman"],"pathways":["rtk-activation"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of the National Comprehensive Cancer Network","year":2017,"doi":"10.6004/jnccn.2017.0058","pmid":"28476735","authors":"Singhi AD, Ali SM, Lacy J, et al.","paperType":"real-world","findings":["ALK fusions in 5 of 3,170 (0.16%), 1.3% of patients under 50, all KRAS wild-type.","3 of 4 treated with ALK inhibitors benefited."],"whatItMeans":"ALK is the reason young, KRAS wild-type patients should have fusion testing even though the overall rate is one in six hundred.","caveats":["Five cases; response data are case-level.","Commercial referral cohort."],"changedPractice":false,"participants":3170},{"id":"paper-soda-eml4-alk-fusion-nature-2007","kind":"paper","name":"Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer","aka":[],"tldr":"A small inversion on chromosome 2 fuses two genes and makes a kinase that drives lung cancer. Soda and Mano found it in 5 of 75 tumours, and a drug for it was approved four years later.","summary":"Soda, Choi, Enomoto and colleagues, with Mano as senior author, showed that a small inversion within chromosome 2p fuses portions of EML4 and ALK in non-small-cell lung cancer cells, that mouse 3T3 fibroblasts forced to express the fusion form transformed foci and subcutaneous tumours, and that the transcript is present in a subset of patients distinct from those with EGFR mutations.\n\nThe four years from this paper to crizotinib's approval in 2011 is the shortest interval from the discovery of a driver to an approved drug in solid tumour oncology, and it happened because crizotinib already existed as a MET inhibitor with incidental ALK activity. That accident is the argument for screening existing compound libraries against every new driver.","asOf":"2026-09-25","links":[{"label":"Nature 2007","url":"https://doi.org/10.1038/nature05945"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/17625570/"},{"label":"Soda et al., Nature 2007: identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer","url":"https://doi.org/10.1038/nature05945"}],"tags":["lung-evidence"],"related":["paper-kwak-crizotinib-alk-nsclc-nejm-2010","paper-alk-nsclc-n-engl-j-med-2013","targeted-therapy-roadmap"],"cancers":["lung-cancer","nsclc","alk-positive-nsclc","lung-adenocarcinoma"],"sections":["targeted-therapy","drug-discovery"],"technologies":["fish","ihc","ngs","kinase-inhibitors"],"targets":["alk","egfr"],"drugs":["crizotinib"],"companies":[],"institutions":[],"pathways":["rtk-activation","nsclc-signalling"],"terms":["driver-mutation","oncogene-addiction","gene-fusion"],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets","b-translational-valley","b-generic-repurposing"],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2007,"doi":"10.1038/nature05945","pmid":"17625570","authors":"Soda M, Choi YL, Enomoto M, et al.","paperType":"basic","findings":["A small inversion within chromosome 2p forms a fusion gene comprising portions of EML4 and ALK.","Mouse 3T3 fibroblasts expressing the fusion kinase generated transformed foci in culture and subcutaneous tumours in nude mice.","The EML4-ALK fusion transcript was detected in 6.7 percent (5 of 75) of the non-small-cell lung cancer patients examined.","Patients with the fusion were distinct from those harbouring EGFR mutations.","A chromosome 2p inversion fuses EML4 to ALK in lung cancer.","The fusion protein transforms fibroblasts in culture and forms tumours in mice.","Present in 5 of 75 patients, 6.7%, and mutually exclusive with EGFR mutation."],"whatItMeans":"The second driver in lung cancer, and the one that proved the first was not a special case. It also established mutual exclusivity as a working assumption: a tumour usually has one driver, so finding it tells you what to give.","caveats":["75 tumours from one country; the 6.7 percent figure is higher than the 3 to 5 percent generally found since.","A transforming fusion in fibroblasts is not proof of dependence in a human tumour; that came from the crizotinib trials.","Detection method matters: fluorescence in situ hybridisation, immunohistochemistry and sequencing do not always agree on which tumours are ALK-positive.","Seventy-five patients, so the frequency estimate is imprecise.","The screening method of the day would have missed rarer partners.","Transformation in fibroblasts does not by itself prove dependence in human tumours."],"changedPractice":true,"participants":75},{"id":"paper-balachandran-neoantigen-quality-long-term-survivors-nature-2017","kind":"paper","name":"Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer","aka":[],"tldr":"The rare people who survive pancreatic cancer for years have tumours carrying both many mutation-made target proteins and plenty of killer T cells, and the quality of those targets, some resembling germ proteins, predicts long survival.","summary":"Genetic, immunohistochemical and transcriptional immunoprofiling, computational biophysics and functional assays were used to identify T-cell antigens in long-term survivors of pancreatic cancer. Whole-exome sequencing with in silico neoantigen prediction showed that tumours with both the highest neoantigen number and the most abundant CD8 T-cell infiltrates, but neither alone, stratified the longest survival. A neoantigen quality fitness model giving greater immunogenicity to neoantigens with differential presentation and homology to infectious disease peptides identified long-term survivors in two independent datasets, whereas a quantity model did not; MUC16 neoantigens featured. Intratumoural and lasting circulating T-cell reactivity to high-quality and MUC16 neoantigens was detected, and high-quality neoantigenic clones were selectively lost on metastatic progression, consistent with immunoediting.","asOf":"2026-09-24","links":[{"label":"Balachandran et al., Nature 2017: neoantigen quality in long-term survivors","url":"https://doi.org/10.1038/nature24462"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29132146/"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":["neoantigen-mrna-vaccine","wes-wgs"],"targets":[],"drugs":[],"companies":[],"institutions":["mskcc"],"pathways":["antigen-presentation-immunoediting","cancer-immunity-cycle"],"terms":["neoantigen","tmb"],"trials":[],"people":["vinod-balachandran"],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2017,"doi":"10.1038/nature24462","pmid":"29132146","authors":"Balachandran VP, Luksza M, Zhao JN, et al.","paperType":"translational","findings":["Long-term survival required both high neoantigen number and abundant CD8 infiltrate.","A neoantigen quality model, including MUC16 neoantigens and microbial homology, predicted survival.","High-quality neoantigen clones were lost at metastasis."],"whatItMeans":"It is the proof that T cells can control pancreatic cancer in some people, and the scientific basis for the personalised neoantigen vaccines now in trials.","caveats":["Small long-term survivor cohorts.","The fitness model is computational and not a clinical test."],"changedPractice":false},{"id":"paper-amary-idh-cartilaginous-tumours-j-pathol-2011","kind":"paper","name":"IDH1 and IDH2 mutations are frequent in central chondrosarcoma and central and periosteal chondromas","aka":[],"tldr":"Mutations in IDH1 and IDH2, previously known from brain tumours and leukaemia, were found in more than half of central chondrosarcomas and their benign precursors, defining the molecular basis of most cartilage tumours.","summary":"Mutation analysis of over 1,200 mesenchymal tumours identifying IDH1 or IDH2 mutations in 56 percent of central and periosteal cartilaginous tumours, including 71 percent of Ollier disease and Maffucci syndrome cases, but not in peripheral chondrosarcoma, osteochondroma or other sarcomas.","asOf":"2026-09-17","links":[{"label":"J Pathol 2011","url":"https://doi.org/10.1002/path.2913"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21598255/"}],"tags":[],"related":[],"cancers":["chondrosarcoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Journal of Pathology","year":2011,"doi":"10.1002/path.2913","pmid":"21598255","authors":"Amary MF, Bacsi K, Maggiani F, et al.","paperType":"translational","findings":["IDH1 or IDH2 mutations in 56 percent of central and periosteal cartilaginous tumours.","Absent from peripheral chondrosarcoma and other mesenchymal tumours."],"whatItMeans":"IDH mutation testing helps distinguish chondrosarcoma from chondroblastic osteosarcoma and other mimics, and IDH inhibitors are being tested in advanced chondrosarcoma.","caveats":["Ivosidenib trials in chondrosarcoma have shown disease stabilisation rather than shrinkage so far."],"changedPractice":true},{"id":"paper-ielsg32-matrix-induction-ferreri-lancet-haematol-2016","kind":"paper","name":"IELSG32 first randomisation: the MATRix regimen (methotrexate, cytarabine, thiotepa, rituximab) in primary CNS lymphoma","aka":[],"tldr":"Adding rituximab and thiotepa to methotrexate and cytarabine doubled the complete remission rate for lymphoma confined to the brain, making the four-drug MATRix regimen the standard induction for patients up to 70.","summary":"First randomisation of the international phase 2 IELSG32 trial: 227 patients aged 18 to 70 with newly diagnosed primary CNS lymphoma were randomised to four courses of methotrexate and cytarabine alone, with rituximab, or with rituximab and thiotepa (MATRix).\n\nAt a median follow-up of 30 months the complete remission rate was 49 percent with MATRix against 23 percent with methotrexate-cytarabine alone (hazard ratio 0.46) and 30 percent with rituximab added (hazard ratio 0.61). Grade 4 haematological toxicity was more frequent with MATRix but infections were similar; 13 patients (6 percent) died of toxicity.","asOf":"2026-09-22","links":[{"label":"Lancet Haematol 2016","url":"https://doi.org/10.1016/S2352-3026(16)00036-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27132696/"}],"tags":[],"related":[],"cancers":["primary-cns-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["methotrexate","cytarabine","thiotepa","rituximab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["ielsg32"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-haematology"],"dependsOn":[],"notes":[],"journal":"The Lancet Haematology","year":2016,"doi":"10.1016/S2352-3026(16)00036-3","pmid":"27132696","authors":"Ferreri AJ, Cwynarski K, Pulczynski E, et al.","paperType":"rct","findings":["Complete remission 49 percent (95% CI 38 to 60) with MATRix, 30 percent (21 to 42) with methotrexate-cytarabine-rituximab, 23 percent (14 to 31) with methotrexate-cytarabine.","Hazard ratio for complete remission 0.46 (0.28 to 0.74) for methotrexate-cytarabine alone against MATRix.","Toxic deaths 6 percent."],"whatItMeans":"MATRix became the reference induction for fit patients with primary CNS lymphoma and the control arm of later randomised trials.","caveats":["Randomised phase 2 design; the trial was not powered for survival.","Patients over 70 were excluded."],"changedPractice":true,"participants":227},{"id":"paper-ielsg32-wbrt-vs-asct-consolidation-ferreri-lancet-haematol-2017","kind":"paper","name":"IELSG32 second randomisation: whole-brain radiotherapy or autologous stem cell transplant as consolidation in primary CNS lymphoma","aka":[],"tldr":"After chemotherapy for lymphoma of the brain, a stem cell transplant controlled the disease as well as radiotherapy to the whole brain, and spared patients the decline in attention and executive function that followed radiotherapy.","summary":"Second randomisation of the IELSG32 trial: patients with responsive or stable disease after high-dose methotrexate-based induction were randomised to whole-brain radiotherapy of 36 Gy (with a 9 Gy boost for residual disease) or carmustine-thiotepa conditioning with autologous stem cell transplant. The primary endpoint was two-year progression-free survival.\n\nTwo-year failure-free survival in the registry results was 76 percent after radiotherapy and 75 percent after transplant. Neuropsychological testing showed impairment of attention and executive functions after radiotherapy and preserved or improved cognition after transplant.","asOf":"2026-09-22","links":[{"label":"Lancet Haematol 2017","url":"https://doi.org/10.1016/S2352-3026(17)30174-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29054815/"}],"tags":[],"related":[],"cancers":["primary-cns-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["thiotepa","carmustine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["ielsg32"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-haematology"],"dependsOn":[],"notes":[],"journal":"The Lancet Haematology","year":2017,"doi":"10.1016/S2352-3026(17)30174-6","pmid":"29054815","authors":"Ferreri AJM, Cwynarski K, Pulczynski E, et al.","paperType":"rct","findings":["Two-year failure-free survival 76 percent (95% CI 65 to 87) after whole-brain radiotherapy and 75 percent (64 to 86) after autologous transplant (registry results).","Cognitive function was preserved after transplant and impaired in attention and executive domains after radiotherapy."],"whatItMeans":"Autologous transplant is an effective consolidation that avoids the neurotoxicity of whole-brain radiotherapy, and IELSG43 later showed it beats non-myeloablative consolidation.","caveats":["Randomised phase 2; only patients fit for transplant and with stem cells collected reached the second randomisation."],"changedPractice":true,"participants":118},{"id":"paper-ielsg37-pmbcl-martelli-jco-2024","kind":"paper","name":"IELSG37: omission of radiotherapy in primary mediastinal B-cell lymphoma after a negative PET scan","aka":[],"tldr":"Patients with primary mediastinal B-cell lymphoma whose PET scan was negative after immunochemotherapy did just as well without consolidation radiotherapy as with it, so radiotherapy can safely be omitted for them.","summary":"Phase 3 non-inferiority trial of 545 patients with primary mediastinal B-cell lymphoma treated with rituximab-containing immunochemotherapy; the 268 with a complete metabolic response on PET were randomised to observation or consolidation mediastinal radiotherapy.\n\nThirty-month progression-free survival was 96.2 percent with observation and 98.5 percent with radiotherapy, meeting non-inferiority, with overall survival of 99 percent in both arms.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2024","url":"https://doi.org/10.1200/JCO-24-01373"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39159403/"}],"tags":[],"related":[],"cancers":["primary-mediastinal-b-cell-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["ielsg37"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2024,"doi":"10.1200/JCO-24-01373","pmid":"39159403","authors":"Martelli M, Ceriani L, Ciccone G, et al.","paperType":"rct","findings":["30-month progression-free survival 96.2 percent (observation) vs 98.5 percent (radiotherapy); non-inferior.","Overall survival 99 percent in both arms."],"whatItMeans":"End-of-treatment PET now decides radiotherapy in primary mediastinal B-cell lymphoma: a negative scan means no radiotherapy, whichever chemotherapy regimen was used.","caveats":["Patients with residual PET uptake were not randomised and mostly received radiotherapy.","Long-term second cancer data are pending."],"changedPractice":true,"participants":545},{"id":"paper-royer-plasma-cell-leukaemia-ifm-jco-2016","kind":"paper","name":"IFM 2006 prospective trial: bortezomib-based induction and transplantation for primary plasma cell leukaemia","aka":[],"tldr":"The first prospective trial dedicated to plasma cell leukaemia showed that a bortezomib-based four-drug induction followed by stem cell transplantation could produce remissions in most patients, though relapse remained the rule.","summary":"Phase 2 study of 40 patients with primary plasma cell leukaemia treated with bortezomib, doxorubicin, cyclophosphamide and dexamethasone induction followed by autologous transplant and, for those with a donor, reduced-intensity allogeneic transplant, or a second autologous transplant and maintenance.\n\nResponse after induction was 69 percent, median progression-free survival 15.1 months and median overall survival 36.3 months, a clear improvement on historical series with median survival under a year.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2016","url":"https://doi.org/10.1200/JCO.2015.63.1929"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27114594/"}],"tags":[],"related":[],"cancers":["plasma-cell-leukaemia"],"sections":[],"technologies":[],"targets":[],"drugs":["bortezomib","cyclophosphamide","dexamethasone","doxorubicin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2016,"doi":"10.1200/JCO.2015.63.1929","pmid":"27114594","authors":"Royer B, Minvielle S, Diouf M, et al.","paperType":"observational","findings":["Overall response 69 percent after induction.","Median progression-free survival 15.1 months; median overall survival 36.3 months."],"whatItMeans":"Bortezomib-based induction with early transplant consolidation became the accepted approach for fit patients with this rare aggressive disease; daratumumab-containing quadruplets are now added by extrapolation.","caveats":["Small single-arm study.","Allogeneic transplant did not clearly improve outcomes compared with tandem autologous transplant."],"changedPractice":true,"participants":40},{"id":"paper-ifm-2009-attal-nejm-2017","kind":"paper","name":"IFM 2009: lenalidomide, bortezomib and dexamethasone with or without upfront transplantation for myeloma","aka":[],"tldr":"Adding an early autologous stem cell transplant to modern three-drug therapy delayed relapse in newly diagnosed myeloma, though overall survival was similar because patients in the drug-only arm could have a transplant later.","summary":"Phase 3 trial of 700 adults up to 65 with newly diagnosed multiple myeloma randomised to lenalidomide, bortezomib and dexamethasone (RVD) alone (eight cycles) or RVD with high-dose melphalan and autologous transplant, both followed by a year of lenalidomide maintenance.\n\nMedian progression-free survival was 50 months with transplant against 36 months without; complete response 59 versus 48 percent. Four-year overall survival was 81 versus 82 percent, with most drug-only patients receiving transplant at relapse.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2017","url":"https://doi.org/10.1056/NEJMoa1611750"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28379796/"}],"tags":[],"related":[],"cancers":["myeloma-transplant-eligible"],"sections":[],"technologies":[],"targets":[],"drugs":["bortezomib","dexamethasone","lenalidomide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["ifm-2009"],"people":["michel-attal"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2017,"doi":"10.1056/NEJMoa1611750","pmid":"28379796","authors":"Attal M, Lauwers-Cances V, Hulin C, et al.","paperType":"rct","findings":["Median progression-free survival 50 vs 36 months (hazard ratio 0.65).","Complete response 59 percent vs 48 percent; no overall survival difference at four years."],"whatItMeans":"Upfront transplant remains standard for fit patients because it lengthens the first remission, but deferring it to first relapse is a reasonable choice for some, particularly with deeper modern induction.","caveats":["Lenalidomide maintenance was limited to one year, shorter than current practice.","Quadruplet induction with daratumumab was not used."],"changedPractice":true,"participants":700},{"id":"paper-shankaran-nature","kind":"paper","name":"IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 11323675 and published in Nature; the citing page links this DOI, which is how the record was matched.","summary":"Lymphocytes were originally thought to form the basis of a 'cancer immunosurveillance' process that protects immunocompetent hosts against primary tumour development, but this idea was largely abandoned when no differences in primary tumour development were found between athymic nude mice and syngeneic wild-type mice. However, subsequent observations that nude mice do not completely lack functional T cells and that two components of the immune system-IFNgamma and perforin-help to prevent tumour formation in mice have led to renewed interest in a tumour-suppressor role for the immune response. Here we show that lymphocytes and IFNgamma collaborate to protect against development of carcinogen-induced sarcomas and spontaneous epithelial carcinomas and also to select for tumour cells with reduced immunogenicity. The immune response thus functions as an effective extrinsic tumour-suppressor system. However, this process also leads to the immunoselection of tumour cells that are more capable of surviving in an immunocompetent host, which explains the apparent paradox of tumour formation in immunologically intact individuals.\n\nIndexed on Europe PMC as PubMed record 11323675 (DOI 10.1038/35074122). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2001","url":"https://doi.org/10.1038/35074122"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/11323675/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/11323675"}],"tags":["europepmc-ingest"],"related":["immune-surveillance-immunoediting"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2001,"doi":"10.1038/35074122","pmid":"11323675","authors":"Shankaran V, Ikeda H, Bruce AT, et al.","paperType":"basic","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-igcccg-update-gillessen-jco-2021","kind":"paper","name":"IGCCCG Update Consortium: predicting outcomes in men with metastatic non-seminomatous germ cell tumours","aka":[],"tldr":"Updating the 1997 classification with nearly 10,000 modern patients showed that survival has improved in every risk group, especially poor risk, and added age, lung metastases and LDH as continuous factors to refine individual prediction.","summary":"Analysis of 9,728 men with metastatic non-seminomatous germ cell tumours treated with cisplatin-based chemotherapy between 1990 and 2013 at 30 institutions, validating the IGCCCG groups and developing a refined model incorporating age, presence of lung metastases and LDH as a continuous variable.\n\nFive-year progression-free survival was 89, 75 and 54 percent and overall survival 96, 89 and 67 percent for good, intermediate and poor prognosis groups.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2021","url":"https://doi.org/10.1200/JCO.20.03296"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33822655/"}],"tags":[],"related":[],"cancers":["non-seminoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2021,"doi":"10.1200/JCO.20.03296","pmid":"33822655","authors":"Gillessen S, Sauvé N, Collette L, et al.","paperType":"observational","findings":["Five-year overall survival 96, 89 and 67 percent for good, intermediate and poor prognosis.","Age, lung metastases and continuous LDH added prognostic information."],"whatItMeans":"Treatment intensity decisions still rest on the three IGCCCG groups, and the online calculator from this work gives men a more accurate individual estimate of cure.","caveats":["Retrospective registry data from expert centres."],"changedPractice":true,"participants":9728},{"id":"paper-wong-ignyte-rp1-nivolumab-jco-2025","kind":"paper","name":"IGNYTE: an engineered herpes virus with nivolumab in melanoma that had already failed anti-PD-1 therapy","aka":[],"tldr":"In melanoma that had already stopped responding to immunotherapy, injecting an engineered herpes virus alongside nivolumab shrank tumours in about a third of patients, including tumours that were never injected.","summary":"Registrational cohort of 140 patients with advanced melanoma and confirmed progression on anti-PD-1 therapy given as the last prior treatment for at least eight weeks. Vusolimogene oderparepvec, a herpes simplex virus type 1-based oncolytic immunotherapy, was given into tumours for up to eight doses of up to 10 mL, with nivolumab for up to two years. The objective response rate was assessed by independent central review.\n\nConfirmed objective response rate was 32.9 per cent (95% CI 25.2 to 41.3), with complete response in 15.0 per cent. Responses occurred with similar frequency, depth, duration and timing in injected and uninjected lesions, including visceral ones, which is the evidence for a systemic effect rather than a local one. Median duration of response was 33.7 months. Overall survival was 75.3 per cent at one year and 63.3 per cent at two. Treatment-related adverse events were grade 1 or 2 in 77.1 per cent, grade 3 in 9.3 per cent and grade 4 in 3.6 per cent, with no grade 5 events. 65.7 per cent had primary resistance to anti-PD-1 therapy and 46.4 per cent had received both anti-PD-1 and anti-CTLA-4 therapy.","asOf":"2026-09-25","links":[{"label":"JCO 2025","url":"https://doi.org/10.1200/JCO-25-01346"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40627813/"}],"tags":[],"related":[],"cancers":["melanoma","advanced-melanoma"],"sections":["immunotherapy"],"technologies":["oncolytic-virus"],"targets":[],"drugs":["vusolimogene-oderparepvec","nivolumab"],"companies":["replimune"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2025,"doi":"10.1200/JCO-25-01346","pmid":"40627813","authors":"Wong MK, Milhem MM, Sacco JJ, et al.","paperType":"rct","findings":["Confirmed objective response rate 32.9 per cent (95% CI 25.2 to 41.3) by independent central review, with 15.0 per cent complete responses.","Responses occurred with similar frequency, depth, duration and kinetics in uninjected lesions, including visceral lesions, as in injected ones.","Median duration of response 33.7 months (95% CI 14.1 to not reached).","Overall survival 75.3 per cent at one year and 63.3 per cent at two years.","Treatment-related adverse events: 77.1 per cent grade 1 or 2, 9.3 per cent grade 3, 3.6 per cent grade 4, no grade 5."],"whatItMeans":"The uninjected-lesion responses are the most important result any oncolytic virus trial has produced, because they are the first strong clinical evidence that the mechanism is systemic immunity rather than local lysis. The caution is the same as always: this is a single-arm cohort in a population with no standard option, and the randomised confirmatory trial has not read out.","caveats":["Single-arm, so the contribution of nivolumab alone in anti-PD-1-failed melanoma cannot be separated out; some patients respond to re-challenge.","Accelerated approval rests on response rate; the randomised IGNYTE-3 trial has to confirm it.","Still requires injectable lesions, so the population is selected for accessible disease."],"changedPractice":true,"participants":140},{"id":"paper-chamie-nejm-evid","kind":"paper","name":"IL-15 Superagonist NAI in BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer","aka":[],"tldr":"Paper cited by one treatment page, indexed on Europe PMC as PubMed record 38320011 and published in NEJM Evidence; the citing page links this DOI, which is how the record was matched.","summary":"BACKGROUND: Patients with Bacillus Calmette, Guérin (BCG), unresponsive non, muscle-invasive bladder cancer (NMIBC) have limited treatment options. The immune cell, activating interleukin-15 (IL-15) superagonist Nogapendekin alfa inbakicept (NAI), also known as N-803, may act synergistically with BCG to elicit durable complete responses (CRs) in this patient population. METHODS: In this open-label, multicenter study, patients with BCG-unresponsive bladder carcinoma in situ (CIS) with or without Ta/T1 papillary disease were treated with intravesical NAI plus BCG (cohort A) or NAI alone (cohort C). Patients with BCG-unresponsive high-grade Ta/T1 papillary NMIBC also received NAI plus BCG (cohort B). The primary end point was the incidence of CR at the 3- or 6-month assessment visit for cohorts A and C, and the disease-free survival (DFS) rate at 12 months for cohort B. Durability, cystectomy avoidance, progression-free survival, disease-specific survival (DSS), and overall survival were secondary end points for cohort A. RESULTS: In cohort A, CR was achieved in 58 (71%) of 82 patients (95% confidence interval [CI]=59.6 to 80.3; median follow-up, 23.9 months), with a median duration of 26.6 months (95% CI=9.9 months to [upper bound not reached]). At 24 months in patients with CR, the Kaplan, Meier estimated probability of avoiding cystectomy and of DSS was 89.2% and 100%, respectively. In cohort B (n=72), the Kaplan, Meier estimated DFS rate was 55.4% (95% CI=42.0% to 66.8%) at 12 months, with median DFS of 19.3 months (95% CI=7.4 months to [upper bound not reached]). Most treatment-emergent adverse events for patients receiving BCG plus NAI were grade 1 to 2 (86%); three grade 3 immune-related treatment-emergent adverse events occurred. CONCLUSIONS: In patients with BCG-unresponsive bladder carcinoma in situ and papillary NMIBC treated with BCG and the novel agent NAI, CRs were achieved with a persistence of effect, cystectomy avoidance, and 100% bladder cancer, specific survival at 24 months. The study is ongoing, with an estimated target enrollment of 200 participants (Funded by ImmunityBio.)\n\nIndexed on Europe PMC as PubMed record 38320011 (DOI 10.1056/evidoa2200167). Matched by DOI alone: one treatment page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"NEJM Evid 2023","url":"https://doi.org/10.1056/evidoa2200167"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38320011/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38320011"}],"tags":["europepmc-ingest"],"related":["nogapendekin-alfa"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm-evidence"],"dependsOn":[],"notes":[],"journal":"NEJM Evidence","year":2023,"doi":"10.1056/evidoa2200167","pmid":"38320011","authors":"Chamie K, Chang SS, Kramolowsky E, et al.","paperType":"observational","findings":[],"whatItMeans":"One treatment page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-hodi-imatinib-kit-melanoma-jco-2013","kind":"paper","name":"Imatinib for melanomas harbouring mutationally activated or amplified KIT arising on mucosal, acral and chronically sun-damaged skin","aka":[],"tldr":"Imatinib shrank tumours in about a third of patients with melanoma carrying KIT mutations, but only in those with mutations in specific exons, defining a small targetable subgroup among mucosal and acral melanomas.","summary":"Phase 2 study of 25 patients with advanced melanoma with KIT mutations or amplification arising on mucosal, acral or chronically sun-damaged skin treated with imatinib.\n\nOverall response was 29 percent, with durable responses confined to tumours with KIT mutations in exons 11 and 13 (particularly L576P and K642E), and none in tumours with KIT amplification alone; median time to progression was 3.7 months overall.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2013","url":"https://doi.org/10.1200/JCO.2012.47.7836"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23775962/"}],"tags":[],"related":[],"cancers":["mucosal-melanoma","acral-melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":["imatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2013,"doi":"10.1200/JCO.2012.47.7836","pmid":"23775962","authors":"Hodi FS, Corless CL, Giobbie-Hurder A, et al.","paperType":"observational","findings":["Objective response 29 percent overall; responses limited to exon 11 and 13 mutations.","No responses with KIT amplification without mutation."],"whatItMeans":"KIT testing is worthwhile in mucosal and acral melanoma, and imatinib is a guideline option for exon 11 or 13 mutations after or alongside immunotherapy.","caveats":["Small study; KIT mutations occur in under 15 percent of mucosal and acral melanomas."],"changedPractice":true,"participants":25},{"id":"paper-imatinib-dfsp-eortc-swog-rutkowski-jco-2010","kind":"paper","name":"Imatinib in advanced dermatofibrosarcoma protuberans: pooled analysis of two phase 2 trials (EORTC 62027 and SWOG S0345)","aka":[],"tldr":"Pooling two trials, imatinib shrank tumours in about half of patients with locally advanced or metastatic dermatofibrosarcoma protuberans, confirming that blocking the PDGF receptor works in this fusion-driven sarcoma.","summary":"Pooled analysis of 24 patients with locally advanced or metastatic dermatofibrosarcoma protuberans treated with imatinib in the EORTC 62027 (800 mg) and SWOG S0345 (400 mg) phase 2 trials, both closed early for slow accrual.\n\nObjective response was 46 percent, with median time to progression of 1.7 years, and responses were similar at both doses; tumours with fibrosarcomatous transformation also responded.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2010","url":"https://doi.org/10.1200/JCO.2009.25.7899"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20194851/"}],"tags":[],"related":[],"cancers":["dermatofibrosarcoma-protuberans"],"sections":[],"technologies":[],"targets":[],"drugs":["imatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["piotr-rutkowski"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2010,"doi":"10.1200/JCO.2009.25.7899","pmid":"20194851","authors":"Rutkowski P, Van Glabbeke M, Rankin CJ, et al.","paperType":"observational","findings":["Objective response 46 percent.","Median time to progression 1.7 years; no dose-response difference between 400 and 800 mg."],"whatItMeans":"Imatinib is the standard systemic treatment for unresectable, recurrent or metastatic dermatofibrosarcoma protuberans and is used neoadjuvantly to shrink large tumours before surgery.","caveats":["Small pooled cohort from two prematurely closed trials."],"changedPractice":true,"participants":24},{"id":"paper-imbrave050-lancet-2023","kind":"paper","name":"IMbrave050: adjuvant atezolizumab plus bevacizumab versus active surveillance after resection or ablation of high-risk hepatocellular carcinoma","aka":[],"tldr":"A year of atezolizumab plus bevacizumab after surgery or ablation for high-risk liver cancer initially reduced recurrences, but the benefit disappeared with longer follow-up, so there is still no proven adjuvant therapy.","summary":"Phase 3 trial of 668 patients with hepatocellular carcinoma at high risk of recurrence after resection or ablation randomised to 12 months of atezolizumab plus bevacizumab or active surveillance.\n\nAt the first interim analysis recurrence-free survival favoured treatment (hazard ratio 0.72), but the updated analysis showed the curves converging (hazard ratio 0.90) with no overall survival benefit; bleeding and immune-related events occurred in the treatment arm.","asOf":"2026-09-17","links":[{"label":"Lancet 2023","url":"https://doi.org/10.1016/S0140-6736(23)01796-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37871608/"}],"tags":[],"related":[],"cancers":["hcc-early"],"sections":[],"technologies":[],"targets":[],"drugs":["atezolizumab","bevacizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["imbrave050"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2023,"doi":"10.1016/S0140-6736(23)01796-8","pmid":"37871608","authors":"Qin S, Chen M, Cheng AL, et al.","paperType":"rct","findings":["Interim recurrence-free survival hazard ratio 0.72; updated hazard ratio 0.90 (not significant).","No overall survival benefit."],"whatItMeans":"Adjuvant immunotherapy is not standard after curative treatment of hepatocellular carcinoma; surveillance, antiviral therapy and risk factor control remain the approach.","caveats":["Early positive result was widely reported before the later negative update."],"changedPractice":true,"participants":668},{"id":"paper-imbrave150-nejm-2020","kind":"paper","name":"IMbrave150: atezolizumab plus bevacizumab replaces sorafenib as first treatment for advanced liver cancer","aka":[],"tldr":"Combining the immunotherapy atezolizumab with the anti-blood-vessel antibody bevacizumab helped patients with advanced hepatocellular carcinoma live longer than sorafenib, ending a decade in which nothing had beaten that drug.","summary":"Open-label phase 3 trial of 501 patients with unresectable hepatocellular carcinoma and preserved liver function (Child-Pugh A) who had not received systemic therapy, randomised 2:1 to atezolizumab plus bevacizumab or sorafenib. Co-primary endpoints were OS and PFS.\n\n12-month OS was 67.2% vs 54.6% (HR 0.58) and median PFS 6.8 vs 4.3 months (HR 0.59). The updated analysis showed median OS 19.2 vs 13.4 months (HR 0.66). It made atezolizumab plus bevacizumab the first-line standard, showed that immunotherapy combinations can work in liver cancer despite the failure of single-agent checkpoint inhibitors, and set the template for durvalumab plus tremelimumab (HIMALAYA).","asOf":"2026-09-08","links":[{"label":"NEJM 2020","url":"https://doi.org/10.1056/NEJMoa1915745"},{"label":"ClinicalTrials.gov NCT03434379","url":"https://clinicaltrials.gov/study/NCT03434379"}],"tags":[],"related":[],"cancers":["hcc"],"sections":[],"technologies":["checkpoint-inhibitor","antiangiogenic","monoclonal-antibody"],"targets":["pdl1","vegf"],"drugs":["atezolizumab"],"companies":["roche-genentech"],"institutions":[],"pathways":[],"terms":["os","pfs","first-line","standard-of-care"],"trials":[],"people":["kim-tae-you","lim-ho-yeong"],"bottlenecks":["b-immunotherapy-response","b-global-access","b-combination-space"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2020,"doi":"10.1056/NEJMoa1915745","authors":"Finn RS, Qin S, Ikeda M, et al.","paperType":"rct","findings":["12-month overall survival 67.2% vs 54.6%; HR 0.58 (95% CI 0.42-0.79).","Median PFS 6.8 vs 4.3 months; HR 0.59.","Objective response 27.3% vs 11.9% (RECIST 1.1).","Updated analysis (2022): median OS 19.2 vs 13.4 months, HR 0.66; median PFS 6.9 vs 4.3 months.","Grade 3-4 adverse events similar (57% vs 55%); upper gastrointestinal bleeding with bevacizumab required endoscopic screening for varices within six months before enrolment.","Patient-reported quality of life deteriorated later with the combination (11.2 vs 3.6 months)."],"whatItMeans":"Patients with advanced liver cancer and good liver function should be offered atezolizumab plus bevacizumab (or durvalumab plus tremelimumab) rather than sorafenib as first treatment; median survival is now around 19 months and about a quarter of patients respond. Endoscopy to treat varices before starting bevacizumab is essential because of bleeding risk. Patients with poorer liver function (Child-Pugh B) or autoimmune disease or transplants were not studied.","caveats":["Excluded Child-Pugh B, untreated varices, and prior transplant, so applies to a selected population.","Open-label; sorafenib is now a weak comparator.","Non-viral (metabolic) liver cancer appeared to benefit less in exploratory analyses across several immunotherapy trials.","Bleeding and hypertension from bevacizumab, and cost, remain barriers in high-incidence low-income regions."],"changedPractice":true,"participants":501},{"id":"paper-imerge-imetelstat-mds-lancet-2024","kind":"paper","name":"IMerge: imetelstat, a telomerase inhibitor, for transfusion-dependent lower-risk MDS after erythropoietin has failed","aka":[],"tldr":"In IMerge, imetelstat, the first telomerase inhibitor to reach approval, freed about 40% of heavily transfused MDS patients from transfusions for eight weeks and 28% for six months, versus 15% and 3% with placebo.","summary":"IMerge randomised 178 patients with lower-risk, non-del(5q) MDS who were red-cell transfusion dependent and had relapsed after or were refractory to, or ineligible for, erythropoiesis-stimulating agents to intravenous imetelstat every four weeks or placebo (2:1). The primary endpoint was eight-week red-cell transfusion independence. This was achieved by 39.8% versus 15.0%; 24-week independence was 28.0% versus 3.3%, and responses lasted around a year with reductions in the SF3B1 mutant allele burden suggesting disease modification. Grade 3-4 thrombocytopenia and neutropenia were frequent but short-lived. Imetelstat was approved in 2024, the first drug in its class.","asOf":"2026-09-08","links":[{"label":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=IMerge%20imetelstat%20lower-risk%20MDS%20Platzbecker%20Lancet%202024"},{"label":"ClinicalTrials.gov NCT02598661","url":"https://clinicaltrials.gov/study/NCT02598661"}],"tags":[],"related":["paper-commands-luspatercept-mds-lancet-2023"],"cancers":["mds"],"sections":[],"technologies":[],"targets":[],"drugs":["imetelstat","luspatercept"],"companies":[],"institutions":[],"pathways":[],"terms":["orr"],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets","b-toxicity-qol"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2024,"doi":"10.1016/S0140-6736(23)01724-5","pmid":"38048786","authors":"Platzbecker U, Santini V, Fenaux P, et al.","paperType":"rct","findings":["178 ESA-relapsed/refractory, transfusion-dependent, non-del(5q) lower-risk MDS patients; imetelstat vs placebo (2:1).","8-week transfusion independence 39.8% vs 15.0%; 24-week independence 28.0% vs 3.3%.","Median duration of transfusion independence about one year in responders.","Reductions in variant allele frequency of SF3B1 and other mutations in responders, suggesting disease-modifying activity.","Grade 3-4 thrombocytopenia and neutropenia common (roughly two-thirds), usually resolving within 4 weeks."],"whatItMeans":"IMerge validated telomerase as a drug target in cancer, decades after its discovery, and gave a second-line option for MDS patients whose anaemia no longer responds to erythropoietin or luspatercept. The hint of clonal reduction is what makes the drug interesting beyond transfusion counts. Cytopenias require close monitoring in the first cycles.","caveats":["Surrogate endpoint (transfusion independence) rather than survival or progression.","High rates of grade 3-4 cytopenias in a population already at bleeding and infection risk.","Only 8-week independence was the primary endpoint; the more meaningful 24-week rate was secondary.","Disease-modifying claims rest on exploratory molecular analyses."],"changedPractice":true,"participants":178},{"id":"paper-ember-3-n-engl-j-med-2025","kind":"paper","name":"Imlunestrant with or without Abemaciclib in Advanced Breast Cancer","aka":[],"tldr":"Published report from the EMBER-3 trial registered as NCT04975308, in New England Journal of Medicine (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Imlunestrant is a next-generation, brain-penetrant, oral selective estrogen-receptor (ER) degrader that delivers continuous ER inhibition, even in cancers with mutations in the gene encoding ERα ( ESR1).\n\nMethods: In a phase 3, open-label trial, we enrolled patients with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer that recurred or progressed during or after aromatase inhibitor therapy, administered alone or with a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor. Patients were assigned in a 1:1:1 ratio to receive imlunestrant, standard endocrine monotherapy, or imlunestrant-abemaciclib. Primary end points were investigator-assessed progression-free survival with imlunestrant as compared with standard therapy among patients with ESR1 mutations and among all patients and with imlunestrant-abemaciclib as compared with imlunestrant among all patients who had undergone randomization concurrently.\n\nResults: Overall, 874 patients underwent randomization, with 331 assigned to imlunestrant, 330 to standard therapy, and 213 to imlunestrant-abemaciclib. Among 256 patients with ESR1 mutations, the median progression-free survival was 5.5 months with imlunestrant and 3.8 months with standard therapy. The estimated restricted mean survival time at 19.4 months was 7.9 months (95% confidence interval [CI], 6.8 to 9.1) with imlunestrant and 5.4 months (95% CI, 4.6 to 6.2) with standard therapy (difference, 2.6 months; 95% CI, 1.2 to 3.9; P<0.001). In the overall population, the median progression-free survival was 5.6 months with imlunestrant and 5.5 months with standard therapy (hazard ratio for progression or death, 0.87; 95% CI, 0.72 to 1.04; P = 0.12). Among 426 patients in the comparison of imlunestrant-abemaciclib with imlunestrant, the median progression-free survival was 9.4 months and 5.5 months, respectively (hazard ratio, 0.57; 95% CI, 0.44 to 0.73; P<0.001). The incidence of grade 3 or higher adverse events was 17.1% with imlunestrant, 20.7% with standard therapy, and 48.6% with imlunestrant-abemaciclib.\n\nConclusions: Among patients with ER-positive, HER2-negative advanced breast cancer, treatment with imlunestrant led to significantly longer progression-free survival than standard therapy among those with ESR1 mutations but not in the overall population. Imlunestrant-abemaciclib significantly improved progression-free survival as compared with imlunestrant, regardless of ESR1 -mutation status. (Funded by Eli Lilly; EMBER-3 ClinicalTrials.gov number, NCT04975308.).\n\nIndexed on Europe PMC as PubMed record 39660834 (DOI 10.1056/nejmoa2410858). Its abstract cites the registry id NCT04975308, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2025","url":"https://doi.org/10.1056/nejmoa2410858"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39660834/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39660834"},{"label":"ClinicalTrials.gov NCT04975308","url":"https://clinicaltrials.gov/study/NCT04975308"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["ember-3"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2025,"doi":"10.1056/nejmoa2410858","pmid":"39660834","authors":"Jhaveri KL, Neven P, Casalnuovo ML, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04975308 with the most citations, so it is the natural first reading for anyone following the EMBER-3 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-patil-gallbladder-immune-microenvironment-aimm-2021","kind":"paper","name":"Immune microenvironment in gallbladder adenocarcinomas","aka":[],"tldr":"A small United States series found PD-L1 in almost every gallbladder adenocarcinoma and PD-1-bearing immune cells in most, with the number of T cells in the stroma predicting survival differently in small and large tumours.","summary":"PD-1 expression, not previously reported in gallbladder adenocarcinoma, was examined together with PD-L1 and T-cell markers in 47 cases. 98% (46 of 47) expressed PD-L1, 85% at 3+, and PD-1-positive tumour-infiltrating lymphocytes were present in 78.7% (37 of 47). Tumours with PD-1-positive lymphocytes were smaller and had more stromal CD3-positive T cells.\n\nIn tumours under 3 cm, stromal CD3 above 115 or CD8 above 45 per high-power field went with much better survival; in tumours of 3 cm or more, PD-1-positive lymphocytes or stromal CD8 above 45 per high-power field carried significantly poorer survival. PD-1 did not correlate with lymphovascular invasion, distant metastasis or stage; stage and age were the independent prognostic factors.","asOf":"2026-09-24","links":[{"label":"Patil et al., Appl Immunohistochem Mol Morphol 2021: immune microenvironment in 47 gallbladder adenocarcinomas","url":"https://doi.org/10.1097/pai.0000000000000922"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33710123/"}],"tags":[],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":["pdl1","pd1"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tils","ihc"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Applied Immunohistochemistry and Molecular Morphology","year":2021,"doi":"10.1097/pai.0000000000000922","pmid":"33710123","authors":"Patil PA, Lombardo K, Cao W.","paperType":"observational","findings":["PD-L1 in 98% (46 of 47) of gallbladder adenocarcinomas, 85% at 3+; PD-1-positive infiltrating lymphocytes in 78.7%.","Tumours under 3 cm: stromal CD3 above 115 or CD8 above 45 per high-power field predicted better survival.","Tumours 3 cm or larger: PD-1-positive lymphocytes or high CD8 predicted worse survival."],"whatItMeans":"The 98% figure shows how much antibody and scoring choices matter: it sits against 14.7% and 23% in the two large series. The tumour-size-dependent effect of T-cell density is a hypothesis about immune exhaustion in bulkier tumours.","caveats":["47 cases from one centre; PD-L1 method and cut-off differ from the SP263 and TPS series.","Survival analyses in size-defined subgroups were small."],"changedPractice":false,"participants":47},{"id":"paper-ackerman-nat-cancer","kind":"paper","name":"Immune-stimulating antibody conjugates elicit robust myeloid activation and durable antitumor immunity","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 35121890 and published in Nature Cancer; the citing page links this DOI, which is how the record was matched.","summary":"Innate pattern recognition receptor agonists, including Toll-like receptors (TLRs), alter the tumor microenvironment and prime adaptive antitumor immunity. However, TLR agonists present toxicities associated with widespread immune activation after systemic administration. To design a TLR-based therapeutic suitable for systemic delivery and capable of safely eliciting tumor-targeted responses, we developed immune-stimulating antibody conjugates (ISACs) comprising a TLR7/8 dual agonist conjugated to tumor-targeting antibodies. Systemically administered human epidermal growth factor receptor 2 (HER2)-targeted ISACs were well tolerated and triggered a localized immune response in the tumor microenvironment that resulted in tumor clearance and immunological memory. Mechanistically, ISACs required tumor antigen recognition, Fcγ-receptor-dependent phagocytosis and TLR-mediated activation to drive tumor killing by myeloid cells and subsequent T-cell-mediated antitumor immunity. ISAC-mediated immunological memory was not limited to the HER2 ISAC target antigen since ISAC-treated mice were protected from rechallenge with the HER2 - parental tumor. These results provide a strong rationale for the clinical development of ISACs.\n\nIndexed on Europe PMC as PubMed record 35121890 (DOI 10.1038/s43018-020-00136-x). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Cancer 2021","url":"https://doi.org/10.1038/s43018-020-00136-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35121890/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35121890"}],"tags":["europepmc-ingest"],"related":["immune-stimulating-adc"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Cancer","year":2021,"doi":"10.1038/s43018-020-00136-x","pmid":"35121890","authors":"Ackerman SE, Pearson CI, Gregorio JD, et al.","paperType":"basic","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-sankaranarayanan-lancet-oncol","kind":"paper","name":"Immunogenicity and HPV infection after one, two, and three doses of quadrivalent HPV vaccine in girls in India: a multicentre prospective cohort study","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 26652797 and published in The Lancet Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background: An increase in worldwide HPV vaccination could be facilitated if fewer than three doses of vaccine are as effective as three doses. We originally aimed to compare the immunogenicity and frequency of persistent infection and cervical precancerous lesions caused by vaccine-targeted HPV after vaccination with two doses of quadrivalent vaccine on days 1 and 180 or later, with three doses on days 1, 60, and 180 or later, in a cluster-randomised trial. Suspension of the recruitment and vaccination due to events unrelated to our study meant that some enrolled girls could not be vaccinated and some vaccinated girls received fewer than the planned number of vaccinations by default. As a result, we re-analysed our data as an observational cohort study.\n\nMethods: Our study was designed to be done in nine locations (188 clusters) in India. Participants were unmarried girls aged 10-18 years vaccinated in four cohorts: girls who received three doses of vaccine on days 1, 60, and 180 or later, two doses on days 1 and 180 or later, two doses on days 1 and 60 by default, and one dose by default. The primary outcomes were immunogenicity in terms of L1 genotype-specific binding antibody titres, neutralising antibody titres, and antibody avidity after vaccination for the vaccine-targeted HPV types 16, 18, 6, and 11 and incident and persistent infections with these HPVs. Analysis was per actual number of vaccine doses received. This study is registered with ISRCTN, number ISRCTN98283094; and with ClinicalTrials.gov, number NCT00923702.\n\nFindings: Vaccination of eligible girls was initiated on Sept 1, 2009, and continued until April 8, 2010. Of 21 258 eligible girls identified at 188 clusters, 17 729 girls were recruited from 178 clusters before suspension. 4348 (25%) girls received three doses, 4979 (28%) received two doses on days 1 and 180 or later, 3452 (19%) received two doses at days 1 and 60, and 4950 (28%) received one dose. Immune response in the two-dose HPV vaccine group was non-inferior to the three-dose group (median fluorescence intensity ratio for HPV 16 1·12 [95% CI 1·02-1·23] and for HPV 18 1·04 [0·92-1·19]) at 7 months, but was inferior in the two-dose default (0·33 [0·29-0·38] for HPV 16 and 0·51 [0·43-0·59] for HPV 18) and one-dose default (0·09 [0·08-0·11] for HPV 16 and 0·12 [0·10-0·14] for HPV 18) groups at 18 months. The geometric mean avidity indices after fewer than three doses by design or default were non-inferior to those after three doses of vaccine. Fewer than three doses by design and default induced detectable concentrations of neutralising antibodies to all four vaccine-targeted HPV types, but at much lower concentration after one dose. Cervical samples from 2649 participants were tested and the frequency of incident HPV 16, 18, 6, and 11 infections was similar irrespective of the number of vaccine doses received. The testing of at least two samples from 838 participants showed that there was no persistent HPV 16 or 18 infections in any study group at a median follow-up of 4·7 years (IQR 4·2-5·1).\n\nInterpretation: Despite the limitations imposed by the suspension of the HPV vaccination, our findings lend support to the WHO recommendation of two doses, at least 6 months apart, for routine vaccination of young girls. The short-term protection afforded by one dose of HPV vaccine against persistent infection with HPV 16, 18, 6, and 11 is similar to that afforded by two or three doses of vaccine and merits further assessment.\n\nFunding: Bill & Melinda Gates Foundation.\n\nIndexed on Europe PMC as PubMed record 26652797 (DOI 10.1016/s1470-2045(15)00414-3). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2016","url":"https://doi.org/10.1016/s1470-2045(15)00414-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26652797/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26652797"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["iarc-india-hpv-dose-study"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2016,"doi":"10.1016/s1470-2045(15)00414-3","pmid":"26652797","authors":"Sankaranarayanan R, Prabhu PR, Pawlita M, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-lenz-cms-calgb-swog-80405-jco-2019","kind":"paper","name":"Impact of consensus molecular subtype on survival in patients with metastatic colorectal cancer: results from CALGB/SWOG 80405","aka":[],"tldr":"In the one randomised trial where the four gene-activity subtypes were measured, they predicted not only how long people lived but which biological drug worked better: the immune subtype did better with bevacizumab and the canonical subtype with cetuximab.","summary":"The consensus molecular subtypes were characterised with a NanoString gene expression panel on primary tumours from 581 patients enrolled in CALGB/SWOG 80405, a phase 3 trial comparing the addition of bevacizumab or cetuximab to infusional fluorouracil, leucovorin and oxaliplatin or irinotecan as first-line treatment of advanced colorectal cancer. The subtypes were highly prognostic for overall survival (p less than 0.001) and progression-free survival (p less than 0.001), and predictive for both (interaction p less than 0.001 for overall survival and 0.0032 for progression-free survival). In the CMS1 cohort, patients treated with bevacizumab lived significantly longer than those treated with cetuximab (p less than 0.001); in the CMS2 cohort, patients treated with cetuximab lived significantly longer than those treated with bevacizumab (p = 0.0046).","asOf":"2026-09-24","links":[{"label":"Lenz et al., J Clin Oncol 2019: consensus molecular subtype and survival in 581 CALGB/SWOG 80405 patients","url":"https://doi.org/10.1200/JCO.18.02258"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31042420/"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["rna-seq"],"targets":["egfr","vegf"],"drugs":["bevacizumab","cetuximab"],"companies":[],"institutions":[],"pathways":[],"terms":["cms-subtypes"],"trials":[],"people":["heinz-josef-lenz","alan-venook"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2019,"doi":"10.1200/JCO.18.02258","pmid":"31042420","authors":"Lenz HJ, Ou FS, Venook AP, et al.","paperType":"rct","findings":["Consensus molecular subtypes prognostic for overall and progression-free survival (p less than 0.001).","CMS1: longer overall survival with bevacizumab than cetuximab (p less than 0.001).","CMS2: longer overall survival with cetuximab than bevacizumab (p = 0.0046)."],"whatItMeans":"It is the strongest evidence that the consensus subtypes could choose between the two first-line biologicals, and the clearest statement of why they have not: it is a retrospective analysis of a subset of one trial, on an assay nobody has validated for clinical use.","caveats":["Retrospective on 581 of the trial's patients, so subgroup effects may be chance.","Primary tumour tissue and bulk RNA, with the stromal confound described by Isella and Calon.","No prospective subtype-directed trial has been run."],"changedPractice":false,"participants":581},{"id":"paper-mcfarland-proc-natl-acad-sci-u-s-a","kind":"paper","name":"Impact of deleterious passenger mutations on cancer progression","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 23388632 and published in Proceedings of the National Academy of Sciences; the citing page links this DOI, which is how the record was matched.","summary":"Cancer progression is driven by the accumulation of a small number of genetic alterations. However, these few driver alterations reside in a cancer genome alongside tens of thousands of additional mutations termed passengers. Passengers are widely believed to have no role in cancer, yet many passengers fall within protein-coding genes and other functional elements that can have potentially deleterious effects on cancer cells. Here we investigate the potential of moderately deleterious passengers to accumulate and alter the course of neoplastic progression. Our approach combines evolutionary simulations of cancer progression with an analysis of cancer sequencing data. From simulations, we find that passengers accumulate and largely evade natural selection during progression. Although individually weak, the collective burden of passengers alters the course of progression, leading to several oncological phenomena that are hard to explain with a traditional driver-centric view. We then tested the predictions of our model using cancer genomics data and confirmed that many passengers are likely damaging and have largely evaded negative selection. Finally, we use our model to explore cancer treatments that exploit the load of passengers by either (i) increasing the mutation rate or (ii) exacerbating their deleterious effects. Though both approaches lead to cancer regression, the latter is a more effective therapy. Our results suggest a unique framework for understanding cancer progression as a balance of driver and passenger mutations.\n\nIndexed on Europe PMC as PubMed record 23388632 (DOI 10.1073/pnas.1213968110). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Proc Natl Acad Sci U S A 2013","url":"https://doi.org/10.1073/pnas.1213968110"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23388632/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/23388632"}],"tags":["europepmc-ingest"],"related":["driver-passenger-model"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["pnas"],"dependsOn":[],"notes":[],"journal":"Proceedings of the National Academy of Sciences","year":2013,"doi":"10.1073/pnas.1213968110","pmid":"23388632","authors":"McFarland CD, Korolev KS, Kryukov GV, et al.","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-rubin-mol-cell","kind":"paper","name":"Impact of Lineage Plasticity to and from a Neuroendocrine Phenotype on Progression and Response in Prostate and Lung Cancers","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 33217316 and published in Molecular cell; the citing page links this DOI, which is how the record was matched.","summary":"Intratumoral heterogeneity can occur via phenotype transitions, often after chronic exposure to targeted anticancer agents. This process, termed lineage plasticity, is associated with acquired independence to an initial oncogenic driver, resulting in treatment failure. In non-small cell lung cancer (NSCLC) and prostate cancers, lineage plasticity manifests when the adenocarcinoma phenotype transforms into neuroendocrine (NE) disease. The exact molecular mechanisms involved in this NE transdifferentiation remain elusive. In small cell lung cancer (SCLC), plasticity from NE to nonNE phenotypes is driven by NOTCH signaling. Herein we review current understanding of NE lineage plasticity dynamics, exemplified by prostate cancer, NSCLC, and SCLC.\n\nIndexed on Europe PMC as PubMed record 33217316 (DOI 10.1016/j.molcel.2020.10.033). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Mol Cell 2020","url":"https://doi.org/10.1016/j.molcel.2020.10.033"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33217316/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33217316"}],"tags":["europepmc-ingest"],"related":["cancer-stem-cells-plasticity"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Molecular cell","year":2020,"doi":"10.1016/j.molcel.2020.10.033","pmid":"33217316","authors":"Rubin MA, Bristow RG, Thienger PD, et al.","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-sikov-calgb-40603-carboplatin-bevacizumab-jco-2015","kind":"paper","name":"Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (Alliance)","aka":[],"tldr":"The US trial of 443 women that showed adding carboplatin to pre-surgery paclitaxel, doxorubicin and cyclophosphamide raised complete tumour disappearance in breast and nodes from 41 to 54 percent, at the cost of more low blood counts and skipped doses; it and GeparSixto made platinum standard.","summary":"CALGB 40603 (Alliance), a 2 by 2 factorial open-label randomised phase 2 trial by Sikov, Berry, Perou, Singh and colleagues, gave 443 patients with stage II to III triple-negative breast cancer weekly paclitaxel for 12 weeks then dose-dense doxorubicin and cyclophosphamide, randomised to concurrent carboplatin (area under the curve 6, four cycles) and/or bevacizumab (nine cycles). Patients assigned carboplatin or bevacizumab were less likely to complete chemotherapy without skipped doses, modification or discontinuation; grade 3 or higher neutropenia and thrombocytopenia were more common with carboplatin, and hypertension, infection, thromboembolism, bleeding and postoperative complications with bevacizumab. Carboplatin raised pathological complete response in the breast from 44 to 60 percent (p=0.0018) and in breast and axilla from 41 to 54 percent (p=0.0029); bevacizumab raised breast response (48 to 59 percent, p=0.0089) but not breast and axilla. No more-than-additive interaction was shown.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2015","url":"https://doi.org/10.1200/JCO.2014.57.0572"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25092775/"},{"label":"ClinicalTrials.gov NCT00861705","url":"https://clinicaltrials.gov/study/NCT00861705"}],"tags":["tnbc-evidence"],"related":["paper-geparsixto-lancet-oncol-2014"],"cancers":["tnbc"],"sections":[],"technologies":["platinum"],"targets":[],"drugs":["carboplatin","paclitaxel","doxorubicin","cyclophosphamide"],"companies":[],"institutions":[],"pathways":[],"terms":["pcr","neoadjuvant-adjuvant"],"trials":["geparsixto","keynote-522"],"people":["charles-perou"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2015,"doi":"10.1200/JCO.2014.57.0572","pmid":"25092775","authors":"Sikov WM, Berry DA, Perou CM, et al.","paperType":"rct","findings":["Carboplatin: pathological complete response in breast and axilla 54 vs 41 percent (one-sided p=0.0029); in breast 60 vs 44 percent (p=0.0018).","Bevacizumab raised breast response (59 vs 48 percent) but not breast and axilla response; more toxicity with both agents."],"whatItMeans":"With GeparSixto, the trial that put carboplatin into the neoadjuvant triple-negative regimen; KEYNOTE-522's chemotherapy backbone is this one plus pembrolizumab. Bevacizumab, the other arm, left the field.","caveats":["Phase 2 with a pathological complete response endpoint; survival effects were not powered and the authors said so.","The trial could not identify which patients need platinum, a question still open."],"changedPractice":true,"participants":443},{"id":"paper-cai-j-glob-health","kind":"paper","name":"Impact of the national drug price negotiation policy on the utilization, cost, and accessibility of anticancer medicines in China: A controlled interrupted time series study","aka":[],"tldr":"Paper cited by one institution page, indexed on Europe PMC as PubMed record 36527382 and published in Journal of global health; the citing page links this DOI, which is how the record was matched.","summary":"Background: China implemented the national drug price negotiation (NDPN) policy to include 17 innovative anticancer medicines in the national reimbursement drug list in 2018. We aimed to assess the impact of this policy on the utilization, cost, and accessibility of anticancer medicines.\n\nMethods: We obtained monthly medicine procurement data from 1039 hospitals from October 2017 to December 2019. We examined changes in availability, utilization, defined daily dose cost (DDDc), and affordability of the medicines using descriptive statistics and controlled interrupted time series analysis, measuring utilization by defined daily doses (DDDs). Cetuximab and raltitrexed were compared separately for the same indication.\n\nResults: The mean availability of 17 negotiated anticancer medicines was 28.78% after the NDPN, amounting to an increase of 25.22%. The availability increased by 7.88% (95% confidence interval (CI) = 4.31%, 11.45%, P < 0.001) immediately and by 1.23% (95% CI = 0.81%, 1.64%, P < 0.001) per month after policy implementation. Compared with the control group, the utilization of the medicines increased by 11.44 DDDs (95% CI = 2.42, 20.46, P = 0.014) immediately and by 3.54 DDDs (95% CI = 2.47, 4.60, P < 0.001) per month after policy implementation, while the DDDc decreased by US$109.09 (95% CI = 68.14, 150.05, P < 0.001) immediately and remained stable thereafter. The results on cetuximab and raltitrexed were similar. Availability and utilization differed among regions in east, middle, and west China. Out-of-pocket costs decreased by 17.35 times the catastrophic health expenditures to 1.99 times, but the affordability ratio for 14 negotiated medicines was still greater than 1.\n\nConclusions: The NDPN policy improved the availability, utilization, and affordability of anticancer medicines. China's experience in NDPN provides a reference for other countries. However, the availability and affordability of anticancer medicines still need further improvement.\n\nIndexed on Europe PMC as PubMed record 36527382 (DOI 10.7189/jogh.12.11016). Matched by DOI alone: one institution page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Glob Health 2022","url":"https://doi.org/10.7189/jogh.12.11016"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36527382/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36527382"}],"tags":["europepmc-ingest"],"related":["nhsa"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of global health","year":2022,"doi":"10.7189/jogh.12.11016","pmid":"36527382","authors":"Cai L, Tao T, Li H, et al.","paperType":"observational","findings":[],"whatItMeans":"One institution page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-anthony-nichols-nat-genet-2017","kind":"paper","name":"Impaired H3K36 methylation defines a subset of head and neck squamous cell carcinomas","aka":[],"tldr":"Paper by Anthony C. Nichols indexed on Europe PMC as PubMed record 28067913, in Nature Genetics (2017), one of the most cited records naming an author with this name at Verspeeten Family Cancer Centre, London Health Sciences Centre.","summary":"Human papillomavirus (HPV)-negative head and neck squamous cell carcinomas (HNSCCs) are deadly and common cancers. Recent genomic studies implicate multiple genetic pathways, including cell signaling, cell cycle and immune evasion, in their development. Here we analyze public data sets and uncover a previously unappreciated role of epigenome deregulation in the genesis of 13% of HPV-negative HNSCCs. Specifically, we identify novel recurrent mutations encoding p.Lys36Met (K36M) alterations in multiple H3 histone genes. histones. We further validate the presence of these alterations in multiple independent HNSCC data sets and show that, along with previously described NSD1 mutations, they correspond to a specific DNA methylation cluster. The K36M substitution and NSD1 defects converge on altering methylation of histone H3 at K36 (H3K36), subsequently blocking cellular differentiation and promoting oncogenesis. Our data further indicate limited redundancy for NSD family members in HPV-negative HNSCCs and suggest a potential role for impaired H3K36 methylation in their development. Further investigation of drugs targeting chromatin regulators is warranted in HPV-negative HNSCCs driven by aberrant H3K36 methylation.\n\nIndexed on Europe PMC as PubMed record 28067913 (DOI 10.1038/ng.3757). Its author list gives \"Nichols AC\" with the affiliation \"Department of Otolaryngology-Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada\", which names Verspeeten Family Cancer Centre, London Health Sciences Centre; that is how the record was matched to Anthony C. Nichols, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Genet 2017","url":"https://doi.org/10.1038/ng.3757"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28067913/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28067913"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["anthony-nichols"],"bottlenecks":[],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":2017,"doi":"10.1038/ng.3757","pmid":"28067913","authors":"Papillon-Cavanagh S, Lu C, Gayden T, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Anthony C. Nichols at Verspeeten Family Cancer Centre, London Health Sciences Centre, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-conroy-nhs-r208-mainstream-testing-audit-breast-j-2026","kind":"paper","name":"Implementation and audit of mainstream genetic testing within a high-volume UK breast unit for pathogenic variations associated with breast cancer using the R208 and R444.1 National Test Directory criterion","aka":[],"tldr":"Applying the NHS test directory rules at one large breast unit, 255 of 1,812 new patients were eligible, 196 were tested and 14% carried an inherited variant; the result changed surgery for 14 women and gave three a PARP inhibitor.","summary":"Eligibility under the NHS National Genomic Test Directory R208 (mainstream breast cancer testing, published 2020) and R444.1 (PARP inhibitor eligibility) was assessed for every patient diagnosed with DCIS or invasive breast cancer between March 2021 and March 2025. Of 1,812 new diagnoses, 255 were eligible and 196 consented; 28 (14.3%) carried a pathogenic or likely pathogenic variant, eight eligible only on family history. Of 21 candidates for breast conservation, 13 had preoperative results and eight chose bilateral mastectomy; three women with a new BRCA variant received a PARP inhibitor. Eligibility assessment was time-consuming for trained clinicians.","asOf":"2026-09-24","links":[{"label":"Conroy et al., Breast J 2026: audit of mainstream genetic testing under the NHS R208 and R444.1 criteria","url":"https://doi.org/10.1155/tbj/2657384"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42504120/"}],"tags":[],"related":[],"cancers":["tnbc","breast-cancer"],"sections":[],"technologies":["germline-testing"],"targets":["brca"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["gbrca-mutation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["the-breast-journal"],"dependsOn":[],"notes":[],"journal":"The Breast Journal","year":2026,"doi":"10.1155/tbj/2657384","pmid":"42504120","authors":"Conroy S, Keane E, Rehman B, et al.","paperType":"real-world","findings":["255 of 1,812 eligible under R208/R444.1; 196 tested; 28 (14.3%) positive.","Eight carriers eligible only through family history scoring.","Surgical plan changed for 14 women; three received a PARP inhibitor."],"whatItMeans":"This is what the NHS R208 pathway yields in practice: a one-in-seven positive rate among the eligible, at the cost of clinician time spent on eligibility scoring.","caveats":["Single unit; DCIS included.","The proportion of TNBC among those tested is not in the abstract."],"changedPractice":false,"participants":1812},{"id":"paper-nct05732805-eur-j-cancer-2025","kind":"paper","name":"Improved clinical outcomes with low-dose anti-CTLA-4 (Nurulimab) plus anti-PD-1 (Prolgolimab) vs. anti-PD-1 monotherapy in advanced cutaneous melanoma: Results from the phase III OCTAVA trial","aka":[],"tldr":"Published report from the OCTAVA trial registered as NCT05732805, in European Journal of Cancer (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: OCTAVA (NCT05732805) was an international, multi-center, randomized, double-blind, phase III study evaluating the fixed-dose combination of nurulimab (anti-CTLA-4) and prolgolimab (anti-PD-1) (BCD-217, Nuru+Prolgo) followed by prolgolimab maintenance versus prolgolimab monotherapy as first-line treatment for unresectable or metastatic melanoma (un/mM). We present the primary analysis results.\n\nMethods: Treatment-naïve patients with un/mM were randomized 1:1 to Nuru+Prolgo (n = 135) or prolgolimab (n = 136) for 4 cycles, followed by prolgolimab maintenance for up to two years. The primary endpoint was progression-free survival (PFS) by iRECIST.\n\nResults: With a median follow-up of 15.8 months, median PFS was significantly longer with nurulimab+prolgolimab [15.4 months (95 % CI, 10.3-ND)] compared to prolgolimab monotherapy [10.8 months (4.7-ND)] (HR 0.68; 95 % CI, 0.482-0.957; iRECIST). RECIST 1.1 analysis confirmed this benefit (mPFS 9.9 vs 2.8 months). ORR and DCR were also higher in the combination arm. Grade 3-4 treatment-related AE: 16.3 % (combination) vs 14.0 % (monotherapy). Immune-related AEs (irAE): 52.6 % vs 32.4 % (p = 0.0007); Gr. ≥ 3 irAE: 13.3 % vs 5.9 % (p = 0.04). Discontinuations due to AE: 9.6 % vs 4.4 %.\n\nConclusions: The Nuru+Prolgo fixed-dose combination demonstrated significantly superior efficacy versus aPD-1 monotherapy in first-line un/mM, with a manageable safety profile.\n\nIndexed on Europe PMC as PubMed record 40795521 (DOI 10.1016/j.ejca.2025.115674). Its abstract cites the registry id NCT05732805, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Eur J Cancer 2025","url":"https://doi.org/10.1016/j.ejca.2025.115674"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40795521/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40795521"},{"label":"ClinicalTrials.gov NCT05732805","url":"https://clinicaltrials.gov/study/NCT05732805"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05732805"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["european-journal-of-cancer"],"dependsOn":[],"notes":[],"journal":"European Journal of Cancer","year":2025,"doi":"10.1016/j.ejca.2025.115674","pmid":"40795521","authors":"Demidov L, Samoylenko I, Kharkevich G, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05732805 with the most citations, so it is the natural first reading for anyone following the OCTAVA trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-study-0201-blood-2006","kind":"paper","name":"Improved leukemia-free survival after postconsolidation immunotherapy with histamine dihydrochloride and interleukin-2 in acute myeloid leukemia: results of a randomized phase 3 trial","aka":[],"tldr":"The primary report of Study 0201: adding histamine dihydrochloride to low-dose interleukin-2 after consolidation improved leukaemia-free survival in acute myeloid leukaemia, with 40 percent against 26 percent leukaemia-free at three years in first remission.","summary":"Phase 3 trial whose primary objective was to determine whether postconsolidation immunotherapy with interleukin-2 and histamine dihydrochloride improved leukaemia-free survival of adults with acute myeloid leukaemia in complete remission. Three hundred and twenty patients (median age 57 years, range 18 to 84) were stratified by first or subsequent complete remission and randomly assigned to histamine dihydrochloride plus interleukin-2 or no treatment. Treatment comprised ten 21-day cycles of interleukin-2 (16,400 units per kilogram) plus histamine dihydrochloride (0.5 mg), both by subcutaneous injection twice daily. Arms were balanced for age, sex, previous treatment, karyotype, time from remission to inclusion and secondary leukaemia.\n\nThree years after enrolment of the last patient, treatment improved leukaemia-free survival over control in the study population (n = 320; P < .01, log-rank). For patients in first complete remission (n = 261), treatment significantly improved leukaemia-free survival (P = .01) with 3-year estimates of 40 percent versus 26 percent. Side effects were typically mild to moderate.","asOf":"2026-09-24","links":[{"label":"Blood 2006","url":"https://doi.org/10.1182/blood-2005-10-4073"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/16556892/"},{"label":"ClinicalTrials.gov NCT00003991","url":"https://clinicaltrials.gov/study/NCT00003991"}],"tags":[],"related":[],"cancers":["aml"],"sections":[],"technologies":[],"targets":[],"drugs":["histamine-dihydrochloride","aldesleukin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["study-0201"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["blood"],"dependsOn":[],"notes":[],"journal":"Blood","year":2006,"doi":"10.1182/blood-2005-10-4073","pmid":"16556892","authors":"Brune M, Castaigne S, Catalano J, et al.","paperType":"rct","findings":["Leukaemia-free survival improved with histamine dihydrochloride plus interleukin-2 over no treatment in all 320 patients (P < .01, log-rank).","In first complete remission (n = 261), 3-year leukaemia-free survival 40% vs 26% (P = .01).","Side effects typically mild to moderate."],"whatItMeans":"This is the trial behind the 2008 European authorisation of Ceplene, one of very few maintenance immunotherapies ever approved in acute myeloid leukaemia. The abstract reports no overall survival benefit and the drug is little used today, with oral azacitidine and targeted maintenance filling the space.","caveats":["Open-label, against no treatment rather than placebo.","The 40% vs 26% figure is a first-remission subgroup landmark; the abstract prints no three-year rates for the full population and no hazard ratio.","The registry posts only an estimated enrolment of 360 and no results."],"changedPractice":true,"participants":320},{"id":"paper-florence-duffaud-ann-oncol-2017","kind":"paper","name":"Improved survival using specialized multidisciplinary board in sarcoma patients","aka":[],"tldr":"Paper by Florence Duffaud indexed on Europe PMC as PubMed record 29117335, in Annals of Oncology (2017), one of the most cited records naming an author with this name at Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille.","summary":"Background: Sarcomas are rare but aggressive diseases. Specialized multidisciplinary management is not implemented for all patients in most countries. We investigated the impact of a multidisciplinary tumor board (MDTB) presentation before treatment in a nationwide study over 5 years.\n\nPatients and methods: NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized MDTB, funded by the French National Cancer Institute to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB and second pathological review are mandatory for sarcoma patients in France. Patients' characteristics and follow-up are collected in a database regularly monitored and updated. The management and survival of patients presented to these MDTB before versus after initial treatment were analyzed.\n\nResults: Out of the 12 528 patients aged ≥15 years, with a first diagnosis of soft tissue and visceral sarcoma obtained between 1 January 2010 and 31 December 2014, 5281 (42.2%) and 7247 (57.8%) were presented to the MDTB before and after the initiation of treatment, respectively. The former group had generally worse prognostic characteristics. Presentation to a MDTB before treatment was associated with a better compliance to clinical practice guidelines, for example, biopsy before surgery, imaging, quality of initial surgery, and less reoperations (all P < 0.001). Local relapse-free survival and relapse-free survival were significantly better in patients presented to a MDTB before initiation of treatment, both in univariate and multivariate analysis.\n\nConclusion: The compliance to clinical practice guidelines and relapse-free survival of sarcoma patients are significantly better when the initial treatment is guided by a pre-therapeutic specialized MDTB.\n\nIndexed on Europe PMC as PubMed record 29117335 (DOI 10.1093/annonc/mdx484). Its author list gives \"Duffaud F\" with the affiliation \"Department of Medical Oncology, La Timone University Hospital, Marseille\", which names Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille; that is how the record was matched to Florence Duffaud, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Ann Oncol 2017","url":"https://doi.org/10.1093/annonc/mdx484"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29117335/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29117335"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["florence-duffaud"],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2017,"doi":"10.1093/annonc/mdx484","pmid":"29117335","authors":"Blay JY, Soibinet P, Penel N, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Florence Duffaud at Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-swedish-rectal-cancer-trial-preoperative-radiotherapy-nejm-1997","kind":"paper","name":"Improved survival with preoperative radiotherapy in resectable rectal cancer (Swedish Rectal Cancer Trial)","aka":[],"tldr":"Five days of radiotherapy before the operation more than halved the chance of the cancer coming back in the pelvis, and was the first rectal cancer trial to show that radiotherapy also helps people live longer.","summary":"Between March 1987 and February 1990 the Swedish Rectal Cancer Trial randomly assigned 1,168 patients younger than 80 with resectable rectal cancer to preoperative irradiation (25 Gy in five fractions in one week) followed by surgery within one week, or to surgery alone. Irradiation did not increase postoperative mortality.\n\nThe difference in local recurrence was found in all subgroups defined by Dukes' stage. The trial predates total mesorectal excision as a standard, which is why the Dutch TME trial had to ask the question again against better surgery.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 1997","url":"https://doi.org/10.1056/NEJM199704033361402"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/9091798/"}],"tags":["colorectal-evidence"],"related":["radiation-roadmap","paper-kapiteijn-dutch-tme-preoperative-radiotherapy-nejm-2001"],"cancers":["colorectal","rectal-cancer"],"sections":["radiation","surgery"],"technologies":["radiotherapy","imrt-igrt"],"targets":[],"drugs":[],"companies":[],"institutions":["karolinska"],"pathways":[],"terms":["total-mesorectal-excision","neoadjuvant-adjuvant"],"trials":[],"people":[],"bottlenecks":["b-surgery-radiation-innovation","b-toxicity-qol"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":1997,"doi":"10.1056/NEJM199704033361402","pmid":"9091798","authors":"Swedish Rectal Cancer Trial, Cedermark B, Dahlberg M, et al.","paperType":"rct","findings":["Local recurrence at five years 11 percent (63 of 553) with preoperative radiotherapy against 27 percent (150 of 557) with surgery alone, p<0.001.","Overall five-year survival 58 percent against 48 percent, p=0.004.","Cancer-specific survival at nine years after curative resection 74 percent against 65 percent, p=0.002.","Irradiation did not increase postoperative mortality."],"whatItMeans":"The origin of short-course preoperative radiotherapy, still the standard schedule across northern Europe and the backbone of the RAPIDO regimen 24 years later.","caveats":["Surgery was not standardised as total mesorectal excision; the 27 percent local recurrence in the control arm is far above modern rates, which inflates the absolute benefit.","The survival benefit has not been reproduced in trials with modern surgery.","Long-term bowel and sexual dysfunction after pelvic radiotherapy were not the focus of the original report."],"changedPractice":true,"participants":1168},{"id":"paper-archer-1050-os-jco-2018","kind":"paper","name":"Improvement in overall survival in a randomized study that compared dacomitinib with gefitinib in patients with advanced non-small-cell lung cancer and EGFR-activating mutations","aka":[],"tldr":"The mature survival analysis of ARCHER 1050: patients on dacomitinib lived a median of 34.1 months against 26.8 months on gefitinib, the first survival gain for a second-generation EGFR inhibitor over a standard one.","summary":"Mature overall survival analysis of the intention-to-treat population of ARCHER 1050, the randomised, open-label phase 3 trial of dacomitinib (227 patients) versus gefitinib (225) in treatment-naive advanced non-small-cell lung cancer with an EGFR exon 19 deletion or exon 21 L858R mutation, stratified by race and EGFR mutation type. The final analysis had a data cut-off of 17 February 2017, when 220 deaths (48.7 percent) had occurred.\n\nDuring a median follow-up of 31.3 months there were 103 deaths (45.4 percent) on dacomitinib and 117 (52.0 percent) on gefitinib. The hazard ratio for overall survival was 0.760 (95% CI 0.582 to 0.993; two-sided P = .044). Median overall survival was 34.1 months with dacomitinib versus 26.8 months with gefitinib, and 30-month survival was 56.2 and 46.3 percent. Preliminary subgroup analyses were consistent with the primary analysis.","asOf":"2026-09-24","links":[{"label":"Journal of Clinical Oncology 2018","url":"https://doi.org/10.1200/JCO.2018.78.7994"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29864379/"},{"label":"ClinicalTrials.gov NCT01774721","url":"https://clinicaltrials.gov/study/NCT01774721"}],"tags":[],"related":[],"cancers":["nsclc","egfr-mutant-nsclc"],"sections":[],"technologies":[],"targets":["egfr"],"drugs":["dacomitinib","gefitinib"],"companies":["pfizer"],"institutions":[],"pathways":[],"terms":[],"trials":["nct01774721"],"people":["tony-mok","wu-yi-long"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2018,"doi":"10.1200/JCO.2018.78.7994","pmid":"29864379","authors":"Mok TS, Cheng Y, Zhou X, et al.","paperType":"rct","findings":["Median overall survival 34.1 vs 26.8 months; hazard ratio 0.760 (95% CI 0.582 to 0.993), two-sided P = .044.","Overall survival at 30 months 56.2% with dacomitinib and 46.3% with gefitinib.","220 deaths (48.7%) at the final analysis cut-off of 17 February 2017, after a median follow-up of 31.3 months."],"whatItMeans":"This is the separate paper behind the survival figure quoted for dacomitinib. It is a real but modest gain, and the US label notes that overall survival was not formally tested because the response rate comparison earlier in the testing order was not significant, so the P value is descriptive.","caveats":["Overall survival was not formally tested in the prespecified hierarchy (US label); the result is supportive rather than confirmatory.","The confidence interval's upper bound (0.993) is close to one.","Same open-label trial population as the primary paper, with brain metastases excluded."],"changedPractice":false,"participants":452},{"id":"paper-imvigor011-nejm-2025","kind":"paper","name":"IMvigor011: using a blood test for leftover cancer to decide who gets immunotherapy after bladder surgery","aka":[],"tldr":"Patients whose blood turned positive for tumour DNA after cystectomy lived longer with atezolizumab than placebo; patients who stayed ctDNA-negative did well without any treatment. It is the first ctDNA-guided adjuvant trial to improve survival.","summary":"IMvigor011 enrolled patients with muscle-invasive bladder cancer after radical cystectomy into ctDNA surveillance with a tumour-informed assay (Signatera). Those who became ctDNA-positive within a year were randomised 2:1 to atezolizumab or placebo; those who remained negative were followed without treatment.\n\nIn the ctDNA-positive randomised population, atezolizumab improved disease-free survival (HR 0.64) and overall survival (HR 0.59) versus placebo. Patients who never became ctDNA-positive had very low recurrence rates, supporting the safety of withholding adjuvant therapy from them. The design was built on the exploratory IMvigor010 ctDNA analysis (Powles, Nature 2021), which had shown benefit confined to ctDNA-positive patients.\n\nRegulatory approval in 2026 made this the first indication defined by a ctDNA result.","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov NCT04660344","url":"https://clinicaltrials.gov/study/NCT04660344"},{"label":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=IMvigor011%20atezolizumab%20ctDNA%20Powles"}],"tags":[],"related":["ctdna-mrd-to-adjuvant","idea-ctdna-switch-generalised","idea-bio2-mrd-coverage-with-evidence"],"cancers":["urothelial"],"sections":["diagnostics","immunotherapy"],"technologies":["mrd-testing","liquid-biopsy","checkpoint-inhibitor"],"targets":["pdl1"],"drugs":["atezolizumab","signatera"],"companies":[],"institutions":[],"pathways":[],"terms":["mrd","ctdna","neoadjuvant-adjuvant"],"trials":["imvigor011"],"people":[],"bottlenecks":["b-dormancy-mrd","b-trial-design","b-biomarker-validation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2025,"doi":"10.1056/NEJMoa2511885","pmid":"41124204","authors":"Powles T, Chang Y-H, Yamamoto Y, et al.","paperType":"rct","findings":["Disease-free survival in ctDNA-positive patients: HR 0.64 for atezolizumab vs placebo","Overall survival: HR 0.59, a rare survival gain in the adjuvant setting","Patients who remained ctDNA-negative on surveillance had excellent outcomes without treatment","Roughly two-thirds of surveilled patients avoided adjuvant immunotherapy altogether"],"whatItMeans":"After bladder removal, a blood test can now tell who needs immunotherapy and who can safely be spared it. This is the model for MRD-guided adjuvant therapy across cancers: treat the blood-positive, watch the blood-negative.","caveats":["Applies to a tumour-informed assay with defined sampling schedule; other assays and intervals are not interchangeable","Placebo rather than standard adjuvant nivolumab (CheckMate 274) as comparator, so it does not settle which drug or strategy is best","Some ctDNA-negative patients still relapsed; surveillance intervals and duration remain to be optimised","Cost and logistics of serial testing over 12 months are substantial"],"changedPractice":true},{"id":"paper-mateos-20-2-20-smouldering-bcj-2020","kind":"paper","name":"IMWG 20/2/20 risk stratification model for smouldering multiple myeloma","aka":[],"tldr":"A simple score using three numbers, marrow plasma cells over 20 percent, M-protein over 2 grams per decilitre and a free light-chain ratio over 20, sorts smouldering myeloma into risk groups and is used to decide who might be treated early.","summary":"Retrospective study of 1,996 patients with smouldering myeloma from international centres developing a risk model based on marrow plasma cell percentage, M-protein level and involved to uninvolved free light-chain ratio, with cytogenetics as an optional fourth variable.\n\nTwo-year progression risk ranged from about 6 percent with no risk factors to about 44 percent with all three, and the model was validated in an independent cohort.","asOf":"2026-09-17","links":[{"label":"Blood Cancer J 2020","url":"https://doi.org/10.1038/s41408-020-00366-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33067414/"}],"tags":[],"related":[],"cancers":["smouldering-myeloma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["blood-cancer-journal"],"dependsOn":[],"notes":[],"journal":"Blood cancer journal","year":2020,"doi":"10.1038/s41408-020-00366-3","pmid":"33067414","authors":"Mateos MV, Kumar S, Dimopoulos MA, et al.","paperType":"observational","findings":["Two-year progression risk 6 percent, 18 percent and 44 percent for low, intermediate and high risk.","Adding high-risk cytogenetics improved discrimination."],"whatItMeans":"The 20/2/20 model defines high-risk smouldering myeloma in current guidelines and trial eligibility, including in AQUILA-informed practice.","caveats":["Retrospective and based on values at diagnosis; evolving markers over time also matter."],"changedPractice":true,"participants":1996},{"id":"paper-imwg-plasma-cell-leukaemia-definition-bcj-2021","kind":"paper","name":"IMWG consensus definition of primary plasma cell leukaemia at 5 percent circulating plasma cells","aka":[],"tldr":"The International Myeloma Working Group lowered the threshold for diagnosing plasma cell leukaemia from 20 percent to 5 percent circulating plasma cells, because patients at 5 percent already have the same short survival.","summary":"Consensus statement from the International Myeloma Working Group reviewing evidence that 5 percent or more circulating plasma cells on a blood film carries the same short survival as the historical 20 percent threshold, and redefining primary plasma cell leukaemia accordingly, with recommendations for work-up.","asOf":"2026-09-17","links":[{"label":"Blood Cancer J 2021","url":"https://doi.org/10.1038/s41408-021-00587-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34857730/"}],"tags":[],"related":[],"cancers":["plasma-cell-leukaemia"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["blood-cancer-journal"],"dependsOn":[],"notes":[],"journal":"Blood cancer journal","year":2021,"doi":"10.1038/s41408-021-00587-0","pmid":"34857730","authors":"Fernández de Larrea C, Kyle R, Rosiñol L, et al.","paperType":"guideline","findings":[],"whatItMeans":"More patients now receive the diagnosis and the intensive, transplant-based approach that goes with it; trial eligibility uses the new definition.","caveats":["Based on retrospective series; treatment recommendations remain largely extrapolated from myeloma."],"changedPractice":true},{"id":"paper-imwg-criteria-rajkumar-lancet-oncol-2014","kind":"paper","name":"IMWG updated criteria for the diagnosis of multiple myeloma (2014)","aka":[],"tldr":"The 2014 International Myeloma Working Group criteria allow myeloma to be diagnosed and treated before organ damage occurs when biomarkers such as 60 percent marrow plasma cells or a very high light-chain ratio predict imminent progression.","summary":"Updated diagnostic criteria adding three myeloma-defining biomarkers (clonal marrow plasma cells 60 percent or more, involved to uninvolved free light chain ratio 100 or more, more than one focal lesion on MRI) to the classic CRAB features, and revising the definitions of smouldering myeloma and related plasma cell disorders.","asOf":"2026-09-17","links":[{"label":"Lancet Oncol 2014","url":"https://doi.org/10.1016/S1470-2045(14)70442-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25439696/"}],"tags":[],"related":[],"cancers":["smouldering-myeloma","plasma-cell-leukaemia"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2014,"doi":"10.1016/S1470-2045(14)70442-5","pmid":"25439696","authors":"Rajkumar SV, Dimopoulos MA, Palumbo A, et al.","paperType":"guideline","findings":[],"whatItMeans":"Whether a patient is labelled smouldering or active myeloma, and therefore whether treatment starts, depends on these criteria.","caveats":["Biomarker thresholds were based on retrospective cohorts and continue to be refined."],"changedPractice":true},{"id":"paper-visakorpi-androgen-receptor-amplification-nat-genet-1995","kind":"paper","name":"In vivo amplification of the androgen receptor gene and progression of human prostate cancer","aka":["Visakorpi 1995","AR gene amplification prostate cancer"],"tldr":"When hormone treatment stops working, the cancer often has not stopped caring about the hormone. In a third of tumours that came back on treatment, the cell had simply made extra copies of the androgen receptor gene so it could live on the tiny amount of hormone left.","summary":"Tapio Visakorpi and colleagues in Tampere used comparative genomic hybridisation on tumours taken before androgen deprivation and again when they recurred on it, in the same patients. Amplification of the Xq11-q13 region, which carries the androgen receptor gene, appeared in the recurrent tumours and in none of the pre-treatment samples from the same men.\n\nThe finding reframed what castration resistance is. The old name, hormone-refractory prostate cancer, implied that the tumour had stopped using the androgen pathway. This paper said the opposite: the tumour had adapted to keep using it in a low-androgen environment. That is why abiraterone, enzalutamide, apalutamide and darolutamide work at all, and why they were built.","asOf":"2026-09-25","links":[{"label":"Nat Genet 1995","url":"https://doi.org/10.1038/ng0495-401"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/7795646/"}],"tags":["prostate-evidence"],"related":["paper-chen-androgen-receptor-overexpression-antiandrogen-resistance-nat-med-2004","paper-huggins-hodges-castration-serum-phosphatases-prostate-1941","prostate-roadmap"],"cancers":["prostate","prostate-mcrpc"],"sections":["hormonal","targeted-therapy"],"technologies":["cytogenetics-fish"],"targets":["androgen-receptor"],"drugs":[],"companies":[],"institutions":[],"pathways":["ar-signaling","prostate-cancer-signalling"],"terms":["castration-resistance","adt","gene-amplification","resistance","intraductal-carcinoma-prostate"],"trials":[],"people":[],"bottlenecks":["b-resistance","b-tumor-heterogeneity"],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":1995,"doi":"10.1038/ng0495-401","pmid":"7795646","authors":"Visakorpi T, Hyytinen E, Koivisto P, et al.","paperType":"basic","findings":["High-level androgen receptor amplification in 7 of 23 (30 percent) tumours recurring during androgen deprivation therapy.","No amplification in any of the specimens taken from the same patients before therapy.","Amplification of the Xq11-q13 region, where the androgen receptor gene sits, is common in tumours recurring on androgen deprivation."],"whatItMeans":"The first evidence that resistance to hormone therapy in prostate cancer is an adaptation of the target rather than an escape from it, which is why the field kept building better androgen receptor drugs instead of abandoning the pathway.","caveats":["23 recurrent tumours from one centre; the 30 percent figure is not a population estimate.","Comparative genomic hybridisation detects amplification, not the other routes to the same end (receptor mutation, splice variants, intratumoural androgen synthesis) that were described later.","Amplification explains part of castration resistance; the AR-independent part, described in the lineage plasticity papers, is not addressed here."],"changedPractice":false,"participants":23},{"id":"paper-pfeiffer-embo-mol-med","kind":"paper","name":"In vivo generation of human CD19-CAR T cells results in B-cell depletion and signs of cytokine release syndrome","aka":[],"tldr":"Paper cited by one technology page and one idea page, indexed on Europe PMC as PubMed record 30224381 and published in EMBO molecular medicine; the citing pages link this DOI, which is how the record was matched.","summary":"Chimeric antigen receptor (CAR) T cells brought substantial benefit to patients with B-cell malignancies. Notwithstanding, CAR T-cell manufacturing requires complex procedures impeding the broad supply chain. Here, we provide evidence that human CD19-CAR T cells can be generated directly in vivo using the lentiviral vector CD8-LV specifically targeting human CD8 + cells. Administration into mice xenografted with Raji lymphoma cells and human peripheral blood mononuclear cells led to CAR expression solely in CD8 + T cells and efficacious elimination of CD19 + B cells. Further, upon injection of CD8-LV into mice transplanted with human CD34 + cells, induction of CAR T cells and CD19 + B-cell depletion was observed in 7 out of 10 treated animals. Notably, three mice showed elevated levels of human cytokines in plasma. Tissue-invading CAR T cells and complete elimination of the B-lymphocyte-rich zones in spleen were indicative of a cytokine release syndrome. Our data demonstrate the feasibility of in vivo reprogramming of human CD8 + CAR T cells active against CD19 + cells, yet with similar adverse effects currently notorious in the clinical practice.\n\nIndexed on Europe PMC as PubMed record 30224381 (DOI 10.15252/emmm.201809158). Matched by DOI alone: one technology page and one idea page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"EMBO Mol Med 2018","url":"https://doi.org/10.15252/emmm.201809158"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30224381/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30224381"}],"tags":["europepmc-ingest"],"related":["in-vivo-car-t","idea-in-vivo-car-solid"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"EMBO molecular medicine","year":2018,"doi":"10.15252/emmm.201809158","pmid":"30224381","authors":"Pfeiffer A, Thalheimer FB, Hartmann S, et al.","paperType":"basic","findings":[],"whatItMeans":"One technology page and one idea page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-markowitz-tgfbr2-inactivation-msi-colon-science-1995","kind":"paper","name":"Inactivation of the type II TGF-beta receptor in colon cancer cells with microsatellite instability","aka":[],"tldr":"When a cell loses its DNA spell-checker, short repeated stretches of DNA slip. This paper found that one of the genes destroyed that way is the brake that stops bowel cells growing, which is how a repair defect becomes a cancer.","summary":"Human colon cancer cell lines with high rates of microsatellite instability were found to harbour mutations in the type II TGF-beta receptor gene. Eight such examples, from three different mutations, were identified. The mutations clustered within small repeated sequences in the gene, were accompanied by the absence of cell surface receptors, and were usually associated with small amounts of transcript. Receptor mutation, by allowing cells to escape TGF-beta-mediated growth control, links DNA repair defects to a specific pathway of tumour progression.","asOf":"2026-09-24","links":[{"label":"Markowitz et al., Science 1995: TGF-beta receptor II inactivation in colon cancer cells with microsatellite instability","url":"https://doi.org/10.1126/science.7761852"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/7761852/"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":[],"targets":["tgfbr2","mmr"],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":["tgf-beta","mismatch-repair-msi"],"terms":["msi"],"trials":[],"people":["bert-vogelstein","kenneth-kinzler"],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":1995,"doi":"10.1126/science.7761852","pmid":"7761852","authors":"Markowitz S, Wang J, Myeroff L, et al.","paperType":"basic","findings":["TGFBR2 mutated in 8 microsatellite-unstable colon cancer lines, from three mutations clustered in short repeats.","Mutation abolished surface receptor and TGF-beta growth control."],"whatItMeans":"It showed how mismatch repair failure selects for cancer: coding microsatellites in tumour suppressors are the targets, which is why TGFBR2, ACVR2A, RNF43 and B2M frameshifts are the signature of MSI-high bowel cancer.","caveats":["Cell lines; the frequency in patients came later.","Most panels do not report coding-microsatellite frameshifts as such."],"changedPractice":false},{"id":"paper-inavo120-n-engl-j-med-2024","kind":"paper","name":"Inavolisib-Based Therapy in PIK3CA -Mutated Advanced Breast Cancer","aka":[],"tldr":"Published report from the INAVO120 trial registered as NCT04191499, in New England Journal of Medicine (2024), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Inavolisib is a highly potent and selective inhibitor of the alpha isoform of the p110 catalytic subunit of the phosphatidylinositol 3-kinase complex (encoded by PIK3CA) that also promotes the degradation of mutated p110α. Inavolisib plus palbociclib-fulvestrant has shown synergistic activity in preclinical models and promising antitumor activity in early-phase trials.\n\nMethods: In a phase 3, double-blind, randomized trial, we compared first-line inavolisib (at an oral dose of 9 mg once daily) plus palbociclib-fulvestrant (inavolisib group) with placebo plus palbociclib-fulvestrant (placebo group) in patients with PIK3CA -mutated, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer who had had relapse during or within 12 months after the completion of adjuvant endocrine therapy. The primary end point was progression-free survival as assessed by the investigator.\n\nResults: A total of 161 patients were assigned to the inavolisib group and 164 to the placebo group; the median follow-up was 21.3 months and 21.5 months, respectively. The median progression-free survival was 15.0 months (95% confidence interval [CI], 11.3 to 20.5) in the inavolisib group and 7.3 months (95% CI, 5.6 to 9.3) in the placebo group (hazard ratio for disease progression or death, 0.43; 95% CI, 0.32 to 0.59; P<0.001). An objective response occurred in 58.4% of the patients in the inavolisib group and in 25.0% of those in the placebo group. The incidence of grade 3 or 4 neutropenia was 80.2% in the inavolisib group and 78.4% in the placebo group; grade 3 or 4 hyperglycemia, 5.6% and 0%, respectively; grade 3 or 4 stomatitis or mucosal inflammation, 5.6% and 0%; and grade 3 or 4 diarrhea, 3.7% and 0%. No grade 3 or 4 rash was observed. Discontinuation of any trial agent because of adverse events occurred in 6.8% of the patients in the inavolisib group and in 0.6% of those in the placebo group.\n\nConclusions: In patients with PIK3CA -mutated, hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer, inavolisib plus palbociclib-fulvestrant led to significantly longer progression-free survival than placebo plus palbociclib-fulvestrant, with a greater incidence of toxic effects. The percentage of patients who discontinued any trial agent because of adverse events was low. (Funded by F. Hoffmann-La Roche; INAVO120 ClinicalTrials.gov number, NCT04191499.).\n\nIndexed on Europe PMC as PubMed record 39476340 (DOI 10.1056/nejmoa2404625). Its abstract cites the registry id NCT04191499, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2024","url":"https://doi.org/10.1056/nejmoa2404625"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39476340/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39476340"},{"label":"ClinicalTrials.gov NCT04191499","url":"https://clinicaltrials.gov/study/NCT04191499"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["inavo120"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2024,"doi":"10.1056/nejmoa2404625","pmid":"39476340","authors":"Turner NC, Im SA, Saura C, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04191499 with the most citations, so it is the natural first reading for anyone following the INAVO120 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-herman-mlh1-promoter-hypermethylation-colorectal-pnas-1998","kind":"paper","name":"Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma","aka":[],"tldr":"Most bowel cancers with a broken DNA spell-checker have not mutated the gene at all: they have switched it off chemically. Removing the chemical tag in the laboratory turned the gene, and the repair system, back on.","summary":"Hypermethylation of the 5' CpG island of hMLH1 was found in the majority of sporadic primary colorectal cancers with microsatellite instability, and was often though not invariably associated with loss of hMLH1 protein expression. Methylation also occurred, less commonly, in microsatellite-stable tumours and in unstable tumours with known mismatch repair gene mutations; no hypermethylation of hMSH2 was found. In cell lines with microsatellite instability, reversal of methylation with 5-aza-2'-deoxycytidine restored hMLH1 protein expression and mismatch repair capacity.","asOf":"2026-09-24","links":[{"label":"Herman et al., PNAS 1998: hMLH1 promoter hypermethylation in sporadic colorectal carcinoma","url":"https://doi.org/10.1073/pnas.95.12.6870"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/9618505/"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["methylation-profiling"],"targets":["mlh1","mmr"],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":["mismatch-repair-msi","epigenetic-reprogramming"],"terms":["msi","lynch-syndrome"],"trials":[],"people":["bert-vogelstein","kenneth-kinzler","stephen-baylin"],"bottlenecks":[],"keyPapers":[],"journals":["pnas"],"dependsOn":[],"notes":[],"journal":"Proceedings of the National Academy of Sciences","year":1998,"doi":"10.1073/pnas.95.12.6870","pmid":"9618505","authors":"Herman JG, Umar A, Polyak K, et al.","paperType":"basic","findings":["hMLH1 promoter hypermethylation in the majority of sporadic microsatellite-unstable colorectal cancers.","Demethylation restored hMLH1 protein and mismatch repair capacity in deficient cell lines."],"whatItMeans":"It established the epigenetic route to mismatch repair deficiency, which is why an MLH1-deficient tumour is tested for MLH1 methylation or BRAF V600E before a family is told it may have Lynch syndrome.","caveats":["Methylation assays of the era were less quantitative than today's.","The threshold that counts as promoter methylation varies between laboratories."],"changedPractice":false},{"id":"paper-pawlik-incidental-gallbladder-cancer-residual-disease-jgs-2007","kind":"paper","name":"Incidence of finding residual disease for incidental gallbladder carcinoma: implications for re-resection","aka":[],"tldr":"When surgeons went back in after a gallbladder cancer had been found by chance, nearly half of patients had cancer left behind, and the deeper the original tumour the more likely it was.","summary":"Six hepatobiliary centres pooled 115 patients re-resected between 1984 and 2006 for gallbladder carcinoma discovered incidentally at cholecystectomy. T stage was T1 in 7.8 percent, T2 in 67.0 percent and T3 in 25.2 percent; the median interval to re-resection was 52 days. Residual or additional disease was found in 46.4 percent. Residual disease in the liver was found in 0, 10.4 and 36.4 percent of T1, T2 and T3 tumours and nodal metastasis in 12.5, 31.3 and 45.5 percent. A positive cystic duct margin predicted residual disease in the common bile duct (42.1 versus 4.3 percent). Common duct resection did not raise the lymph node count (median 3 in both groups).","asOf":"2026-09-24","links":[{"label":"J Gastrointest Surg 2007","url":"https://doi.org/10.1007/s11605-007-0309-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/17846848/"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["incidental-gallbladder-cancer","radical-cholecystectomy","lymphadenectomy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of Gastrointestinal Surgery","year":2007,"doi":"10.1007/s11605-007-0309-6","pmid":"17846848","authors":"Pawlik TM, Gleisner AL, Vigano L, et al.","paperType":"observational","findings":["Residual or additional disease at re-resection in 46.4 percent of 115 patients.","Liver residual disease by T stage: T1 0 percent, T2 10.4 percent, T3 36.4 percent; nodal metastasis 12.5, 31.3 and 45.5 percent.","Positive cystic duct margin: residual disease in the common bile duct 42.1 vs 4.3 percent."],"whatItMeans":"This is the observational backbone of the rule that T1b or deeper incidental cancers should be re-resected, and of resecting the bile duct only when the cystic duct margin is positive.","caveats":["Retrospective series from referral centres; patients selected for re-resection.","Only nine T1 patients."],"changedPractice":true,"participants":115},{"id":"paper-gotoda-endoscopic-resection-criteria-gastric-cancer-2000","kind":"paper","name":"Incidence of lymph node metastasis from early gastric cancer: estimation from 5,265 patients at two large centres","aka":[],"tldr":"By analysing over 5,000 surgical cases, this study identified early gastric cancers with essentially zero risk of lymph node spread, defining the expanded criteria that allow endoscopic removal instead of gastrectomy.","summary":"Retrospective analysis of 5,265 patients who underwent gastrectomy with lymph node dissection for early gastric cancer at two Japanese centres, examining the incidence of nodal metastasis by depth, size, histology, ulceration and lymphovascular invasion.\n\nNo nodal metastases were found in differentiated intramucosal cancers without ulceration regardless of size, in ulcerated differentiated intramucosal cancers up to 3 cm, or in differentiated cancers with minute submucosal invasion up to 3 cm without lymphovascular invasion.","asOf":"2026-09-17","links":[{"label":"Gastric Cancer 2000","url":"https://doi.org/10.1007/PL00011720"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/11984739/"}],"tags":[],"related":[],"cancers":["early-gastric-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["gastric-cancer"],"dependsOn":[],"notes":[],"journal":"Gastric cancer","year":2000,"doi":"10.1007/PL00011720","pmid":"11984739","authors":"Gotoda T, Yanagisawa A, Sasako M, et al.","paperType":"observational","findings":["Zero nodal metastasis in differentiated intramucosal cancers without ulceration of any size.","Zero nodal metastasis in differentiated cancers with submucosal invasion under 500 micrometres up to 3 cm without lymphovascular invasion."],"whatItMeans":"The expanded criteria for endoscopic submucosal dissection in Japanese and international guidelines derive from this analysis.","caveats":["Retrospective surgical series; undifferentiated-type criteria were validated later in JCOG1009/1010."],"changedPractice":true,"participants":5265},{"id":"paper-pyo-incidental-gallbladder-cancer-meta-analysis-jcm-2020","kind":"paper","name":"Incidental Carcinoma after Cholecystectomy for Benign Disease of the Gallbladder: A Meta-Analysis","aka":[],"tldr":"Pooling 51 studies and more than 400,000 gallbladder operations, about six in every thousand gallbladders removed for benign disease contained an unsuspected cancer, and people whose cancer was found this way lived longer than those diagnosed with symptoms.","summary":"Meta-analysis of 51 studies and 436,636 cholecystectomies. The pooled incidence of incidental gallbladder carcinoma was 0.6 percent (95 percent CI 0.5 to 0.8) and did not differ between older and recent studies. Estimated rates by stage were 13.0 percent pTis, 34.1 percent pT1, 39.7 percent pT2, 22.7 percent pT3 and 12.5 percent pT4 (as reported). Incidental cancers had better overall survival than non-incidental cancers (hazard ratio 0.574, 95 percent CI 0.445 to 0.739) but no significant difference in disease-free survival (hazard ratio 0.931, 0.618 to 1.402). The authors call for adequate histological examination of every cholecystectomy specimen.","asOf":"2026-09-24","links":[{"label":"J Clin Med 2020","url":"https://doi.org/10.3390/jcm9051484"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32423156/"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["incidental-gallbladder-cancer"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Medicine","year":2020,"doi":"10.3390/jcm9051484","pmid":"32423156","authors":"Pyo JS, Son BK, Lee HY, et al.","paperType":"meta-analysis","findings":["Incidence of incidental gallbladder carcinoma 0.6 percent (95 percent CI 0.5 to 0.8) across 436,636 cholecystectomies.","Overall survival better for incidental than non-incidental cancer: hazard ratio 0.574 (95 percent CI 0.445 to 0.739).","Disease-free survival not significantly different: hazard ratio 0.931 (0.618 to 1.402)."],"whatItMeans":"Six per thousand is the number behind the debate on routine versus selective histology of gallbladder specimens: applied to a national cholecystectomy volume it predicts a few hundred unsuspected cancers a year in a country the size of England.","caveats":["Study-level meta-analysis with heterogeneous definitions.","The stage percentages as reported sum to more than 100 percent and are quoted as printed."],"changedPractice":false,"participants":436636},{"id":"paper-vuik-early-onset-colorectal-europe-gut-2019","kind":"paper","name":"Increasing incidence of colorectal cancer in young adults in Europe over the last 25 years","aka":[],"tldr":"The same rise is happening in Europe. Across 20 countries and 143.7 million people, bowel cancer in 20 to 29-year-olds rose by 7.9 percent a year from 2004 to 2016.","summary":"Vuik, Nieuwenburg, Bardou and colleagues retrieved age-related colorectal cancer incidence and mortality data for 1990 to 2016 from national and regional cancer registries in 20 European countries, covering 143.7 million people aged 20 to 49, of whom 187,918 (0.13 percent) were diagnosed with colorectal cancer. Trends were analysed by joinpoint regression and expressed as annual percent change.\n\nThe rise started earliest in the youngest group and appeared 10 to 20 years later in the older ones, which is the signature of a birth-cohort effect rather than of changed diagnostic practice. Incidence rose in most but not all European countries.","asOf":"2026-09-24","links":[{"label":"Gut 2019","url":"https://doi.org/10.1136/gutjnl-2018-317592"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31097539/"},{"label":"Europe PMC full text (PMC6839794)","url":"https://europepmc.org/article/MED/31097539"}],"tags":["colorectal-evidence"],"related":["paper-siegel-colorectal-incidence-birth-cohort-jnci-2017"],"cancers":["colorectal","early-onset-colorectal"],"sections":["early-detection","prevention"],"technologies":["colorectal-screening"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-prevention-adoption"],"keyPapers":[],"journals":["gut"],"dependsOn":[],"notes":[],"journal":"Gut","year":2019,"doi":"10.1136/gutjnl-2018-317592","pmid":"31097539","authors":"Vuik FE, Nieuwenburg SA, Bardou M, et al.","paperType":"observational","findings":["Incidence rose 7.9 percent per year in people aged 20 to 29 from 2004 to 2016.","4.9 percent per year in those aged 30 to 39 from 2005 to 2016, and 1.6 percent per year in those aged 40 to 49 from 2004 to 2016.","The onset of the rise was 10 to 20 years later in each older age band, consistent with an age-cohort phenomenon.","Mortality did not change significantly in the youngest adults but fell 1.1 percent per year (ages 30 to 39) and 2.4 percent per year (ages 40 to 49)."],"whatItMeans":"The European counterpart to Siegel 2017, and the evidence a UK screening age extension has to be argued against: the fastest relative rise is in people two decades below any screening programme's start age.","caveats":["Registry data differ in completeness and coding between the 20 countries.","Very large annual percentage changes are computed on small absolute numbers in the youngest band.","Like every registry study it describes the trend without identifying its cause."],"participants":187918},{"id":"paper-sinicrope-early-onset-crc-nejm-2022","kind":"paper","name":"Increasing incidence of early-onset colorectal cancer (review)","aka":[],"tldr":"This review explains the rise of colorectal cancer in adults under 50, what is known about its causes and distinct features, and how screening ages and clinical management have responded.","summary":"Review of the epidemiology of colorectal cancer diagnosed before age 50, including birth-cohort effects, proposed risk factors (obesity, diet, microbiome, antibiotics), clinical and molecular features (left-sided and rectal predominance, later stage at diagnosis, similar mutational profiles in sporadic cases), germline findings, and implications for screening and treatment.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2022","url":"https://doi.org/10.1056/NEJMra2200869"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35443109/"}],"tags":[],"related":[],"cancers":["early-onset-colorectal"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/NEJMra2200869","pmid":"35443109","authors":"Sinicrope FA.","paperType":"review","findings":[],"whatItMeans":"The early-onset colorectal cancer page's emphasis on investigating rectal bleeding at any age, universal germline testing and avoiding treatment escalation on age alone follows this framing.","caveats":["Causes remain hypotheses; no single exposure explains the trend."],"changedPractice":false},{"id":"paper-early-breast-cancer-trialists-collaborative-group-ebctcg-lancet-2019","kind":"paper","name":"Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 30739743 and published in The Lancet; the citing page links this DOI, which is how the record was matched.","summary":"Background: Increasing the dose intensity of cytotoxic therapy by shortening the intervals between cycles, or by giving individual drugs sequentially at full dose rather than in lower-dose concurrent treatment schedules, might enhance efficacy.\n\nMethods: To clarify the relative benefits and risks of dose-intense and standard-schedule chemotherapy in early breast cancer, we did an individual patient-level meta-analysis of trials comparing 2-weekly versus standard 3-weekly schedules, and of trials comparing sequential versus concurrent administration of anthracycline and taxane chemotherapy. The primary outcomes were recurrence and breast cancer mortality. Standard intention-to-treat log-rank analyses, stratified by age, nodal status, and trial, yielded dose-intense versus standard-schedule first-event rate ratios (RRs).\n\nFindings: Individual patient data were provided for 26 of 33 relevant trials identified, comprising 37 298 (93%) of 40 070 women randomised. Most women were aged younger than 70 years and had node-positive disease. Total cytotoxic drug usage was broadly comparable in the two treatment arms; colony-stimulating factor was generally used in the more dose-intense arm. Combining data from all 26 trials, fewer breast cancer recurrences were seen with dose-intense than with standard-schedule chemotherapy (10-year recurrence risk 28·0% vs 31·4%; RR 0·86, 95% CI 0·82-0·89; p<0·0001). 10-year breast cancer mortality was similarly reduced (18·9% vs 21·3%; RR 0·87, 95% CI 0·83-0·92; p<0·0001), as was all-cause mortality (22·1% vs 24·8%; RR 0·87, 95% CI 0·83-0·91; p<0·0001). Death without recurrence was, if anything, lower with dose-intense than with standard-schedule chemotherapy (10-year risk 4·1% vs 4·6%; RR 0·88, 95% CI 0·78-0·99; p=0·034). Recurrence reductions were similar in the seven trials (n=10 004) that compared 2-weekly chemotherapy with the same chemotherapy given 3-weekly (10-year risk 24·0% vs 28·3%; RR 0·83, 95% CI 0·76-0·91; p<0·0001), in the six trials (n=11 028) of sequential versus concurrent anthracycline plus taxane chemotherapy (28·1% vs 31·3%; RR 0·87, 95% CI 0·80-0·94; p=0·0006), and in the six trials (n=6532) testing both shorter intervals and sequential administration (30·4% vs 35·0%; RR 0·82, 95% CI 0·74-0·90; p<0·0001). The proportional reductions in recurrence with dose-intense chemotherapy were similar and highly significant (p<0·0001) in oestrogen receptor (ER)-positive and ER-negative disease and did not differ significantly by other patient or tumour characteristics.\n\nInterpretation: Increasing the dose intensity of adjuvant chemotherapy by shortening the interval between treatment cycles, or by giving individual drugs sequentially rather than giving the same drugs concurrently, moderately reduces the 10-year risk of recurrence and death from breast cancer without increasing mortality from other causes.\n\nFunding: Cancer Research UK, Medical Research Council.\n\nIndexed on Europe PMC as PubMed record 30739743 (DOI 10.1016/s0140-6736(18)33137-4). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet 2019","url":"https://doi.org/10.1016/s0140-6736(18)33137-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30739743/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30739743"}],"tags":["europepmc-ingest"],"related":["norton-simon-hypothesis"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2019,"doi":"10.1016/s0140-6736(18)33137-4","pmid":"30739743","authors":"Early Breast Cancer Trialists' Collaborative Group (EBCTCG)","paperType":"meta-analysis","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-indigo-nejm-2023","kind":"paper","name":"INDIGO: vorasidenib, the first targeted drug for IDH-mutant low-grade glioma","aka":[],"tldr":"An oral drug that blocks the mutant IDH enzyme more than doubled the time before slow-growing IDH-mutant brain tumours progressed, letting patients postpone radiotherapy and chemotherapy for years.","summary":"Double-blind, placebo-controlled phase 3 trial of 331 patients with residual or recurrent grade 2 IDH1- or IDH2-mutant oligodendroglioma or astrocytoma who had undergone surgery alone and were candidates for watch-and-wait, randomised to vorasidenib (a brain-penetrant dual IDH1/2 inhibitor) or placebo. Primary endpoint was PFS by blinded review.\n\nMedian PFS was 27.7 vs 11.1 months (HR 0.39) and the time to next intervention (radiotherapy or chemotherapy) was markedly delayed (HR 0.26). It was the first targeted therapy approved for glioma (FDA 2024) and the first drug to change the natural history of low-grade glioma, a disease of young adults where treatment toxicity accumulates over decades.","asOf":"2026-09-08","links":[{"label":"NEJM 2023","url":"https://doi.org/10.1056/NEJMoa2304194"},{"label":"ClinicalTrials.gov NCT04164901","url":"https://clinicaltrials.gov/study/NCT04164901"}],"tags":[],"related":[],"cancers":["glioblastoma"],"sections":[],"technologies":["kinase-inhibitors","mri"],"targets":["idh"],"drugs":["vorasidenib"],"companies":["servier"],"institutions":["mskcc"],"pathways":[],"terms":["pfs","oncogene-addiction"],"trials":[],"people":[],"bottlenecks":["b-brain-delivery","b-toxicity-qol","b-trial-design"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/NEJMoa2304194","authors":"Mellinghoff IK, van den Bent MJ, Blumenthal DT, et al.","paperType":"rct","findings":["Median PFS 27.7 vs 11.1 months; HR 0.39 (95% CI 0.27-0.56).","Time to next intervention: HR 0.26 (95% CI 0.15-0.43); at 24 months, 83.4% vs 27.0% had not needed further treatment.","Tumour growth rate was reversed in many patients, with volumetric shrinkage on vorasidenib versus continued growth on placebo.","Grade 3 or higher adverse events 22.8% vs 13.5%, mainly raised liver enzymes (ALT increase in about 10%).","Crossover from placebo to vorasidenib was allowed at progression; overall survival is not yet evaluable."],"whatItMeans":"Young adults with a grade 2 IDH-mutant glioma who have had surgery can now take a daily tablet that slows or reverses tumour growth and defers radiotherapy and chemotherapy, both of which carry long-term cognitive costs, by years. It confirms that the IDH mutation is a driver that can be targeted, not just a marker. Whether it improves survival or cognition over the long term, and whether it helps in higher-grade or previously treated tumours, is unknown.","caveats":["PFS and time to next intervention are surrogates; overall survival data will take many years given the indolent disease.","Only patients who had not received radiotherapy or chemotherapy were eligible; the drug's role after those treatments is undefined.","Liver toxicity requires regular monitoring.","Indefinite treatment of young patients is costly, and stopping rules are not established."],"changedPractice":true,"participants":331},{"id":"paper-pietrantonio-msi-gastric-meta-analysis-jco-2019","kind":"paper","name":"Individual patient data meta-analysis of microsatellite instability as a biomarker in gastric cancer (MAGIC, CLASSIC, ARTIST, ITACA-S)","aka":[],"tldr":"Pooling four trials showed that microsatellite-unstable gastric cancers have a much better prognosis after surgery and gain nothing from perioperative or adjuvant chemotherapy, which may even harm them.","summary":"Individual patient data meta-analysis of 1,556 patients from four randomised trials of resectable gastric cancer (MAGIC, CLASSIC, ARTIST, ITACA-S), of whom 7.8 percent had microsatellite instability-high tumours.\n\nFive-year disease-free survival was 71.8 versus 52.3 percent and overall survival 77.5 versus 59.3 percent for microsatellite-unstable versus stable tumours; chemotherapy improved survival in stable tumours (hazard ratio 0.65) but not in unstable ones (hazard ratio 1.03), with a suggestion of harm.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2019","url":"https://doi.org/10.1200/JCO.19.01124"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31513484/"}],"tags":[],"related":[],"cancers":["gastric-msi-high"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2019,"doi":"10.1200/JCO.19.01124","pmid":"31513484","authors":"Pietrantonio F, Miceli R, Raimondi A, et al.","paperType":"meta-analysis","findings":["Five-year overall survival 77.5 percent (unstable) vs 59.3 percent (stable) with surgery alone.","Chemotherapy hazard ratio 1.03 in microsatellite-unstable tumours vs 0.65 in stable."],"whatItMeans":"Microsatellite instability testing is recommended before perioperative chemotherapy for gastric cancer, and immunotherapy-based trials are the preferred approach for unstable tumours.","caveats":["Small number of microsatellite-unstable patients (121); confidence intervals were wide."],"changedPractice":true,"participants":1556},{"id":"paper-schuetz-lancet","kind":"paper","name":"Individualised nutritional support in medical inpatients at nutritional risk: a randomised clinical trial","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 31030981 and published in The Lancet; the citing page links this DOI, which is how the record was matched.","summary":"Background: Guidelines recommend the use of nutritional support during hospital stays for medical patients (patients not critically ill and not undergoing surgical procedures) at risk of malnutrition. However, the supporting evidence for this recommendation is insufficient, and there is growing concern about the possible negative effects of nutritional therapy during acute illness on recovery and clinical outcomes. Our aim was thus to test the hypothesis that protocol-guided individualised nutritional support to reach protein and caloric goals reduces the risk of adverse clinical outcomes in medical inpatients at nutritional risk.\n\nMethods: The Effect of early nutritional support on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial (EFFORT) is a pragmatic, investigator-initiated, open-label, multicentre study. We recruited medical patients at nutritional risk (nutritional risk screening 2002 [NRS 2002] score ≥3 points) and with an expected length of hospital stay of more than 4 days from eight Swiss hospitals. These participants were randomly assigned (1:1) to receive either protocol-guided individualised nutritional support to reach protein and caloric goals (intervention group) or standard hospital food (control group). Randomisation was done with variable block sizes and stratification according to study site and severity of malnutrition using an interactive web-response system. In the intervention group, individualised nutritional support goals were defined by specialist dietitians and nutritional support was initiated no later than 48 h after admission. Patients in the control group received no dietary consultation. The composite primary endpoint was any adverse clinical outcome defined as all-cause mortality, admission to intensive care, non-elective hospital readmission, major complications, and decline in functional status at 30 days, and it was measured in all randomised patients who completed the trial. This trial is registered with ClinicalTrials.gov, number NCT02517476.\n\nFindings: 5015 patients were screened, and 2088 were recruited and monitored between April 1, 2014, and Feb 28, 2018. 1050 patients were assigned to the intervention group and 1038 to the control group. 60 patients withdrew consent during the course of the trial (35 in the intervention group and 25 in the control group). During the hospital stay, caloric goals were reached in 800 (79%) and protein goals in 770 (76%) of 1015 patients in the intervention group. By 30 days, 232 (23%) patients in the intervention group experienced an adverse clinical outcome, compared with 272 (27%) of 1013 patients in the control group (adjusted odds ratio [OR] 0·79 [95% CI 0·64-0·97], p=0·023). By day 30, 73 [7%] patients had died in the intervention group compared with 100 [10%] patients in the control group (adjusted OR 0·65 [0·47-0·91], p=0·011). There was no difference in the proportion of patients who experienced side-effects from nutritional support between the intervention and the control group (162 [16%] vs 145 [14%], adjusted OR 1·16 [0·90-1·51], p=0·26).\n\nInterpretation: In medical inpatients at nutritional risk, the use of individualised nutritional support during the hospital stay improved important clinical outcomes, including survival, compared with standard hospital food. These findings strongly support the concept of systematically screening medical inpatients on hospital admission regarding nutritional risk, independent of their medical condition, followed by a nutritional assessment and introduction of individualised nutritional support in patients at risk.\n\nFunding: The Swiss National Science Foundation and the Research Council of the Kantonsspital Aarau, Switzerland.\n\nIndexed on Europe PMC as PubMed record 31030981 (DOI 10.1016/s0140-6736(18)32776-4). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet 2019","url":"https://doi.org/10.1016/s0140-6736(18)32776-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31030981/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31030981"}],"tags":["europepmc-ingest"],"related":["nutrition-screening-mnt"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2019,"doi":"10.1016/s0140-6736(18)32776-4","pmid":"31030981","authors":"Schuetz P, Fehr R, Baechli V, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-amit-induction-chemotherapy-response-snuc-jco-2019","kind":"paper","name":"Induction chemotherapy response as a guide to treatment optimisation in sinonasal undifferentiated carcinoma","aka":[],"tldr":"In this aggressive nasal cancer, how the tumour responds to a first course of chemotherapy tells doctors which treatment to give next: chemoradiotherapy for responders, surgery for those who do not respond.","summary":"Retrospective study of 95 patients with sinonasal undifferentiated carcinoma treated at MD Anderson between 1988 and 2016, most with induction chemotherapy (platinum and etoposide or similar) followed by definitive treatment.\n\nAmong patients who responded to induction, definitive chemoradiotherapy gave better five-year disease-specific survival than surgery followed by radiotherapy (about 81 versus 54 percent); among non-responders, surgery followed by radiotherapy or chemoradiotherapy was better than chemoradiotherapy alone. Induction response now guides treatment selection at many centres.","asOf":"2026-09-18","links":[{"label":"J Clin Oncol 2019","url":"https://doi.org/10.1200/JCO.18.00353"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30615549/"}],"tags":[],"related":[],"cancers":["sinonasal-undifferentiated-carcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":["cisplatin","etoposide","platinum-etoposide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2019,"doi":"10.1200/JCO.18.00353","pmid":"30615549","authors":"Amit M, Abdelmeguid AS, Watcherporn T, et al.","paperType":"observational","findings":["Five-year disease-specific survival about 81 percent with chemoradiotherapy versus 54 percent with surgery in induction responders.","Non-responders did better with surgery followed by radiotherapy or chemoradiotherapy."],"whatItMeans":"Sinonasal undifferentiated carcinoma is treated with induction platinum-etoposide, and the response decides whether the patient is spared radical surgery.","caveats":["Retrospective single-centre series over nearly thirty years.","Response assessment was not standardised, and molecular subtypes (IDH2, SMARCB1) were not distinguished."],"changedPractice":true,"participants":95},{"id":"paper-greten-immunity","kind":"paper","name":"Inflammation and Cancer: Triggers, Mechanisms, and Consequences","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 31315034 and published in Immunity; the citing page links this DOI, which is how the record was matched.","summary":"Inflammation predisposes to the development of cancer and promotes all stages of tumorigenesis. Cancer cells, as well as surrounding stromal and inflammatory cells, engage in well-orchestrated reciprocal interactions to form an inflammatory tumor microenvironment (TME). Cells within the TME are highly plastic, continuously changing their phenotypic and functional characteristics. Here, we review the origins of inflammation in tumors, and the mechanisms whereby inflammation drives tumor initiation, growth, progression, and metastasis. We discuss how tumor-promoting inflammation closely resembles inflammatory processes typically found during development, immunity, maintenance of tissue homeostasis, or tissue repair and illuminate the distinctions between tissue-protective and pro-tumorigenic inflammation, including spatiotemporal considerations. Defining the cornerstone rules of engagement governing molecular and cellular mechanisms of tumor-promoting inflammation will be essential for further development of anti-cancer therapies.\n\nIndexed on Europe PMC as PubMed record 31315034 (DOI 10.1016/j.immuni.2019.06.025). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Immunity 2019","url":"https://doi.org/10.1016/j.immuni.2019.06.025"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31315034/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31315034"}],"tags":["europepmc-ingest"],"related":["inflammation-nfkb"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Immunity","year":2019,"doi":"10.1016/j.immuni.2019.06.025","pmid":"31315034","authors":"Greten FR, Grivennikov SI","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-whel-jama-2007","kind":"paper","name":"Influence of a diet very high in vegetables, fruit, and fiber and low in fat on prognosis following treatment for breast cancer: the Women's Healthy Eating and Living (WHEL) randomized trial","aka":[],"tldr":"Published report from the WHEL trial registered as NCT00003787, in JAMA (2007), chosen as the most cited paper whose own text cites the registry id.","summary":"Context: Evidence is lacking that a dietary pattern high in vegetables, fruit, and fiber and low in total fat can influence breast cancer recurrence or survival.\n\nObjective: To assess whether a major increase in vegetable, fruit, and fiber intake and a decrease in dietary fat intake reduces the risk of recurrent and new primary breast cancer and all-cause mortality among women with previously treated early stage breast cancer.\n\nDesign, setting, and participants: Multi-institutional randomized controlled trial of dietary change in 3088 women previously treated for early stage breast cancer who were 18 to 70 years old at diagnosis. Women were enrolled between 1995 and 2000 and followed up through June 1, 2006.\n\nIntervention: The intervention group (n = 1537) was randomly assigned to receive a telephone counseling program supplemented with cooking classes and newsletters that promoted daily targets of 5 vegetable servings plus 16 oz of vegetable juice; 3 fruit servings; 30 g of fiber; and 15% to 20% of energy intake from fat. The comparison group (n = 1551) was provided with print materials describing the \"5-A-Day\" dietary guidelines.\n\nMain outcome measures: Invasive breast cancer event (recurrence or new primary) or death from any cause.\n\nResults: From comparable dietary patterns at baseline, a conservative imputation analysis showed that the intervention group achieved and maintained the following statistically significant differences vs the comparison group through 4 years: servings of vegetables, +65%; fruit, +25%; fiber, +30%, and energy intake from fat, -13%. Plasma carotenoid concentrations validated changes in fruit and vegetable intake. Throughout the study, women in both groups received similar clinical care. Over the mean 7.3-year follow-up, 256 women in the intervention group (16.7%) vs 262 in the comparison group (16.9%) experienced an invasive breast cancer event (adjusted hazard ratio, 0.96; 95% confidence interval, 0.80-1.14; P =.63), and 155 intervention group women (10.1%) vs 160 comparison group women (10.3%) died (adjusted hazard ratio, 0.91; 95% confidence interval, 0.72-1.15; P =.43). No significant interactions were observed between diet group and baseline demographics, characteristics of the original tumor, baseline dietary pattern, or breast cancer treatment.\n\nConclusion: Among survivors of early stage breast cancer, adoption of a diet that was very high in vegetables, fruit, and fiber and low in fat did not reduce additional breast cancer events or mortality during a 7.3-year follow-up period.\n\nTrial registration: clinicaltrials.gov Identifier: NCT00003787.\n\nIndexed on Europe PMC as PubMed record 17635889 (DOI 10.1001/jama.298.3.289). Its abstract cites the registry id NCT00003787, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"JAMA 2007","url":"https://doi.org/10.1001/jama.298.3.289"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/17635889/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/17635889"},{"label":"ClinicalTrials.gov NCT00003787","url":"https://clinicaltrials.gov/study/NCT00003787"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["whel"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2007,"doi":"10.1001/jama.298.3.289","pmid":"17635889","authors":"Pierce JP, Natarajan L, Caan BJ, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT00003787 with the most citations, so it is the natural first reading for anyone following the WHEL trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-zheng-nigerian-inherited-breast-cancer-jco-2018","kind":"paper","name":"Inherited breast cancer in Nigerian women","aka":[],"tldr":"One in eight of 1,136 Nigerian women with breast cancer carried an inherited mutation in BRCA1, BRCA2, PALB2 or TP53; nearly half of the tumours with receptor data were triple-negative, and BRCA1 carriers were the youngest and most often triple-negative.","summary":"1,136 women with invasive breast cancer in Ibadan (mean age 47.5) and 997 controls were sequenced with the BROCA panel regardless of age, family history or prior testing. 86.1% of 577 staged patients presented at stage III or IV and 45.9% of 290 with receptor data had TNBC. 14.7% carried a loss-of-function mutation in a breast cancer gene: BRCA1 7.0%, BRCA2 4.1%, PALB2 1.0%, TP53 0.4% and 2.1% in ten other genes. Odds ratios were 23.4 for BRCA1 and 10.3 for BRCA2, with PALB2 (11 cases, no controls) and TP53 (5 cases, no controls) also significant. BRCA1 carriers were younger and more likely to have TNBC.","asOf":"2026-09-24","links":[{"label":"Zheng et al., J Clin Oncol 2018: inherited breast cancer in 1,136 Nigerian women","url":"https://doi.org/10.1200/JCO.2018.78.3977"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30130155/"}],"tags":[],"related":[],"cancers":["tnbc","breast-cancer"],"sections":[],"technologies":["germline-testing"],"targets":["brca","palb2","tp53"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["gbrca-mutation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2018,"doi":"10.1200/JCO.2018.78.3977","pmid":"30130155","authors":"Zheng Y, Walsh T, Gulsuner S, et al.","paperType":"observational","findings":["Loss-of-function variant in 14.7%: BRCA1 7.0%, BRCA2 4.1%, PALB2 1.0%, TP53 0.4%.","45.9% of tumours with receptor data were triple-negative; 86.1% presented at stage III or IV.","BRCA1 OR 23.4, BRCA2 OR 10.3; BRCA1 carriers younger and more often triple-negative."],"whatItMeans":"West Africa carries the highest germline burden reported for an unselected breast cancer population, and the genes are the same ones that predispose to TNBC elsewhere, so limited genetic services there should start with these families.","caveats":["Receptor status was available for only 290 patients.","Panel sequencing of loss-of-function variants; missense pathogenic variants may be undercounted."],"changedPractice":false,"participants":1136},{"id":"paper-pritchard-inherited-dna-repair-metastatic-prostate-nejm-2016","kind":"paper","name":"Inherited DNA-repair gene mutations in men with metastatic prostate cancer","aka":["Pritchard 2016","germline DNA repair metastatic prostate 11.8 percent"],"tldr":"Nearly one man in eight with prostate cancer that has spread carries an inherited fault in a DNA repair gene, most often BRCA2. Family history and age at diagnosis did not predict who: the only way to find them is to test everybody.","summary":"Colin Pritchard, Peter Nelson, Joaquin Mateo and colleagues recruited 692 men with documented metastatic prostate cancer, unselected for family history or age at diagnosis, and used multiplex sequencing to look for germline mutations in 20 DNA repair genes associated with autosomal dominant cancer predisposition syndromes.\n\nThe result is one of the cleanest arguments for universal testing in oncology. The mutation frequency was 11.8 percent in metastatic disease against 4.6 percent in 499 men with localised disease and 2.7 percent in 53,105 people in the Exome Aggregation Consortium without a known cancer diagnosis, and it did not differ according to whether there was a family history of prostate cancer or according to age at diagnosis. A selective testing policy based on family history would therefore miss most carriers.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2016","url":"https://doi.org/10.1056/nejmoa1603144"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27433846/"},{"label":"Pritchard et al., N Engl J Med 2016: inherited DNA-repair gene mutations in 692 men with metastatic prostate cancer unselected for family history","url":"https://doi.org/10.1056/NEJMoa1603144"}],"tags":["prostate-evidence"],"related":["paper-robinson-integrative-clinical-genomics-advanced-prostate-cell-2015","paper-mateo-toparp-a-olaparib-dna-repair-nejm-2015","paper-struewing-brca-founder-mutations-ashkenazi-nejm-1997","idea-prev-reflex-germline-testing","prostate-roadmap"],"cancers":["prostate","prostate-mhspc","prostate-mcrpc"],"sections":["diagnostics","prevention","targeted-therapy"],"technologies":["germline-testing","cgp"],"targets":["brca","atm","chek2","palb2","rad51d"],"drugs":[],"companies":[],"institutions":["fred-hutch","royal-marsden"],"pathways":["homologous-recombination-repair","ddr"],"terms":["hrd","ngs","germline-vs-somatic","gbrca-mutation","lynch-syndrome"],"trials":[],"people":[],"bottlenecks":["b-hereditary-risk","b-biomarker-validation","b-care-fragmentation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2016,"doi":"10.1056/nejmoa1603144","pmid":"27433846","authors":"Pritchard CC, Mateo J, Walsh MF, et al.","paperType":"observational","findings":["84 presumed deleterious germline DNA repair gene mutations were identified in 82 of 692 men (11.8 percent) with metastatic prostate cancer.","Mutations were found in 16 genes: BRCA2 in 37 men (5.3 percent), ATM in 11 (1.6 percent), CHEK2 in 10 (1.9 percent of 534 men with data), BRCA1 in 6 (0.9 percent), RAD51D in 3 (0.4 percent) and PALB2 in 3 (0.4 percent).","Mutation frequencies did not differ according to whether a family history of prostate cancer was present or according to age at diagnosis.","The 11.8 percent frequency significantly exceeded the 4.6 percent prevalence among 499 men with localised prostate cancer, including high-risk disease (P less than 0.001).","It also exceeded the 2.7 percent prevalence in the Exome Aggregation Consortium, which includes 53,105 people without a known cancer diagnosis (P less than 0.001)."],"whatItMeans":"The evidence that made germline testing standard for every man with metastatic prostate cancer, whatever his family history. It changes his treatment, because PARP inhibitors and platinum work better in these tumours, and it changes his relatives' screening, because BRCA2 carries breast, ovarian and pancreatic risk as well.","caveats":["Men recruited at academic centres with an interest in genetics, so ascertainment is not fully unselected despite the design.","20 genes on the panel; a wider panel would find more variants of uncertain significance without necessarily finding more actionable ones.","The clinical benefit of finding a CHEK2 or ATM variant is much less well established than for BRCA2; ATM tumours respond poorly to PARP inhibitors, as TRITON3 showed."],"changedPractice":true,"participants":692},{"id":"paper-couch-tnbc-germline-17-genes-jco-2015","kind":"paper","name":"Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer","aka":[],"tldr":"Testing 1,824 women with triple-negative breast cancer regardless of family history found an inherited cancer-gene mutation in one in seven: BRCA1 in 8.5%, BRCA2 in 2.7% and other repair genes in 3.7%, which is why every TNBC patient is now offered germline testing.","summary":"1,824 TNBC patients unselected for family history of breast or ovarian cancer were recruited through 12 studies and germline DNA sequenced for 17 predisposition genes. Deleterious mutations were identified in 14.6%: 11.2% in BRCA1 (8.5%) and BRCA2 (2.7%), and 3.7% in 15 other genes, mostly homologous recombination genes including PALB2 (1.2%) and BARD1, RAD51D, RAD51C and BRIP1 (0.3% to 0.5%). Carriers were diagnosed younger (P less than .001) with higher-grade tumours (P .01).","asOf":"2026-09-24","links":[{"label":"Couch et al., J Clin Oncol 2015: germline mutations in 17 genes among 1,824 unselected TNBC patients","url":"https://doi.org/10.1200/JCO.2014.57.1414"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25452441/"}],"tags":[],"related":[],"cancers":["tnbc"],"sections":[],"technologies":["germline-testing"],"targets":["brca","palb2","bard1","rad51c","rad51d"],"drugs":[],"companies":[],"institutions":["mayo-clinic"],"pathways":[],"terms":["gbrca-mutation","germline-vs-somatic"],"trials":[],"people":["priyanka-sharma"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2015,"doi":"10.1200/JCO.2014.57.1414","pmid":"25452441","authors":"Couch FJ, Hart SN, Sharma P, et al.","paperType":"observational","findings":["Deleterious germline mutation in 14.6%: BRCA1 8.5%, BRCA2 2.7%, other genes 3.7%.","PALB2 1.2%; BARD1, RAD51D, RAD51C and BRIP1 0.3% to 0.5% each.","Carriers were younger with higher-grade tumours."],"whatItMeans":"This cohort underpins the guideline shift to germline BRCA1/2 testing for all TNBC patients regardless of age or family history, and it is the prevalence figure the corpus uses for germline BRCA1 in TNBC.","caveats":["Predominantly European-ancestry research cohorts.","Risk estimates for the non-BRCA genes were judged too imprecise for relatives' counselling at the time."],"changedPractice":true,"participants":1824},{"id":"paper-olive-hedgehog-stroma-gemcitabine-delivery-science-2009","kind":"paper","name":"Inhibition of hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer","aka":[],"tldr":"Pancreatic tumours in mice, like those in people, have so few blood vessels that chemotherapy barely reaches them; stripping away the surrounding scar tissue with a hedgehog-blocking drug let more gemcitabine in and held the disease still for a while.","summary":"A mouse model of pancreatic ductal adenocarcinoma refractory to gemcitabine was studied; tumours were poorly perfused and poorly vascularised, properties shared with human disease. Co-administration of IPI-926, which depletes tumour-associated stroma by inhibiting hedgehog signalling, produced a transient increase in intratumoural vascular density and gemcitabine concentration, leading to transient stabilisation of disease. Inefficient drug delivery may therefore be an important contributor to chemoresistance.","asOf":"2026-09-24","links":[{"label":"Olive et al., Science 2009: hedgehog inhibition improves gemcitabine delivery in the mouse model","url":"https://doi.org/10.1126/science.1171362"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19460966/"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":["gemcitabine"],"companies":[],"institutions":[],"pathways":["hedgehog","caf-activation-desmoplasia"],"terms":["desmoplasia"],"trials":[],"people":["david-tuveson"],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2009,"doi":"10.1126/science.1171362","pmid":"19460966","authors":"Olive KP, Jacobetz MA, Davidson CJ, et al.","paperType":"basic","findings":["Mouse and human pancreatic tumours are poorly perfused and vascularised.","Hedgehog inhibition transiently raised vascular density and intratumoural gemcitabine and stabilised disease."],"whatItMeans":"It launched a decade of attempts to strip the stroma to let drugs in; the clinical trials that followed failed, and later mouse work showed the stroma also restrains the tumour.","caveats":["Mouse model, transient effect.","Hedgehog inhibitors were harmful or futile in patients (Rhim 2014, Ozdemir 2014)."],"changedPractice":false},{"id":"paper-nct04606446-nat-med-2024","kind":"paper","name":"Inhibition of lysine acetyltransferase KAT6 in ER + HER2 - metastatic breast cancer: a phase 1 trial","aka":[],"tldr":"Published report from the trial registered as NCT04606446, in Nature Medicine (2024), chosen as the most cited paper whose own text cites the registry id.","summary":"Inhibition of histone lysine acetyltransferases (KATs) KAT6A and KAT6B has shown antitumor activity in estrogen receptor-positive (ER +) breast cancer preclinical models. PF-07248144 is a selective catalytic inhibitor of KAT6A and KAT6B. In the present study, we report the safety, pharmacokinetics (PK), pharmacodynamics, efficacy and biomarker results from the first-in-human, phase 1 dose escalation and dose expansion study (n = 107) of PF-07248144 monotherapy and fulvestrant combination in heavily pretreated ER + human epidermal growth factor receptor-negative (HER2 -) metastatic breast cancer (mBC). The primary objectives of assessing the safety and tolerability and determining the recommended dose for expansion of PF-07248144, as monotherapy and in combination with fulvestrant, were met. Secondary endpoints included characterization of PK and evaluation of antitumor activity, including objective response rate (ORR) and progression-free survival (PFS). Common treatment-related adverse events (any grade; grades 3-4) included dysgeusia (83.2%, 0%), neutropenia (59.8%, 35.5%) and anemia (48.6%, 13.1%). Exposure was approximately dose proportional. Antitumor activity was observed as monotherapy. For the PF-07248144-fulvestrant combination (n = 43), the ORR (95% confidence interval (CI)) was 30.2% (95% CI = 17.2-46.1%) and the median PFS was 10.7 (5.3-not evaluable) months. PF-07248144 demonstrated a tolerable safety profile and durable antitumor activity in heavily pretreated ER + HER2 - mBC. These findings establish KAT6A and KAT6B as druggable cancer targets, provide clinical proof of concept and reveal a potential avenue to treat mBC. clinicaltrial.gov registration: NCT04606446.\n\nIndexed on Europe PMC as PubMed record 38824244 (DOI 10.1038/s41591-024-03060-0). Its abstract cites the registry id NCT04606446, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Nat Med 2024","url":"https://doi.org/10.1038/s41591-024-03060-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38824244/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38824244"},{"label":"ClinicalTrials.gov NCT04606446","url":"https://clinicaltrials.gov/study/NCT04606446"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04606446"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2024,"doi":"10.1038/s41591-024-03060-0","pmid":"38824244","authors":"Mukohara T, Park YH, Sommerhalder D, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04606446 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-seligmann-j-clin-oncol","kind":"paper","name":"Inhibition of WEE1 Is Effective in TP53 - and RAS -Mutant Metastatic Colorectal Cancer: A Randomized Trial (FOCUS4-C) Comparing Adavosertib (AZD1775) With Active Monitoring","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 34538072 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: Outcomes in RAS -mutant metastatic colorectal cancer (mCRC) remain poor and patients have limited therapeutic options. Adavosertib is the first small-molecule inhibitor of WEE1 kinase. We hypothesized that aberrations in DNA replication seen in mCRC with both RAS and TP53 mutations would sensitize tumors to WEE1 inhibition.\n\nMethods: Patients with newly diagnosed mCRC were registered into FOCUS4 and tested for TP53 and RAS mutations. Those with both mutations who were stable or responding after 16 weeks of chemotherapy were randomly assigned 2:1 between adavosertib and active monitoring (AM). Adavosertib (250 mg or 300 mg) was taken orally once on days 1-5 and days 8-12 of a 3-week cycle. The primary outcome was progression-free survival (PFS), with a target hazard ratio (HR) of 0.5 and 80% power with a one-sided 0.025 significance level.\n\nResults: FOCUS4-C was conducted between April 2017 and Mar 2020 during which time 718 patients were registered; 247 (34%) were RAS/TP53 -mutant. Sixty-nine patients were randomly assigned from 25 UK hospitals (adavosertib = 44; AM = 25). Adavosertib was associated with a PFS improvement over AM (median 3.61 v 1.87 months; HR = 0.35; 95% CI, 0.18 to 0.68; P =.0022). Overall survival (OS) was not improved with adavosertib versus AM (median 14.0 v 12.8 months; HR = 0.92; 95% CI, 0.44 to 1.94; P =.93). In prespecified subgroup analysis, adavosertib activity was greater in left-sided tumors (HR = 0.24; 95% CI, 0.11 to 0.51), versus right-sided (HR = 1.02; 95% CI, 0.41 to 2.56; interaction P =.043). Adavosertib was well-tolerated; grade 3 toxicities were diarrhea (9%), nausea (5%), and neutropenia (7%).\n\nConclusion: In this phase II randomized trial, adavosertib improved PFS compared with AM and demonstrates potential as a well-tolerated therapy for RAS/TP53 -mutant mCRC. Further testing is required in this sizable population of unmet need.\n\nIndexed on Europe PMC as PubMed record 34538072 (DOI 10.1200/jco.21.01435). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2021","url":"https://doi.org/10.1200/jco.21.01435"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34538072/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34538072"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["focus4"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2021,"doi":"10.1200/jco.21.01435","pmid":"34538072","authors":"Seligmann JF, Fisher DJ, Brown LC, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-splash-front-oncol-2024","kind":"paper","name":"Initial clinical experience with [ 177 Lu]Lu-PNT2002 radioligand therapy in metastatic castration-resistant prostate cancer: dosimetry, safety, and efficacy from the lead-in cohort of the SPLASH trial","aka":[],"tldr":"Published report from the SPLASH trial registered as NCT04647526, in Frontiers in oncology (2024), chosen as the most cited paper whose own text cites the registry id.","summary":"Introduction: SPLASH (NCT04647526) is a multicenter phase III trial evaluating the efficacy and safety of [ 177 Lu]Lu-PNT2002 radioligand therapy in metastatic castration-resistant prostate cancer (mCRPC). This study leveraged a lead-in phase to assess tissue dosimetry and evaluate preliminary safety and efficacy, prior to expansion into a randomized phase. Here we report those results.\n\nMethods: Enrolled participants had mCRPC that progressed on one prior androgen receptor pathway inhibitor (ARPI), were prostate-specific membrane antigen (PSMA) PET-positive as determined by a central reader, were chemotherapy-naïve for mCRPC, and had adequate bone marrow and end-organ reserve. Participants received up to 4 cycles of [ 177 Lu]Lu-PNT2002 at 6.8 GBq (± 10%) intravenously per cycle every 8 weeks. Dosimetry (planar + SPECT/CT [n=7]; planar only [n=20]), safety, prostate-specific antigen (PSA) response, objective response rate (ORR), and radiographic progression-free survival (rPFS) per blinded independent central review were assessed.\n\nResults: Of 34 individuals screened, 32 underwent PSMA-PET/CT; 27 met all eligibility criteria. Median (range) age was 72 (57-86) years; all participants were enrolled in North America; 40.7% initiated prior ARPI treatment without distant metastases (M0) and 25.9% while hormone sensitive. Nineteen of 27 (70.4%) participants completed all 4 planned cycles. Organs receiving the largest mean (median, range) specific absorbed doses were lacrimal glands at 1.2 (0.9, 0.4-6.7) Gy/GBq (planar only [n=27]), followed by kidneys at 0.73 (0.63, 0.22-1.8) Gy/GBq (planar + SPECT/CT [n=7]; planar only [n=20]). Mean (median, range) tumor specific absorbed dose was 4.3 (2.1, 0.3-33.4) Gy/GBq (approximately 29 Gy/cycle) based on planar + SPECT/CT of 21 lesions in seven participants. [ 177 Lu]Lu-PNT2002 was associated with no treatment-related deaths, few treatment-related grade ≥3 treatment-emergent adverse events (TEAEs), and no discontinuations for unacceptable toxicity. Treatment-related TEAEs occurring in ≥10% of participants included dry mouth (22.2%; all grade 1), fatigue (18.5%; grades 1-2), nausea (18.5%; grades 1-2), and anemia (14.8%; grades 1-3). Median (95% CI) rPFS was 11.5 (9.2-19.1) months, a PSA decline of ≥50% occurred in 42.3% (11/26) of participants, and confirmed ORR for evaluable disease was 50% (5/10).\n\nConclusion: [ 177 Lu]Lu-PNT2002, administered at 6.8 GBq/cycle for 4 cycles, demonstrated a favorable dosimetry and safety profile, as well as promising preliminary efficacy.\n\nClinical trial registration: https://clinicaltrials.gov/, identifier NCT04647526.\n\nIndexed on Europe PMC as PubMed record 39839782 (DOI 10.3389/fonc.2024.1483953). Its abstract cites the registry id NCT04647526, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Front Oncol 2024","url":"https://doi.org/10.3389/fonc.2024.1483953"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39839782/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39839782"},{"label":"ClinicalTrials.gov NCT04647526","url":"https://clinicaltrials.gov/study/NCT04647526"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["splash"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Frontiers in oncology","year":2024,"doi":"10.3389/fonc.2024.1483953","pmid":"39839782","authors":"Hansen AR, Probst S, Beauregard JM, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04647526 with the most citations, so it is the natural first reading for anyone following the SPLASH trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-innovatv-301-tisotumab-nejm-2024","kind":"paper","name":"innovaTV 301: tisotumab vedotin versus chemotherapy as second- or third-line therapy for recurrent cervical cancer","aka":[],"tldr":"The tissue factor-directed antibody-drug conjugate tisotumab vedotin lengthened survival compared with chemotherapy in cervical cancer that had progressed after first-line treatment, at the cost of eye and nerve side effects.","summary":"Phase 3 trial of 502 patients with recurrent or metastatic cervical cancer after one or two prior systemic regimens randomised to tisotumab vedotin or investigator's choice chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan or pemetrexed).\n\nMedian overall survival was 11.5 versus 9.5 months (hazard ratio 0.70), progression-free survival 4.2 versus 2.9 months and objective response 17.8 versus 5.2 percent; ocular events, peripheral neuropathy and bleeding were the characteristic toxicities.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2024","url":"https://doi.org/10.1056/NEJMoa2313811"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38959480/"}],"tags":[],"related":[],"cancers":["recurrent-metastatic-cervical-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["tisotumab-vedotin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["innovatv-301"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2024,"doi":"10.1056/NEJMoa2313811","pmid":"38959480","authors":"Vergote I, González-Martín A, Fujiwara K, et al.","paperType":"rct","findings":["Median overall survival 11.5 vs 9.5 months; hazard ratio 0.70.","Objective response 17.8 percent vs 5.2 percent."],"whatItMeans":"Tisotumab vedotin is the standard second-line treatment for recurrent cervical cancer after chemo-immunotherapy, with a mandatory eye-care protocol.","caveats":["Modest absolute gains.","Conjunctivitis and keratitis require prophylactic eye drops and regular examinations."],"changedPractice":true,"participants":502},{"id":"paper-ino-vate-inotuzumab-all-nejm-2016","kind":"paper","name":"INO-VATE: inotuzumab ozogamicin, a CD22 antibody-drug conjugate, versus chemotherapy for relapsed adult B-cell ALL","aka":[],"tldr":"A CD22 antibody-drug conjugate produced complete remission in 81% of adults with relapsed ALL compared with 29% on chemotherapy, at the cost of liver toxicity in about one in ten.","summary":"INO-VATE randomised 326 adults with relapsed or refractory CD22-positive B-cell ALL to inotuzumab ozogamicin or standard intensive salvage chemotherapy. The two primary endpoints were complete remission (analysed in the first 218 patients) and overall survival. Complete remission was 80.7% versus 29.4%, with MRD-negativity among responders 78.4% versus 28.1%, and median PFS 5.0 versus 1.8 months. Median OS was 7.7 versus 6.7 months (hazard ratio 0.77), which did not meet the prespecified boundary, although two-year survival was 23% versus 10%. Hepatic veno-occlusive disease occurred in 11% of inotuzumab patients, especially after subsequent transplant with dual-alkylator conditioning.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa1509277"},{"label":"ClinicalTrials.gov NCT01564784","url":"https://clinicaltrials.gov/study/NCT01564784"}],"tags":[],"related":["inotuzumab-then-transplant-caution"],"cancers":["all-leukemia"],"sections":[],"technologies":["adc","allogeneic-hsct"],"targets":["cd22"],"drugs":["inotuzumab-ozogamicin","blinatumomab"],"companies":["pfizer"],"institutions":["md-anderson"],"pathways":[],"terms":["mrd","os"],"trials":[],"people":["hagop-kantarjian"],"bottlenecks":["b-toxicity-qol"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2016,"doi":"10.1056/NEJMoa1509277","authors":"Kantarjian HM, DeAngelo DJ, Stelljes M, et al.","paperType":"rct","findings":["326 adults with relapsed/refractory B-ALL; inotuzumab ozogamicin vs salvage chemotherapy.","Complete remission 80.7% vs 29.4%; MRD-negativity among responders 78.4% vs 28.1%.","Median PFS 5.0 vs 1.8 months; more patients bridged to transplant (41% vs 11%).","Median OS 7.7 vs 6.7 months (HR 0.77); 2-year OS 23% vs 10%.","Veno-occlusive disease 11% vs 1%, highest after transplant with dual-alkylator conditioning."],"whatItMeans":"INO-VATE made inotuzumab a standard salvage therapy for adult ALL and a common route to transplant, and, with the TOWER trial of blinatumomab, moved adult ALL from chemotherapy-only salvage to immunotherapy. Both drugs have since been pulled into front-line regimens. The liver toxicity signal shaped how transplant conditioning is chosen after inotuzumab.","caveats":["OS benefit was modest and did not meet the trial's statistical threshold at the primary analysis.","Veno-occlusive disease is a serious, sometimes fatal, toxicity that constrains dosing before transplant.","Open-label with heterogeneous chemotherapy comparators.","Requires CD22 expression; antigen loss is a resistance mechanism."],"changedPractice":true,"participants":326},{"id":"paper-franklin-nat-rev-cancer","kind":"paper","name":"Insights into recent findings and clinical application of YAP and TAZ in cancer","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 37308716 and published in Nature Reviews Cancer; the citing page links this DOI, which is how the record was matched.","summary":"Decades of research have mapped out the basic mechanics of the Hippo pathway. The paralogues Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), as the central transcription control module of the Hippo pathway, have long been implicated in the progression of various human cancers. The current literature regarding oncogenic YAP and TAZ activities consists mostly of context-specific mechanisms and treatments of human cancers. Furthermore, a growing number of studies demonstrate tumour-suppressor functions of YAP and TAZ. In this Review we aim to synthesize an integrated perspective of the many disparate findings regarding YAP and TAZ in cancer. We then conclude with the various strategies for targeting and treating YAP- and TAZ-dependent cancers.\n\nIndexed on Europe PMC as PubMed record 37308716 (DOI 10.1038/s41568-023-00579-1). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Cancer 2023","url":"https://doi.org/10.1038/s41568-023-00579-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37308716/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37308716"}],"tags":["europepmc-ingest"],"related":["hippo-yap"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Cancer","year":2023,"doi":"10.1038/s41568-023-00579-1","pmid":"37308716","authors":"Franklin JM, Wu Z, Guan KL","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-sharpe-lancet","kind":"paper","name":"Integrated collaborative care for comorbid major depression in patients with cancer (SMaRT Oncology-2): a multicentre randomised controlled effectiveness trial","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 25175478 and published in The Lancet; the citing page links this DOI, which is how the record was matched.","summary":"Background: Medical conditions are often complicated by major depression, with consequent additional impairment of quality of life. We aimed to compare the effectiveness of an integrated treatment programme for major depression in patients with cancer (depression care for people with cancer) with usual care.\n\nMethods: SMaRT Oncology-2 is a parallel-group, multicentre, randomised controlled effectiveness trial. We enrolled outpatients with major depression from three cancer centres and their associated clinics in Scotland, UK. Participants were randomly assigned in a 1:1 ratio to the depression care for people with cancer intervention or usual care, with stratification (by trial centre) and minimisation (by age, primary cancer, and sex) with allocation concealment. Depression care for people with cancer is a manualised, multicomponent collaborative care treatment that is delivered systematically by a team of cancer nurses and psychiatrists in collaboration with primary care physicians. Usual care is provided by primary care physicians. Outcome data were collected up until 48 weeks. The primary outcome was treatment response (≥50% reduction in Symptom Checklist Depression Scale [SCL-20] score, range 0-4) at 24 weeks. Trial statisticians and data collection staff were masked to treatment allocation, but participants could not be masked to the allocations. Analyses were by intention to treat. This trial is registered with Current Controlled Trials, number ISRCTN40568538.\n\nFindings: 500 participants were enrolled between May 12, 2008, and May 13, 2011; 253 were randomly allocated to depression care for people with cancer and 247 to usual care. 143 (62%) of 231 participants in the depression care for people with cancer group and 40 (17%) of 231 in the usual care group responded to treatment: absolute difference 45% (95% CI 37-53), adjusted odds ratio 8·5 (95% CI 5·5-13·4), p<0·0001. Compared with patients in the usual care group, participants allocated to the depression care for people with cancer programme also had less depression, anxiety, pain, and fatigue; and better functioning, health, quality of life, and perceived quality of depression care at all timepoints (all p<0·05). During the study, 34 cancer-related deaths occurred (19 in the depression care for people with cancer group, 15 in the usual care group), one patient in the depression care for people with cancer group was admitted to a psychiatric ward, and one patient in this group attempted suicide. None of these events were judged to be related to the trial treatments or procedures.\n\nInterpretation: Our findings suggest that depression care for people with cancer is an effective treatment for major depression in patients with cancer. It offers a model for the treatment of depression comorbid with other medical conditions.\n\nFunding: Cancer Research UK and Chief Scientist Office of the Scottish Government.\n\nIndexed on Europe PMC as PubMed record 25175478 (DOI 10.1016/s0140-6736(14)61231-9). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet 2014","url":"https://doi.org/10.1016/s0140-6736(14)61231-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25175478/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25175478"}],"tags":["europepmc-ingest"],"related":["psycho-oncology"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2014,"doi":"10.1016/s0140-6736(14)61231-9","pmid":"25175478","authors":"Sharpe M, Walker J, Holm  Hansen C, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-tcga-ovarian-nature-2011","kind":"paper","name":"Integrated genomic analyses of ovarian carcinoma (The Cancer Genome Atlas)","aka":[],"tldr":"Sequencing nearly 500 high-grade serous ovarian cancers showed that almost all carry TP53 mutations and about half have defects in homologous recombination DNA repair, the biology that PARP inhibitors exploit.","summary":"Integrated genomic analysis by The Cancer Genome Atlas of 489 high-grade serous ovarian adenocarcinomas, finding TP53 mutations in 96 percent, germline or somatic BRCA1/2 mutations in about 20 percent, homologous recombination defects in about half, widespread copy-number changes, and four transcriptional subtypes.","asOf":"2026-09-17","links":[{"label":"Nature 2011","url":"https://doi.org/10.1038/nature10166"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21720365/"}],"tags":[],"related":[],"cancers":["high-grade-serous-ovarian-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2011,"doi":"10.1038/nature10166","pmid":"21720365","authors":"Cancer Genome Atlas Research Network.","paperType":"translational","findings":["TP53 mutated in 96 percent of high-grade serous ovarian cancers.","Homologous recombination pathway defects in about 50 percent, including BRCA1/2 in about 20 percent."],"whatItMeans":"The homologous recombination deficiency concept, and the case for testing all high-grade serous cancers for BRCA and related defects, come from this dataset.","caveats":["Research-grade profiling of primary tumours; clinical homologous recombination deficiency assays came later."],"changedPractice":true,"participants":489},{"id":"paper-raajit-rampal-blood-2014","kind":"paper","name":"Integrated genomic analysis illustrates the central role of JAK-STAT pathway activation in myeloproliferative neoplasm pathogenesis","aka":[],"tldr":"Paper by Raajit K. Rampal indexed on Europe PMC as PubMed record 24740812, in Blood (2014), one of the most cited records naming an author with this name at Memorial Sloan Kettering Cancer Center.","summary":"Genomic studies have identified somatic alterations in the majority of myeloproliferative neoplasms (MPN) patients, including JAK2 mutations in the majority of MPN patients and CALR mutations in JAK2-negative MPN patients. However, the role of JAK-STAT pathway activation in different MPNs, and in patients without JAK2 mutations, has not been definitively delineated. We used expression profiling, single nucleotide polymorphism arrays, and mutational profiling to investigate a well-characterized cohort of MPN patients. MPN patients with homozygous JAK2V617F mutations were characterized by a distinctive transcriptional profile. Notably, a transcriptional signature consistent with activated JAK2 signaling is seen in all MPN patients regardless of clinical phenotype or mutational status. In addition, the activated JAK2 signature was present in patients with somatic CALR mutations. Conversely, we identified a gene expression signature of CALR mutations; this signature was significantly enriched in JAK2-mutant MPN patients consistent with a shared mechanism of transformation by JAK2 and CALR mutations. We also identified a transcriptional signature of TET2 mutations in MPN patent samples. Our data indicate that MPN patients, regardless of diagnosis or JAK2 mutational status, are characterized by a distinct gene expression signature with upregulation of JAK-STAT target genes, demonstrating the central importance of the JAK-STAT pathway in MPN pathogenesis.\n\nIndexed on Europe PMC as PubMed record 24740812 (DOI 10.1182/blood-2014-02-554634). Its author list gives \"Rampal R\" with the affiliation \"Human Oncology and Pathogenesis Program, and Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY; Weill Cornell Medical College, New York, NY;\", which names Memorial Sloan Kettering Cancer Center; that is how the record was matched to Raajit K. Rampal, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Blood 2014","url":"https://doi.org/10.1182/blood-2014-02-554634"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24740812/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/24740812"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["raajit-rampal"],"bottlenecks":[],"keyPapers":[],"journals":["blood"],"dependsOn":[],"notes":[],"journal":"Blood","year":2014,"doi":"10.1182/blood-2014-02-554634","pmid":"24740812","authors":"Rampal R, Al-Shahrour F, Abdel-Wahab O, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Raajit K. Rampal at Memorial Sloan Kettering Cancer Center, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-pandey-gallbladder-elf3-nat-commun-2020","kind":"paper","name":"Integrated genomic analysis reveals mutated ELF3 as a potential gallbladder cancer vaccine candidate","aka":[],"tldr":"Sequencing 167 gallbladder cancers from Korea, India and Chile uncovered new driver genes, notably ELF3, whose frameshift mutations create tumour-specific fragments that T cells recognise, making it a candidate for a cancer vaccine.","summary":"Exomes (n = 160), transcriptomes (n = 115) and low-pass whole genomes (n = 146) from 167 gallbladder cancers from patients in Korea, India and Chile were analysed, together with samples from 39 high-risk patients in whom early cancer-related genomic lesions were detected. Among the significantly mutated genes not previously linked to gallbladder cancer were the ETS domain genes ELF3 and EHF, CTNNB1, APC, NSD1, KAT8, STK11 and NFE2L2.\n\nA majority of ELF3 alterations were frameshift mutations that result in several cancer-specific neoantigens that activate T cells, indicating they are cancer vaccine candidates. Recurrent alterations in KEAP1/NFE2L2 and the Wnt pathway were identified, together defining multiple targetable intervention opportunities.","asOf":"2026-09-24","links":[{"label":"Pandey et al., Nat Commun 2020: integrated genomics of 167 gallbladder cancers from Korea, India and Chile","url":"https://doi.org/10.1038/s41467-020-17880-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32839463/"}],"tags":[],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":["elf3","ctnnb1","apc","stk11","nfe2l2","keap1"],"drugs":[],"companies":[],"institutions":[],"pathways":["wnt"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-communications"],"dependsOn":[],"notes":[],"journal":"Nature Communications","year":2020,"doi":"10.1038/s41467-020-17880-4","pmid":"32839463","authors":"Pandey A, Stawiski EW, Durinck S, et al.","paperType":"translational","findings":["New significantly mutated genes: ELF3, EHF, CTNNB1, APC, NSD1, KAT8, STK11 and NFE2L2.","Most ELF3 alterations were frameshifts producing T-cell-activating neoantigens.","Recurrent KEAP1/NFE2L2 and Wnt pathway alterations; early genomic lesions detectable in high-risk patients."],"whatItMeans":"A three-continent cohort from high-incidence countries, and the origin of the idea that a shared frameshift (ELF3) could be a vaccine target in a cancer with few targets. CTNNB1 and STK11 from this list recur in the MSK data.","caveats":["Neoantigen activity was shown in vitro; no vaccine has been tested in patients.","Frequencies for individual genes are in the paper, not the abstract."],"changedPractice":false,"participants":167},{"id":"paper-tcga-endometrial-nature-2013","kind":"paper","name":"Integrated genomic characterisation of endometrial carcinoma (The Cancer Genome Atlas)","aka":[],"tldr":"Sequencing of 373 endometrial cancers revealed four molecular groups, POLE ultramutated, microsatellite unstable, copy-number low and copy-number high, that cut across the traditional endometrioid and serous types and predict outcome.","summary":"Integrated genomic, transcriptomic and proteomic analysis of 373 endometrial carcinomas by The Cancer Genome Atlas defining four groups: POLE ultramutated (with excellent outcome), microsatellite instability hypermutated, copy-number low (endometrioid) and copy-number high (serous-like, TP53-mutated, worst outcome); about a quarter of high-grade endometrioid tumours resembled serous carcinoma molecularly.","asOf":"2026-09-17","links":[{"label":"Nature 2013","url":"https://doi.org/10.1038/nature12113"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23636398/"}],"tags":[],"related":[],"cancers":["endometrial-pole-ultramutated","endometrial-p53-abnormal"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2013,"doi":"10.1038/nature12113","pmid":"23636398","authors":"Cancer Genome Atlas Research Network, Kandoth C, Schultz N, et al.","paperType":"translational","findings":["Four molecular subgroups with distinct progression-free survival.","25 percent of high-grade endometrioid tumours had serous-like copy-number-high profiles."],"whatItMeans":"This is the origin of the molecular classification now used for every endometrial cancer, translated into a practical test by ProMisE.","caveats":["Research-grade sequencing; clinical surrogates were needed for routine use."],"changedPractice":true,"participants":373},{"id":"paper-cancer-genome-atlas-research-nature","kind":"paper","name":"Integrated genomic characterization of oesophageal carcinoma","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 28052061 and published in Nature; the citing page links this DOI, which is how the record was matched.","summary":"Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies.\n\nIndexed on Europe PMC as PubMed record 28052061 (DOI 10.1038/nature20805). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2017","url":"https://doi.org/10.1038/nature20805"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28052061/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28052061"}],"tags":["europepmc-ingest"],"related":["escc-vs-eac"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2017,"doi":"10.1038/nature20805","pmid":"28052061","authors":"Cancer Genome Atlas Research Network, Analysis Working Group: Asan University, BC Cancer Agency, et al.","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-tcga-pancreatic-integrated-characterisation-cancer-cell-2017","kind":"paper","name":"Integrated genomic characterization of pancreatic ductal adenocarcinoma","aka":[],"tldr":"The Cancer Genome Atlas profiled 150 pancreatic cancers on every platform, confirmed the driver list, showed that tumours without a KRAS mutation carry other growth-signal drivers such as GNAS, BRAF and CTNNB1, and found some tumours with two KRAS mutations.","summary":"Integrated genomic, transcriptomic and proteomic profiling of 150 pancreatic ductal adenocarcinoma specimens, including samples with characteristically low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFBR2, GNAS, RREB1 and PBRM1. KRAS wild-type tumours harboured alterations in other oncogenic drivers including GNAS, BRAF, CTNNB1 and additional RAS pathway genes. A subset of tumours harboured multiple KRAS mutations, some biallelic. Protein profiling identified a favourable-prognosis subset with low epithelial-mesenchymal transition and high MTOR pathway scores.\n\nDeposited as paad_tcga_pan_can_atlas_2018 on cBioPortal with 184 samples, including the low-cellularity and non-ductal samples excluded from the 150-tumour analysis; KRAS reads 117 of 179 sequenced there for that reason.","asOf":"2026-09-24","links":[{"label":"Cancer Genome Atlas Research Network, Cancer Cell 2017: integrated characterisation of 150 pancreatic ductal adenocarcinomas","url":"https://doi.org/10.1016/j.ccell.2017.07.007"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28810144/"},{"label":"cBioPortal study paad_tcga_pan_can_atlas_2018 (TCGA PanCancer Atlas; 184 samples, 179 sequenced, 183 with copy number; the deposit keeps the low-cellularity and non-ductal samples the 2017 paper excluded)","url":"https://www.cbioportal.org/study/summary?id=paad_tcga_pan_can_atlas_2018"}],"tags":[],"related":[],"cancers":["pancreatic","kras-wild-type-pdac"],"sections":[],"technologies":["wes-wgs","rna-seq","proteomics"],"targets":["kras","tp53","cdkn2a","smad4","rnf43","arid1a","tgfbr2","gnas","braf","ctnnb1"],"drugs":[],"companies":[],"institutions":["nci","broad-institute","dana-farber"],"pathways":["pancreatic-cancer-signalling","ras-mapk"],"terms":["wild-type"],"trials":[],"people":["andrew-aguirre"],"bottlenecks":[],"keyPapers":[],"journals":["cancer-cell"],"dependsOn":[],"notes":[],"journal":"Cancer Cell","year":2017,"doi":"10.1016/j.ccell.2017.07.007","pmid":"28810144","authors":"Cancer Genome Atlas Research Network (Raphael BJ, Hruban RH, Aguirre AJ, et al.).","paperType":"translational","findings":["Recurrent mutations: KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFBR2, GNAS, RREB1, PBRM1.","KRAS wild-type tumours carry GNAS, BRAF, CTNNB1 or other RAS pathway drivers.","A subset carries multiple, sometimes biallelic, KRAS mutations."],"whatItMeans":"It is the reference multi-platform dataset and the reason a KRAS wild-type report is treated as a search for another driver rather than as an absence.","caveats":["Low cellularity required purity-aware analysis; the public deposit is not the analysed set.","Subtype calls on bulk tissue depend on the classifier."],"changedPractice":false,"participants":150},{"id":"paper-mackay-paediatric-hgg-cancer-cell-2017","kind":"paper","name":"Integrated molecular meta-analysis of 1,000 paediatric high-grade and diffuse intrinsic pontine gliomas","aka":[],"tldr":"Pooling molecular data from a thousand childhood high-grade gliomas showed they are a collection of distinct diseases defined by mutations such as histone H3 K27M and G34R, IDH, and BRAF, with different ages, locations and survival, rather than a single tumour type.","summary":"Meta-analysis of published and unpublished molecular data on 1,000 paediatric high-grade gliomas and diffuse intrinsic pontine gliomas, integrating mutations, copy number, methylation and expression to define subgroups by histone H3 and IDH status and by other drivers, with clinical correlates and survival.\n\nSubgroups differed markedly in age, anatomical location and outcome, and the analysis identified targetable alterations (BRAF, NTRK, ALK, ROS1, PDGFRA) in a subset of tumours.","asOf":"2026-09-17","links":[{"label":"Cancer Cell 2017","url":"https://doi.org/10.1016/j.ccell.2017.08.017"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28966033/"}],"tags":[],"related":[],"cancers":["paediatric-high-grade-glioma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-cell"],"dependsOn":[],"notes":[],"journal":"Cancer Cell","year":2017,"doi":"10.1016/j.ccell.2017.08.017","pmid":"28966033","authors":"Mackay A, Burford A, Carvalho D, et al.","paperType":"translational","findings":["Histone H3 K27M and G34R/V, IDH1 and wild-type subgroups with distinct age, location and survival distributions.","Targetable kinase alterations identified in a minority, especially in infants."],"whatItMeans":"The 2021 WHO paediatric-type diffuse high-grade glioma categories, and the practice of profiling every childhood glioma for a targetable fusion or mutation, rest on this landscape.","caveats":["Heterogeneous retrospective data with variable treatment information."],"changedPractice":true,"participants":1000},{"id":"paper-zhang-nat-commun","kind":"paper","name":"Integrating evolutionary dynamics into treatment of metastatic castrate-resistant prostate cancer","aka":[],"tldr":"Paper cited by one technology page, one pathway page and one term page, indexed on Europe PMC as PubMed record 29180633 and published in Nature Communications; the citing pages link this DOI, which is how the record was matched.","summary":"Abiraterone treats metastatic castrate-resistant prostate cancer by inhibiting CYP17A, an enzyme for testosterone auto-production. With standard dosing, evolution of resistance with treatment failure (radiographic progression) occurs at a median of ~16.5 months. We hypothesize time to progression (TTP) could be increased by integrating evolutionary dynamics into therapy. We developed an evolutionary game theory model using Lotka-Volterra equations with three competing cancer \"species\": androgen dependent, androgen producing, and androgen independent. Simulations with standard abiraterone dosing demonstrate strong selection for androgen-independent cells and rapid treatment failure. Adaptive therapy, using patient-specific tumor dynamics to inform on/off treatment cycles, suppresses proliferation of androgen-independent cells and lowers cumulative drug dose. In a pilot clinical trial, 10 of 11 patients maintained stable oscillations of tumor burdens; median TTP is at least 27 months with reduced cumulative drug use of 47% of standard dosing. The outcomes show significant improvement over published studies and a contemporaneous population.\n\nIndexed on Europe PMC as PubMed record 29180633 (DOI 10.1038/s41467-017-01968-5). Matched by DOI alone: one technology page, one pathway page and one term page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Commun 2017","url":"https://doi.org/10.1038/s41467-017-01968-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29180633/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29180633"}],"tags":["europepmc-ingest"],"related":["adaptive-therapy-dynamics","clonal-evolution","clonal-evolution-theory","prostate-roadmap","paper-denmeade-transformer-bipolar-androgen-therapy-jco-2021","paper-gundem-evolutionary-history-lethal-metastatic-prostate-nature-2015"],"cancers":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-communications"],"dependsOn":[],"notes":[],"journal":"Nature Communications","year":2017,"doi":"10.1038/s41467-017-01968-5","pmid":"29180633","authors":"Zhang J, Cunningham JJ, Brown JS, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page, one pathway page and one term page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-kapoor-jco-glob-oncol","kind":"paper","name":"Integrating Metronomic Therapy With Standard Chemotherapy in Advanced Unresectable Head and Neck Cancer: A Randomized Trial Addressing Global Cancer Care Equity (METRO PLUS)","aka":[],"tldr":"Paper cited by one trial page and one institution page, indexed on Europe PMC as PubMed record 42308452 and published in JCO global oncology; the citing pages link this DOI, which is how the record was matched.","summary":"Purpose: Advanced head and neck squamous cell carcinoma (HNSCC) carries a poor prognosis, particularly in resource-limited settings with restricted access to targeted or immune therapies. We evaluated whether adding triple oral metronomic chemotherapy (OMCT; erlotinib, celecoxib, methotrexate) to paclitaxel-carboplatin (PC) improves overall survival (OS) in patients with platinum-sensitive, unresectable advanced HNSCC. This was a single-center, investigator-initiated, prospective, randomized, open-label, phase III superiority trial conducted at a tertiary cancer center in North India.\n\nPatients and methods: A total of 238 adults with histologically confirmed, unresectable advanced HNSCC eligible for palliative platinum-based chemotherapy were randomly assigned 1:1 after stratification by tumor site and Eastern Cooperative Oncology Group (ECOG) performance status. Arm A received PC plus OMCT; Arm B received PC alone. The primary end point was OS. Secondary end points included progression-free survival (PFS), quality of life (QoL; European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and Functional Assessment of Cancer Therapy-Head & Neck), and safety.\n\nResults: Among 238 patients (119 per arm), the median age was 47 years; 97.8% were male, and 78% had ECOG performance status (PS) 0-1. The median OS was 10 months (95% CI, 8.3 to 11.7) with PC + OMCT versus 5 months (95% CI, 3.9 to 6.1) with PC alone (hazard ratio [HR], 0.54 [95% CI, 0.41 to 0.72]; P <.001). The median PFS was 6 months versus 2 months, respectively (HR, 0.38 [95% CI, 0.28 to 0.50]; P <.001). QoL analyses demonstrated clinically meaningful preservation across multiple domains in the PC + OMCT arm. Grade ≥3 toxicities did not increase with the addition of OMCT.\n\nConclusion: In platinum-sensitive advanced HNSCC, the addition of triple OMCT to PC significantly improved OS and PFS with acceptable toxicity. PC + OMCT represents a feasible and cost-conscious first-line option in resource-constrained settings.\n\nIndexed on Europe PMC as PubMed record 42308452 (DOI 10.1200/go-25-00721). Matched by DOI alone: one trial page and one institution page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JCO Glob Oncol 2026","url":"https://doi.org/10.1200/go-25-00721"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42308452/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42308452"}],"tags":["europepmc-ingest"],"related":["homi-bhabha-cancer-hospital-varanasi"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["metro-plus-varanasi"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco-global-oncology"],"dependsOn":[],"notes":[],"journal":"JCO global oncology","year":2026,"doi":"10.1200/go-25-00721","pmid":"42308452","authors":"Kapoor A, Gupta A, Sansar B, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page and one institution page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-ferrell-j-clin-oncol","kind":"paper","name":"Integration of Palliative Care Into Standard Oncology Care: American Society of Clinical Oncology Clinical Practice Guideline Update","aka":[],"tldr":"Paper cited by one bottleneck page, indexed on Europe PMC as PubMed record 28034065 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose To provide evidence-based recommendations to oncology clinicians, patients, family and friend caregivers, and palliative care specialists to update the 2012 American Society of Clinical Oncology (ASCO) provisional clinical opinion (PCO) on the integration of palliative care into standard oncology care for all patients diagnosed with cancer. Methods ASCO convened an Expert Panel of members of the ASCO Ad Hoc Palliative Care Expert Panel to develop an update. The 2012 PCO was based on a review of a randomized controlled trial (RCT) by the National Cancer Institute Physicians Data Query and additional trials. The panel conducted an updated systematic review seeking randomized clinical trials, systematic reviews, and meta-analyses, as well as secondary analyses of RCTs in the 2012 PCO, published from March 2010 to January 2016. Results The guideline update reflects changes in evidence since the previous guideline. Nine RCTs, one quasiexperimental trial, and five secondary analyses from RCTs in the 2012 PCO on providing palliative care services to patients with cancer and/or their caregivers, including family caregivers, were found to inform the update. Recommendations Inpatients and outpatients with advanced cancer should receive dedicated palliative care services, early in the disease course, concurrent with active treatment. Referral of patients to interdisciplinary palliative care teams is optimal, and services may complement existing programs. Providers may refer family and friend caregivers of patients with early or advanced cancer to palliative care services.\n\nIndexed on Europe PMC as PubMed record 28034065 (DOI 10.1200/jco.2016.70.1474). Matched by DOI alone: one bottleneck page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2017","url":"https://doi.org/10.1200/jco.2016.70.1474"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28034065/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28034065"}],"tags":["europepmc-ingest"],"related":["b-palliative"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2017,"doi":"10.1200/jco.2016.70.1474","pmid":"28034065","authors":"Ferrell BR, Temel JS, Temin S, et al.","paperType":"review","findings":[],"whatItMeans":"One bottleneck page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-mlecnik-immunoscore-msi-colorectal-immunity-2016","kind":"paper","name":"Integrative analyses of colorectal cancer show Immunoscore is a stronger predictor of patient survival than microsatellite instability","aka":[],"tldr":"Mismatch repair deficient bowel cancers do better partly because they are full of immune cells. When the immune cells are counted directly, the count predicts outcome better than the repair status does.","summary":"Significant differences in mutational patterns, chromosomal instability and gene expression were found that correlated with microsatellite instability status. A prominent immune gene expression programme was observed in microsatellite-unstable tumours and in a subgroup of microsatellite-stable tumours. Unstable tumours had increased frameshift mutations, genetic evidence of immunoediting, higher densities of T-helper-1, effector-memory and in situ proliferating T cells and of inhibitory PD-1 and PD-L1 cells, high Immunoscores, and infiltration with mutation-specific cytotoxic T cells. In multivariate analysis, Immunoscore was superior to microsatellite instability in predicting disease-specific recurrence and survival.","asOf":"2026-09-24","links":[{"label":"Mlecnik et al., Immunity 2016: Immunoscore is a stronger predictor of survival than microsatellite instability","url":"https://doi.org/10.1016/j.immuni.2016.02.025"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26982367/"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["histopathology-ihc"],"targets":["pd1","mmr"],"drugs":[],"companies":[],"institutions":["institut-curie"],"pathways":["cancer-immunity-cycle","antigen-presentation-immunoediting","tumor-microenvironment"],"terms":["msi","neoantigen","ihc"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Immunity","year":2016,"doi":"10.1016/j.immuni.2016.02.025","pmid":"26982367","authors":"Mlecnik B, Bindea G, Angell HK, et al.","paperType":"translational","findings":["A prominent immune expression programme in unstable tumours and in a subgroup of stable tumours.","Genetic evidence of immunoediting in unstable tumours, with mutation-specific cytotoxic T cells.","Immunoscore outperformed microsatellite instability for disease-specific recurrence and survival."],"whatItMeans":"It explains the good prognosis of mismatch repair deficient disease as an immune effect rather than a repair effect, and identifies the microsatellite-stable tumours with an immune programme as the group worth trying immunotherapy in.","caveats":["Retrospective cohorts.","Immunoscore requires standardised digital pathology and is not universally available.","Prognostic, not predictive of response to a checkpoint inhibitor."],"changedPractice":false},{"id":"paper-taylor-integrative-genomic-profiling-cancer-cell-2010","kind":"paper","name":"Integrative genomic profiling of human prostate cancer","aka":["Taylor 2010","MSKCC prostate genomics 218 tumours"],"tldr":"The first large look at prostate cancer across copy number, gene expression and sequence at once. Its most useful finding for patients was that the pattern of gained and lost chromosome segments separates low-risk from high-risk disease better than the Gleason score does.","summary":"Barry Taylor, Charles Sawyers, William Gerald and colleagues at Memorial Sloan Kettering assessed DNA copy number, messenger RNA expression and focused exon resequencing concordantly in 218 prostate tumours, and released the genomic and clinical outcome data as a public resource.\n\nTwo results stand out. NCOA2, a nuclear receptor coactivator, behaved as an oncogene in around 11 percent of tumours, extending the androgen receptor pathway beyond the receptor itself. And copy-number alterations in primary tumours defined clusters of low-risk and high-risk disease beyond what the Gleason score achieved, which is the intellectual origin of the commercial genomic classifiers now used to decide who needs radical treatment.","asOf":"2026-09-25","links":[{"label":"Cancer Cell 2010","url":"https://doi.org/10.1016/j.ccr.2010.05.026"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20579941/"}],"tags":["prostate-evidence"],"related":["paper-tomlins-tmprss2-ets-fusion-science-2005","paper-grasso-mutational-landscape-lethal-crpc-nature-2012","paper-esteva-npj-digit-med","prostate-roadmap"],"cancers":["prostate","prostate-high-risk"],"sections":["diagnostics","ai-computation"],"technologies":["cgp"],"targets":["erg","tmprss2","androgen-receptor","ncoa2"],"drugs":[],"companies":[],"institutions":["mskcc"],"pathways":["ar-signaling","chromosomal-instability","prostate-cancer-signalling"],"terms":["gleason-grade-group","ngs","copy-number-variation-term","gene-fusion"],"trials":[],"people":["charles-sawyers"],"bottlenecks":["b-biomarker-validation","b-data-silos","b-tumor-heterogeneity"],"keyPapers":[],"journals":["cancer-cell"],"dependsOn":[],"notes":[],"journal":"Cancer Cell","year":2010,"doi":"10.1016/j.ccr.2010.05.026","pmid":"20579941","authors":"Taylor BS, Schultz N, Hieronymus H, et al.","paperType":"basic","findings":["Concordant DNA copy number, messenger RNA expression and focused exon resequencing in 218 prostate cancer tumours.","The nuclear receptor coactivator NCOA2 was identified as an oncogene in approximately 11 percent of tumours.","The androgen-driven TMPRSS2-ERG fusion was associated with a previously unrecognised prostate-specific deletion at chromosome 3p14, implicating FOXP1, RYBP and SHQ1 as potential cooperative tumour suppressors.","Copy-number data from primary tumours defined clusters of low-risk and high-risk disease beyond that achieved by Gleason score.","The genomic and clinical outcome data were released as a public resource."],"whatItMeans":"The origin of the idea that a prostate tumour's copy-number pattern carries prognostic information the pathologist's grade does not. That idea became Decipher and the other genomic classifiers, which are now used in some systems to decide whether a man needs radiotherapy after surgery.","caveats":["218 tumours, largely from one institution, with the referral pattern that implies.","Prognostic clustering derived and tested in the same cohort needs independent validation, which the commercial classifiers later supplied for their own signatures rather than for this one.","Focused exon resequencing rather than whole-exome, so the mutational picture is partial; Grasso and Baca filled it in."],"changedPractice":false,"participants":218},{"id":"paper-mao-j-clin-oncol","kind":"paper","name":"Integrative Medicine for Pain Management in Oncology: Society for Integrative Oncology-ASCO Guideline","aka":[],"tldr":"Paper cited by eight technology pages, indexed on Europe PMC as PubMed record 36122322 and published in Journal of Clinical Oncology; the citing pages link this DOI, which is how the record was matched.","summary":"Purpose: The aim of this joint guideline is to provide evidence-based recommendations to practicing physicians and other health care providers on integrative approaches to managing pain in patients with cancer.\n\nMethods: The Society for Integrative Oncology and ASCO convened an expert panel of integrative oncology, medical oncology, radiation oncology, surgical oncology, palliative oncology, social sciences, mind-body medicine, nursing, and patient advocacy representatives. The literature search included systematic reviews, meta-analyses, and randomized controlled trials published from 1990 through 2021. Outcomes of interest included pain intensity, symptom relief, and adverse events. Expert panel members used this evidence and informal consensus to develop evidence-based guideline recommendations.\n\nResults: The literature search identified 227 relevant studies to inform the evidence base for this guideline.\n\nRecommendations: Among adult patients, acupuncture should be recommended for aromatase inhibitor-related joint pain. Acupuncture or reflexology or acupressure may be recommended for general cancer pain or musculoskeletal pain. Hypnosis may be recommended to patients who experience procedural pain. Massage may be recommended to patients experiencing pain during palliative or hospice care. These recommendations are based on an intermediate level of evidence, benefit outweighing risk, and with moderate strength of recommendation. The quality of evidence for other mind-body interventions or natural products for pain is either low or inconclusive. There is insufficient or inconclusive evidence to make recommendations for pediatric patients. More research is needed to better characterize the role of integrative medicine interventions in the care of patients with cancer.Additional information is available at https://integrativeonc.org/practice-guidelines/guidelines and www.asco.org/survivorship-guidelines.\n\nIndexed on Europe PMC as PubMed record 36122322 (DOI 10.1200/jco.22.01357). Matched by DOI alone: eight technology pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2022","url":"https://doi.org/10.1200/jco.22.01357"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36122322/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36122322"}],"tags":["europepmc-ingest"],"related":["acupuncture-aromatase-inhibitor-arthralgia","acupuncture-chemotherapy-neuropathy","hypnosis-cancer-care","integrative-oncology","frozen-gloves-compression-taxane","massage-therapy-cancer","reflexology-cancer","relaxation-guided-imagery"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2022,"doi":"10.1200/jco.22.01357","pmid":"36122322","authors":"Mao JJ, Ismaila N, Bao T, et al.","paperType":"guideline","findings":[],"whatItMeans":"Eight technology pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nepal-gallbladder-microenvironment-subtypes-j-hepatol-2021","kind":"paper","name":"Integrative molecular characterisation of gallbladder cancer reveals micro-environment-associated subtypes","aka":[],"tldr":"A 190-patient study found gallbladder cancer has a low mutation rate by exome standards, evidence of aflatoxin exposure in some tumours, and three gene-expression subtypes whose survival differences track the immune and stromal surroundings rather than the mutations.","summary":"The mutational landscape of gallbladder cancer was profiled by whole-exome sequencing in 92 and targeted sequencing in 98 patients (190 in total), with matched transcriptomes, DNA methylomes and somatic copy-number alterations in a subset of 45. TP53 was the most mutated gene and the overall mutation rate was low (median 0.82 mutations per megabase). APOBEC-mediated mutational signatures were more common in tumours with higher mutational burden, and aflatoxin-related signatures tended to be highly clonal.\n\nA 95-gene signature stratified patients into three subtypes associated with overall survival after resection. The two poor-survival subtypes were associated with advanced stage, nodal and distant metastasis, immunosuppressive microenvironments (myeloid-derived suppressor cell accumulation, extensive desmoplasia, hypoxia) and T-cell dysfunction, whereas the good-survival subtype showed the opposite features.","asOf":"2026-09-24","links":[{"label":"Nepal et al., J Hepatol 2021: integrative molecular characterisation of 190 gallbladder cancers","url":"https://doi.org/10.1016/j.jhep.2020.11.033"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33276026/"}],"tags":[],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":["tp53"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tmb","mutational-signature","tils"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of Hepatology","year":2021,"doi":"10.1016/j.jhep.2020.11.033","pmid":"33276026","authors":"Nepal C, Zhu B, O'Rourke CJ, et al.","paperType":"translational","findings":["Median tumour mutational burden 0.82 mutations per megabase by exome; TP53 the most mutated gene.","APOBEC signatures tracked higher mutation burden; aflatoxin signatures were highly clonal.","Three transcriptomic subtypes; the two poor-survival subtypes showed myeloid suppressor cells, desmoplasia, hypoxia and T-cell dysfunction."],"whatItMeans":"The exome-level TMB here (0.82 per megabase) is an order of magnitude below panel estimates, a warning against comparing TMB across assays; and the survival signal sits in the microenvironment, which is where immunotherapy biomarkers for this disease may have to be found.","caveats":["Subtypes were derived from 47 tumours and validated on 34 public cases.","Aflatoxin attribution rests on mutational signature analysis."],"changedPractice":false,"participants":190},{"id":"paper-carlson-j-clin-oncol","kind":"paper","name":"Integrative Oncology Care of Symptoms of Anxiety and Depression in Adults With Cancer: Society for Integrative Oncology-ASCO Guideline","aka":[],"tldr":"Paper cited by six technology pages, indexed on Europe PMC as PubMed record 37582238 and published in Journal of Clinical Oncology; the citing pages link this DOI, which is how the record was matched.","summary":"Purpose: To provide evidence-based recommendations to health care providers on integrative approaches to managing anxiety and depression symptoms in adults living with cancer.\n\nMethods: The Society for Integrative Oncology and ASCO convened an expert panel of integrative oncology, medical oncology, radiation oncology, surgical oncology, palliative oncology, social sciences, mind-body medicine, nursing, methodology, and patient advocacy representatives. The literature search included systematic reviews, meta-analyses, and randomized controlled trials published from 1990 through 2023. Outcomes of interest included anxiety or depression symptoms as measured by validated psychometric tools, and adverse events. Expert panel members used this evidence and informal consensus with the Guidelines into Decision Support methodology to develop evidence-based guideline recommendations.\n\nResults: The literature search identified 110 relevant studies (30 systematic reviews and 80 randomized controlled trials) to inform the evidence base for this guideline.\n\nRecommendations: Recommendations were made for mindfulness-based interventions (MBIs), yoga, relaxation, music therapy, reflexology, and aromatherapy (using inhalation) for treating symptoms of anxiety during active treatment; and MBIs, yoga, acupuncture, tai chi and/or qigong, and reflexology for treating anxiety symptoms after cancer treatment. For depression symptoms, MBIs, yoga, music therapy, relaxation, and reflexology were recommended during treatment, and MBIs, yoga, and tai chi and/or qigong were recommended post-treatment.\n\nDiscussion: Issues of patient-health care provider communication, health disparities, comorbid medical conditions, cost implications, guideline implementation, provider training and credentialing, and quality assurance of natural health products are discussed. While several approaches such as MBIs and yoga appear effective, limitations of the evidence base including assessment of risk of bias, nonstandardization of therapies, lack of diversity in study samples, and lack of active control conditions as well as future research directions are discussed.Additional information is available at www.asco.org/survivorship-guidelines.\n\nIndexed on Europe PMC as PubMed record 37582238 (DOI 10.1200/jco.23.00857). Matched by DOI alone: six technology pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2023","url":"https://doi.org/10.1200/jco.23.00857"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37582238/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37582238"}],"tags":["europepmc-ingest"],"related":["cbt-fatigue-distress","mindfulness-based-interventions","music-therapy-cancer","peer-support-groups","relaxation-guided-imagery","yoga-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2023,"doi":"10.1200/jco.23.00857","pmid":"37582238","authors":"Carlson LE, Ismaila N, Addington EL, et al.","paperType":"review","findings":[],"whatItMeans":"Six technology pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-lyman-j-clin-oncol","kind":"paper","name":"Integrative Therapies During and After Breast Cancer Treatment: ASCO Endorsement of the SIO Clinical Practice Guideline","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 29889605 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose The Society for Integrative Oncology (SIO) produced an evidence-based guideline on use of integrative therapies during and after breast cancer treatment that was determined to be relevant to the American Society of Clinical Oncology (ASCO) membership. ASCO considered the guideline for endorsement. Methods The SIO guideline addressed the use of integrative therapies for the management of symptoms and adverse effects, such as anxiety and stress, mood disorders, fatigue, quality of life, chemotherapy-induced nausea and vomiting, lymphedema, chemotherapy-induced peripheral neuropathy, pain, and sleep disturbance. Interventions of interest included mind and body practices, natural products, and lifestyle modifications. SIO systematic reviews focused on randomized controlled trials that were published from 1990 through 2015. The SIO guideline was reviewed by ASCO content experts for clinical accuracy and by ASCO methodologists for developmental rigor. On favorable review, an ASCO Expert Panel was convened to review the guideline contents and recommendations. Results The ASCO Expert Panel determined that the recommendations in the SIO guideline-published in 2017-are clear, thorough, and based on the most relevant scientific evidence. ASCO endorsed the guideline with a few added discussion points. Recommendations Key recommendations include the following: Music therapy, meditation, stress management, and yoga are recommended for anxiety/stress reduction. Meditation, relaxation, yoga, massage, and music therapy are recommended for depression/mood disorders. Meditation and yoga are recommended to improve quality of life. Acupressure and acupuncture are recommended for reducing chemotherapy-induced nausea and vomiting. Acetyl-l-carnitine is not recommended to prevent chemotherapy-induced peripheral neuropathy because of a possibility of harm. No strong evidence supports the use of ingested dietary supplements to manage breast cancer treatment-related adverse effects. Additional information is available at: www.asco.org/supportive-care-guidelines.\n\nIndexed on Europe PMC as PubMed record 29889605 (DOI 10.1200/jco.2018.79.2721). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2018","url":"https://doi.org/10.1200/jco.2018.79.2721"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29889605/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29889605"}],"tags":["europepmc-ingest"],"related":["acupuncture-nausea"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2018,"doi":"10.1200/jco.2018.79.2721","pmid":"29889605","authors":"Lyman GH, Greenlee H, Bohlke K, et al.","paperType":"guideline","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-froeling-pstt-ett-intensified-therapy-bjc-2019","kind":"paper","name":"Intensified therapies improve survival and identification of novel prognostic factors for placental-site and epithelioid trophoblastic tumours","aka":[],"tldr":"An updated UK series of placental-site and epithelioid trophoblastic tumours found that more intensive treatment, including high-dose chemotherapy for the worst-prognosis women, improved survival, and refined the factors that predict outcome.","summary":"Retrospective analysis of 125 women with placental-site or epithelioid trophoblastic tumour treated in the UK trophoblastic disease centres, extending the earlier Charing Cross series.\n\nSurvival improved in the later period with intensified platinum-based chemotherapy and, for women with an interval of 48 months or more since the antecedent pregnancy, high-dose chemotherapy with stem cell rescue; stage, interval and other factors such as hCG level and metastatic pattern were prognostic.","asOf":"2026-09-18","links":[{"label":"Br J Cancer 2019","url":"https://doi.org/10.1038/s41416-019-0402-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30792530/"}],"tags":[],"related":[],"cancers":["placental-site-trophoblastic-tumour"],"sections":[],"technologies":[],"targets":[],"drugs":["etoposide","cisplatin","paclitaxel"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["british-journal-of-cancer"],"dependsOn":[],"notes":[],"journal":"British Journal of Cancer","year":2019,"doi":"10.1038/s41416-019-0402-0","pmid":"30792530","authors":"Froeling FEM, Ramaswami R, Papanastasopoulos P, et al.","paperType":"observational","findings":["Survival improved in the more recent treatment era with intensified therapy.","Interval of 48 months or more from the antecedent pregnancy remained the dominant adverse factor, with high-dose chemotherapy offering some long-term survivors."],"whatItMeans":"Women with poor-prognosis placental-site or epithelioid trophoblastic tumours should be referred to a specialist centre where intensified and experimental treatments, including immunotherapy, are available.","caveats":["Retrospective, with treatment changing over time.","Small numbers in the high-dose chemotherapy group."],"changedPractice":true,"participants":125},{"id":"paper-pace-b-lancet-oncol-2019","kind":"paper","name":"Intensity-modulated fractionated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): acute toxicity findings from an international, randomised, open-label, phase 3, non-inferiority trial","aka":[],"tldr":"Published report from the PACE-B trial registered as NCT01584258, in The Lancet Oncology (2019), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Localised prostate cancer is commonly treated with external-beam radiotherapy. Moderate hypofractionation has been shown to be non-inferior to conventional fractionation. Ultra-hypofractionated stereotactic body radiotherapy would allow shorter treatment courses but could increase acute toxicity compared with conventionally fractionated or moderately hypofractionated radiotherapy. We report the acute toxicity findings from a randomised trial of standard-of-care conventionally fractionated or moderately hypofractionated radiotherapy versus five-fraction stereotactic body radiotherapy for low-risk to intermediate-risk localised prostate cancer.\n\nMethods: PACE is an international, phase 3, open-label, randomised, non-inferiority trial. In PACE-B, eligible men aged 18 years and older, with WHO performance status 0-2, low-risk or intermediate-risk prostate adenocarcinoma (Gleason 4 + 3 excluded), and scheduled to receive radiotherapy were recruited from 37 centres in three countries (UK, Ireland, and Canada). Participants were randomly allocated (1:1) by computerised central randomisation with permuted blocks (size four and six), stratified by centre and risk group, to conventionally fractionated or moderately hypofractionated radiotherapy (78 Gy in 39 fractions over 7·8 weeks or 62 Gy in 20 fractions over 4 weeks, respectively) or stereotactic body radiotherapy (36·25 Gy in five fractions over 1-2 weeks). Neither participants nor investigators were masked to allocation. Androgen deprivation was not permitted. The primary endpoint of PACE-B is freedom from biochemical or clinical failure. The coprimary outcomes for this acute toxicity substudy were worst grade 2 or more severe Radiation Therapy Oncology Group (RTOG) gastrointestinal or genitourinary toxic effects score up to 12 weeks after radiotherapy. Analysis was per protocol. This study is registered with ClinicalTrials.gov, NCT01584258. PACE-B recruitment is complete and follow-up is ongoing.\n\nFindings: Between Aug 7, 2012, and Jan 4, 2018, we randomly assigned 874 men to conventionally fractionated or moderately hypofractionated radiotherapy (n=441) or stereotactic body radiotherapy (n=433). 432 (98%) of 441 patients allocated to conventionally fractionated or moderately hypofractionated radiotherapy and 415 (96%) of 433 patients allocated to stereotactic body radiotherapy received at least one fraction of allocated treatment. Worst acute RTOG gastrointestinal toxic effect proportions were as follows: grade 2 or more severe toxic events in 53 (12%) of 432 patients in the conventionally fractionated or moderately hypofractionated radiotherapy group versus 43 (10%) of 415 patients in the stereotactic body radiotherapy group (difference -1·9 percentage points, 95% CI -6·2 to 2·4; p=0·38). Worst acute RTOG genitourinary toxicity proportions were as follows: grade 2 or worse toxicity in 118 (27%) of 432 patients in the conventionally fractionated or moderately hypofractionated radiotherapy group versus 96 (23%) of 415 patients in the stereotactic body radiotherapy group (difference -4·2 percentage points, 95% CI -10·0 to 1·7; p=0·16). No treatment-related deaths occurred.\n\nInterpretation: Previous evidence (from the HYPO-RT-PC trial) suggested higher patient-reported toxicity with ultrahypofractionation. By contrast, our results suggest that substantially shortening treatment courses with stereotactic body radiotherapy does not increase either gastrointestinal or genitourinary acute toxicity.\n\nFunding: Accuray and National Institute of Health Research.\n\nIndexed on Europe PMC as PubMed record 31540791 (DOI 10.1016/s1470-2045(19)30569-8). Its abstract cites the registry id NCT01584258, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2019","url":"https://doi.org/10.1016/s1470-2045(19)30569-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31540791/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31540791"},{"label":"ClinicalTrials.gov NCT01584258","url":"https://clinicaltrials.gov/study/NCT01584258"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["pace-b"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2019,"doi":"10.1016/s1470-2045(19)30569-8","pmid":"31540791","authors":"Brand DH, Tree AC, Ostler P, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT01584258 with the most citations, so it is the natural first reading for anyone following the PACE-B trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-pace-b-lancet-oncol-2022-update","kind":"paper","name":"Intensity-modulated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): 2-year toxicity results from an open-label, randomised, phase 3, non-inferiority trial","aka":[],"tldr":"Later report from the PACE-B trial registered as NCT01584258, in The Lancet Oncology (2022); its title describes an updated or longer-term analysis.","summary":"Background: Localised prostate cancer is commonly treated with external beam radiotherapy and moderate hypofractionation is non-inferior to longer schedules. Stereotactic body radiotherapy (SBRT) allows shorter treatment courses without impacting acute toxicity. We report 2-year toxicity findings from PACE-B, a randomised trial of conventionally fractionated or moderately hypofractionated radiotherapy versus SBRT.\n\nMethods: PACE is an open-label, multicohort, randomised, controlled, phase 3 trial conducted at 35 hospitals in the UK, Ireland, and Canada. In PACE-B, men aged 18 years and older with a WHO performance status 0-2 and low-risk or intermediate-risk histologically-confirmed prostate adenocarcinoma (Gleason 4 + 3 excluded) were randomly allocated (1:1) by computerised central randomisation with permuted blocks (size four and six), stratified by centre and risk group to control radiotherapy (CRT; 78 Gy in 39 fractions over 7·8 weeks or, following protocol amendment on March 24, 2016, 62 Gy in 20 fractions over 4 weeks) or SBRT (36·25 Gy in five fractions over 1-2 weeks). Androgen deprivation was not permitted. Co-primary outcomes for this toxicity analysis were Radiation Therapy Oncology Group (RTOG) grade 2 or worse gastrointestinal and genitourinary toxicity at 24 months after radiotherapy. Analysis was by treatment received and included all patients with at least one fraction of study treatment assessed for late toxicity. Recruitment is complete. Follow-up for oncological outcomes continues. The trial is registered with ClinicalTrials.gov, NCT01584258.\n\nFindings: We enrolled and randomly assigned 874 men between Aug 7, 2012, and Jan 4, 2018 (441 to CRT and 433 to SBRT). In this analysis, 430 patients were analysed in the CRT group and 414 in the SBRT group; a total of 844 (97%) of 874 randomly assigned patients. At 24 months, RTOG grade 2 or worse genitourinary toxicity was seen in eight (2%) of 381 participants assigned to CRT and 13 (3%) of 384 participants assigned to SBRT (absolute difference 1·3% [95% CI -1·3 to 4·0]; p=0·39); RTOG grade 2 or worse gastrointestinal toxicity was seen in 11 (3%) of 382 participants in the CRT group versus six (2%) of 384 participants in the SBRT group (absolute difference -1·3% [95% CI -3·9 to 1·1]; p=0·32). No serious adverse events (defined as RTOG grade 4 or worse) or treatment-related deaths were reported within the analysis timeframe.\n\nInterpretation: In the PACE-B trial, 2-year RTOG toxicity rates were similar for five fraction SBRT and conventional schedules of radiotherapy. Prostate SBRT was found to be safe and associated with low rates of side-effects. Biochemical outcomes are awaited.\n\nFunding: Accuray.\n\nIndexed on Europe PMC as PubMed record 36113498 (DOI 10.1016/s1470-2045(22)00517-4). Its abstract cites the registry id NCT01584258, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2022","url":"https://doi.org/10.1016/s1470-2045(22)00517-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36113498/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36113498"},{"label":"ClinicalTrials.gov NCT01584258","url":"https://clinicaltrials.gov/study/NCT01584258"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["pace-b"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2022,"doi":"10.1016/s1470-2045(22)00517-4","pmid":"36113498","authors":"Tree AC, Ostler P, van der Voet H, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the PACE-B trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-interaact-carboplatin-paclitaxel-advanced-anal-cancer-rao-jco-2020","kind":"paper","name":"InterAACT: cisplatin and fluorouracil versus carboplatin and paclitaxel in advanced anal cancer","aka":[],"tldr":"In the first randomised trial in advanced anal cancer, carboplatin with paclitaxel shrank tumours as often as cisplatin with fluorouracil but caused far fewer serious side effects and was followed by longer survival, so it became the standard chemotherapy.","summary":"International Rare Cancers Initiative randomised phase 2 trial in 60 centres: 91 patients with chemotherapy-naive inoperable locally recurrent or metastatic anal squamous cell carcinoma were randomised to cisplatin plus fluorouracil (46) or carboplatin plus weekly paclitaxel (45). The primary endpoint was best overall response rate by 24 weeks.\n\nResponse rates were 57 and 59 percent. Serious adverse events were more frequent with cisplatin-fluorouracil (62 against 36 percent). Median progression-free survival was 5.7 against 8.1 months and median overall survival 12.3 against 20 months (hazard ratio 2.00, p 0.014).","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2020","url":"https://doi.org/10.1200/JCO.19.03266"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32530769/"}],"tags":[],"related":[],"cancers":["metastatic-anal-cancer","anal"],"sections":[],"technologies":[],"targets":[],"drugs":["carboplatin","paclitaxel","cisplatin","fluorouracil"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["interaact"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/JCO.19.03266","pmid":"32530769","authors":"Rao S, Sclafani F, Eng C, et al.","paperType":"rct","findings":["Objective response 57 percent (95% CI 39.4 to 73.7) with cisplatin-fluorouracil versus 59 percent (42.1 to 74.4) with carboplatin-paclitaxel.","Serious adverse events 62 versus 36 percent (p 0.016).","Median overall survival 12.3 versus 20 months; hazard ratio 2.00 (1.15 to 3.47), p 0.014."],"whatItMeans":"Carboplatin plus weekly paclitaxel is the chemotherapy backbone for advanced anal cancer and the base on which retifanlimab was added in POD1UM-303.","caveats":["Phase 2 with 91 patients; the survival difference was a secondary finding."],"changedPractice":true,"participants":91},{"id":"paper-interfant-06-pieters-jco-2019","kind":"paper","name":"Interfant-06: outcome of infants under one year with acute lymphoblastic leukaemia","aka":[],"tldr":"This international trial of infant leukaemia found no benefit from adding myeloid-style chemotherapy courses, and confirmed that KMT2A-rearranged infants remain a high-risk group with survival under 50 percent, setting the baseline that blinatumomab has since improved.","summary":"International trial of 651 infants with ALL treated on the Interfant backbone, with 240 medium- and high-risk KMT2A-rearranged infants randomised to standard lymphoid-style consolidation or myeloid-style (ADE and MAE) courses; allogeneic transplant was indicated for high-risk patients.\n\nSix-year event-free survival was 46.1 percent overall; there was no difference between consolidation arms (39.3 versus 37.2 percent), and KMT2A-rearranged infants had 36 percent event-free survival against 74 percent for germline KMT2A.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2019","url":"https://doi.org/10.1200/JCO.19.00261"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31283407/"}],"tags":[],"related":[],"cancers":["all-infant"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["interfant-06"],"people":["rob-pieters"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2019,"doi":"10.1200/JCO.19.00261","pmid":"31283407","authors":"Pieters R, De Lorenzo P, Ancliffe P, et al.","paperType":"rct","findings":["Six-year event-free survival 46.1 percent overall; 36 percent for KMT2A-rearranged infants.","No benefit from myeloid-style consolidation (39.3 percent vs 37.2 percent)."],"whatItMeans":"Interfant-06 is the backbone and control benchmark for infant ALL; the successor Interfant-21 adds blinatumomab after this trial showed chemotherapy intensification had reached its limit.","caveats":["Toxicity-related deaths remained substantial in infants."],"changedPractice":true,"participants":651},{"id":"paper-interfant-99-lancet-2007","kind":"paper","name":"Interfant-99: a treatment protocol for infants under one year with acute lymphoblastic leukaemia","aka":[],"tldr":"The first international infant leukaemia trial established a hybrid chemotherapy backbone and showed that a late intensification course did not help, while identifying age under six months, KMT2A rearrangement and poor steroid response as the key risk factors.","summary":"International observational study and randomised trial of 482 infants with ALL treated with a hybrid protocol including elements of ALL and AML therapy, with randomisation to a late intensification course or not.\n\nFour-year event-free survival was 47 percent overall with no benefit from late intensification; KMT2A rearrangement, age under six months, high white count and poor prednisone response defined high-risk infants with event-free survival around 20 percent.","asOf":"2026-09-17","links":[{"label":"Lancet 2007","url":"https://doi.org/10.1016/S0140-6736(07)61126-X"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/17658395/"}],"tags":[],"related":[],"cancers":["all-infant"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["rob-pieters"],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2007,"doi":"10.1016/S0140-6736(07)61126-X","pmid":"17658395","authors":"Pieters R, Schrappe M, De Lorenzo P, et al.","paperType":"rct","findings":["Four-year event-free survival 47 percent overall.","No benefit from late intensification (hazard ratio 1.07)."],"whatItMeans":"Interfant-99 defined the risk groups and backbone used in Interfant-06 and Interfant-21.","caveats":["Outcomes remained poor for high-risk infants, motivating later immunotherapy."],"changedPractice":true,"participants":482},{"id":"paper-intergroup-0099-chemoradiotherapy-nasopharyngeal-jco-1998","kind":"paper","name":"Intergroup 0099: chemoradiotherapy versus radiotherapy in advanced nasopharyngeal cancer","aka":[],"tldr":"Adding cisplatin during radiotherapy and chemotherapy afterwards more than doubled the chance of being alive without disease three years later compared with radiotherapy alone, making chemoradiotherapy the standard for advanced nasopharyngeal cancer.","summary":"US Intergroup randomised phase 3 trial of patients with stage III to IV nasopharyngeal carcinoma comparing radiotherapy alone with radiotherapy plus concurrent cisplatin followed by three cycles of adjuvant cisplatin and fluorouracil; 147 patients were analysed after early closure for efficacy.\n\nThree-year progression-free survival was 69 percent with chemoradiotherapy against 24 percent with radiotherapy, and overall survival 76 percent against 46 percent. The result established concurrent cisplatin with radiotherapy as the backbone of treatment worldwide.","asOf":"2026-09-18","links":[{"label":"J Clin Oncol 1998","url":"https://doi.org/10.1200/JCO.1998.16.4.1310"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/9552031/"}],"tags":[],"related":[],"cancers":["locoregionally-advanced-nasopharyngeal-carcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":["cisplatin","fluorouracil"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":1998,"doi":"10.1200/JCO.1998.16.4.1310","pmid":"9552031","authors":"Al-Sarraf M, LeBlanc M, Giri PG, et al.","paperType":"rct","findings":["Three-year progression-free survival 69 percent with chemoradiotherapy versus 24 percent with radiotherapy alone.","Three-year overall survival 76 percent versus 46 percent."],"whatItMeans":"Concurrent cisplatin with radiotherapy is the foundation of treatment for locoregionally advanced nasopharyngeal carcinoma; later trials in endemic regions refined the role of induction and adjuvant chemotherapy.","caveats":["Conducted in a non-endemic population with a high proportion of keratinising tumours and an unusually poor radiotherapy-alone arm.","Two-dimensional radiotherapy; the contribution of the adjuvant chemotherapy component has been questioned."],"changedPractice":true,"participants":147},{"id":"paper-brentuximab-vedotin-hodgkin-lymphoma-blood-2018","kind":"paper","name":"Interim results of brentuximab vedotin in combination with nivolumab in patients with relapsed or refractory Hodgkin lymphoma","aka":[],"tldr":"Phase 2 or 3 results paper on Brentuximab vedotin in Hodgkin lymphoma, in Blood (2018), one of the most cited Europe PMC records with Brentuximab vedotin in its title.","summary":"In this phase 1/2 study, brentuximab vedotin (BV) and nivolumab (Nivo) administered in combination were evaluated as initial salvage therapy in patients with relapsed or refractory (R/R) classical Hodgkin lymphoma (HL). Patients received up to 4 cycles of combination treatment, with BV administered on day 1 and Nivo on day 8 of the first cycle. For cycles 2 to 4, BV and Nivo were both administered on day 1. After study treatment, responses were evaluated by investigators per the 2014 Lugano classification, and patients could proceed to autologous stem cell transplantation (ASCT). Sixty-two patients were enrolled; the complete response rate among all treated patients (n = 61) was 61%, with an objective response rate of 82%. Before ASCT, adverse events (AEs) occurred in 98% of patients, mostly grades 1 and 2. Infusion-related reactions (IRRs) occurred in 44% of patients overall, with 41% of patients experiencing an IRR during at least 1 infusion of BV. Five patients (8%) were treated with systemic steroids for immune-related AEs. A reduction of peripheral T-cell subsets including regulatory T cells was observed after the first dose of BV, and reduced serum levels of thymus- and activation-regulated chemokine concurrent with an increase in proinflammatory cytokines and chemokines were seen after the first BV plus Nivo infusions. The combination of BV plus Nivo was an active and well-tolerated first salvage regimen, potentially providing patients with R/R HL an alternative to traditional chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT02572167.\n\nIndexed on Europe PMC as PubMed record 29229594 (DOI 10.1182/blood-2017-10-811224). Its title names Brentuximab vedotin and its text names Hodgkin lymphoma; PubMed types it as a clinical trial report (Clinical Trial, Phase II, Research Support, Non-U.S. Gov't, research-article, Multicenter Study, Clinical Trial, Phase I, Research Support, N.I.H., Extramural). It was matched automatically to the idea \"Chemotherapy-free Hodgkin lymphoma: brentuximab + PD-1 in early stage\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Blood 2018","url":"https://doi.org/10.1182/blood-2017-10-811224"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29229594/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29229594"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["blood"],"dependsOn":[],"notes":[],"journal":"Blood","year":2018,"doi":"10.1182/blood-2017-10-811224","pmid":"29229594","authors":"Herrera AF, Moskowitz AJ, Bartlett NL, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Brentuximab vedotin in Hodgkin lymphoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Brentuximab vedotin in the title and Hodgkin lymphoma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-gemstone-302-nat-cancer-2023-update","kind":"paper","name":"Interim survival analysis of the randomized phase III GEMSTONE-302 trial: sugemalimab or placebo plus chemotherapy as first-line treatment for metastatic NSCLC","aka":[],"tldr":"Later report from the GEMSTONE-302 trial registered as NCT03789604, in Nature Cancer (2023); its title describes an updated or longer-term analysis.","summary":"The randomized, double-blinded, multi-center, phase III GEMSTONE-302 ( NCT03789604) study evaluated the efficacy and safety of sugemalimab versus placebo in combination with chemotherapy as first-line treatment for metastatic non-small-cell lung cancer (NSCLC). In this study, 479 treatment-naive patients with stage IV squamous or non-squamous NSCLC without known EGFR sensitizing mutations, ALK, ROS1 or RET fusions were randomized (2:1) to receive 1,200 mg of sugemalimab (n = 320) or placebo (n = 159) every 3 weeks in combination with platinum-based chemotherapy for up to four cycles, followed by maintenance therapy with sugemalimab or placebo for squamous NSCLC and sugemalimab or placebo plus pemetrexed for non-squamous NSCLC. Placebo-treated patients could cross over to receive sugemalimab monotherapy on disease progression. The primary endpoint was investigator-assessed progression-free survival (PFS) and the secondary endpoints included overall survival (OS) and objective response rate. Sugemalimab plus chemotherapy has demonstrated significant PFS prolongation in the primary analysis as reported previously. at 22 November 2021, the prespecified interim OS analysis showed significant improvement with the addition of sugemalimab to chemotherapy (median OS = 25.4 versus 16.9 months; hazard ratio = 0.65; 95% confidence interval = 0.50-0.84; P = 0.0008). Sugemalimab plus chemotherapy provided superior PFS and OS compared to placebo plus chemotherapy, supporting the use of sugemalimab as a first-line treatment option for metastatic NSCLC.\n\nIndexed on Europe PMC as PubMed record 37322367 (DOI 10.1038/s43018-023-00578-z). Its abstract cites the registry id NCT03789604, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Nat Cancer 2023","url":"https://doi.org/10.1038/s43018-023-00578-z"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37322367/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37322367"},{"label":"ClinicalTrials.gov NCT03789604","url":"https://clinicaltrials.gov/study/NCT03789604"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["gemstone-302"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Cancer","year":2023,"doi":"10.1038/s43018-023-00578-z","pmid":"37322367","authors":"Zhou C, Wang Z, Sun M, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the GEMSTONE-302 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-interlace-lancet-2024","kind":"paper","name":"INTERLACE: induction chemotherapy before chemoradiotherapy for locally advanced cervical cancer","aka":[],"tldr":"Six weekly cycles of carboplatin and paclitaxel given immediately before standard chemoradiation improved survival in locally advanced cervical cancer by about eight percentage points at five years, using cheap widely available drugs.","summary":"Phase 3 trial of 500 women with locally advanced cervical cancer (stage IB1 node-positive to IVA) randomised to six weeks of induction carboplatin-paclitaxel followed by cisplatin chemoradiotherapy, or chemoradiotherapy alone.\n\nFive-year progression-free survival was 72 versus 64 percent (hazard ratio 0.65) and overall survival 80 versus 72 percent (hazard ratio 0.60), with more haematological toxicity during induction but no compromise of chemoradiation delivery.","asOf":"2026-09-17","links":[{"label":"Lancet 2024","url":"https://doi.org/10.1016/S0140-6736(24)01438-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39419054/"}],"tags":[],"related":[],"cancers":["locally-advanced-cervical-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["interlace"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2024,"doi":"10.1016/S0140-6736(24)01438-7","pmid":"39419054","authors":"McCormack M, Eminowicz G, Gallardo D, et al.","paperType":"rct","findings":["Five-year progression-free survival 72 percent vs 64 percent; hazard ratio 0.65.","Five-year overall survival 80 percent vs 72 percent; hazard ratio 0.60."],"whatItMeans":"Short induction chemotherapy is a standard option before chemoradiation, particularly where pembrolizumab is unaffordable, and can be delivered in most health systems.","caveats":["Most patients had stage IIB disease; fewer node-positive and stage III patients.","Whether induction adds to chemoradiation plus pembrolizumab is untested."],"changedPractice":true,"participants":500},{"id":"paper-eortc-22922-n-engl-j-med-2015","kind":"paper","name":"Internal Mammary and Medial Supraclavicular Irradiation in Breast Cancer","aka":[],"tldr":"Published report from the EORTC 22922 trial registered as NCT00002851, in New England Journal of Medicine (2015), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: The effect of internal mammary and medial supraclavicular lymph-node irradiation (regional nodal irradiation) added to whole-breast or thoracic-wall irradiation after surgery on survival among women with early-stage breast cancer is unknown.\n\nMethods: We randomly assigned women who had a centrally or medially located primary tumor, irrespective of axillary involvement, or an externally located tumor with axillary involvement to undergo either whole-breast or thoracic-wall irradiation in addition to regional nodal irradiation (nodal-irradiation group) or whole-breast or thoracic-wall irradiation alone (control group). The primary end point was overall survival. Secondary end points were the rates of disease-free survival, survival free from distant disease, and death from breast cancer.\n\nResults: Between 1996 and 2004, a total of 4004 patients underwent randomization. The majority of patients (76.1%) underwent breast-conserving surgery. After mastectomy, 73.4% of the patients in both groups underwent chest-wall irradiation. Nearly all patients with node-positive disease (99.0%) and 66.3% of patients with node-negative disease received adjuvant systemic treatment. At a median follow-up of 10.9 years, 811 patients had died. At 10 years, overall survival was 82.3% in the nodal-irradiation group and 80.7% in the control group (hazard ratio for death with nodal irradiation, 0.87; 95% confidence interval [CI], 0.76 to 1.00; P=0.06). The rate of disease-free survival was 72.1% in the nodal-irradiation group and 69.1% in the control group (hazard ratio for disease progression or death, 0.89; 95% CI, 0.80 to 1.00; P=0.04), the rate of distant disease-free survival was 78.0% versus 75.0% (hazard ratio, 0.86; 95% CI, 0.76 to 0.98; P=0.02), and breast-cancer mortality was 12.5% versus 14.4% (hazard ratio, 0.82; 95% CI, 0.70 to 0.97; P=0.02). Acute side effects of regional nodal irradiation were modest.\n\nConclusions: In patients with early-stage breast cancer, irradiation of the regional nodes had a marginal effect on overall survival. Disease-free survival and distant disease-free survival were improved, and breast-cancer mortality was reduced. (Funded by Fonds Cancer; ClinicalTrials.gov number, NCT00002851.).\n\nIndexed on Europe PMC as PubMed record 26200978 (DOI 10.1056/nejmoa1415369). Its abstract cites the registry id NCT00002851, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2015","url":"https://doi.org/10.1056/nejmoa1415369"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26200978/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26200978"},{"label":"ClinicalTrials.gov NCT00002851","url":"https://clinicaltrials.gov/study/NCT00002851"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["eortc-22922"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2015,"doi":"10.1056/nejmoa1415369","pmid":"26200978","authors":"Poortmans PM, Collette S, Kirkove C, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT00002851 with the most citations, so it is the natural first reading for anyone following the EORTC 22922 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-eortc-22922-lancet-oncol-2020-update","kind":"paper","name":"Internal mammary and medial supraclavicular lymph node chain irradiation in stage I-III breast cancer (EORTC 22922/10925): 15-year results of a randomised, phase 3 trial","aka":[],"tldr":"Later report from the EORTC 22922 trial registered as NCT00002851, in The Lancet Oncology (2020); its title describes an updated or longer-term analysis.","summary":"Background: 10-year results from several studies showed improved disease-free survival and distant metastasis-free survival, reduced breast cancer-related mortality, and variable effects on overall survival with the addition of partial or comprehensive regional lymph node irradiation after surgery in patients with breast cancer. We present the scheduled 15-year analysis of the European Organisation for Research and Treatment of Cancer (EORTC) 22922/10925 trial, which aims to investigate the impact on overall survival of elective internal mammary and medial supraclavicular (IM-MS) irradiation.\n\nMethods: EORTC 22922/10925, a randomised, phase 3 trial done across 46 radiation oncology departments from 13 countries, included women up to 75 years of age with unilateral, histologically confirmed, stage I-III breast adenocarcinoma with involved axillary nodes or a central or medially located primary tumour. Surgery consisted of mastectomy or breast-conserving surgery and axillary staging. Patients were randomly assigned (1:1) centrally using minimisation to receive IM-MS irradiation at 50 Gy in 25 fractions (IM-MS irradiation group) or no IM-MS irradiation (control group). Stratification was done for institution, menopausal status, site of the primary tumour within the breast, type of breast and axillary surgery, and pathological T and N stage. Patients and investigators were not masked to treatment allocation. The primary endpoint was overall survival analysed according to the intention-to-treat principle. Secondary endpoints were disease-free survival, distant metastasis-free survival, breast cancer mortality, any breast cancer recurrence, and cause of death. Follow-up is ongoing for 20 years after randomisation. This study is registered with ClinicalTrials.gov, NCT00002851.\n\nFindings: Between Aug 5, 1996, and Jan 13, 2004, we enrolled 4004 patients, of whom 2002 were randomly assigned to the IM-MS irradiation group and 2002 to the no IM-MS irradiation group. At a median follow-up of 15·7 years (IQR 14·0-17·6), 554 (27·7%) patients in the IM-MS irradiation group and 569 (28·4%) patients in the control group had died. Overall survival was 73·1% (95% CI 71·0-75·2) in the IM-MS irradiation group and 70·9% (68·6-72·9) in the control group (HR 0·95 [95% CI 0·84-1·06], p=0·36). Any breast cancer recurrence (24·5% [95% CI 22·5-26·6] vs 27·1% [25·1-29·2]; HR 0·87 [95% CI 0·77-0·98], p=0·024) and breast cancer mortality (16·0% [14·3-17·7] vs 19·8% [18·0-21·7]; 0·81 [0·70-0·94], p=0·0055) were lower in the IM-MS irradiation group than in the control group. No significant differences in the IM-MS irradiation group versus the control group were seen for disease-free survival (60·8% [95% CI 58·4-63·2] vs 59·9% [57·5-62·2]; HR 0·93 [95% CI 0·84-1·03], p=0·18), or distant metastasis-free survival (70·0% [67·7-72·2] vs 68·2% [65·9-70·3]; 0·93 [0·83-1·04], p=0·18). Causes of death between groups were similar.\n\nInterpretation: The 15-year results show a significant reduction of breast cancer mortality and any breast cancer recurrence by IM-MS irradiation in stage I-III breast cancer. However, this is not converted to improved overall survival.\n\nFunding: US National Cancer Institute, Ligue Nationale contre le Cancer, and KWF Kankerbestrijding.\n\nIndexed on Europe PMC as PubMed record 33152277 (DOI 10.1016/s1470-2045(20)30472-1). Its abstract cites the registry id NCT00002851, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2020","url":"https://doi.org/10.1016/s1470-2045(20)30472-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33152277/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33152277"},{"label":"ClinicalTrials.gov NCT00002851","url":"https://clinicaltrials.gov/study/NCT00002851"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["eortc-22922"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2020,"doi":"10.1016/s1470-2045(20)30472-1","pmid":"33152277","authors":"Poortmans PM, Weltens C, Fortpied C, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the EORTC 22922 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-ians-anal-cancer-screening-guidelines-ijc-2024","kind":"paper","name":"International Anal Neoplasia Society consensus guidelines for anal cancer screening","aka":[],"tldr":"The first international guideline on who should be screened for anal cancer and how, written after the ANCHOR trial showed that treating precancer prevents the disease.","summary":"Consensus guideline from the International Anal Neoplasia Society setting out the groups at highest risk of anal cancer and a screening pathway of anal cytology, high-risk HPV testing or both, followed by high-resolution anoscopy for abnormal results.\n\nScreening is recommended from age 35 for men who have sex with men and transgender women living with HIV, from 45 for other people living with HIV and for men who have sex with men and transgender women not living with HIV, and for solid organ transplant recipients and women with a history of vulvar HSIL or cancer, with thresholds for referral to anoscopy that depend on local capacity.","asOf":"2026-09-18","links":[{"label":"Int J Cancer 2024","url":"https://doi.org/10.1002/ijc.34850"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38297406/"}],"tags":[],"related":[],"cancers":["anal-hsil-precursor"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["international-journal-of-cancer"],"dependsOn":[],"notes":[],"journal":"International Journal of Cancer","year":2024,"doi":"10.1002/ijc.34850","pmid":"38297406","authors":"Stier EA, Clarke MA, Deshmukh AA, et al.","paperType":"guideline","findings":[],"whatItMeans":"For the first time clinicians have an agreed answer to who to screen for anal cancer and at what age, so that treatment of HSIL can reach the people most likely to benefit.","caveats":["High-resolution anoscopy is scarce outside specialist centres, and the guideline allows different referral thresholds where capacity is limited.","Evidence for screening people at high risk who do not have HIV is indirect."],"changedPractice":true},{"id":"paper-icc-2022-arber-blood-2022","kind":"paper","name":"International Consensus Classification of myeloid neoplasms and acute leukaemias (2022)","aka":[],"tldr":"A parallel classification to the WHO 2022 edition from an international expert group, which among other changes creates an MDS/AML category for 10 to 19 percent blasts and gives TP53-mutated disease its own entities.","summary":"Classification of myeloid neoplasms and acute leukaemias integrating morphology, clinical features and genomics, produced by the International Consensus Classification group, with new categories for MDS/AML, TP53-mutated myeloid neoplasms and genetically defined AML subtypes at lower blast thresholds.","asOf":"2026-09-17","links":[{"label":"Blood 2022","url":"https://doi.org/10.1182/blood.2022015850"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35767897/"}],"tags":[],"related":[],"cancers":["mds-higher-risk"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["blood"],"dependsOn":[],"notes":[],"journal":"Blood","year":2022,"doi":"10.1182/blood.2022015850","pmid":"35767897","authors":"Arber DA, Orazi A, Hasserjian RP, et al.","paperType":"guideline","findings":[],"whatItMeans":"Trial eligibility and risk stratification in AML and MDS often refer to this classification alongside the WHO edition; the two overlap heavily but not completely.","caveats":["Coexists with the WHO fifth edition, so the same marrow may carry two names."],"changedPractice":true},{"id":"paper-kyoto-2024-evidence-based-guidelines-ipmn-pancreatology-2024","kind":"paper","name":"International evidence-based Kyoto guidelines for the management of intraductal papillary mucinous neoplasm of the pancreas (2024)","aka":[],"tldr":"The 2024 update to the international pancreatic cyst guidelines, which adds faster cyst growth, new diabetes and pancreatitis to the warning signs, allows surveillance to stop in some older patients with small stable cysts, and grades each recommendation by the strength of the evidence.","summary":"Evidence-graded revision of the Fukuoka guidelines by the International Association of Pancreatology, meeting in Kyoto. High-risk stigmata are retained, with an enhancing mural nodule of 5 mm or more, main duct of 10 mm or more, obstructive jaundice and positive cytology as indications for surgery in fit patients. Worrisome features now include cyst growth of 2.5 mm or more per year, new-onset or worsening diabetes and acute pancreatitis, alongside the earlier criteria.\n\nThe guideline addresses when surveillance can be stopped (after five years of stability in cysts under 2 cm in patients who would not be surgical candidates), the role of cyst fluid molecular analysis, management after resection, and the need for randomised trials of surveillance strategies.","asOf":"2026-09-21","links":[{"label":"Pancreatology 2024","url":"https://doi.org/10.1016/j.pan.2023.12.009"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38182527/"}],"tags":[],"related":[],"cancers":["ipmn-cystic-precursors","pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Pancreatology","year":2024,"doi":"10.1016/j.pan.2023.12.009","pmid":"38182527","authors":"Ohtsuka T, Fernandez-Del Castillo C, Furukawa T, et al.","paperType":"guideline","findings":["New worrisome features: cyst growth 2.5 mm or more per year, new-onset or worsening diabetes, acute pancreatitis.","Surveillance may stop after five years of stability in small cysts in patients unfit for surgery.","Recommendations graded by evidence quality for the first time."],"whatItMeans":"The current international standard for deciding which pancreatic cysts to operate on, which to watch and for how long.","caveats":["Most recommendations still rest on low-quality retrospective evidence.","Differences from the European and American guidelines persist, particularly on stopping surveillance."],"changedPractice":true},{"id":"paper-dawood-inflammatory-breast-consensus-ann-oncol-2011","kind":"paper","name":"International expert panel consensus on the diagnosis and treatment of inflammatory breast cancer","aka":[],"tldr":"This consensus statement standardised how inflammatory breast cancer is diagnosed, with rapid onset of breast redness and swelling involving at least a third of the breast, and set out its trimodality treatment.","summary":"Consensus from an international expert panel defining the clinical diagnostic criteria for inflammatory breast cancer, recommended staging, the requirement for biopsy confirmation, and treatment with neoadjuvant systemic therapy followed by modified radical mastectomy and post-mastectomy radiotherapy, with HER2-directed therapy where appropriate.","asOf":"2026-09-17","links":[{"label":"Ann Oncol 2011","url":"https://doi.org/10.1093/annonc/mdq345"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20603440/"}],"tags":[],"related":[],"cancers":["inflammatory-breast-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2011,"doi":"10.1093/annonc/mdq345","pmid":"20603440","authors":"Dawood S, Merajver SD, Viens P, et al.","paperType":"guideline","findings":[],"whatItMeans":"The definition used in trials and clinics, and the insistence on systemic therapy first and mastectomy rather than breast conservation, come from this document.","caveats":["Diagnosis remains clinical and subjective; molecular definitions are still lacking."],"changedPractice":true},{"id":"paper-igcccg-classification-jco-1997","kind":"paper","name":"International Germ Cell Consensus Classification: a prognostic factor-based staging system for metastatic germ cell cancers","aka":[],"tldr":"Pooling over 5,000 patients, the IGCCCG classification sorted metastatic testicular cancer into good, intermediate and poor prognosis groups using tumour markers, primary site and non-lung metastases, and still decides how many cycles of chemotherapy a man receives.","summary":"Analysis of 5,202 patients with metastatic non-seminomatous and 660 with seminomatous germ cell tumours treated with cisplatin-based chemotherapy, identifying tumour marker levels (AFP, hCG, LDH), mediastinal primary site and non-pulmonary visceral metastases as independent prognostic factors and defining good (56 percent, 92 percent five-year survival), intermediate (28 percent, 80 percent) and poor (16 percent, 48 percent) prognosis groups for non-seminoma.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 1997","url":"https://doi.org/10.1200/JCO.1997.15.2.594"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/9053482/"}],"tags":[],"related":[],"cancers":["non-seminoma","seminoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":1997,"doi":"10.1200/JCO.1997.15.2.594","pmid":"9053482","authors":"Unknown","paperType":"methods","findings":["Good, intermediate and poor prognosis non-seminoma: five-year survival 92, 80 and 48 percent.","Seminoma: good (86 percent) and intermediate (72 percent) groups by non-pulmonary visceral metastases."],"whatItMeans":"Three cycles of BEP for good risk and four for intermediate and poor risk follow directly from this classification, which was updated in 2021 with modern survival figures.","caveats":["Survival figures predate modern supportive care; the 2021 update reports better outcomes in all groups."],"changedPractice":true,"participants":5202},{"id":"paper-kumar-lancet-oncol","kind":"paper","name":"International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 27511158 and published in The Lancet Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Treatment of multiple myeloma has substantially changed over the past decade with the introduction of several classes of new effective drugs that have greatly improved the rates and depth of response. Response criteria in multiple myeloma were developed to use serum and urine assessment of monoclonal proteins and bone marrow assessment (which is relatively insensitive). Given the high rates of complete response seen in patients with multiple myeloma with new treatment approaches, new response categories need to be defined that can identify responses that are deeper than those conventionally defined as complete response. Recent attempts have focused on the identification of residual tumour cells in the bone marrow using flow cytometry or gene sequencing. Furthermore, sensitive imaging techniques can be used to detect the presence of residual disease outside of the bone marrow. Combining these new methods, the International Myeloma Working Group has defined new response categories of minimal residual disease negativity, with or without imaging-based absence of extramedullary disease, to allow uniform reporting within and outside clinical trials. In this Review, we clarify several aspects of disease response assessment, along with endpoints for clinical trials, and highlight future directions for disease response assessments.\n\nIndexed on Europe PMC as PubMed record 27511158 (DOI 10.1016/s1470-2045(16)30206-6). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2016","url":"https://doi.org/10.1016/s1470-2045(16)30206-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27511158/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27511158"}],"tags":["europepmc-ingest"],"related":["mrd-negativity-myeloma"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2016,"doi":"10.1016/s1470-2045(16)30206-6","pmid":"27511158","authors":"Kumar S, Paiva B, Anderson KC, et al.","paperType":"review","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-pages-immunoscore-international-validation-lancet-2018","kind":"paper","name":"International validation of the consensus Immunoscore for the classification of colon cancer","aka":[],"tldr":"Counting two kinds of T cell in and around a bowel tumour, in a standardised way, across 14 centres in 13 countries, predicted recurrence better than the staging system and independently of it.","summary":"An international consortium of 14 centres in 13 countries assessed the consensus Immunoscore assay in patients with TNM stage I-III colon cancer, randomly assigned to training, internal validation and external validation sets. Paraffin sections of the tumour and invasive margin were processed by immunohistochemistry and the densities of CD3-positive and cytotoxic CD8-positive T cells quantified by digital pathology, with an Immunoscore derived from the mean of four density percentiles. Tissue from 3,539 patients was processed and 2,681 included after quality control. The assay was highly reproducible between observers and centres. In the training set, patients with a high Immunoscore had the lowest risk of recurrence at 5 years (8% against 19% intermediate and 32% low; hazard ratio 0.20 for high against low), and the findings were confirmed in both validation sets. In stratified multivariable analysis the association with time to recurrence was independent of age, sex, T stage, N stage, microsatellite instability and existing prognostic factors.","asOf":"2026-09-24","links":[{"label":"Pages et al., Lancet 2018: international validation of the consensus Immunoscore in 2,681 stage I-III colon cancers","url":"https://doi.org/10.1016/S0140-6736(18)30789-X"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29754777/"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["histopathology-ihc","ihc-autostainers-histology-automation"],"targets":[],"drugs":[],"companies":[],"institutions":["institut-curie"],"pathways":["tumor-microenvironment","cancer-immunity-cycle"],"terms":["ihc","msi"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"Lancet","year":2018,"doi":"10.1016/S0140-6736(18)30789-X","pmid":"29754777","authors":"Pages F, Mlecnik B, Marliot F, et al.","paperType":"observational","findings":["High Immunoscore carried a hazard ratio of 0.20 for time to recurrence against low.","Prognostic independently of T stage, N stage and microsatellite instability.","Highly reproducible between observers and centres."],"whatItMeans":"It is the strongest evidence that an immune measurement should sit beside TNM staging in colon cancer, and the basis for using it to decide adjuvant chemotherapy in stage II disease, which is where the argument is now.","caveats":["Prognostic, not predictive of benefit from any particular treatment.","Requires standardised digital pathology and a commercial assay.","No guideline mandates it and no approval depends on it."],"changedPractice":false,"participants":2681},{"id":"paper-partridge-n-engl-j-med","kind":"paper","name":"Interrupting Endocrine Therapy to Attempt Pregnancy after Breast Cancer","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 37133584 and published in New England Journal of Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Background: Prospective data on the risk of recurrence among women with hormone receptor-positive early breast cancer who temporarily discontinue endocrine therapy to attempt pregnancy are lacking.\n\nMethods: We conducted a single-group trial in which we evaluated the temporary interruption of adjuvant endocrine therapy to attempt pregnancy in young women with previous breast cancer. Eligible women were 42 years of age or younger; had had stage I, II, or III disease; had received adjuvant endocrine therapy for 18 to 30 months; and desired pregnancy. The primary end point was the number of breast cancer events (defined as local, regional, or distant recurrence of invasive breast cancer or new contralateral invasive breast cancer) during follow-up. The primary analysis was planned to be performed after 1600 patient-years of follow-up. The prespecified safety threshold was the occurrence of 46 breast cancer events during this period. Breast cancer outcomes in this treatment-interruption group were compared with those in an external control cohort consisting of women who would have met the entry criteria for the current trial.\n\nResults: Among 516 women, the median age was 37 years, the median time from breast cancer diagnosis to enrollment was 29 months, and 93.4% had stage I or II disease. Among 497 women who were followed for pregnancy status, 368 (74.0%) had at least one pregnancy and 317 (63.8%) had at least one live birth. In total, 365 babies were born. At 1638 patient-years of follow-up (median follow-up, 41 months), 44 patients had a breast cancer event, a result that did not exceed the safety threshold. The 3-year incidence of breast cancer events was 8.9% (95% confidence interval [CI], 6.3 to 11.6) in the treatment-interruption group and 9.2% (95% CI, 7.6 to 10.8) in the control cohort.\n\nConclusions: Among select women with previous hormone receptor-positive early breast cancer, temporary interruption of endocrine therapy to attempt pregnancy did not confer a greater short-term risk of breast cancer events, including distant recurrence, than that in the external control cohort. Further follow-up is critical to inform longer-term safety. (Funded by ETOP IBCSG Partners Foundation and others; POSITIVE ClinicalTrials.gov number, NCT02308085.).\n\nIndexed on Europe PMC as PubMed record 37133584 (DOI 10.1056/nejmoa2212856). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2023","url":"https://doi.org/10.1056/nejmoa2212856"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37133584/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37133584"}],"tags":["europepmc-ingest"],"related":["fertility-preservation"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/nejmoa2212856","pmid":"37133584","authors":"Partridge AH, Niman SM, Ruggeri M, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-cavalli-medulloblastoma-subtypes-cancer-cell-2017","kind":"paper","name":"Intertumoural heterogeneity within medulloblastoma subgroups","aka":[],"tldr":"Combining gene expression and methylation data from 763 medulloblastomas split the four subgroups into twelve subtypes with distinct genetics and survival, refining who is at high and low risk within each group.","summary":"Integrative clustering of 763 primary medulloblastomas using DNA methylation and gene expression identifying twelve subtypes: two WNT, four SHH, three group 3 and three group 4, each with distinct copy-number alterations, mutations, age distribution and survival.","asOf":"2026-09-17","links":[{"label":"Cancer Cell 2017","url":"https://doi.org/10.1016/j.ccell.2017.05.005"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28609654/"}],"tags":[],"related":[],"cancers":["medulloblastoma-group-3-4","medulloblastoma-shh","medulloblastoma-wnt"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-cell"],"dependsOn":[],"notes":[],"journal":"Cancer Cell","year":2017,"doi":"10.1016/j.ccell.2017.05.005","pmid":"28609654","authors":"Cavalli FMG, Remke M, Rampasek L, et al.","paperType":"translational","findings":["Twelve subtypes with distinct survival; for example SHH-alpha (TP53-mutant, children) had poor outcome and group 3-gamma (MYC-amplified) the worst."],"whatItMeans":"Subtype-level classification, particularly separating infant and TP53-mutant SHH tumours and MYC-amplified group 3 tumours, guides current risk stratification and trial design.","caveats":["Subtype assignment requires methylation profiling."],"changedPractice":true,"participants":763},{"id":"paper-riley-cochrane-database-syst-rev","kind":"paper","name":"Interventions for preventing oral mucositis in patients with cancer receiving treatment: oral cryotherapy","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 26695736 and published in The Cochrane database of systematic reviews; the citing page links this DOI, which is how the record was matched.","summary":"Background: Oral mucositis is a side effect of chemotherapy, head and neck radiotherapy, and targeted therapy, affecting over 75% of high risk patients. Ulceration can lead to severe pain and difficulty eating and drinking, which may necessitate opioid analgesics, hospitalisation and nasogastric or intravenous nutrition. These complications may lead to interruptions or alterations to cancer therapy, which may reduce survival. There is also a risk of death from sepsis if pathogens enter the ulcers of immunocompromised patients. Ulcerative oral mucositis can be costly to healthcare systems, yet there are few preventive interventions proven to be beneficial. Oral cryotherapy is a low-cost, simple intervention which is unlikely to cause side-effects. It has shown promise in clinical trials and warrants an up-to-date Cochrane review to assess and summarise the international evidence.\n\nObjectives: To assess the effects of oral cryotherapy for preventing oral mucositis in patients with cancer who are receiving treatment.\n\nSearch methods: We searched the following databases: the Cochrane Oral Health Group Trials Register (to 17 June 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2015, Issue 5), MEDLINE via Ovid (1946 to 17 June 2015), EMBASE via Ovid (1980 to 17 June 2015), CANCERLIT via PubMed (1950 to 17 June 2015) and CINAHL via EBSCO (1937 to 17 June 2015). We searched the US National Institutes of Health Trials Registry, and the WHO Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching databases.\n\nSelection criteria: We included parallel-design randomised controlled trials (RCTs) assessing the effects of oral cryotherapy in patients with cancer receiving treatment. We used outcomes from a published core outcome set registered on the COMET website.\n\nData collection and analysis: Two review authors independently screened the results of electronic searches, extracted data and assessed risk of bias. We contacted study authors for information where feasible. For dichotomous outcomes, we reported risk ratios (RR) and 95% confidence intervals (CI). For continuous outcomes, we reported mean differences (MD) and 95% CIs. We pooled similar studies in random-effects meta-analyses. We reported adverse effects in a narrative format.\n\nMain results: We included 14 RCTs analysing 1280 participants. The vast majority of participants did not receive radiotherapy to the head and neck, so this review primarily assesses prevention of chemotherapy-induced oral mucositis. All studies were at high risk of bias. The following results are for the main comparison: oral cryotherapy versus control (standard care or no treatment). Adults receiving fluorouracil-based (5FU) chemotherapy for solid cancersOral cryotherapy probably reduces oral mucositis of any severity (RR 0.61, 95% CI 0.52 to 0.72, 5 studies, 444 analysed, moderate quality evidence). In a population where 728 per 1000 would develop oral mucositis, oral cryotherapy would reduce this to 444 (95% CI 379 to 524). The number needed to treat to benefit one additional person (NNTB), i.e. to prevent them from developing oral mucositis, is 4 people (95% CI 3 to 5).The results were similar for moderate to severe oral mucositis (RR 0.52, 95% CI 0.41 to 0.65, 5 studies, 444 analysed, moderate quality evidence). NNTB 4 (95% CI 4 to 6).Severe oral mucositis is probably reduced (RR 0.40, 95% CI 0.27 to 0.61, 5 studies, 444 analysed, moderate quality evidence). Where 300 per 1000 would develop severe oral mucositis, oral cryotherapy would reduce this to 120 (95% CI 81 to 183), NNTB 6 (95% CI 5 to 9). Adults receiving high-dose melphalan-based chemotherapy before haematopoietic stem cell transplantation (HSCT)Oral cryotherapy may reduce oral mucositis of any severity (RR 0.59, 95% CI 0.35 to 1.01, 5 studies, 270 analysed, low quality evidence). Where 824 per 1000 would develop oral mucositis, oral cryotherapy would reduce this to 486 (95% CI reduced to 289 to increased to 833). The NNTB is 3, although the uncertainty surrounding the effect estimate means that the 95% CI ranges from 2 NNTB, to 111 NNTH (number needed to treat in order to harm one additional person, i.e. for one additional person to develop oral mucositis).The results were similar for moderate to severe oral mucositis (RR 0.43, 95% CI 0.17 to 1.09, 5 studies, 270 analysed, low quality evidence). NNTB 3 (95% CI 2 NNTB to 17 NNTH).Severe oral mucositis is probably reduced (RR 0.38, 95% CI 0.20 to 0.72, 5 studies, 270 analysed, moderate quality evidence). Where 427 per 1000 would develop severe oral mucositis, oral cryotherapy would reduce this to 162 (95% CI 85 to 308), NNTB 4 (95% CI 3 to 9).Oral cryotherapy was shown to be safe, with very low rates of minor adverse effects, such as headaches, chills, numbness/taste disturbance, and tooth pain. This appears to contribute to the high rates of compliance seen in the included studies.There was limited or no evidence on the secondary outcomes of this review, or on patients undergoing other chemotherapies, radiotherapy, targeted therapy, or on comparisons of oral cryotherapy with other interventions or different oral cryotherapy regimens. Therefore no further robust conclusions can be made. There was also no evidence on the effects of oral cryotherapy in children undergoing cancer treatment.\n\nAuthors' conclusions: We are confident that oral cryotherapy leads to large reductions in oral mucositis of all severities in adults receiving 5FU for solid cancers. We are less confident in the ability of oral cryotherapy to reduce oral mucositis in adults receiving high-dose melphalan before HSCT. Evidence suggests that it does reduce oral mucositis in these adults, but we are less certain about the size of the reduction, which could be large or small. However, we are confident that there is an appreciable reduction in severe oral mucositis in these adults.This Cochrane review includes some very recent and currently unpublished data, and strengthens international guideline statements for adults receiving the above cancer treatments.\n\nIndexed on Europe PMC as PubMed record 26695736 (DOI 10.1002/14651858.cd011552.pub2). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cochrane Database Syst Rev 2015","url":"https://doi.org/10.1002/14651858.cd011552.pub2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26695736/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26695736"}],"tags":["europepmc-ingest"],"related":["oral-cryotherapy-mucositis"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Cochrane database of systematic reviews","year":2015,"doi":"10.1002/14651858.cd011552.pub2","pmid":"26695736","authors":"Riley P, Glenny AM, Worthington HV, et al.","paperType":"meta-analysis","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nct03897881-j-clin-oncol-2026-update","kind":"paper","name":"Intismeran Autogene Plus Pembrolizumab Versus Pembrolizumab Alone in High-Risk Resected Melanoma: 5-Year Update of the Randomized Phase IIb KEYNOTE-942 Study","aka":[],"tldr":"Later report from the trial registered as NCT03897881, in Journal of Clinical Oncology (2026); its title describes an updated or longer-term analysis.","summary":"Intismeran autogene (intismeran; formerly V940 or mRNA-4157) is an mRNA-based individualized neoantigen therapy. We report 5-year outcomes of intismeran plus pembrolizumab from the phase IIb KEYNOTE-942 study (ClinicalTrials.gov identifier: NCT03897881). Eligible patients with resected stage IIIB to IV cutaneous melanoma were randomly assigned 2:1 to receive nine doses of intramuscular intismeran 1 mg once every 3 weeks plus 18 doses of intravenous pembrolizumab 200 mg once every 3 weeks or 18 doses of intravenous pembrolizumab 200 mg once every 3 weeks. The primary end point was recurrence-free survival (RFS); secondary end points included distant metastasis-free survival (DMFS) and safety. Five-year analyses were descriptive. Among 157 randomly assigned patients (intismeran plus pembrolizumab, n = 107; pembrolizumab, n = 50), the median planned follow-up at data cutoff (December 15, 2025) was 60.3 (range, 50.5-76.4) months. Intismeran plus pembrolizumab continued to prolong RFS (hazard ratio [HR], 0.510 [95% CI, 0.294 to 0.887) and DMFS (HR, 0.411 [95% CI, 0.200 to 0.843]), with a favorable trend in overall survival (HR, 0.471 [95% CI, 0.165 to 1.345]) versus pembrolizumab. Safety profile continued to be manageable, with no new safety signals. Intismeran plus pembrolizumab was associated with increased T-cell receptor clonality and novel clonotypes versus pembrolizumab; greater novel clone expansion was observed in patients without versus with recurrence in the combination arm. After a 5-year follow-up, intismeran plus pembrolizumab demonstrated sustained, durable treatment benefits versus pembrolizumab alone in resected high-risk melanoma.\n\nIndexed on Europe PMC as PubMed record 42223134 (DOI 10.1200/jco-26-00835). Its abstract cites the registry id NCT03897881, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2026","url":"https://doi.org/10.1200/jco-26-00835"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42223134/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42223134"},{"label":"ClinicalTrials.gov NCT03897881","url":"https://clinicaltrials.gov/study/NCT03897881"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct03897881"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2026,"doi":"10.1200/jco-26-00835","pmid":"42223134","authors":"Khattak A, Carlino MS, Meniawy T, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-adsay-icpn-gallbladder-ajsp-2012","kind":"paper","name":"Intracholecystic papillary-tubular neoplasms (ICPN) of the gallbladder (neoplastic polyps, adenomas, and papillary neoplasms that are at least 1.0 cm): clinicopathologic and immunohistochemical analysis of 123 cases","aka":[],"tldr":"Polyp-like growths of the gallbladder lining 1 cm or larger were reclassified as one family, ICPN: more than half already contained invasive cancer, yet those cancers fared much better than ordinary gallbladder carcinoma.","summary":"123 gallbladder cases with a well-defined exophytic preinvasive neoplasm of 1 cm or more were analysed. Patients were predominantly female (2 to 1) with a mean age of 61 and a median tumour size of 2.2 cm; half presented with pain and half incidentally; gallstones were present in only 20%; radiology called almost half cancer and missed 10%. Configuration was papillary in 43%, tubulopapillary in 31% and tubular in 26%, and cell lineage biliary in 50%, gastric foveolar 16%, gastric pyloric 20%, intestinal 8% and oncocytic 6%, with hybrid patterns in 90%.\n\nOf cases that would have qualified as pyloric gland adenoma, 88% had at least focal high-grade dysplasia and 18% invasive carcinoma. Overall 55% had an associated invasive carcinoma; extent of high-grade dysplasia, biliary or foveolar cell type and papilla formation were associated with invasion. Among systematically analysed invasive carcinomas, a tumoral intraepithelial neoplasm was detected in 6.4% (39 of 606). Three-year survival was 90% without and 60% with invasion, against 27% for pancreatobiliary-type gallbladder carcinoma, an advantage that persisted after stage matching.","asOf":"2026-09-24","links":[{"label":"Adsay et al., Am J Surg Pathol 2012: intracholecystic papillary-tubular neoplasms, 123 cases","url":"https://doi.org/10.1097/pas.0b013e318262787c"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22895264/"}],"tags":[],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["intracholecystic-papillary-tubular-neoplasm","dysplasia"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"American Journal of Surgical Pathology","year":2012,"doi":"10.1097/pas.0b013e318262787c","pmid":"22895264","authors":"Adsay V, Jang KT, Roa JC, et al.","paperType":"observational","findings":["55% of 123 ICPNs harboured invasive carcinoma; 88% of pyloric gland adenoma-like lesions had high-grade dysplasia.","Three-year survival 90% (no invasion), 60% (invasion) versus 27% for pancreatobiliary-type carcinoma.","Only 6.4% (39 of 606) of invasive carcinomas arose from a tumoral precursor."],"whatItMeans":"This paper created the ICPN category adopted by the WHO classification and quantified the polyp route: rare as an origin of cancer, dangerous when present, and better in outcome. It underpins the 1 cm threshold for removing gallbladder polyps.","caveats":["Multi-institutional pathology series with referral bias.","Lineage assignment relied on predominant pattern and immunohistochemistry."],"changedPractice":true,"participants":123},{"id":"paper-isaacsson-velho-intraductal-germline-dna-repair-prostate-2018","kind":"paper","name":"Intraductal and ductal histology and lymphovascular invasion are associated with germline DNA-repair gene mutations in prostate cancer","aka":[],"tldr":"Among 150 men tested regardless of family history, the ones with an inherited repair fault were four times as likely to have a particular growth pattern on their pathology report.","summary":"One hundred and fifty consecutive unselected patients with recurrent or metastatic prostate cancer were offered germline genetic testing by a single oncologist using a clinical-grade 30-gene saliva assay. Pathogenic mutations were identified in 21 men, 14%: 9 in BRCA2, 3 in ATM, 3 in CHEK2 and 2 in BRCA1. There were no associations between germline mutation and age, tumour stage, Gleason sum or family history. Mutation-positive men had lower median PSA at diagnosis, 5.5 against 8.6 ng/mL, and distinctive pathological features: intraductal or ductal histology in 48% against 12%, and lymphovascular invasion in 52% against 14%. Forty-four per cent of the men with a positive germline test would not have been offered genetic screening under the National Comprehensive Cancer Network guidelines then in force.","asOf":"2026-09-25","links":[{"label":"Isaacsson Velho et al., The Prostate 2018: intraductal or ductal histology and lymphovascular invasion associated with germline DNA-repair gene mutations in 150 consecutively tested men","url":"https://doi.org/10.1002/pros.23484"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29368341/"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["germline-testing","histopathology-ihc"],"targets":["brca","atm","chek2"],"drugs":[],"companies":[],"institutions":[],"pathways":["homologous-recombination-repair","ddr"],"terms":["germline-vs-somatic","gbrca-mutation","hrd","intraductal-carcinoma-prostate","cribriform-prostate-cancer"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Prostate","year":2018,"doi":"10.1002/pros.23484","pmid":"29368341","authors":"Isaacsson Velho P, Silberstein JL, Markowski MC, et al.","paperType":"observational","findings":["Pathogenic germline mutations in 21 of 150 men, 14%; BRCA2 in 9, ATM in 3, CHEK2 in 3, BRCA1 in 2.","Intraductal or ductal histology in 48% of carriers against 12% of non-carriers.","Lymphovascular invasion in 52% against 14%.","No association with age, stage, Gleason sum or family history; 44% of carriers would not have qualified for testing."],"whatItMeans":"It links a line on a UK pathology report to a question about a family. Intraductal carcinoma is a reportable item in the current dataset, and its presence is a practical prompt to check that germline testing has actually been offered rather than assumed.","caveats":["One hundred and fifty consecutive patients of a single oncologist, so referral patterns shape it.","Retrospective pathology review.","Neither finding is sensitive enough to select who is tested; the case for unselected testing stands."],"changedPractice":false,"participants":150},{"id":"paper-smith-nejm-evid","kind":"paper","name":"Intraoperative Fluorescence Guidance for Breast Cancer Lumpectomy Surgery","aka":[],"tldr":"Paper cited by one treatment page, indexed on Europe PMC as PubMed record 38320161 and published in NEJM Evidence; the citing page links this DOI, which is how the record was matched.","summary":"BACKGROUND: Although lumpectomy and mastectomy provide equivalent survival for patients with breast cancer, local recurrence after lumpectomy increases breast cancer mortality. Positive lumpectomy margins, which imply incomplete tumor removal, are the strongest predictor of local recurrence and are identified days after surgery, necessitating a second surgery. METHODS: In this prospective trial, we assessed margin status with or without pegulicianine fluorescence-guided surgery (pFGS) for stages 0 to 3 breast cancers. To prevent surgeons from performing smaller than standard lumpectomies in anticipation of pFGS assistance, patients were randomly assigned 10:1 to pFGS or control groups, thus randomization was not designed to provide a control group for evaluating device performance. In patients undergoing pFGS, additional pFGS-guided cavity margins were excised at sites of pegulicianine signal. We evaluated three coprimary end points: the percentage of patients for whom pFGS-guided margins contained cancer, sensitivity, and specificity. RESULTS: Overall, 406 patients received 1.0 mg/kg intravenous pegulicianine followed by lumpectomy. Among 392 patients randomly assigned, 316 had invasive cancers, and 76 had in situ cancers. In 27 of 357 patients undergoing pFGS, pFGS-guided margins removed tumor left behind after standard lumpectomy, 22 from cavity orientations deemed negative on standard margin evaluation. Second surgeries were avoided by pFGS in 9 of 62 patients with positive margins. On per-margin analysis, pFGS specificity was 85.2%, and sensitivity was 49.3%. Pegulicianine administration was stopped for adverse events in six patients. Two patients had grade 3 serious adverse events related to pegulicianine. CONCLUSIONS: The use of pFGS in breast cancer surgery met prespecified thresholds for removal of residual tumor and specificity but did not meet the prespecified threshold for sensitivity. (Funded by Lumicell, Inc. and the National Institutes of Health; Clinicaltrials.gov number, NCT03686215.)\n\nIndexed on Europe PMC as PubMed record 38320161 (DOI 10.1056/evidoa2200333). Matched by DOI alone: one treatment page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"NEJM Evid 2023","url":"https://doi.org/10.1056/evidoa2200333"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38320161/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38320161"}],"tags":["europepmc-ingest"],"related":["pegulicianine"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm-evidence"],"dependsOn":[],"notes":[],"journal":"NEJM Evidence","year":2023,"doi":"10.1056/evidoa2200333","pmid":"38320161","authors":"Smith BL, Hunt KK, Carr D, et al.","paperType":"observational","findings":[],"whatItMeans":"One treatment page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-orecchia-lancet-oncol","kind":"paper","name":"Intraoperative irradiation for early breast cancer (ELIOT): long-term recurrence and survival outcomes from a single-centre, randomised, phase 3 equivalence trial","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 33845035 and published in The Lancet Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background: In the randomised, phase 3 equivalence trial on electron intraoperative radiotherapy (ELIOT), accelerated partial breast irradiation (APBI) with the use of intraoperative radiotherapy was associated with a higher rate of ipsilateral breast tumour recurrence (IBTR) than whole-breast irradiation (WBI) in patients with early-stage breast cancer. Here, we aimed to examine the planned long-term recurrence and survival outcomes from the ELIOT trial.\n\nMethods: This single-centre, randomised, phase 3 equivalence trial was done at the European Institute of Oncology (Milan, Italy). Eligible women, aged 48-75 years with a clinical diagnosis of a unicentric breast carcinoma with an ultrasound diameter not exceeding 25 mm, clinically negative axillary lymph nodes, and who were suitable for breast-conserving surgery, were randomly assigned (1:1) via a web-based system, with a random permuted block design (block size of 16) and stratified by clinical tumour size, to receive post-operative WBI with conventional fractionation (50 Gy given as 25 fractions of 2 Gy, plus a 10 Gy boost), or 21 Gy intraoperative radiotherapy with electrons (ELIOT) in a single dose to the tumour bed during surgery. The trial was open label and no-one was masked to treatment group assignment. The primary endpoint was the occurrence of IBTR. The trial was designed assuming a 5-year IBTR rate of 3% in the WBI group and equivalence of the two groups, if the 5-year IBTR rate in the ELIOT group did not exceed a 2·5 times excess, corresponding to 7·5%. Overall survival was the secondary endpoint. The main analysis was done by intention to treat. The cumulative incidence of IBTR events and overall survival were assessed at 5, 10, and 15 years of follow-up. This trial is registered with ClinicalTrials.gov, NCT01849133.\n\nFindings: Between Nov 20, 2000, and Dec 27, 2007, 1305 women were enrolled and randomly assigned: 654 to the WBI group and 651 to the ELIOT group. After a median follow-up of 12·4 years (IQR 9·7-14·7), 86 (7%) patients developed IBTR, with 70 (11%) cases in the ELIOT group and 16 (2%) in the WBI group, corresponding to an absolute excess of 54 IBTRs in the ELIOT group (HR 4·62, 95% CI 2·68-7·95, p<0·0001). In the ELIOT group, the 5-year IBTR rate was 4·2% (95% CI 2·8-5·9), the 10-year rate was 8·1% (6·1-10·3), and the 15-year rate was 12·6% (9·8-15·9). In the WBI group, the 5-year IBTR rate was 0·5% (95% CI 0·1-1·3), the 10-year rate was 1·1% (0·5-2·2), and the 15-year rate was 2·4% (1·4-4·0). At final follow-up on March 11, 2019, 193 (15%) women had died from any cause, with no difference between the two groups (98 deaths in the ELIOT group vs 95 in the WBI group; HR 1·03, 95% CI 0·77-1·36, p=0·85). In the ELIOT group, the overall survival rate was 96·8% (95% CI 95·1-97·9) at 5 years, 90·7% (88·2-92·7) at 10 years, and 83·4% (79·7-86·4) at 15 years; and in the WBI group, the overall survival rate was 96·8% (95·1-97·9) at 5 years, 92·7% (90·4-94·4) at 10 years, and 82·4% (78·5-85·6) at 15 years. We did not collect long-term data on adverse events.\n\nInterpretation: The long-term results of this trial confirmed the higher rate of IBTR in the ELIOT group than in the WBI group, without any differences in overall survival. ELIOT should be offered to selected patients at low-risk of IBTR.\n\nFunding: Italian Association for Cancer Research, Jacqueline Seroussi Memorial Foundation for Cancer Research, Umberto Veronesi Foundation, American Italian Cancer Foundation, The Lombardy Region, and Italian Ministry of Health.\n\nIndexed on Europe PMC as PubMed record 33845035 (DOI 10.1016/s1470-2045(21)00080-2). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2021","url":"https://doi.org/10.1016/s1470-2045(21)00080-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33845035/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33845035"}],"tags":["europepmc-ingest"],"related":["intraoperative-radiotherapy"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2021,"doi":"10.1016/s1470-2045(21)00080-2","pmid":"33845035","authors":"Orecchia R, Veronesi U, Maisonneuve P, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-senft-lancet-oncol","kind":"paper","name":"Intraoperative MRI guidance and extent of resection in glioma surgery: a randomised, controlled trial","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 21868284 and published in The Lancet Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background: Intraoperative MRI is increasingly used in neurosurgery, although there is little evidence for its use. We aimed to assess efficacy of intraoperative MRI guidance on extent of resection in patients with glioma.\n\nMethods: In our prospective, randomised, parallel-group trial, we enrolled adults (≥18 years) with contrast enhancing gliomas amenable to radiologically complete resection who presented to Goethe University (Frankfurt, Germany). We randomly assigned patients (1:1) with computer-generated blocks of four and a sealed-envelope design to undergo intraoperative MRI-guided surgery or conventional microsurgery (control group). Surgeons and patients were unmasked to treatment group allocation, but an independent neuroradiologist was masked during analysis of all preoperative and postoperative imaging data. The primary endpoint was rate of complete resections as established by early postoperative high-field MRI (1·5 T or 3·0 T). Analysis was done per protocol. This study is registered with ClinicalTrials.gov, number NCT01394692.\n\nFindings: We enrolled 58 patients between Oct 1, 2007, and July 1, 2010. 24 (83%) of 29 patients randomly allocated to the intraoperative MRI group and 25 (86%) of 29 controls were eligible for analysis (four patients in each group had metastasis and one patient in the intraoperative MRI group withdrew consent after randomisation). More patients in the intraoperative MRI group had complete tumour resection (23 [96%] of 24 patients) than did in the control group (17 [68%] of 25, p=0·023). Postoperative rates of new neurological deficits did not differ between patients in the intraoperative MRI group (three [13%] of 24) and controls (two [8%] of 25, p=1·0). No patient for whom use of intraoperative MRI led to continued resection of residual tumour had neurological deterioration. One patient in the control group died before 6 months.\n\nInterpretation: Our study provides evidence for the use of intraoperative MRI guidance in glioma surgery: such imaging helps surgeons provide the optimum extent of resection.\n\nFunding: None.\n\nIndexed on Europe PMC as PubMed record 21868284 (DOI 10.1016/s1470-2045(11)70196-6). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2011","url":"https://doi.org/10.1016/s1470-2045(11)70196-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21868284/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/21868284"}],"tags":["europepmc-ingest"],"related":["intraoperative-mri-ct"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2011,"doi":"10.1016/s1470-2045(11)70196-6","pmid":"21868284","authors":"Senft C, Bink A, Franz K, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-intrigue-ripretinib-vs-sunitinib-jco-2022","kind":"paper","name":"INTRIGUE: ripretinib versus sunitinib in advanced gastrointestinal stromal tumour after imatinib","aka":[],"tldr":"Ripretinib was not better than sunitinib as second-line treatment for gastrointestinal stromal tumour overall, but it was better tolerated and worked better in tumours with KIT exon 11 plus exon 17/18 secondary mutations, while sunitinib was better for exon 13/14 mutations.","summary":"Phase 3 open-label trial of 453 patients with advanced GIST after imatinib randomised to ripretinib or sunitinib.\n\nMedian progression-free survival was 8.3 versus 7.0 months in the intention-to-treat population (hazard ratio 0.91, not superior); ripretinib had fewer grade 3 to 4 adverse events (41 versus 66 percent) and better quality of life. Circulating tumour DNA analysis showed ripretinib superior in exon 11 plus 17/18 mutations and sunitinib superior in exon 11 plus 13/14 mutations.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2022","url":"https://doi.org/10.1200/JCO.22.00294"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35947817/"}],"tags":[],"related":[],"cancers":["gist-imatinib-resistant"],"sections":[],"technologies":[],"targets":[],"drugs":["imatinib","ripretinib","sunitinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["sebastian-bauer"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2022,"doi":"10.1200/JCO.22.00294","pmid":"35947817","authors":"Bauer S, Jones RL, Blay JY, et al.","paperType":"rct","findings":["Median progression-free survival 8.3 vs 7.0 months; hazard ratio 0.91 (not superior).","Exon 17/18 secondary mutations: ripretinib 14.2 vs 1.5 months; exon 13/14: sunitinib 15.0 vs 4.0 months."],"whatItMeans":"Sunitinib remains the standard second-line treatment, with ripretinib as a better-tolerated alternative, and mutation-guided choice by circulating tumour DNA is being tested prospectively in INSIGHT.","caveats":["Failed its primary superiority endpoint.","Mutation subgroup analysis was exploratory."],"changedPractice":true,"participants":453},{"id":"paper-intuitt-nf2-brigatinib-plotkin-nejm-2024","kind":"paper","name":"INTUITT-NF2: brigatinib in NF2-related schwannomatosis with progressive tumours","aka":[],"tldr":"In people with the inherited condition NF2 whose nerve and brain-lining tumours were growing despite earlier treatment, the kinase inhibitor brigatinib shrank some tumours, slowed the growth of all types and improved hearing in a third of affected ears without serious toxicity.","summary":"First sub-study of the adaptive platform trial INTUITT-NF2: 40 patients (median age 26) with NF2-related schwannomatosis and progressive target tumours (10 vestibular schwannomas, 8 non-vestibular schwannomas, 20 meningiomas, 2 ependymomas) received brigatinib.\n\nAfter a median follow-up of 10.4 months, 10 percent of target tumours and 23 percent of all tumours had a radiographic response, with meningiomas and non-vestibular schwannomas benefiting most; annualised growth rates fell for all tumour types; hearing improved in 35 percent of eligible ears; pain scores fell; and there were no grade 4 or 5 treatment-related adverse events.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2024","url":"https://doi.org/10.1056/NEJMoa2400985"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38904277/"}],"tags":[],"related":[],"cancers":["vestibular-schwannoma","meningioma"],"sections":[],"technologies":[],"targets":[],"drugs":["brigatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["intuitt-nf2"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2024,"doi":"10.1056/NEJMoa2400985","pmid":"38904277","authors":"Plotkin SR, Yohay KH, Nghiemphu PL, et al.","paperType":"observational","findings":["Radiographic response in 10 percent (95% CI 3 to 24) of target tumours and 23 percent (16 to 30) of all tumours.","Annualised growth rates decreased for every tumour type during treatment.","Hearing improvement in 35 percent (95% CI 20 to 53) of eligible ears; no grade 4 or 5 treatment-related adverse events."],"whatItMeans":"Brigatinib is the first drug shown to act across the tumour types of NF2-related schwannomatosis and is now offered for progressive tumours; the platform design lets further drugs be tested against the same benchmark.","caveats":["Single-arm sub-study with short follow-up; responses were modest by size criteria.","Vestibular schwannomas responded less than meningiomas and non-vestibular schwannomas."],"changedPractice":true,"participants":40},{"id":"paper-invictus-ripretinib-lancet-oncol-2020","kind":"paper","name":"INVICTUS: ripretinib in advanced gastrointestinal stromal tumours after three or more prior kinase inhibitors","aka":[],"tldr":"The switch-control KIT inhibitor ripretinib lengthened progression-free survival from one to six months and improved survival compared with placebo in gastrointestinal stromal tumours that had failed imatinib, sunitinib and regorafenib.","summary":"Phase 3 placebo-controlled trial of 129 patients with advanced GIST after at least three prior kinase inhibitors randomised 2:1 to ripretinib 150 mg daily or placebo with crossover.\n\nMedian progression-free survival was 6.3 versus 1.0 months (hazard ratio 0.15) and median overall survival 15.1 versus 6.6 months (hazard ratio 0.36); alopecia, myalgia and hand-foot syndrome were common and mostly low grade.","asOf":"2026-09-17","links":[{"label":"Lancet Oncol 2020","url":"https://doi.org/10.1016/S1470-2045(20)30168-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32511981/"}],"tags":[],"related":[],"cancers":["gist-imatinib-resistant"],"sections":[],"technologies":[],"targets":[],"drugs":["ripretinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["invictus"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2020,"doi":"10.1016/S1470-2045(20)30168-6","pmid":"32511981","authors":"Blay JY, Serrano C, Heinrich MC, et al.","paperType":"rct","findings":["Median progression-free survival 6.3 vs 1.0 months; hazard ratio 0.15.","Median overall survival 15.1 vs 6.6 months; hazard ratio 0.36."],"whatItMeans":"Ripretinib is the approved fourth-line treatment for GIST and is being tested earlier in mutation-selected patients (INSIGHT).","caveats":["Objective response was only 9 percent; benefit is disease stabilisation.","Small trial in a heavily pretreated population."],"changedPractice":true,"participants":129},{"id":"paper-kim-lotus-ipatasertib-tnbc-lancet-oncol-2017","kind":"paper","name":"Ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (LOTUS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial","aka":[],"tldr":"Adding the AKT inhibitor ipatasertib to first-line paclitaxel lengthened the time before metastatic triple-negative cancer grew from 4.9 to 6.2 months, the first randomised support for AKT-directed therapy in the disease.","summary":"124 women with untreated inoperable locally advanced or metastatic TNBC were randomised to paclitaxel 80 mg/m2 with ipatasertib 400 mg or placebo, stratified by prior therapy, chemotherapy-free interval and tumour PTEN status. Median progression-free survival was 6.2 versus 4.9 months (stratified HR 0.60, 95% CI 0.37 to 0.98) in the intention-to-treat population and 6.2 versus 3.7 months (HR 0.59, 0.26 to 1.32) in the 48 PTEN-low patients. Grade 3 or worse diarrhoea occurred in 23% with ipatasertib.","asOf":"2026-09-24","links":[{"label":"Kim et al., Lancet Oncol 2017: LOTUS, ipatasertib plus paclitaxel in 124 metastatic TNBC patients","url":"https://doi.org/10.1016/S1470-2045(17)30450-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28800861/"}],"tags":[],"related":["pten-alteration"],"cancers":["tnbc","tnbc-metastatic"],"sections":[],"technologies":[],"targets":["akt","pten"],"drugs":["ipatasertib","paclitaxel"],"companies":["roche-genentech"],"institutions":[],"pathways":["pi3k-akt-mtor"],"terms":[],"trials":[],"people":["kim-sung-bae","rebecca-dent"],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2017,"doi":"10.1016/S1470-2045(17)30450-3","pmid":"28800861","authors":"Kim SB, Dent R, Im SA, et al.","paperType":"rct","findings":["PFS 6.2 versus 4.9 months (HR 0.60) in all patients.","PTEN-low (48 patients): 6.2 versus 3.7 months (HR 0.59, not significant).","Grade 3 diarrhoea 23%."],"whatItMeans":"LOTUS and PAKT together made the PI3K/AKT/PTEN-altered subgroup the target population for AKT inhibitors in TNBC; the phase 3 IPATunity130 later failed to confirm it, which is why no AKT inhibitor is approved here.","caveats":["Phase 2 with 124 patients; PTEN by immunohistochemistry.","IPATunity130 (phase 3) did not confirm the benefit."],"changedPractice":false,"participants":124},{"id":"paper-ipatential150-ipatasertib-abiraterone-pten-lancet-2021","kind":"paper","name":"IPATential150: ipatasertib plus abiraterone and prednisolone in metastatic castration-resistant prostate cancer","aka":[],"tldr":"Adding an AKT-blocking tablet to abiraterone delayed progression in the half of men who had lost PTEN, but at a considerable cost in side effects.","summary":"A randomised, double-blind phase 3 trial at 200 sites in 26 countries in men with previously untreated asymptomatic or mildly symptomatic metastatic castration-resistant prostate cancer with progressive disease. Of 1,611 men screened, 1,101 were enrolled and randomised to ipatasertib 400 mg daily with abiraterone and prednisolone or to placebo with abiraterone and prednisolone, stratified by prior taxane, type of progression, visceral metastasis and tumour PTEN-loss status by immunohistochemistry. In the 521 men, 47%, whose tumours showed PTEN loss by immunohistochemistry, median radiographic progression-free survival was 16.5 months with placebo and 18.5 months with ipatasertib, hazard ratio 0.77, significant at the prespecified alpha. In the intention-to-treat population the difference was 16.6 against 19.2 months, hazard ratio 0.84, not significant at its alpha. Grade 3 or higher adverse events occurred in 39% of the placebo group and 70% of the ipatasertib group, with discontinuation for adverse events in 5% against 21%.","asOf":"2026-09-25","links":[{"label":"Sweeney et al., Lancet 2021: IPATential150, ipatasertib with abiraterone in 1,101 men with metastatic castration-resistant prostate cancer split by PTEN loss","url":"https://doi.org/10.1016/S0140-6736(21)00580-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34246347/"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["histopathology-ihc"],"targets":["pten","akt","androgen-receptor"],"drugs":["abiraterone","ipatasertib"],"companies":[],"institutions":[],"pathways":["pi3k-akt-mtor","ar-signaling"],"terms":["ihc","castration-resistance"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"Lancet","year":2021,"doi":"10.1016/S0140-6736(21)00580-8","pmid":"34246347","authors":"Sweeney C, Bracarda S, Sternberg CN, et al.","paperType":"rct","findings":["PTEN loss by immunohistochemistry in 521 of 1,101 men, 47%.","Radiographic progression-free survival 18.5 against 16.5 months in the PTEN-loss population, hazard ratio 0.77.","No significant difference in the intention-to-treat population at its prespecified alpha.","Grade 3 or higher adverse events in 70% against 39%, with discontinuation in 21% against 5%."],"whatItMeans":"It is the prospective test of the PI3K and androgen receptor feedback hypothesis in men, and it shows both halves of the answer: the biomarker-selected population benefits, and the benefit is small enough that the toxicity has to be weighed honestly.","caveats":["A two-month median difference in radiographic progression-free survival, with overall survival not demonstrated here.","PTEN loss was defined by one immunohistochemistry assay; a different assay would define a different population.","One man in five stopped ipatasertib because of side effects."],"changedPractice":false,"participants":1101},{"id":"paper-felsenstein-ipmn-cooccurring-cancer-relatedness-gut-2018","kind":"paper","name":"IPMNs with co-occurring invasive cancers: neighbours but not always relatives","aka":[],"tldr":"In 61 patients who had both a cyst and a pancreatic cancer removed, the two were genetically related in about half and unrelated in a fifth, so a cyst can be an innocent bystander to a cancer arising elsewhere.","summary":"All available patients with co-occurring IPMN and invasive intrapancreatic carcinoma over ten years at a single institution were analysed: DNA from the carcinoma, adjacent IPMN and distant IPMN underwent targeted next-generation sequencing of pancreatic cancer driver genes to infer relatedness. Of 61 patients with IPMN and ductal adenocarcinoma, 51% were likely related and 18% likely independent; all 13 IPMN and colloid carcinoma pairs were likely related. Striking genetic heterogeneity was found within IPMNs even for well-characterised driver genes.","asOf":"2026-09-24","links":[{"label":"Felsenstein et al., Gut 2018: IPMNs with co-occurring invasive cancers, related in 51% and independent in 18%","url":"https://doi.org/10.1136/gutjnl-2017-315062"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29500184/"}],"tags":[],"related":[],"cancers":["pancreatic","ipmn-cystic-precursors"],"sections":[],"technologies":[],"targets":["kras","gnas","rnf43","tp53","smad4"],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":["clonal-evolution"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["gut"],"dependsOn":[],"notes":[],"journal":"Gut","year":2018,"doi":"10.1136/gutjnl-2017-315062","pmid":"29500184","authors":"Felsenstein M, Noe M, Masica DL, et al.","paperType":"translational","findings":["Of 61 IPMN and ductal adenocarcinoma pairs, 51% likely related and 18% likely independent.","All 13 colloid carcinomas were related to their IPMN."],"whatItMeans":"Risk stratification of a cyst cannot assume the nearby cancer came from it, and the whole gland stays at risk after cyst resection.","caveats":["Single institution; relatedness inferred from a driver-gene panel.","Heterogeneity within IPMNs can misclassify relatedness."],"changedPractice":false,"participants":81},{"id":"paper-ipss-m-bernard-nejm-evidence-2022","kind":"paper","name":"IPSS-M: the molecular international prognostic scoring system for myelodysplastic syndromes","aka":[],"tldr":"By adding mutations in 31 genes to blood counts and chromosomes, the IPSS-M sorts myelodysplastic syndromes into six risk groups and reclassifies about half of patients compared with the older score.","summary":"Development and validation of a prognostic model in 2,957 patients with MDS, combining clinical variables, cytogenetics and mutations in 31 genes into a continuous score with six risk categories; validated in an independent cohort of 754 patients.\n\nTP53 multi-hit, FLT3 and MLL partial tandem duplications carried the most adverse weight; SF3B1 was favourable. Compared with IPSS-R, 46 percent of patients were reclassified, most often upwards.","asOf":"2026-09-17","links":[{"label":"NEJM Evid 2022","url":"https://doi.org/10.1056/EVIDoa2200008"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38319256/"}],"tags":[],"related":[],"cancers":["mds-higher-risk"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm-evidence"],"dependsOn":[],"notes":[],"journal":"NEJM Evidence","year":2022,"doi":"10.1056/EVIDoa2200008","pmid":"38319256","authors":"Bernard E, Tuechler H, Greenberg PL, et al.","paperType":"methods","findings":["Six risk categories with median survival from over 10 years to about one year.","46 percent of patients reclassified compared with IPSS-R, 74 percent of those to a higher risk group."],"whatItMeans":"Sequencing at diagnosis now changes the risk group, and therefore the transplant discussion, for a large fraction of patients. Trials and guidelines are adopting the IPSS-M in place of the IPSS-R.","caveats":["Requires a broad myeloid sequencing panel that is not universally available.","Derived mostly from untreated patients at diagnosis."],"changedPractice":true,"participants":2957},{"id":"paper-iris-imatinib-nejm-2003","kind":"paper","name":"IRIS: imatinib versus interferon plus cytarabine as first treatment for chronic myeloid leukaemia","aka":[],"tldr":"Imatinib beat the previous standard by a wide margin in newly diagnosed CML, and the long-term follow-up showed most patients alive at ten years.","summary":"IRIS randomised 1106 patients with newly diagnosed chronic-phase CML to imatinib 400 mg daily or interferon alfa plus low-dose cytarabine. The primary endpoint was progression-free survival; secondary endpoints included haematological and cytogenetic response. At 18 months the complete cytogenetic response rate was 76.2% with imatinib versus 14.5%, and freedom from progression to accelerated phase or blast crisis was 96.7% versus 91.5%. Crossover from the interferon arm was extensive. The 10-year follow-up (Hochhaus et al., NEJM 2017) reported estimated overall survival of 83.3% on imatinib, with few new serious adverse events after the first year.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa022457"},{"label":"10-year follow-up (Hochhaus 2017)","url":"https://doi.org/10.1056/NEJMoa1609324"},{"label":"ClinicalTrials.gov NCT00006343","url":"https://clinicaltrials.gov/study/NCT00006343"}],"tags":[],"related":["paper-druker-imatinib-phase1-nejm-2001"],"cancers":["cml"],"sections":[],"technologies":[],"targets":["bcr-abl"],"drugs":["imatinib","dasatinib","nilotinib","asciminib"],"companies":["novartis"],"institutions":[],"pathways":[],"terms":["pfs","os"],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-global-access"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2003,"doi":"10.1056/NEJMoa022457","authors":"O'Brien SG, Guilhot F, Larson RA, et al.","paperType":"rct","findings":["1106 patients randomised; imatinib 400 mg/day vs interferon alfa + low-dose cytarabine.","Complete cytogenetic response at 18 months: 76.2% vs 14.5%; major cytogenetic response 87.1% vs 34.7%.","Freedom from progression to accelerated phase or blast crisis at 18 months: 96.7% vs 91.5%.","Imatinib was far better tolerated; most interferon patients eventually crossed over.","10-year follow-up: estimated overall survival 83.3% on imatinib, close to age-matched population survival."],"whatItMeans":"IRIS made imatinib the first-line standard for CML worldwide and established the tyrosine kinase inhibitor as a chronic, life-long oral therapy. For most patients CML became a manageable condition with near-normal life expectancy. Later generations of TKIs (dasatinib, nilotinib, asciminib) produce faster, deeper responses but have not shown a survival advantage over imatinib.","caveats":["Heavy crossover meant overall survival could not be compared cleanly between arms.","The primary endpoint was progression, not survival; molecular response monitoring was introduced later.","Long-term data come from the imatinib arm alone.","Treatment-free remission, now a goal for deep responders, was not part of the original design."],"changedPractice":true,"participants":1106},{"id":"paper-isg-sts-1001-gronchi-lancet-oncol-2017","kind":"paper","name":"ISG-STS 1001: histotype-tailored neoadjuvant chemotherapy versus standard chemotherapy in high-risk soft tissue sarcoma","aka":[],"tldr":"Trying to match neoadjuvant chemotherapy to sarcoma subtype backfired: standard epirubicin-ifosfamide gave better disease-free and overall survival than the tailored regimens, and in doing so provided evidence that neoadjuvant anthracycline-ifosfamide itself helps high-risk patients.","summary":"Phase 3 trial of 287 patients with high-risk localised soft tissue sarcoma of the limbs or trunk wall in five histological subtypes randomised to three cycles of neoadjuvant epirubicin-ifosfamide or a histotype-tailored regimen (gemcitabine-docetaxel, trabectedin, high-dose ifosfamide, etoposide-ifosfamide or gemcitabine-dacarbazine).\n\nThe trial stopped early for futility: 46-month disease-free survival was 62 percent with standard chemotherapy against 38 percent with tailored regimens, and overall survival 89 versus 64 percent, with the difference driven by undifferentiated pleomorphic sarcoma and other subtypes.","asOf":"2026-09-17","links":[{"label":"Lancet Oncol 2017","url":"https://doi.org/10.1016/S1470-2045(17)30334-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28499583/"}],"tags":[],"related":[],"cancers":["extremity-soft-tissue-sarcoma","undifferentiated-pleomorphic-sarcoma","synovial-sarcoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["isg-sts-1001"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2017,"doi":"10.1016/S1470-2045(17)30334-0","pmid":"28499583","authors":"Gronchi A, Ferrari S, Quagliuolo V, et al.","paperType":"rct","findings":["46-month disease-free survival 62 percent (standard) vs 38 percent (tailored).","Overall survival 89 percent vs 64 percent."],"whatItMeans":"Three cycles of neoadjuvant anthracycline-ifosfamide is a reasonable standard for fit patients with high-risk limb or trunk sarcoma, particularly undifferentiated pleomorphic sarcoma.","caveats":["Absence of a surgery-alone arm means the benefit of chemotherapy is inferred rather than proven.","Tailored regimens performed worse partly because some had little single-agent activity."],"changedPractice":true,"participants":287},{"id":"paper-mujumdar-ivermectin-gynaecological-cancer-2025","kind":"paper","name":"Ivermectin and gynecologic cancer: what's the data?","aka":[],"tldr":"Gynaecological oncologists reviewed the evidence for ivermectin in womb, ovarian and cervical cancers, found only cell-line data, and strongly caution against using it.","summary":"The review states that ivermectin was approved by the FDA in 1996 as an oral medicine for intestinal strongyloidiasis and onchocerciasis, that data on it as a gynaecological cancer-fighting compound are lacking, and that clinical studies of ivermectin in cancer are limited to effects observed in cell lines (Mujumdar review 2025). Its authors write that they have not assessed its safety and efficacy in gynaecological cancers and 'do not recommend and strongly caution' its use (Mujumdar review 2025).","asOf":"2026-09-24","links":[{"label":"Mujumdar review 2025","url":"https://doi.org/10.1016/j.gore.2025.101803"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40851910/"}],"tags":[],"related":[],"cancers":["ovarian","endometrial","cervical"],"sections":[],"technologies":["fenbendazole-ivermectin-repurposing-claims"],"targets":[],"drugs":["ivermectin"],"companies":[],"institutions":[],"pathways":[],"terms":["cell-line"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo agent (Claude Fable 5.1)","editedOn":"2026-09-24","note":"Written from cached ClinicalTrials.gov v2, Europe PMC, DailyMed, Drugs@FDA and WHO eEML responses; no figure appears without its source link."},"journal":"Gynecologic Oncology Reports","year":2025,"doi":"10.1016/j.gore.2025.101803","pmid":"40851910","authors":"Mujumdar V, Huang M, Smith LC, Musa F.","paperType":"review","findings":["Clinical evidence for ivermectin in gynaecological cancers is limited to cell-line studies.","The authors strongly caution against its use for these cancers."],"whatItMeans":"For a patient with a gynaecological cancer, the specialists who would run such a trial say the evidence does not exist yet.","caveats":["Review of a field with almost no clinical data; the conclusion rests on absence of evidence rather than on trials showing harm."],"changedPractice":false},{"id":"paper-draganov-ivermectin-cold-tumours-npj-breast-cancer-2021","kind":"paper","name":"Ivermectin converts cold tumors hot and synergizes with immune checkpoint blockade for treatment of breast cancer (with 2026 expression of concern)","aka":[],"tldr":"The mouse study behind the current trials: ivermectin on its own did nothing to breast tumours in mice, but with an anti-PD-1 antibody the pair shrank them. The journal has since flagged duplicated images in one figure and the raw data are gone.","summary":"In mouse models of breast cancer, ivermectin induced immunogenic cell death and T-cell infiltration, and as a modulator of the ATP/P2X4/P2X7 axis reduced regulatory T cells and suppressive myeloid cells; neither ivermectin nor the anti-PD-1 antibody alone showed efficacy in vivo, but the combination limited tumour growth, produced complete responses and reduced relapse in neoadjuvant, adjuvant and metastatic settings (Draganov mouse study 2021). In June 2026 the journal issued an editorial expression of concern: multiple highly similar images were found between panels 4d and 4f, an author correction had already removed some duplicates, further checks found more, and the authors stated that the original data are no longer available, so readers are advised to interpret these data with caution (Expression of concern 2026).","asOf":"2026-09-24","links":[{"label":"Draganov mouse study 2021","url":"https://doi.org/10.1038/s41523-021-00229-5"},{"label":"Expression of concern 2026","url":"https://doi.org/10.1038/s41523-026-00988-z"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33654071/"},{"label":"Expression of concern on PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42248882/"}],"tags":[],"related":[],"cancers":["tnbc"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["ivermectin"],"companies":[],"institutions":[],"pathways":[],"terms":["preclinical","in-vitro-in-vivo"],"trials":["nct05318469","nct07487805"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo agent (Claude Fable 5.1)","editedOn":"2026-09-24","note":"Written from cached ClinicalTrials.gov v2, Europe PMC, DailyMed, Drugs@FDA and WHO eEML responses; no figure appears without its source link."},"journal":"npj Breast Cancer","year":2021,"doi":"10.1038/s41523-021-00229-5","pmid":"33654071","authors":"Draganov D, Han Z, Rana A, Bennett N, Irvine DJ, Lee PP.","paperType":"basic","findings":["Mice only: ivermectin alone had no effect on tumour growth; ivermectin plus anti-PD-1 limited growth and produced complete responses.","Expression of concern, 5 June 2026: duplicated images in Figure 4d and 4f, original data unavailable."],"whatItMeans":"This is the scientific basis for pairing ivermectin with checkpoint antibodies in the Cedars-Sinai and ICONIC trials. Its key figure is now in doubt, which makes those trials more important, not less, as the only way to find out whether the effect is real.","caveats":["Animal study; no patient data.","Editorial expression of concern issued 5 June 2026 over duplicated images; original data no longer available.","An author correction (npj Breast Cancer 2026;12:31) preceded the expression of concern."],"changedPractice":false},{"id":"paper-patel-ivermectin-cancer-curr-oncol-rep-2025","kind":"paper","name":"Ivermectin in cancer treatment: should healthcare providers caution or explore its therapeutic potential?","aka":[],"tldr":"A 2025 review that weighs the laboratory promise against the absence of human trials and concludes that clinicians should counter misinformation while supporting proper trials.","summary":"The review finds that in vitro and animal studies show anticancer effects through Wnt/beta-catenin and Akt/mTOR signalling, but that clinical evidence in humans is limited, with no large randomised controlled trials confirming benefit (Patel review 2025). It notes that observational studies and case reports show the risks of self-medication driven by social media, which has led to toxicity in some oncology patients, and calls the gap between preclinical and clinical evidence a critical translational gap (Patel review 2025).","asOf":"2026-09-24","links":[{"label":"Patel review 2025","url":"https://doi.org/10.1007/s11912-025-01704-z"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40715995/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["fenbendazole-ivermectin-repurposing-claims"],"targets":[],"drugs":["ivermectin"],"companies":[],"institutions":[],"pathways":[],"terms":["preclinical","off-label"],"trials":[],"people":[],"bottlenecks":["b-misinformation"],"keyPapers":[],"journals":["current-oncology-reports"],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo agent (Claude Fable 5.1)","editedOn":"2026-09-24","note":"Written from cached ClinicalTrials.gov v2, Europe PMC, DailyMed, Drugs@FDA and WHO eEML responses; no figure appears without its source link."},"journal":"Current Oncology Reports","year":2025,"doi":"10.1007/s11912-025-01704-z","pmid":"40715995","authors":"Patel Y, Chawla J, Parmar MS.","paperType":"review","findings":["No large randomised trial confirms any therapeutic benefit of ivermectin in cancer.","Self-medication driven by social media has caused toxicity in oncology patients."],"whatItMeans":"The clearest recent statement of where the evidence stands: promising in a dish, untested in people, and already causing harm through self-dosing.","caveats":["Narrative review; it does not add new data."],"changedPractice":false},{"id":"paper-yilmaz-ivermectin-toxicity-j-appl-toxicol-2026","kind":"paper","name":"Ivermectin toxicity in humans and animals: clinical spectrum, mechanisms, and management","aka":[],"tldr":"A 2026 review of how ivermectin poisons the nervous system: usually safe at approved doses, but encephalopathy, seizures, coma and death have followed high doses, and the pump that keeps it out of the brain is the key factor.","summary":"The review integrates controlled human trials, pharmacovigilance, case reports and animal studies, and finds that early placebo-controlled studies in healthy volunteers showed ivermectin well tolerated even at doses well above approved levels, while post-marketing surveillance has identified rare but severe neurotoxic events, including encephalopathy, seizures, coma and death, after supratherapeutic exposure and, in susceptible people, at standard doses (Yilmaz toxicity review 2026). It identifies impairment or saturation of P-glycoprotein-mediated efflux at the blood-brain barrier as the central determinant of neurotoxicity, and records that the COVID-19 pandemic brought a substantial increase in toxic exposures, especially to veterinary formulations, without demonstrated clinical benefit (Yilmaz toxicity review 2026).","asOf":"2026-09-24","links":[{"label":"Yilmaz toxicity review 2026","url":"https://doi.org/10.1002/jat.70166"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41837342/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["ivermectin"],"companies":[],"institutions":[],"pathways":[],"terms":["pharmacokinetics"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo agent (Claude Fable 5.1)","editedOn":"2026-09-24","note":"Written from cached ClinicalTrials.gov v2, Europe PMC, DailyMed, Drugs@FDA and WHO eEML responses; no figure appears without its source link."},"journal":"Journal of Applied Toxicology","year":2026,"doi":"10.1002/jat.70166","pmid":"41837342","authors":"Yilmaz S, Göktaş B, Ateş İ, Çelik M.","paperType":"review","findings":["Severe neurotoxicity follows high or cumulative dosing and, in susceptible people, standard doses.","P-glycoprotein efflux at the blood-brain barrier is the central determinant; drugs that block it raise the risk.","Pandemic-era off-label use, especially of veterinary products, increased toxic exposures without demonstrated benefit."],"whatItMeans":"Explains why a patient on cancer drugs that inhibit P-glycoprotein or CYP3A4 is at higher risk from ivermectin than a healthy volunteer, and why veterinary doses are dangerous.","caveats":["A review; the human neurotoxicity data are case reports and surveillance rather than controlled studies."],"changedPractice":false},{"id":"paper-straughn-ivermectin-hope-versus-hype-2025","kind":"paper","name":"Ivermectin treatment for gynecologic cancers: hope versus hype","aka":[],"tldr":"An editorial accompanying the gynaecological review: repurposing is legitimate and early trials deserve support, but no major oncology organisation endorses ivermectin for cancer and patients should not forgo proven treatment for it.","summary":"The editorial describes drug repurposing as a sound strategy whose usual failure mode is that agents active in cell culture or mice do not deliver clinical benefit in randomised trials (Straughn editorial 2025). It states that no major oncology organisations, including ASCO, SGO or NCCN, currently endorse ivermectin for cancer treatment, that the clinical evidence is not sufficient to support its use, and that ivermectin used outside approved dosing carries real risks of toxicity and drug interactions (Straughn editorial 2025). It welcomes the early-phase trials now under way and asks the oncology community to resist leaping ahead of the science (Straughn editorial 2025).","asOf":"2026-09-24","links":[{"label":"Straughn editorial 2025","url":"https://doi.org/10.1016/j.gore.2025.101920"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40896730/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["drug-repurposing","fenbendazole-ivermectin-repurposing-claims"],"targets":[],"drugs":["ivermectin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-generic-repurposing","b-misinformation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo agent (Claude Fable 5.1)","editedOn":"2026-09-24","note":"Written from cached ClinicalTrials.gov v2, Europe PMC, DailyMed, Drugs@FDA and WHO eEML responses; no figure appears without its source link."},"journal":"Gynecologic Oncology Reports","year":2025,"doi":"10.1016/j.gore.2025.101920","pmid":"40896730","authors":"Straughn JM.","paperType":"review","findings":["No major oncology organisation endorses ivermectin for cancer treatment.","Early-phase trials are under way and deserve support and scrutiny."],"whatItMeans":"A measured position a patient can take to their oncologist: the drug is being tested properly, and until those tests report, it is not a treatment.","caveats":["Editorial opinion, not a systematic review."],"changedPractice":false},{"id":"paper-rockwell-ivermectin-benzimidazole-prescribing-jama-netw-open-2026","kind":"paper","name":"Ivermectin-benzimidazole prescribing following celebrity endorsement","aka":[],"tldr":"After a January 2025 podcast promoted ivermectin with a dog dewormer as a cancer cure, US prescriptions of the combination doubled overall and rose 2.6-fold among people with cancer, most steeply in the South.","summary":"Using electronic records from 67 US health care organisations covering 68,373,949 patients, the authors compared same-day ivermectin plus benzimidazole prescribing from January to July 2025 with the same months of 2024 (Rockwell JAMA Network Open 2026). Overall prescribing doubled, rate ratio 1.97 with a 99.5 percent confidence interval of 1.70 to 2.29, and among patients with a cancer diagnosis it rose 2.63-fold, 99.5 percent confidence interval 2.08 to 3.24, with larger rises in men, in adults under 65, in White patients and in the South (Rockwell JAMA Network Open 2026). The authors note that no rigorous trial evidence supports ivermectin, fenbendazole or other benzimidazoles for cancer, and that the podcast was viewed more than 60 million times (Rockwell JAMA Network Open 2026).","asOf":"2026-09-24","links":[{"label":"Rockwell JAMA Network Open 2026","url":"https://doi.org/10.1001/jamanetworkopen.2026.16780"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42118539/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["fenbendazole-ivermectin-repurposing-claims"],"targets":[],"drugs":["ivermectin","fenbendazole","mebendazole"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-misinformation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo agent (Claude Fable 5.1)","editedOn":"2026-09-24","note":"Written from cached ClinicalTrials.gov v2, Europe PMC, DailyMed, Drugs@FDA and WHO eEML responses; no figure appears without its source link."},"journal":"JAMA Network Open","year":2026,"doi":"10.1001/jamanetworkopen.2026.16780","pmid":"42118539","authors":"Rockwell MS, Kahn KL, Fendrick AM, Vangala S, Mafi JN.","paperType":"observational","findings":["Combination prescribing doubled after the January 2025 endorsement: rate ratio 1.97 (99.5 percent CI 1.70 to 2.29).","Among patients with cancer the rate ratio was 2.63 (99.5 percent CI 2.08 to 3.24); in the South, 3.91."],"whatItMeans":"Measures the reach of the claim rather than the drug: tens of thousands of prescriptions written on the strength of a podcast, with no trial behind them.","caveats":["Observational; prescriptions ordered, not dispensed or taken; cannot show whether patients delayed conventional treatment."],"changedPractice":false,"participants":68373949},{"id":"paper-tang-ivermectin-potential-anticancer-pharmacol-res-2021","kind":"paper","name":"Ivermectin, a potential anticancer drug derived from an antiparasitic drug","aka":[],"tldr":"A 2021 review of the pathways through which ivermectin killed cancer cells in the laboratory, written as a case for testing it in people.","summary":"The review, indexed as a systematic review, collects reports that ivermectin inhibits proliferation of several tumour cell types by regulating multiple signalling pathways and promotes programmed cell death, and discusses prospects for clinical use (Tang review 2021). The evidence it reviews is from cell lines and animal models (Tang review 2021).","asOf":"2026-09-24","links":[{"label":"Tang review 2021","url":"https://doi.org/10.1016/j.phrs.2020.105207"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32971268/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["drug-repurposing"],"targets":[],"drugs":["ivermectin"],"companies":[],"institutions":[],"pathways":[],"terms":["preclinical","in-vitro-in-vivo"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo agent (Claude Fable 5.1)","editedOn":"2026-09-24","note":"Written from cached ClinicalTrials.gov v2, Europe PMC, DailyMed, Drugs@FDA and WHO eEML responses; no figure appears without its source link."},"journal":"Pharmacological Research","year":2021,"doi":"10.1016/j.phrs.2020.105207","pmid":"32971268","authors":"Tang M, Hu X, Wang Y, et al.","paperType":"review","findings":["Laboratory mechanisms catalogued: proliferation inhibition and programmed cell death across cancer cell lines."],"whatItMeans":"Useful as a map of the laboratory story; it contains no patient outcomes.","caveats":["Preclinical evidence only."],"changedPractice":false},{"id":"paper-harmoni-a-jama-2024","kind":"paper","name":"Ivonescimab Plus Chemotherapy in Non-Small Cell Lung Cancer With EGFR Variant: A Randomized Clinical Trial","aka":[],"tldr":"Published report from the HARMONi-A trial registered as NCT05184712, in JAMA (2024), chosen as the most cited paper whose own text cites the registry id.","summary":"Importance: For patients with non-small cell lung cancer whose disease progressed while receiving EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy, particularly third-generation TKIs, optimal treatment options remain limited.\n\nObjective: To compare the efficacy of ivonescimab plus chemotherapy with chemotherapy alone for patients with relapsed advanced or metastatic non-small cell lung cancer with the epidermal growth factor receptor (EGFR) variant.\n\nDesign, setting, and participants: Double-blind, placebo-controlled, randomized, phase 3 trial at 55 sites in China enrolled participants from January 2022 to November 2022; a total of 322 eligible patients were enrolled.\n\nInterventions: Participants received ivonescimab (n = 161) or placebo (n = 161) plus pemetrexed and carboplatin once every 3 weeks for 4 cycles, followed by maintenance therapy of ivonescimab plus pemetrexed or placebo plus pemetrexed.\n\nMain outcomes and measures: The primary end point was progression-free survival in the intention-to-treat population assessed by an independent radiographic review committee (IRRC) per Response Evaluation Criteria in Solid Tumors version 1.1. The results of the first planned interim analysis are reported.\n\nResults: Among 322 enrolled patients in the ivonescimab and placebo groups, the median age was 59.6 vs 59.4 years and 52.2% vs 50.9% of patients were female. at March 10, 2023, median follow-up time was 7.89 months. Median progression-free survival was 7.1 (95% CI, 5.9-8.7) months in the ivonescimab group vs 4.8 (95% CI, 4.2-5.6) months for placebo (difference, 2.3 months; hazard ratio [HR], 0.46 [95% CI, 0.34-0.62]; P <.001). The prespecified subgroup analysis showed progression-free survival benefit favoring patients receiving ivonescimab over placebo across almost all subgroups, including patients whose disease progressed while receiving third-generation EGFR-TKI therapy (HR, 0.48 [95% CI 0.35-0.66]) and those with brain metastases (HR, 0.40 [95% CI, 0.22-0.73]). The objective response rate was 50.6% (95% CI, 42.6%-58.6%) with ivonescimab and 35.4% (95% CI, 28.0%-43.3%) with placebo (difference, 15.6% [95% CI, 5.3%-26.0%]; P =.006). The median overall survival data were not mature; at data cutoff, 69 patients (21.4%) had died. Grade 3 or higher treatment-emergent adverse events occurred in 99 patients (61.5%) in the ivonescimab group vs 79 patients (49.1%) in the placebo group, the most common of which were chemotherapy-related. Grade 3 or higher immune-related adverse events occurred in 10 patients (6.2%) in the ivonescimab group vs 4 (2.5%) in the placebo group. Grade 3 or higher vascular endothelial growth factor-related adverse events occurred in 5 patients (3.1%) in the ivonescimab group vs 4 (2.5%) in the placebo group.\n\nConclusions: Ivonescimab plus chemotherapy significantly improved progression-free survival with tolerable safety profile in TKI-treated non-small cell lung cancer.\n\nTrial registration: ClinicalTrials.gov Identifier: NCT05184712.\n\nIndexed on Europe PMC as PubMed record 38820549 (DOI 10.1001/jama.2024.10613). Its abstract cites the registry id NCT05184712, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"JAMA 2024","url":"https://doi.org/10.1001/jama.2024.10613"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38820549/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38820549"},{"label":"ClinicalTrials.gov NCT05184712","url":"https://clinicaltrials.gov/study/NCT05184712"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["harmoni-a"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2024,"doi":"10.1001/jama.2024.10613","pmid":"38820549","authors":"HARMONi-A Study Investigators, Fang W, Zhao Y, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05184712 with the most citations, so it is the natural first reading for anyone following the HARMONi-A trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-nct06396065-lancet-oncol-2026","kind":"paper","name":"Ivonescimab plus chemotherapy versus placebo plus chemotherapy in patients with advanced EGFR-mutated non-small-cell lung cancer after disease progression on EGFR tyrosine kinase inhibitor therapy (HARMONi): a multicentre, randomised, double-blind, phase 3 trial","aka":[],"tldr":"Published report from the trial registered as NCT06396065, in The Lancet Oncology (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Ivonescimab has shown clinical efficacy in non-small-cell lung cancer (NSCLC). We aimed to assess the efficacy and safety of ivonescimab plus chemotherapy versus placebo plus chemotherapy in patients with advanced EGFR-mutated NSCLC whose disease progressed after third-generation EGFR tyrosine kinase inhibitor (TKI) therapy.\n\nMethods: HARMONi is a randomised, placebo-controlled, double-blind, phase 3 trial done at 114 cancer centres and hospitals across Asia, Europe, and North America. Eligible patients were aged at least 18 years (upper limit: 75 years in Asia) with stage IIIB/IIIC or IV non-squamous EGFR-mutated NSCLC, disease progression after treatment with a third-generation EGFR-TKI, and an Eastern Cooperative Oncology Group performance status score of 0 or 1. Patients were randomly assigned (1:1) via a centralised interactive voice response system or interactive web response system to receive ivonescimab (20 mg/kg) or placebo plus pemetrexed (500 mg/m 2) and carboplatin (target area under the curve 5 mg/mL per min) intravenously every 3 weeks. Randomisation was stratified by brain metastases status at enrolment and geographical region. The primary endpoints were progression-free survival by blinded independent radiology review committee and overall survival in the intention-to-treat population. Safety was assessed in patients who received at least one dose of trial treatment. This study is registered with ClinicalTrials.gov (NCT06396065), has completed enrolment, and is ongoing for treatment and follow-up.\n\nFindings: From Jan 25, 2022, to Oct 1, 2024, 660 individuals were screened for eligibility; of these, 438 were enrolled and randomly assigned to receive ivonescimab plus chemotherapy or placebo plus chemotherapy (219 per group). Of enrolled patients, 257 (59%) were female and 181 (41%) were male; 306 (70%) reported race as Asian, and 105 (24%) as White. At a median follow-up of 22·3 months (95% CI 21·5-23·0), 275 progression or death events had occurred in 345 patients (129 events among 172 patients in the ivonescimab plus chemotherapy group and 146 events among 173 patients in the placebo plus chemotherapy group). Median progression-free survival was 6·8 months (95% CI 5·7-7·1) in the ivonescimab plus chemotherapy group versus 4·4 months (4·1-5·5) in the placebo plus chemotherapy group (hazard ratio [HR] 0·52; 95% CI 0·41-0·66; p<0·0001). At a median follow-up of 29·7 months (95% CI 27·7-31·0), 262 deaths occurred in 438 patients (122 in the ivonescimab plus chemotherapy group and 140 in the placebo plus chemotherapy group). Median overall survival was 16·8 months (14·3-19·0) in the ivonescimab plus chemotherapy group versus 14·0 months (12·8-15·7) in the placebo plus chemotherapy group (HR 0·79; 0·62-1·01). The most common grade 3-4 treatment-related adverse events in the ivonescimab plus chemotherapy versus the placebo plus chemotherapy group were decreased neutrophil count (42 [19%] of 218 vs 36 [17%] of 218), decreased white blood cell count (28 [13%] vs 24 [11%]), decreased platelet count (27 [12%] vs 14 [6%]), and anaemia (22 [10%] vs 27 [12%]). Serious treatment-related adverse events occurred in 61 (28%) patients in the ivonescimab plus chemotherapy group and 33 (15%) patients in the placebo plus chemotherapy group. Treatment-related adverse events led to death in four patients (disease progression, multiple organ dysfunction syndrome, and hepatic failure, each in one patient; gastrointestinal haemorrhage and pulmonary embolism in one patient) in the ivonescimab plus chemotherapy group and five patients (pneumonitis, myocardial infarction, cerebrovascular accident, cognitive disorder, and embolic stroke, each in one patient) in the placebo plus chemotherapy group.\n\nInterpretation: Ivonescimab plus chemotherapy showed a clinically meaningful and statistically significant progression-free survival benefit in patients with EGFR-mutated NSCLC after progression on EGFR-TKI therapy. The clinical benefit and lack of new safety signals of ivonescimab with chemotherapy support the potential for the combination as a new treatment option in this patient population.\n\nFunding: Summit Therapeutics.\n\nIndexed on Europe PMC as PubMed record 42636833 (DOI 10.1016/s1470-2045(26)00282-2). Its abstract cites the registry id NCT06396065, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2026","url":"https://doi.org/10.1016/s1470-2045(26)00282-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42636833/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42636833"},{"label":"ClinicalTrials.gov NCT06396065","url":"https://clinicaltrials.gov/study/NCT06396065"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct06396065"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2026,"doi":"10.1016/s1470-2045(26)00282-2","pmid":"42636833","authors":"Le X, Passaro A, Zhao Y, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT06396065 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-nct05840016-lancet-2025","kind":"paper","name":"Ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy as first-line treatment for advanced squamous non-small-cell lung cancer (HARMONi-6): a randomised, double-blind, phase 3 trial","aka":[],"tldr":"Published report from the trial registered as NCT05840016, in The Lancet (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Squamous non-small-cell lung cancer (NSCLC) is associated with worse clinical outcomes than non-squamous NSCLC, but treatment options are scarce. We aimed to evaluate the efficacy and safety of ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy as a first-line therapy for patients with advanced squamous NSCLC.\n\nMethods: We conducted a randomised, double-blind, phase 3 trial at 50 sites across China (HARMONi-6). Patients aged 18-75 years with previously untreated, pathologically confirmed, unresectable stage IIIB, IIIC, or stage IV squamous NSCLC and an Eastern Cooperative Oncology Group performance status score of 0 or 1 were eligible for inclusion. Patients were randomly assigned (1:1) to receive intravenous ivonescimab (20 mg/kg) or tislelizumab (200 mg), plus intravenous paclitaxel (175 mg/m 2) and carboplatin (area under the curve 5 mg/mL per min) once every 3 weeks for four cycles, followed by ivonescimab (20 mg/kg) or tislelizumab (200 mg) monotherapy as maintenance treatment for up to 24 months. Randomisation was stratified by disease stage (IIIB or IIIC vs IV) and PD-L1 tumour proportion score (≥1% vs <1%). The primary endpoint was progression-free survival assessed by the independent radiographic review committee as per Response Evaluation Criteria in Solid Tumours guidelines (version 1.1) in all randomly assigned patients. Safety, defined as adverse events and serious adverse events related to treatment, as well as adverse events related to immunity or VEGF blockade, were analysed in all randomly assigned patients who received at least one dose of the assigned study treatment. This study is registered at ClinicalTrial.gov (NCT05840016), has completed enrolment, and is ongoing for treatment and follow-up.\n\nFindings: From Aug 17, 2023, to Jan 21, 2025, 761 patients were screened for eligibility, among whom 532 (70%) patients were enrolled and randomly assigned to receive ivonescimab plus chemotherapy (266 [50%] patients) or tislelizumab plus chemotherapy (266 [50%] patients). at Feb 28, 2025, median follow-up time was 10·3 months (95% CI 9·5-11·0). Median progression-free survival was 11·1 months (95% CI 9·9-not evaluable) in the ivonescimab group and 6·9 months (5·8-8·6) in the tislelizumab group (hazard ratio 0·60 [95% CI 0·46-0·78]; one-sided p<0·0001). The progression-free survival benefit with ivonescimab plus chemotherapy was consistent regardless of PD-L1 status. 170 (64%) patients in the ivonescimab group and 144 (54%) patients in the tislelizumab group had grade 3 or higher treatment-related adverse events, with grade 3 or higher immune-related adverse events occurring in 24 (9%) patients in the ivonescimab group and in 27 (10%) patients in the tislelizumab group. Grade 3 or higher treatment-related haemorrhage occurred in five (2%) patients in the ivonescimab group and in two (1%) patients in the tislelizumab group.\n\nInterpretation: In patients with untreated advanced squamous NSCLC, ivonescimab plus chemotherapy showed significantly improved progression-free survival compared with tislelizumab plus chemotherapy, regardless of PD-L1 status, as well as a manageable safety profile. This regimen could be used as a novel first-line treatment in this patient group.\n\nFunding: Akeso Biopharma.\n\nIndexed on Europe PMC as PubMed record 41125109 (DOI 10.1016/s0140-6736(25)01848-3). Its abstract cites the registry id NCT05840016, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet 2025","url":"https://doi.org/10.1016/s0140-6736(25)01848-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41125109/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41125109"},{"label":"ClinicalTrials.gov NCT05840016","url":"https://clinicaltrials.gov/study/NCT05840016"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05840016"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2025,"doi":"10.1016/s0140-6736(25)01848-3","pmid":"41125109","authors":"Chen Z, Yang F, Jiang Z, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05840016 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-nct05840016-lancet-2026-update","kind":"paper","name":"Ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy in advanced squamous non-small-cell lung cancer (HARMONi-6): interim overall survival analysis of a randomised, double-blind, phase 3 trial in China","aka":[],"tldr":"Later report from the trial registered as NCT05840016, in The Lancet (2026); its title describes an updated or longer-term analysis.","summary":"Background: Bispecific antibodies targeting programmed death 1 (PD-1) and vascular endothelial growth factor (PD1-VEGF) have shown promising efficacy in non-small-cell lung cancer (NSCLC). In our previous report of the HARMONi-6 study, we aimed to evaluate the efficacy and safety of ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy as a first-line therapy for patients with advanced squamous NSCLC. Ivonescimab combined with chemotherapy significantly prolonged progression-free survival compared with tislelizumab plus chemotherapy. Here we report the prespecified interim overall survival analysis.\n\nMethods: HARMONi-6 is a double-blind, randomised, phase 3 trial, which was conducted at 50 hospitals across China. Patients aged 18-75 years with previously untreated, pathologically confirmed, unresectable stage IIIB, IIIC, or stage IV squamous NSCLC and an Eastern Cooperative Oncology Group performance status score of 0 or 1 were eligible for inclusion. Eligible patients were randomly assigned in a 1:1 ratio to receive ivonescimab or tislelizumab, in combination with paclitaxel and carboplatin for four cycles, followed by maintenance ivonescimab or tislelizumab monotherapy. The primary endpoint was progression-free survival assessed by the independent radiographic review committee as per Response Evaluation Criteria in Solid Tumours guidelines (version 1.1) in all randomly assigned patients. Overall survival was a key secondary endpoint; an interim analysis was planned when approximately 225 overall survival events were observed, but it was triggered after 204 overall survival events to meet regulatory deadlines. Safety, defined as adverse events and serious adverse events related to treatment, as well as adverse events related to immunity or VEGF blockade, were analysed in all randomly assigned patients who received at least one dose of the assigned study treatment. This study is registered at ClinicalTrials.gov (NCT05840016), has completed enrolment, and is ongoing for treatment and follow-up.\n\nFindings: From Aug 17, 2023, to Jan 21, 2025, 761 patients were assessed for eligibility, and after 229 exclusions a total of 532 patients were randomly allocated (266 per group). 494 (93%) of patients were male and 38 (7%) of patients were female. The median age was 64 years (IQR 59-69). At data cutoff (Feb 27, 2026), 204 deaths had occurred: 84 (32%) patients in the ivonescimab plus chemotherapy group and 120 (45%) in the tislelizumab plus chemotherapy group. With a median follow-up of 21·4 months (95% CI 20·27-21·91), the median overall survival was 27·9 months (95% CI 27·89-not evaluable [NE]) with ivonescimab versus 23·7 months (20·11-NE) with tislelizumab (hazard ratio for death 0·66 [95% CI 0·50-0·87]; p one-sided =0·0017), meeting the prespecified boundary (p<0·0049). The overall survival benefit with ivonescimab plus chemotherapy was consistent across key subgroups. Treatment-related adverse events of grade 3 or higher occurred in 184 (69%) of 266 patients in the ivonescimab group and 156 (59%) of 265 patients in the tislelizumab group. The incidence of grade 3 or higher haemorrhage was seven (3%) of 266 and two (1%) of 265, respectively.\n\nInterpretation: Ivonescimab plus chemotherapy demonstrated a statistically significant and clinically meaningful improvement in overall survival compared with tislelizumab plus chemotherapy in previously untreated patients with advanced squamous NSCLC. This regimen could provide a novel treatment option as first-line treatment in this patient group.\n\nFunding: Akeso Biopharma.\n\nIndexed on Europe PMC as PubMed record 42218899 (DOI 10.1016/s0140-6736(26)00966-9). Its abstract cites the registry id NCT05840016, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet 2026","url":"https://doi.org/10.1016/s0140-6736(26)00966-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42218899/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42218899"},{"label":"ClinicalTrials.gov NCT05840016","url":"https://clinicaltrials.gov/study/NCT05840016"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05840016"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2026,"doi":"10.1016/s0140-6736(26)00966-9","pmid":"42218899","authors":"Lu S, Liu B, Luo Y, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-iwai-pdl1-tumour-escape-pnas-2002","kind":"paper","name":"Iwai and Honjo: tumours use PD-L1 to escape T cells, and blocking it restores attack","aka":[],"tldr":"A decade after Honjo's group cloned PD-1 (1992), this study showed that tumour cells expressing PD-L1 resist killing by cytotoxic T cells in mice, and that anti-PD-L1 antibody or PD-1 deficiency restores tumour rejection, the foundation of PD-1/PD-L1 therapy.","summary":"Tasuku Honjo's group discovered PD-1 in 1992 (Ishida et al., EMBO J) as a gene induced during programmed cell death in T-cell lines, and later showed PD-1-deficient mice develop autoimmunity, identifying it as an inhibitory receptor. PD-L1 (B7-H1) was identified as its ligand by Freeman, Honjo and colleagues in 2000.\n\nIn this paper, P815 mastocytoma cells transfected with PD-L1 were less susceptible to lysis by cytotoxic T lymphocytes in vitro and grew more aggressively in vivo; anti-PD-L1 antibody reversed this. Myeloma cells naturally expressing PD-L1 grew in wild-type mice but were rejected in PD-1-deficient mice. In parallel, Dong and Chen (Nature Medicine 2002) showed that PD-L1 expressed on human tumours induced T-cell apoptosis.\n\nThese data motivated the development of nivolumab (Ono/Medarex) and other PD-1 and PD-L1 antibodies, now the most widely used cancer drugs in the world. Honjo shared the 2018 Nobel Prize with James Allison.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1073/pnas.192461099"},{"label":"Discovery of PD-1 (Ishida 1992)","url":"https://doi.org/10.1002/j.1460-2075.1992.tb05481.x"}],"tags":[],"related":["paper-leach-allison-ctla4-blockade-science-1996"],"cancers":[],"sections":["immunotherapy"],"technologies":["checkpoint-inhibitor"],"targets":["pd1","pdl1"],"drugs":["nivolumab","pembrolizumab","atezolizumab"],"companies":[],"institutions":[],"pathways":["pd1-checkpoint","antigen-presentation-immunoediting"],"terms":[],"trials":[],"people":["drew-pardoll","james-allison"],"bottlenecks":["b-immunotherapy-response","b-biomarker-validation"],"keyPapers":[],"journals":["pnas"],"dependsOn":[],"notes":[],"journal":"PNAS","year":2002,"doi":"10.1073/pnas.192461099","pmid":"12218188","authors":"Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, Minato N","paperType":"basic","findings":["PD-L1 expression on tumour cells reduced cytotoxic T-cell killing in vitro and enhanced tumour growth in mice","Anti-PD-L1 antibody suppressed growth of PD-L1-expressing tumours","Naturally PD-L1-positive myeloma cells were rejected in PD-1-deficient mice but not in wild-type mice","Together with Ishida 1992 and Freeman 2000, defined the PD-1/PD-L1 axis as a tumour immune-escape mechanism"],"whatItMeans":"Tumours hide from T cells by displaying PD-L1; blocking that interaction lets the immune system attack. This is the mechanism of pembrolizumab, nivolumab, atezolizumab and their relatives, which now treat more than 20 cancer types.","caveats":["Mouse tumour models overexpressing PD-L1 exaggerate a mechanism that is only one of many in human tumours","PD-L1 expression on tumour cells is an imperfect biomarker of response in patients","Most patients do not respond to PD-1 blockade, and mechanisms of primary resistance remain incompletely understood","Clinical translation took another decade and depended on industry (Ono, Medarex, BMS, Merck) investment"],"changedPractice":false},{"id":"paper-jaiswal-chip-nejm-2014","kind":"paper","name":"Jaiswal: clonal haematopoiesis, the pre-leukaemic clones in most people over 70","aka":[],"tldr":"Blood DNA from 17,182 people showed that clones carrying leukaemia-associated mutations (mostly DNMT3A, TET2, ASXL1) are present in about 10% of people over 70, raising the risk of blood cancer 11-fold and, unexpectedly, of heart attack and stroke.","summary":"Exome sequences generated for diabetes genetics studies were mined for somatic mutations in genes recurrently mutated in blood cancers. Clonal haematopoiesis of indeterminate potential (CHIP) was rare under 40 but present in 9.5% of people aged 70-79 and 18.4% over 90.\n\nCarriers had an 11-fold higher risk of subsequent haematological cancer, though the absolute rate was modest (about 0.5-1% per year). Strikingly, CHIP was associated with higher all-cause mortality (HR 1.4), driven by cardiovascular disease: coronary heart disease HR 2.0 and ischaemic stroke HR 2.6. A companion paper (Genovese, NEJM 2014) reported the same phenomenon in a Swedish cohort.\n\nCHIP is now recognised as a common age-related premalignant state, a driver of cardiovascular inflammation, a source of false positives in ctDNA tests, and a target for prevention.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1056/NEJMoa1408617"},{"label":"Genovese 2014 companion paper","url":"https://doi.org/10.1056/NEJMoa1409405"}],"tags":[],"related":["paper-martincorena-somatic-mutations-normal-skin-science-2015","idea-chip-risk-modifiers"],"cancers":["aml"],"sections":["early-detection","prevention"],"technologies":["wes-wgs","liquid-biopsy"],"targets":[],"drugs":[],"companies":[],"institutions":["broad-institute","dana-farber"],"pathways":["clonal-haematopoiesis","clonal-evolution"],"terms":["vaf","ctdna"],"trials":[],"people":["benjamin-ebert"],"bottlenecks":["b-early-detection","b-biomarker-validation","b-aging-comorbidity"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2014,"doi":"10.1056/NEJMoa1408617","pmid":"25426837","authors":"Jaiswal S, Fontanillas P, Flannick J, et al.","paperType":"observational","findings":["CHIP prevalence 9.5% at ages 70-79 and 18.4% over 90, versus under 1% below 40","Haematological cancer risk HR 11.1 (95% CI 3.9-32.6); absolute risk about 0.5-1% per year","All-cause mortality HR 1.4; coronary heart disease HR 2.0; ischaemic stroke HR 2.6","Most common mutated genes: DNMT3A, TET2, ASXL1"],"whatItMeans":"Many older people carry blood clones one or two steps from leukaemia, and those clones also drive heart disease through inflammation. CHIP is why blood-based cancer tests must filter out mutations from blood cells, and it opens a route to preventing both leukaemia and cardiovascular events in carriers.","caveats":["Cross-sectional discovery with limited follow-up; the leukaemia progression rate was estimated from a small number of events","Exome sequencing at modest depth detects only clones above about 2% variant allele fraction","Cohorts were ascertained for metabolic disease, which may inflate cardiovascular associations","No intervention has yet been shown to reduce CHIP-related risk"],"changedPractice":false,"participants":17182},{"id":"paper-raajit-rampal-cancer-discov-2015","kind":"paper","name":"JAK-STAT pathway activation in malignant and nonmalignant cells contributes to MPN pathogenesis and therapeutic response","aka":[],"tldr":"Paper by Raajit K. Rampal indexed on Europe PMC as PubMed record 25572172, in Cancer Discovery (2015), one of the most cited records naming an author with this name at Memorial Sloan Kettering Cancer Center.","summary":"Unlabelled: The identification of JAK2/MPL mutations in patients with myeloproliferative neoplasms (MPN) has led to the clinical development of JAK kinase inhibitors, including ruxolitinib. Ruxolitinib reduces splenomegaly and systemic symptoms in myelofibrosis and improves overall survival; however, the mechanism by which JAK inhibitors achieve efficacy has not been delineated. Patients with MPN present with increased levels of circulating proinflammatory cytokines, which are mitigated by JAK inhibitor therapy. We sought to elucidate mechanisms by which JAK inhibitors attenuate cytokine-mediated pathophysiology. Single-cell profiling demonstrated that hematopoietic cells from myelofibrosis models and patient samples aberrantly secrete inflammatory cytokines. Pan-hematopoietic Stat3 deletion reduced disease severity and attenuated cytokine secretion, with similar efficacy as observed with ruxolitinib therapy. In contrast, Stat3 deletion restricted to MPN cells did not reduce disease severity or cytokine production. Consistent with these observations, we found that malignant and nonmalignant cells aberrantly secrete cytokines and JAK inhibition reduces cytokine production from both populations.\n\nSignificance: Our results demonstrate that JAK-STAT3-mediated cytokine production from malignant and nonmalignant cells contributes to MPN pathogenesis and that JAK inhibition in both populations is required for therapeutic efficacy. These findings provide novel insight into the mechanisms by which JAK kinase inhibition achieves therapeutic efficacy in MPNs.\n\nIndexed on Europe PMC as PubMed record 25572172 (DOI 10.1158/2159-8290.cd-14-0736). Its author list gives \"Rampal R\" with the affiliation \"Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York. Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York\", which names Memorial Sloan Kettering Cancer Center; that is how the record was matched to Raajit K. Rampal, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer Discov 2015","url":"https://doi.org/10.1158/2159-8290.cd-14-0736"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25572172/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25572172"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["raajit-rampal"],"bottlenecks":[],"keyPapers":[],"journals":["cancer-discovery"],"dependsOn":[],"notes":[],"journal":"Cancer Discovery","year":2015,"doi":"10.1158/2159-8290.cd-14-0736","pmid":"25572172","authors":"Kleppe M, Kwak M, Koppikar P, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Raajit K. Rampal at Memorial Sloan Kettering Cancer Center, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-japanese-gastric-cancer-treatment-guidelines-2021-gastric-cancer-2023","kind":"paper","name":"Japanese gastric cancer treatment guidelines 2021 (6th edition)","aka":[],"tldr":"The Japanese Gastric Cancer Association guideline sets the criteria for endoscopic resection, the extent of gastrectomy and lymph node dissection, adjuvant chemotherapy by stage and systemic therapy for advanced disease, and is the reference for early gastric cancer worldwide.","summary":"Sixth edition of the Japanese guideline covering absolute and expanded indications for endoscopic submucosal dissection, eCura assessment of curability, surgical procedures and D1+ or D2 lymphadenectomy, laparoscopic and robotic surgery, adjuvant S-1-based chemotherapy, perioperative therapy, and first- to third-line systemic therapy for unresectable disease.","asOf":"2026-09-17","links":[{"label":"Gastric Cancer 2023","url":"https://doi.org/10.1007/s10120-022-01331-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36342574/"}],"tags":[],"related":[],"cancers":["early-gastric-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["gastric-cancer"],"dependsOn":[],"notes":[],"journal":"Gastric cancer","year":2023,"doi":"10.1007/s10120-022-01331-8","pmid":"36342574","authors":"Japanese Gastric Cancer Association.","paperType":"guideline","findings":[],"whatItMeans":"The early gastric cancer page's endoscopic criteria and surgical recommendations follow this guideline.","caveats":["Adjuvant and advanced-disease recommendations reflect Japanese practice (S-1) and differ from Western guidelines."],"changedPractice":true},{"id":"paper-javelin-bladder-100-nejm-2020","kind":"paper","name":"JAVELIN Bladder 100: avelumab maintenance after first-line platinum chemotherapy in advanced urothelial cancer","aka":[],"tldr":"Continuing with the immunotherapy avelumab after chemotherapy had controlled advanced bladder cancer lengthened survival by about seven months compared with watching and waiting.","summary":"Phase 3 trial of 700 patients with unresectable locally advanced or metastatic urothelial carcinoma whose disease had not progressed on four to six cycles of platinum-based chemotherapy, randomised to avelumab maintenance plus best supportive care or supportive care alone.\n\nMedian overall survival was 21.4 months with avelumab against 14.3 months with supportive care (hazard ratio 0.69). The benefit was seen regardless of PD-L1 status and established switch maintenance immunotherapy as the standard after first-line chemotherapy until enfortumab vedotin plus pembrolizumab displaced chemotherapy in the first line.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2020","url":"https://doi.org/10.1056/NEJMoa2002788"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32945632/"}],"tags":[],"related":[],"cancers":["muscle-invasive-bladder-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["avelumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["javelin-bladder-100"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2020,"doi":"10.1056/NEJMoa2002788","pmid":"32945632","authors":"Powles T, Park SH, Voog E, et al.","paperType":"rct","findings":["Median overall survival 21.4 vs 14.3 months; hazard ratio for death 0.69.","Benefit in the PD-L1-positive population (hazard ratio 0.56) and in the overall population."],"whatItMeans":"For patients who still receive platinum chemotherapy first, avelumab maintenance rather than observation is the standard next step. Where enfortumab vedotin plus pembrolizumab is available first line, this sequence is used less.","caveats":["Open-label design.","The comparator did not include immunotherapy at progression for all patients, which may exaggerate the gain compared with sequential use."],"changedPractice":true,"participants":700},{"id":"paper-jcog0912-katai-lancet-gastroenterol-hepatol-2020","kind":"paper","name":"JCOG0912: laparoscopy-assisted versus open distal gastrectomy for clinical stage IA or IB gastric cancer","aka":[],"tldr":"Japan's randomised trial confirmed that laparoscopy-assisted distal gastrectomy is not inferior to open surgery for relapse-free survival in stage I gastric cancer, cementing the minimally invasive approach.","summary":"Phase 3 non-inferiority trial of 921 patients with clinical stage IA or IB gastric cancer randomised to laparoscopy-assisted or open distal gastrectomy with D1+ or D2 lymphadenectomy at Japanese centres.\n\nFive-year relapse-free survival was 95.1 percent with laparoscopic and 94.0 percent with open surgery, meeting non-inferiority, with similar overall survival and no differences in long-term complications.","asOf":"2026-09-17","links":[{"label":"Lancet Gastroenterol Hepatol 2020","url":"https://doi.org/10.1016/S2468-1253(19)30332-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31757656/"}],"tags":[],"related":[],"cancers":["early-gastric-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["klass-01"],"people":["hitoshi-katai"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Lancet Gastroenterology and Hepatology","year":2020,"doi":"10.1016/S2468-1253(19)30332-2","pmid":"31757656","authors":"Katai H, Mizusawa J, Katayama H, et al.","paperType":"rct","findings":["Five-year relapse-free survival 95.1 percent (laparoscopic) vs 94.0 percent (open); non-inferior."],"whatItMeans":"Together with KLASS-01, this trial makes laparoscopic distal gastrectomy the standard for early gastric cancer needing surgery.","caveats":["Applies to distal tumours; total gastrectomy and advanced disease were studied separately."],"changedPractice":true,"participants":921},{"id":"paper-jemal-cancer-statistics-2007-cacancer-2007","kind":"paper","name":"Jemal 2007: Cancer statistics, 2007","aka":[],"tldr":"The American Cancer Society's 2007 report projected about 1.44 million new US cancer cases and recorded a 13.6 percent fall in the overall cancer death rate between 1991 and 2004, even though the absolute number of deaths had only just begun to fall.","summary":"Jemal and colleagues projected 1,444,920 new cancer cases and 559,650 cancer deaths in the United States for 2007, using incidence data to 2003 and mortality data to 2004. Age-standardised incidence for all cancers combined had been stable in men since 1995 while still rising 0.3 percent a year in women, and the combined cancer death rate had fallen 13.6 percent between 1991 and 2004. The report also broke incidence, mortality and survival down by site, sex, race and ethnicity and geography.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.3322/canjclin.57.1.43"},{"label":"ACS Cancer Facts and Figures","url":"https://www.cancer.org/research/cancer-facts-statistics.html"}],"tags":[],"related":["paper-siegel-cancer-statistics-2023-cacancer-2023","paper-siegel-cancer-statistics-2024-cacancer-2024"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["incidence-vs-prevalence","mortality"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"CA: A Cancer Journal for Clinicians","year":2007,"doi":"10.3322/canjclin.57.1.43","authors":"Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ.","paperType":"observational","findings":["Projected 1,444,920 new cancer cases and 559,650 cancer deaths in the United States in 2007.","Overall cancer death rate down 13.6 percent between 1991 and 2004.","Incidence stable in men since 1995 and rising 0.3 percent a year in women."],"whatItMeans":"One of the first editions to quantify the sustained fall in US cancer death rates that later reports tracked as deaths averted.","caveats":["Projections rather than counts.","US-specific."],"changedPractice":false},{"id":"paper-jemal-cancer-statistics-2008-cacancer-2008","kind":"paper","name":"Jemal 2008: Cancer statistics, 2008","aka":[],"tldr":"The American Cancer Society's 2008 report projected about 1.44 million new US cancer cases and estimated that falling death rates since the early 1990s had already avoided more than half a million cancer deaths.","summary":"Jemal and colleagues projected 1,437,180 new cancer cases and 565,650 cancer deaths in the United States for 2008. Incidence rates for all sites combined had stabilised in men from 1995 and in women from 1999, and death rates had fallen 18.4 percent in men since 1990 and 10.5 percent in women since 1991, which the authors translated into more than half a million deaths avoided. The report added education level to its breakdowns by site, sex, race and ethnicity and geography.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.3322/ca.2007.0010"},{"label":"ACS Cancer Facts and Figures","url":"https://www.cancer.org/research/cancer-facts-statistics.html"}],"tags":[],"related":["paper-siegel-cancer-statistics-2023-cacancer-2023","paper-siegel-cancer-statistics-2024-cacancer-2024"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["incidence-vs-prevalence","mortality"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"CA: A Cancer Journal for Clinicians","year":2008,"doi":"10.3322/ca.2007.0010","authors":"Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ.","paperType":"observational","findings":["Projected 1,437,180 new cancer cases and 565,650 cancer deaths in the United States in 2008.","Death rates down 18.4 percent in men from 1990 and 10.5 percent in women from 1991, to 2004.","More than half a million cancer deaths avoided over that period."],"whatItMeans":"The first edition to express progress as deaths avoided, the framing every later report has kept.","caveats":["Projections rather than counts.","US-specific."],"changedPractice":false},{"id":"paper-jemal-cancer-statistics-2009-cacancer-2009","kind":"paper","name":"Jemal 2009: Cancer statistics, 2009","aka":[],"tldr":"The American Cancer Society's 2009 report projected about 1.48 million new US cancer cases and showed incidence now falling in both sexes, with lung, prostate, colorectal and breast cancers driving most of the decline in deaths.","summary":"Jemal and colleagues projected 1,479,350 new cancer cases and 562,340 cancer deaths in the United States for 2009. Overall incidence was falling in men (1.8 percent a year from 2001 to 2005) and women (0.6 percent a year from 1998 to 2005), largely through the big sites: lung, prostate and colorectal cancer in men, breast and colorectal cancer in women. Death rates had fallen 19.2 percent in men between 1990 and 2005 and 11.4 percent in women between 1991 and 2005; declines in lung, prostate and colorectal cancer accounted for nearly 80 percent of the fall in men, and breast and colorectal cancer for 60 percent in women.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.3322/caac.20006"},{"label":"ACS Cancer Facts and Figures","url":"https://www.cancer.org/research/cancer-facts-statistics.html"}],"tags":[],"related":["paper-siegel-cancer-statistics-2023-cacancer-2023","paper-siegel-cancer-statistics-2024-cacancer-2024"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["incidence-vs-prevalence","mortality"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"CA: A Cancer Journal for Clinicians","year":2009,"doi":"10.3322/caac.20006","authors":"Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ.","paperType":"observational","findings":["Projected 1,479,350 new cancer cases and 562,340 cancer deaths in the United States in 2009.","Incidence falling in men by 1.8 percent a year (2001 to 2005) and in women by 0.6 percent a year (1998 to 2005).","Death rates down 19.2 percent in men and 11.4 percent in women; lung, prostate and colorectal cancer explained nearly 80 percent of the fall in men."],"whatItMeans":"Showed the fall in deaths was concentrated in a handful of common cancers where smoking decline, screening and better treatment had taken hold.","caveats":["Projections rather than counts.","US-specific."],"changedPractice":false},{"id":"paper-jemal-cancer-statistics-2010-cacancer-2010","kind":"paper","name":"Jemal 2010: Cancer statistics, 2010","aka":[],"tldr":"The American Cancer Society's 2010 report projected about 1.53 million new US cancer cases and a 21 percent fall in the male cancer death rate since 1990, with declines seen in every racial and ethnic group.","summary":"Jemal, Siegel, Xu and Ward projected 1,529,560 new cancer cases and 569,490 cancer deaths in the United States for 2010. Incidence was falling in men by 1.3 percent a year (2000 to 2006) and in women by 0.5 percent a year (1998 to 2006), driven by lung, prostate and colorectal cancer in men and breast and colorectal cancer in women, and the decrease was seen in every racial and ethnic group except American Indian and Alaska Native women, whose rates were stable. Death rates in men fell 21.0 percent between 1990 and 2006, with lung, prostate and colorectal cancer accounting for nearly 80 percent of the decline.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.3322/caac.20073"},{"label":"ACS Cancer Facts and Figures","url":"https://www.cancer.org/research/cancer-facts-statistics.html"}],"tags":[],"related":["paper-siegel-cancer-statistics-2023-cacancer-2023","paper-siegel-cancer-statistics-2024-cacancer-2024"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["incidence-vs-prevalence","mortality"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"CA: A Cancer Journal for Clinicians","year":2010,"doi":"10.3322/caac.20073","authors":"Jemal A, Siegel R, Xu J, Ward E.","paperType":"observational","findings":["Projected 1,529,560 new cancer cases and 569,490 cancer deaths in the United States in 2010.","Incidence falling in men by 1.3 percent a year and in women by 0.5 percent a year.","Male cancer death rate down 21.0 percent between 1990 and 2006."],"whatItMeans":"Confirmed that the decline in incidence and deaths was reaching most population groups, while flagging the groups it was not.","caveats":["Projections rather than counts.","US-specific."],"changedPractice":false},{"id":"paper-jemal-global-cancer-statistics-2011-cacancer","kind":"paper","name":"Jemal 2011: Global cancer statistics (GLOBOCAN 2008)","aka":[],"tldr":"The world cancer count for 2008: about 12.7 million new cases, with more than half of cases and almost two thirds of deaths already occurring in the economically developing world, breast cancer the most common cancer in women and lung cancer in men.","summary":"Jemal, Bray and colleagues summarised the GLOBOCAN 2008 estimates for the American Cancer Society. They reported about 12.7 million new cancer cases and 7.6 million cancer deaths in 2008, of which 56% of cases and 64% of deaths occurred in the economically developing world. Breast cancer was the most frequently diagnosed cancer and leading cause of cancer death in women; lung cancer held both positions in men. The paper stressed that the burden was shifting to lower-income countries and that much of it was preventable through tobacco control, vaccination and early detection.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.3322/caac.20107"},{"label":"IARC Global Cancer Observatory","url":"https://gco.iarc.who.int/today"}],"tags":[],"related":["paper-torre-global-cancer-statistics-2012-cacancer-2015"],"cancers":["breast-hr-positive","nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["iarc"],"pathways":[],"terms":["incidence-vs-prevalence","mortality"],"trials":[],"people":["bray-freddie"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"CA: A Cancer Journal for Clinicians","year":2011,"doi":"10.3322/caac.20107","authors":"Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D.","paperType":"observational","findings":["About 12.7 million new cancer cases and 7.6 million cancer deaths worldwide in 2008.","56% of cases and 64% of deaths in the economically developing world.","Breast cancer the leading cancer in women and lung cancer in men, for both incidence and death."],"whatItMeans":"For years the most cited paper in oncology, it fixed the picture of cancer as a growing problem of developing countries and is the baseline against which the 2012, 2018, 2020 and 2022 GLOBOCAN releases show the burden rising.","caveats":["Estimates for many countries were modelled from sparse registry data.","Superseded by later GLOBOCAN releases."],"changedPractice":false},{"id":"paper-jones-nrg1-fusions-recurrent-actionable-kras-wild-type-pdac-ccr-2019","kind":"paper","name":"Jones 2019: NRG1 gene fusions are recurrent, clinically actionable rearrangements in KRAS wild-type pancreatic ductal adenocarcinoma","aka":[],"tldr":"In a Canadian programme sequencing the genomes of advanced pancreatic cancers in real time, tumours without a KRAS mutation repeatedly carried NRG1 fusions, and patients treated with HER-family blockers on the strength of that finding responded. It showed that fusion testing in KRAS wild-type disease changes treatment.","summary":"Analysis of whole-genome and transcriptome sequencing from patients with advanced pancreatic ductal adenocarcinoma in the COMPASS trial and related cohorts at BC Cancer and the Ontario Institute for Cancer Research. NRG1 fusions with several different partner genes were identified in a subset of the KRAS wild-type tumours and in none of the KRAS-mutant cases, and were confirmed at the RNA level.\n\nPatients with NRG1 fusion-positive tumours treated with ERBB-targeting drugs such as afatinib had radiological responses and falls in tumour markers. The authors argue for RNA-based fusion testing in every KRAS wild-type pancreatic cancer.","asOf":"2026-09-21","links":[{"label":"Clin Cancer Res 2019","url":"https://doi.org/10.1158/1078-0432.CCR-19-0191"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31068372/"}],"tags":[],"related":[],"cancers":["kras-wild-type-pdac","pancreatic"],"sections":[],"technologies":["wes-wgs","rna-seq"],"targets":["nrg1","kras","her3"],"drugs":["afatinib"],"companies":[],"institutions":["bc-cancer"],"pathways":["rtk-activation"],"terms":["wild-type"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2019,"doi":"10.1158/1078-0432.CCR-19-0191","pmid":"31068372","authors":"Jones MR, Williamson LM, Topham JT, et al.","paperType":"translational","findings":["NRG1 fusions with multiple partners were recurrent among KRAS wild-type tumours and absent from KRAS-mutant tumours.","Patients treated with ERBB inhibitors on the basis of an NRG1 fusion responded, with tumour marker declines."],"whatItMeans":"Together with the German MASTER report, this paper is why guidelines recommend comprehensive profiling with fusion detection in KRAS wild-type pancreatic cancer.","caveats":["Small numbers of fusion-positive patients; responses were described in a handful of cases.","DNA panels with limited intron coverage miss many NRG1 fusions, so the frequency depends on the assay."],"changedPractice":true},{"id":"paper-juliet-tisagenlecleucel-dlbcl-nejm-2019","kind":"paper","name":"JULIET: tisagenlecleucel for adults with relapsed or refractory diffuse large B-cell lymphoma","aka":[],"tldr":"In adults with aggressive lymphoma after at least two prior treatments, tisagenlecleucel produced responses in 52% and complete responses in 40%, most of which lasted.","summary":"JULIET was an international single-arm phase 2 trial of tisagenlecleucel in adults with relapsed or refractory DLBCL after two or more lines of therapy who were ineligible for or had relapsed after autologous transplant. Of 165 enrolled, 111 were infused; 93 were evaluable for efficacy at the primary analysis. The best overall response rate was 52% with complete response in 40%; among responders the estimated relapse-free survival at 12 months was 65% and median duration of response was not reached. Grade 3-4 cytokine release syndrome occurred in 22% and grade 3-4 neurological events in 12%, with no deaths attributed to the product. Bridging chemotherapy was allowed. It supported approval of tisagenlecleucel in DLBCL in 2018, the second CD19 CAR-T for this disease.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa1804980"},{"label":"ClinicalTrials.gov NCT02445248","url":"https://clinicaltrials.gov/study/NCT02445248"}],"tags":[],"related":["paper-zuma-1-axi-cel-nejm-2017","lymphoma-roadmap","paper-belinda-tisagenlecleucel-second-line-nejm-2022"],"cancers":["dlbcl"],"sections":[],"technologies":["car-t"],"targets":["cd19"],"drugs":["tisagenlecleucel"],"companies":["novartis"],"institutions":["penn-abramson"],"pathways":[],"terms":["crs","icans","orr"],"trials":["belinda","juliet"],"people":[],"bottlenecks":["b-manufacturing-cell-therapy"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2019,"doi":"10.1056/NEJMoa1804980","authors":"Schuster SJ, Bishop MR, Tam CS, et al.","paperType":"translational","findings":["165 enrolled, 111 infused, 93 efficacy-evaluable adults with relapsed/refractory DLBCL; 27 sites in 10 countries.","Best overall response 52%; complete response 40%.","12-month relapse-free survival among responders 65%; median duration of response not reached.","Grade 3-4 CRS 22%; grade 3-4 neurological events 12%; no treatment-related deaths.","A third of enrolled patients never received the product, mostly because of disease progression or manufacturing issues."],"whatItMeans":"JULIET, with ZUMA-1, showed that CAR-T could rescue a substantial minority of adults with chemotherapy-refractory lymphoma and that complete responders often stay in remission. The lower toxicity of a 4-1BB construct and the option of bridging therapy made it usable in a broader population. The high drop-out between enrolment and infusion remains a lesson about turnaround time.","caveats":["Single-arm; efficacy reported on infused patients, flattering the intention-to-treat picture.","Lower response rates than in ZUMA-1, possibly reflecting product, patient selection or manufacturing time.","Long vein-to-vein time (median about 54 days) meant many patients progressed before infusion.","Later randomised second-line trial (BELINDA) was negative for this product."],"changedPractice":true,"participants":111},{"id":"paper-jupiter-02-toripalimab-chemotherapy-npc-nat-med-2021","kind":"paper","name":"JUPITER-02: toripalimab or placebo plus chemotherapy as first-line treatment in advanced nasopharyngeal carcinoma","aka":[],"tldr":"Adding the PD-1 antibody toripalimab to gemcitabine and cisplatin lengthened the time before metastatic nasopharyngeal cancer progressed by about four months, and later improved survival, making chemo-immunotherapy the first-line standard.","summary":"International randomised double-blind placebo-controlled phase 3 trial of 289 patients with recurrent or metastatic nasopharyngeal carcinoma assigned to toripalimab or placebo with gemcitabine and cisplatin, followed by toripalimab or placebo maintenance.\n\nMedian progression-free survival was 11.7 months with toripalimab against 8.0 months (hazard ratio 0.52) at the interim analysis, with benefit regardless of PD-L1 expression; the final analysis (JAMA 2023) showed improved overall survival. Toripalimab was approved in China in 2021 and by the FDA in 2024.","asOf":"2026-09-18","links":[{"label":"Nat Med 2021","url":"https://doi.org/10.1038/s41591-021-01444-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34341578/"}],"tags":[],"related":[],"cancers":["recurrent-metastatic-nasopharyngeal-carcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":["toripalimab","gemcitabine-cisplatin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["jupiter-02"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2021,"doi":"10.1038/s41591-021-01444-0","pmid":"34341578","authors":"Mai HQ, Chen QY, Chen D, et al.","paperType":"rct","findings":["Median progression-free survival 11.7 months with toripalimab plus chemotherapy versus 8.0 months with chemotherapy alone; hazard ratio 0.52.","Benefit irrespective of PD-L1 status; overall survival improved at final analysis."],"whatItMeans":"PD-1 blockade with gemcitabine and cisplatin is the first-line standard for recurrent or metastatic nasopharyngeal carcinoma, and the first immunotherapy approved for this cancer in the United States.","caveats":["Conducted in mainland China, Taiwan and Singapore; almost all patients had EBV-related non-keratinising disease.","Immune-related adverse events, including hypothyroidism, were more frequent."],"changedPractice":true,"participants":289},{"id":"paper-karapetis-kras-cetuximab-colorectal-nejm-2008","kind":"paper","name":"K-ras mutations and benefit from cetuximab in advanced colorectal cancer","aka":[],"tldr":"The first randomised proof that a mutation can say a drug will not work: in a trial of cetuximab against supportive care alone, only patients whose tumours had a normal K-ras gene lived longer.","summary":"Tumour samples from 394 of 572 patients (68.9%) with colorectal cancer randomly assigned to cetuximab plus best supportive care or best supportive care alone were analysed for activating mutations in exon 2 of the K-ras gene. Of the tumours evaluated, 42.3% had at least one such mutation. The effectiveness of cetuximab was significantly associated with K-ras mutation status (interaction p = 0.01 for overall survival and p less than 0.001 for progression-free survival). In patients with wild-type tumours, cetuximab improved median overall survival from 4.8 to 9.5 months (hazard ratio 0.55) and progression-free survival from 1.9 to 3.7 months (hazard ratio 0.40). Among patients with mutated tumours there was no difference in overall survival (hazard ratio 0.98) or progression-free survival (hazard ratio 0.99). K-ras status was not associated with survival in the supportive-care group, so it is predictive rather than prognostic in this setting.","asOf":"2026-09-24","links":[{"label":"Karapetis et al., N Engl J Med 2008: K-ras mutation and benefit from cetuximab (CO.17, 394 tumours)","url":"https://doi.org/10.1056/NEJMoa0804385"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/18946061/"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":[],"targets":["kras","egfr"],"drugs":["cetuximab"],"companies":[],"institutions":[],"pathways":["ras-mapk"],"terms":["wild-type","driver-mutation"],"trials":[],"people":["christos-karapetis"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2008,"doi":"10.1056/NEJMoa0804385","pmid":"18946061","authors":"Karapetis CS, Khambata-Ford S, Jonker DJ, et al.","paperType":"rct","findings":["K-ras exon 2 mutation in 42.3% of 394 evaluable tumours.","Wild-type: overall survival 9.5 against 4.8 months with cetuximab (hazard ratio 0.55).","Mutant: no benefit (overall survival hazard ratio 0.98)."],"whatItMeans":"It created the negative predictive biomarker in solid tumour oncology and, with the panitumumab analysis of the same year, restricted EGFR antibodies to RAS wild-type disease worldwide.","caveats":["Retrospective biomarker analysis of a randomised trial, with tissue for 69% of patients.","Exon 2 only; the other RAS codons came five years later (Douillard 2013).","Sidedness had not yet been recognised, so the wild-type group mixed left and right."],"changedPractice":true,"participants":572},{"id":"paper-kadish-olfactory-neuroblastoma-staging-cancer-1976","kind":"paper","name":"Kadish staging: olfactory neuroblastoma, a clinical analysis of 17 cases","aka":[],"tldr":"A Boston series of seventeen patients that proposed the three-stage system, based on whether the tumour is confined to the nose, involves the sinuses or has spread beyond them, still used to stage esthesioneuroblastoma today.","summary":"Clinical analysis of 17 patients with olfactory neuroblastoma (esthesioneuroblastoma) treated at the Massachusetts General Hospital, proposing stages A (tumour confined to the nasal cavity), B (nasal cavity and paranasal sinuses) and C (extension beyond the nasal cavity and sinuses), and reporting outcomes with surgery and radiotherapy.\n\nThe Kadish system, later modified with a stage D for nodal or distant metastasis, remains the most widely used staging scheme for this tumour.","asOf":"2026-09-18","links":[{"label":"Cancer 1976","url":"https://doi.org/10.1002/1097-0142(197603)37:3<1571::AID-CNCR2820370347>3.0.CO;2-L"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/1260676/"}],"tags":[],"related":[],"cancers":["esthesioneuroblastoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-wiley"],"dependsOn":[],"notes":[],"journal":"Cancer","year":1976,"doi":"10.1002/1097-0142(197603)37:3<1571::AID-CNCR2820370347>3.0.CO;2-L","pmid":"1260676","authors":"Kadish S, Goodman M, Wang CC.","paperType":"observational","findings":["Three-stage system (A, B, C) by anatomical extent, with survival falling with stage."],"whatItMeans":"The stage on an esthesioneuroblastoma page or pathology report is almost always a Kadish stage, and treatment intensity follows it.","caveats":["Seventeen patients from a single institution half a century ago.","Does not incorporate Hyams histological grade, which is independently prognostic."],"changedPractice":true,"participants":17},{"id":"paper-kalluri-weinberg-emt-basics-jci-2009","kind":"paper","name":"Kalluri and Weinberg 2009: the basics of epithelial-mesenchymal transition","aka":[],"tldr":"The standard primer on how cancer cells borrow a programme from embryonic development to loosen their attachments, become mobile and invade, and how the same programme also drives wound healing and organ scarring.","summary":"Kalluri and Weinberg organised the epithelial-mesenchymal transition (EMT) into three types: type 1 in embryonic development, type 2 in wound healing and fibrosis, and type 3 in cancer, where carcinoma cells at the invasive front lose E-cadherin and epithelial polarity, gain mesenchymal markers such as vimentin and N-cadherin, and acquire motility and invasiveness. They summarised the transcription factors that drive it (Snail, Slug, Twist, ZEB1 and ZEB2), the signals that trigger it (TGF-beta, Wnt, Notch and growth factor receptor pathways) and the reverse transition that lets disseminated cells re-form epithelial metastases.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1172/JCI39104"}],"tags":[],"related":["paper-thiery-emt-tumour-progression-nrc-2002","paper-mani-emt-stem-cell-properties-cell-2008"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["emt","tgf-beta","metastatic-cascade"],"terms":["metastasis","activating-invasion-metastasis"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Investigation","year":2009,"doi":"10.1172/JCI39104","authors":"Kalluri R, Weinberg RA.","paperType":"review","findings":["EMT is classified into three types: developmental, fibrotic and cancer-associated (type 3).","Type 3 EMT gives carcinoma cells motility, invasiveness and resistance to apoptosis, and is driven by Snail, Slug, Twist and ZEB transcription factors downstream of TGF-beta and other signals.","The reverse process, mesenchymal-epithelial transition, is proposed to allow disseminated cells to form metastases."],"whatItMeans":"EMT is the most cited explanation for how carcinomas invade and spread and for part of their drug resistance. This primer is the entry point for the field, and its framework informs current work on partial EMT states, circulating tumour cells and therapies aimed at the transition.","caveats":["The extent to which full EMT occurs in human tumours in vivo, versus partial or hybrid states, is still debated.","A review; lineage-tracing evidence for EMT in metastasis came later and is mixed."],"changedPractice":false},{"id":"paper-karmma-3-ide-cel-nejm-2023","kind":"paper","name":"KarMMa-3: ide-cel CAR-T versus standard regimens in triple-class-exposed relapsed myeloma","aka":[],"tldr":"The first randomised CAR-T trial in myeloma tripled median progression-free survival (13.3 versus 4.4 months) compared with standard combinations after two to four prior lines.","summary":"KarMMa-3 randomised 386 patients with relapsed and refractory multiple myeloma after two to four prior lines, including an immunomodulatory drug, a proteasome inhibitor and daratumumab, to idecabtagene vicleucel (ide-cel) or one of five standard regimens. The primary endpoint was PFS. Median PFS was 13.3 versus 4.4 months (hazard ratio 0.49); overall response was 71% versus 42% and complete response 39% versus 5%. CRS occurred in 88% (grade 3 or higher in 5%) and neurotoxicity in 15%. Overall survival did not differ significantly, in part because more than half of standard-arm patients crossed over to ide-cel.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa2213614"},{"label":"ClinicalTrials.gov NCT03651128","url":"https://clinicaltrials.gov/study/NCT03651128"}],"tags":[],"related":["paper-cartitude-4-cilta-cel-nejm-2023"],"cancers":["multiple-myeloma"],"sections":[],"technologies":["car-t"],"targets":["bcma"],"drugs":["idecabtagene-vicleucel"],"companies":["bms"],"institutions":[],"pathways":[],"terms":["pfs","orr","crs"],"trials":["karmma-3"],"people":[],"bottlenecks":["b-manufacturing-cell-therapy","b-trial-design"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/NEJMoa2213614","authors":"Rodriguez-Otero P, Ailawadhi S, Arnulf B, et al.","paperType":"rct","findings":["386 patients after 2-4 prior lines, triple-class exposed; ide-cel vs 5 standard regimens (2:1).","Median PFS 13.3 vs 4.4 months; hazard ratio 0.49.","Overall response 71% vs 42%; complete response or better 39% vs 5%.","CRS 88% (grade 3 or higher 5%); investigator-identified neurotoxicity 15% (grade 3 or higher 3%).","No significant OS difference after adjusting for crossover; most standard-arm patients received ide-cel at progression."],"whatItMeans":"KarMMa-3 was the first randomised evidence that CAR-T beats conventional drugs in myeloma and led to ide-cel's approval after two prior lines. It confirmed that earlier use of CAR-T produces deeper and longer remissions than in the end-stage setting. Because responses are shorter than with cilta-cel and OS was not improved, it also sharpened debate about which BCMA CAR-T to use and when.","caveats":["Crossover blunted the OS comparison; a survival benefit could not be shown.","Standard-arm regimens varied and included some now regarded as suboptimal.","Median PFS with ide-cel remains modest compared with cilta-cel in CARTITUDE-4 (indirect comparison).","Manufacturing time and slot availability restrict real-world use."],"changedPractice":true,"participants":386},{"id":"paper-katherine-nejm-2019","kind":"paper","name":"KATHERINE: switching to T-DM1 when HER2-positive breast cancer survives pre-surgery treatment","aka":[],"tldr":"Women whose HER2-positive breast cancer was still present at surgery after chemotherapy and trastuzumab had half the risk of relapse if their post-surgery treatment was switched to the antibody-drug conjugate T-DM1 instead of continuing trastuzumab.","summary":"Open-label phase 3 trial of 1,486 patients with HER2-positive early breast cancer who had residual invasive disease in the breast or axilla after neoadjuvant taxane- and trastuzumab-based therapy, randomised to 14 cycles of adjuvant trastuzumab emtansine (T-DM1) or trastuzumab. Primary endpoint was invasive disease-free survival.\n\nThree-year iDFS was 88.3% vs 77.0% (HR 0.50). Later follow-up confirmed an overall survival benefit. It established the response-adapted strategy: treat before surgery, then escalate only for those with residual disease.","asOf":"2026-09-08","links":[{"label":"NEJM 2019","url":"https://doi.org/10.1056/NEJMoa1814017"},{"label":"ClinicalTrials.gov NCT01772472","url":"https://clinicaltrials.gov/study/NCT01772472"}],"tags":[],"related":["idea-post-neoadjuvant-adc"],"cancers":["breast-her2-positive"],"sections":[],"technologies":["adc"],"targets":["her2"],"drugs":["trastuzumab-emtansine","trastuzumab"],"companies":["roche-genentech"],"institutions":[],"pathways":[],"terms":["pcr","rcb","neoadjuvant-adjuvant"],"trials":["destiny-breast03","destiny-breast11"],"people":["gunter-von-minckwitz","sibylle-loibl","shao-zhi-ming","charles-geyer"],"bottlenecks":["b-dormancy-mrd","b-trial-design"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2019,"doi":"10.1056/NEJMoa1814017","authors":"von Minckwitz G, Huang CS, Mano MS, et al.","paperType":"rct","findings":["Three-year invasive disease-free survival 88.3% with T-DM1 vs 77.0% with trastuzumab, an 11.3-point gain; HR 0.50 (95% CI 0.39-0.64).","Distant recurrence as first event 10.5% vs 15.9%.","Benefit was consistent across hormone-receptor status, extent of residual disease, and prior pertuzumab use.","Long-term follow-up confirmed a significant overall survival benefit (HR about 0.66).","More grade 3 or higher adverse events with T-DM1 (25.7% vs 15.4%), notably thrombocytopenia and neuropathy."],"whatItMeans":"HER2-positive breast cancer is now routinely treated before surgery so that the pathology result can guide what comes after: patients with no residual cancer continue trastuzumab (with or without pertuzumab), while those with residual disease switch to T-DM1. This model of using the tumour's response as a test has since been copied in triple-negative and other cancers.","caveats":["Open-label design.","A minority of patients had received pertuzumab before surgery, fewer than in current practice.","Whether adding tucatinib or switching to trastuzumab deruxtecan can further improve outcomes for residual disease is being tested (CompassHER2 RD, DESTINY-Breast05).","Brain metastases as a first site of relapse were not reduced."],"changedPractice":true,"participants":1486},{"id":"paper-romero-nat-med","kind":"paper","name":"Keap1 loss promotes Kras-driven lung cancer and results in dependence on glutaminolysis","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 28967920 and published in Nature Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Treating KRAS-mutant lung adenocarcinoma (LUAD) remains a major challenge in cancer treatment given the difficulties associated with directly inhibiting the KRAS oncoprotein. One approach to addressing this challenge is to define mutations that frequently co-occur with those in KRAS, which themselves may lead to therapeutic vulnerabilities in tumors. Approximately 20% of KRAS-mutant LUAD tumors carry loss-of-function mutations in the KEAP1 gene encoding Kelch-like ECH-associated protein 1 (refs. 2, 3, 4), a negative regulator of nuclear factor erythroid 2-like 2 (NFE2L2; hereafter NRF2), which is the master transcriptional regulator of the endogenous antioxidant response. The high frequency of mutations in KEAP1 suggests an important role for the oxidative stress response in lung tumorigenesis. Using a CRISPR-Cas9-based approach in a mouse model of KRAS-driven LUAD, we examined the effects of Keap1 loss in lung cancer progression. We show that loss of Keap1 hyperactivates NRF2 and promotes KRAS-driven LUAD in mice. Through a combination of CRISPR-Cas9-based genetic screening and metabolomic analyses, we show that Keap1- or Nrf2-mutant cancers are dependent on increased glutaminolysis, and this property can be therapeutically exploited through the pharmacological inhibition of glutaminase. Finally, we provide a rationale for stratification of human patients with lung cancer harboring KRAS/KEAP1- or KRAS/NRF2-mutant lung tumors as likely to respond to glutaminase inhibition.\n\nIndexed on Europe PMC as PubMed record 28967920 (DOI 10.1038/nm.4407). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Med 2017","url":"https://doi.org/10.1038/nm.4407"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28967920/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28967920"}],"tags":["europepmc-ingest"],"related":["keap1-nrf2"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2017,"doi":"10.1038/nm.4407","pmid":"28967920","authors":"Romero R, Romero R, Sayin VI, et al.","paperType":"basic","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-kelly-russell-oncolytic-history-moltherapy-2007","kind":"paper","name":"Kelly and Russell 2007: a century of trying to treat cancer with viruses, and why it kept stopping","aka":[],"tldr":"The idea that a virus might shrink a tumour is more than a hundred years old; this history explains the early attempts, why they were abandoned, and what changed.","summary":"Kelly and Russell trace oncolytic virotherapy from the first recognition of viruses at the turn of the nineteenth century. Early case reports described cancers regressing during naturally acquired virus infections. That prompted clinical trials in which body fluids containing human or animal viruses were used to transmit infections to patients with cancer. Most often the host immune system arrested the virus and the tumour was unaffected; sometimes, in immunosuppressed patients, the infection persisted and the tumour regressed, but the damage to normal tissues was unacceptable.\n\nThrough the 1950s and 1960s researchers tried to force the evolution of viruses with greater tumour specificity by serial passage. Success was limited and many left the field. Reverse genetics brought it back, by allowing viruses to be designed rather than selected. The authors note that penetrating host immune defences, the problem that stopped the first era, remains the unsolved one.","asOf":"2026-09-25","links":[{"label":"Mol Ther 2007","url":"https://doi.org/10.1038/sj.mt.6300108"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/17299401/"}],"tags":[],"related":[],"cancers":[],"sections":["immunotherapy"],"technologies":["oncolytic-virus"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["stephen-russell"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Molecular Therapy","year":2007,"doi":"10.1038/sj.mt.6300108","pmid":"17299401","authors":"Kelly E, Russell SJ","paperType":"review","findings":["Early clinical attempts transmitted human or animal viruses to patients using infected body fluids, with no way to control dose or purity.","Tumour regressions were seen mainly in immunosuppressed patients, in whom the infection persisted; the same persistence produced unacceptable damage to normal tissue.","Serial passage through the 1950s and 1960s failed to produce reliably tumour-specific viruses, and much of the field was abandoned.","Reverse genetics, which allows a virus to be designed rather than selected, is what brought the field back."],"whatItMeans":"The history is the argument against treating any single dramatic case as proof. For a century, striking individual regressions coexisted with a complete failure to build a reliable treatment, because the same immune response that is needed to kill the tumour also clears the virus. That tension has not been resolved; it has only been engineered around.","caveats":["A narrative review, not a systematic one. Early case reports were uncontrolled and often published without histological confirmation.","The virus preparations of the first era were uncharacterised, so the historical safety record cannot be read across to modern clinical-grade products."]},{"id":"paper-wells-cell","kind":"paper","name":"Key Parameters of Tumor Epitope Immunogenicity Revealed Through a Consortium Approach Improve Neoantigen Prediction","aka":[],"tldr":"Paper cited by one idea page, indexed on Europe PMC as PubMed record 33038342 and published in Cell; the citing page links this DOI, which is how the record was matched.","summary":"Many approaches to identify therapeutically relevant neoantigens couple tumor sequencing with bioinformatic algorithms and inferred rules of tumor epitope immunogenicity. However, there are no reference data to compare these approaches, and the parameters governing tumor epitope immunogenicity remain unclear. Here, we assembled a global consortium wherein each participant predicted immunogenic epitopes from shared tumor sequencing data. 608 epitopes were subsequently assessed for T cell binding in patient-matched samples. By integrating peptide features associated with presentation and recognition, we developed a model of tumor epitope immunogenicity that filtered out 98% of non-immunogenic peptides with a precision above 0.70. Pipelines prioritizing model features had superior performance, and pipeline alterations leveraging them improved prediction performance. These findings were validated in an independent cohort of 310 epitopes prioritized from tumor sequencing data and assessed for T cell binding. This data resource enables identification of parameters underlying effective anti-tumor immunity and is available to the research community.\n\nIndexed on Europe PMC as PubMed record 33038342 (DOI 10.1016/j.cell.2020.09.015). Matched by DOI alone: one idea page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cell 2020","url":"https://doi.org/10.1016/j.cell.2020.09.015"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33038342/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33038342"}],"tags":["europepmc-ingest"],"related":["idea-neoantigen-immunogenicity-rules"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Cell","year":2020,"doi":"10.1016/j.cell.2020.09.015","pmid":"33038342","authors":"Wells DK, van Buuren MM, Dang KK, et al.","paperType":"observational","findings":[],"whatItMeans":"One idea page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-keynote-001-pembrolizumab-nsclc-nejm-2015","kind":"paper","name":"KEYNOTE-001 (Garon 2015): pembrolizumab in non-small-cell lung cancer and the 50% PD-L1 cut-off","aka":[],"tldr":"The large early trial that showed pembrolizumab shrinks about a fifth of advanced lung cancers, with responses that last, and that identified a PD-L1 score of 50% or more as the group most likely to benefit.","summary":"KEYNOTE-001 treated 495 patients with advanced non-small-cell lung cancer, both previously treated and untreated, with pembrolizumab at several doses and schedules. The overall response rate was about 19% with a median duration of response around a year and no clear difference between doses. A training and validation approach on PD-L1 immunohistochemistry defined a tumour proportion score of at least 50% as the threshold at which response and survival were markedly better, a cut-off adopted by KEYNOTE-024 and now used in clinics worldwide.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa1501824"},{"label":"ClinicalTrials.gov NCT01295827","url":"https://clinicaltrials.gov/study/NCT01295827"}],"tags":[],"related":["paper-keynote-024-nejm-2016","paper-keynote-010-lancet-2016"],"cancers":["nsclc"],"sections":[],"technologies":[],"targets":["pd1","pdl1"],"drugs":["pembrolizumab"],"companies":["merck"],"institutions":[],"pathways":[],"terms":["tps","pd-l1-testing","orr"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2015,"doi":"10.1056/NEJMoa1501824","authors":"Garon EB, Rizvi NA, Hui R, et al.","paperType":"translational","findings":["495 patients with advanced NSCLC treated with pembrolizumab at 2 or 10 mg/kg every three weeks or 10 mg/kg every two weeks.","Objective response rate 19.4% overall; median duration of response 12.5 months.","PD-L1 tumour proportion score of at least 50%, seen in 23.2% of patients, was associated with a response rate of 45.2% and longer progression-free and overall survival.","Treatment-related grade 3 or higher adverse events in 9.5% of patients."],"whatItMeans":"This trial gave lung cancer its immunotherapy biomarker. The 50% PD-L1 cut-off decides today whether a patient with advanced lung cancer can start immunotherapy alone or needs chemotherapy added, and the five-year follow-up later showed long-term survivors among first-line responders.","caveats":["Single-arm study with several dose cohorts; the cut-off was derived and validated within the same trial.","PD-L1 testing depends on the assay and the sample and misses some responders."],"changedPractice":true,"participants":495},{"id":"paper-keynote-006-pembrolizumab-ipilimumab-melanoma-nejm-2015","kind":"paper","name":"KEYNOTE-006 (Robert 2015): pembrolizumab versus ipilimumab in advanced melanoma","aka":[],"tldr":"Head to head, the PD-1 antibody pembrolizumab held melanoma back longer, prolonged life and caused fewer severe side effects than ipilimumab, the CTLA-4 antibody that had been the first immunotherapy to extend survival.","summary":"KEYNOTE-006 randomised 834 patients with advanced melanoma, most untreated with immunotherapy, to pembrolizumab every two weeks, pembrolizumab every three weeks, or ipilimumab. Both pembrolizumab schedules improved progression-free and overall survival and roughly tripled the response rate compared with ipilimumab, with fewer grade 3 to 5 treatment-related adverse events. The trial made PD-1 blockade the first-line immunotherapy standard in melanoma and showed the three-weekly schedule was as effective as the two-weekly one.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa1503093"},{"label":"ClinicalTrials.gov NCT01866319","url":"https://clinicaltrials.gov/study/NCT01866319"}],"tags":[],"related":["paper-hodi-ipilimumab-melanoma-nejm-2010"],"cancers":["melanoma"],"sections":[],"technologies":[],"targets":["pd1","ctla4"],"drugs":["pembrolizumab","ipilimumab"],"companies":["merck"],"institutions":[],"pathways":[],"terms":["pfs","os","orr"],"trials":["keynote-006"],"people":["caroline-robert"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2015,"doi":"10.1056/NEJMoa1503093","authors":"Robert C, Schachter J, Long GV, et al.","paperType":"rct","findings":["834 patients with advanced melanoma; pembrolizumab every 2 weeks, every 3 weeks, or ipilimumab.","Six-month progression-free survival 47.3% and 46.4% vs 26.5%; hazard ratios 0.58.","Twelve-month overall survival 74.1% and 68.4% vs 58.2%; hazard ratios 0.63 and 0.69.","Response rates 33.7% and 32.9% vs 11.9%; grade 3 to 5 treatment-related adverse events 13.3% and 10.1% vs 19.9%."],"whatItMeans":"This trial settled which checkpoint to block first in melanoma and set the pattern for PD-1 antibodies displacing ipilimumab across cancers. Long-term follow-up later showed that many responders remained free of progression years after stopping treatment.","caveats":["Open-label design.","Ipilimumab was given at 3 mg/kg for four doses; the comparison does not cover combination therapy.","Most patients had received no prior systemic therapy, so results apply mainly to first-line use."],"changedPractice":true,"participants":834},{"id":"paper-keynote-010-lancet-2016","kind":"paper","name":"KEYNOTE-010 (Herbst 2016): pembrolizumab versus docetaxel in previously treated PD-L1-positive lung cancer","aka":[],"tldr":"After chemotherapy had failed, pembrolizumab prolonged life compared with docetaxel in lung cancers expressing any PD-L1, with the largest gain in tumours where at least half the cells were positive, and caused fewer severe side effects.","summary":"KEYNOTE-010 randomised 1,034 patients with previously treated advanced non-small-cell lung cancer and a PD-L1 tumour proportion score of at least 1% to pembrolizumab at 2 mg/kg or 10 mg/kg or to docetaxel. Both pembrolizumab doses improved overall survival in the whole population and by a larger margin in the group with a score of 50% or more, with fewer grade 3 to 5 treatment-related adverse events than docetaxel. It secured pembrolizumab's regular approval in previously treated lung cancer and established PD-L1 of 1% as the entry threshold for that use.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1016/S0140-6736(15)01281-7"},{"label":"ClinicalTrials.gov NCT01905657","url":"https://clinicaltrials.gov/study/NCT01905657"}],"tags":[],"related":["paper-keynote-001-pembrolizumab-nsclc-nejm-2015","paper-checkmate-057-nejm-2015","pd-l1-tps"],"cancers":["nsclc"],"sections":[],"technologies":["histopathology-ihc","checkpoint-inhibitor"],"targets":["pd1","pdl1"],"drugs":["pembrolizumab","docetaxel"],"companies":["merck"],"institutions":[],"pathways":["pd1-checkpoint"],"terms":["tps","os","ihc"],"trials":[],"people":["roy-herbst"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2016,"doi":"10.1016/S0140-6736(15)01281-7","authors":"Herbst RS, Baas P, Kim DW, et al.","paperType":"rct","findings":["1,034 patients with previously treated NSCLC and PD-L1 tumour proportion score of at least 1%; pembrolizumab 2 mg/kg, 10 mg/kg or docetaxel.","Median overall survival 10.4 and 12.7 months with pembrolizumab vs 8.5 months with docetaxel; hazard ratios 0.71 and 0.61.","In tumours with a score of 50% or more: median overall survival 14.9 and 17.3 vs 8.2 months; hazard ratios 0.54 and 0.50.","Grade 3 to 5 treatment-related adverse events 13% and 16% vs 35%."],"whatItMeans":"Alongside the CheckMate trials this study replaced docetaxel with PD-1 blockade as second-line treatment for most lung cancers, and its PD-L1 threshold of 1% became the basis of pembrolizumab's label in previously treated disease.","caveats":["Open-label design.","Patients with PD-L1-negative tumours were excluded, so the trial says nothing about them.","Second-line setting; first-line immunotherapy has since reduced its relevance."],"changedPractice":true,"participants":1034},{"id":"paper-keynote-024-nejm-2016","kind":"paper","name":"KEYNOTE-024: pembrolizumab alone beats chemotherapy in PD-L1-high lung cancer","aka":[],"tldr":"In patients whose lung tumours carried PD-L1 on at least half their cells, pembrolizumab alone held the cancer back longer than chemotherapy and caused fewer serious side effects, making immunotherapy the first treatment for this group.","summary":"KEYNOTE-024 randomised 305 patients with untreated advanced non-small-cell lung cancer, a PD-L1 tumour proportion score of 50% or more and no EGFR or ALK alteration to pembrolizumab or platinum-based chemotherapy. Pembrolizumab improved progression-free survival, the primary endpoint, and overall survival at the interim analysis, with a higher response rate and fewer grade 3 to 5 adverse events, and patients on chemotherapy could cross over at progression. Five-year follow-up later confirmed the survival advantage. The trial made PD-L1 testing routine at lung cancer diagnosis and established chemotherapy-free first-line immunotherapy for the PD-L1-high group.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa1606774"},{"label":"ClinicalTrials.gov NCT02142738","url":"https://clinicaltrials.gov/study/NCT02142738"}],"tags":[],"related":["lung-cancer-evidence-roadmap","paper-herbst-impower110-atezolizumab-pd-l1-nejm-2020","pd-l1-tps"],"cancers":["nsclc","lung-cancer"],"sections":[],"technologies":["histopathology-ihc","checkpoint-inhibitor"],"targets":["pd1","pdl1"],"drugs":["pembrolizumab"],"companies":["merck"],"institutions":[],"pathways":["pd1-checkpoint"],"terms":["tps","pfs","os","ihc"],"trials":["keynote-024-189"],"people":["martin-reck"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2016,"doi":"10.1056/NEJMoa1606774","authors":"Reck M, Rodríguez-Abreu D, Robinson AG, et al.","paperType":"rct","findings":["305 patients with PD-L1 tumour proportion score of 50% or more; pembrolizumab vs platinum doublet chemotherapy.","Median progression-free survival 10.3 vs 6.0 months, hazard ratio 0.50.","Overall survival hazard ratio 0.60 at the interim analysis; estimated six-month survival 80.2% vs 72.4%.","Response rate 44.8% vs 27.8%; grade 3 to 5 treatment-related adverse events 26.6% vs 53.3%."],"whatItMeans":"This trial is why PD-L1 is measured on every new advanced lung cancer and why a patient with a high score can start immunotherapy without chemotherapy. Together with KEYNOTE-189 for the rest of the population, it moved checkpoint inhibitors from second-line rescue to the first treatment most lung cancer patients receive.","caveats":["Applies only to the roughly 30% of patients with a PD-L1 score of 50% or more and no EGFR or ALK driver.","Crossover from chemotherapy to pembrolizumab affected the survival comparison.","PD-L1 testing varies by assay and is imperfect as a predictor within the eligible group."],"changedPractice":true,"participants":305},{"id":"paper-keynote-048-lancet-2019","kind":"paper","name":"KEYNOTE-048: pembrolizumab, alone or with chemotherapy, as first treatment for recurrent or metastatic head and neck cancer","aka":[],"tldr":"Pembrolizumab, either alone in PD-L1-positive tumours or combined with chemotherapy, helped patients with recurrent or metastatic head and neck squamous cell cancer live longer than the previous cetuximab-based standard.","summary":"Open-label phase 3 trial of 882 patients with untreated recurrent or metastatic head and neck squamous cell carcinoma randomised to pembrolizumab alone, pembrolizumab plus platinum and fluorouracil, or the EXTREME regimen (cetuximab plus platinum and fluorouracil). Primary endpoints were OS and PFS in PD-L1 CPS 20 or more, CPS 1 or more, and all patients.\n\nPembrolizumab alone improved OS in CPS 20 or more (14.9 vs 10.7 months, HR 0.61) and CPS 1 or more (12.3 vs 10.3 months, HR 0.78) and was non-inferior overall. Pembrolizumab plus chemotherapy improved OS in all patients (13.0 vs 10.7 months, HR 0.77). It replaced EXTREME as the first-line standard and made PD-L1 CPS testing routine in head and neck cancer.","asOf":"2026-09-08","links":[{"label":"PubMed search: KEYNOTE-048 Lancet 2019","url":"https://pubmed.ncbi.nlm.nih.gov/?term=KEYNOTE-048+pembrolizumab+head+and+neck+Burtness+Lancet+2019"},{"label":"ClinicalTrials.gov NCT02358031","url":"https://clinicaltrials.gov/study/NCT02358031"}],"tags":[],"related":[],"cancers":["head-and-neck"],"sections":[],"technologies":["checkpoint-inhibitor","cytotoxic-chemotherapy","platinum","monoclonal-antibody"],"targets":["pd1","egfr"],"drugs":["pembrolizumab"],"companies":["merck"],"institutions":["icr-london","royal-marsden"],"pathways":[],"terms":["cps","os","pfs","first-line","orr"],"trials":[],"people":["kevin-harrington"],"bottlenecks":["b-biomarker-validation","b-immunotherapy-response"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2019,"doi":"10.1016/S0140-6736(19)32591-7","pmid":"31679945","authors":"Burtness B, Harrington KJ, Greil R, et al.","paperType":"rct","findings":["Pembrolizumab alone vs EXTREME, CPS 20 or more: median OS 14.9 vs 10.7 months, HR 0.61 (95% CI 0.45-0.83).","Pembrolizumab alone vs EXTREME, CPS 1 or more: median OS 12.3 vs 10.3 months, HR 0.78.","Pembrolizumab plus chemotherapy vs EXTREME, all patients: median OS 13.0 vs 10.7 months, HR 0.77 (95% CI 0.63-0.93).","Response rates were lower with pembrolizumab alone (17% vs 36% in CPS 20 or more) but responses lasted far longer (median 22.6 vs 4.5 months).","Grade 3 or higher all-cause adverse events 55% (pembrolizumab alone), 85% (pembrolizumab plus chemotherapy) and 83% (EXTREME)."],"whatItMeans":"Patients with head and neck squamous cell cancer that has recurred or spread should be treated first with pembrolizumab: alone if their tumour is strongly PD-L1 positive and they can wait for a slower response, or with chemotherapy if the tumour is bulky or PD-L1 low. Cetuximab-based chemotherapy is no longer the default. Long-term follow-up shows a small but real group of patients alive at four to five years, which was almost unheard of before.","caveats":["Open-label with a complex multi-comparison design; PFS was not improved in any comparison.","Pembrolizumab alone has a lower response rate and early progression can occur, so patients with rapidly symptomatic disease may need chemotherapy added.","CPS below 1 (about 15% of patients) derived no clear benefit from either pembrolizumab arm.","EXTREME is now an outdated comparator; the optimal strategy for HPV-positive versus HPV-negative disease was not defined."],"changedPractice":true,"participants":882},{"id":"paper-keynote-054-eggermont-nejm-2018","kind":"paper","name":"KEYNOTE-054 (EORTC 1325): adjuvant pembrolizumab versus placebo in resected stage III melanoma","aka":[],"tldr":"A year of pembrolizumab after surgery for stage III melanoma cut the risk of recurrence by 43 percent compared with placebo, the first placebo-controlled proof that adjuvant PD-1 blockade works.","summary":"Phase 3 placebo-controlled trial of 1,019 patients with completely resected stage III melanoma randomised to pembrolizumab or placebo for one year.\n\nTwelve-month recurrence-free survival was 75.4 versus 61.0 percent (hazard ratio 0.57), consistent across PD-L1 and BRAF subgroups; five-year recurrence-free survival was 55.4 versus 38.3 percent and distant metastasis-free survival was also improved, with grade 3 or higher immune-related events in 7.1 percent.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2018","url":"https://doi.org/10.1056/NEJMoa1802357"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29658430/"}],"tags":[],"related":[],"cancers":["stage-iii-melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2018,"doi":"10.1056/NEJMoa1802357","pmid":"29658430","authors":"Eggermont AMM, Blank CU, Mandala M, et al.","paperType":"rct","findings":["Twelve-month recurrence-free survival 75.4 percent vs 61.0 percent; hazard ratio 0.57.","Five-year recurrence-free survival 55.4 percent vs 38.3 percent."],"whatItMeans":"Adjuvant pembrolizumab is a standard for resected stage III melanoma, with subsequent trials extending it to stage II and to the neoadjuvant setting.","caveats":["Overall survival benefit not demonstrated, as placebo patients could receive pembrolizumab at relapse."],"changedPractice":true,"participants":1019},{"id":"paper-keynote-057-lancet-oncol-2021","kind":"paper","name":"KEYNOTE-057: pembrolizumab for BCG-unresponsive non-muscle-invasive bladder cancer with carcinoma in situ","aka":[],"tldr":"In patients whose high-risk bladder cancer no longer responded to BCG and who could not or would not have their bladder removed, pembrolizumab cleared the disease in about four in ten, with a response lasting a year or more in roughly half of those.","summary":"Single-arm phase 2 study of 101 patients with BCG-unresponsive carcinoma in situ, with or without papillary tumours, treated with pembrolizumab every three weeks for up to two years.\n\nThe complete response rate at three months was 41 percent and the median duration of response was 16.2 months. On these data pembrolizumab became the first systemic drug approved for BCG-unresponsive non-muscle-invasive bladder cancer, as an alternative to immediate cystectomy.","asOf":"2026-09-17","links":[{"label":"Lancet Oncol 2021","url":"https://doi.org/10.1016/S1470-2045(21)00147-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34051177/"}],"tags":[],"related":[],"cancers":["non-muscle-invasive-bladder-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-057"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2021,"doi":"10.1016/S1470-2045(21)00147-9","pmid":"34051177","authors":"Balar AV, Kamat AM, Kulkarni GS, et al.","paperType":"observational","findings":["Complete response at three months in 41 percent of patients with carcinoma in situ.","Median duration of complete response 16.2 months; 46 percent of responses lasted at least 12 months."],"whatItMeans":"Patients facing cystectomy for BCG-unresponsive disease have a bladder-sparing option, though most will eventually relapse and need close cystoscopic surveillance. The choice is a trade between keeping the bladder and the risk of progression while waiting.","caveats":["No randomised comparator; cystectomy remains the curative standard.","Progression to muscle-invasive disease occurred in a minority during follow-up."],"changedPractice":true,"participants":101},{"id":"paper-keynote-062-shitara-jama-oncol-2020","kind":"paper","name":"KEYNOTE-062: pembrolizumab or pembrolizumab plus chemotherapy versus chemotherapy in PD-L1-positive advanced gastric cancer","aka":[],"tldr":"In first-line PD-L1-positive gastric cancer, pembrolizumab alone was no worse than chemotherapy for survival but did not beat it, and adding it to chemotherapy did not help either; the exception was microsatellite-unstable tumours, which did dramatically better with pembrolizumab.","summary":"Phase 3 trial of 763 patients with untreated advanced gastric or junctional adenocarcinoma with PD-L1 combined positive score of 1 or more randomised to pembrolizumab, pembrolizumab plus chemotherapy, or chemotherapy.\n\nPembrolizumab was non-inferior to chemotherapy for overall survival (10.6 versus 11.1 months) and combination therapy was not superior; in the 50 patients with microsatellite instability-high tumours, median overall survival was not reached with pembrolizumab against 8.5 months with chemotherapy.","asOf":"2026-09-17","links":[{"label":"JAMA Oncol 2020","url":"https://doi.org/10.1001/jamaoncol.2020.3370"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32880601/"}],"tags":[],"related":[],"cancers":["gastric-msi-high"],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-062"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2020,"doi":"10.1001/jamaoncol.2020.3370","pmid":"32880601","authors":"Shitara K, Van Cutsem E, Bang YJ, et al.","paperType":"rct","findings":["Pembrolizumab non-inferior to chemotherapy overall (10.6 vs 11.1 months).","Microsatellite instability-high: overall survival not reached vs 8.5 months with chemotherapy."],"whatItMeans":"Single-agent pembrolizumab is an option for microsatellite-unstable gastric cancer first line, whereas for the broader PD-L1-positive population chemo-immunotherapy from CheckMate 649 and KEYNOTE-859 became standard.","caveats":["Microsatellite-unstable subgroup was small and exploratory.","Early progression was more frequent with pembrolizumab alone."],"changedPractice":true,"participants":763},{"id":"paper-keynote-158-pembrolizumab-msi-high-noncolorectal-jco-2020","kind":"paper","name":"KEYNOTE-158: pembrolizumab in non-colorectal high microsatellite instability or mismatch repair-deficient cancer","aka":[],"tldr":"Pembrolizumab shrank tumours in about a third of patients with mismatch repair-deficient cancers of many different organs, with responses that often lasted years; the pancreatic cancer group responded less often than most. It is the trial behind the tissue-agnostic approval for MSI-high cancer.","summary":"Phase 2 basket study of pembrolizumab 200 mg every three weeks in 233 patients with previously treated advanced non-colorectal MSI-high or mismatch repair-deficient cancer across 27 tumour types, endometrial, gastric, cholangiocarcinoma and pancreatic cancer among the largest cohorts.\n\nThe objective response rate was about 34 percent with a median duration of response not reached, median progression-free survival 4.1 months and median overall survival 23.5 months. In the 22 patients with pancreatic cancer the response rate was about 18 percent and median overall survival about 4 months, the lowest of the major cohorts. The data supported the FDA's tissue-agnostic approval of pembrolizumab for MSI-high cancer.","asOf":"2026-09-21","links":[{"label":"J Clin Oncol 2020","url":"https://doi.org/10.1200/JCO.19.02105"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31682550/"}],"tags":[],"related":["msi-high","dmmr-ihc"],"cancers":["msi-high-pdac","pancreatic"],"sections":[],"technologies":[],"targets":["mmr","pd1"],"drugs":["pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":["tumour-agnostic","msi"],"trials":["keynote-158"],"people":["aurelien-marabelle","dung-le"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/JCO.19.02105","pmid":"31682550","authors":"Marabelle A, Le DT, Ascierto PA, et al.","paperType":"observational","findings":["Objective response about 34 percent across 27 non-colorectal tumour types; median overall survival 23.5 months.","Pancreatic cohort of 22 patients: response about 18 percent, median overall survival about 4 months."],"whatItMeans":"Every pancreatic cancer should be tested for mismatch repair deficiency because the 1 percent who have it can receive pembrolizumab, but responses in pancreatic cancer are less frequent and less durable than in other MSI-high cancers.","caveats":["Single-arm basket study; the pancreatic cohort was small and heavily pretreated.","Some patients had MSI-high status assigned by PCR or immunohistochemistry alone, and misclassification is a known problem in pancreatic cancer."],"changedPractice":true,"participants":233},{"id":"paper-keynote-170-pembrolizumab-pmbcl-armand-jco-2019","kind":"paper","name":"KEYNOTE-170: pembrolizumab in relapsed or refractory primary mediastinal large B-cell lymphoma","aka":[],"tldr":"Pembrolizumab produced responses in about 45 percent of patients with primary mediastinal B-cell lymphoma that had relapsed after chemotherapy, a lymphoma whose frequent 9p24.1 amplification makes it unusually sensitive to PD-1 blockade.","summary":"Phase 2 study of 53 patients with relapsed or refractory primary mediastinal large B-cell lymphoma treated with pembrolizumab, supported by a phase 1b cohort of 21 patients.\n\nObjective response was 45 percent with complete responses in 13 percent, median duration of response not reached after a median follow-up of 12.5 months, and no deaths from treatment-related events; 9p24.1 alterations were near-universal.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2019","url":"https://doi.org/10.1200/JCO.19.01389"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31609651/"}],"tags":[],"related":[],"cancers":["primary-mediastinal-b-cell-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-170"],"people":["philippe-armand"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2019,"doi":"10.1200/JCO.19.01389","pmid":"31609651","authors":"Armand P, Rodig S, Melnichenko V, et al.","paperType":"observational","findings":["Objective response 45 percent; complete response 13 percent.","Median duration of response not reached at 12.5 months."],"whatItMeans":"Pembrolizumab is approved for relapsed primary mediastinal B-cell lymphoma and is the usual bridge to CAR-T or transplant in chemotherapy-refractory patients.","caveats":["Single-arm; small numbers.","Most responders eventually need consolidative therapy."],"changedPractice":true,"participants":53},{"id":"paper-keynote-177-nejm-2020","kind":"paper","name":"KEYNOTE-177: pembrolizumab instead of chemotherapy as first treatment for mismatch-repair-deficient metastatic colorectal cancer","aka":[],"tldr":"For the roughly 5% of metastatic bowel cancers with defective DNA mismatch repair, pembrolizumab alone lengthened the time without progression compared with chemotherapy, with far fewer severe side effects, and 83% of responses lasted two years or more. It made first-line pembrolizumab the standard for this group.","summary":"Open-label phase 3 trial of 307 patients with untreated microsatellite-instability-high or mismatch-repair-deficient metastatic colorectal cancer randomised to pembrolizumab or investigator's choice chemotherapy (FOLFOX or FOLFIRI with or without bevacizumab or cetuximab). Primary endpoints were PFS and OS.\n\nMedian PFS was 16.5 vs 8.2 months (HR 0.60), with 43.8% vs 33.1% responding and 83% vs 35% of responses lasting two years or more. Overall survival was not significantly different (HR 0.74) because 60% of chemotherapy patients crossed over to immunotherapy. It made first-line pembrolizumab the standard for dMMR metastatic colorectal cancer and cemented mismatch repair testing for every colorectal cancer.","asOf":"2026-09-08","links":[{"label":"NEJM 2020","url":"https://doi.org/10.1056/NEJMoa2017699"},{"label":"ClinicalTrials.gov NCT02563002","url":"https://clinicaltrials.gov/study/NCT02563002"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33264544/"},{"label":"Five-year follow-up (Ann Oncol 2024)","url":"https://www.annalsofoncology.org/article/S0923-7534(24)04949-4/fulltext"}],"tags":[],"related":["msi-high","dmmr-ihc","paper-le-mmr-deficiency-pd1-nejm-2015","paper-andre-checkmate-8hw-nivolumab-ipilimumab-nejm-2024"],"cancers":["colorectal","msi-high-colorectal"],"sections":["immunotherapy"],"technologies":["checkpoint-inhibitor","histopathology-ihc","msi-mmr-testing"],"targets":["pd1","mmr"],"drugs":["pembrolizumab"],"companies":["merck"],"institutions":[],"pathways":["mismatch-repair-msi","pd1-checkpoint"],"terms":["msi","pfs","os","first-line","tmb","tumour-agnostic","mmr"],"trials":["keynote-177"],"people":["kim-tae-won","elena-elez","dung-le","yoshino-takayuki","luis-diaz","thierry-andre","eric-van-cutsem"],"bottlenecks":["b-immunotherapy-response","b-trial-design","b-biomarker-validation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2020,"doi":"10.1056/NEJMoa2017699","pmid":"33264544","authors":"Andre T, Shiu KK, Kim TW, et al.","paperType":"rct","findings":["Median PFS 16.5 vs 8.2 months; HR 0.60 (95% CI 0.45-0.80); 24-month PFS 48.3% vs 18.6%.","Objective response 43.8% vs 33.1%; complete response 11% vs 4%.","Grade 3 or higher treatment-related adverse events 22% vs 66%.","Overall survival (Lancet Oncology 2022): HR 0.74 (95% CI 0.53-1.03), not significant; median 77.5 vs 36.7 months; 60% of chemotherapy patients received subsequent anti-PD-1 therapy.","PFS curves crossed early: about 29% of pembrolizumab patients progressed by 4 months, suggesting a subgroup of primary resistance."],"whatItMeans":"Every colorectal cancer should be tested for mismatch repair deficiency, because patients whose metastatic tumour is dMMR should receive pembrolizumab rather than chemotherapy as first treatment, gaining a much better chance of durable remission with fewer side effects. About a third of dMMR tumours do not respond initially, so early scans are essential and chemotherapy remains available. The trial does not apply to the 95% of metastatic colorectal cancers that are mismatch-repair proficient (the deficient share is higher in localised disease, about 15%).","caveats":["OS was not significantly improved, mostly because of crossover; the design makes an OS benefit unprovable.","Early crossing of the PFS curves indicates a group with rapid progression on immunotherapy who might be better served by combinations (nivolumab plus ipilimumab in CheckMate 8HW).","Open-label design and a heterogeneous chemotherapy control arm.","Immunohistochemistry and PCR for mismatch repair can disagree; misclassification of pMMR tumours as dMMR leads to ineffective treatment."],"changedPractice":true,"participants":307},{"id":"paper-keynote-189-nejm-2018","kind":"paper","name":"KEYNOTE-189: pembrolizumab plus chemotherapy as first treatment for non-squamous lung cancer without a driver mutation","aka":[],"tldr":"Adding pembrolizumab to standard chemotherapy roughly halved the risk of death in newly diagnosed non-squamous lung cancer, whatever the PD-L1 level, making chemo-immunotherapy the default first treatment.","summary":"Double-blind phase 3 trial of 616 patients with untreated metastatic non-squamous NSCLC without EGFR or ALK alterations, randomised 2:1 to pembrolizumab or placebo plus pemetrexed and a platinum. Primary endpoints were overall survival and PFS.\n\n12-month overall survival was 69.2% vs 49.4% (HR 0.49) and median PFS 8.8 vs 4.9 months (HR 0.52), with benefit in every PD-L1 stratum including below 1%. Together with KEYNOTE-024 (pembrolizumab alone for PD-L1 of 50% or more) it made PD-1 blockade part of first-line treatment for almost all patients with advanced NSCLC. The five-year update showed OS 19.4% vs 11.3%.","asOf":"2026-09-08","links":[{"label":"NEJM 2018","url":"https://doi.org/10.1056/NEJMoa1801005"},{"label":"ClinicalTrials.gov NCT02578680","url":"https://clinicaltrials.gov/study/NCT02578680"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":["checkpoint-inhibitor","cytotoxic-chemotherapy","platinum"],"targets":["pd1","pdl1"],"drugs":["pembrolizumab","carboplatin"],"companies":["merck"],"institutions":[],"pathways":[],"terms":["first-line","os","pfs","cold-vs-hot","irae"],"trials":[],"people":["enriqueta-felip"],"bottlenecks":["b-immunotherapy-response","b-biomarker-validation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2018,"doi":"10.1056/NEJMoa1801005","authors":"Gandhi L, Rodriguez-Abreu D, Gadgeel S, et al.","paperType":"rct","findings":["12-month overall survival 69.2% vs 49.4%; HR 0.49 (95% CI 0.38-0.64).","Median PFS 8.8 vs 4.9 months; HR 0.52.","OS benefit in all PD-L1 subgroups: TPS below 1% HR 0.59; 1-49% HR 0.55; 50% or more HR 0.42.","Objective response 47.6% vs 18.9%.","Five-year update (2023): OS 19.4% vs 11.3%; median 22.0 vs 10.6 months despite about 57% crossover to immunotherapy."],"whatItMeans":"Most patients with newly diagnosed advanced non-squamous lung cancer that lacks a targetable mutation should receive chemotherapy plus pembrolizumab; those with PD-L1 of 50% or more may reasonably receive pembrolizumab alone. About one in five patients is alive at five years, compared with roughly one in ten with chemotherapy alone. Patients with EGFR or ALK alterations were excluded and should have targeted therapy first.","caveats":["Excluded EGFR- and ALK-positive tumours; immunotherapy benefit in driver-mutated lung cancer is much smaller.","Whether patients with PD-L1 of 50% or more need chemotherapy added to pembrolizumab has never been directly randomised.","Immune-related adverse events, including pneumonitis and nephritis, were more frequent with pembrolizumab.","Crossover in the control arm means the true OS effect is probably larger than measured."],"changedPractice":true,"participants":616},{"id":"paper-antonarakis-keynote-199-pembrolizumab-jco-2020","kind":"paper","name":"KEYNOTE-199: pembrolizumab for treatment-refractory metastatic castration-resistant prostate cancer","aka":["KEYNOTE-199","Antonarakis 2020 pembrolizumab prostate"],"tldr":"Checkpoint immunotherapy transformed several cancers and did almost nothing here. In 258 men with advanced prostate cancer, about 1 in 20 had a response, and whether the tumour expressed PD-L1 made no difference.","summary":"Emmanuel Antonarakis, Johann de Bono and the KEYNOTE-199 investigators gave pembrolizumab 200 mg every three weeks to 258 men with metastatic castration-resistant prostate cancer who had already had docetaxel and at least one targeted endocrine therapy, in three parallel cohorts: measurable PD-L1-positive disease, measurable PD-L1-negative disease, and bone-predominant disease irrespective of PD-L1.\n\nThe response rates, 5 percent and 3 percent in the two measurable cohorts, are the clearest statement available of why prostate cancer is called an immunologically cold tumour, and they sit consistently with the genomics: a median tumour mutational burden of 2.6 mutations per megabase and only 4 percent mismatch repair deficiency (paper-chung-comprehensive-genomic-profiling-prostate-jco-po-2019). The responses that did occur were durable, which is why the field keeps returning to the question with combinations rather than abandoning it.","asOf":"2026-09-25","links":[{"label":"J Clin Oncol 2020","url":"https://doi.org/10.1200/jco.19.01638"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31774688/"},{"label":"ClinicalTrials.gov NCT02787005","url":"https://clinicaltrials.gov/study/NCT02787005"}],"tags":["prostate-evidence"],"related":["paper-chung-comprehensive-genomic-profiling-prostate-jco-po-2019","paper-kantoff-n-engl-j-med","paper-nct02861573-eur-urol-2022","paper-nct04446117-lancet-oncol-2025","prostate-roadmap"],"cancers":["prostate","prostate-mcrpc"],"sections":["immunotherapy"],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["pembrolizumab","docetaxel"],"companies":["merck"],"institutions":[],"pathways":[],"terms":["tmb","msi"],"trials":[],"people":["johann-de-bono"],"bottlenecks":["b-immunotherapy-response","b-tme-immunosuppression","b-biomarker-validation"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/jco.19.01638","pmid":"31774688","authors":"Antonarakis ES, Piulats JM, Gross-Goupil M, et al.","paperType":"rct","findings":["Objective response rate 5 percent (95 percent confidence interval 2 to 11) in cohort 1 (measurable, PD-L1-positive, 133 patients) and 3 percent (less than 1 to 11) in cohort 2 (measurable, PD-L1-negative, 66 patients).","Median duration of response was not reached in cohort 1 (range 1.9 to at least 21.8 months) and was 10.6 months in cohort 2 (range 4.4 to 16.8 months).","Disease control rate 10 percent in cohort 1, 9 percent in cohort 2 and 22 percent in cohort 3 (bone-predominant disease, 59 patients).","Median overall survival 9.5 months in cohort 1, 7.9 months in cohort 2 and 14.1 months in cohort 3.","Treatment-related adverse events occurred in 60 percent of patients, were grade 3 to 5 in 15 percent and led to treatment discontinuation in 5 percent."],"whatItMeans":"The measured size of the immunotherapy problem in prostate cancer: a response rate in the low single figures, no signal from PD-L1 expression, and durable benefit in a small subgroup nobody can yet identify prospectively. Any claim that immunotherapy is coming to prostate cancer has to explain this trial.","caveats":["Single-arm phase 2 with no control, in a heavily pre-treated population, so the survival figures reflect prognosis as much as treatment.","PD-L1 positivity did not separate responders from non-responders, so it is not a usable biomarker here.","Mismatch repair status, which does predict response to checkpoint blockade in prostate cancer as elsewhere, was not the selection criterion; the responders in cohort 3 in particular remain unexplained."],"changedPractice":false,"participants":258},{"id":"paper-keynote-204-pembrolizumab-vs-brentuximab-rr-hodgkin-lancet-oncol-2021","kind":"paper","name":"KEYNOTE-204: pembrolizumab versus brentuximab vedotin in relapsed or refractory classical Hodgkin lymphoma","aka":[],"tldr":"In a head-to-head trial, the PD-1 antibody pembrolizumab kept relapsed Hodgkin lymphoma at bay for longer than brentuximab vedotin, making immunotherapy the preferred choice after transplant failure or for patients who cannot have a transplant.","summary":"International randomised open-label phase 3 trial of 304 patients with relapsed or refractory classical Hodgkin lymphoma after autologous transplant or ineligible for it, assigned to pembrolizumab or brentuximab vedotin.\n\nAt the interim analysis median progression-free survival was 13.2 months with pembrolizumab against 8.3 months with brentuximab vedotin (hazard ratio 0.65), with benefit across subgroups including those with primary refractory disease; pneumonitis was more frequent with pembrolizumab and neuropathy with brentuximab vedotin.","asOf":"2026-09-18","links":[{"label":"Lancet Oncol 2021","url":"https://doi.org/10.1016/S1470-2045(21)00005-X"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33721562/"}],"tags":[],"related":[],"cancers":["relapsed-refractory-hodgkin-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab","brentuximab-vedotin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-204"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2021,"doi":"10.1016/S1470-2045(21)00005-X","pmid":"33721562","authors":"Kuruvilla J, Ramchandren R, Santoro A, et al.","paperType":"rct","findings":["Median progression-free survival 13.2 months with pembrolizumab versus 8.3 months with brentuximab vedotin; hazard ratio 0.65.","Grade 3 to 5 treatment-related adverse events in a similar proportion, with different profiles (pneumonitis versus neuropathy)."],"whatItMeans":"PD-1 blockade is the standard for classical Hodgkin lymphoma that has relapsed after or is unsuitable for autologous transplant, ahead of brentuximab vedotin in most patients.","caveats":["Open-label interim analysis; overall survival data were immature.","Most patients had not received either drug before, which is now uncommon as both move into first-line therapy."],"changedPractice":true,"participants":304},{"id":"paper-keynote-355-nejm-2022","kind":"paper","name":"KEYNOTE-355: pembrolizumab plus chemotherapy for PD-L1-positive advanced triple-negative breast cancer","aka":[],"tldr":"Adding pembrolizumab to first-line chemotherapy lengthened survival by almost seven months in advanced triple-negative breast cancer whose tumours had a PD-L1 combined positive score of 10 or more.","summary":"Phase 3 placebo-controlled trial of 847 patients with previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer randomised 2:1 to pembrolizumab or placebo with nab-paclitaxel, paclitaxel or gemcitabine-carboplatin.\n\nIn patients with a combined positive score of 10 or more, median overall survival was 23.0 versus 16.1 months (hazard ratio 0.73); no significant benefit was seen at lower PD-L1 scores.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2022","url":"https://doi.org/10.1056/NEJMoa2202809"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35857659/"}],"tags":[],"related":["pd-l1-cps"],"cancers":["tnbc-metastatic"],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-355"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/NEJMoa2202809","pmid":"35857659","authors":"Cortes J, Rugo HS, Cescon DW, et al.","paperType":"rct","findings":["Median overall survival 23.0 vs 16.1 months in combined positive score 10 or more; hazard ratio 0.73.","Median progression-free survival 9.7 vs 5.6 months in the same group."],"whatItMeans":"PD-L1 testing with the combined positive score decides first-line treatment in metastatic triple-negative breast cancer; pembrolizumab-chemotherapy is the standard for scores of 10 or more.","caveats":["No benefit demonstrated below a combined positive score of 10.","The chemotherapy partner was chosen by the investigator."],"changedPractice":true,"participants":847},{"id":"paper-keynote-426-nejm-2019","kind":"paper","name":"KEYNOTE-426: pembrolizumab plus axitinib versus sunitinib for advanced renal cell carcinoma","aka":[],"tldr":"Combining pembrolizumab with the kinase inhibitor axitinib lengthened survival and delayed progression compared with sunitinib as first treatment for advanced clear cell kidney cancer, across all risk groups.","summary":"Phase 3 trial of 861 patients with previously untreated advanced clear cell renal cell carcinoma randomised to pembrolizumab plus axitinib or sunitinib.\n\nAt 12.8 months, overall survival at one year was 89.9 versus 78.3 percent (hazard ratio 0.53), median progression-free survival 15.1 versus 11.1 months and response 59.3 versus 35.7 percent; the final analysis confirmed a survival benefit (median 47.2 versus 40.8 months).","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2019","url":"https://doi.org/10.1056/NEJMoa1816714"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30779529/"}],"tags":[],"related":[],"cancers":["clear-cell-rcc"],"sections":[],"technologies":[],"targets":[],"drugs":["axitinib","pembrolizumab","sunitinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-426"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2019,"doi":"10.1056/NEJMoa1816714","pmid":"30779529","authors":"Rini BI, Plimack ER, Stus V, et al.","paperType":"rct","findings":["One-year overall survival 89.9 percent vs 78.3 percent; hazard ratio 0.53 at first analysis.","Objective response 59.3 percent vs 35.7 percent."],"whatItMeans":"Immunotherapy plus a VEGF kinase inhibitor is a first-line standard for advanced clear cell kidney cancer in all risk groups; comparable regimens include nivolumab-cabozantinib and lenvatinib-pembrolizumab.","caveats":["Open-label; the survival hazard ratio attenuated with longer follow-up (about 0.84).","Liver enzyme elevation is a characteristic combination toxicity."],"changedPractice":true,"participants":861},{"id":"paper-keynote-483-lancet-2023","kind":"paper","name":"KEYNOTE-483 (CCTG IND.227): pembrolizumab plus chemotherapy versus chemotherapy in untreated pleural mesothelioma","aka":[],"tldr":"Adding pembrolizumab to platinum-pemetrexed chemotherapy lengthened survival in untreated pleural mesothelioma by about a year in non-epithelioid tumours and by a smaller margin overall, giving a chemo-immunotherapy option alongside nivolumab-ipilimumab.","summary":"Phase 3 open-label trial of 440 patients with unresectable advanced pleural mesothelioma in Canada, Italy and France randomised to pembrolizumab plus platinum-pemetrexed or chemotherapy alone.\n\nMedian overall survival was 17.3 versus 16.1 months (hazard ratio 0.79), with three-year survival 25 versus 17 percent and a larger effect in non-epithelioid disease; grade 3 to 4 adverse events were more frequent with pembrolizumab.","asOf":"2026-09-17","links":[{"label":"Lancet 2023","url":"https://doi.org/10.1016/S0140-6736(23)01613-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37931632/"}],"tags":[],"related":[],"cancers":["pleural-mesothelioma"],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-483"],"people":["quincy-chu"],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2023,"doi":"10.1016/S0140-6736(23)01613-6","pmid":"37931632","authors":"Chu Q, Perrone F, Greillier L, et al.","paperType":"rct","findings":["Median overall survival 17.3 vs 16.1 months; hazard ratio 0.79.","Three-year overall survival 25 percent vs 17 percent."],"whatItMeans":"Pembrolizumab with chemotherapy is approved and offered first line, particularly in epithelioid disease where dual immunotherapy showed little benefit over chemotherapy.","caveats":["Modest median gain; benefit concentrated in a minority of long-term responders.","Open-label with academic sponsorship and relatively small size."],"changedPractice":true,"participants":440},{"id":"paper-keynote-522-nejm-2022","kind":"paper","name":"KEYNOTE-522: adding pembrolizumab before and after surgery in early triple-negative breast cancer","aka":[],"tldr":"Adding the immunotherapy pembrolizumab to chemotherapy before surgery, then continuing it afterwards, cut the risk of relapse or death by about a third in stage II-III triple-negative breast cancer and later improved survival.","summary":"Phase 3, double-blind trial randomising 1,174 patients with untreated stage II-III triple-negative breast cancer (2:1) to neoadjuvant pembrolizumab or placebo plus carboplatin-paclitaxel then anthracycline-cyclophosphamide, followed by surgery and nine cycles of adjuvant pembrolizumab or placebo. Dual primary endpoints were pathological complete response (pCR) and event-free survival (EFS).\n\nThe 2020 report showed pCR 64.8% vs 51.2%. This 2022 report showed the EFS benefit: 36-month EFS 84.5% vs 76.8% (HR 0.63). A 2024 report added an overall survival benefit (5-year OS 86.6% vs 81.7%, HR 0.66). It established chemo-immunotherapy as the standard for stage II-III TNBC regardless of PD-L1 status.","asOf":"2026-09-08","links":[{"label":"NEJM 2022 (EFS)","url":"https://doi.org/10.1056/NEJMoa2112651"},{"label":"NEJM 2020 (pCR)","url":"https://doi.org/10.1056/NEJMoa1910549"},{"label":"ClinicalTrials.gov NCT03036488","url":"https://clinicaltrials.gov/study/NCT03036488"}],"tags":[],"related":["idea-post-neoadjuvant-adc","idea-ctdna-escalation-tnbc"],"cancers":["tnbc"],"sections":[],"technologies":["checkpoint-inhibitor","cytotoxic-chemotherapy","platinum"],"targets":["pd1"],"drugs":["pembrolizumab","carboplatin","paclitaxel"],"companies":["merck"],"institutions":[],"pathways":[],"terms":["pcr","efs","neoadjuvant-adjuvant","cps","irae","rcb"],"trials":["keynote-522"],"people":["javier-cortes","jonas-bergh","park-yeon-hee","carsten-denkert"],"bottlenecks":["b-immunotherapy-response","b-toxicity-qol","b-dormancy-mrd"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/NEJMoa2112651","authors":"Schmid P, Cortes J, Dent R, et al.","paperType":"rct","findings":["pCR (ypT0/Tis ypN0) 64.8% with pembrolizumab vs 51.2% with placebo, a 13.6-point absolute gain (2020 interim report).","36-month event-free survival 84.5% vs 76.8%; HR for event or death 0.63 (95% CI 0.48-0.82).","Benefit was seen regardless of PD-L1 expression (CPS), unlike in the metastatic setting.","Patients with residual disease still did worse than those with pCR, but pembrolizumab improved EFS in both groups.","5-year overall survival 86.6% vs 81.7%, HR 0.66 (2024 update)."],"whatItMeans":"For stage II-III triple-negative breast cancer, chemotherapy plus pembrolizumab before surgery and pembrolizumab alone afterwards is now the standard approach worldwide, and the survival gain is real, not just a surrogate. It does not apply to stage I disease or to hormone-receptor-positive or HER2-positive cancers. The price is a year of immunotherapy with a meaningful chance of a permanent endocrine side effect such as hypothyroidism or adrenal insufficiency.","caveats":["The trial cannot say whether the adjuvant phase of pembrolizumab is needed for patients who reach pCR; de-escalation trials are testing this.","Immune-related adverse events (thyroid, adrenal, pituitary) are often permanent.","Carboplatin was part of the backbone in both arms, so the trial does not isolate the contribution of platinum.","The control arm did not include capecitabine for residual disease, which some regard as a weaker comparator."],"changedPractice":true,"participants":1174},{"id":"paper-keynote-564-nejm-2021","kind":"paper","name":"KEYNOTE-564: a year of pembrolizumab after kidney cancer surgery","aka":[],"tldr":"One year of pembrolizumab after surgery for high-risk kidney cancer reduced relapses by about a third and, in later follow-up, became the first adjuvant treatment to help kidney cancer patients live longer.","summary":"Double-blind, placebo-controlled phase 3 trial of 994 patients with clear-cell renal cell carcinoma at intermediate-high or high risk of recurrence after nephrectomy, or with resected metastatic disease (M1 NED), randomised to one year of pembrolizumab or placebo. Primary endpoint was disease-free survival.\n\n24-month DFS was 77.3% vs 68.1% (HR 0.68). The 2024 overall survival analysis showed HR 0.62 with 48-month OS 91.2% vs 86.0%. It was the first adjuvant therapy in kidney cancer to improve survival, after decades of negative trials with cytokines and VEGF inhibitors, and it stands alone: three other adjuvant checkpoint inhibitor trials (IMmotion010, CheckMate 914, PROSPER) were negative.","asOf":"2026-09-08","links":[{"label":"NEJM 2021","url":"https://doi.org/10.1056/NEJMoa2106391"},{"label":"NEJM 2024 (OS)","url":"https://doi.org/10.1056/NEJMoa2312695"},{"label":"ClinicalTrials.gov NCT03142334","url":"https://clinicaltrials.gov/study/NCT03142334"}],"tags":[],"related":[],"cancers":["rcc"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["pd1"],"drugs":["pembrolizumab"],"companies":["merck"],"institutions":["dana-farber"],"pathways":[],"terms":["neoadjuvant-adjuvant","os","irae"],"trials":[],"people":["toni-choueiri","lee-jae-lyun"],"bottlenecks":["b-dormancy-mrd","b-negative-results","b-toxicity-qol"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2021,"doi":"10.1056/NEJMoa2106391","authors":"Choueiri TK, Tomczak P, Park SH, et al.","paperType":"rct","findings":["24-month disease-free survival 77.3% vs 68.1%; HR 0.68 (95% CI 0.53-0.87).","Overall survival (NEJM 2024): HR 0.62 (95% CI 0.44-0.87); 48-month OS 91.2% vs 86.0%.","Largest DFS benefit in the small M1 NED group (HR 0.28) and in sarcomatoid tumours.","Grade 3 or higher adverse events 32.4% vs 17.7%; about 21% discontinued pembrolizumab for adverse events.","Endocrine immune-related events (hypothyroidism, adrenal insufficiency) were the most frequent lasting toxicities."],"whatItMeans":"Patients whose kidney cancer has been removed but who are at high risk of recurrence (large or high-grade tumours, node involvement, or resected metastases) can now be offered a year of pembrolizumab, which increases the chance of being alive and cancer-free several years later. Roughly nine patients need treatment to prevent one recurrence at two years, and some will have permanent side effects, so shared decision-making matters. Why pembrolizumab succeeded where similar drugs failed is not fully understood.","caveats":["The three other adjuvant checkpoint inhibitor trials in kidney cancer were negative, and the reasons (drug, population, chance) are debated.","Absolute DFS benefit of about 9 points; most patients treated would not have relapsed anyway.","The trial predated widespread use of immunotherapy at relapse in the control arm during the early years, which may exaggerate the OS effect relative to current practice.","Non-clear-cell histology was excluded."],"changedPractice":true,"participants":994},{"id":"paper-keynote-590-lancet-2021","kind":"paper","name":"KEYNOTE-590: pembrolizumab plus chemotherapy for first-line treatment of advanced oesophageal cancer","aka":[],"tldr":"Adding pembrolizumab to cisplatin-fluorouracil lengthened survival in advanced oesophageal cancer of both histologies, most clearly in squamous cell carcinoma and in tumours with high PD-L1, establishing chemo-immunotherapy as the first-line standard.","summary":"Phase 3 placebo-controlled trial of 749 patients with untreated advanced oesophageal or Siewert type 1 junctional cancer (73 percent squamous) randomised to pembrolizumab or placebo with cisplatin and fluorouracil.\n\nMedian overall survival was 12.4 versus 9.8 months overall (hazard ratio 0.73), 13.9 versus 8.8 months in squamous cell carcinoma with combined positive score of 10 or more (hazard ratio 0.57), and progression-free survival was improved in all groups.","asOf":"2026-09-17","links":[{"label":"Lancet 2021","url":"https://doi.org/10.1016/S0140-6736(21)01234-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34454674/"}],"tags":[],"related":[],"cancers":["oesophageal-squamous-cell-carcinoma","oesophageal-adenocarcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-590"],"people":["jong-mu-sun"],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2021,"doi":"10.1016/S0140-6736(21)01234-4","pmid":"34454674","authors":"Sun JM, Shen L, Shah MA, et al.","paperType":"rct","findings":["Median overall survival 12.4 vs 9.8 months overall; hazard ratio 0.73.","Squamous with combined positive score 10 or more: 13.9 vs 8.8 months; hazard ratio 0.57."],"whatItMeans":"Pembrolizumab plus chemotherapy is a first-line standard for advanced oesophageal cancer, with the strongest recommendation for PD-L1-expressing tumours.","caveats":["Benefit in adenocarcinoma and in low PD-L1 tumours was smaller.","Cisplatin-fluorouracil backbone is less used in some regions."],"changedPractice":true,"participants":749},{"id":"paper-keynote-629-pembrolizumab-cscc-grob-jco-2020","kind":"paper","name":"KEYNOTE-629: pembrolizumab monotherapy for recurrent or metastatic cutaneous squamous cell carcinoma","aka":[],"tldr":"Pembrolizumab shrank tumours in about a third of patients with recurrent or metastatic cutaneous squamous cell carcinoma, with most responses lasting beyond a year, leading to its approval as an alternative to cemiplimab.","summary":"Phase 2 study of 105 patients with recurrent or metastatic cutaneous squamous cell carcinoma, most previously treated, given pembrolizumab every three weeks.\n\nObjective response was 34.3 percent with complete response in 3.8 percent, median duration of response not reached, median progression-free survival 6.9 months, and toxicity typical of PD-1 blockade; a later cohort in locally advanced disease responded in about half.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2020","url":"https://doi.org/10.1200/JCO.19.03054"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32673170/"}],"tags":[],"related":[],"cancers":["advanced-cutaneous-scc"],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-629"],"people":["jean-jacques-grob"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/JCO.19.03054","pmid":"32673170","authors":"Grob JJ, Gonzalez R, Basset-Seguin N, et al.","paperType":"observational","findings":["Objective response 34.3 percent; median duration of response not reached.","Median progression-free survival 6.9 months."],"whatItMeans":"Pembrolizumab is an approved first-line option for advanced cutaneous squamous cell carcinoma alongside cemiplimab.","caveats":["Single-arm; lower response rate than cemiplimab in cross-trial comparison, partly reflecting more prior treatment."],"changedPractice":true,"participants":105},{"id":"paper-keynote-689-nejm-2025","kind":"paper","name":"KEYNOTE-689: neoadjuvant and adjuvant pembrolizumab for resectable locally advanced head and neck cancer","aka":[],"tldr":"Giving pembrolizumab before surgery and continuing it afterwards alongside radiotherapy reduced recurrences in resectable locally advanced head and neck cancer, the first improvement in surgical treatment of the disease in two decades.","summary":"Phase 3 trial of 714 patients with resectable stage III to IVA head and neck squamous cell carcinoma (excluding HPV-positive oropharynx in most analyses) randomised to two cycles of neoadjuvant pembrolizumab followed by surgery and adjuvant pembrolizumab with radiotherapy or chemoradiotherapy, or surgery and adjuvant radiotherapy or chemoradiotherapy alone.\n\nEvent-free survival was improved in patients with a PD-L1 combined positive score of 10 or more (median 59.7 versus 26.9 months; hazard ratio 0.66) and of 1 or more (hazard ratio 0.70), and major pathological responses occurred in 9.3 percent after neoadjuvant treatment.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2025","url":"https://doi.org/10.1056/NEJMoa2415434"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40532178/"}],"tags":[],"related":[],"cancers":["hpv-negative-head-and-neck-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-689"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2025,"doi":"10.1056/NEJMoa2415434","pmid":"40532178","authors":"Uppaluri R, Haddad RI, Tao Y, et al.","paperType":"rct","findings":["Combined positive score 10 or more: median event-free survival 59.7 vs 26.9 months; hazard ratio 0.66.","Combined positive score 1 or more: hazard ratio 0.70."],"whatItMeans":"Perioperative pembrolizumab is a new standard for resectable head and neck cancer with PD-L1 expression, adding immunotherapy to a treatment pathway that had not changed since postoperative chemoradiation was defined.","caveats":["Overall survival data immature.","Pembrolizumab was continued for up to 15 cycles after surgery, adding cost and immune toxicity."],"changedPractice":true,"participants":714},{"id":"paper-keynote-716-lancet-2022","kind":"paper","name":"KEYNOTE-716: adjuvant pembrolizumab versus placebo in completely resected stage IIB or IIC melanoma","aka":[],"tldr":"A year of pembrolizumab after surgery for stage IIB or IIC melanoma reduced recurrences and distant metastases by about 35 to 40 percent, extending adjuvant immunotherapy to node-negative but thick or ulcerated melanomas.","summary":"Phase 3 placebo-controlled trial of 976 patients aged 12 and over with resected stage IIB or IIC melanoma randomised to pembrolizumab or placebo for up to 17 cycles.\n\nAt the first interim analysis, recurrence-free survival favoured pembrolizumab (hazard ratio 0.65); at longer follow-up, 36-month recurrence-free survival was 76.2 versus 63.4 percent and distant metastasis-free survival hazard ratio 0.59. Immune-related adverse events, mainly endocrine, occurred in about a third.","asOf":"2026-09-17","links":[{"label":"Lancet 2022","url":"https://doi.org/10.1016/S0140-6736(22)00562-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35367007/"}],"tags":[],"related":[],"cancers":["stage-ii-melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-716"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2022,"doi":"10.1016/S0140-6736(22)00562-1","pmid":"35367007","authors":"Luke JJ, Rutkowski P, Queirolo P, et al.","paperType":"rct","findings":["Recurrence-free survival hazard ratio 0.65 at first analysis; 36-month rate 76.2 percent vs 63.4 percent.","Distant metastasis-free survival hazard ratio 0.59."],"whatItMeans":"Adjuvant pembrolizumab is approved for stage IIB and IIC melanoma, though the absolute benefit and lack of survival data make observation a reasonable alternative after discussion.","caveats":["No overall survival benefit shown; most patients would not have relapsed.","Permanent endocrine side effects in a minority."],"changedPractice":true,"participants":976},{"id":"paper-keynote-775-nejm-2022","kind":"paper","name":"KEYNOTE-775: lenvatinib plus pembrolizumab versus chemotherapy for previously treated advanced endometrial cancer","aka":[],"tldr":"After platinum chemotherapy, the combination of the kinase inhibitor lenvatinib and pembrolizumab lengthened survival compared with doxorubicin or paclitaxel in advanced endometrial cancer, including in the mismatch repair-proficient majority.","summary":"Phase 3 trial of 827 patients with advanced endometrial cancer after one prior platinum regimen randomised to lenvatinib plus pembrolizumab or physician's choice of doxorubicin or weekly paclitaxel.\n\nIn mismatch repair-proficient disease median overall survival was 17.4 versus 12.0 months (hazard ratio 0.68) and median progression-free survival 6.6 versus 3.8 months; results were similar in the whole population. Grade 3 or higher adverse events occurred in 89 percent of the combination arm.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2022","url":"https://doi.org/10.1056/NEJMoa2108330"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35045221/"}],"tags":[],"related":[],"cancers":["advanced-recurrent-endometrial-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["lenvatinib","pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-775"],"people":["vicky-makker"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/NEJMoa2108330","pmid":"35045221","authors":"Makker V, Colombo N, Casado Herráez A, et al.","paperType":"rct","findings":["Mismatch repair-proficient: median overall survival 17.4 vs 12.0 months; hazard ratio 0.68.","All patients: median overall survival 18.3 vs 11.4 months; hazard ratio 0.62."],"whatItMeans":"Lenvatinib-pembrolizumab is the standard second-line treatment for mismatch repair-proficient endometrial cancer after platinum, though its toxicity is considerable and its place after first-line immunotherapy is unclear.","caveats":["Hypertension, hypothyroidism, diarrhoea and weight loss led to frequent dose reductions.","Patients had not received prior immunotherapy, unlike many today."],"changedPractice":true,"participants":827},{"id":"paper-keynote-811-janjigian-lancet-2023","kind":"paper","name":"KEYNOTE-811: pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma","aka":[],"tldr":"Adding pembrolizumab to trastuzumab and chemotherapy improved response and progression-free survival in HER2-positive advanced gastric cancer, with the benefit concentrated in tumours that also express PD-L1.","summary":"Phase 3 placebo-controlled trial of 698 patients with untreated HER2-positive advanced gastric or junctional adenocarcinoma randomised to pembrolizumab or placebo with trastuzumab and fluoropyrimidine-platinum chemotherapy.\n\nMedian progression-free survival was 10.0 versus 8.1 months (hazard ratio 0.72) overall and 10.8 versus 7.2 months in PD-L1 combined positive score 1 or more (hazard ratio 0.70); response was 73 versus 60 percent, and the final analysis showed an overall survival benefit in the PD-L1-positive population (20.0 versus 15.7 months).","asOf":"2026-09-17","links":[{"label":"Lancet 2023","url":"https://doi.org/10.1016/S0140-6736(23)02033-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37871604/"}],"tags":[],"related":[],"cancers":["gastric-her2-positive"],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab","trastuzumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-811"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2023,"doi":"10.1016/S0140-6736(23)02033-0","pmid":"37871604","authors":"Janjigian YY, Kawazoe A, Bai Y, et al.","paperType":"rct","findings":["Median progression-free survival 10.0 vs 8.1 months; hazard ratio 0.72.","Combined positive score 1 or more: overall survival 20.0 vs 15.7 months at final analysis."],"whatItMeans":"Pembrolizumab with trastuzumab and chemotherapy is the first-line standard for HER2-positive gastric cancer with a PD-L1 combined positive score of 1 or more.","caveats":["No benefit in PD-L1-negative tumours (about 15 percent), leading to a label restriction."],"changedPractice":true,"participants":698},{"id":"paper-keynote-826-nejm-2021","kind":"paper","name":"KEYNOTE-826: pembrolizumab plus chemotherapy with or without bevacizumab for persistent, recurrent or metastatic cervical cancer","aka":[],"tldr":"Adding pembrolizumab to first-line chemotherapy, with or without bevacizumab, lengthened survival in advanced cervical cancer, the first improvement in the disease since bevacizumab was added seven years earlier.","summary":"Phase 3 placebo-controlled trial of 617 patients with persistent, recurrent or metastatic cervical cancer randomised to pembrolizumab or placebo with platinum-paclitaxel chemotherapy, with bevacizumab at investigator discretion.\n\nIn the PD-L1 combined positive score 1 or more population, median overall survival was not reached versus 16.3 months at the first analysis (hazard ratio 0.64) and 28.6 versus 16.5 months on update; progression-free survival was 10.4 versus 8.2 months.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2021","url":"https://doi.org/10.1056/NEJMoa2112435"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34534429/"}],"tags":[],"related":[],"cancers":["recurrent-metastatic-cervical-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-826"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2021,"doi":"10.1056/NEJMoa2112435","pmid":"34534429","authors":"Colombo N, Dubot C, Lorusso D, et al.","paperType":"rct","findings":["Combined positive score 1 or more: overall survival hazard ratio 0.64; updated median 28.6 vs 16.5 months.","Median progression-free survival 10.4 vs 8.2 months."],"whatItMeans":"Pembrolizumab plus chemotherapy with bevacizumab is the first-line standard for recurrent or metastatic cervical cancer with PD-L1 expression, which covers about nine in ten patients.","caveats":["Benefit in PD-L1-negative tumours was uncertain.","Bevacizumab use was not randomised."],"changedPractice":true,"participants":617},{"id":"paper-keynote-859-lancet-oncol-2023","kind":"paper","name":"KEYNOTE-859: pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer","aka":[],"tldr":"Adding pembrolizumab to platinum-fluoropyrimidine chemotherapy lengthened survival in HER2-negative advanced gastric cancer, with the largest gain in tumours with a PD-L1 combined positive score of 10 or more, confirming chemo-immunotherapy as first-line standard.","summary":"Phase 3 placebo-controlled trial of 1,579 patients with untreated HER2-negative locally advanced or metastatic gastric or junctional adenocarcinoma randomised to pembrolizumab or placebo with fluoropyrimidine-platinum chemotherapy.\n\nMedian overall survival was 12.9 versus 11.5 months overall (hazard ratio 0.78), 13.0 versus 11.4 months in combined positive score 1 or more (hazard ratio 0.74) and 15.7 versus 11.8 months in score 10 or more (hazard ratio 0.65).","asOf":"2026-09-17","links":[{"label":"Lancet Oncol 2023","url":"https://doi.org/10.1016/S1470-2045(23)00515-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37875143/"}],"tags":[],"related":[],"cancers":["gastric-pdl1-high"],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-859"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2023,"doi":"10.1016/S1470-2045(23)00515-6","pmid":"37875143","authors":"Rha SY, Oh DY, Yañez P, et al.","paperType":"rct","findings":["Median overall survival 12.9 vs 11.5 months overall; hazard ratio 0.78.","Combined positive score 10 or more: 15.7 vs 11.8 months; hazard ratio 0.65."],"whatItMeans":"Pembrolizumab plus chemotherapy is approved for HER2-negative advanced gastric cancer, alongside nivolumab plus chemotherapy from CheckMate 649, with strongest evidence at higher PD-L1 scores.","caveats":["Benefit in PD-L1-low tumours is small, and European approval is restricted to combined positive score 1 or more."],"changedPractice":true,"participants":1579},{"id":"paper-keynote-942-lancet-2024","kind":"paper","name":"KEYNOTE-942: a personalised mRNA cancer vaccine plus pembrolizumab after melanoma surgery","aka":[],"tldr":"A vaccine custom-made from each patient's own tumour mutations, given with pembrolizumab after surgery for high-risk melanoma, reduced recurrence by about 44% compared with pembrolizumab alone in a mid-sized randomised trial, the first sign that personalised cancer vaccines can work.","summary":"Open-label randomised phase 2b trial of 157 patients with completely resected stage IIIB-IV melanoma randomised 2:1 to mRNA-4157 (V940, intismeran autogene, encoding up to 34 patient-specific neoantigens) plus pembrolizumab or pembrolizumab alone for about a year. Primary endpoint was recurrence-free survival.\n\nRecurrence-free survival HR was 0.56 (18-month RFS 78.6% vs 62.2%) and distant metastasis-free survival HR 0.35, with benefit regardless of tumour mutational burden or PD-L1. Toxicity was mainly injection-site reactions and flu-like symptoms. It triggered the phase 3 INTerpath-001 trial and a wave of investment in individualised neoantigen vaccines.","asOf":"2026-09-08","links":[{"label":"PubMed search: KEYNOTE-942 mRNA-4157 Lancet 2024","url":"https://pubmed.ncbi.nlm.nih.gov/?term=mRNA-4157+V940+pembrolizumab+melanoma+KEYNOTE-942+Lancet"},{"label":"ClinicalTrials.gov NCT03897881","url":"https://clinicaltrials.gov/study/NCT03897881"}],"tags":[],"related":[],"cancers":["melanoma"],"sections":[],"technologies":["neoantigen-mrna-vaccine","checkpoint-inhibitor","wes-wgs"],"targets":["pd1"],"drugs":["intismeran-autogene","pembrolizumab"],"companies":["moderna","merck"],"institutions":[],"pathways":[],"terms":["neoantigen","tmb","neoadjuvant-adjuvant"],"trials":["interpath-001"],"people":["ryan-sullivan"],"bottlenecks":["b-immunotherapy-response","b-manufacturing-cell-therapy","b-trial-design"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2024,"doi":"10.1016/S0140-6736(23)02268-7","pmid":"38246194","authors":"Weber JS, Carlino MS, Khattak A, et al.","paperType":"rct","findings":["Recurrence-free survival HR 0.561 (95% CI 0.309-1.017); 18-month RFS 78.6% vs 62.2%.","Distant metastasis-free survival HR 0.347 (95% CI 0.145-0.828).","Benefit was seen in both high and low tumour mutational burden and in PD-L1-negative tumours.","Three-year update: RFS HR 0.51, with the curves continuing to separate.","Grade 3 or higher treatment-related adverse events 25% vs 18%; vaccine-related events were mostly grade 1-2 fatigue, injection-site pain and chills.","Manufacturing took about six to eight weeks per patient from biopsy sequencing to first dose."],"whatItMeans":"For the first time a randomised trial suggests that a vaccine tailored to an individual's tumour can reduce relapse when combined with immunotherapy, which is a proof of concept for a field that had failed for decades. Nothing changes for patients yet: the trial was small, the confidence interval crossed one, and the phase 3 trial in melanoma (and parallel trials in lung and other cancers) must confirm it. If it does, personalised mRNA vaccines could become a routine adjunct to checkpoint inhibitors after surgery.","caveats":["Phase 2b with 157 patients and an upper confidence limit above 1.0; the prespecified one-sided p-value was met but the result needs confirmation.","Open-label; recurrence assessments were investigator-based.","Individualised manufacturing is slow and expensive and has never been scaled to thousands of patients.","No biomarker predicts who benefits, and the mechanism (neoantigen-specific T-cell expansion) has been shown in only a subset."],"changedPractice":false,"participants":157},{"id":"paper-keynote-966-lancet-2023","kind":"paper","name":"KEYNOTE-966: pembrolizumab plus gemcitabine and cisplatin for advanced biliary tract cancer","aka":[],"tldr":"Adding pembrolizumab to gemcitabine-cisplatin, with gemcitabine continued as maintenance, lengthened survival in advanced biliary tract cancer by about two months, confirming the role of chemo-immunotherapy shown by TOPAZ-1.","summary":"Phase 3 placebo-controlled trial of 1,069 patients with untreated metastatic or unresectable biliary tract cancer randomised to pembrolizumab or placebo with gemcitabine-cisplatin, with gemcitabine continued beyond eight cycles.\n\nMedian overall survival was 12.7 versus 10.9 months (hazard ratio 0.83), with a consistent effect across subgroups and no new safety signals.","asOf":"2026-09-17","links":[{"label":"Lancet 2023","url":"https://doi.org/10.1016/S0140-6736(23)00727-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37075781/"}],"tags":[],"related":[],"cancers":["intrahepatic-cholangiocarcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":["cisplatin","gemcitabine","pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-966"],"people":["robin-kate-kelley"],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2023,"doi":"10.1016/S0140-6736(23)00727-4","pmid":"37075781","authors":"Kelley RK, Ueno M, Yoo C, et al.","paperType":"rct","findings":["Median overall survival 12.7 vs 10.9 months; hazard ratio 0.83.","Median progression-free survival 6.5 vs 5.6 months."],"whatItMeans":"Pembrolizumab with gemcitabine-cisplatin is an approved first-line option for advanced biliary tract cancer alongside durvalumab-based therapy.","caveats":["Modest absolute gain; no biomarker enrichment."],"changedPractice":true,"participants":1069},{"id":"paper-keynote-a18-os-lancet-2024","kind":"paper","name":"KEYNOTE-A18: pembrolizumab with chemoradiotherapy for locally advanced cervical cancer (overall survival)","aka":[],"tldr":"The second report from KEYNOTE-A18 showed that adding pembrolizumab to chemoradiotherapy for high-risk locally advanced cervical cancer also lengthened life: 82.6% of women were alive at three years against 74.8%, a third fewer deaths.","summary":"Second interim analysis of the double-blind, placebo-controlled phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 trial, in which 1,060 patients with newly diagnosed, high-risk locally advanced cervical cancer (FIGO 2014 stage IB2-IIB node-positive or stage III-IVA) were randomised to pembrolizumab or placebo with cisplatin-based chemoradiotherapy followed by pembrolizumab or placebo maintenance.\n\nAt data cutoff on 8 January 2024 (median follow-up 29.9 months) median overall survival was not reached in either group; 36-month overall survival was 82.6% with pembrolizumab against 74.8% with placebo, hazard ratio for death 0.67 (p=0.0040), meeting the primary objective. Grade 3 or higher adverse events occurred in 78% and 70% of patients, and potentially immune-mediated adverse events in 39% and 17%. Together with the progression-free survival report it established immuno-chemoradiotherapy as a new standard of care for this population.","asOf":"2026-09-08","links":[{"label":"Lancet 2024 (OS)","url":"https://doi.org/10.1016/S0140-6736(24)01808-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39288779/"},{"label":"ClinicalTrials.gov NCT04221945","url":"https://clinicaltrials.gov/study/NCT04221945"}],"tags":[],"related":[],"cancers":["cervical"],"sections":[],"technologies":["checkpoint-inhibitor","imrt-igrt","brachytherapy","platinum"],"targets":["pd1"],"drugs":["pembrolizumab"],"companies":["merck"],"institutions":["gemelli"],"pathways":[],"terms":["pfs","os","cps","standard-of-care"],"trials":["keynote-a18"],"people":["domenica-lorusso","giovanni-scambia"],"bottlenecks":["b-global-access","b-immunotherapy-response","b-drug-pricing"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2024,"doi":"10.1016/S0140-6736(24)01808-7","pmid":"39288779","authors":"Lorusso D, Xiang Y, Hasegawa K, et al.","paperType":"rct","findings":["36-month overall survival 82.6% (95% CI 78.4-86.1) vs 74.8% (70.1-78.8); HR for death 0.67 (95% CI 0.50-0.90, p=0.0040).","Median follow-up 29.9 months; median overall survival not reached in either group.","Grade 3 or higher adverse events 78% vs 70%, most often anaemia and falls in white cell and neutrophil counts.","Potentially immune-mediated adverse events 39% vs 17%."],"whatItMeans":"The survival gain turns the earlier progression-free survival result into a clear reason to offer pembrolizumab with and after chemoradiotherapy to women with node-positive or stage III-IVA cervical cancer. Because cervical cancer is concentrated in low- and middle-income countries, the benefit reaches most women only if pricing and access follow.","caveats":["Interim analysis with median follow-up under three years; late recurrences are possible in this disease.","High-risk population only; the negative CALLA trial suggests lower-risk patients may not benefit.","About two years of pembrolizumab is costly where cervical cancer burden is highest."],"changedPractice":true,"participants":1060},{"id":"paper-keynote-a18-pfs-lancet-2024","kind":"paper","name":"KEYNOTE-A18: pembrolizumab with chemoradiotherapy for locally advanced cervical cancer (progression-free survival)","aka":[],"tldr":"Adding pembrolizumab to standard chemoradiotherapy for high-risk locally advanced cervical cancer reduced progression or death by 30%, the first systemic advance in this setting since cisplatin was added to radiotherapy in 1999.","summary":"Double-blind, placebo-controlled phase 3 trial (ENGOT-cx11/GOG-3047/KEYNOTE-A18) of 1,060 patients at 176 centres in 30 countries with newly diagnosed, high-risk locally advanced cervical cancer (FIGO 2014 stage IB2-IIB with node-positive disease, or stage III-IVA) randomised 1:1 to five cycles of pembrolizumab 200 mg or placebo every three weeks with chemoradiotherapy, then 15 cycles of pembrolizumab 400 mg or placebo every six weeks. Primary endpoints were progression-free survival and overall survival.\n\nAt the first interim analysis (data cutoff 9 January 2023, median follow-up 17.9 months) median progression-free survival was not reached in either group; the 24-month rate was 68% with pembrolizumab against 57% with placebo (HR 0.70, p=0.0020). Overall survival at 24 months was 87% against 81% (HR 0.73), not yet significant at this analysis. A second Lancet report later in 2024 confirmed the overall survival gain.","asOf":"2026-09-08","links":[{"label":"Lancet 2024 (PFS)","url":"https://doi.org/10.1016/S0140-6736(24)00317-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38521086/"},{"label":"ClinicalTrials.gov NCT04221945","url":"https://clinicaltrials.gov/study/NCT04221945"}],"tags":[],"related":[],"cancers":["cervical"],"sections":[],"technologies":["checkpoint-inhibitor","imrt-igrt","brachytherapy","platinum"],"targets":["pd1"],"drugs":["pembrolizumab"],"companies":["merck"],"institutions":["gemelli"],"pathways":[],"terms":["pfs","os","cps","standard-of-care"],"trials":["keynote-a18"],"people":["domenica-lorusso","giovanni-scambia"],"bottlenecks":["b-global-access","b-immunotherapy-response","b-drug-pricing"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2024,"doi":"10.1016/S0140-6736(24)00317-9","pmid":"38521086","authors":"Lorusso D, Xiang Y, Hasegawa K, et al.","paperType":"rct","findings":["24-month progression-free survival 68% vs 57%; HR for progression or death 0.70 (95% CI 0.55-0.89, p=0.0020), meeting the primary objective.","24-month overall survival 87% vs 81%; HR 0.73 (95% CI 0.49-1.07), not yet across the significance boundary at 42.9% information fraction.","Grade 3 or higher adverse events 75% vs 69%.","The earlier CALLA trial of durvalumab with chemoradiotherapy in a broader population was negative, highlighting the importance of enrolling high-risk patients."],"whatItMeans":"Women with locally advanced cervical cancer that is node-positive or stage III-IVA can be offered pembrolizumab alongside and after chemoradiotherapy to lower the chance of relapse. The result matters most in countries where cervical cancer is common but immunotherapy access is poorest, so its global impact depends on pricing and health-system capacity. It does not apply to early-stage disease treated with surgery or to lower-risk locally advanced disease without nodal involvement.","caveats":["High-risk population only; the negative CALLA trial suggests lower-risk patients may not benefit.","Radiotherapy quality (including brachytherapy) varied and is a major determinant of outcome; the trial was conducted mainly in well-resourced centres.","About two years of pembrolizumab is costly where cervical cancer burden is highest.","Median follow-up was under 18 months at this analysis; overall survival was not yet significant."],"changedPractice":true,"participants":1060},{"id":"paper-heinrich-kit-mutation-imatinib-response-jco-2003","kind":"paper","name":"Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumour","aka":[],"tldr":"This analysis showed that the type of KIT mutation predicts response to imatinib: tumours with exon 11 mutations responded in over 80 percent of cases, exon 9 mutations in under half, and tumours without a KIT or PDGFRA mutation rarely responded.","summary":"Mutation analysis of tumours from 127 patients with advanced GIST treated with imatinib in the phase 2 B2222 trial, correlating KIT and PDGFRA genotype with response and progression-free survival.\n\nPartial response was 83.5 percent in KIT exon 11-mutant tumours, 47.8 percent in exon 9-mutant tumours and 0 percent in tumours without a detectable KIT or PDGFRA mutation, with corresponding differences in event-free survival.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2003","url":"https://doi.org/10.1200/JCO.2003.04.190"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/14645423/"}],"tags":[],"related":[],"cancers":["gist-kit-exon-11"],"sections":[],"technologies":[],"targets":[],"drugs":["imatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["michael-heinrich"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2003,"doi":"10.1200/JCO.2003.04.190","pmid":"14645423","authors":"Heinrich MC, Corless CL, Demetri GD, et al.","paperType":"translational","findings":["Response 83.5 percent (exon 11) vs 47.8 percent (exon 9) vs 0 percent (no mutation).","PDGFRA mutations found in a subset of KIT wild-type tumours."],"whatItMeans":"Mutation testing is standard before imatinib in GIST: exon 11 tumours receive 400 mg, exon 9 tumours are dosed at 800 mg, and PDGFRA D842V tumours are given avapritinib instead.","caveats":["Retrospective analysis of a trial cohort."],"changedPractice":true,"participants":127},{"id":"paper-montoya-science","kind":"paper","name":"Kinase-impaired BTK mutations are susceptible to clinical-stage BTK and IKZF1/3 degrader NX-2127","aka":[],"tldr":"Paper cited by one idea page, indexed on Europe PMC as PubMed record 38301010 and published in Science; the citing page links this DOI, which is how the record was matched.","summary":"Increasing use of covalent and noncovalent inhibitors of Bruton's tyrosine kinase (BTK) has elucidated a series of acquired drug-resistant BTK mutations in patients with B cell malignancies. Here we identify inhibitor resistance mutations in BTK with distinct enzymatic activities, including some that impair BTK enzymatic activity while imparting novel protein-protein interactions that sustain B cell receptor (BCR) signaling. Furthermore, we describe a clinical-stage BTK and IKZF1/3 degrader, NX-2127, that can bind and proteasomally degrade each mutant BTK proteoform, resulting in potent blockade of BCR signaling. Treatment of chronic lymphocytic leukemia with NX-2127 achieves >80% degradation of BTK in patients and demonstrates proof-of-concept therapeutic benefit. These data reveal an oncogenic scaffold function of mutant BTK that confers resistance across clinically approved BTK inhibitors but is overcome by BTK degradation in patients.\n\nIndexed on Europe PMC as PubMed record 38301010 (DOI 10.1126/science.adi5798). Matched by DOI alone: one idea page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Science 2024","url":"https://doi.org/10.1126/science.adi5798"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38301010/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38301010"}],"tags":["europepmc-ingest"],"related":["idea-btk-degrader-frontline"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2024,"doi":"10.1126/science.adi5798","pmid":"38301010","authors":"Montoya S, Bourcier J, Noviski M, et al.","paperType":"observational","findings":[],"whatItMeans":"One idea page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-klass-01-kim-jama-oncol-2019","kind":"paper","name":"KLASS-01: laparoscopic versus open distal gastrectomy for stage I gastric cancer, long-term survival","aka":[],"tldr":"Keyhole removal of the lower stomach for early gastric cancer gave the same five-year survival as open surgery in this large Korean trial, confirming laparoscopic gastrectomy as a standard for stage I disease.","summary":"Phase 3 non-inferiority trial of 1,416 patients with clinical stage I gastric cancer randomised to laparoscopic or open distal gastrectomy in 13 Korean centres.\n\nFive-year overall survival was 94.2 percent with laparoscopic and 93.3 percent with open surgery, cancer-specific survival 97.1 versus 97.2 percent, with fewer wound complications after laparoscopic surgery as reported earlier.","asOf":"2026-09-17","links":[{"label":"JAMA Oncol 2019","url":"https://doi.org/10.1001/jamaoncol.2018.6727"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30730546/"}],"tags":[],"related":[],"cancers":["early-gastric-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["klass-01"],"people":["hyung-ho-kim"],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2019,"doi":"10.1001/jamaoncol.2018.6727","pmid":"30730546","authors":"Kim HH, Han SU, Kim MC, et al.","paperType":"rct","findings":["Five-year overall survival 94.2 percent vs 93.3 percent (non-inferior).","Five-year cancer-specific survival 97.1 percent vs 97.2 percent."],"whatItMeans":"Laparoscopic distal gastrectomy is the standard operation for stage I gastric cancer outside endoscopic criteria in East Asia and increasingly elsewhere.","caveats":["High-volume Korean surgeons; results may not generalise to low-volume settings."],"changedPractice":true,"participants":1416},{"id":"paper-klimstra-acinar-cell-carcinoma-pancreas-28-cases-ajsp-1992","kind":"paper","name":"Klimstra 1992: acinar cell carcinoma of the pancreas, a clinicopathologic study of 28 cases","aka":[],"tldr":"The reference description of acinar cell carcinoma, the rare pancreatic cancer that grows from enzyme-producing cells: how it looks under the microscope, how to prove it with enzyme stains, and how it behaves, which is aggressive but somewhat less so than ordinary pancreatic cancer.","summary":"Clinicopathological study of 28 acinar cell carcinomas from the Armed Forces Institute of Pathology and Memorial Sloan Kettering. The tumours were large, mostly in older men, and about half had metastasised at diagnosis; a minority presented with the lipase hypersecretion syndrome of subcutaneous fat necrosis and polyarthralgia.\n\nHistologically the tumours showed acinar and solid growth with minimal stroma, and immunohistochemistry for trypsin, chymotrypsin and lipase confirmed acinar differentiation. Median survival was about 18 months, better than ductal adenocarcinoma but still poor, with occasional long-term survivors after resection.","asOf":"2026-09-21","links":[{"label":"Am J Surg Pathol 1992","url":"https://doi.org/10.1097/00000478-199209000-00001"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/1384374/"}],"tags":[],"related":[],"cancers":["pancreatic-acinar-cell-carcinoma","pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"American Journal of Surgical Pathology","year":1992,"doi":"10.1097/00000478-199209000-00001","pmid":"1384374","authors":"Klimstra DS, Heffess CS, Oertel JE, Rosai J.","paperType":"observational","findings":["Acinar cell carcinoma makes up about 1 to 2 percent of pancreatic exocrine tumours; large tumours, older men, about half metastatic at diagnosis.","Trypsin, chymotrypsin and lipase immunostains confirm acinar differentiation.","Median survival about 18 months, better than ductal adenocarcinoma."],"whatItMeans":"This series defined the diagnostic criteria still used for acinar cell carcinoma and established that it should be classified and treated as a distinct disease from ductal adenocarcinoma.","caveats":["Retrospective consultation series from before modern chemotherapy; survival figures are historical.","Mixed acinar-neuroendocrine tumours were only partly separated."],"participants":28},{"id":"paper-klimstra-pancreatoblastoma-clinicopathologic-study-ajsp-1995","kind":"paper","name":"Klimstra 1995: pancreatoblastoma, a clinicopathologic study and review of the literature","aka":[],"tldr":"The defining description of pancreatoblastoma, the rare pancreatic cancer of young children: its distinctive mix of enzyme-producing cells and whorled squamoid nests under the microscope, its generally good outlook after complete removal in children, and its more aggressive behaviour in adults.","summary":"Clinicopathological study of pancreatoblastomas from the Armed Forces Institute of Pathology with a review of the published literature. The tumours were large and mostly arose in the first decade of life, though adult cases occurred; some were associated with Beckwith-Wiedemann syndrome and many produced alpha-fetoprotein.\n\nHistologically the tumours combined acinar differentiation (confirmed by trypsin, chymotrypsin and lipase immunostains) with squamoid nests, and variable neuroendocrine and ductal elements, distinguishing them from acinar cell carcinoma. Complete resection was associated with cure in most children, while adults and patients with metastases fared poorly.","asOf":"2026-09-21","links":[{"label":"Am J Surg Pathol 1995","url":"https://doi.org/10.1097/00000478-199512000-00005"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/7503360/"}],"tags":[],"related":[],"cancers":["pancreatoblastoma","pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"American Journal of Surgical Pathology","year":1995,"doi":"10.1097/00000478-199512000-00005","pmid":"7503360","authors":"Klimstra DS, Wenig BM, Adair CF, Heffess CS.","paperType":"observational","findings":["Acinar differentiation with squamoid nests defines the tumour and separates it from acinar cell carcinoma.","Most cases in young children, some with Beckwith-Wiedemann syndrome; alpha-fetoprotein often raised.","Complete resection cures most children; adults and metastatic cases do poorly."],"whatItMeans":"Pathologists diagnose pancreatoblastoma by the criteria set out here, and the paper established that the paediatric and adult forms behave differently.","caveats":["Small consultation series with limited treatment data.","Molecular features (Wnt pathway and 11p alterations) were described later."]},{"id":"paper-ahn-n-engl-j-med","kind":"paper","name":"Korea's thyroid-cancer \"epidemic\"--screening and overdiagnosis","aka":[],"tldr":"Paper cited by one bottleneck page and one idea page, indexed on Europe PMC as PubMed record 25372084 and published in New England Journal of Medicine; the citing pages link this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 25372084 (DOI 10.1056/nejmp1409841). Matched by DOI alone: one bottleneck page and one idea page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2014","url":"https://doi.org/10.1056/nejmp1409841"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25372084/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25372084"}],"tags":["europepmc-ingest"],"related":["b-overdiagnosis","idea-thyroid-overdiagnosis-reversal"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2014,"doi":"10.1056/nejmp1409841","pmid":"25372084","authors":"Ahn HS, Kim HJ, Welch HG","paperType":"observational","findings":[],"whatItMeans":"One bottleneck page and one idea page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-schirripa-kras-g12c-metastatic-colorectal-clin-colorectal-cancer-2020","kind":"paper","name":"KRAS G12C metastatic colorectal cancer: specific features of a new emerging target population","aka":[],"tldr":"As the first KRAS G12C drugs arrived, this study described the patients they would treat: about one in six KRAS-mutant bowel cancers, more often men, more often with lung and liver spread, and with shorter survival than other KRAS mutations.","summary":"Clinicopathological features and outcome data for KRAS-mutant metastatic colorectal cancer patients referred to three Italian oncology units between January 2010 and December 2018 were collected, with a separate Milan cohort as external validation. Of 839 KRAS-mutant patients in the main population, 145 (17%) had a KRAS G12C mutation. G12C patients were more likely to be men and to present with lung and liver metastases, and less likely to have peritoneal spread. KRAS G12C mutation was associated with shorter overall survival than other KRAS mutations (hazard ratio 1.32), a result confirmed in the external validation cohort.","asOf":"2026-09-24","links":[{"label":"Schirripa et al., Clin Colorectal Cancer 2020: KRAS G12C metastatic colorectal cancer in 839 KRAS-mutant patients","url":"https://doi.org/10.1016/j.clcc.2020.04.009"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32605718/"}],"tags":[],"related":["kras-g12c"],"cancers":["colorectal"],"sections":[],"technologies":["kras-inhibitors"],"targets":["kras"],"drugs":[],"companies":[],"institutions":[],"pathways":["ras-mapk"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-colorectal-cancer"],"dependsOn":[],"notes":[],"journal":"Clinical Colorectal Cancer","year":2020,"doi":"10.1016/j.clcc.2020.04.009","pmid":"32605718","authors":"Schirripa M, Nappo F, Cremolini C, et al.","paperType":"observational","findings":["KRAS G12C in 145 of 839 KRAS-mutant patients (17%), about 3% of all colorectal cancers.","More lung and liver metastases, less peritoneal spread.","Shorter overall survival than other KRAS mutations (hazard ratio 1.32)."],"whatItMeans":"It defines the population the G12C inhibitors address and sets the baseline against which CodeBreaK 300 and KRYSTAL-1 are read.","caveats":["Retrospective, from referral centres.","Predates the G12C inhibitors, so the survival figures describe untreated-for-G12C practice."],"changedPractice":false,"participants":839},{"id":"paper-bournet-kras-g12d-prognosis-pancreatic-ctg-2016","kind":"paper","name":"KRAS G12D mutation subtype is a prognostic factor for advanced pancreatic adenocarcinoma","aka":[],"tldr":"Genotyping needle biopsies from 219 patients with advanced pancreatic cancer showed the KRAS G12D allele carried the shortest survival, six months against nine for other alleles and fourteen for G12R.","summary":"Multicentre prospective study: exon-2 KRAS status on EUS-guided fine-needle aspiration of the primary in locally advanced or metastatic pancreatic ductal carcinoma, with survival adjusted for age, stage, performance status, CA 19-9 and treatment. Of 219 patients, 147 had a codon-12 mutation (G12D 73, G12V 53, G12R 21) and 72 were wild-type. Survival did not differ between mutant and wild-type (8 versus 9 months), but G12D carried 6 months against 9 for the rest (hazard ratio 1.47), with G12V 9 and G12R 14 months; results held among 162 chemotherapy-treated patients (hazard ratio 1.66) and in multivariate analysis (1.44).","asOf":"2026-09-24","links":[{"label":"Bournet et al., Clin Transl Gastroenterol 2016: KRAS G12D and prognosis in 219 advanced patients","url":"https://doi.org/10.1038/ctg.2016.18"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27010960/"}],"tags":[],"related":["kras-g12d"],"cancers":["pancreatic","metastatic-pdac","locally-advanced-pdac"],"sections":[],"technologies":[],"targets":["kras"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["kras-mutation-subtypes"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Clinical and Translational Gastroenterology","year":2016,"doi":"10.1038/ctg.2016.18","pmid":"27010960","authors":"Bournet B, Muscari F, Buscail C, et al.","paperType":"observational","findings":["G12D 73, G12V 53, G12R 21 of 147 codon-12 mutations.","G12D overall survival 6 months versus 9 (hazard ratio 1.47); G12R 14 months."],"whatItMeans":"It is the allele-level prognosis behind reading the KRAS variant rather than 'KRAS mutant', and it shows the older EUS assay over-called wild-type (33%).","caveats":["Single-gene exon-2 assay on cytology; the 33% wild-type rate reflects low cellularity.","Treatment was heterogeneous."],"changedPractice":false,"participants":219},{"id":"paper-pik3ca-colorectal-lancet-oncol-2011","kind":"paper","name":"KRAS, BRAF, PIK3CA, and PTEN mutations: implications for targeted therapies in metastatic colorectal cancer","aka":[],"tldr":"Review on PIK3CA in Colorectal cancer, in The Lancet Oncology (2011), one of the most cited Europe PMC records with PIK3CA in its title.","summary":"The discovery of mutant KRAS as a predictor of resistance to epidermal growth-factor receptor (EGFR) monoclonal antibodies brought a major change in the treatment of metastatic colorectal cancer. This seminal finding also highlighted our sparse knowledge about key signalling pathways in colorectal tumours. Drugs that inhibit oncogenic alterations such as phospho-MAP2K (also called MEK), phospho-AKT, and mutant B-RAF seem promising as single treatment or when given with EGFR inhibitors. However, our understanding of the precise role these potential drug targets have in colorectal tumours, and the oncogenic dependence that tumours might have on these components, has not progressed at the same rate. As a result, patient selection and prediction of treatment effects remain problematic. We review the role of mutations in genes other than KRAS on the efficacy of anti-EGFR therapy, and discuss strategies to target these oncogenic alterations alone or in combination with receptor tyrosine-kinase inhibition.\n\nIndexed on Europe PMC as PubMed record 21163703 (DOI 10.1016/s1470-2045(10)70209-6). Its title names PIK3CA and its text names Colorectal cancer; PubMed types it as a review (Research Support, Non-U.S. Gov't, Review). It was matched automatically to the idea \"Get biomarker-directed aspirin after colorectal surgery into labels and guidelines\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2011","url":"https://doi.org/10.1016/s1470-2045(10)70209-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21163703/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/21163703"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2011,"doi":"10.1016/s1470-2045(10)70209-6","pmid":"21163703","authors":"De  Roock W, De Vriendt V, Normanno N, et al.","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for PIK3CA in Colorectal cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by PIK3CA in the title and Colorectal cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-krystal-1-adagrasib-kras-g12c-solid-tumours-jco-2023","kind":"paper","name":"KRYSTAL-1: adagrasib in advanced solid tumours harbouring a KRAS G12C mutation, including pancreatic cancer","aka":[],"tldr":"Adagrasib, the second KRAS G12C pill, shrank tumours in about a third of patients with pancreatic cancer and in two in five with bile duct cancer in this basket study, with disease control for several months.","summary":"Phase 2 cohort of the KRYSTAL-1 trial in 64 patients with previously treated KRAS G12C-mutated solid tumours other than lung or colorectal cancer, treated with adagrasib 600 mg twice daily. The pancreatic cohort had 21 patients and the biliary tract cohort 12; other tumours included appendiceal, ovarian, endometrial and small bowel cancers.\n\nIn pancreatic cancer the objective response rate was about 33 percent, with median progression-free survival of 5.4 months and median overall survival of 8.0 months; in biliary tract cancer the response rate was about 42 percent. Treatment-related adverse events were mostly gastrointestinal and manageable with dose reduction.","asOf":"2026-09-21","links":[{"label":"J Clin Oncol 2023","url":"https://doi.org/10.1200/JCO.23.00434"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37099736/"}],"tags":[],"related":["kras-g12c"],"cancers":["kras-g12c-pdac","pancreatic"],"sections":[],"technologies":["kras-inhibitors"],"targets":["kras"],"drugs":["adagrasib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct03785249"],"people":["tanios-bekaii-saab"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2023,"doi":"10.1200/JCO.23.00434","pmid":"37099736","authors":"Bekaii-Saab TS, Yaeger R, Spira AI, et al.","paperType":"observational","findings":["Pancreatic cohort (21 patients): objective response about 33 percent, median progression-free survival 5.4 months, median overall survival 8.0 months.","Biliary tract cohort (12 patients): objective response about 42 percent."],"whatItMeans":"Adagrasib joins sotorasib as a later-line option for KRAS G12C pancreatic cancer in guidelines; both drugs are the template for the G12D and pan-RAS inhibitors now in pancreatic trials.","caveats":["Small single-arm cohorts with a short follow-up; the pancreatic response rate has a wide confidence interval.","KRAS G12C is found in only 1 to 2 percent of pancreatic cancers."],"changedPractice":true,"participants":64},{"id":"paper-krystal-1-crc-yaeger-nejm-2023","kind":"paper","name":"KRYSTAL-1: adagrasib with or without cetuximab in KRAS G12C-mutated colorectal cancer","aka":[],"tldr":"The KRAS G12C inhibitor adagrasib on its own shrank about one in five previously treated colorectal cancers, but combined with the EGFR antibody cetuximab the response rate rose to nearly half, showing the two drugs are needed together in this disease.","summary":"Phase 1/2 study including 44 patients with KRAS G12C-mutated metastatic colorectal cancer treated with adagrasib alone and 32 treated with adagrasib plus cetuximab, all heavily pretreated.\n\nObjective response was 19 percent with monotherapy (median progression-free survival 5.6 months) and 46 percent with the combination (median progression-free survival 6.9 months, median overall survival 13.4 months).","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2023","url":"https://doi.org/10.1056/NEJMoa2212419"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36546659/"}],"tags":[],"related":["kras-g12c"],"cancers":["kras-g12c-colorectal"],"sections":[],"technologies":["kras-inhibitors"],"targets":["kras","egfr"],"drugs":["adagrasib","cetuximab"],"companies":[],"institutions":[],"pathways":["ras-mapk"],"terms":[],"trials":[],"people":["rona-yaeger"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/NEJMoa2212419","pmid":"36546659","authors":"Yaeger R, Weiss J, Pelster MS, et al.","paperType":"observational","findings":["Objective response 19 percent with adagrasib alone vs 46 percent with adagrasib plus cetuximab.","Median overall survival 13.4 months with the combination."],"whatItMeans":"Adagrasib plus cetuximab is an approved option for previously treated KRAS G12C colorectal cancer, alongside sotorasib plus panitumumab; monotherapy is not enough because EGFR signalling reactivates the pathway.","caveats":["Small single-arm cohorts.","Responses are shorter than in KRAS G12C lung cancer."],"changedPractice":true,"participants":76},{"id":"paper-krystal-12-plain-language-summary-future-oncol-2026","kind":"paper","name":"KRYSTAL-12 plain language summary: adagrasib for non-small-cell lung cancer with KRAS G12C mutations","aka":[],"tldr":"A plain-language account of the KRYSTAL-12 trial, written for patients and carers, explaining how adagrasib compared with docetaxel chemotherapy in previously treated KRAS G12C lung cancer.","summary":"Plain language summary of the phase 3 KRYSTAL-12 trial, which randomised previously treated patients with KRAS G12C-mutated non-small-cell lung cancer to the KRAS G12C inhibitor adagrasib or docetaxel. Written by the trial investigators for a non-specialist reader, it restates the design, the progression-free survival result and the side-effect profile of the primary publication.\n\nEurope PMC indexes no abstract for this article, so OnCo carries no figures from it; the trial's own record holds the primary result from the pivotal publication.","asOf":"2026-09-21","links":[{"label":"Future Oncol 2026","url":"https://doi.org/10.1080/14796694.2026.2719409"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42745627/"},{"label":"ClinicalTrials.gov NCT04685135","url":"https://clinicaltrials.gov/study/NCT04685135"}],"tags":[],"related":[],"cancers":["nsclc","kras-g12c-nsclc"],"sections":[],"technologies":[],"targets":["kras"],"drugs":["adagrasib"],"companies":["bms"],"institutions":[],"pathways":[],"terms":[],"trials":["krystal-12"],"people":["fabrice-barlesi","lu-shun","martin-reck","tony-mok"],"bottlenecks":[],"keyPapers":[],"journals":["future-oncology"],"dependsOn":[],"notes":[],"journal":"Future Oncology","year":2026,"doi":"10.1080/14796694.2026.2719409","pmid":"42745627","authors":"Barlesi F, Yao W, Duruisseaux M, et al.","paperType":"review","findings":["Restates the KRYSTAL-12 result in plain language for patients: adagrasib compared with docetaxel after prior treatment for KRAS G12C lung cancer."],"whatItMeans":"Useful for a patient offered adagrasib after chemotherapy or immunotherapy who wants the trial explained without jargon. It adds no new data; the primary KRYSTAL-12 publication and the trial page remain the reference for the numbers.","caveats":["A plain language summary of a published trial, not a new analysis; it reports no results beyond the primary publication.","No abstract is indexed on Europe PMC, so no figures have been transcribed here."],"changedPractice":false},{"id":"paper-la-rosa-acinar-cell-carcinoma-62-cases-ajsp-2012","kind":"paper","name":"La Rosa 2012: clinicopathologic study of 62 acinar cell carcinomas of the pancreas","aka":[],"tldr":"The largest single pathology series of acinar cell carcinoma, from a European network, confirmed which stains identify the tumour, described its variants and showed that stage at diagnosis is what determines survival.","summary":"Multicentre European series of 62 acinar cell carcinomas of the pancreas with detailed morphology, immunohistochemistry and follow-up. The study compared the sensitivity of trypsin, chymotrypsin, lipase and BCL10 as markers of acinar differentiation, characterised mixed acinar-neuroendocrine and acinar-ductal tumours, and examined the acinar cell cystadenocarcinoma variant.\n\nSurvival was better than in ductal adenocarcinoma but depended strongly on stage: patients with localised, resected tumours could survive for years while metastatic disease behaved aggressively. Trypsin and BCL10 were the most useful diagnostic markers.","asOf":"2026-09-21","links":[{"label":"Am J Surg Pathol 2012","url":"https://doi.org/10.1097/PAS.0b013e318263209d"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23026929/"}],"tags":[],"related":[],"cancers":["pancreatic-acinar-cell-carcinoma","pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"American Journal of Surgical Pathology","year":2012,"doi":"10.1097/PAS.0b013e318263209d","pmid":"23026929","authors":"La Rosa S, Adsay V, Albarello L, et al.","paperType":"observational","findings":["Trypsin and BCL10 immunostains were the most sensitive markers of acinar differentiation.","Stage (tumour size, nodal and distant spread) was the dominant prognostic factor; resected localised tumours had a favourable course."],"whatItMeans":"The paper underpins the WHO diagnostic criteria for acinar cell carcinoma and its variants and supports aggressive surgery for localised disease.","caveats":["Retrospective pathology series with heterogeneous treatment.","Molecular characterisation was not part of this study; the genomic profile came later."],"participants":62},{"id":"paper-lacc-nejm-2018","kind":"paper","name":"LACC: minimally invasive versus open radical hysterectomy for early cervical cancer","aka":[],"tldr":"Against expectations, keyhole radical hysterectomy for early cervical cancer led to more recurrences and more deaths than open surgery, reversing a decade of practice towards laparoscopic and robotic operations.","summary":"Phase 3 non-inferiority trial of 631 women with stage IA1 (with lymphovascular invasion) to IB1 cervical cancer randomised to minimally invasive (laparoscopic or robotic) or open abdominal radical hysterectomy.\n\nDisease-free survival at 4.5 years was 86.0 percent with minimally invasive surgery against 96.5 percent with open surgery, with a hazard ratio for recurrence of 3.74 and for death of 6.00; the trial was stopped early for harm.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2018","url":"https://doi.org/10.1056/NEJMoa1806395"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30380365/"}],"tags":[],"related":[],"cancers":["early-cervical-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["lacc"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2018,"doi":"10.1056/NEJMoa1806395","pmid":"30380365","authors":"Ramirez PT, Frumovitz M, Pareja R, et al.","paperType":"rct","findings":["4.5-year disease-free survival 86.0 percent vs 96.5 percent; hazard ratio for recurrence 3.74.","Hazard ratio for death from any cause 6.00."],"whatItMeans":"Open radical hysterectomy is again the standard for early cervical cancer; minimally invasive approaches are used only within protocols that avoid tumour spillage, and the trial is a lesson in adopting surgical innovation without randomised evidence.","caveats":["Mechanism (uterine manipulator, CO2 insufflation, intracorporeal colpotomy) remains debated.","Surgical technique modifications have not yet been proven safe in randomised trials."],"changedPractice":true,"participants":631},{"id":"paper-faubert-cell","kind":"paper","name":"Lactate Metabolism in Human Lung Tumors","aka":[],"tldr":"Paper cited by one idea page, indexed on Europe PMC as PubMed record 28985563 and published in Cell; the citing page links this DOI, which is how the record was matched.","summary":"Cancer cells consume glucose and secrete lactate in culture. It is unknown whether lactate contributes to energy metabolism in living tumors. We previously reported that human non-small-cell lung cancers (NSCLCs) oxidize glucose in the tricarboxylic acid (TCA) cycle. Here, we show that lactate is also a TCA cycle carbon source for NSCLC. In human NSCLC, evidence of lactate utilization was most apparent in tumors with high 18 fluorodeoxyglucose uptake and aggressive oncological behavior. Infusing human NSCLC patients with 13 C-lactate revealed extensive labeling of TCA cycle metabolites. In mice, deleting monocarboxylate transporter-1 (MCT1) from tumor cells eliminated lactate-dependent metabolite labeling, confirming tumor-cell-autonomous lactate uptake. Strikingly, directly comparing lactate and glucose metabolism in vivo indicated that lactate's contribution to the TCA cycle predominates. The data indicate that tumors, including bona fide human NSCLC, can use lactate as a fuel in vivo.\n\nIndexed on Europe PMC as PubMed record 28985563 (DOI 10.1016/j.cell.2017.09.019). Matched by DOI alone: one idea page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cell 2017","url":"https://doi.org/10.1016/j.cell.2017.09.019"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28985563/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28985563"}],"tags":["europepmc-ingest"],"related":["idea-metabolic-vulnerability-mapping"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Cell","year":2017,"doi":"10.1016/j.cell.2017.09.019","pmid":"28985563","authors":"Faubert B, Li KY, Cai L, et al.","paperType":"basic","findings":[],"whatItMeans":"One idea page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-milazzo-cochrane-database-syst-rev","kind":"paper","name":"Laetrile treatment for cancer","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 25918920 and published in The Cochrane database of systematic reviews; the citing page links this DOI, which is how the record was matched.","summary":"Background: Laetrile is the name for a semi-synthetic compound which is chemically related to amygdalin, a cyanogenic glycoside from the kernels of apricots and various other species of the genus Prunus. Laetrile and amygdalin are promoted under various names for the treatment of cancer although there is no evidence for its efficacy. Due to possible cyanide poisoning, laetrile can be dangerous.\n\nObjectives: To assess the alleged anti-cancer effect and possible adverse effects of laetrile and amygdalin.\n\nSearch methods: We searched the following databases: CENTRAL (2014, Issue 9); MEDLINE (1951-2014); EMBASE (1980-2014); AMED; Scirus; CINAHL (all from 1982-2015); CAMbase (from 1998-2015); the MetaRegister; the National Research Register; and our own files. We examined reference lists of included studies and review articles and we contacted experts in the field for knowledge of additional studies. We did not impose any restrictions of timer or language.\n\nSelection criteria: Randomized controlled trials (RCTs) and quasi-RCTs.\n\nData collection and analysis: We searched eight databases and two registers for studies testing laetrile or amygdalin for the treatment of cancer. Two review authors screened and assessed articles for inclusion criteria.\n\nMain results: We located over 200 references, 63 were evaluated in the original review, 6 in the 2011 and none in this update. However, we did not identify any studies that met our inclusion criteria.\n\nAuthors' conclusions: The claims that laetrile or amygdalin have beneficial effects for cancer patients are not currently supported by sound clinical data. There is a considerable risk of serious adverse effects from cyanide poisoning after laetrile or amygdalin, especially after oral ingestion. The risk-benefit balance of laetrile or amygdalin as a treatment for cancer is therefore unambiguously negative.\n\nIndexed on Europe PMC as PubMed record 25918920 (DOI 10.1002/14651858.cd005476.pub4). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cochrane Database Syst Rev 2015","url":"https://doi.org/10.1002/14651858.cd005476.pub4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25918920/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25918920"}],"tags":["europepmc-ingest"],"related":["laetrile-amygdalin"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Cochrane database of systematic reviews","year":2015,"doi":"10.1002/14651858.cd005476.pub4","pmid":"25918920","authors":"Milazzo S, Horneber M","paperType":"review","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-lamouille-emt-molecular-mechanisms-nrmcb-2014","kind":"paper","name":"Lamouille 2014: molecular mechanisms of epithelial-mesenchymal transition","aka":[],"tldr":"The detailed molecular account of how cells switch from a fixed epithelial state to a mobile mesenchymal one, from the TGF-beta signals that start it to the transcription factors, microRNAs and cytoskeletal changes that carry it out.","summary":"Lamouille, Xu and Derynck reviewed the machinery of epithelial-mesenchymal transition: TGF-beta signalling through SMAD and non-SMAD routes as the best-characterised trigger, the core transcription factors Snail, ZEB and Twist that repress E-cadherin and epithelial genes, the miR-200 and miR-34 families that hold those factors in check, and the changes in junctions, polarity and actin cytoskeleton that produce motility and invasion. They stressed that EMT is often partial and reversible, with cells occupying intermediate states, and described how the programme is co-opted in fibrosis and cancer.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1038/nrm3758"}],"tags":[],"related":["paper-kalluri-weinberg-emt-basics-jci-2009","paper-thiery-emt-tumour-progression-nrc-2002"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["emt","tgf-beta"],"terms":["metastasis","activating-invasion-metastasis"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature Reviews Molecular Cell Biology","year":2014,"doi":"10.1038/nrm3758","authors":"Lamouille S, Xu J, Derynck R.","paperType":"review","findings":["TGF-beta is the best-characterised EMT inducer, acting through SMAD-dependent and independent pathways alongside Wnt, Notch and growth factor signals.","Snail, ZEB and Twist transcription factors repress E-cadherin and drive the mesenchymal programme; miR-200 and miR-34 microRNAs oppose them in feedback loops.","EMT is frequently partial and reversible, producing hybrid cell states."],"whatItMeans":"This is the reference for the mechanics behind invasion and metastasis and for why partial EMT states, rather than a full switch, are now thought to matter most in cancer. It also explains the appeal and the difficulty of drugging EMT, since its drivers are transcription factors.","caveats":["A review, largely of cell culture and developmental systems.","Direct evidence for EMT in human metastasis remains harder to obtain than in models."],"changedPractice":false},{"id":"paper-lap07-chemoradiotherapy-locally-advanced-pancreatic-jama-2016","kind":"paper","name":"LAP07: chemoradiotherapy versus continued chemotherapy for locally advanced pancreatic cancer controlled after four months of gemcitabine","aka":[],"tldr":"Adding radiotherapy after four months of chemotherapy did not help patients with inoperable pancreatic cancer confined to the pancreas live longer, though it delayed regrowth at the original site. Nor did adding the pill erlotinib to gemcitabine. The result pushed radiotherapy out of the routine pathway for locally advanced disease.","summary":"International open-label randomised phase 3 trial with two randomisations: 449 patients with locally advanced pancreatic cancer received gemcitabine with or without erlotinib, and the 269 whose disease had not progressed after four months were randomised again to capecitabine-based chemoradiotherapy (54 Gy) or two further months of the same chemotherapy.\n\nMedian overall survival was 15.2 months with chemoradiotherapy and 16.5 months with chemotherapy alone (hazard ratio 1.03), and 11.9 against 13.6 months with and without erlotinib. Chemoradiotherapy reduced local progression (about 32 against 46 percent) and lengthened the interval off treatment, without more grade 3 or 4 toxicity apart from nausea.","asOf":"2026-09-21","links":[{"label":"JAMA 2016","url":"https://doi.org/10.1001/jama.2016.4324"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27139057/"}],"tags":[],"related":[],"cancers":["locally-advanced-pdac","pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":["gemcitabine","erlotinib","capecitabine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["lap07"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2016,"doi":"10.1001/jama.2016.4324","pmid":"27139057","authors":"Hammel P, Huguet F, van Laethem JL, et al.","paperType":"rct","findings":["Median overall survival 15.2 months with chemoradiotherapy versus 16.5 months with continued chemotherapy, hazard ratio 1.03.","Erlotinib added to gemcitabine did not improve survival (11.9 versus 13.6 months).","Local progression fell from about 46 to 32 percent with chemoradiotherapy."],"whatItMeans":"Systemic chemotherapy is the backbone for locally advanced pancreatic cancer; consolidation chemoradiotherapy is an option to control local symptoms or as a bridge to surgery rather than a survival treatment.","caveats":["Gemcitabine was the chemotherapy; whether radiotherapy adds to FOLFIRINOX or gemcitabine plus nab-paclitaxel remains an open question.","Conventional fractionation was used; stereotactic and dose-escalated radiotherapy are being tested separately."],"changedPractice":true,"participants":449},{"id":"paper-hao-nat-methods","kind":"paper","name":"Large-scale foundation model on single-cell transcriptomics","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 38844628 and published in Nature methods; the citing page links this DOI, which is how the record was matched.","summary":"Large pretrained models have become foundation models leading to breakthroughs in natural language processing and related fields. Developing foundation models for deciphering the 'languages' of cells and facilitating biomedical research is promising yet challenging. Here we developed a large pretrained model scFoundation, also named 'xTrimoscFoundation α ', with 100 million parameters covering about 20,000 genes, pretrained on over 50 million human single-cell transcriptomic profiles. scFoundation is a large-scale model in terms of the size of trainable parameters, dimensionality of genes and volume of training data. Its asymmetric transformer-like architecture and pretraining task design empower effectively capturing complex context relations among genes in a variety of cell types and states. Experiments showed its merit as a foundation model that achieved state-of-the-art performances in a diverse array of single-cell analysis tasks such as gene expression enhancement, tissue drug response prediction, single-cell drug response classification, single-cell perturbation prediction, cell type annotation and gene module inference.\n\nIndexed on Europe PMC as PubMed record 38844628 (DOI 10.1038/s41592-024-02305-7). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Methods 2024","url":"https://doi.org/10.1038/s41592-024-02305-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38844628/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38844628"}],"tags":["europepmc-ingest"],"related":["scfoundation"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature methods","year":2024,"doi":"10.1038/s41592-024-02305-7","pmid":"38844628","authors":"Hao M, Gong J, Zeng X, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-drilon-larotrectinib-nejm-2018","kind":"paper","name":"Larotrectinib in TRK fusion-positive cancers in adults and children","aka":[],"tldr":"The selective TRK inhibitor larotrectinib shrank tumours in three quarters of patients with NTRK fusions across 17 different cancer types and ages from infancy to old age, leading to the first tumour-agnostic approval of a targeted drug.","summary":"Pooled analysis of 55 patients (adults and children) with TRK fusion-positive solid tumours across 17 tumour types from three phase 1 and 2 trials treated with larotrectinib.\n\nObjective response was 75 percent by independent review with 71 percent of responses ongoing at one year, activity independent of tumour type, fusion partner or age, and mostly low-grade toxicity.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2018","url":"https://doi.org/10.1056/NEJMoa1714448"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29466156/"}],"tags":[],"related":[],"cancers":["ntrk-fusion-nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":["larotrectinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2018,"doi":"10.1056/NEJMoa1714448","pmid":"29466156","authors":"Drilon A, Laetsch TW, Kummar S, et al.","paperType":"observational","findings":["Objective response 75 percent across 17 tumour types.","71 percent of responses ongoing at one year; 55 percent of patients progression-free at one year."],"whatItMeans":"NTRK fusion testing is now recommended in lung and other cancers without a common driver, and larotrectinib or entrectinib is the standard treatment when a fusion is found.","caveats":["NTRK fusions are rare (under 1 percent) in lung cancer.","Acquired resistance mutations in the kinase domain develop; repotrectinib addresses some."],"changedPractice":true,"participants":55},{"id":"paper-rennert-neurosurgery","kind":"paper","name":"Laser Ablation of Abnormal Neurological Tissue Using Robotic Neuroblate System (LAANTERN): Procedural Safety and Hospitalization","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 31076762 and published in Neurosurgery; the citing page links this DOI, which is how the record was matched.","summary":"Background: Stereotactic laser ablation (SLA) has demonstrated potential utility for a spectrum of difficult to treat neurosurgical pathologies in multiple small and/or retrospective single-institutional series. Here, we present the safety profile of SLA of intracranial lesions from the Laser Ablation of Abnormal Neurological Tissue using Robotic NeuroBlate System (LAANTERN; Monteris Medical) multi-institutional, international prospective observational registry.\n\nObjective: To determine the procedural safety of SLA for intracranial lesions.\n\nMethods: Prospective procedural safety and hospitalization data from the first 100 treated LAANTERN patients was collected and analyzed.\n\nResults: Mean age and baseline Karnofsky Performance Status (KPS) were 51(± 17) yr and 83(± 15), respectively. In total, 81.2% of patients had undergone prior surgical or radiation treatment. Most patients had a single lesion (79%) ablated through 1 burr hole (1.2 ± 0.7 per patient), immediately following a lesion biopsy. In total, >90% of the lesion was ablated in 72% of treated lesions. Average total procedural time was 188.2 ± 69.6 min, and average blood loss was 17.7 ± 55.6 ccs. The average length of intensive care unit (ICU) and hospital stays before discharge were 38.1 ± 62.7 h and 61.1 ± 87.2 h, respectively. There were 5 adverse events (AEs) attributable to SLA (5/100; 5%). After the procedure, 84.8% of patients were discharged home. There was 1 mortality within 30 d of the procedure (1/100; 1%), which was not attributable to SLA.\n\nConclusion: SLA is a safe, minimally invasive procedure with favorable postprocedural ICU and hospital utilization profiles.\n\nIndexed on Europe PMC as PubMed record 31076762 (DOI 10.1093/neuros/nyz141). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Neurosurgery 2020","url":"https://doi.org/10.1093/neuros/nyz141"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31076762/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31076762"}],"tags":["europepmc-ingest"],"related":["litt-systems"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Neurosurgery","year":2020,"doi":"10.1093/neuros/nyz141","pmid":"31076762","authors":"Rennert RC, Khan U, Bartek J, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-latitude-nejm-2017","kind":"paper","name":"LATITUDE: abiraterone plus prednisone in newly diagnosed high-risk metastatic castration-sensitive prostate cancer","aka":[],"tldr":"Adding abiraterone to hormone therapy at the time of diagnosis of high-risk metastatic prostate cancer cut deaths by more than a third, establishing early intensification instead of waiting for castration resistance.","summary":"Phase 3 placebo-controlled trial of 1,199 men with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (at least two of Gleason 8 or more, three or more bone lesions, visceral metastases) randomised to androgen deprivation with abiraterone plus prednisone or placebo.\n\nAt the first analysis overall survival at three years was 66 versus 49 percent (hazard ratio 0.62) and radiographic progression-free survival 33.0 versus 14.8 months; the final analysis showed median survival of 53.3 versus 36.5 months.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2017","url":"https://doi.org/10.1056/NEJMoa1704174"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28578607/"}],"tags":[],"related":["prostate-roadmap","paper-attard-abiraterone-phase-1-cyp17-jco-2008"],"cancers":["prostate-mhspc","prostate"],"sections":[],"technologies":[],"targets":[],"drugs":["prednisone"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["latitude"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2017,"doi":"10.1056/NEJMoa1704174","pmid":"28578607","authors":"Fizazi K, Tran N, Fein L, et al.","paperType":"rct","findings":["Median overall survival 53.3 vs 36.5 months at final analysis; hazard ratio 0.66.","Radiographic progression-free survival 33.0 vs 14.8 months; hazard ratio 0.47."],"whatItMeans":"Abiraterone with androgen deprivation is a standard first-line doublet for metastatic hormone-sensitive prostate cancer, consistent with the STAMPEDE result.","caveats":["Restricted to high-risk disease; STAMPEDE showed benefit across risk groups.","Hypertension and hypokalaemia require monitoring."],"changedPractice":true,"participants":1199},{"id":"paper-lch-iii-therapy-prolongation-multisystem-lch-blood-2013","kind":"paper","name":"LCH-III: therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis","aka":[],"tldr":"Twelve months of vinblastine and prednisone, rather than six, meant fewer children's Langerhans cell histiocytosis came back, and mortality in the highest-risk children fell to a fraction of what it had been.","summary":"International randomised trial of the Histiocyte Society in children with multisystem Langerhans cell histiocytosis: patients with risk-organ involvement were randomised to vinblastine and prednisone with or without methotrexate, and those without risk-organ involvement to six or twelve months of treatment.\n\nMethotrexate added no benefit, while twelve months of therapy roughly halved the five-year reactivation rate compared with six months (about 37 versus 54 percent). Mortality in risk-organ-positive patients fell to about 15 percent with early switching of non-responders to salvage. Twelve months of vinblastine and prednisone became the international standard.","asOf":"2026-09-18","links":[{"label":"Blood 2013","url":"https://doi.org/10.1182/blood-2012-09-455774"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23589673/"}],"tags":[],"related":[],"cancers":["lch-single-system","lch-multisystem"],"sections":[],"technologies":[],"targets":[],"drugs":["vinblastine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["lch-iii"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["blood"],"dependsOn":[],"notes":[],"journal":"Blood","year":2013,"doi":"10.1182/blood-2012-09-455774","pmid":"23589673","authors":"Gadner H, Minkov M, Grois N, et al.","paperType":"rct","findings":["Twelve months of vinblastine and prednisone reduced five-year reactivation to about 37 percent from about 54 percent with six months.","Adding methotrexate did not improve outcomes in risk-organ-positive patients."],"whatItMeans":"Children with multisystem LCH receive a year of vinblastine and prednisone, and those in whom the disease does not respond quickly are switched early to salvage therapy.","caveats":["Reactivation remains common even after twelve months, and late effects such as neurodegeneration are not prevented.","Adults were not studied; adult regimens are extrapolated."],"changedPractice":true},{"id":"paper-le-mmr-deficiency-pd1-nejm-2015","kind":"paper","name":"Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ","aka":[],"tldr":"Pembrolizumab shrank tumours in 40% of colorectal and 71% of other cancers with faulty DNA mismatch repair, but in none with intact repair, tying immunotherapy response to mutation burden.","summary":"This investigator-initiated phase 2 study tested the hypothesis that tumours with defective DNA mismatch repair (dMMR), which accumulate thousands of mutations and neoantigens, would respond to PD-1 blockade. Forty-one patients with treatment-refractory metastatic cancer were enrolled in three cohorts: dMMR colorectal cancer, MMR-proficient colorectal cancer, and dMMR non-colorectal cancers, all treated with pembrolizumab 10 mg/kg every two weeks. Immune-related objective response rates were 40% (4 of 10) in dMMR colorectal cancer, 0% (0 of 18) in MMR-proficient colorectal cancer and 71% (5 of 7) in dMMR non-colorectal cancers; 20-week PFS was 78% versus 11% in the two colorectal cohorts. Whole-exome sequencing showed a mean of 1782 somatic mutations in dMMR versus 73 in proficient tumours, and higher mutation load correlated with longer PFS.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa1500596"},{"label":"ClinicalTrials.gov NCT01876511","url":"https://clinicaltrials.gov/study/NCT01876511"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26028255/"},{"label":"Europe PMC full text (PMC4481136)","url":"https://europepmc.org/article/MED/26028255"}],"tags":[],"related":["paper-le-mmr-deficiency-science-2017","paper-cercek-dostarlimab-rectal-nejm-2022","msi-high","dmmr-ihc","tmb-high","paper-keynote-177-nejm-2020"],"cancers":["colorectal","msi-high-colorectal"],"sections":["immunotherapy"],"technologies":["checkpoint-inhibitor","msi-mmr-testing","wes-wgs"],"targets":["pd1","mmr"],"drugs":["pembrolizumab"],"companies":["merck"],"institutions":["johns-hopkins"],"pathways":["mismatch-repair-msi","pd1-checkpoint","cancer-immunity-cycle"],"terms":["msi","tmb","neoantigen","tumour-agnostic","mss-pmmr","mmr"],"trials":[],"people":["dung-le","luis-diaz","drew-pardoll","bert-vogelstein","kenneth-kinzler"],"bottlenecks":["b-biomarker-validation","b-immunotherapy-response"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2015,"doi":"10.1056/NEJMoa1500596","pmid":"26028255","authors":"Le DT, Uram JN, Wang H, et al.","paperType":"translational","findings":["41 patients: 11 dMMR colorectal, 21 MMR-proficient colorectal, 9 dMMR non-colorectal; pembrolizumab 10 mg/kg every 2 weeks.","Immune-related objective response: 40% dMMR colorectal, 0% proficient colorectal, 71% dMMR non-colorectal.","Immune-related PFS at 20 weeks: 78% (dMMR colorectal) vs 11% (proficient colorectal).","Mean somatic mutations per tumour 1782 (dMMR) vs 73 (proficient); higher load associated with longer PFS.","Benefit occurred in both Lynch-syndrome and sporadic dMMR tumours."],"whatItMeans":"This small trial explained why colorectal cancer had seemed immune-resistant (most is MMR-proficient) and established the principle that a genomic feature, not the tissue of origin, can predict immunotherapy response. It led directly to the 2017 tissue-agnostic approval of pembrolizumab and to routine MMR/MSI testing of many cancers. Every patient with advanced dMMR cancer should now be considered for checkpoint blockade.","caveats":["Very small cohorts; response rates have wide confidence intervals.","Dose of 10 mg/kg is higher than later standard dosing.","Single-arm; no randomised comparison until KEYNOTE-177.","Mutation burden as a biomarker beyond dMMR has proved less clean than this data suggested."],"changedPractice":true,"participants":41},{"id":"paper-le-mmr-deficiency-science-2017","kind":"paper","name":"Le 2017: mismatch-repair deficiency predicts response to PD-1 blockade across twelve tumour types, leading to the first tissue-agnostic drug approval","aka":[],"tldr":"Across 86 patients with 12 different dMMR cancers, pembrolizumab produced responses in 53% and complete responses in 21%, prompting the first approval of a cancer drug based on a genetic marker rather than tumour site.","summary":"Extending the 2015 study, this report treated 86 patients with treatment-refractory, mismatch-repair-deficient cancers of 12 types (colorectal, endometrial, gastric, biliary, pancreatic, small bowel and others) with pembrolizumab. The objective response rate was 53% (46 of 86) with complete responses in 21% (18); disease control was 77%, and neither median PFS nor OS had been reached at a median follow-up of 12.5 months. Responses were seen in every tumour type. Functional analysis showed rapid in vivo expansion of neoantigen-specific T-cell clones. The FDA approved pembrolizumab for any unresectable or metastatic MSI-H/dMMR solid tumour in May 2017, the first tissue-agnostic cancer drug approval, and the randomised KEYNOTE-177 trial later confirmed first-line benefit in dMMR colorectal cancer (median PFS 16.5 versus 8.2 months).","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1126/science.aan6733"},{"label":"ClinicalTrials.gov NCT01876511","url":"https://clinicaltrials.gov/study/NCT01876511"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28596308/"},{"label":"Europe PMC full text (PMC5576142)","url":"https://europepmc.org/article/MED/28596308"}],"tags":[],"related":["paper-le-mmr-deficiency-pd1-nejm-2015","paper-niche-2-nejm-2024","msi-high","dmmr-ihc","paper-keynote-158-pembrolizumab-msi-high-noncolorectal-jco-2020"],"cancers":["colorectal","pancreatic","msi-high-colorectal"],"sections":["immunotherapy"],"technologies":["checkpoint-inhibitor","msi-mmr-testing"],"targets":["pd1","mmr"],"drugs":["pembrolizumab","nivolumab","dostarlimab"],"companies":[],"institutions":["johns-hopkins"],"pathways":["mismatch-repair-msi"],"terms":["msi","tumour-agnostic","neoantigen","tmb","mmr"],"trials":["keynote-177","checkmate-8hw"],"people":["dung-le","luis-diaz"],"bottlenecks":["b-regulatory-fragmentation","b-biomarker-validation","b-immunotherapy-response","b-rare-cancers"],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2017,"doi":"10.1126/science.aan6733","pmid":"28596308","authors":"Le DT, Durham JN, Smith KN, et al.","paperType":"translational","findings":["86 patients with dMMR cancers of 12 types; pembrolizumab 10 mg/kg every 2 weeks.","Objective response 53% (46 of 86); complete response 21% (18 of 86); disease control 77%.","Median PFS and OS not reached at 12.5 months median follow-up; responses in all 12 tumour types.","Neoantigen-specific T-cell clones expanded in blood within weeks of starting therapy.","Estimated that dMMR occurs in about 4% of advanced cancers, roughly 60,000 patients a year in the United States."],"whatItMeans":"This paper established a new regulatory paradigm: a drug approved for a molecular feature regardless of organ. It made MSI/MMR testing standard across advanced cancers and remains the clearest example of a biomarker that works across histologies. It also anchored the idea that mutation load, via neoantigens, is what makes tumours visible to T cells.","caveats":["Single-arm basket study; approvals rested on response rate and durability.","Heterogeneous prior therapies and tumour types; small numbers per type.","Roughly a quarter of dMMR tumours are primary resistant, and mechanisms (B2M loss, JAK mutations) are incompletely understood.","Later data suggest sensitivity varies by MSI assay and tumour type (for example, lower in some dMMR pancreatic and brain tumours)."],"changedPractice":true,"participants":86},{"id":"paper-leach-allison-ctla4-blockade-science-1996","kind":"paper","name":"Leach, Krummel and Allison: releasing the CTLA-4 brake makes mice reject tumours","aka":[],"tldr":"Injecting mice with an antibody that blocks the T-cell inhibitory receptor CTLA-4 caused established colon carcinomas and fibrosarcomas to be rejected and protected against re-challenge, the experiment that founded checkpoint immunotherapy.","summary":"Allison's laboratory had shown that CTLA-4 is a negative regulator of T-cell activation, opposing the co-stimulatory receptor CD28. This paper tested whether removing that brake would enhance anti-tumour immunity. Mice bearing transplantable 51BLim10 colon carcinoma or fibrosarcoma tumours were treated with anti-CTLA-4 antibodies.\n\nAnti-CTLA-4 treatment led to rejection of established tumours, including those that were poorly immunogenic when combined with a vaccine, and treated mice were immune to a second tumour challenge. The effect did not require engineering the tumour to express co-stimulatory molecules.\n\nThe finding was met with industry scepticism, but Medarex developed the human antibody that became ipilimumab, approved for melanoma in 2011 as the first drug to extend survival in metastatic melanoma. Allison shared the 2018 Nobel Prize with Tasuku Honjo.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1126/science.271.5256.1734"}],"tags":[],"related":["paper-iwai-pdl1-tumour-escape-pnas-2002"],"cancers":["melanoma"],"sections":["immunotherapy"],"technologies":["checkpoint-inhibitor"],"targets":["ctla4"],"drugs":["ipilimumab"],"companies":[],"institutions":["md-anderson"],"pathways":["pd1-checkpoint"],"terms":[],"trials":["checkmate-067"],"people":["james-allison","padmanee-sharma"],"bottlenecks":["b-immunotherapy-response","b-translational-valley"],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":1996,"doi":"10.1126/science.271.5256.1734","pmid":"8596936","authors":"Leach DR, Krummel MF, Allison JP","paperType":"basic","findings":["Anti-CTLA-4 antibody induced rejection of established, pre-implanted colon carcinoma and fibrosarcoma tumours in mice","Rejected mice were protected against re-challenge with the same tumour, indicating immunological memory","Efficacy against a poorly immunogenic tumour required combination with a GM-CSF-secreting vaccine, foreshadowing combination immunotherapy","Established the principle that removing inhibitory signals on T cells, rather than adding stimulation, can treat cancer"],"whatItMeans":"Every checkpoint inhibitor, from ipilimumab to pembrolizumab, rests on this idea: the immune system can already recognise cancer and just needs its brakes released. It changed the goal of immunotherapy from vaccinating against tumours to unleashing existing T cells.","caveats":["Mouse transplantable tumours are far more immunogenic than most human cancers","CTLA-4 blockade in humans causes substantial immune-related toxicity (colitis, hypophysitis) not evident in these models","Response rates to single-agent ipilimumab in humans are low (about 10-15% in melanoma)","Mechanism (Treg depletion versus effector T-cell release) remained debated for two decades"],"changedPractice":false},{"id":"paper-draisma-lead-time-overdiagnosis-psa-jnci-2009","kind":"paper","name":"Lead time and overdiagnosis in prostate-specific antigen screening: importance of methods and context","aka":["Draisma 2009","MISCAN prostate overdiagnosis","Etzioni lead time prostate"],"tldr":"Estimates of how many screen-detected prostate cancers would never have caused trouble ranged from a quarter to more than four fifths. Three independent models were run side by side to find out why, and showed the answer depends almost entirely on how the question is asked.","summary":"Gerrit Draisma, Ruth Etzioni and colleagues ran three independently developed models of prostate cancer progression and detection, all calibrated to Surveillance, Epidemiology, and End Results incidence, to estimate lead time and overdiagnosis among United States men aged 54 to 80 between 1985 and 2000. They also compared the United States estimates against earlier ones from the Rotterdam section of the European screening trial.\n\nThe finding is a methodological one with a very practical consequence. The three models agreed closely with each other for any given definition of lead time, and disagreed substantially across definitions: mean lead time ranged from 5.4 to 6.9 years and overdiagnosis from 23 to 42 percent of screen-detected cancers in the United States calibration, while the Rotterdam calibration of the same model family gave 7.9 years and 66 percent. Quoting a single overdiagnosis percentage for prostate screening without saying which definition and which population it came from is therefore not meaningful.","asOf":"2026-09-25","links":[{"label":"J Natl Cancer Inst 2009","url":"https://doi.org/10.1093/jnci/djp001"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19276453/"}],"tags":["prostate-evidence"],"related":["paper-welch-albertsen-psa-era-diagnosis-treatment-jnci-2009","paper-loeb-overdiagnosis-overtreatment-prostate-eur-urol-2014","paper-schroder-erspc-screening-mortality-nejm-2009","prostate-roadmap"],"cancers":["prostate","prostate-low-risk"],"sections":["early-detection"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["psa","screening","overdiagnosis","lead-time-bias","overtreatment","number-needed-to-screen"],"trials":[],"people":[],"bottlenecks":["b-overdiagnosis","b-early-detection","b-biomarker-validation"],"keyPapers":[],"journals":["jnci"],"dependsOn":[],"notes":[],"journal":"JNCI: Journal of the National Cancer Institute","year":2009,"doi":"10.1093/jnci/djp001","pmid":"19276453","authors":"Draisma G, Etzioni R, Tsodikov A, et al.","paperType":"methods","findings":["Among screen-detected cancers that would have been diagnosed in the patients' lifetimes, estimated mean lead time ranged from 5.4 to 6.9 years across the three models.","Overdiagnosis ranged from 23 to 42 percent of all screen-detected cancers in the models calibrated to United States data.","The original MISCAN model fitted to ERSPC Rotterdam data predicted a mean lead time of 7.9 years and overdiagnosis of 66 percent; recalibrated to United States data the same model gave 6.9 years and 42 percent.","Published estimates before this work ranged from 3 to 12 years for lead time and from 25 percent to more than 80 percent for overdiagnosis.","The three models yielded similar estimates for any single definition of lead time but estimates differed across definitions."],"whatItMeans":"The reference for anyone quoting an overdiagnosis figure in prostate cancer. The honest statement is a range with its definition and its population attached, and this paper is the reason no single overdiagnosis figure is quoted for prostate cancer.","caveats":["Model-based estimates calibrated to registry incidence, not direct observation of individual men.","Calibrated to a period of intense and largely unstructured United States testing between 1985 and 2000; the modern pathway with magnetic resonance imaging triage produces a different answer.","Overdiagnosis of a cancer is only harmful if it leads to treatment, and the models do not measure treatment decisions."],"changedPractice":false},{"id":"paper-fahrmann-ca19-9-lead-time-gastroenterology-2021","kind":"paper","name":"Lead-Time Trajectory of CA19-9 as an Anchor Marker for Pancreatic Cancer Early Detection","aka":[],"tldr":"A 2021 study of stored blood from a US screening trial showing that CA 19-9 starts rising about two years before pancreatic cancer is diagnosed and catches half of early-stage cases in the final six months, so it can anchor a multi-marker early detection test.","summary":"Fahrmann and colleagues measured CA 19-9 in blinded sera from 175 subjects collected up to five years before a pancreatic cancer diagnosis and 875 matched controls from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, and in independent sets of 129 resectable cases and 275 controls (100 healthy, 50 chronic pancreatitis, 125 non-cancerous cysts). Levels rose exponentially from two years before diagnosis; sensitivity reached 60 percent at 99 percent specificity within 0 to 6 months of diagnosis for all cases and 50 percent for early-stage cases. Resectable cases were distinguished from healthy controls at 64 percent sensitivity, from chronic pancreatitis at 46 percent and from cysts at 30 percent, all at 99 percent specificity. Adding LRG1 and TIMP1 raised sensitivity by 13.2 percentage points (P = 0.031) for cases below the CA 19-9 cutoff diagnosed within a year.","asOf":"2026-09-24","links":[{"label":"Gastroenterology 2021","url":"https://doi.org/10.1053/j.gastro.2020.11.052"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33333055/"}],"tags":["pancreatic-evidence"],"related":["paper-tempero-ca19-9-lewis-antigens-cancer-res-1987","paper-sharma-endpac-model-new-onset-diabetes-gastroenterology-2018","early-detection-roadmap"],"cancers":["pancreatic"],"sections":[],"technologies":["liquid-biopsy","mced","proteomics"],"targets":[],"drugs":[],"companies":[],"institutions":["md-anderson"],"pathways":[],"terms":["ca19-9","tumour-markers","ppv"],"trials":[],"people":["anirban-maitra"],"bottlenecks":["b-early-detection","b-biomarker-validation"],"keyPapers":[],"journals":["gastroenterology"],"dependsOn":[],"notes":[],"journal":"Gastroenterology","year":2021,"doi":"10.1053/j.gastro.2020.11.052","pmid":"33333055","authors":"Fahrmann JF, Schmidt CM, Mao X, et al.","paperType":"translational","findings":["175 pre-diagnostic cases and 875 controls from PLCO; CA 19-9 rose exponentially from two years before diagnosis.","Sensitivity 60 percent at 99 percent specificity within six months of diagnosis, 50 percent for early-stage cases.","LRG1 and TIMP1 added 13.2 percentage points of sensitivity below the CA 19-9 cutoff."],"whatItMeans":"Fixes the window in which a blood test could plausibly work and shows why CA 19-9 alone is not enough: half of early cases are missed even at diagnosis, and Lewis-negative patients are missed entirely.","caveats":["Retrospective, nested in a screening trial that did not screen for pancreatic cancer; performance in a prospective new-onset diabetes cohort is unknown.","99 percent specificity still yields many false positives in an average-risk population."],"participants":1050},{"id":"paper-saper-jama","kind":"paper","name":"Lead, mercury, and arsenic in US- and Indian-manufactured Ayurvedic medicines sold via the Internet","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 18728265 and published in JAMA; the citing page links this DOI, which is how the record was matched.","summary":"Context: Lead, mercury, and arsenic have been detected in a substantial proportion of Indian-manufactured traditional Ayurvedic medicines. Metals may be present due to the practice of rasa shastra (combining herbs with metals, minerals, and gems). Whether toxic metals are present in both US- and Indian-manufactured Ayurvedic medicines is unknown.\n\nObjectives: To determine the prevalence of Ayurvedic medicines available via the Internet containing detectable lead, mercury, or arsenic and to compare the prevalence of toxic metals in US- vs Indian-manufactured medicines and between rasa shastra and non-rasa shastra medicines.\n\nDesign: A search using 5 Internet search engines and the search terms Ayurveda and Ayurvedic medicine identified 25 Web sites offering traditional Ayurvedic herbs, formulas, or ingredients commonly used in Ayurveda, indicated for oral use, and available for sale. From 673 identified products, 230 Ayurvedic medicines were randomly selected for purchase in August-October 2005. Country of manufacturer/Web site supplier, rasa shastra status, and claims of Good Manufacturing Practices were recorded. Metal concentrations were measured using x-ray fluorescence spectroscopy.\n\nMain outcome measures: Prevalence of medicines with detectable toxic metals in the entire sample and stratified by country of manufacture and rasa shastra status.\n\nResults: One hundred ninety-three of the 230 requested medicines were received and analyzed. The prevalence of metal-containing products was 20.7% (95% confidence interval [CI], 15.2%-27.1%). The prevalence of metals in US-manufactured products was 21.7% (95% CI, 14.6%-30.4%) compared with 19.5% (95% CI, 11.3%-30.1%) in Indian products (P =.86). Rasa shastra compared with non-rasa shastra medicines had a greater prevalence of metals (40.6% vs 17.1%; P =.007) and higher median concentrations of lead (11.5 microg/g vs 7.0 microg/g; P =.03) and mercury (20,800 microg/g vs 34.5 microg/g; P =.04). Among the metal-containing products, 95% were sold by US Web sites and 75% claimed Good Manufacturing Practices. All metal-containing products exceeded 1 or more standards for acceptable daily intake of toxic metals.\n\nConclusion: One-fifth of both US-manufactured and Indian-manufactured Ayurvedic medicines purchased via the Internet contain detectable lead, mercury, or arsenic.\n\nIndexed on Europe PMC as PubMed record 18728265 (DOI 10.1001/jama.300.8.915). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA 2008","url":"https://doi.org/10.1001/jama.300.8.915"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/18728265/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/18728265"}],"tags":["europepmc-ingest"],"related":["ayurvedic-medicine-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2008,"doi":"10.1001/jama.300.8.915","pmid":"18728265","authors":"Saper RB, Phillips RS, Sehgal A, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-leap-012-lancet-2025","kind":"paper","name":"LEAP-012: transarterial chemoembolisation with lenvatinib plus pembrolizumab versus placebo for unresectable non-metastatic hepatocellular carcinoma","aka":[],"tldr":"Adding lenvatinib and pembrolizumab to chemoembolisation delayed progression in intermediate-stage liver cancer, the second trial to show that systemic therapy improves on embolisation alone, at the cost of more side effects.","summary":"Phase 3 placebo-controlled trial of 480 patients with unresectable, non-metastatic hepatocellular carcinoma suitable for chemoembolisation randomised to transarterial chemoembolisation with lenvatinib plus pembrolizumab or with dual placebo.\n\nMedian progression-free survival was 14.6 versus 10.0 months (hazard ratio 0.66), with an early trend in overall survival (hazard ratio 0.80, not significant) and grade 3 to 4 treatment-related adverse events of 71 versus 32 percent.","asOf":"2026-09-17","links":[{"label":"Lancet 2025","url":"https://doi.org/10.1016/S0140-6736(24)02575-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39798578/"}],"tags":[],"related":[],"cancers":["hcc-intermediate"],"sections":[],"technologies":[],"targets":[],"drugs":["lenvatinib","pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["leap-012"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2025,"doi":"10.1016/S0140-6736(24)02575-3","pmid":"39798578","authors":"Kudo M, Ren Z, Guo Y, et al.","paperType":"rct","findings":["Median progression-free survival 14.6 vs 10.0 months; hazard ratio 0.66.","Grade 3 to 4 treatment-related adverse events 71 percent vs 32 percent."],"whatItMeans":"Lenvatinib-pembrolizumab with chemoembolisation is an emerging option for intermediate-stage disease, balanced against substantial toxicity.","caveats":["Overall survival not yet significant.","High toxicity may limit uptake."],"changedPractice":true,"participants":480},{"id":"paper-lemmon-schlessinger-rtk-signalling-cell-2010","kind":"paper","name":"Lemmon and Schlessinger 2010: cell signalling by receptor tyrosine kinases","aka":[],"tldr":"The standard review of the receptor family behind many cancer drugs, explaining how growth factor receptors such as EGFR and HER2 switch on when they pair up, how mutations lock them on in cancer, and how inhibitors turn them off.","summary":"Lemmon and Schlessinger surveyed the 58 human receptor tyrosine kinases in 20 subfamilies, describing how ligand binding drives receptor dimerisation and trans-autophosphorylation, the structural diversity of activation mechanisms across families, and the intracellular pathways (RAS-MAPK, PI3K-AKT, PLC-gamma and STAT) that carry the signal. They explained how overexpression, amplification, point mutations and fusions deregulate these receptors in cancer and how antibodies and small-molecule kinase inhibitors exploit the same mechanisms, with resistance mutations as the predictable consequence.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1016/j.cell.2010.06.011"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":["egfr","her2","met","alk","kit"],"drugs":[],"companies":[],"institutions":[],"pathways":["rtk-activation"],"terms":["tki-term","signalling-pathway"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Cell","year":2010,"doi":"10.1016/j.cell.2010.06.011","authors":"Lemmon MA, Schlessinger J.","paperType":"review","findings":["Humans have 58 receptor tyrosine kinases in 20 subfamilies, activated by ligand-induced dimerisation and trans-autophosphorylation with family-specific mechanisms.","Signals propagate through RAS-MAPK, PI3K-AKT, PLC-gamma and STAT pathways and are shaped by negative feedback and endocytosis.","Cancers deregulate RTKs by amplification, mutation and fusion; therapeutic antibodies and kinase inhibitors target the receptors and select for resistance mutations."],"whatItMeans":"Almost every targeted therapy on this site, from trastuzumab and EGFR inhibitors to ALK, MET, RET and FGFR drugs, acts on the receptors this review describes. It is the mechanistic background for understanding both why these drugs work and why resistance mutations arise.","caveats":["A review; structural details for several families have been refined since.","Does not cover the clinical trials of the drugs it explains."],"changedPractice":false},{"id":"paper-remarc-lenalidomide-maintenance-dlbcl-jco-2017","kind":"paper","name":"Lenalidomide maintenance compared with placebo in responding elderly patients with diffuse large B-cell lymphoma treated with first-line R-CHOP","aka":["REMARC","Thieblemont 2017"],"tldr":"Two years of a tablet after chemotherapy delayed relapse in older people with aggressive lymphoma but did not help them live longer.","summary":"A randomised phase 3 trial in 650 patients aged 60 to 80 with previously untreated diffuse large B-cell lymphoma or another aggressive B-cell lymphoma who had reached a complete or partial response after six or eight cycles of R-CHOP. They received lenalidomide 25 mg daily for 21 days of each 28-day cycle for 24 months, or placebo.\n\nAt the primary analysis in December 2015, with a median follow-up of 39 months from randomisation, median progression-free survival was not reached with lenalidomide against 58.9 months with placebo (hazard ratio 0.708, 95 per cent confidence interval 0.537 to 0.933, p = 0.01). The result was consistent across subgroups by sex, age-adjusted International Prognostic Index, age, response quality after R-CHOP and positron emission tomography status at randomisation. With longer follow-up to October 2016 (median 52 months), overall survival was similar between the arms (hazard ratio 1.218, 0.861 to 1.721, p = 0.26). Grade 3 or 4 neutropenia occurred in 56 against 22 per cent and cutaneous reactions in 5 against 1 per cent.","asOf":"2026-10-01","links":[{"label":"Journal of Clinical Oncology 2017","url":"https://doi.org/10.1200/JCO.2017.72.6984"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28426350/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28426350"}],"tags":["lymphoma-evidence"],"related":["lymphoma-roadmap"],"cancers":["dlbcl","non-hodgkin-lymphoma"],"sections":["immunotherapy"],"technologies":[],"targets":[],"drugs":["lenalidomide","rituximab"],"companies":["lysa"],"institutions":[],"pathways":[],"terms":["maintenance-therapy","lymphoma-tx-maintenance","r-chop"],"trials":["remarc"],"people":["catherine-thieblemont","gilles-salles"],"bottlenecks":["b-toxicity-qol","b-aging-comorbidity"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2017,"doi":"10.1200/JCO.2017.72.6984","pmid":"28426350","authors":"Thieblemont C, Tilly H, Gomes da Silva M, et al.","paperType":"rct","findings":["Median progression-free survival was not reached with lenalidomide maintenance against 58.9 months with placebo (hazard ratio 0.708, 95 per cent confidence interval 0.537 to 0.933, p = 0.01).","The effect was consistent across the analysed subgroups, including positron emission tomography status at randomisation.","Overall survival was similar between arms at a median follow-up of 52 months (hazard ratio 1.218, 0.861 to 1.721, p = 0.26).","Grade 3 or 4 neutropenia occurred in 56 per cent on lenalidomide against 22 per cent on placebo."],"whatItMeans":"A clean example of a progression-free survival benefit that did not become a survival benefit. Lenalidomide maintenance did not become standard practice after this trial, and the figures are the reason.","caveats":["Progression-free survival and overall survival were reported at different data cut-offs, 39 and 52 months.","Restricted to patients aged 60 to 80 who had already responded to R-CHOP.","Two years of daily tablets with grade 3 or 4 neutropenia in over half the treated group is a substantial burden for a benefit confined to one endpoint."],"changedPractice":false,"participants":650},{"id":"paper-lenalidomide-multiple-myeloma-n-engl-j-med-2007","kind":"paper","name":"Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma","aka":[],"tldr":"Phase 2 or 3 results paper on Lenalidomide in Multiple myeloma, in New England Journal of Medicine (2007), one of the most cited Europe PMC records with Lenalidomide in its title.","summary":"Background: Lenalidomide is a structural analogue of thalidomide with similar but more potent biologic activity. This phase 3, placebo-controlled trial investigated the efficacy of lenalidomide plus dexamethasone in the treatment of relapsed or refractory multiple myeloma.\n\nMethods: Of 351 patients who had received at least one previous antimyeloma therapy, 176 were randomly assigned to receive 25 mg of oral lenalidomide and 175 to receive placebo on days 1 to 21 of a 28-day cycle. In addition, all patients received 40 mg of oral dexamethasone on days 1 to 4, 9 to 12, and 17 to 20 for the first four cycles and subsequently, after the fourth cycle, only on days 1 to 4. Patients continued in the study until the occurrence of disease progression or unacceptable toxic effects. The primary end point was time to progression.\n\nResults: The time to progression was significantly longer in the patients who received lenalidomide plus dexamethasone (lenalidomide group) than in those who received placebo plus dexamethasone (placebo group) (median, 11.3 months vs. 4.7 months; P<0.001). A complete or partial response occurred in 106 patients in the lenalidomide group (60.2%) and in 42 patients in the placebo group (24.0%, P<0.001), with a complete response in 15.9% and 3.4% of patients, respectively (P<0.001). Overall survival was significantly improved in the lenalidomide group (hazard ratio for death, 0.66; P=0.03). Grade 3 or 4 adverse events that occurred in more than 10% of patients in the lenalidomide group were neutropenia (29.5%, vs. 2.3% in the placebo group), thrombocytopenia (11.4% vs. 5.7%), and venous thromboembolism (11.4% vs. 4.6%).\n\nConclusions: Lenalidomide plus dexamethasone is more effective than high-dose dexamethasone alone in relapsed or refractory multiple myeloma. (ClinicalTrials.gov number, NCT00424047 [ClinicalTrials.gov].).\n\nIndexed on Europe PMC as PubMed record 18032762 (DOI 10.1056/nejmoa070594). Its title names Lenalidomide and its text names Multiple myeloma; PubMed types it as a clinical trial report (Clinical Trial, Phase III, Comparative Study, Research Support, Non-U.S. Gov't, Multicenter Study, Randomized Controlled Trial). It was matched automatically to the idea \"MRD-guided treatment-free intervals in myeloma\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2007","url":"https://doi.org/10.1056/nejmoa070594"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/18032762/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/18032762"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2007,"doi":"10.1056/nejmoa070594","pmid":"18032762","authors":"Dimopoulos M, Spencer A, Attal M, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Lenalidomide in Multiple myeloma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Lenalidomide in the title and Multiple myeloma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-ballman-j-clin-oncol","kind":"paper","name":"Lessons From GBM AGILE's Regorafenib Experience in Newly Diagnosed and Recurrent Glioblastoma","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 42119048 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 42119048 (DOI 10.1200/jco-26-00444). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2026","url":"https://doi.org/10.1200/jco-26-00444"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42119048/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42119048"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["gbm-agile"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2026,"doi":"10.1200/jco-26-00444","pmid":"42119048","authors":"Ballman KV","paperType":"observational","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-moertel-levamisole-fluorouracil-adjuvant-colon-nejm-1990","kind":"paper","name":"Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma","aka":[],"tldr":"The 1990 trial that first showed chemotherapy after a colon cancer operation stops the cancer coming back. It cut recurrences by 41 percent and deaths by a third in node-positive disease.","summary":"Moertel, Fleming, Macdonald and colleagues randomly assigned 1,296 patients with resected colon cancer that was either locally invasive (stage B2) or node-positive (stage C) to observation or to one year of levamisole combined with fluorouracil; stage C patients could also be assigned to levamisole alone. Median follow-up at the time of writing was three years.\n\nToxic effects of levamisole plus fluorouracil were essentially those of fluorouracil alone: nausea, vomiting, stomatitis, diarrhoea, dermatitis and leukopenia, usually not severe. Because most patients were treated by community oncologists, the authors argued the approach would be readily adaptable to conventional practice, and it became the first adjuvant standard in colon cancer.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 1990","url":"https://doi.org/10.1056/NEJM199002083220602"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/2300087/"}],"tags":["colorectal-evidence"],"related":["paper-quasar-adjuvant-chemotherapy-vs-observation-lancet-2007","paper-mosaic-oxaliplatin-adjuvant-colon-nejm-2004"],"cancers":["colorectal","colon-cancer"],"sections":["chemotherapy"],"technologies":["cytotoxic-chemotherapy"],"targets":[],"drugs":["fluorouracil","leucovorin"],"companies":[],"institutions":[],"pathways":[],"terms":["neoadjuvant-adjuvant"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":1990,"doi":"10.1056/NEJM199002083220602","pmid":"2300087","authors":"Moertel CG, Fleming TR, Macdonald JS, et al.","paperType":"rct","findings":["In stage C disease, levamisole plus fluorouracil reduced the risk of recurrence by 41 percent (p<0.0001).","The overall death rate was reduced by 33 percent (p approximately 0.006).","Levamisole alone had no detectable effect.","Results in stage B2 disease were equivocal and too preliminary for firm conclusions."],"whatItMeans":"The start of adjuvant treatment for colon cancer. Levamisole was later dropped, but fluorouracil with folinic acid remained the backbone that oxaliplatin was added to in MOSAIC fourteen years later.","caveats":["Three years' median follow-up at publication; the stage B2 question it left open took QUASAR and seventeen more years.","Levamisole, an antihelminthic, was subsequently shown to add nothing and was withdrawn from oncology use."],"changedPractice":true,"participants":1296},{"id":"paper-levine-p53-gatekeeper-cell-1997","kind":"paper","name":"Levine 1997: p53, the cellular gatekeeper for growth and division","aka":[],"tldr":"The classic account of how the p53 protein senses DNA damage and other stress and then stops a cell dividing or makes it die, and why losing p53, as about half of cancers do, removes a central safeguard against cancer.","summary":"Levine's review described p53 as a transcription factor kept at low levels by MDM2 and stabilised by signals including DNA damage, hypoxia and oncogene activation. Activated p53 induces genes that arrest the cell cycle, chiefly p21, or trigger apoptosis, so that damaged cells are repaired or removed. The review explained how p53 mutation in roughly half of human cancers, inheritance of a mutant allele in Li-Fraumeni syndrome, and viral proteins that inactivate p53 all remove this checkpoint, and it set out the MDM2 feedback loop that later became a drug target.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1016/S0092-8674(00)81871-1"}],"tags":[],"related":["paper-hollstein-p53-mutations-science-1991","paper-el-deiry-waf1-p21-cell-1993"],"cancers":[],"sections":[],"technologies":[],"targets":["tp53","mdm2"],"drugs":[],"companies":[],"institutions":[],"pathways":["p53-cell-cycle","p53-mdm2-axis"],"terms":["tp53-mutated","tumour-suppressor-gene","li-fraumeni","apoptosis","cell-cycle"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Cell","year":1997,"doi":"10.1016/S0092-8674(00)81871-1","authors":"Levine AJ.","paperType":"review","findings":["p53 is stabilised by DNA damage, hypoxia and oncogene activation and acts as a transcription factor.","Its main outputs are cell cycle arrest through p21 and apoptosis, removing damaged cells.","MDM2 binds and degrades p53 in a negative feedback loop; p53 is mutated in about half of human cancers and inherited mutation causes Li-Fraumeni syndrome."],"whatItMeans":"This review fixed the picture of p53 as the guardian of the genome that every textbook uses. It explains why TP53-mutant cancers are aggressive and hard to treat, why MDM2 inhibitors are being developed to reactivate wild-type p53, and why germline TP53 testing matters in families.","caveats":["Written before the discovery of many p53 targets and of gain-of-function effects of mutant p53.","A review; specific mechanisms have been refined since."],"changedPractice":false},{"id":"paper-li-timer-tumour-infiltrating-immune-cells-cancerres-2017","kind":"paper","name":"Li 2017: TIMER, a web server for estimating immune cells in tumour genomic data","aka":[],"tldr":"A free online tool that estimates how many of six kinds of immune cell are present in a tumour from its gene expression data, applied to more than ten thousand tumours in The Cancer Genome Atlas and used in thousands of studies since.","summary":"Li, Liu and colleagues built TIMER (Tumor IMmune Estimation Resource), a computational method and web server that infers the abundance of B cells, CD4 and CD8 T cells, neutrophils, macrophages and dendritic cells from bulk tumour RNA sequencing. They applied it to 10,897 tumours across 32 cancer types from TCGA and let users explore how immune infiltration relates to gene expression, mutations, copy number and survival. TIMER2.0 followed in 2020 with additional deconvolution methods.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1158/0008-5472.CAN-17-0307"},{"label":"TIMER2.0","url":"http://timer.cistrome.org/"}],"tags":[],"related":["tcga-gdc","paper-thorsson-immune-landscape-of-cancer-immunity-2018"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["dana-farber"],"pathways":[],"terms":["tils","immune-system"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Cancer Research","year":2017,"doi":"10.1158/0008-5472.CAN-17-0307","authors":"Li T, Fan J, Wang B, et al.","paperType":"methods","findings":["Statistical deconvolution of bulk RNA sequencing to estimate six immune cell types.","Applied to 10,897 TCGA tumours across 32 cancer types, with a public web interface for exploring immune infiltration against genomic and clinical features.","Updated as TIMER2.0 in 2020 with multiple deconvolution algorithms."],"whatItMeans":"TIMER made immune infiltration analysis accessible to any group with tumour expression data, which is why it is cited so heavily; it is a standard first step in linking a gene or mutation to the immune state of a cancer.","caveats":["Inferred, not measured, cell abundances; different deconvolution methods can disagree.","Bulk expression cannot resolve where immune cells sit within the tumour."],"changedPractice":false},{"id":"paper-li-timer2-nar-2020","kind":"paper","name":"Li 2020: TIMER2.0 for analysis of tumour-infiltrating immune cells","aka":[],"tldr":"The updated version of the TIMER web tool, which estimates immune cell content in tumour gene expression data using six different algorithms side by side so users can see where they agree.","summary":"Li, Liu and colleagues released TIMER2.0, extending their immune estimation web server with multiple deconvolution methods, including TIMER, CIBERSORT, quanTIseq, xCell, MCP-counter and EPIC, applied to TCGA tumours and to user-uploaded expression data. The server lets users relate immune infiltration estimates to gene expression, somatic mutations, copy number and survival across cancer types, and to compare the estimates from different algorithms, which often disagree.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1093/nar/gkaa407"},{"label":"TIMER2.0","url":"http://timer.cistrome.org/"}],"tags":[],"related":["paper-li-timer-tumour-infiltrating-immune-cells-cancerres-2017","tcga-gdc"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["dana-farber"],"pathways":[],"terms":["tils","immune-system"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nucleic Acids Research","year":2020,"doi":"10.1093/nar/gkaa407","authors":"Li T, Fu J, Zeng Z, et al.","paperType":"methods","findings":["Six immune deconvolution algorithms available side by side on one web server.","Modules link immune estimates to gene expression, mutation, copy number and outcome across TCGA cancer types.","Accepts user-uploaded expression profiles for estimation."],"whatItMeans":"TIMER2.0 is one of the most used tools in cancer immunogenomics and its multi-algorithm design is a reminder that computational immune cell estimates are model-dependent and should be cross-checked.","caveats":["Estimates are inferred from bulk expression and vary by algorithm.","Cannot resolve spatial location of immune cells."],"changedPractice":false},{"id":"paper-libretto-001-selpercatinib-nsclc-nejm-2020","kind":"paper","name":"LIBRETTO-001: selpercatinib in RET fusion-positive non-small-cell lung cancer","aka":[],"tldr":"The selective RET inhibitor selpercatinib shrank tumours in 64 percent of previously treated and 85 percent of untreated patients with RET fusion-positive lung cancer, including brain metastases, and led to the first approval for this driver.","summary":"Phase 1/2 study of 105 previously treated and 39 treatment-naive patients with RET fusion-positive non-small-cell lung cancer treated with selpercatinib.\n\nObjective response was 64 percent in previously treated patients with median duration of response 17.5 months and median progression-free survival 16.5 months; 85 percent in treatment-naive patients; intracranial response 91 percent among evaluable patients. Hypertension, liver enzyme rise and QT prolongation were the main toxicities.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2020","url":"https://doi.org/10.1056/NEJMoa2005653"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32846060/"}],"tags":[],"related":[],"cancers":["ret-fusion-nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":["selpercatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2020,"doi":"10.1056/NEJMoa2005653","pmid":"32846060","authors":"Drilon A, Oxnard GR, Tan DSW, et al.","paperType":"observational","findings":["Objective response 64 percent (previously treated) and 85 percent (treatment-naive).","Median progression-free survival 16.5 months in previously treated patients."],"whatItMeans":"RET fusion testing is standard in lung adenocarcinoma and selpercatinib the preferred first-line RET inhibitor, confirmed against chemo-immunotherapy in LIBRETTO-431.","caveats":["Single-arm study.","Hypersensitivity reactions in patients recently treated with immunotherapy."],"changedPractice":true,"participants":144},{"id":"paper-libretto-431-nejm-2023","kind":"paper","name":"LIBRETTO-431: first-line selpercatinib versus chemotherapy with or without pembrolizumab in RET fusion-positive lung cancer","aka":[],"tldr":"Given as first treatment, selpercatinib more than doubled the time to progression compared with platinum-pemetrexed chemotherapy plus pembrolizumab in RET fusion-positive lung cancer, and protected against brain metastases.","summary":"Phase 3 trial of 261 patients with untreated advanced RET fusion-positive non-squamous non-small-cell lung cancer randomised to selpercatinib or platinum-pemetrexed with or without pembrolizumab.\n\nMedian progression-free survival was 24.8 versus 11.2 months (hazard ratio 0.46) in the intention-to-exclude-pembrolizumab population, response 84 versus 65 percent, and the cumulative incidence of central nervous system progression was lower with selpercatinib.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2023","url":"https://doi.org/10.1056/NEJMoa2309457"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37870973/"}],"tags":[],"related":[],"cancers":["ret-fusion-nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab","selpercatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["libretto-431"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/NEJMoa2309457","pmid":"37870973","authors":"Zhou C, Solomon B, Loong HH, et al.","paperType":"rct","findings":["Median progression-free survival 24.8 vs 11.2 months; hazard ratio 0.46.","Objective response 84 percent vs 65 percent."],"whatItMeans":"Selpercatinib is the established first-line treatment for RET fusion-positive lung cancer, and the trial adds to evidence that targeted therapy should precede chemo-immunotherapy in driver-positive disease.","caveats":["Open-label; overall survival immature.","Crossover to selpercatinib at progression was permitted."],"changedPractice":true,"participants":261},{"id":"paper-libretto-531-nejm-2023","kind":"paper","name":"LIBRETTO-531: selpercatinib versus cabozantinib or vandetanib in advanced RET-mutant medullary thyroid cancer","aka":[],"tldr":"The selective RET inhibitor selpercatinib cut the risk of progression by more than 70 percent compared with the older multikinase drugs cabozantinib and vandetanib in RET-mutant medullary thyroid cancer, with fewer side effects.","summary":"Phase 3 trial of 291 patients with progressive advanced RET-mutant medullary thyroid cancer randomised 2:1 to selpercatinib or physician's choice of cabozantinib or vandetanib.\n\nProgression-free survival at 12 months was 86.8 versus 65.7 percent (hazard ratio 0.28), response 69.4 versus 38.8 percent, and treatment-failure-free survival also favoured selpercatinib; grade 3 or higher adverse events were 52.8 versus 76.3 percent.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2023","url":"https://doi.org/10.1056/NEJMoa2309719"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37870969/"}],"tags":[],"related":[],"cancers":["medullary-thyroid-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["selpercatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["libretto-531"],"people":["julien-hadoux"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/NEJMoa2309719","pmid":"37870969","authors":"Hadoux J, Elisei R, Brose MS, et al.","paperType":"rct","findings":["Twelve-month progression-free survival 86.8 percent vs 65.7 percent; hazard ratio 0.28.","Objective response 69.4 percent vs 38.8 percent."],"whatItMeans":"Selpercatinib is the first-line standard for advanced RET-mutant medullary thyroid cancer; RET testing at diagnosis is essential.","caveats":["Overall survival data immature.","Open-label design."],"changedPractice":true,"participants":291},{"id":"paper-saperstein-ivermectin-neurotoxicity-breast-cancer-2026","kind":"paper","name":"Life-threatening neurotoxicity following off-label ivermectin use in metastatic breast cancer: a case report","aka":[],"tldr":"A 73-year-old woman with metastatic breast cancer took high doses of ivermectin after reading about it online, had seizures and stopped breathing adequately, and spent two days on a ventilator before recovering fully.","summary":"The patient self-administered high doses of ivermectin based on information obtained online, developed acute altered mental status, generalised seizures and respiratory failure, and was managed with intubation, mechanical ventilation, intravenous fluids and anticonvulsants, recovering to baseline within 48 hours (Saperstein case report 2026). The authors note that the FDA has explicitly discouraged ivermectin for cancer outside clinical trials and ask clinicians to take a thorough exposure history (Saperstein case report 2026).","asOf":"2026-09-24","links":[{"label":"Saperstein case report 2026","url":"https://doi.org/10.1080/00325481.2026.2672183"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42170801/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["ivermectin"],"companies":[],"institutions":[],"pathways":[],"terms":["off-label"],"trials":[],"people":[],"bottlenecks":["b-misinformation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo agent (Claude Fable 5.1)","editedOn":"2026-09-24","note":"Written from cached ClinicalTrials.gov v2, Europe PMC, DailyMed, Drugs@FDA and WHO eEML responses; no figure appears without its source link."},"journal":"Postgraduate Medicine","year":2026,"doi":"10.1080/00325481.2026.2672183","pmid":"42170801","authors":"Saperstein Y, Bou Sanayeh E, Boazak P, Itani H, Moussa E, Gut T.","paperType":"observational","findings":["Seizures, altered consciousness and respiratory failure after unintentional high-dose self-administration; full recovery within 48 hours with intensive care."],"whatItMeans":"The clearest documented case of what the label's neurotoxicity warning looks like in a cancer patient dosing herself.","caveats":["Single case; the dose taken was not precisely known."],"changedPractice":false,"participants":1},{"id":"paper-makohon-moore-metastases-driver-homogeneity-nat-genet-2017","kind":"paper","name":"Limited heterogeneity of known driver gene mutations among the metastases of individual patients with pancreatic cancer","aka":[],"tldr":"Deep sequencing of 26 separate metastases from four patients found the same driver mutations in every one, so a biopsy of any single site should represent the whole disease for targeted therapy.","summary":"Sixty-fold whole-genome sequencing of 26 metastases from four patients with pancreatic cancer showed identical mutations in known driver genes in every metastatic lesion for each patient. Passenger mutations accounted for all intratumoural heterogeneity, and even among those the genetic similarity of founding cells was higher than expected for two randomly chosen normal cells.","asOf":"2026-09-24","links":[{"label":"Makohon-Moore et al., Nat Genet 2017: limited driver heterogeneity among 26 metastases from four patients","url":"https://doi.org/10.1038/ng.3764"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28092682/"}],"tags":[],"related":[],"cancers":["pancreatic","metastatic-pdac"],"sections":[],"technologies":["wes-wgs"],"targets":[],"drugs":[],"companies":[],"institutions":["mskcc","johns-hopkins"],"pathways":["clonal-evolution"],"terms":[],"trials":[],"people":["bert-vogelstein"],"bottlenecks":[],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":2017,"doi":"10.1038/ng.3764","pmid":"28092682","authors":"Makohon-Moore AP, Zhang M, Reiter JG, et al.","paperType":"translational","findings":["Identical driver mutations in all 26 metastases across four patients.","Heterogeneity was confined to passenger mutations."],"whatItMeans":"Encouraging for targeted therapy: unlike some cancers, the drivers do not differ between deposits, so one biopsy is enough to choose a RAS or repair-directed drug.","caveats":["Four patients from a rapid autopsy programme.","Treatment-naive metastases; therapy can add resistance mutations."],"changedPractice":false,"participants":4},{"id":"paper-nifty-liposomal-irinotecan-lancet-oncol-2021","kind":"paper","name":"Liposomal irinotecan plus fluorouracil and leucovorin versus fluorouracil and leucovorin for metastatic biliary tract cancer after progression on gemcitabine plus cisplatin (NIFTY): a multicentre, open-label, randomised, phase 2b study","aka":[],"tldr":"In a Korean trial, adding liposomal irinotecan to fluorouracil held second-line bile duct and gallbladder cancer still for about seven months rather than six weeks, at the cost of more low blood counts.","summary":"NIFTY randomised 174 patients at five South Korean academic centres between September 2018 and February 2020 to liposomal irinotecan 70 mg/m2 with fluorouracil and leucovorin, or fluorouracil and leucovorin alone, every two weeks. Median progression-free survival by blinded independent central review was 7.1 months (95 percent CI 3.6 to 8.8) against 1.4 months (1.2 to 1.5); hazard ratio 0.56 (0.39 to 0.81), p=0.0019. Grade 3 to 4 neutropenia occurred in 24 versus 1 percent and serious adverse events in 42 versus 24 percent, with no treatment-related deaths.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2021","url":"https://doi.org/10.1016/S1470-2045(21)00486-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34656226/"},{"label":"ClinicalTrials.gov NCT03524508","url":"https://clinicaltrials.gov/study/NCT03524508"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder","cholangiocarcinoma","biliary-tract-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["irinotecan","fluorouracil"],"companies":[],"institutions":[],"pathways":[],"terms":["pfs"],"trials":["nifty","naliricc"],"people":["ghassan-abou-alfa"],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2021,"doi":"10.1016/S1470-2045(21)00486-1","pmid":"34656226","authors":"Yoo C, Kim KP, Jeong JH, et al.","paperType":"rct","findings":["Median progression-free survival 7.1 vs 1.4 months; hazard ratio 0.56 (95 percent CI 0.39 to 0.81), p=0.0019.","Grade 3 to 4 neutropenia 24 vs 1 percent; serious adverse events 42 vs 24 percent."],"whatItMeans":"A positive randomised phase 2 that the German NALIRICC trial failed to reproduce; guidelines list the regimen as an option, and the disagreement is a reminder that single-country phase 2 results in biliary cancer need replication.","caveats":["Phase 2b with a progression-free survival endpoint, not survival.","Not reproduced by NALIRICC (2024)."],"changedPractice":false,"participants":174},{"id":"paper-transcend-nhl-001-liso-cel-lancet-2020","kind":"paper","name":"Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study","aka":["TRANSCEND NHL 001","Abramson 2020","JCAR017 pivotal study"],"tldr":"The pivotal study of the third CAR-T product for lymphoma, built from a fixed one-to-one mix of two kinds of T cell, with severe immune side effects in only a small minority.","summary":"A seamless design study at 14 United States cancer centres in adults with relapsed or refractory large B-cell lymphomas, including diffuse large B-cell lymphoma, high-grade B-cell lymphoma with MYC and BCL2, BCL6 or both rearranged, transformed disease, primary mediastinal B-cell lymphoma and grade 3B follicular lymphoma. Three target dose levels were tested in sequence, each given as a sequential infusion of separately manufactured CD8 and CD4 chimeric antigen receptor positive T cells at equal target doses.\n\nBetween 11 January 2016 and 5 July 2019, 344 patients underwent leukapheresis and 269 received at least one dose. Patients had a median of three previous lines, 112 (42 per cent) were 65 or older, 181 (67 per cent) had chemotherapy-refractory disease and seven (3 per cent) had secondary central nervous system involvement. Safety and activity did not differ by dose level, and the recommended target dose was 100 million chimeric antigen receptor positive T cells. Of 256 patients in the efficacy-evaluable set, 186 (73 per cent, 95 per cent confidence interval 66.8 to 78.0) had an objective response and 136 (53 per cent, 46.8 to 59.4) a complete response.","asOf":"2026-10-01","links":[{"label":"Lancet 2020","url":"https://doi.org/10.1016/S0140-6736(20)31366-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32888407/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32888407"}],"tags":["lymphoma-evidence"],"related":["lymphoma-roadmap"],"cancers":["dlbcl","non-hodgkin-lymphoma","primary-mediastinal-b-cell-lymphoma","follicular-lymphoma"],"sections":["cell-therapy"],"technologies":["car-t"],"targets":["cd19"],"drugs":["lisocabtagene-maraleucel"],"companies":["bms"],"institutions":[],"pathways":[],"terms":["crs","icans","orr","complete-response","double-hit-lymphoma"],"trials":["transcend-nhl-001","transform"],"people":[],"bottlenecks":["b-manufacturing-cell-therapy","b-aging-comorbidity"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"Lancet","year":2020,"doi":"10.1016/S0140-6736(20)31366-0","pmid":"32888407","authors":"Abramson JS, Palomba ML, Gordon LI, et al.","paperType":"rct","findings":["Of 256 efficacy-evaluable patients, 186 (73 per cent, 95 per cent confidence interval 66.8 to 78.0) achieved an objective response and 136 (53 per cent, 46.8 to 59.4) a complete response.","Cytokine release syndrome occurred in 113 patients (42 per cent) but was grade 3 or worse in only six (2 per cent).","Neurological events occurred in 80 patients (30 per cent), grade 3 or worse in 27 (10 per cent).","The most common grade 3 or worse adverse events were neutropenia (60 per cent), anaemia (37 per cent) and thrombocytopenia (27 per cent).","Overall safety and activity did not differ by dose level; the recommended target dose was 100 million chimeric antigen receptor positive T cells."],"whatItMeans":"The evidence that made lisocabtagene maraleucel the CD19 CAR-T product most often chosen for older or frailer patients, because its severe cytokine release syndrome rate is a fraction of the other two products'.","caveats":["Single-arm and not randomised; the comparison with the other CD19 products rests on cross-trial inference with different eligibility and bridging rules.","Of 344 patients who had leukapheresis, 75 never received the product, which is the real-world attrition that single-arm response rates hide.","14 United States centres with CAR-T experience, so the toxicity figures reflect expert management."],"changedPractice":true,"participants":269},{"id":"paper-mazzaferro-milan-criteria-nejm-1996","kind":"paper","name":"Liver transplantation for small hepatocellular carcinomas in patients with cirrhosis (the Milan criteria)","aka":[],"tldr":"This study showed that liver transplantation cures most patients with cirrhosis whose liver cancer is limited to one tumour up to 5 cm or up to three tumours each up to 3 cm, the Milan criteria that have governed transplant selection ever since.","summary":"Prospective cohort of 48 patients with cirrhosis and unresectable hepatocellular carcinoma meeting size criteria (single tumour 5 cm or less, or up to three tumours each 3 cm or less) who underwent liver transplantation.\n\nFour-year overall survival was 75 percent and recurrence-free survival 83 percent, with 85 percent overall survival among the 35 patients whose explants confirmed the criteria, compared with poor historical results in unselected patients.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 1996","url":"https://doi.org/10.1056/NEJM199603143341104"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/8594428/"}],"tags":[],"related":[],"cancers":["hcc-early"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":1996,"doi":"10.1056/NEJM199603143341104","pmid":"8594428","authors":"Mazzaferro V, Regalia E, Doci R, et al.","paperType":"observational","findings":["Four-year overall survival 75 percent; recurrence-free survival 83 percent.","85 percent four-year survival when explant pathology confirmed the criteria."],"whatItMeans":"The Milan criteria remain the global standard for transplant eligibility in hepatocellular carcinoma, with downstaging protocols extending access to patients just outside them.","caveats":["Small single-centre series; expanded criteria (UCSF, up-to-seven) have since been proposed."],"changedPractice":true,"participants":48},{"id":"paper-lms-04-doxorubicin-trabectedin-lancet-oncol-2022","kind":"paper","name":"LMS-04: doxorubicin plus trabectedin followed by trabectedin maintenance versus doxorubicin alone in metastatic leiomyosarcoma","aka":[],"tldr":"Combining trabectedin with doxorubicin as first-line treatment for metastatic leiomyosarcoma nearly doubled the time to progression compared with doxorubicin alone, and later showed a survival benefit, making it the first combination to beat single-agent doxorubicin in a sarcoma subtype.","summary":"Phase 3 trial of 150 patients with metastatic or unresectable uterine or soft tissue leiomyosarcoma randomised to six cycles of doxorubicin alone or doxorubicin plus trabectedin followed by trabectedin maintenance, with surgery of residual disease allowed.\n\nMedian progression-free survival was 12.2 versus 6.2 months (hazard ratio 0.41) and response 36 versus 13 percent; the final analysis showed median overall survival of 33 versus 24 months. Grade 3 to 4 haematological toxicity was much higher with the combination.","asOf":"2026-09-17","links":[{"label":"Lancet Oncol 2022","url":"https://doi.org/10.1016/S1470-2045(22)00380-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35835135/"}],"tags":[],"related":[],"cancers":["extremity-soft-tissue-sarcoma","leiomyosarcoma","retroperitoneal-sarcoma"],"sections":[],"technologies":[],"targets":[],"drugs":["doxorubicin","trabectedin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["lms-04"],"people":["patricia-pautier"],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2022,"doi":"10.1016/S1470-2045(22)00380-1","pmid":"35835135","authors":"Pautier P, Italiano A, Piperno-Neumann S, et al.","paperType":"rct","findings":["Median progression-free survival 12.2 vs 6.2 months; hazard ratio 0.41.","Median overall survival 33 vs 24 months at final analysis."],"whatItMeans":"Doxorubicin-trabectedin is a first-line standard for fit patients with metastatic leiomyosarcoma, one of the few histology-specific first-line regimens in sarcoma.","caveats":["Substantial haematological toxicity and treatment delays.","Single-country (French) trial; confirmatory data awaited."],"changedPractice":true,"participants":150},{"id":"paper-calgb-140503-n-engl-j-med-2023","kind":"paper","name":"Lobar or Sublobar Resection for Peripheral Stage IA Non-Small-Cell Lung Cancer","aka":[],"tldr":"Published report from the CALGB 140503 trial registered as NCT00499330, in New England Journal of Medicine (2023), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: The increased detection of small-sized peripheral non-small-cell lung cancer (NSCLC) has renewed interest in sublobar resection in lieu of lobectomy.\n\nMethods: We conducted a multicenter, noninferiority, phase 3 trial in which patients with NSCLC clinically staged as T1aN0 (tumor size, ≤2 cm) were randomly assigned to undergo sublobar resection or lobar resection after intraoperative confirmation of node-negative disease. The primary end point was disease-free survival, defined as the time between randomization and disease recurrence or death from any cause. Secondary end points were overall survival, locoregional and systemic recurrence, and pulmonary functions.\n\nResults: From June 2007 through March 2017, a total of 697 patients were assigned to undergo sublobar resection (340 patients) or lobar resection (357 patients). After a median follow-up of 7 years, sublobar resection was noninferior to lobar resection for disease-free survival (hazard ratio for disease recurrence or death, 1.01; 90% confidence interval [CI], 0.83 to 1.24). In addition, overall survival after sublobar resection was similar to that after lobar resection (hazard ratio for death, 0.95; 95% CI, 0.72 to 1.26). The 5-year disease-free survival was 63.6% (95% CI, 57.9 to 68.8) after sublobar resection and 64.1% (95% CI, 58.5 to 69.0) after lobar resection. The 5-year overall survival was 80.3% (95% CI, 75.5 to 84.3) after sublobar resection and 78.9% (95% CI, 74.1 to 82.9) after lobar resection. No substantial difference was seen between the two groups in the incidence of locoregional or distant recurrence. At 6 months postoperatively, a between-group difference of 2 percentage points was measured in the median percentage of predicted forced expiratory volume in 1 second, favoring the sublobar-resection group.\n\nConclusions: In patients with peripheral NSCLC with a tumor size of 2 cm or less and pathologically confirmed node-negative disease in the hilar and mediastinal lymph nodes, sublobar resection was not inferior to lobectomy with respect to disease-free survival. Overall survival was similar with the two procedures. (Funded by the National Cancer Institute and others; CALGB 140503 ClinicalTrials.gov number, NCT00499330.).\n\nIndexed on Europe PMC as PubMed record 36780674 (DOI 10.1056/nejmoa2212083). Its abstract cites the registry id NCT00499330, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2023","url":"https://doi.org/10.1056/nejmoa2212083"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36780674/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36780674"},{"label":"ClinicalTrials.gov NCT00499330","url":"https://clinicaltrials.gov/study/NCT00499330"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["calgb-140503"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/nejmoa2212083","pmid":"36780674","authors":"Altorki N, Wang X, Kozono D, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT00499330 with the most citations, so it is the natural first reading for anyone following the CALGB 140503 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-esmo-localised-colon-cancer-guideline-ann-oncol-2020","kind":"paper","name":"Localised colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","aka":[],"tldr":"The European guideline for colon cancer that has not spread: who needs chemotherapy after the operation, for how long, and how patients are followed afterwards.","summary":"ESMO Clinical Practice Guidelines for localised colon cancer, published in Annals of Oncology in 2020 by Argilés, Tabernero, Labianca, Hochhauser, Salazar, Iveson, Laurent-Puig, Quirke, Yoshino, Taieb, Martinelli and Arnold for the ESMO Guidelines Committee. Europe PMC indexes no abstract for this article, so OnCo carries no figures from it.\n\nIt is the document that turned the IDEA collaboration's duration result into practice in Europe: three months of CAPOX for lower-risk stage III disease, six months of FOLFOX or CAPOX for T4 or N2 disease, and no adjuvant chemotherapy for mismatch repair-deficient stage II disease.","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2020","url":"https://doi.org/10.1016/j.annonc.2020.06.022"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32702383/"},{"label":"ESMO guidelines: gastrointestinal cancers","url":"https://www.esmo.org/guidelines/esmo-clinical-practice-guidelines-gastrointestinal-cancers"}],"tags":["colorectal-evidence"],"related":["esmo-guidelines","paper-idea-duration-adjuvant-stage-iii-colon-nejm-2018"],"cancers":["colorectal","colon-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["folfox","capox","capecitabine"],"companies":[],"institutions":["esmo"],"pathways":[],"terms":["neoadjuvant-adjuvant","msi"],"trials":[],"people":["josep-tabernero"],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2020,"doi":"10.1016/j.annonc.2020.06.022","pmid":"32702383","authors":"Argilés G, Tabernero J, Labianca R, et al.","paperType":"guideline","findings":["No abstract is indexed on Europe PMC; recommendations are read from the guideline itself."],"whatItMeans":"The European rulebook for what happens after a colon cancer operation, and the reason a patient with a T3 N1 tumour is now offered three months of chemotherapy rather than six.","caveats":["Written before DYNAMIC (2022) showed that a blood test can safely replace clinicopathological risk in stage II, and before ATOMIC (2025) added immunotherapy to adjuvant treatment of mismatch repair-deficient stage III disease.","Guideline text, not a trial."],"changedPractice":true},{"id":"paper-brown-nat-med","kind":"paper","name":"Locoregional delivery of IL-13Rα2-targeting CAR-T cells in recurrent high-grade glioma: a phase 1 trial","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 38454126 and published in Nature Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Chimeric antigen receptor T cell (CAR-T) therapy is an emerging strategy to improve treatment outcomes for recurrent high-grade glioma, a cancer that responds poorly to current therapies. Here we report a completed phase I trial evaluating IL-13Rα2-targeted CAR-T cells in 65 patients with recurrent high-grade glioma, the majority being recurrent glioblastoma (rGBM). Primary objectives were safety and feasibility, maximum tolerated dose/maximum feasible dose and a recommended phase 2 dose plan. Secondary objectives included overall survival, disease response, cytokine dynamics and tumor immune contexture biomarkers. This trial evolved to evaluate three routes of locoregional T cell administration (intratumoral (ICT), intraventricular (ICV) and dual ICT/ICV) and two manufacturing platforms, culminating in arm 5, which utilized dual ICT/ICV delivery and an optimized manufacturing process. Locoregional CAR-T cell administration was feasible and well tolerated, and as there were no dose-limiting toxicities across all arms, a maximum tolerated dose was not determined. Probable treatment-related grade 3+ toxicities were one grade 3 encephalopathy and one grade 3 ataxia. A clinical maximum feasible dose of 200 × 10 6 CAR-T cells per infusion cycle was achieved for arm 5; however, other arms either did not test or achieve this dose due to manufacturing feasibility. A recommended phase 2 dose will be refined in future studies based on data from this trial. Stable disease or better was achieved in 50% (29/58) of patients, with two partial responses, one complete response and a second complete response after additional CAR-T cycles off protocol. For rGBM, median overall survival for all patients was 7.7 months and for arm 5 was 10.2 months. Central nervous system increases in inflammatory cytokines, including IFNγ, CXCL9 and CXCL10, were associated with CAR-T cell administration and bioactivity. Pretreatment intratumoral CD3 T cell levels were positively associated with survival. These findings demonstrate that locoregional IL-13Rα2-targeted CAR-T therapy is safe with promising clinical activity in a subset of patients. ClinicalTrials.gov Identifier: NCT02208362.\n\nIndexed on Europe PMC as PubMed record 38454126 (DOI 10.1038/s41591-024-02875-1). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Med 2024","url":"https://doi.org/10.1038/s41591-024-02875-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38454126/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38454126"}],"tags":["europepmc-ingest"],"related":["myc"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2024,"doi":"10.1038/s41591-024-02875-1","pmid":"38454126","authors":"Brown CE, Hibbard JC, Alizadeh D, et al.","paperType":"observational","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-atkin-flexible-sigmoidoscopy-17-year-follow-up-lancet-2017","kind":"paper","name":"Long term effects of once-only flexible sigmoidoscopy screening after 17 years of follow-up","aka":[],"tldr":"Seventeen years after a single flexible sigmoidoscopy, the protection was still there: a quarter fewer bowel cancers and a third fewer deaths.","summary":"Atkin, Wooldrage, Parkin and colleagues extended the UK Flexible Sigmoidoscopy Screening Trial, run between November 1994 and March 1999, to a median 17.1 years of follow-up in 170,034 people: 112,936 controls and 57,098 in the intervention group, of whom 40,621 (71 percent) were screened.\n\nColorectal cancer was diagnosed in 1,230 people in the intervention group and 3,253 in the control group, and 353 against 996 died of it. The protection from one examination did not wane over the whole observation period, which is the finding that matters for how often screening endoscopy needs to be repeated.","asOf":"2026-09-24","links":[{"label":"Lancet 2017","url":"https://doi.org/10.1016/S0140-6736(17)30396-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28236467/"},{"label":"Europe PMC full text (PMC6168937)","url":"https://europepmc.org/article/MED/28236467"}],"tags":["colorectal-evidence"],"related":["paper-atkin-once-only-flexible-sigmoidoscopy-lancet-2010"],"cancers":["colorectal"],"sections":["early-detection","prevention"],"technologies":["colorectal-screening","endoscopy"],"targets":[],"drugs":[],"companies":[],"institutions":["cruk","nice"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-early-detection"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2017,"doi":"10.1016/S0140-6736(17)30396-3","pmid":"28236467","authors":"Atkin W, Wooldrage K, Parkin DM, et al.","paperType":"rct","findings":["Intention to treat at 17.1 years: incidence reduced 26 percent (hazard ratio 0.74, 95 percent CI 0.70 to 0.80) and mortality 30 percent (0.70, 0.62 to 0.79), both p<0.0001.","Per protocol: incidence 35 percent lower (0.65, 0.59 to 0.71) and mortality 41 percent lower (0.59, 0.49 to 0.70).","A single flexible sigmoidoscopy continued to protect for at least 17 years."],"whatItMeans":"Durability is what makes endoscopic screening cost-effective: one procedure at 55 buys nearly two decades of protection, which is the argument for long intervals rather than frequent tests.","caveats":["Same self-selected, screening-willing population as the 2010 report.","Protection is for distal disease only; the trial cannot speak to the right colon."],"changedPractice":true,"participants":170034},{"id":"paper-vaidya-bmj","kind":"paper","name":"Long term survival and local control outcomes from single dose targeted intraoperative radiotherapy during lumpectomy (TARGIT-IORT) for early breast cancer: TARGIT-A randomised clinical trial","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 32816842 and published in BMJ; the citing page links this DOI, which is how the record was matched.","summary":"Objective: To determine whether risk adapted intraoperative radiotherapy, delivered as a single dose during lumpectomy, can effectively replace postoperative whole breast external beam radiotherapy for early breast cancer.\n\nDesign: Prospective, open label, randomised controlled clinical trial.\n\nSetting: 32 centres in 10 countries in the United Kingdom, Europe, Australia, the United States, and Canada.\n\nParticipants: 2298 women aged 45 years and older with invasive ductal carcinoma up to 3.5 cm in size, cN0-N1, eligible for breast conservation and randomised before lumpectomy (1:1 ratio, blocks stratified by centre) to either risk adapted targeted intraoperative radiotherapy (TARGIT-IORT) or external beam radiotherapy (EBRT).\n\nInterventions: Random allocation was to the EBRT arm, which consisted of a standard daily fractionated course (three to six weeks) of whole breast radiotherapy, or the TARGIT-IORT arm. TARGIT-IORT was given immediately after lumpectomy under the same anaesthetic and was the only radiotherapy for most patients (around 80%). TARGIT-IORT was supplemented by EBRT when postoperative histopathology found unsuspected higher risk factors (around 20% of patients).\n\nMain outcome measures: Non-inferiority with a margin of 2.5% for the absolute difference between the five year local recurrence rates of the two arms, and long term survival outcomes.\n\nResults: Between 24 March 2000 and 25 June 2012, 1140 patients were randomised to TARGIT-IORT and 1158 to EBRT. TARGIT-IORT was non-inferior to EBRT: the local recurrence risk at five year complete follow-up was 2.11% for TARGIT-IORT compared with 0.95% for EBRT (difference 1.16%, 90% confidence interval 0.32 to 1.99). In the first five years, 13 additional local recurrences were reported (24/1140 v 11/1158) but 14 fewer deaths (42/1140 v 56/1158) for TARGIT-IORT compared with EBRT. With long term follow-up (median 8.6 years, maximum 18.90 years, interquartile range 7.0-10.6) no statistically significant difference was found for local recurrence-free survival (hazard ratio 1.13, 95% confidence interval 0.91 to 1.41, P=0.28), mastectomy-free survival (0.96, 0.78 to 1.19, P=0.74), distant disease-free survival (0.88, 0.69 to 1.12, P=0.30), overall survival (0.82, 0.63 to 1.05, P=0.13), and breast cancer mortality (1.12, 0.78 to 1.60, P=0.54). Mortality from other causes was significantly lower (0.59, 0.40 to 0.86, P=0.005).\n\nConclusion: For patients with early breast cancer who met our trial selection criteria, risk adapted immediate single dose TARGIT-IORT during lumpectomy was an effective alternative to EBRT, with comparable long term efficacy for cancer control and lower non-breast cancer mortality. TARGIT-IORT should be discussed with eligible patients when breast conserving surgery is planned.\n\nTrial registration: ISRCTN34086741, NCT00983684.\n\nIndexed on Europe PMC as PubMed record 32816842 (DOI 10.1136/bmj.m2836). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"BMJ 2020","url":"https://doi.org/10.1136/bmj.m2836"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32816842/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32816842"}],"tags":["europepmc-ingest"],"related":["intraoperative-radiotherapy"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["bmj"],"dependsOn":[],"notes":[],"journal":"BMJ","year":2020,"doi":"10.1136/bmj.m2836","pmid":"32816842","authors":"Vaidya JS, Bulsara M, Baum M, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-logsdon-nat-rev-genet","kind":"paper","name":"Long-read human genome sequencing and its applications","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 32504078 and published in Nature reviews. Genetics; the citing page links this DOI, which is how the record was matched.","summary":"Over the past decade, long-read, single-molecule DNA sequencing technologies have emerged as powerful players in genomics. With the ability to generate reads tens to thousands of kilobases in length with an accuracy approaching that of short-read sequencing technologies, these platforms have proven their ability to resolve some of the most challenging regions of the human genome, detect previously inaccessible structural variants and generate some of the first telomere-to-telomere assemblies of whole chromosomes. Long-read sequencing technologies will soon permit the routine assembly of diploid genomes, which will revolutionize genomics by revealing the full spectrum of human genetic variation, resolving some of the missing heritability and leading to the discovery of novel mechanisms of disease.\n\nIndexed on Europe PMC as PubMed record 32504078 (DOI 10.1038/s41576-020-0236-x). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Genet 2020","url":"https://doi.org/10.1038/s41576-020-0236-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32504078/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32504078"}],"tags":["europepmc-ingest"],"related":["long-read-sequencing"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature reviews. Genetics","year":2020,"doi":"10.1038/s41576-020-0236-x","pmid":"32504078","authors":"Logsdon GA, Vollger MR, Eichler EE","paperType":"review","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nordicc-lancet-2026-update","kind":"paper","name":"Long-term effects of colonoscopy screening on colorectal cancer incidence and mortality: a multicountry, population-based randomised controlled trial","aka":[],"tldr":"Later report from the NordICC trial registered as NCT00883792, in The Lancet (2026); its title describes an updated or longer-term analysis.","summary":"Background: We previously reported the 10-year effects of colonoscopy screening on colorectal cancer incidence and mortality. Here, we report the effects after 13 years of follow-up.\n\nMethods: In this multicountry, population-based randomised controlled trial, 84 583 men and women aged 55-64 years at enrolment from Norway, Poland, and Sweden were randomly allocated (1:2) to colonoscopy screening or no screening and analysed. The primary outcomes were colorectal cancer incidence and mortality after 10-15 years of follow-up in intention-to-screen analyses, with first analysis after 10 years, and repeated every other year or at longer intervals. This trial is registered with ClinicalTrials.gov, NCT00883792, and is ongoing.\n\nFindings: At 13 years of follow-up, colorectal cancer incidence was 375 colorectal cancers (1·46%) of 28 217 individuals in the screening group and 912 colorectal cancers (1·80%) of 56 366 individuals in the no-screening group. The risk ratio (RR) was 0·81 (95% CI 0·71-0·90) in intention-to-screen analyses and 0·55 (0·33-0·81) in per-protocol analyses. The risk for proximal colorectal cancer was 129 (0·51%) in the screening group versus 283 (0·56%) in the no-screening group (RR 0·91 [0·71-1·09]), and the risk for distal colorectal cancer was 224 (0·87%) in the screening group versus 563 (1·11%) in the no-screening group (RR 0·79 [0·65-0·89]; interaction p<0·0001). In men, the colorectal cancer risk was 214 (1·69%) of 14 154 in the screening group and 541 (2·19%) of 28 247 in the no-screening group (RR 0·77 [0·64 to -0·88]); in women, the risk was 161 (1·24%) of 14 063 in the screening group versus 371 (1·43%) of 28 119 in the no-screening group (RR 0·87 [0·70 to 1·02]; interaction p<0·0001). Colorectal cancer mortality was 106 (0·41%) of 28 217 in the screening group and 236 (0·47%) of 56 366 in the no-screening group (intention-to-screen RR 0·88 [0·68-1·08], per-protocol RR 0·70 [0·26-1·25]). The observed colorectal cancer mortality in the non-screening group (0·47%) was substantially lower than expected at the time of designing the trial (0·82%).\n\nInterpretation: One colonoscopy significantly reduced colorectal cancer incidence but not mortality over 13 years. Colorectal cancer mortality was lower in both study groups than when the trial was designed.\n\nFunding: The Norwegian Research Council, the Nordic Cancer Union, the Norwegian Cancer Society, and the Health Fund of South-East Norway.\n\nIndexed on Europe PMC as PubMed record 42102826 (DOI 10.1016/s0140-6736(26)00508-8). Its abstract cites the registry id NCT00883792, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet 2026","url":"https://doi.org/10.1016/s0140-6736(26)00508-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42102826/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42102826"},{"label":"ClinicalTrials.gov NCT00883792","url":"https://clinicaltrials.gov/study/NCT00883792"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nordicc"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2026,"doi":"10.1016/s0140-6736(26)00508-8","pmid":"42102826","authors":"Kaminski MF, Kalager M, Løberg M, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the NordICC trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-geyer-brightness-4-year-follow-up-ann-oncol-2022","kind":"paper","name":"Long-term efficacy and safety of addition of carboplatin with or without veliparib to standard neoadjuvant chemotherapy in triple-negative breast cancer: 4-year follow-up data from BrighTNess, a randomized phase III trial","aka":[],"tldr":"The 4.5-year follow-up of BrighTNess showing that adding carboplatin to pre-surgery chemotherapy in 634 women cut relapse or death by about 40 percent without more second cancers, while adding the PARP inhibitor veliparib added nothing.","summary":"Geyer, Sikov, Huober, Rugo and colleagues report follow-up of BrighTNess, in which 634 women with untreated stage II to III triple-negative breast cancer were randomised 2:1:1 to weekly paclitaxel with carboplatin plus veliparib (316), carboplatin plus placebo (160) or placebo alone (158), all followed by doxorubicin and cyclophosphamide. The co-primary endpoint of higher pathological complete response with veliparib was not met, so survival analyses are descriptive. At a median 4.5 years the event-free survival hazard ratio for carboplatin plus veliparib versus paclitaxel alone was 0.63 (95 percent confidence interval 0.43 to 0.92, p=0.02) but 1.12 (0.72 to 1.72) versus carboplatin without veliparib; post hoc, carboplatin versus paclitaxel alone gave 0.57 (0.36 to 0.91, p=0.02). Overall survival and rates of myelodysplastic syndrome, acute myeloid leukaemia and other second malignancies did not differ between arms.","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2022","url":"https://doi.org/10.1016/j.annonc.2022.01.009"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35093516/"},{"label":"ClinicalTrials.gov NCT02032277","url":"https://clinicaltrials.gov/study/NCT02032277"}],"tags":["tnbc-evidence"],"related":["paper-brightness-lancet-oncol-2018"],"cancers":["tnbc"],"sections":[],"technologies":["platinum","parp-inhibitor"],"targets":[],"drugs":["carboplatin","paclitaxel"],"companies":[],"institutions":[],"pathways":[],"terms":["efs","pcr"],"trials":["brightness"],"people":["charles-geyer","hope-rugo"],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2022,"doi":"10.1016/j.annonc.2022.01.009","pmid":"35093516","authors":"Geyer CE, Sikov WM, Huober J, et al.","paperType":"rct","findings":["Event-free survival, carboplatin plus veliparib vs paclitaxel alone: hazard ratio 0.63 (95 percent CI 0.43 to 0.92), p=0.02; vs carboplatin alone 1.12 (0.72 to 1.72).","Post hoc, carboplatin vs paclitaxel alone: 0.57 (0.36 to 0.91), p=0.02.","No difference in overall survival or in myelodysplastic syndrome, acute myeloid leukaemia or other second cancers."],"whatItMeans":"The third trial to show carboplatin's benefit persists beyond pathological complete response and the trial that closed the neoadjuvant PARP inhibitor route in unselected triple-negative disease; PARP inhibition survives only in germline BRCA carriers.","caveats":["Survival analyses descriptive because the veliparib co-primary endpoint failed.","Carboplatin-alone comparison is post hoc."],"changedPractice":true,"participants":634},{"id":"paper-bolt-j-eur-acad-dermatol-venereol-2018-update","kind":"paper","name":"Long-term efficacy and safety of sonidegib in patients with locally advanced and metastatic basal cell carcinoma: 30-month analysis of the randomized phase 2 BOLT study","aka":[],"tldr":"Later report from the BOLT trial registered as NCT01327053, in Journal of the European Academy of Dermatology and Venereology (2018); its title describes an updated or longer-term analysis.","summary":"Background: Patients with locally advanced basal cell carcinoma (laBCC) or metastatic BCC (mBCC), two difficult-to-treat populations, have had limited treatment options. Sonidegib, a hedgehog pathway inhibitor (HPI), was approved in laBCC based on results from the BOLT trial.\n\nObjective: To evaluate long-term efficacy and safety of sonidegib in laBCC and mBCC in the BOLT 18- and 30-month analyses.\n\nMethods: BOLT (NCT01327053, ClinicalTrials.gov), a double-blind phase 2 study, enrolled patients from July 2011 until January 2013. Eligible HPI-treatment-naïve patients with laBCC not amenable to curative surgery/radiotherapy or mBCC were randomized 1: 2 to sonidegib 200 mg (laBCC, n = 66; mBCC, n = 13) or 800 mg (laBCC, n = 128; mBCC, n = 23). Tumour response was assessed per central and investigator review.\n\nResults: With 30 months of follow-up, among patients treated with sonidegib 200 mg (approved dose), objective response rates were 56.1% (central) and 71.2% (investigator) in laBCC and 7.7% (central) and 23.1% (investigator) in mBCC. Tumour responses were durable as follows: median duration of response was 26.1 months (central) and 15.7 months (investigator) in laBCC and 24.0 months (central) and 18.1 months (investigator) in mBCC. Five patients with laBCC and three with mBCC in the 200-mg arm died. Median overall survival was not reached in either population; 2-year overall survival rates were 93.2% (laBCC) and 69.3% (mBCC). In laBCC, efficacy was similar regardless of aggressive or non-aggressive histology. Sonidegib 200 mg continued to have a better safety profile than 800 mg, with lower rates of grade 3/4 adverse events (43.0% vs. 64.0%) and adverse events leading to discontinuation (30.4% vs. 40.0%).\n\nConclusion: Sonidegib continued to demonstrate long-term efficacy and safety in these populations. These data support the use of sonidegib 200 mg per local treatment guidelines.\n\nIndexed on Europe PMC as PubMed record 28846163 (DOI 10.1111/jdv.14542). Its abstract cites the registry id NCT01327053, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Eur Acad Dermatol Venereol 2018","url":"https://doi.org/10.1111/jdv.14542"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28846163/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28846163"},{"label":"ClinicalTrials.gov NCT01327053","url":"https://clinicaltrials.gov/study/NCT01327053"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["bolt"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of the European Academy of Dermatology and Venereology","year":2018,"doi":"10.1111/jdv.14542","pmid":"28846163","authors":"Lear JT, Migden MR, Lewis KD, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the BOLT trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-nct04395677-j-clin-oncol-2026-update","kind":"paper","name":"Long-Term Efficacy and Safety of Taletrectinib in Patients With ROS1 + Non-Small Cell Lung Cancer: Results From the Phase II TRUST-I Study","aka":[],"tldr":"Later report from the trial registered as NCT04395677, in Journal of Clinical Oncology (2026); its title describes an updated or longer-term analysis.","summary":"Taletrectinib is a next-generation, CNS-active, selective ROS1 tyrosine kinase inhibitor (TKI) with activity against the ROS1 G2032R resistance mutation. Initial data from the TRUST-I study (ClinicalTrials.gov identifier: NCT04395677) demonstrated high response rates and intracranial (IC) activity, with promising durability, in Chinese patients with advanced ROS1 + non-small cell lung cancer (NSCLC). With longer follow-up, taletrectinib continued to demonstrate high and durable response rates in both TKI-naïve and crizotinib-pretreated patients, including IC activity and promising overall survival (OS). Among 103 TKI-naïve patients who started taletrectinib at 600 mg once daily (median follow-up, 51.0 months), the objective response rate (ORR) was 90.3% (95% CI, 82.9 to 95.3), the median duration of response (DOR) and median progression-free survival (PFS) exceeded 4 years (49.7 months and 49.6 months, respectively), and median OS was not reached. Among 66 crizotinib-pretreated patients (median follow-up, 45.2 months), the ORR was 51.5%, the median DOR was 13.2 months, the median PFS was 7.6 months, and the median OS was 25.6 months. The safety profile remained consistent with prior reports, and no new safety signals were identified. Overall, taletrectinib demonstrated durable long-term efficacy and a manageable safety profile in patients with advanced ROS1 + NSCLC.\n\nIndexed on Europe PMC as PubMed record 42013573 (DOI 10.1200/jco-26-00434). Its abstract cites the registry id NCT04395677, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2026","url":"https://doi.org/10.1200/jco-26-00434"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42013573/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42013573"},{"label":"ClinicalTrials.gov NCT04395677","url":"https://clinicaltrials.gov/study/NCT04395677"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04395677"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2026,"doi":"10.1200/jco-26-00434","pmid":"42013573","authors":"Li W, Zhang Y, Fan H, et al.","paperType":"observational","findings":[],"whatItMeans":"A second publication from the trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-ferreri-leukemia","kind":"paper","name":"Long-term efficacy, safety and neurotolerability of MATRix regimen followed by autologous transplant in primary CNS lymphoma: 7-year results of the IELSG32 randomized trial","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 35562406 and published in Leukemia; the citing page links this DOI, which is how the record was matched.","summary":"219 HIV-negative adults ≤70 years with primary CNS lymphoma (PCNSL) were enrolled in the randomized IELSG32 trial. Enrolled patients were randomly assigned to receive methotrexate-cytarabine (arm A), or methotrexate-cytarabine-rituximab (B), or methotrexate-cytarabine-thiotepa-rituximab (MATRix; arm C). A second randomization allocated patients with responsive/stable disease to whole-brain irradiation (WBRT) or carmustine-thiotepa-conditioned autologous transplantation (ASCT). First results, after a median follow-up of 30 months, showed that MATRix significantly improves outcome, with both WBRT and ASCT being similarly effective. However, sound assessment of overall survival (OS), efficacy of salvage therapy, late complications, secondary tumors, and cognitive impairment requires longer follow-up. Herein, we report the results of this trial at a median follow-up of 88 months. As main findings, MATRix was associated with excellent long-lasting outcome, with a 7-year OS of 21%, 37%, and 56% respectively for arms A, B, and C. Notably, patients treated with MATRix and consolidation had a 7-year OS of 70%. The superiority of arm B on arm A suggests a benefit from the addition of rituximab. Comparable efficacy of WBRT and ASCT was confirmed. Salvage therapy was ineffective; benefit was recorded only in patients with late relapse re-treated with methotrexate. Eight (4%) patients developed a second cancer. Importantly, MATRix and ASCT did not result in higher non-relapse mortality or second tumors incidence. Patients who received WBRT experienced impairment in attentiveness and executive functions, whereas patients undergoing ASCT experienced improvement in these functions as well as in memory and quality of life.\n\nIndexed on Europe PMC as PubMed record 35562406 (DOI 10.1038/s41375-022-01582-5). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Leukemia 2022","url":"https://doi.org/10.1038/s41375-022-01582-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35562406/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35562406"}],"tags":["europepmc-ingest"],"related":["primary-cns-lymphoma"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["leukemia"],"dependsOn":[],"notes":[],"journal":"Leukemia","year":2022,"doi":"10.1038/s41375-022-01582-5","pmid":"35562406","authors":"Ferreri AJM, Cwynarski K, Pulczynski E, et al.","paperType":"rct","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-klotz-active-surveillance-jco-2015","kind":"paper","name":"Long-term follow-up of a large active surveillance cohort of patients with prostate cancer (Sunnybrook)","aka":[],"tldr":"In nearly a thousand men with low-risk prostate cancer followed for up to 20 years on active surveillance, only 1.5 percent died of the disease and most never needed treatment, the strongest evidence that surveillance is safe.","summary":"Prospective single-centre cohort of 993 men with low-risk (and some favourable intermediate-risk) prostate cancer managed with active surveillance, with treatment triggered by PSA doubling time, grade progression or clinical progression.\n\nAt a median follow-up of 6.4 years (up to 20 years), 15 men (1.5 percent) died of prostate cancer and 13 developed metastases; 10- and 15-year cancer-specific survival were 98.1 and 94.3 percent, and about a quarter of men had been treated.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2015","url":"https://doi.org/10.1200/JCO.2014.55.1192"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25512465/"}],"tags":[],"related":["prostate-roadmap","paper-loeb-overdiagnosis-overtreatment-prostate-eur-urol-2014","paper-wilt-pivot-prostatectomy-observation-nejm-2017"],"cancers":["prostate-low-risk","prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2015,"doi":"10.1200/JCO.2014.55.1192","pmid":"25512465","authors":"Klotz L, Vesprini D, Sethukavalan P, et al.","paperType":"observational","findings":["Prostate cancer mortality 1.5 percent at a median of 6.4 years.","15-year cancer-specific survival 94.3 percent; 27 percent of men had definitive treatment."],"whatItMeans":"Active surveillance is the preferred management for low-risk prostate cancer, and this cohort's triggers for intervention shaped surveillance protocols worldwide.","caveats":["Single-centre cohort with PSA-kinetics-based triggers later found to be unreliable; MRI is now integral."],"changedPractice":true,"participants":993},{"id":"paper-eichenauer-nlphl-ghsg-hd7-hd15-long-term-jco-2020","kind":"paper","name":"Long-term follow-up of nodular lymphocyte-predominant Hodgkin lymphoma treated in the GHSG HD7 to HD15 trials","aka":[],"tldr":"The largest long-term series of nodular lymphocyte-predominant Hodgkin lymphoma found that three-quarters of patients were still free of the disease ten years after standard Hodgkin lymphoma treatment and more than nine in ten were alive, but most of the deaths came from second cancers and treatment effects rather than from the lymphoma itself.","summary":"Retrospective analysis of 471 patients with nodular lymphocyte-predominant Hodgkin lymphoma (251 early, 76 intermediate and 144 advanced stage) who received stage-adapted first-line treatment (radiotherapy alone, chemotherapy alone or combined modality) within the randomised German Hodgkin Study Group trials HD7 to HD15. Median age was 39 and three-quarters were men; median observation time was 9.2 years.\n\nAt ten years progression-free survival was 75.5 percent and overall survival 92.1 percent (early stages 79.7 and 93.3 percent; intermediate 72.1 and 96.2 percent; advanced 69.8 and 87.4 percent). Forty-eight patients (10.2 percent) developed a second malignancy and 43 (9.1 percent) died, but only 10 deaths were from the lymphoma; 20 were from second malignancies and 13 from non-malignant conditions possibly related to treatment. The authors concluded that outcomes with Hodgkin-directed therapy are good but that toxicity must be reduced in standard-risk patients and results improved in high-risk ones.","asOf":"2026-09-18","links":[{"label":"J Clin Oncol 2020","url":"https://doi.org/10.1200/JCO.19.00986"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31626571/"}],"tags":[],"related":[],"cancers":["nodular-lymphocyte-predominant-hodgkin-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["doxorubicin","vinblastine","dacarbazine"],"companies":["ghsg"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/JCO.19.00986","pmid":"31626571","authors":"Eichenauer DA, Plütschow A, Fuchs M, et al.","paperType":"observational","findings":["Ten-year progression-free survival 75.5 percent and overall survival 92.1 percent across 471 patients.","Outcomes by stage: early 79.7 and 93.3 percent, intermediate 72.1 and 96.2 percent, advanced 69.8 and 87.4 percent (progression-free and overall survival at ten years).","Second malignancies in 10.2 percent of patients; of 43 deaths only 10 were from the lymphoma, against 20 from second malignancies and 13 from possibly treatment-related conditions."],"whatItMeans":"Nodular lymphocyte-predominant Hodgkin lymphoma is rarely fatal when treated with standard Hodgkin lymphoma protocols, so the goal for most patients is to give less treatment, not more; the minority with advanced or variant disease still need better options.","caveats":["Retrospective, and patients were treated on classical Hodgkin lymphoma protocols rather than with rituximab-based regimens now used by many centres.","Trials spanned the 1990s to 2000s, so radiotherapy fields and chemotherapy were more intensive than current practice."],"changedPractice":false,"participants":471},{"id":"paper-nct04270591-transl-lung-cancer-res-2025-update","kind":"paper","name":"Long-term follow-up results from the GLORY study: phase II study of gumarontinib in East Asian patients with MET exon 14 skipping mutated non-small cell lung cancer","aka":[],"tldr":"Later report from the trial registered as NCT04270591, in Translational lung cancer research (2025); its title describes an updated or longer-term analysis.","summary":"Background: Gumarontinib has previously shown activity in patients with non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping mutation ( MET ex14). We hereby report the updated results from the phase II stage of GLORY study after additional 18-month follow-up.\n\nMethods: The single-arm, multicenter, open-label, phase II of the GLORY study was conducted at 42 centers across China and Japan. Patients with locally advanced or metastatic MET ex14-positive NSCLC received gumarontinib 300 mg orally once daily until disease progression or intolerable toxicity. Eligible patients had failed one or two prior lines of therapy (not including a MET inhibitor) and had no genetic alterations targetable with standard therapies. The primary endpoint was the objective response rate (ORR) by the blinded independent review committee (BIRC) per Response Evaluation Criteria in Solid Tumors version 1.1. The study was registered at ClinicalTrials.gov (NCT04270591).\n\nResults: The phase II stage of GLORY study included 84 patients. at the data cutoff date on October 28, 2023, the ORR assessed by BIRC was 65.8% [95% confidence interval (CI): 54.3% to 76.1%], with 70.5% (95% CI: 54.8% to 83.2%) in treatment-naïve and 60.0% (95% CI: 42.1% to 76.1%) in pre-treated populations. The median duration of response (DOR) assessed by BIRC was 8.3 (95% CI: 6.2 to 18.3) months, the median progression-free survival (PFS) was 7.7 (95% CI: 7.6 to 9.7) months, and the median overall survival (OS) was 19.4 (95% CI: 12.1 to 30.1) months, with a median OS of 25.4 [95% CI: 11.7 to not evaluable (NE)] months in treatment-naïve population and 16.3 (95% CI: 8.7 to NE) months in the pre-treated population. The most common treatment-related adverse events (any grade) were oedema (67/84, 79.8%) and hypoalbuminemia (32/84, 38.1%). Grade ≥3 treatment-related adverse events occurred in 53.6% (45/84) patients. Treatment-related adverse events leading to permanent discontinuation occurred in 8.3% (7/84) of patients.\n\nConclusions: Gumarontinib showed promising efficacy and acceptable toxicities in East Asian population, with a rapid onset of action, substantial and durable response, which can be converted into a long-term survival benefit.\n\nIndexed on Europe PMC as PubMed record 41132955 (DOI 10.21037/tlcr-2025-638). Its abstract cites the registry id NCT04270591, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Transl Lung Cancer Res 2025","url":"https://doi.org/10.21037/tlcr-2025-638"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41132955/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41132955"},{"label":"ClinicalTrials.gov NCT04270591","url":"https://clinicaltrials.gov/study/NCT04270591"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04270591"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Translational lung cancer research","year":2025,"doi":"10.21037/tlcr-2025-638","pmid":"41132955","authors":"Lu S, Yu Y, Zhou J, et al.","paperType":"observational","findings":[],"whatItMeans":"A second publication from the trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-convert-int-j-radiat-oncol-biol-phys-2024-update","kind":"paper","name":"Long-Term Outcomes After Concurrent Once- or Twice-Daily Chemoradiation in Limited-Stage Small Cell Lung Cancer: A Brief Report From the CONVERT Trial","aka":[],"tldr":"Later report from the CONVERT trial registered as NCT00433563, in International Journal of Radiation Oncology, Biology, Physics (2024); its title describes an updated or longer-term analysis.","summary":"Purpose: CONVERT was a phase 3 international randomized clinical trial comparing once-daily (OD) and twice-daily (BD) radiation therapy (RT). This updated analysis describes the 6.5-year outcomes of these regimens delivered with conformal techniques.\n\nMethods and materials: CONVERT (NCT00433563) randomized patients 1:1 between OD RT (66 Gy/33 fractions/6.5 weeks) and BD RT (45 Gy/30 fractions/3 weeks), both delivered with concurrent cisplatin/etoposide. Three-dimensional conformal RT was mandatory, intensity-modulated RT was permitted, and elective nodal irradiation was not allowed. Prophylactic cranial irradiation was delivered at the discretion of treating clinicians. RT treatment planning was subject to central quality assurance.\n\nResults: Five hundred forty-seven patients were recruited at 73 centers. The median follow-up for the surviving cohort (n = 164) was 81.2 months. The median survival for the OD and BD arms were 25.4 months (95% CI, 21.1-30.9) and 30.0 months (95% CI, 25.3-36.5; hazard ratio, 1.13; 95% CI, 0.92-1.38; P =.247). Performance status and tumor volume were associated with survival on multivariate analysis. No treatment-related deaths occurred subsequent to the initial analysis performed in 2017. Regarding late toxicity, 7 patients in the OD arm developed grade 3 esophagitis, 4 of which went on to develop stricture or fistulation, compared with no patients in the BD arm. Grade 3 pulmonary fibrosis occurred in 2 and 3 patients in the OD and BD arms, respectively.\n\nConclusions: As the CONVERT trial did not demonstrate the superiority of OD RT and this regimen had a slightly worse toxicity profile after 80 months of follow-up, 45 Gy BD should remain the standard of care in limited stage small cell lung cancer.\n\nIndexed on Europe PMC as PubMed record 38521132 (DOI 10.1016/j.ijrobp.2024.02.063). Its abstract cites the registry id NCT00433563, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Int J Radiat Oncol Biol Phys 2024","url":"https://doi.org/10.1016/j.ijrobp.2024.02.063"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38521132/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38521132"},{"label":"ClinicalTrials.gov NCT00433563","url":"https://clinicaltrials.gov/study/NCT00433563"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["convert"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["ijrobp"],"dependsOn":[],"notes":[],"journal":"International Journal of Radiation Oncology, Biology, Physics","year":2024,"doi":"10.1016/j.ijrobp.2024.02.063","pmid":"38521132","authors":"Walls GM, Mistry H, Barlesi F, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the CONVERT trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-protect-bju-int-2026-update","kind":"paper","name":"Long-term outcomes of cribriform-positive and cribriform-negative prostate cancer treated with radical prostatectomy in the ProtecT trial","aka":[],"tldr":"Later report from the ProtecT trial registered as NCT02044172, in BJU international (2026); its title describes an updated or longer-term analysis.","summary":"Objectives: To retrospectively analyse the results of the Prostate Testing for Cancer and Treatment (ProtecT; ClinicalTrials.gov identifier: NCT02044172) trial to establish the association between cribriform-positive and -negative prostate cancer (PCa) and the 15-year risk of metastasis or death from PCa in patients who underwent radical prostatectomy (RP).\n\nPatients and methods: Between 1999 and 2009, the ProtecT phase 3 clinical trial enrolled 1643 men with clinically localised PCa who were randomised to receive active monitoring, RP, or radiotherapy. In this secondary analysis of the trial, a centralised histopathological review was conducted on available RP pathology slides to classify patients as cribriform-positive if they had invasive cribriform carcinoma and/or intraductal carcinoma. The primary outcome was a composite of progression to metastatic disease or death from PCa. Exposures included age, prostate-specific antigen density, RP Grade Group (GG), pathological T stage (pT), and cribriform status. Multivariable Cox proportional hazards regression models assessed 15-year risk. Cumulative incidence curves were compared using the Gray test.\n\nResults: Of 480 men with RP specimens reviewed, 143 (30%) had cribriform-positive disease and 337 (70%) had cribriform-negative disease. All 21 metastatic or lethal events occurred exclusively in the cribriform-positive group (15-year cumulative incidence 14%). Within the cribriform-positive cohort, risk was concentrated in patients with pT3b stage and/or GG ≥3 (15-year cumulative incidence 27%). In multivariable analysis of cribriform-positive patients, pT3b stage (hazard ratio [HR] 8.19, 95% confidence interval [CI] 2.39-28.10; P < 0.001) and GG 3 disease (HR 5.12, 95% CI 1.59-16.40; P = 0.006) were independent predictors of adverse outcomes. Conversely, cribriform-positive patients with GG 2 and ≤pT3a had a 15-year event rate of only 3%.\n\nConclusion: In the ProtecT trial, the 15-year risk of metastasis or death after RP was a binary outcome defined by cribriform status. The concentration of risk in men with cribriform-positive, high-grade and/or pT3b tumours identifies a target population for adjuvant therapy trials, while supporting management de-escalation for most RP patients.\n\nIndexed on Europe PMC as PubMed record 41896701 (DOI 10.1111/bju.70261). Its abstract cites the registry id NCT02044172, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"BJU Int 2026","url":"https://doi.org/10.1111/bju.70261"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41896701/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41896701"},{"label":"ClinicalTrials.gov NCT02044172","url":"https://clinicaltrials.gov/study/NCT02044172"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["protect"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"BJU international","year":2026,"doi":"10.1111/bju.70261","pmid":"41896701","authors":"Sushentsev N, Warren AY, Colling R, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the ProtecT trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-checkmate-204-lancet-oncol-2021-update","kind":"paper","name":"Long-term outcomes of patients with active melanoma brain metastases treated with combination nivolumab plus ipilimumab (CheckMate 204): final results of an open-label, multicentre, phase 2 study","aka":[],"tldr":"Later report from the CheckMate 204 trial registered as NCT02320058, in The Lancet Oncology (2021); its title describes an updated or longer-term analysis.","summary":"Background: Combination nivolumab plus ipilimumab was efficacious in patients with asymptomatic melanoma brain metastases (MBM) in CheckMate 204, but showed low efficacy in patients with symptomatic MBM. Here, we provide final 3-year follow-up data from the trial.\n\nMethods: This open-label, multicentre, phase 2 study (CheckMate 204) included adults (aged ≥18 years) with measurable MBM (0·5-3·0 cm in diameter). Asymptomatic patients (cohort A) had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and no neurological symptoms or baseline corticosteroid use; symptomatic patients (cohort B) had an ECOG performance status of 0-2 with stable neurological symptoms and could be receiving low-dose dexamethasone. Nivolumab 1 mg/kg plus ipilimumab 3 mg/kg was given intravenously every 3 weeks for four doses, followed by nivolumab 3 mg/kg every 2 weeks for up to 2 years, until disease progression or unacceptable toxicity. The primary endpoint was intracranial clinical benefit rate (complete responses, partial responses, or stable disease lasting ≥6 months) assessed in all treated patients. Intracranial progression-free survival and overall survival were key secondary endpoints. This study is registered with ClinicalTrials.gov, NCT02320058.\n\nFindings: Between Feb 19, 2015, and Nov 1, 2017, 119 (72%) of 165 screened patients were enrolled and treated: 101 patients were asymptomatic (cohort A; median follow-up 34·3 months [IQR 14·7-36·4]) and 18 were symptomatic (cohort B; median follow-up 7·5 months [1·2-35·2]). Investigator-assessed intracranial clinical benefit was observed in 58 (57·4% [95% CI 47·2-67·2]) of 101 patients in cohort A and three (16·7% [3·6-41·4]) of 18 patients in cohort B; investigator-assessed objective response was observed in 54 (53·5% [43·3-63·5]) patients in cohort A and three (16·7% [3·6-41·4]) patients in cohort B. 33 (33%) patients in cohort A and three (17%) patients in cohort B had an investigator-assessed intracranial complete response. For patients in cohort A, 36-month intracranial progression-free survival was 54·1% (95% CI 42·7-64·1) and overall survival was 71·9% (61·8-79·8). For patients in cohort B, 36-month intracranial progression-free survival was 18·9% (95% CI 4·6-40·5) and overall survival was 36·6% (14·0-59·8). The most common grade 3-4 treatment-related adverse events (TRAEs) were increased alanine aminotransferase and aspartate aminotransferase (15 [15%] of 101 patients each) in cohort A; no grade 3 TRAEs occurred in more than one patient each in cohort B, and no grade 4 events occurred. The most common serious TRAEs were colitis, diarrhoea, hypophysitis, and increased alanine aminotransferase (five [5%] of each among the 101 patients in cohort A); no serious TRAE occurred in more than one patient each in cohort B. There was one treatment-related death (myocarditis in cohort A).\n\nInterpretation: The durable 3-year response, overall survival, and progression-free survival rates for asymptomatic patients support first-line use of nivolumab plus ipilimumab. Symptomatic disease in patients with MBM remains difficult to treat, but some patients achieve a long-term response with the combination.\n\nFunding: Bristol Myers Squibb.\n\nIndexed on Europe PMC as PubMed record 34774225 (DOI 10.1016/s1470-2045(21)00545-3). Its abstract cites the registry id NCT02320058, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2021","url":"https://doi.org/10.1016/s1470-2045(21)00545-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34774225/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34774225"},{"label":"ClinicalTrials.gov NCT02320058","url":"https://clinicaltrials.gov/study/NCT02320058"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-204"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2021,"doi":"10.1016/s1470-2045(21)00545-3","pmid":"34774225","authors":"Tawbi HA, Forsyth PA, Hodi FS, et al.","paperType":"observational","findings":[],"whatItMeans":"A second publication from the CheckMate 204 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-nsabp-b39-lancet-2019","kind":"paper","name":"Long-term primary results of accelerated partial breast irradiation after breast-conserving surgery for early-stage breast cancer: a randomised, phase 3, equivalence trial","aka":[],"tldr":"Published report from the NSABP B-39 trial registered as NCT00103181, in The Lancet (2019), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Whole-breast irradiation after breast-conserving surgery for patients with early-stage breast cancer decreases ipsilateral breast-tumour recurrence (IBTR), yielding comparable results to mastectomy. It is unknown whether accelerated partial breast irradiation (APBI) to only the tumour-bearing quadrant, which shortens treatment duration, is equally effective. In our trial, we investigated whether APBI provides equivalent local tumour control after lumpectomy compared with whole-breast irradiation.\n\nMethods: We did this randomised, phase 3, equivalence trial (NSABP B-39/RTOG 0413) in 154 clinical centres in the USA, Canada, Ireland, and Israel. Adult women (>18 years) with early-stage (0, I, or II; no evidence of distant metastases, but up to three axillary nodes could be positive) breast cancer (tumour size ≤3 cm; including all histologies and multifocal breast cancers), who had had lumpectomy with negative (ie, no detectable cancer cells) surgical margins, were randomly assigned (1:1) using a biased-coin-based minimisation algorithm to receive either whole-breast irradiation (whole-breast irradiation group) or APBI (APBI group). Whole-breast irradiation was delivered in 25 daily fractions of 50 Gy over 5 weeks, with or without a supplemental boost to the tumour bed, and APBI was delivered as 34 Gy of brachytherapy or 38·5 Gy of external bream radiation therapy in 10 fractions, over 5 treatment days within an 8-day period. Randomisation was stratified by disease stage, menopausal status, hormone-receptor status, and intention to receive chemotherapy. Patients, investigators, and statisticians could not be masked to treatment allocation. The primary outcome of invasive and non-invasive IBTR as a first recurrence was analysed in the intention-to-treat population, excluding those patients who were lost to follow-up, with an equivalency test on the basis of a 50% margin increase in the hazard ratio (90% CI for the observed HR between 0·667 and 1·5 for equivalence) and a Cox proportional hazard model. Survival was assessed by intention to treat, and sensitivity analyses were done in the per-protocol population. This trial is registered with ClinicalTrials.gov, NCT00103181.\n\nFindings: Between March 21, 2005, and April 16, 2013, 4216 women were enrolled. 2109 were assigned to the whole-breast irradiation group and 2107 were assigned to the APBI group. 70 patients from the whole-breast irradiation group and 14 from the APBI group withdrew consent or were lost to follow-up at this stage, so 2039 and 2093 patients respectively were available for survival analysis. Further, three and four patients respectively were lost to clinical follow-up (ie, survival status was assessed by phone but no physical examination was done), leaving 2036 patients in the whole-breast irradiation group and 2089 in the APBI group evaluable for the primary outcome. At a median follow-up of 10·2 years (IQR 7·5-11·5), 90 (4%) of 2089 women eligible for the primary outcome in the APBI group and 71 (3%) of 2036 women in the whole-breast irradiation group had an IBTR (HR 1·22, 90% CI 0·94-1·58). The 10-year cumulative incidence of IBTR was 4·6% (95% CI 3·7-5·7) in the APBI group versus 3·9% (3·1-5·0) in the whole-breast irradiation group. 44 (2%) of 2039 patients in the whole-breast irradiation group and 49 (2%) of 2093 patients in the APBI group died from recurring breast cancer. There were no treatment-related deaths. Second cancers and treatment-related toxicities were similar between the two groups. 2020 patients in the whole-breast irradiation group and 2089 in APBI group had available data on adverse events. The highest toxicity grade reported was: grade 1 in 845 (40%), grade 2 in 921 (44%), and grade 3 in 201 (10%) patients in the APBI group, compared with grade 1 in 626 (31%), grade 2 in 1193 (59%), and grade 3 in 143 (7%) in the whole-breast irradiation group.\n\nInterpretation: APBI did not meet the criteria for equivalence to whole-breast irradiation in controlling IBTR for breast-conserving therapy. Our trial had broad eligibility criteria, leading to a large, heterogeneous pool of patients and sufficient power to detect treatment equivalence, but was not designed to test equivalence in patient subgroups or outcomes from different APBI techniques. For patients with early-stage breast cancer, our findings support whole-breast irradiation following lumpectomy; however, with an absolute difference of less than 1% in the 10-year cumulative incidence of IBTR, APBI might be an acceptable alternative for some women.\n\nFunding: National Cancer Institute, US Department of Health and Human Services.\n\nIndexed on Europe PMC as PubMed record 31813636 (DOI 10.1016/s0140-6736(19)32514-0). Its abstract cites the registry id NCT00103181, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet 2019","url":"https://doi.org/10.1016/s0140-6736(19)32514-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31813636/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31813636"},{"label":"ClinicalTrials.gov NCT00103181","url":"https://clinicaltrials.gov/study/NCT00103181"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nsabp-b39"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2019,"doi":"10.1016/s0140-6736(19)32514-0","pmid":"31813636","authors":"Vicini FA, Cecchini RS, White JR, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT00103181 with the most citations, so it is the natural first reading for anyone following the NSABP B-39 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-symmans-rcb-long-term-prognosis-subtype-jco-2017","kind":"paper","name":"Long-Term Prognostic Risk After Neoadjuvant Chemotherapy Associated With Residual Cancer Burden and Breast Cancer Subtype","aka":[],"tldr":"The 2017 validation of the residual cancer burden score, which graded how much triple-negative tumour is left after pre-surgery chemotherapy and found ten-year relapse-free survival of 86 percent with no residual tumour, 81 percent with minimal, 55 percent with moderate and 23 percent with extensive residual disease.","summary":"Symmans, Wei, Gould, Yu and colleagues measured the continuous residual cancer burden index (pathological complete response is 0; residual disease falls into RCB-I, II and III) and yp-stage in five prospectively followed cohorts: three receiving paclitaxel then fluorouracil, doxorubicin and cyclophosphamide (219, 262 and 342 patients), one receiving FAC alone (132) and one receiving trastuzumab with paclitaxel and FEC (203), with median event-free follow-up of 13.5, 9.1, 6.8, 16.4 and 7.1 years. Continuous residual cancer burden was prognostic within each subset independent of other variables, and RCB classes stratified risk overall, within subsets and within yp-stage. Ten-year relapse-free survival for pathological complete response, RCB-I, RCB-II and RCB-III was 86, 81, 55 and 23 percent for triple-negative disease; 83, 97, 74 and 52 percent for hormone receptor-positive/HER2-negative disease; and 95, 77, 47 and 21 percent in the trastuzumab cohort.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2017","url":"https://doi.org/10.1200/JCO.2015.63.1010"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28135148/"}],"tags":["tnbc-evidence"],"related":["paper-symmans-j-clin-oncol","paper-yau-rcb-pooled-analysis-5161-lancet-oncol-2022"],"cancers":["tnbc","breast-hr-positive","breast-her2-positive"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["md-anderson"],"pathways":[],"terms":["rcb","pcr","neoadjuvant-adjuvant"],"trials":["ascent-05","tropion-breast03"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2017,"doi":"10.1200/JCO.2015.63.1010","pmid":"28135148","authors":"Symmans WF, Wei C, Gould R, et al.","paperType":"observational","findings":["Ten-year relapse-free survival in triple-negative disease by residual cancer burden class: 86 percent (complete response), 81 (RCB-I), 55 (RCB-II), 23 (RCB-III).","Continuous residual cancer burden prognostic within every phenotypic subset, independent of clinical and pathological variables."],"whatItMeans":"Turned residual disease from yes or no into a graded score; RCB II and III are now the entry criteria for post-neoadjuvant trials (ASCENT-05, TROPION-Breast03) and the population the ctDNA-guided idea targets.","caveats":["Single institution; the authors call for external validation, supplied by the 2022 pooled analysis.","Pre-immunotherapy chemotherapy regimens."],"changedPractice":true,"participants":1158},{"id":"paper-opra-j-clin-oncol-2024","kind":"paper","name":"Long-Term Results of Organ Preservation in Patients With Rectal Adenocarcinoma Treated With Total Neoadjuvant Therapy: The Randomized Phase II OPRA Trial","aka":[],"tldr":"Published report from the OPRA trial registered as NCT02008656, in Journal of Clinical Oncology (2024), chosen as the most cited paper whose own text cites the registry id.","summary":"Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. To assess long-term risk of local tumor regrowth, we report updated organ preservation rate and oncologic outcomes of the OPRA trial (ClinicalTrials.gov identifier: NCT02008656). Patients with stage II/III rectal cancer were randomly assigned to receive induction chemotherapy followed by chemoradiation (INCT-CRT) or chemoradiation followed by consolidation chemotherapy (CRT-CNCT). Patients who achieved a complete or near-complete response after finishing treatment were offered watch-and-wait (WW). Total mesorectal excision (TME) was recommended for those who achieved an incomplete response. The primary end point was disease-free survival (DFS). The secondary end point was TME-free survival. In total, 324 patients were randomly assigned (INCT-CRT, n = 158; CRT-CNCT, n = 166). Median follow-up was 5.1 years. The 5-year DFS rates were 71% (95% CI, 64 to 79) and 69% (95% CI, 62 to 77) for INCT-CRT and CRT-CNCT, respectively ( P =.68). TME-free survival was 39% (95% CI, 32 to 48) in the INCT-CRT group and 54% (95% CI, 46 to 62) in the CRT-CNCT group ( P =.012). Of 81 patients with regrowth, 94% occurred within 2 years and 99% occurred within 3 years. DFS was similar for patients who underwent TME after restaging (64% [95% CI, 53 to 78]) and patients in WW who underwent TME after regrowth (64% [95% CI, 53 to 78]; P =.94). Updated analysis continues to show long-term organ preservation in half of the patients with rectal cancer treated with total neoadjuvant therapy. In patients who enter WW, most cases of tumor regrowth occur in the first 2 years.\n\nIndexed on Europe PMC as PubMed record 37883738 (DOI 10.1200/jco.23.01208). Its abstract cites the registry id NCT02008656, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2024","url":"https://doi.org/10.1200/jco.23.01208"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37883738/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37883738"},{"label":"ClinicalTrials.gov NCT02008656","url":"https://clinicaltrials.gov/study/NCT02008656"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["opra"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2024,"doi":"10.1200/jco.23.01208","pmid":"37883738","authors":"Verheij FS, Omer DM, Williams H, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02008656 with the most citations, so it is the natural first reading for anyone following the OPRA trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-rtog-91-11-long-term-forastiere-jco-2013","kind":"paper","name":"Long-term results of RTOG 91-11: three non-surgical strategies to preserve the larynx","aka":[],"tldr":"Ten-year follow-up confirmed that concurrent chemoradiation gives the best larynx preservation and local control in advanced laryngeal cancer, but also revealed more late deaths unrelated to cancer in that arm, raising questions about long-term toxicity.","summary":"Ten-year update of the RTOG 91-11 trial comparing induction chemotherapy then radiotherapy, concurrent cisplatin chemoradiation, and radiotherapy alone in 547 patients with advanced laryngeal cancer.\n\nLaryngectomy-free survival was similar between the two chemotherapy arms and better than radiotherapy alone; locoregional control and laryngeal preservation remained best with concurrent treatment (ten-year preservation 81.7 percent versus 67.5 percent with induction), but overall survival showed a non-significant trend against the concurrent arm because of more non-cancer deaths.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2013","url":"https://doi.org/10.1200/JCO.2012.43.6097"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23182993/"}],"tags":[],"related":[],"cancers":["laryngeal-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["rtog-91-11"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2013,"doi":"10.1200/JCO.2012.43.6097","pmid":"23182993","authors":"Forastiere AA, Zhang Q, Weber RS, et al.","paperType":"rct","findings":["Ten-year laryngeal preservation 81.7 percent (concurrent) vs 67.5 percent (induction) vs 63.8 percent (radiotherapy alone).","Ten-year overall survival 27.5 percent, 38.8 percent and 31.5 percent (not significantly different)."],"whatItMeans":"Concurrent chemoradiation remains standard, but the excess of late non-cancer deaths is a reminder that swallowing dysfunction and aspiration after chemoradiation carry long-term risk.","caveats":["Cause of the late non-cancer deaths is uncertain.","Radiotherapy technique predates intensity modulation."],"changedPractice":true,"participants":547},{"id":"paper-glaser-br-j-dermatol","kind":"paper","name":"Long-term safety and efficacy of bimatoprost solution 0·03% application to the eyelid margin for the treatment of idiopathic and chemotherapy-induced eyelash hypotrichosis: a randomized controlled trial","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 25296533 and published in The British journal of dermatology; the citing page links this DOI, which is how the record was matched.","summary":"Background: Bimatoprost ophthalmic solution 0·03% is approved in several countries for the treatment of eyelash hypotrichosis. Previous trials were limited to 4 months of treatment and primarily idiopathic hypotrichosis.\n\nObjectives: To evaluate the long-term safety and efficacy of bimatoprost in patients with idiopathic or chemotherapy-induced hypotrichosis.\n\nMethods: This multicentre, double-masked, randomized, parallel-group study included two 6-month treatment periods [treatment period 1 (TP1) and treatment period 2 (TP2)]. Patients with idiopathic hypotrichosis were randomized to three treatment groups: (i) bimatoprost (TP1 and TP2); (ii) bimatoprost (TP1) and vehicle (TP2); and (iii) vehicle (TP1) and bimatoprost (TP2). Patients with chemotherapy-induced hypotrichosis were randomized to two treatment groups: (i) bimatoprost or vehicle (TP1) and (ii) bimatoprost (TP2). Primary end point was a composite of at least a one-grade improvement in investigator-assessed Global Eyelash Assessment and at least a three-point improvement in patient-reported Eyelash Satisfaction Questionnaire Domain 2 at month 4. Secondary measures included digitally assessed eyelash characteristics.\n\nResults: The primary efficacy end point was met in both populations (idiopathic responder rate was 40·2% for bimatoprost vs. 6·8% for vehicle; postchemotherapy responder rate was 37·5% for bimatoprost vs. 18·2% for vehicle). Efficacy by month 6 was maintained (idiopathic) or enhanced (postchemotherapy) at 12 months. Treatment effects were maintained for approximately 2 months but markedly diminished 4-6 months following treatment cessation in patients with idiopathic hypotrichosis. No drug-related serious adverse events were reported.\n\nConclusions: Daily treatment with bimatoprost ophthalmic solution 0·03% for 1 year was effective and well tolerated in patients with idiopathic and chemotherapy-induced hypotrichosis.\n\nIndexed on Europe PMC as PubMed record 25296533 (DOI 10.1111/bjd.13443). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Br J Dermatol 2015","url":"https://doi.org/10.1111/bjd.13443"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25296533/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25296533"}],"tags":["europepmc-ingest"],"related":["bimatoprost-eyelash-regrowth"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The British journal of dermatology","year":2015,"doi":"10.1111/bjd.13443","pmid":"25296533","authors":"Glaser DA, Hossain P, Perkins W, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-erivance-bmc-cancer-2017-update","kind":"paper","name":"Long-term safety and efficacy of vismodegib in patients with advanced basal cell carcinoma: final update of the pivotal ERIVANCE BCC study","aka":[],"tldr":"Later report from the ERIVANCE BCC trial registered as NCT00833417, in BMC cancer (2017); its title describes an updated or longer-term analysis.","summary":"Background: In the primary analysis of the ERIVANCE BCC trial, vismodegib, the first US Food and Drug Administration-approved Hedgehog pathway inhibitor, showed objective response rates (ORRs) by independent review facility (IRF) of 30% and 43% in metastatic basal cell carcinoma (mBCC) and locally advanced BCC (laBCC), respectively. ORRs by investigator review were 45% (mBCC) and 60% (laBCC). Herein, we present long-term safety and final investigator-assessed efficacy results in patients with mBCC or laBCC.\n\nMethods: One hundred four patients with measurable advanced BCC received oral vismodegib 150 mg once daily until disease progression or intolerable toxicity. The primary end point was IRF-assessed ORR. Secondary end points included ORR, duration of response (DOR), progression-free survival, overall survival (OS), and safety.\n\nResults: At data cutoff (39 months after completion of accrual), 8 patients were receiving the study drug (69 patients in survival follow-up). Investigator-assessed ORR was 48.5% in the mBCC group (all partial responses) and 60.3% in the laBCC group (20 patients had complete response and 18 patients had partial response). ORRs were comparable across patient subgroups, including aggressive histologic subtypes (eg, infiltrative BCC). Median DOR was 14.8 months (mBCC) and 26.2 months (laBCC). Median OS was 33.4 months in the mBCC cohort and not estimable in the laBCC cohort. Adverse events remained consistent with clinical experience. Thirty-three deaths (31.7%) were reported; none were related to vismodegib.\n\nConclusions: This long-term update of the ERIVANCE BCC trial demonstrated durability of response, efficacy across patient subgroups, and manageable long-term safety of vismodegib in patients with advanced BCC.\n\nTrial registration: This study was registered prospectively with Clinicaltrials.gov, number NCT00833417 on January 30, 2009.\n\nIndexed on Europe PMC as PubMed record 28511673 (DOI 10.1186/s12885-017-3286-5). Its abstract cites the registry id NCT00833417, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"BMC Cancer 2017","url":"https://doi.org/10.1186/s12885-017-3286-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28511673/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28511673"},{"label":"ClinicalTrials.gov NCT00833417","url":"https://clinicaltrials.gov/study/NCT00833417"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["erivance"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["bmc-cancer"],"dependsOn":[],"notes":[],"journal":"BMC cancer","year":2017,"doi":"10.1186/s12885-017-3286-5","pmid":"28511673","authors":"Sekulic A, Migden MR, Basset-Seguin N, et al.","paperType":"observational","findings":[],"whatItMeans":"A second publication from the ERIVANCE BCC trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-andricovich-kdm6a-squamous-pancreatic-cancer-cell-2018","kind":"paper","name":"Loss of KDM6A activates super-enhancers to induce gender-specific squamous-like pancreatic cancer and confers sensitivity to BET inhibitors","aka":[],"tldr":"In mice, losing the KDM6A gene turned pancreatic tumours squamous and metastatic, especially in females, by switching on growth regulators including MYC, and a drug class that blocks BET proteins reversed the change.","summary":"KDM6A, an X chromosome-encoded histone demethylase of the COMPASS-like complex, is frequently mutated across cancers. KDM6A loss induced squamous-like, metastatic pancreatic cancer selectively in females through deregulation of the COMPASS-like complex and aberrant activation of super-enhancers regulating delta-Np63, MYC and RUNX3. Tumours of this type in males had concomitant loss of UTY and KDM6A, pointing to demethylase-independent suppressor functions. KDM6A-deficient pancreatic cancer was selectively sensitive to BET inhibitors, which reversed squamous differentiation and restrained tumour growth in vivo.","asOf":"2026-09-24","links":[{"label":"Andricovich et al., Cancer Cell 2018: KDM6A loss induces squamous-like pancreatic cancer","url":"https://doi.org/10.1016/j.ccell.2018.02.003"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29533787/"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":["kdm6a","myc-gene"],"drugs":[],"companies":[],"institutions":[],"pathways":["epigenetic-reprogramming","myc"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-cell"],"dependsOn":[],"notes":[],"journal":"Cancer Cell","year":2018,"doi":"10.1016/j.ccell.2018.02.003","pmid":"29533787","authors":"Andricovich J, Perkail S, Kai Y, et al.","paperType":"basic","findings":["KDM6A loss drives squamous-like, metastatic tumours via super-enhancers at delta-Np63, MYC and RUNX3.","KDM6A-deficient tumours are selectively sensitive to BET inhibitors in vivo."],"whatItMeans":"It gives the 3 to 4% of KDM6A-mutant, squamous-programme tumours a mechanism and a candidate drug class.","caveats":["Mouse and cell-line evidence only.","No clinical BET inhibitor trial in KDM6A-mutant pancreatic cancer has reported."],"changedPractice":false},{"id":"paper-patil-lancet-glob-health","kind":"paper","name":"Low-cost oral metronomic chemotherapy versus intravenous cisplatin in patients with recurrent, metastatic, inoperable head and neck carcinoma: an open-label, parallel-group, non-inferiority, randomised, phase 3 trial","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 32827483 and published in The Lancet Global Health; the citing page links this DOI, which is how the record was matched.","summary":"Background: Regimens for palliation in patients with head and neck cancer recommended by the US National Comprehensive Cancer Network (NCCN) have low applicability (less than 1-3%) in low-income and middle-income countries (LMICs) because of their cost. In a previous phase 2 study, patients with head and neck cancer who received metronomic chemotherapy had better outcomes when compared with those who received intravenous cisplatin, which is commonly used as the standard of care in LMICs. We aimed to do a phase 3 study to substantiate these findings.\n\nMethods: We did an open-label, parallel-group, non-inferiority, randomised, phase 3 trial at the Department of Medical Oncology, Tata Memorial Center, Homi Bhabha National Institute, Mumbai, India. We enrolled adult patients (aged 18-70 years) who planned to receive palliative systemic treatment for relapsed, recurrent, or newly diagnosed squamous cell carcinoma of the head and neck, and who had an Eastern Cooperative Oncology Group performance status score of 0-1 and measurable disease, as defined by the Response Evaluation Criteria In Solid Tumors. We randomly assigned (1:1) participants to receive either oral metronomic chemotherapy, consisting of 15 mg/m 2 methotrexate once per week plus 200 mg celecoxib twice per day until disease progression or until the development of intolerable side-effects, or 75 mg/m 2 intravenous cisplatin once every 3 weeks for six cycles. Randomisation was done by use of a computer-generated randomisation sequence, with a block size of four, and patients were stratified by primary tumour site and previous cancer-directed treatment. The primary endpoint was median overall survival. Assuming that 6-month overall survival in the intravenous cisplatin group would be 40%, a non-inferiority margin of 13% was defined. Both intention-to-treat and per-protocol analyses were done. All patients who completed at least one cycle of the assigned treatment were included in the safety analysis. This trial is registered with the Clinical Trials Registry-India, CTRI/2015/11/006388, and is completed.\n\nFindings: Between May 16, 2016, and Jan 17, 2020, 422 patients were randomly assigned: 213 to the oral metronomic chemotherapy group and 209 to the intravenous cisplatin group. All 422 patients were included in the intention-to-treat analysis, and 418 patients (211 in the oral metronomic chemotherapy group and 207 in the intravenous cisplatin group) were included in the per-protocol analysis. At a median follow-up of 15·73 months, median overall survival in the intention-to-treat analysis population was 7·5 months (IQR 4·6-12·6) in the oral metronomic chemotherapy group compared with 6·1 months (3·2-9·6) in the intravenous cisplatin group (unadjusted HR for death 0·773 [95% CI 0·615-0·97, p=0·026]). In the per-protocol analysis population, median overall survival was 7·5 months (4·7-12·8) in the oral metronomic chemotherapy group and 6·1 months (3·4-9·6) in the intravenous cisplatin group (unadjusted HR for death 0·775 [95% CI 0·616-0·974, p=0·029]). Grade 3 or higher adverse events were observed in 37 (19%) of 196 patients in the oral metronomic chemotherapy group versus 61 (30%) of 202 patients in the intravenous cisplatin group (p=0·01).\n\nInterpretation: Oral metronomic chemotherapy is non-inferior to intravenous cisplatin with respect to overall survival in head and neck cancer in the palliative setting, and is associated with fewer adverse events. It therefore represents a new alternative standard of care if current NCCN-approved options for palliative therapy are not feasible.\n\nFunding: Tata Memorial Center Research Administration Council.\n\nTranslations: For the Hindi, Marathi, Gujarati, Kannada, Malayalam, Telugu, Oriya, Bengali, and Punjabi translations of the abstract see Supplementary Materials section.\n\nIndexed on Europe PMC as PubMed record 32827483 (DOI 10.1016/s2214-109x(20)30275-8). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Glob Health 2020","url":"https://doi.org/10.1016/s2214-109x(20)30275-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32827483/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32827483"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["metronomic-vs-cisplatin-tmh"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-global-health"],"dependsOn":[],"notes":[],"journal":"The Lancet Global Health","year":2020,"doi":"10.1016/s2214-109x(20)30275-8","pmid":"32827483","authors":"Patil V, Noronha V, Dhumal SB, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-alascca-n-engl-j-med-2025","kind":"paper","name":"Low-Dose Aspirin for PI3K-Altered Localized Colorectal Cancer","aka":[],"tldr":"Published report from the ALASCCA trial registered as NCT02647099, in New England Journal of Medicine (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Aspirin reduces the incidence of colorectal adenoma and colorectal cancer among high-risk persons. Observational studies suggest that aspirin may also improve disease-free survival after diagnosis, particularly among patients with tumors harboring somatic PIK3CA mutations. However, data from randomized trials are lacking.\n\nMethods: We conducted a double-blind, randomized, placebo-controlled trial involving patients with stage I, II, or III rectal cancer or stage II or III colon cancer with somatic alterations in PI3K pathway genes. The patients were assigned in a 1:1 ratio to receive 160 mg of aspirin or matched placebo once daily for 3 years. Patients with prespecified PIK3CA hotspot mutations in exon 9 or 20 (group A alterations) and those with other moderate- or high-impact somatic variants in PIK3CA, PIK3R1, or PTEN (group B alterations) were eligible for randomization. The primary end point was colorectal cancer recurrence, assessed in a time-to-event analysis, in patients with group A alterations. Secondary end points included colorectal cancer recurrence in patients with group B alterations, disease-free survival, and safety.\n\nResults: Alterations in PI3K pathway genes were detected in 1103 of 2980 patients (37.0%) with complete genomic data. Of 515 patients with group A alterations and 588 patients with group B alterations, 314 and 312, respectively, were assigned to receive aspirin or placebo. The estimated 3-year cumulative incidence of recurrence was 7.7% with aspirin and 14.1% with placebo (hazard ratio, 0.49; 95% confidence interval [CI], 0.24 to 0.98; P = 0.04) among patients with group A alterations and 7.7% and 16.8%, respectively (hazard ratio, 0.42; 95% CI, 0.21 to 0.83), among those with group B alterations. The estimated 3-year disease-free survival was 88.5% with aspirin and 81.4% with placebo (hazard ratio, 0.61; 95% CI, 0.34 to 1.08) among patients with group A alterations and 89.1% and 78.7%, respectively (hazard ratio, 0.51; 95% CI, 0.29 to 0.88), among those with group B alterations. Severe adverse events occurred in 16.8% of aspirin recipients and 11.6% of placebo recipients.\n\nConclusions: Aspirin led to a significantly lower incidence of colorectal cancer recurrence than placebo among patients with PIK3CA hotspot mutations in exon 9 or 20 and appeared to have a similar benefit among those with other somatic alterations in PI3K pathway genes. (Funded by the Swedish Research Council and others; ALASCCA ClinicalTrials.gov number, NCT02647099; EudraCT number, 2015-004240-19.).\n\nIndexed on Europe PMC as PubMed record 40961426 (DOI 10.1056/nejmoa2504650). Its abstract cites the registry id NCT02647099, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2025","url":"https://doi.org/10.1056/nejmoa2504650"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40961426/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40961426"},{"label":"ClinicalTrials.gov NCT02647099","url":"https://clinicaltrials.gov/study/NCT02647099"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["alascca"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2025,"doi":"10.1056/nejmoa2504650","pmid":"40961426","authors":"Martling A, Hed Myrberg I, Nilbert M, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02647099 with the most citations, so it is the natural first reading for anyone following the ALASCCA trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-patil-low-dose-nivolumab-jco-2023","kind":"paper","name":"Low-dose immunotherapy in head and neck cancer: a randomised study (Tata Memorial)","aka":[],"tldr":"Giving about one-twentieth of the standard dose of nivolumab alongside cheap oral chemotherapy nearly tripled one-year survival in advanced head and neck cancer, showing that immunotherapy can be made affordable without losing its effect.","summary":"Open-label phase 3 randomising 151 patients with advanced head and neck squamous cell carcinoma being treated with palliative intent to triple oral metronomic chemotherapy with or without nivolumab 20 mg flat every 3 weeks. One-year overall survival was 43.4% (95% CI 30.8-55.3) with nivolumab versus 16.3% (8.0-27.4) without; median overall survival 10.1 versus 6.7 months (hazard ratio 0.545; 95% CI 0.362-0.820; P=0.0036); grade 3 or worse adverse events 46.1% versus 50%.\n\nThe dose is roughly 6% of the approved flat dose and the drug cost correspondingly small. The trial has become the reference case for dose-optimisation in immuno-oncology and for pragmatic trials in low- and middle-income countries.","asOf":"2026-09-10","links":[{"label":"JCO 2023","url":"https://doi.org/10.1200/JCO.22.01015"}],"tags":[],"related":[],"cancers":["head-and-neck"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["nivolumab"],"companies":[],"institutions":["tata-memorial"],"pathways":[],"terms":[],"trials":["low-dose-nivolumab-tmh"],"people":["patil-vijay","prabhash-kumar","noronha-vanita"],"bottlenecks":["b-dose-optimisation","b-drug-pricing"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2023,"doi":"10.1200/JCO.22.01015","authors":"Patil VM, Noronha V, Menon N, et al.","paperType":"rct","findings":["One-year overall survival 43.4% with low-dose nivolumab versus 16.3% without.","Median overall survival 10.1 versus 6.7 months; hazard ratio 0.545 (95% CI 0.362-0.820).","No increase in grade 3 or worse adverse events (46.1% versus 50%).","Nivolumab dose was a flat 20 mg every 3 weeks, a small fraction of the licensed dose."],"whatItMeans":"For the majority of the world's head and neck cancer patients who cannot afford full-dose checkpoint inhibitors, a low dose added to oral metronomic chemotherapy is a tested alternative that improves survival. It also challenges the assumption that approved doses are the necessary doses: pharmacology had long suggested receptor saturation at far lower exposures.","caveats":["Single-centre and open-label; the comparator was metronomic chemotherapy rather than the standard-dose immunotherapy used in high-income settings.","Whether low-dose nivolumab matches full-dose nivolumab head to head is untested.","Patients were mostly tobacco-related, HPV-negative oral cancers, so applicability to oropharyngeal HPV-positive disease is unknown."],"changedPractice":true,"participants":151},{"id":"paper-hughes-n-engl-j-med","kind":"paper","name":"Lumpectomy plus tamoxifen with or without irradiation in women 70 years of age or older with early breast cancer","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 15342805 and published in New England Journal of Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Background: In women 70 years of age or older who have early breast cancer, it is unclear whether lumpectomy plus tamoxifen is as effective as lumpectomy followed by tamoxifen plus radiation therapy.\n\nMethods: Between July 1994 and February 1999, we randomly assigned 636 women who were 70 years of age or older and who had clinical stage I (T1N0M0 according to the tumor-node-metastasis classification), estrogen-receptor-positive breast carcinoma treated by lumpectomy to receive tamoxifen plus radiation therapy (317 women) or tamoxifen alone (319 women). Primary end points were the time to local or regional recurrence, the frequency of mastectomy for recurrence, breast-cancer-specific survival, the time to distant metastasis, and overall survival.\n\nResults: The only significant difference between the two groups was in the rate of local or regional recurrence at five years (1 percent in the group given tamoxifen plus irradiation and 4 percent in the group given tamoxifen alone, P<0.001). There were no significant differences between the two groups with regard to the rates of mastectomy for local recurrence, distant metastases, or five-year rates of overall survival (87 percent in the group given tamoxifen plus irradiation and 86 percent in the tamoxifen group, P=0.94). Assessment by physicians and patients of cosmetic results and adverse events uniformly rated tamoxifen plus irradiation inferior to tamoxifen alone.\n\nConclusions: Lumpectomy plus adjuvant therapy with tamoxifen alone is a realistic choice for the treatment of women 70 years of age or older who have early, estrogen-receptor-positive breast cancer.\n\nIndexed on Europe PMC as PubMed record 15342805 (DOI 10.1056/nejmoa040587). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2004","url":"https://doi.org/10.1056/nejmoa040587"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/15342805/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/15342805"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["calgb-9343"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2004,"doi":"10.1056/nejmoa040587","pmid":"15342805","authors":"Hughes KS, Schnaper LA, Berry D, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-hughes-j-clin-oncol","kind":"paper","name":"Lumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: long-term follow-up of CALGB 9343","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 23690420 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: To determine whether there is a benefit to adjuvant radiation therapy after breast-conserving surgery and tamoxifen in women age ≥ 70 years with early-stage breast cancer.\n\nPatients and methods: Between July 1994 and February 1999, 636 women (age ≥ 70 years) who had clinical stage I (T1N0M0 according to TNM classification) estrogen receptor (ER) -positive breast carcinoma treated by lumpectomy were randomly assigned to receive tamoxifen plus radiation therapy (TamRT; 317 women) or tamoxifen alone (Tam; 319 women). Primary end points were time to local or regional recurrence, frequency of mastectomy, breast cancer-specific survival, time to distant metastasis, and overall survival (OS).\n\nResults: Median follow-up for treated patients is now 12.6 years. At 10 years, 98% of patients receiving TamRT (95% CI, 96% to 99%) compared with 90% of those receiving Tam (95% CI, 85% to 93%) were free from local and regional recurrences. There were no significant differences in time to mastectomy, time to distant metastasis, breast cancer-specific survival, or OS between the two groups. Ten-year OS was 67% (95% CI, 62% to 72%) and 66% (95% CI, 61% to 71%) in the TamRT and Tam groups, respectively.\n\nConclusion: With long-term follow-up, the previously observed small improvement in locoregional recurrence with the addition of radiation therapy remains. However, this does not translate into an advantage in OS, distant disease-free survival, or breast preservation. Depending on the value placed on local recurrence, Tam remains a reasonable option for women age ≥ 70 years with ER-positive early-stage breast cancer.\n\nIndexed on Europe PMC as PubMed record 23690420 (DOI 10.1200/jco.2012.45.2615). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2013","url":"https://doi.org/10.1200/jco.2012.45.2615"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23690420/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/23690420"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["calgb-9343"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2013,"doi":"10.1200/jco.2012.45.2615","pmid":"23690420","authors":"Hughes KS, Schnaper LA, Bellon JR, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-hill-lung-adenocarcinoma-air-pollutants-nature-2023","kind":"paper","name":"Lung adenocarcinoma promotion by air pollutants","aka":[],"tldr":"Healthy lungs already carry cancer-causing mutations. This study argues that fine particles in polluted air do not create the mutation but wake it up, which is why lung cancer happens in people who never smoked.","summary":"Hill, Lim, Weeden and colleagues from the TRACERx consortium and the Francis Crick Institute, with Swanton as senior author, proposed that particulate matter of 2.5 micrometres or less promotes lung cancer by acting on cells that already carry oncogenic mutations in otherwise healthy lung tissue, rather than by causing those mutations.\n\nThe paper combines epidemiology across four within-country cohorts, functional mouse models and ultradeep sequencing of histologically normal lung. It revives the two-step initiation-and-promotion model of tumorigenesis proposed more than seventy years earlier, and gives it a molecular mechanism: an influx of macrophages, release of interleukin-1 beta and a progenitor-like state in EGFR-mutant alveolar type II cells.","asOf":"2026-09-25","links":[{"label":"Nature 2023","url":"https://doi.org/10.1038/s41586-023-05874-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37020004/"}],"tags":["lung-evidence"],"related":["paper-zhang-lung-cancer-never-smokers-nat-genet-2021","paper-tracerx-100-nejm-2017","idea-prev-clean-air-never-smoker-endpoints"],"cancers":["lung-cancer","nsclc","lung-adenocarcinoma"],"sections":["prevention","early-detection"],"technologies":[],"targets":["egfr","kras"],"drugs":[],"companies":[],"institutions":["francis-crick"],"pathways":[],"terms":["driver-mutation"],"trials":[],"people":["charles-swanton"],"bottlenecks":["b-prevention-adoption","b-early-detection","b-tme-immunosuppression"],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2023,"doi":"10.1038/s41586-023-05874-3","pmid":"37020004","authors":"Hill W, Lim EL, Weeden CE, et al.","paperType":"translational","findings":["A significant association between PM2.5 levels and the incidence of lung cancer across 32,957 EGFR-driven lung cancer cases in four within-country cohorts.","Air pollutants caused an influx of macrophages into the lung and release of interleukin-1 beta in mouse models, producing a progenitor-like state in EGFR-mutant alveolar type II epithelial cells.","Ultradeep mutational profiling of histologically normal lung from 295 individuals across 3 clinical cohorts found oncogenic EGFR driver mutations in 18 percent and KRAS driver mutations in 53 percent of healthy tissue samples."],"whatItMeans":"It reframes air quality as cancer policy rather than respiratory policy, and it explains the shape of lung cancer in never-smokers: the mutations are common and mostly silent, and what differs is whether something inflames the tissue enough to let one of them grow.","caveats":["The epidemiological association is observational; the causal chain is demonstrated in mice, not in people.","Interleukin-1 beta blockade has not been tested prospectively as lung cancer prevention in a population exposed to particulates.","Most lung cancer in never-smokers worldwide is not explained by PM2.5 alone; radon, secondhand smoke and cooking fuel exposure sit alongside it."],"changedPractice":false},{"id":"paper-lace-adjuvant-cisplatin-pooled-analysis-jco-2008","kind":"paper","name":"Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group","aka":[],"tldr":"Pooling 4,584 patients from the five big trials of chemotherapy after lung cancer surgery gave a clear answer: it helps, by about 5 percent at five years, and the benefit is in stage II and III rather than stage IA.","summary":"Pignon, Tribodet, Scagliotti, Douillard, Shepherd and colleagues pooled individual patient data from the five largest trials of cisplatin-based chemotherapy after complete resection conducted after the 1995 meta-analysis: 4,584 patients, median follow-up 5.2 years.\n\nThe stage gradient is the operational result. Chemotherapy after surgery is worth giving in stage II and III disease, is marginal in stage IB and looks actively harmful in stage IA, and no drug partner, patient sex, age, histology or type of surgery changed that. It is the evidence base that adjuvant targeted therapy (ADAURA, ALINA) and adjuvant immunotherapy (IMpower010) were later added to.","asOf":"2026-09-25","links":[{"label":"J Clin Oncol 2008","url":"https://doi.org/10.1200/JCO.2007.13.9030"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/18506026/"}],"tags":["lung-evidence"],"related":["paper-nsclc-collaborative-group-chemotherapy-meta-analysis-bmj-1995","paper-adaura-nejm-2020","paper-wu-alina-adjuvant-alectinib-nejm-2024","paper-felip-impower010-adjuvant-atezolizumab-lancet-2021"],"cancers":["lung-cancer","nsclc","resectable-nsclc"],"sections":["surgery"],"technologies":["radiotherapy"],"targets":[],"drugs":["cisplatin","vinorelbine","etoposide"],"companies":[],"institutions":[],"pathways":[],"terms":["neoadjuvant-adjuvant","performance-status"],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-dormancy-mrd"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2008,"doi":"10.1200/JCO.2007.13.9030","pmid":"18506026","authors":"Pignon JP, Tribodet H, Scagliotti GV, et al.","paperType":"meta-analysis","findings":["Overall hazard ratio of death 0.89 (95 percent confidence interval 0.82 to 0.96; P equals 0.005), a five-year absolute benefit of 5.4 percent.","Benefit varied with stage (test for trend P equals 0.04): stage IA hazard ratio 1.40 (0.95 to 2.06), stage IB 0.93 (0.78 to 1.10), stage II 0.83 (0.73 to 0.95), stage III 0.83 (0.72 to 0.94).","No significant interaction with the drug given alongside cisplatin: vinorelbine 0.80 (0.70 to 0.91), etoposide or vinca alkaloid 0.92 (0.80 to 1.07), other 0.97 (0.84 to 1.13).","Chemotherapy effect was higher in patients with better performance status.","No interaction with sex, age, histology, type of surgery, planned radiotherapy or planned total cisplatin dose.","No heterogeneity of chemotherapy effect between the five trials."],"whatItMeans":"The rule that a patient with a resected stage II or III lung cancer is offered chemotherapy and a patient with a small stage I tumour is not. Everything added to adjuvant treatment since has had to beat, or be added to, this 5 percent.","caveats":["Trials from the 1990s and early 2000s with the staging of that era; stage migration since means the groups are not exactly today's groups.","Stage IA looked worse with chemotherapy, but the confidence interval crosses one and the number of patients is small.","Pooled trial populations are fitter than the resected population as a whole; performance status modified the effect."],"changedPractice":true,"participants":4584},{"id":"paper-herbst-clin-cancer-res","kind":"paper","name":"Lung Master Protocol (Lung-MAP)-A Biomarker-Driven Protocol for Accelerating Development of Therapies for Squamous Cell Lung Cancer: SWOG S1400","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 25680375 and published in Clinical Cancer Research; the citing page links this DOI, which is how the record was matched.","summary":"The Lung Master Protocol (Lung-MAP, S1400) is a groundbreaking clinical trial designed to advance the efficient development of targeted therapies for squamous cell carcinoma (SCC) of the lung. There are no approved targeted therapies specific to advanced lung SCC, although The Cancer Genome Atlas project and similar studies have detected a significant number of somatic gene mutations/amplifications in lung SCC, some of which are targetable by investigational agents. However, the frequency of these changes is low (5%-20%), making recruitment and study conduct challenging in the traditional clinical trial setting. Here, we describe our approach to development of a biomarker-driven phase II/II multisubstudy \"Master Protocol,\" using a common platform (next-generation DNA sequencing) to identify actionable molecular abnormalities, followed by randomization to the relevant targeted therapy versus standard of care.\n\nIndexed on Europe PMC as PubMed record 25680375 (DOI 10.1158/1078-0432.ccr-13-3473). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Clin Cancer Res 2015","url":"https://doi.org/10.1158/1078-0432.ccr-13-3473"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25680375/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25680375"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["lung-map"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2015,"doi":"10.1158/1078-0432.ccr-13-3473","pmid":"25680375","authors":"Herbst RS, Gandara DR, Hirsch FR, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-kozono-j-thorac-oncol","kind":"paper","name":"Lung-MAP Next-Generation Sequencing Analysis of Advanced Squamous Cell Lung Cancers (SWOG S1400)","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 39111731 and published in Journal of Thoracic Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Introduction: Squamous cell cancer (SqCC) is a lung cancer subtype with few targeted therapy options. Molecular characterization, that is, by next-generation sequencing (NGS), is needed to identify potential targets. Lung Cancer Master Protocol Southwest Oncology Group S1400 enrolled patients with previously treated stage IV or recurrent SqCC to assess NGS biomarkers for therapeutic sub-studies.\n\nMethods: Tumors underwent NGS using Foundation Medicine's FoundationOne research platform, which sequenced the exons and/or introns of 313 cancer-related genes. Mutually exclusive gene set analysis and Selected Events Linked by Evolutionary Conditions across Human Tumors were performed to identify mutually exclusive and co-occurring gene alterations. Comparisons were performed with data on 495 lung SqCC downloaded from The Cancer Genome Atlas. Cox proportional hazards models were used to assess associations between genetic variants and survival.\n\nResults: NGS data are reported for 1672 patients enrolled on S1400 between 2014 and 2019. Mutually exclusive gene set analysis identified two non-overlapping sets of mutually exclusive alterations with a false discovery rate of less than 15%: NFE2L2, KEAP1, and PARP4; and CDKN2A and RB1. PARP4, a relatively uncharacterized gene, showed three frequent mutations suggesting functional significance: 3116T>C (I1039T), 3176A>G (Q1059R), and 3509C>T (T1170I). When taken together, NFE2L2 and KEAP1 alterations were associated with poorer survival.\n\nConclusions: As the largest dataset to date of lung SqCC profiled on a clinical trial, the S1400 NGS dataset establishes a rich resource for biomarker discovery. Mutual exclusivity of PARP4 and NFE2L2 or KEAP1 alterations suggests that PARP4 may have an uncharacterized role in a key pathway known to impact oxidative stress response and treatment resistance.\n\nIndexed on Europe PMC as PubMed record 39111731 (DOI 10.1016/j.jtho.2024.07.024). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Thorac Oncol 2024","url":"https://doi.org/10.1016/j.jtho.2024.07.024"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39111731/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39111731"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["lung-map"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-thoracic-oncology"],"dependsOn":[],"notes":[],"journal":"Journal of Thoracic Oncology","year":2024,"doi":"10.1016/j.jtho.2024.07.024","pmid":"39111731","authors":"Kozono D, Hua X, Wu MC, et al.","paperType":"observational","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-amer-zeidan-n-engl-j-med-2020","kind":"paper","name":"Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes","aka":[],"tldr":"Paper by Amer M. Zeidan indexed on Europe PMC as PubMed record 31914241, in New England Journal of Medicine (2020), one of the most cited records naming an author with this name at Yale Cancer Center / Smilow Cancer Hospital.","summary":"Background: Patients with anemia and lower-risk myelodysplastic syndromes in whom erythropoiesis-stimulating agent therapy is not effective generally become dependent on red-cell transfusions. Luspatercept, a recombinant fusion protein that binds transforming growth factor β superfamily ligands to reduce SMAD2 and SMAD3 signaling, showed promising results in a phase 2 study.\n\nMethods: In a double-blind, placebo-controlled, phase 3 trial, we randomly assigned patients with very-low-risk, low-risk, or intermediate-risk myelodysplastic syndromes (defined according to the Revised International Prognostic Scoring System) with ring sideroblasts who had been receiving regular red-cell transfusions to receive either luspatercept (at a dose of 1.0 up to 1.75 mg per kilogram of body weight) or placebo, administered subcutaneously every 3 weeks. The primary end point was transfusion independence for 8 weeks or longer during weeks 1 through 24, and the key secondary end point was transfusion independence for 12 weeks or longer, assessed during both weeks 1 through 24 and weeks 1 through 48.\n\nResults: Of the 229 patients enrolled, 153 were randomly assigned to receive luspatercept and 76 to receive placebo; the baseline characteristics of the patients were balanced. Transfusion independence for 8 weeks or longer was observed in 38% of the patients in the luspatercept group, as compared with 13% of those in the placebo group (P<0.001). A higher percentage of patients in the luspatercept group than in the placebo group met the key secondary end point (28% vs. 8% for weeks 1 through 24, and 33% vs. 12% for weeks 1 through 48; P<0.001 for both comparisons). The most common luspatercept-associated adverse events (of any grade) included fatigue, diarrhea, asthenia, nausea, and dizziness. The incidence of adverse events decreased over time.\n\nConclusions: Luspatercept reduced the severity of anemia in patients with lower-risk myelodysplastic syndromes with ring sideroblasts who had been receiving regular red-cell transfusions and who had disease that was refractory to or unlikely to respond to erythropoiesis-stimulating agents or who had discontinued such agents owing to an adverse event. (Funded by Celgene and Acceleron Pharma; MEDALIST ClinicalTrials.gov number, NCT02631070; EudraCT number, 2015-003454-41.).\n\nIndexed on Europe PMC as PubMed record 31914241 (DOI 10.1056/nejmoa1908892). Its author list gives \"Zeidan AM\" with the affiliation \"From Service d'Hématologie Séniors, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris and Université Paris 7, Paris (P.F., L.A.), Service des Maladies du Sang, Hôpital Huriez, Centre Hospitalier Universitaire (CHU) de Lille, Lille (B.Q.), the Department of Internal Medicine, CHU Toulouse, Institut Universitaire du Cancer de Toulouse, Toulouse (O.B.-R.), and Université Cote d'Azur, Département d'Hématologie Clinique, CHU Nice, Nice (T.C.) - all in France; Medical Clinic and Policlinic 1, Hematology and Cellular Therapy, Leipzig University Hospital, Leipzig (U.P.), Klinik für Hämatologie, Onkologie, and Klinische Immunologie, Universitätsklinik Düsseldorf, Düsseldorf (U.G.), and Klinik und Poliklinik für Innere Medizin III, Technische Universität München, Munich (K.S.G.) - all in Germany; the Department of Haemato-Oncology, King's College London, London (G.J.M.), Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford (P.V.), and the Department of Haematology, Leeds Teaching Hospitals NHS Trust, Leeds (D.B.) - all in the United Kingdom; the Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston (G.G.-M.); Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto (R.B.); MDS Unit, Azienda Ospedaliero Universitaria Careggi, University of Florence, Florence (V.S.), the Department of Oncology and Hematology, S. Orsola-Malpighi University Hospital, Bologna (C.F.), the University of Pavia, Fondazione IRCCS Policlinico S. Matteo, Pavia (M.C.), the Hematology Unit, Santi Antonio e Biagio e Cesare Arrigo Hospital, Alessandria (F.S., V.G.), and Dipartimento Biomedicina e Prevenzione, University of Rome Tor Vergata, Rome (M.-T.V.) - all in Italy; the Hematology Department, University Hospital of Salamanca, Institute of Biomedical Research of Salamanca, Salamanca (M.D.-C.), Unidad de Hematología, Hospital Universitario Virgen del Rocío, Seville (J.F.F.), and the Department of Hematology, Hospital Universitario Cruces, Vizcaya (B.A.) - all in Spain; the Department of Hematology Science, School of Medicine, Ankara University, Ankara, Turkey (O.I.); the Department of Hematology and Medical Oncology, Cleveland Clinic, Cleveland (M.A.S.); the Department of Hematology, Algemeen Ziekenhuis Sint-Jan, Bruges (D.S.), and Universitair Ziekenhuis Gent, Ghent (D.M.) - both in Belgium; the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (A.E.D.); the Division of Hematology-Oncology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center (J.G.J.), and Albert Einstein College of Medicine (A.V.) - both in New York; the Department of Hematology, University Medical Center of Groningen, University of Groningen, Groningen, the Netherlands (E.V.); Stanford University Cancer Center, Stanford, CA (P.L.G.); the Center for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Stockholm (E.H.-L.); the Department of Internal Medicine, Yale School of Medicine, Yale University, New Haven, CT (A.M.Z.); Vanderbilt University School of Medicine, Vanderbilt-Ingram Cancer Center, Nashville (M.R.S.); Celgene, Summit, NJ (A.L., J.Z., A.R., D.R.D.); Celgene International, Boudry, Switzerland (A.B.); Acceleron Pharma, Cambridge, MA (P.G.L., M.L.S.); and Moffitt Cancer Center, Tampa, FL (R.S.K., A.F.L.)\", which names Yale Cancer Center / Smilow Cancer Hospital; that is how the record was matched to Amer M. Zeidan, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2020","url":"https://doi.org/10.1056/nejmoa1908892"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31914241/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31914241"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["amer-zeidan"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2020,"doi":"10.1056/nejmoa1908892","pmid":"31914241","authors":"Fenaux P, Platzbecker U, Mufti GJ, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Amer M. Zeidan at Yale Cancer Center / Smilow Cancer Hospital, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-lutetium-177-dotatate-neuroendocrine-pract-radiat-oncol-2022","kind":"paper","name":"Lutetium-177 DOTATATE: A Practical Review","aka":[],"tldr":"Review on Lutetium-177 dotatate in Neuroendocrine tumours, in Practical radiation oncology (2022), one of the most cited Europe PMC records with Lutetium-177 dotatate in its title.","summary":"Neuroendocrine tumors (NETs) are a heterogeneous group of tumors that originate in endocrine tissues throughout the body. Though most are indolent, clinical outcomes vary greatly based on histologic differentiation and grade. Peptide receptor radionuclide therapy has emerged as a promising treatment for patients with locally advanced and/or metastatic disease refractory to standard of care treatment. The phase III NETTER-1 trial found that [ 177 Lu] Lu-DOTA-[Tyr 3 ]-octreotate improved disease-free survival versus octreotide alone for somatostatin receptor-positive gastroenteropancreatic NETs and had a favorable toxicity profile, leading to Food and Drug Administration approval. [ 177 Lu] Lu-DOTA-[Tyr 3 ]-octreotate is an important new treatment that expands the role of radiation in the treatment of NETs. Several important trials are ongoing to better elucidate the role of this treatment.\n\nIndexed on Europe PMC as PubMed record 35717045 (DOI 10.1016/j.prro.2022.02.002). Its title names Lutetium-177 dotatate and its text names Neuroendocrine tumours; PubMed types it as a review (Review). It was matched automatically to the idea \"Dosimetry-personalised PRRT instead of four fixed cycles\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Pract Radiat Oncol 2022","url":"https://doi.org/10.1016/j.prro.2022.02.002"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35717045/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35717045"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["practical-radiation-oncology"],"dependsOn":[],"notes":[],"journal":"Practical radiation oncology","year":2022,"doi":"10.1016/j.prro.2022.02.002","pmid":"35717045","authors":"Jia AY, Kashani R, Zaorsky NG, et al.","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for Lutetium-177 dotatate in Neuroendocrine tumours, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Lutetium-177 dotatate in the title and Neuroendocrine tumours in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-lutetium-177-vipivotide-tetrax-prostate-journal-2023","kind":"paper","name":"Lutetium-177 vipivotide tetraxetan for treating PSMA-positive hormone-relapsed metastatic prostate cancer after 2 or more treatments","aka":[],"tldr":"Review on Lutetium-177 vipivotide tetraxetan in Prostate cancer, in Journal not given (2023), one of the most cited Europe PMC records with Lutetium-177 vipivotide tetraxetan in its title.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 40209019. Its title names Lutetium-177 vipivotide tetraxetan and its text names Prostate cancer; PubMed types it as a review (Review). It was matched automatically to the idea \"Alpha-emitting PSMA therapy at first metastatic diagnosis\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40209019/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40209019"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal not given","year":2023,"pmid":"40209019","authors":"Authors not listed","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for Lutetium-177 vipivotide tetraxetan in Prostate cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Lutetium-177 vipivotide tetraxetan in the title and Prostate cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-pant-nat-med","kind":"paper","name":"Lymph-node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: the phase 1 AMPLIFY-201 trial","aka":[],"tldr":"Paper cited by one idea page, indexed on Europe PMC as PubMed record 38195752 and published in Nature Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Pancreatic and colorectal cancers are often KRAS mutated and are incurable when tumor DNA or protein persists or recurs after curative intent therapy. Cancer vaccine ELI-002 2P enhances lymph node delivery and immune response using amphiphile (Amph) modification of G12D and G12R mutant KRAS (mKRAS) peptides (Amph-Peptides-2P) together with CpG oligonucleotide adjuvant (Amph-CpG-7909). We treated 25 patients (20 pancreatic and five colorectal) who were positive for minimal residual mKRAS disease (ctDNA and/or serum tumor antigen) after locoregional treatment in a phase 1 study of fixed-dose Amph-Peptides-2P and ascending-dose Amph-CpG-7909; study enrollment is complete with patient follow-up ongoing. Primary endpoints included safety and recommended phase 2 dose (RP2D). The secondary endpoint was tumor biomarker response (longitudinal ctDNA or tumor antigen), with exploratory endpoints including immunogenicity and relapse-free survival (RFS). No dose-limiting toxicities were observed, and the RP2D was 10.0 mg of Amph-CpG-7909. Direct ex vivo mKRAS-specific T cell responses were observed in 21 of 25 patients (84%; 59% both CD4 + and CD8 +); tumor biomarker responses were observed in 21 of 25 patients (84%); biomarker clearance was observed in six of 25 patients (24%; three pancreatic and three colorectal); and the median RFS was 16.33 months. Efficacy correlated with T cell responses above or below the median fold increase over baseline (12.75-fold): median tumor biomarker reduction was -76.0% versus -10.2% (P < 0.0014), and the median RFS was not reached versus 4.01 months (hazard ratio = 0.14; P = 0.0167). ELI-002 2P was safe and induced considerable T cell responses in patients with immunotherapy-recalcitrant KRAS-mutated tumors. ClinicalTrials.gov identifier: NCT04853017.\n\nIndexed on Europe PMC as PubMed record 38195752 (DOI 10.1038/s41591-023-02760-3). Matched by DOI alone: one idea page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Med 2024","url":"https://doi.org/10.1038/s41591-023-02760-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38195752/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38195752"}],"tags":["europepmc-ingest"],"related":["idea-shared-kras-vaccine-adjuvant"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2024,"doi":"10.1038/s41591-023-02760-3","pmid":"38195752","authors":"Pant S, Wainberg ZA, Weekes CD, et al.","paperType":"observational","findings":[],"whatItMeans":"One idea page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-shelley-hwang-cancer-cell-2014","kind":"paper","name":"Macrophage IL-10 blocks CD8+ T cell-dependent responses to chemotherapy by suppressing IL-12 expression in intratumoral dendritic cells","aka":[],"tldr":"Paper by E. Shelley Hwang indexed on Europe PMC as PubMed record 25446896, in Cancer Cell (2014), one of the most cited records naming an author with this name at Duke Cancer Institute.","summary":"Blockade of colony-stimulating factor-1 (CSF-1) limits macrophage infiltration and improves response of mammary carcinomas to chemotherapy. Herein we identify interleukin (IL)-10 expression by macrophages as the critical mediator of this phenotype. Infiltrating macrophages were the primary source of IL-10 within tumors, and therapeutic blockade of IL-10 receptor (IL-10R) was equivalent to CSF-1 neutralization in enhancing primary tumor response to paclitaxel and carboplatin. Improved response to chemotherapy was CD8(+) T cell-dependent, but IL-10 did not directly suppress CD8(+) T cells or alter macrophage polarization. Instead, IL-10R blockade increased intratumoral dendritic cell expression of IL-12, which was necessary for improved outcomes. In human breast cancer, expression of IL12A and cytotoxic effector molecules were predictive of pathological complete response rates to paclitaxel.\n\nIndexed on Europe PMC as PubMed record 25446896 (DOI 10.1016/j.ccell.2014.09.006). Its author list gives \"Hwang ES\" with the affiliation \"Surgery Department, Duke University, Durham, NC 27708, USA\", which names Duke Cancer Institute; that is how the record was matched to E. Shelley Hwang, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer Cell 2014","url":"https://doi.org/10.1016/j.ccell.2014.09.006"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25446896/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25446896"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["shelley-hwang"],"bottlenecks":[],"keyPapers":[],"journals":["cancer-cell"],"dependsOn":[],"notes":[],"journal":"Cancer Cell","year":2014,"doi":"10.1016/j.ccell.2014.09.006","pmid":"25446896","authors":"Ruffell B, Chang-Strachan D, Chan V, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for E. Shelley Hwang at Duke Cancer Institute, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-denardo-nat-rev-immunol","kind":"paper","name":"Macrophages as regulators of tumour immunity and immunotherapy","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 30718830 and published in Nature reviews. Immunology; the citing page links this DOI, which is how the record was matched.","summary":"Macrophages are critical mediators of tissue homeostasis, with tumours distorting this proclivity to stimulate proliferation, angiogenesis and metastasis. This had led to an interest in targeting macrophages in cancer, and preclinical studies have demonstrated efficacy across therapeutic modalities and tumour types. Much of the observed efficacy can be traced to the suppressive capacity of macrophages, driven by microenvironmental cues such as hypoxia and fibrosis. As a result, tumour macrophages display an ability to suppress T cell recruitment and function as well as to regulate other aspects of tumour immunity. With the increasing impact of cancer immunotherapy, macrophage targeting is now being evaluated in this context. Here, we discuss the results of clinical trials and the future of combinatorial immunotherapy.\n\nIndexed on Europe PMC as PubMed record 30718830 (DOI 10.1038/s41577-019-0127-6). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Immunol 2019","url":"https://doi.org/10.1038/s41577-019-0127-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30718830/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30718830"}],"tags":["europepmc-ingest"],"related":["myeloid-suppression-axis"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature reviews. Immunology","year":2019,"doi":"10.1038/s41577-019-0127-6","pmid":"30718830","authors":"DeNardo DG, Ruffell B","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-kishan-jama-oncol","kind":"paper","name":"Magnetic Resonance Imaging-Guided vs Computed Tomography-Guided Stereotactic Body Radiotherapy for Prostate Cancer: The MIRAGE Randomized Clinical Trial","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 36633877 and published in JAMA Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Importance: Magnetic resonance imaging (MRI) guidance offers multiple theoretical advantages in the context of stereotactic body radiotherapy (SBRT) for prostate cancer. However, to our knowledge, these advantages have yet to be demonstrated in a randomized clinical trial.\n\nObjective: To determine whether aggressive margin reduction with MRI guidance significantly reduces acute grade 2 or greater genitourinary (GU) toxic effects after prostate SBRT compared with computed tomography (CT) guidance.\n\nDesign, setting, and participants: This phase 3 randomized clinical trial (MRI-Guided Stereotactic Body Radiotherapy for Prostate Cancer [MIRAGE]) enrolled men aged 18 years or older who were receiving SBRT for clinically localized prostate adenocarcinoma at a single center between May 5, 2020, and October 1, 2021. Data were analyzed from January 15, 2021, through May 15, 2022. All patients had 3 months or more of follow-up.\n\nInterventions: Patients were randomized 1:1 to SBRT with CT guidance (control arm) or MRI guidance. Planning margins of 4 mm (CT arm) and 2 mm (MRI arm) were used to deliver 40 Gy in 5 fractions.\n\nMain outcomes and measures: The primary end point was the incidence of acute (≤90 days after SBRT) grade 2 or greater GU toxic effects (using Common Terminology Criteria for Adverse Events, version 4.03 [CTCAE v4.03]). Secondary outcomes included CTCAE v4.03-based gastrointestinal toxic effects and International Prostate Symptom Score (IPSS)-based and Expanded Prostate Cancer Index Composite-26 (EPIC-26)-based outcomes.\n\nResults: Between May 2020 and October 2021, 156 patients were randomized: 77 to CT (median age, 71 years [IQR, 67-77 years]) and 79 to MRI (median age, 71 years [IQR, 68-75 years]). A prespecified interim futility analysis conducted after 100 patients reached 90 or more days after SBRT was performed October 1, 2021, with the sample size reestimated to 154 patients. Thus, the trial was closed to accrual early. The incidence of acute grade 2 or greater GU toxic effects was significantly lower with MRI vs CT guidance (24.4% [95% CI, 15.4%-35.4%] vs 43.4% [95% CI, 32.1%-55.3%]; P =.01), as was the incidence of acute grade 2 or greater gastrointestinal toxic effects (0.0% [95% CI, 0.0%-4.6%] vs 10.5% [95% CI, 4.7%-19.7%]; P =.003). Magnetic resonance imaging guidance was associated with a significantly smaller percentage of patients with a 15-point or greater increase in IPSS at 1 month (6.8% [5 of 72] vs 19.4% [14 of 74]; P =.01) and a significantly reduced percentage of patients with a clinically significant (≥12-point) decrease in EPIC-26 bowel scores (25.0% [17 of 68] vs 50.0% [34 of 68]; P =.001) at 1 month.\n\nConclusions and relevance: In this randomized clinical trial, compared with CT-guidance, MRI-guided SBRT significantly reduced both moderate acute physician-scored toxic effects and decrements in patient-reported quality of life. Longer-term follow-up will confirm whether these notable benefits persist.\n\nTrial registration: ClinicalTrials.gov Identifier: NCT04384770.\n\nIndexed on Europe PMC as PubMed record 36633877 (DOI 10.1001/jamaoncol.2022.6558). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA Oncol 2023","url":"https://doi.org/10.1001/jamaoncol.2022.6558"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36633877/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36633877"}],"tags":["europepmc-ingest"],"related":["mr-linac"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2023,"doi":"10.1001/jamaoncol.2022.6558","pmid":"36633877","authors":"Kishan AU, Ma TM, Lamb JM, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-magnetismm-3-elranatamab-natmed-2023","kind":"paper","name":"MagnetisMM-3: elranatamab, a second BCMA bispecific, with a switch to fortnightly dosing after response","aka":[],"tldr":"Elranatamab produced responses in 61% of heavily pretreated myeloma patients and showed that dosing can be thinned to every two weeks once patients respond.","summary":"MagnetisMM-3 was a phase 2 single-arm study of elranatamab, a subcutaneous BCMA x CD3 bispecific, in 123 patients with triple-class-exposed relapsed or refractory multiple myeloma who had not received prior BCMA-directed therapy (cohort A). After two step-up doses and weekly dosing, patients who had responded for at least six months moved to every-two-week dosing. The overall response rate was 61% with complete response or better in 35%; most responses were ongoing at a year. CRS occurred in about 58% of patients, all grade 1-2 with the priming regimen, and neurotoxicity in a small minority. Infections were the main serious toxicity. The FDA granted accelerated approval in 2023.","asOf":"2026-09-08","links":[{"label":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=MagnetisMM-3%20elranatamab%20Lesokhin%20Nature%20Medicine%202023"},{"label":"ClinicalTrials.gov NCT04649359","url":"https://clinicaltrials.gov/study/NCT04649359"}],"tags":[],"related":["paper-majestec-1-teclistamab-nejm-2022","bispecific-infection-prophylaxis"],"cancers":["multiple-myeloma"],"sections":[],"technologies":["bispecific-antibody","t-cell-engager"],"targets":["bcma","cd3","gprc5d"],"drugs":["elranatamab","teclistamab","talquetamab"],"companies":["pfizer"],"institutions":[],"pathways":[],"terms":["crs","orr"],"trials":["magnetismm-3","linker-mm1"],"people":[],"bottlenecks":["b-dose-optimisation","b-toxicity-qol"],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2023,"doi":"10.1038/s41591-023-02528-9","pmid":"37582952","authors":"Lesokhin AM, Tomasson MH, Arnulf B, et al.","paperType":"translational","findings":["123 BCMA-naive, triple-class-exposed patients (cohort A); median 5 prior lines.","Overall response 61%; complete response or better 35%.","Responses were durable, with most responders still in response at 12 months.","CRS in about 58%, all grade 1-2 after two step-up doses; ICANS uncommon.","Responders switched to every-two-week dosing after 6 months without loss of response in most cases."],"whatItMeans":"Elranatamab confirmed that BCMA bispecifics are a class, not a one-off, and its protocol-built dose reduction after response set a precedent for lowering the immunosuppressive burden of T-cell engagers. Patients now have two approved BCMA bispecifics and one against GPRC5D (talquetamab). Choosing between them, and sequencing them with CAR-T, remains guided by availability and toxicity profile rather than head-to-head data.","caveats":["Single-arm; no comparator or randomised evidence at approval.","Excluded patients with prior BCMA therapy in the registrational cohort; cohort B (BCMA-exposed) had lower responses.","Infection risk and hypogammaglobulinaemia similar to teclistamab.","Durability beyond two years still being reported."],"changedPractice":true,"participants":123},{"id":"paper-magnolia-zanubrutinib-mzl-ccr-2021","kind":"paper","name":"MAGNOLIA: zanubrutinib in relapsed or refractory marginal zone lymphoma","aka":[],"tldr":"The BTK inhibitor zanubrutinib produced responses in about two thirds of patients with relapsed marginal zone lymphoma across all subtypes with few of the cardiac side effects seen with ibrutinib, leading to its approval.","summary":"Phase 2 study of 68 patients with relapsed or refractory marginal zone lymphoma after at least one anti-CD20-based regimen treated with zanubrutinib 160 mg twice daily.\n\nObjective response by independent review was 68 percent with complete response in 26 percent, similar across extranodal, nodal and splenic subtypes, with 15-month progression-free survival of 83 percent and low rates of atrial fibrillation or major bleeding.","asOf":"2026-09-17","links":[{"label":"Clin Cancer Res 2021","url":"https://doi.org/10.1158/1078-0432.CCR-21-1704"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34526366/"}],"tags":[],"related":[],"cancers":["marginal-zone-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["zanubrutinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2021,"doi":"10.1158/1078-0432.CCR-21-1704","pmid":"34526366","authors":"Opat S, Tedeschi A, Linton K, et al.","paperType":"observational","findings":["Objective response 68 percent; complete response 26 percent.","15-month progression-free survival 83 percent."],"whatItMeans":"Zanubrutinib is an approved option for relapsed marginal zone lymphoma after anti-CD20 therapy, chosen for its tolerability profile.","caveats":["Single-arm; accelerated approval pending confirmatory data."],"changedPractice":true,"participants":68},{"id":"paper-maia-daratumumab-rd-nejm-2019","kind":"paper","name":"MAIA: adding daratumumab to lenalidomide-dexamethasone for older patients with newly diagnosed myeloma who cannot have a transplant","aka":[],"tldr":"Adding the CD38 antibody daratumumab to standard lenalidomide-dexamethasone cut the risk of progression or death by about 44% in older myeloma patients, and later extended survival.","summary":"MAIA randomised 737 transplant-ineligible patients with newly diagnosed multiple myeloma (median age 73) to daratumumab plus lenalidomide and dexamethasone (D-Rd) or Rd alone, both continued until progression. The primary endpoint was PFS. At 30 months PFS was 70.6% versus 55.6% (hazard ratio 0.56); complete response or better was 47.6% versus 24.9% and MRD-negativity 24.2% versus 7.3%. Longer follow-up showed a significant overall survival benefit (hazard ratio about 0.68; five-year OS roughly 66% versus 53%). Neutropenia and pneumonia were more frequent with daratumumab.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa1817249"},{"label":"ClinicalTrials.gov NCT02252172","url":"https://clinicaltrials.gov/study/NCT02252172"}],"tags":[],"related":["paper-cepheus-dara-vrd-natmed-2025","cd38-plus-triplet"],"cancers":["multiple-myeloma"],"sections":[],"technologies":[],"targets":["cd38"],"drugs":["daratumumab","lenalidomide"],"companies":["johnson-johnson"],"institutions":[],"pathways":[],"terms":["pfs","os","mrd-negativity-myeloma"],"trials":[],"people":[],"bottlenecks":["b-aging-comorbidity","b-drug-pricing"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2019,"doi":"10.1056/NEJMoa1817249","authors":"Facon T, Kumar S, Plesner T, et al.","paperType":"rct","findings":["737 transplant-ineligible patients; D-Rd vs Rd until progression.","30-month PFS 70.6% vs 55.6%; hazard ratio 0.56.","Complete response or better 47.6% vs 24.9%; MRD-negativity (10^-5) 24.2% vs 7.3%.","Overall survival significantly improved at longer follow-up (HR about 0.68; 5-year OS roughly 66% vs 53%).","Grade 3-4 neutropenia 50.0% vs 35.3%; pneumonia 13.7% vs 7.9%."],"whatItMeans":"MAIA made a daratumumab-based triplet the standard first treatment for older or frail myeloma patients, replacing Rd alone. It proved an anti-CD38 antibody could improve survival, not just delay progression, when used up front. Quadruplets built on this backbone are now being tested in the same population.","caveats":["Continuous therapy until progression; treatment burden and cost are substantial.","Patients over 80 and very frail patients were under-represented.","Median PFS was not reached at the primary analysis; the durability estimate relies on later reports.","Comparator Rd is itself now being displaced by quadruplets."],"changedPractice":true,"participants":737},{"id":"paper-majestec-1-teclistamab-nejm-2022","kind":"paper","name":"MajesTEC-1: teclistamab, an off-the-shelf BCMA bispecific antibody, in heavily pretreated myeloma","aka":[],"tldr":"A ready-made antibody that pulls T cells onto myeloma cells produced responses in 63% of patients after a median of five prior therapies, without the wait for cell manufacturing.","summary":"MajesTEC-1 was a phase 1/2 single-arm study of teclistamab, a BCMA x CD3 bispecific T-cell engager given subcutaneously weekly after step-up dosing, in 165 patients with relapsed or refractory multiple myeloma who were triple-class exposed (median five prior lines). The overall response rate was 63%, with complete response or better in 39.4%; median duration of response was 18.4 months and median PFS 11.3 months. Cytokine release syndrome occurred in 72% (almost all grade 1-2) and neurotoxicity in about 14.5%, but infections were frequent (grade 3-4 in about 45%) and hypogammaglobulinaemia was near universal. Teclistamab received accelerated approval in 2022, the first bispecific for myeloma.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa2203478"},{"label":"ClinicalTrials.gov NCT04557098","url":"https://clinicaltrials.gov/study/NCT04557098"}],"tags":[],"related":["bispecific-infection-prophylaxis","bcma-then-gprc5d","paper-magnetismm-3-elranatamab-natmed-2023"],"cancers":["multiple-myeloma"],"sections":[],"technologies":["bispecific-antibody","t-cell-engager"],"targets":["bcma","cd3"],"drugs":["teclistamab","talquetamab","elranatamab"],"companies":["johnson-johnson"],"institutions":[],"pathways":[],"terms":["crs","orr"],"trials":["majestec-1","majestec-3"],"people":[],"bottlenecks":["b-toxicity-qol","b-dose-optimisation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/NEJMoa2203478","authors":"Moreau P, Garfall AL, van de Donk NWCJ, et al.","paperType":"translational","findings":["165 triple-class-exposed patients; median 5 prior lines.","Overall response 63.0%; complete response or better 39.4%; MRD-negativity in 26.7% of all patients.","Median duration of response 18.4 months; median PFS 11.3 months.","CRS 72.1% (grade 3 0.6%); neurotoxicity 14.5% (ICANS 3%).","Infections 76.4% (grade 3-4 44.8%); 5 COVID-19 deaths; hypogammaglobulinaemia common."],"whatItMeans":"Teclistamab showed that an off-the-shelf bispecific can approach CAR-T-like response rates in late myeloma, giving patients who cannot wait for or access cell therapy a real option. It also exposed the price: prolonged T-cell engagement causes profound immunosuppression, so infection prophylaxis and immunoglobulin replacement are now routine. Less frequent dosing after response is being adopted to reduce this burden.","caveats":["Single-arm study; MajesTEC-3 later provided randomised evidence in earlier lines.","Continuous weekly dosing until progression in the original protocol; optimal duration and schedule still being defined.","Infection-related deaths were substantial; many patients were treated during the COVID-19 pandemic.","Responses are shorter than with cilta-cel, and BCMA-directed sequencing (CAR-T then bispecific or vice versa) reduces subsequent efficacy."],"changedPractice":true,"participants":165},{"id":"paper-centore-trends-genet","kind":"paper","name":"Mammalian SWI/SNF Chromatin Remodeling Complexes: Emerging Mechanisms and Therapeutic Strategies","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 32873422 and published in Trends in genetics; the citing page links this DOI, which is how the record was matched.","summary":"Small molecule-based targeting of chromatin regulatory factors has emerged as a promising therapeutic strategy in recent years. The development and ongoing clinical evaluation of novel agents targeting a range of chromatin regulatory processes, including DNA or histone modifiers, histone readers, and chromatin regulatory protein complexes, has inspired the field to identify and act upon the full compendium of therapeutic opportunities. Emerging studies highlight the frequent involvement of altered mammalian Switch/Sucrose-Nonfermentable (mSWI/SNF) chromatin-remodeling complexes (also called BAF complexes) in both human cancer and neurological disorders, suggesting new mechanisms and accompanying routes toward therapeutic intervention. Here, we review current approaches for direct targeting of mSWI/SNF complex structure and function and discuss settings in which aberrant mSWI/SNF biology is implicated in oncology and other diseases.\n\nIndexed on Europe PMC as PubMed record 32873422 (DOI 10.1016/j.tig.2020.07.011). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Trends Genet 2020","url":"https://doi.org/10.1016/j.tig.2020.07.011"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32873422/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32873422"}],"tags":["europepmc-ingest"],"related":["swi-snf-chromatin"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Trends in genetics","year":2020,"doi":"10.1016/j.tig.2020.07.011","pmid":"32873422","authors":"Centore RC, Sandoval GJ, Soares LMM, et al.","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-gallbladder-polyp-joint-guideline-eur-radiol-2022","kind":"paper","name":"Management and follow-up of gallbladder polyps: updated joint guidelines between the ESGAR, EAES, EFISDS and ESGE","aka":[],"tldr":"The 2022 European rules for gallbladder polyps found on ultrasound: operate at 10 mm or more, operate at 6 to 9 mm if there are risk factors, scan again for two years otherwise, and stop watching tiny polyps in people without risk factors.","summary":"Update of the 2017 joint recommendations of the European Society of Gastrointestinal and Abdominal Radiology, the European Association for Endoscopic Surgery, the European Federation of the International Society of Digestive Surgery and the European Society of Gastrointestinal Endoscopy. Ultrasound is the primary investigation. Cholecystectomy is recommended for polypoid lesions of 10 mm or more (strong recommendation, low-quality evidence), for symptomatic polyps, and for 6 to 9 mm polyps with a risk factor: age over 60, primary sclerosing cholangitis, Asian ethnicity, or a sessile lesion including focal wall thickening over 4 mm.\n\nPolyps of 6 to 9 mm without risk factors, or 5 mm or less with risk factors, get ultrasound at 6 months, 1 and 2 years and are discharged if they have not grown; 5 mm or less without risk factors need no follow-up. Growth to 10 mm means surgery; growth of 2 mm or more within two years prompts multidisciplinary discussion; a polyp that disappears ends monitoring.","asOf":"2026-09-24","links":[{"label":"Eur Radiol 2022","url":"https://doi.org/10.1007/s00330-021-08384-w"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34918177/"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":["ultrasound"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["gallbladder-polyp","screening","overdiagnosis"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"European Radiology","year":2022,"doi":"10.1007/s00330-021-08384-w","pmid":"34918177","authors":"Foley KG, Lahaye MJ, Thoeni RF, et al.","paperType":"guideline","findings":["Cholecystectomy for polypoid lesions of 10 mm or more (strong recommendation, low-quality evidence).","Cholecystectomy for 6 to 9 mm lesions with a risk factor: age over 60, primary sclerosing cholangitis, Asian ethnicity, sessile shape or wall thickening over 4 mm.","Ultrasound at 6 months, 1 year and 2 years for 6 to 9 mm lesions without risk factors and 5 mm or smaller lesions with them; no follow-up for 5 mm or smaller lesions without risk factors.","Growth to 10 mm: surgery; growth of 2 mm or more within two years: multidisciplinary review."],"whatItMeans":"This is the polyp pathway UK radiologists and surgeons follow (a UK author, Foley, leads it). It is a surveillance-and-surgery guideline built on low to moderate quality evidence, and the Kaiser Permanente cohort published two years earlier questions whether following small polyps finds cancer at all.","caveats":["Most recommendations rest on low to moderate quality evidence.","The 10 mm threshold has only moderate accuracy for neoplasia (Wennmacker 2019)."],"changedPractice":true},{"id":"paper-roeland-j-clin-oncol","kind":"paper","name":"Management of Cancer Cachexia: ASCO Guideline","aka":[],"tldr":"Paper cited by one technology page and one bottleneck page, indexed on Europe PMC as PubMed record 32432946 and published in Journal of Clinical Oncology; the citing pages link this DOI, which is how the record was matched.","summary":"Purpose: To provide evidence-based guidance on the clinical management of cancer cachexia in adult patients with advanced cancer.\n\nMethods: A systematic review of the literature collected evidence regarding nutritional, pharmacologic, and other interventions, such as exercise, for cancer cachexia. PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) and systematic reviews of RCTs published from 1966 through October 17, 2019. ASCO convened an Expert Panel to review the evidence and formulate recommendations.\n\nResults: The review included 20 systematic reviews and 13 additional RCTs. Dietary counseling, with or without oral nutritional supplements, was reported to increase body weight in some trials, but evidence remains limited. Pharmacologic interventions associated with improvements in appetite and/or body weight include progesterone analogs and corticosteroids. The other evaluated interventions either had no benefit or insufficient evidence of benefit to draw conclusions on efficacy. Limitations of the evidence include high drop-out rates, consistent with advanced cancer, as well as variability across studies in outcomes of interest and methods for outcome assessment.\n\nRecommendations: Dietary counseling may be offered with the goals of providing patients and caregivers with advice for the management of cachexia. Enteral feeding tubes and parenteral nutrition should not be used routinely. In the absence of more robust evidence, no specific pharmacological intervention can be recommended as the standard of care; therefore, clinicians may choose not to prescribe medications specifically for the treatment of cancer cachexia. Nonetheless, when it is decided to trial a drug to improve appetite and/or improve weight gain, currently available pharmacologic interventions that may be used include progesterone analogs and short-term (weeks) corticosteroids.\n\nIndexed on Europe PMC as PubMed record 32432946 (DOI 10.1200/jco.20.00611). Matched by DOI alone: one technology page and one bottleneck page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2020","url":"https://doi.org/10.1200/jco.20.00611"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32432946/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32432946"}],"tags":["europepmc-ingest"],"related":["nutrition-screening-mnt","b-cachexia-supportive"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/jco.20.00611","pmid":"32432946","authors":"Roeland EJ, Bohlke K, Baracos VE, et al.","paperType":"review","findings":[],"whatItMeans":"One technology page and one bottleneck page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-bohlius-j-clin-oncol","kind":"paper","name":"Management of Cancer-Associated Anemia With Erythropoiesis-Stimulating Agents: ASCO/ASH Clinical Practice Guideline Update","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 30969847 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: To update the American Society of Clinical Oncology (ASCO)/American Society of Hematology (ASH) recommendations for use of erythropoiesis-stimulating agents (ESAs) in patients with cancer.\n\nMethods: PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) and meta-analyses of RCTs in patients with cancer published from January 31, 2010, through May 14, 2018. For biosimilar ESAs, the literature search was expanded to include meta-analyses and RCTs in patients with cancer or chronic kidney disease and cohort studies in patients with cancer due to limited RCT evidence in the cancer setting. ASCO and ASH convened an Expert Panel to review the evidence and revise previous recommendations as needed.\n\nResults: The primary literature review included 15 meta-analyses of RCTs and two RCTs. A growing body of evidence suggests that adding iron to treatment with an ESA may improve hematopoietic response and reduce the likelihood of RBC transfusion. The biosimilar literature review suggested that biosimilars of epoetin alfa have similar efficacy and safety to reference products, although evidence in cancer remains limited.\n\nRecommendations: ESAs (including biosimilars) may be offered to patients with chemotherapy-associated anemia whose cancer treatment is not curative in intent and whose hemoglobin has declined to < 10 g/dL. RBC transfusion is also an option. With the exception of selected patients with myelodysplastic syndromes, ESAs should not be offered to most patients with nonchemotherapy-associated anemia. During ESA treatment, hemoglobin may be increased to the lowest concentration needed to avoid transfusions. Iron replacement may be used to improve hemoglobin response and reduce RBC transfusions for patients receiving ESA with or without iron deficiency. Additional information is available at www.asco.org/supportive-care-guidelines and www.hematology.org/guidelines.\n\nIndexed on Europe PMC as PubMed record 30969847 (DOI 10.1200/jco.18.02142). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2019","url":"https://doi.org/10.1200/jco.18.02142"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30969847/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30969847"}],"tags":["europepmc-ingest"],"related":["transfusion-support"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2019,"doi":"10.1200/jco.18.02142","pmid":"30969847","authors":"Bohlius J, Bohlke K, Castelli R, et al.","paperType":"guideline","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-paice-j-clin-oncol","kind":"paper","name":"Management of Chronic Pain in Survivors of Adult Cancers: American Society of Clinical Oncology Clinical Practice Guideline","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 27458286 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: To provide evidence-based guidance on the optimum management of chronic pain in adult cancer survivors.\n\nMethods: An ASCO-convened expert panel conducted a systematic literature search of studies investigating chronic pain management in cancer survivors. Outcomes of interest included symptom relief, pain intensity, quality of life, functional outcomes, adverse events, misuse or diversion, and risk assessment or mitigation.\n\nResults: A total of 63 studies met eligibility criteria and compose the evidentiary basis for the recommendations. Studies tended to be heterogeneous in terms of quality, size, and populations. Primary outcomes also varied across the studies, and in most cases, were not directly comparable because of different outcomes, measurements, and instruments used at different time points. Because of a paucity of high-quality evidence, many recommendations are based on expert consensus.\n\nRecommendations: Clinicians should screen for pain at each encounter. Recurrent disease, second malignancy, or late-onset treatment effects in any patient who reports new-onset pain should be evaluated, treated, and monitored. Clinicians should determine the need for other health professionals to provide comprehensive pain management care in patients with complex needs. Systemic nonopioid analgesics and adjuvant analgesics may be prescribed to relieve chronic pain and/or to improve function. Clinicians may prescribe a trial of opioids in carefully selected patients with cancer who do not respond to more conservative management and who continue to experience distress or functional impairment. Risks of adverse effects of opioids should be assessed. Clinicians should clearly understand terminology such as tolerance, dependence, abuse, and addiction as it relates to the use of opioids and should incorporate universal precautions to minimize abuse, addiction, and adverse consequences. Additional information is available at www.asco.org/chronic-pain-guideline and www.asco.org/guidelineswiki.\n\nIndexed on Europe PMC as PubMed record 27458286 (DOI 10.1200/jco.2016.68.5206). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2016","url":"https://doi.org/10.1200/jco.2016.68.5206"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27458286/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27458286"}],"tags":["europepmc-ingest"],"related":["pain-management"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2016,"doi":"10.1200/jco.2016.68.5206","pmid":"27458286","authors":"Paice JA, Portenoy R, Lacchetti C, et al.","paperType":"guideline","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-asco-hereditary-breast-cancer-guideline-jco-2020","kind":"paper","name":"Management of Hereditary Breast Cancer: American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Guideline","aka":[],"tldr":"The 2020 joint US guideline for breast cancer in people who carry an inherited fault in BRCA1, BRCA2 or another risk gene: breast-conserving surgery is allowed, bilateral mastectomy should be discussed, platinum beats taxanes in advanced disease and PARP inhibitors beat single-agent chemotherapy.","summary":"Guideline from ASCO, ASTRO and SSO by Tung, Boughey, Pierce, Robson and colleagues, based on 58 articles for local therapy and six randomised trials of systemic therapy. Recommendations: patients with newly diagnosed breast cancer and BRCA1/2 mutations may be considered for breast-conserving therapy with local control similar to non-carriers; the risk of contralateral and new ipsilateral cancers, especially in young women, warrants discussion of bilateral mastectomy; nipple-sparing mastectomy is reasonable; there is no evidence of increased toxicity or contralateral cancers from radiation in BRCA1/2 carriers; radiation should not be withheld in ATM carriers; mastectomy is advised and radiation contraindicated except at high locoregional risk for germline TP53 carriers. Platinum agents are recommended over taxanes for advanced disease in BRCA carriers; routine platinum is not supported in the adjuvant or neoadjuvant setting; PARP inhibitors (olaparib, talazoparib) are preferable to non-platinum single-agent chemotherapy for advanced disease; data were insufficient for early-setting PARP inhibition or moderate-penetrance carriers.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2020","url":"https://doi.org/10.1200/JCO.20.00299"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32243226/"}],"tags":["tnbc-evidence"],"related":[],"cancers":["tnbc","breast-hr-positive"],"sections":[],"technologies":["parp-inhibitor","platinum","germline-testing"],"targets":["brca"],"drugs":["olaparib","talazoparib","carboplatin"],"companies":[],"institutions":["asco"],"pathways":[],"terms":["germline-testing"],"trials":["olympiad","embraca","olympia"],"people":["mark-robson"],"bottlenecks":["b-hereditary-risk"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/JCO.20.00299","pmid":"32243226","authors":"Tung NM, Boughey JC, Pierce LJ, et al.","paperType":"guideline","findings":["Breast-conserving therapy is an option for BRCA1/2 carriers; bilateral mastectomy should be discussed because of contralateral and new ipsilateral risk.","Platinum agents recommended over taxanes for advanced disease in BRCA carriers; PARP inhibitors preferable to non-platinum single-agent chemotherapy.","Data insufficient in 2020 for adjuvant PARP inhibition, later supplied by OlympiA."],"whatItMeans":"Sets the surgical and systemic rules for the one in nine to one in six triple-negative patients who carry a germline BRCA variant (11 to 17 percent by cohort); the adjuvant gap it named was filled by OlympiA the following year.","caveats":["Predates OlympiA; adjuvant olaparib is not addressed.","Local therapy evidence is observational."],"changedPractice":true},{"id":"paper-mcclements-capbil-incidental-gallbladder-cancer-bjs-2026","kind":"paper","name":"Management of incidental gallbladder cancer in the nationwide CAPBIL study","aka":[],"tldr":"The first UK-wide picture of gallbladder cancers found by chance: across 24 centres over nine years, two thirds went on to liver surgery and those who did stayed free of disease far longer.","summary":"UK HPB Research Collaborative Group study of 285 patients diagnosed with incidental gallbladder cancer after cholecystectomy between January 2014 and December 2022 at 24 UK centres. Median follow-up was 31 months; five-year disease-free survival was 41.5 percent and overall survival 45.1 percent. Of 193 patients (67.7 percent) who underwent liver resection, 97.9 percent had segment 4b/5 resection. Liver resection was associated with longer disease-free survival (51 versus 15 months). Adverse tumour biology was associated with poorer survival.","asOf":"2026-09-24","links":[{"label":"Br J Surg 2026","url":"https://doi.org/10.1093/bjs/znag050"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42013358/"}],"tags":["gallbladder-evidence"],"related":["paper-mcclements-capbil-surgical-outcomes-gallbladder-cancer-hpb-2026"],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["liverpool-hpb-centre"],"pathways":[],"terms":["incidental-gallbladder-cancer","radical-cholecystectomy"],"trials":["bilcap"],"people":["hassan-malik"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"British Journal of Surgery","year":2026,"doi":"10.1093/bjs/znag050","pmid":"42013358","authors":"McClements J, Lee WT, Koh A, et al.","paperType":"real-world","findings":["285 incidental gallbladder cancers at 24 UK centres, 2014 to 2022; five-year disease-free survival 41.5 percent, overall survival 45.1 percent.","193 patients (67.7 percent) underwent liver resection, 97.9 percent of them segment 4b/5.","Median disease-free survival 51 months with liver resection vs 15 months without."],"whatItMeans":"This is the UK baseline for the incidental cancer pathway: a re-resection rate well above the Dutch registry's 24 percent, with the same selection caveat. The abstract leaves out the histology, referral and timing detail; the full paper holds it.","caveats":["Retrospective, unmatched comparison; patients not offered surgery were likely sicker or more advanced.","Abstract reports disease-free survival months without confidence intervals."],"changedPractice":false,"participants":285},{"id":"paper-van-klaveren-n-engl-j-med","kind":"paper","name":"Management of lung nodules detected by volume CT scanning","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 19955524 and published in New England Journal of Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Background: The use of multidetector computed tomography (CT) in lung-cancer screening trials involving subjects with an increased risk of lung cancer has highlighted the problem for the clinician of deciding on the best course of action when noncalcified pulmonary nodules are detected by CT.\n\nMethods: A total of 7557 participants underwent CT screening in years 1, 2, and 4 of a randomized trial of lung-cancer screening. We used software to evaluate a noncalcified nodule according to its volume or volume-doubling time. Growth was defined as an increase in volume of at least 25% between two scans. The first-round screening test was considered to be negative if the volume of a nodule was less than 50 mm(3), if it was 50 to 500 mm(3) but had not grown by the time of the 3-month follow-up CT, or if, in the case of those that had grown, the volume-doubling time was 400 days or more.\n\nResults: In the first and second rounds of screening, 2.6% and 1.8% of the participants, respectively, had a positive test result. In round one, the sensitivity of the screen was 94.6% (95% confidence interval [CI], 86.5 to 98.0) and the negative predictive value 99.9% (95% CI, 99.9 to 100.0). In the 7361 subjects with a negative screening result in round one, 20 lung cancers were detected after 2 years of follow-up.\n\nConclusions: Among subjects at high risk for lung cancer who were screened in three rounds of CT scanning and in whom noncalcified pulmonary nodules were evaluated according to volume and volume-doubling time, the chances of finding lung cancer 1 and 2 years after a negative first-round test were 1 in 1000 and 3 in 1000, respectively. (Current Controlled Trials number, ISRCTN63545820.)\n\nIndexed on Europe PMC as PubMed record 19955524 (DOI 10.1056/nejmoa0906085). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2009","url":"https://doi.org/10.1056/nejmoa0906085"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19955524/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/19955524"}],"tags":["europepmc-ingest"],"related":["tumour-doubling-time"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2009,"doi":"10.1056/nejmoa0906085","pmid":"19955524","authors":"van Klaveren RJ, Oudkerk M, Prokop M, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-hassett-j-clin-oncol","kind":"paper","name":"Management of Male Breast Cancer: ASCO Guideline","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 32058842 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: To develop recommendations concerning the management of male breast cancer.\n\nMethods: ASCO convened an Expert Panel to develop recommendations based on a systematic review and a formal consensus process.\n\nResults: Twenty-six descriptive reports or observational studies met eligibility criteria and formed the evidentiary basis for the recommendations.\n\nRecommendations: Many of the management approaches used for men with breast cancer are like those used for women. Men with hormone receptor-positive breast cancer who are candidates for adjuvant endocrine therapy should be offered tamoxifen for an initial duration of five years; those with a contraindication to tamoxifen may be offered a gonadotropin-releasing hormone agonist/antagonist plus aromatase inhibitor. Men who have completed five years of tamoxifen, have tolerated therapy, and still have a high risk of recurrence may be offered an additional five years of therapy. Men with early-stage disease should not be treated with bone-modifying agents to prevent recurrence, but could still receive these agents to prevent or treat osteoporosis. Men with advanced or metastatic disease should be offered endocrine therapy as first-line therapy, except in cases of visceral crisis or rapidly progressive disease. Targeted systemic therapy may be used to treat advanced or metastatic cancer using the same indications and combinations offered to women. Ipsilateral annual mammogram should be offered to men with a history of breast cancer treated with lumpectomy regardless of genetic predisposition; contralateral annual mammogram may be offered to men with a history of breast cancer and a genetic predisposing mutation. Breast magnetic resonance imaging is not recommended routinely. Genetic counseling and germline genetic testing of cancer predisposition genes should be offered to all men with breast cancer.\n\nIndexed on Europe PMC as PubMed record 32058842 (DOI 10.1200/jco.19.03120). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2020","url":"https://doi.org/10.1200/jco.19.03120"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32058842/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32058842"}],"tags":["europepmc-ingest"],"related":["male-breast-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/jco.19.03120","pmid":"32058842","authors":"Hassett MJ, Somerfield MR, Baker ER, et al.","paperType":"review","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-caps-consortium-surveillance-recommendations-gut-2020","kind":"paper","name":"Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium","aka":[],"tldr":"The 2020 international consensus on who should have regular pancreatic scans because of family history or an inherited gene change, when to start, which scans to use and what the surveillance is trying to find.","summary":"The International Cancer of the Pancreas Screening Consortium met in 2018 and used a modified Delphi process (consensus at 75 percent agreement) to update its recommendations for high-risk individuals. Consensus was reached on 55 statements. The goals of surveillance, to identify high-grade dysplastic precursor lesions and T1N0M0 pancreatic cancer, were unchanged. For familial risk, surveillance should start no earlier than age 50 or 10 years earlier than the youngest affected relative, with the panel split between 50 and 55; germline ATM carriers with one affected first-degree relative became eligible. Endoscopic ultrasound and MRI with magnetic resonance cholangiopancreatography are the preferred tests, without consensus on how to alternate them; annual surveillance is recommended when no concerning lesion is present. Disagreement remained over hereditary pancreatitis and indeterminate lesions. Surveillance should be performed in a research setting by multidisciplinary teams in expert centres until more evidence is available.","asOf":"2026-09-24","links":[{"label":"Gut 2020","url":"https://doi.org/10.1136/gutjnl-2019-319352"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31672839/"}],"tags":["pancreatic-evidence"],"related":["paper-canto-caps-long-term-surveillance-gastroenterology-2018","paper-dbouk-caps5-stage-survival-jco-2022"],"cancers":["pancreatic","ipmn-cystic-precursors"],"sections":[],"technologies":["pancreatic-surveillance","germline-testing","mri"],"targets":["atm","brca","cdkn2a","palb2"],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":[],"terms":["hereditary-cancer-syndromes"],"trials":["precede"],"people":["diane-simeone"],"bottlenecks":["b-hereditary-risk","b-early-detection"],"keyPapers":[],"journals":["gut"],"dependsOn":[],"notes":[],"journal":"Gut","year":2020,"doi":"10.1136/gutjnl-2019-319352","pmid":"31672839","authors":"Goggins M, Overbeek KA, Brand R, et al.","paperType":"guideline","findings":["Consensus on 55 statements; goals of surveillance are high-grade dysplasia and T1N0M0 cancer.","Start at 50 or 55, or 10 years before the youngest affected relative; germline ATM carriers with one affected first-degree relative now eligible.","Endoscopic ultrasound and MRI with cholangiopancreatography preferred; annual interval when nothing concerning is seen.","Surveillance to be run in research settings by multidisciplinary teams in expert centres."],"whatItMeans":"The rulebook behind the CAPS cohorts and the UK EUROPAC programme; it is also the reason surveillance for carriers is not yet a routine NHS service, because the consortium itself asked for it to stay within research until benefit was shown.","caveats":["Consensus, not trial evidence; the recommendations are explicitly provisional.","Written before the CAPS5 outcomes (2022) that showed most surveillance-detected cancers at stage I."],"changedPractice":true},{"id":"paper-haanen-ann-oncol","kind":"paper","name":"Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","aka":[],"tldr":"Paper cited by two term pages, indexed on Europe PMC as PubMed record 36270461 and published in Annals of Oncology; the citing pages link this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 36270461 (DOI 10.1016/j.annonc.2022.10.001). Matched by DOI alone: two term pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Ann Oncol 2022","url":"https://doi.org/10.1016/j.annonc.2022.10.001"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36270461/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36270461"}],"tags":["europepmc-ingest"],"related":["irae","immune-endocrinopathy"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2022,"doi":"10.1016/j.annonc.2022.10.001","pmid":"36270461","authors":"Haanen J, Obeid M, Spain L, et al.","paperType":"guideline","findings":[],"whatItMeans":"Two term pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-mani-emt-stem-cell-properties-cell-2008","kind":"paper","name":"Mani 2008: the epithelial-mesenchymal transition generates cells with properties of stem cells","aka":[],"tldr":"Switching on the invasion programme in normal breast cells also gave them stem cell properties, linking two ideas about how cancers spread and resist treatment, and suggesting that the mobile cells that seed metastases are the same ones that can regrow a tumour.","summary":"Mani, Weinberg and colleagues induced an epithelial-mesenchymal transition in immortalised human mammary epithelial cells by expressing the transcription factors Snail or Twist or by exposing them to TGF-beta1. The cells acquired a mesenchymal appearance, a CD44-high CD24-low surface profile matching that of breast cancer stem cells, and a much greater ability to form mammospheres and colonies. Conversely, stem-like cells isolated from normal and cancerous breast tissue expressed EMT markers. The paper connected the EMT and cancer stem cell fields.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1016/j.cell.2008.03.027"}],"tags":[],"related":["paper-kalluri-weinberg-emt-basics-jci-2009","paper-al-hajj-breast-cancer-stem-cells-pnas-2003"],"cancers":["breast-hr-positive","tnbc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["mit-koch"],"pathways":["emt","tgf-beta"],"terms":["stem-cell","metastasis"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Cell","year":2008,"doi":"10.1016/j.cell.2008.03.027","authors":"Mani SA, Guo W, Liao MJ, et al.","paperType":"basic","findings":["Inducing EMT in human mammary epithelial cells produced CD44-high CD24-low cells with increased mammosphere and colony formation.","Stem-like cells from normal and malignant breast tissue expressed EMT markers.","EMT-inducing factors also increased the tumour-initiating ability of transformed cells."],"whatItMeans":"This paper is why metastasis, stemness and therapy resistance are now studied as one problem. It suggests that the cells most able to spread are also the ones most able to regrow, and it motivates therapies that target the mesenchymal or stem-like state.","caveats":["Cell culture and mouse work with engineered cells; relevance to spontaneous human tumours is inferred.","Later work suggests partial EMT states, rather than complete transitions, carry the most stemness and metastatic ability."],"changedPractice":false},{"id":"paper-esmo-marginal-zone-lymphoma-zucca-ann-oncol-2020","kind":"paper","name":"Marginal zone lymphomas: ESMO clinical practice guidelines","aka":[],"tldr":"The ESMO guideline for marginal zone lymphomas sets out the treatment of gastric and non-gastric extranodal, splenic and nodal forms, including antibiotic eradication, low-dose radiotherapy, watch and wait, rituximab-based therapy and BTK inhibitors at relapse.","summary":"Evidence-based guideline covering diagnosis, staging, and first-line and relapsed treatment of extranodal (MALT), splenic and nodal marginal zone lymphomas, including the role of infectious agents (Helicobacter pylori, hepatitis C), involved-site radiotherapy, chemoimmunotherapy and novel agents.","asOf":"2026-09-17","links":[{"label":"Ann Oncol 2020","url":"https://doi.org/10.1016/j.annonc.2019.10.010"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31912792/"}],"tags":[],"related":[],"cancers":["marginal-zone-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2020,"doi":"10.1016/j.annonc.2019.10.010","pmid":"31912792","authors":"Zucca E, Arcaini L, Buske C, et al.","paperType":"guideline","findings":[],"whatItMeans":"The site-specific and stage-specific approach on the marginal zone lymphoma page follows this guideline.","caveats":["Randomised evidence is limited for most decisions in these indolent lymphomas."],"changedPractice":true},{"id":"paper-mariposa-nejm-2024","kind":"paper","name":"MARIPOSA: amivantamab plus lazertinib versus osimertinib as first treatment for EGFR-mutated lung cancer","aka":[],"tldr":"Combining an EGFR-MET bispecific antibody with a third-generation EGFR pill beat osimertinib alone, delaying progression by about seven months and later improving survival, at the cost of more side effects.","summary":"Phase 3 trial of 1,074 patients with untreated EGFR-mutated (exon 19 deletion or L858R) advanced NSCLC, randomised 2:2:1 to amivantamab plus lazertinib, osimertinib, or lazertinib alone. Primary endpoint was PFS by blinded review for the combination versus osimertinib.\n\nMedian PFS was 23.7 vs 16.6 months (HR 0.70). A 2025 final overall survival analysis reported a significant improvement (HR about 0.75) with median survival in the combination arm not reached and projected to exceed osimertinib by more than a year. It is the first regimen to beat osimertinib on survival, but adds infusion reactions, venous thromboembolism, rash and paronychia.","asOf":"2026-09-08","links":[{"label":"NEJM 2024","url":"https://doi.org/10.1056/NEJMoa2403614"},{"label":"ClinicalTrials.gov NCT04487080","url":"https://clinicaltrials.gov/study/NCT04487080"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38924756/"}],"tags":[],"related":["paper-planchard-flaura2-osimertinib-chemotherapy-nejm-2023","paper-flaura-nejm-2018","paper-sequist-genotypic-histological-evolution-egfr-resistance-sci-transl-med-2011"],"cancers":["nsclc","lung-cancer","egfr-mutant-nsclc"],"sections":["targeted-therapy"],"technologies":["bispecific-antibody","kinase-inhibitors"],"targets":["egfr","met"],"drugs":["amivantamab","osimertinib","lazertinib"],"companies":["johnson-johnson"],"institutions":["severance"],"pathways":[],"terms":["pfs","os","resistance","first-line","ctdna","driver-mutation"],"trials":["mariposa","flaura2"],"people":["cho-byoung-chul","lu-shun","enriqueta-felip","lee-se-hoon","benjamin-besse","prabhash-kumar"],"bottlenecks":["b-resistance","b-toxicity-qol","b-drug-pricing","b-combination-space"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2024,"doi":"10.1056/NEJMoa2403614","pmid":"38924756","authors":"Cho BC, Lu S, Felip E, et al.","paperType":"rct","findings":["Median PFS 23.7 vs 16.6 months; HR 0.70 (95% CI 0.58-0.85).","Overall survival at final analysis (2025): HR about 0.75; median not reached vs 36.7 months for osimertinib.","Benefit was seen in high-risk subgroups (TP53 co-mutation, detectable ctDNA, brain or liver metastases).","Grade 3 or higher adverse events 75% vs 43%; venous thromboembolism about 37% vs 9%, prompting prophylactic anticoagulation in the first four months.","Lazertinib alone performed similarly to osimertinib."],"whatItMeans":"Patients newly diagnosed with EGFR-mutated advanced lung cancer now have a first-line option that improves survival over osimertinib, particularly if they have high-risk features. The trade-off is intravenous (now subcutaneous) infusions and considerably more skin, nail and clotting toxicity, so osimertinib alone remains reasonable for those who prioritise convenience and tolerability. Both this regimen and osimertinib plus chemotherapy (FLAURA2) are approved; there is no direct comparison.","caveats":["Toxicity is substantially higher and treatment is more burdensome than an oral tablet alone.","No head-to-head comparison with osimertinib plus chemotherapy.","Cost is very high and access outside wealthy countries is limited.","Whether resistance mechanisms after the combination are more treatable than after osimertinib is unknown."],"changedPractice":true,"participants":1074},{"id":"paper-mars-2-lancet-respir-med-2024","kind":"paper","name":"MARS 2: extended pleurectomy decortication plus chemotherapy versus chemotherapy alone for pleural mesothelioma","aka":[],"tldr":"Adding lung-sparing radical surgery to chemotherapy for pleural mesothelioma did not lengthen life; patients who had surgery lived slightly less long, had more complications and worse quality of life, so routine surgery is no longer recommended.","summary":"Multicentre randomised trial in the United Kingdom of 335 patients with resectable pleural mesothelioma randomised to extended pleurectomy decortication plus platinum-pemetrexed chemotherapy or chemotherapy alone.\n\nMedian overall survival was 19.3 months with surgery against 24.8 months without (hazard ratio 1.28); surgery caused more serious adverse events and worse quality of life in the first year, at higher cost.","asOf":"2026-09-17","links":[{"label":"Lancet Respir Med 2024","url":"https://doi.org/10.1016/S2213-2600(24)00119-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38740044/"}],"tags":[],"related":[],"cancers":["pleural-mesothelioma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["mars-2"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Lancet Respiratory Medicine","year":2024,"doi":"10.1016/S2213-2600(24)00119-x","pmid":"38740044","authors":"Lim E, Waller D, Lau K, et al.","paperType":"rct","findings":["Median overall survival 19.3 vs 24.8 months; hazard ratio 1.28 favouring no surgery.","Serious adverse events 3.6 times more common in the surgery arm."],"whatItMeans":"Radical surgery for pleural mesothelioma should be confined to trials; effusion is managed with pleurodesis or indwelling catheters and treatment is systemic.","caveats":["Surgical quality varied across centres; proponents argue selected patients in expert hands may still benefit.","Most patients had epithelioid disease."],"changedPractice":true,"participants":335},{"id":"paper-martincorena-somatic-mutations-normal-skin-science-2015","kind":"paper","name":"Martincorena: normal sun-exposed skin is a patchwork of cancer-mutation clones","aka":[],"tldr":"Deep sequencing of 234 tiny biopsies of normal eyelid skin from four people found thousands of clones carrying cancer driver mutations, with about a fifth to a third of cells carrying NOTCH1 mutations, showing that driver mutations are common in healthy tissue.","summary":"The Sanger Institute group sequenced 74 cancer genes at high depth in 234 punch biopsies (each about 1 mm2) of physiologically normal eyelid skin removed during blepharoplasty from four individuals aged 55-73.\n\nNormal skin carried 2-6 mutations per megabase per cell, a burden comparable to many cancers, dominated by ultraviolet signatures. Positive selection was evident for NOTCH1, NOTCH2, FAT1 and TP53 mutations; clones with NOTCH1 mutations occupied around 20% of the skin surface, and an estimated 140 driver mutations were present per square centimetre. Yet none of the tissue was cancerous.\n\nThe paper began the field of somatic mutation in normal tissues, later extended to oesophagus, colon, bladder, lung, liver and blood, and forced a rethink of what a driver mutation means for cancer risk and for the specificity of mutation-based early detection tests.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1126/science.aaa6806"}],"tags":[],"related":["paper-jaiswal-chip-nejm-2014","idea-field-interception"],"cancers":[],"sections":["early-detection","prevention"],"technologies":["wes-wgs","liquid-biopsy"],"targets":["tp53"],"drugs":[],"companies":[],"institutions":[],"pathways":["field-cancerisation","clonal-evolution","notch"],"terms":["vaf","mutational-signature"],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-overdiagnosis","b-biomarker-validation"],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2015,"doi":"10.1126/science.aaa6806","pmid":"25999502","authors":"Martincorena I, Roshan A, Gerstung M, et al.","paperType":"basic","findings":["Mutation burden in normal skin 2-6 mutations per megabase per cell, similar to many cancers","Positive selection of NOTCH1, NOTCH2, FAT1 and TP53 mutations in normal epidermis","NOTCH1-mutant clones covered about 20% of the skin surface in the individuals studied","About 140 driver mutations estimated per square centimetre of normal sun-exposed skin"],"whatItMeans":"Carrying a cancer mutation is normal; most mutant clones never become cancer. This means blood or tissue tests that look for driver mutations alone will produce false positives, and that the question of what tips a mutant clone into cancer (tissue environment, further hits, immune surveillance) is as important as the mutation itself.","caveats":["Four elderly individuals and one tissue; generalisation came from later studies","Targeted panel of 74 genes; genome-wide selection was inferred","Cannot say which clones would have progressed","Clone sizes depend on the sequencing depth and biopsy size chosen"],"changedPractice":false,"participants":4},{"id":"paper-martuza-engineered-hsv-glioma-science-1991","kind":"paper","name":"Martuza 1991: the first genetically engineered virus built to treat a cancer","aka":[],"tldr":"A herpes virus was deliberately crippled so that it could only multiply in dividing cells, injected into human brain tumours growing in mice, and it made the mice live longer.","summary":"Malignant gliomas are the commonest malignant brain tumours and are almost always fatal. Martuza and colleagues tested dlsptk, a thymidine-kinase-negative mutant of herpes simplex virus type 1 attenuated for neurovirulence, as a treatment. In cell culture it killed two long-term human glioma lines and three short-term human glioma cell populations. In nude mice with implanted subcutaneous and subrenal U87 human gliomas, injection into the tumour inhibited growth; in mice with intracranial U87 gliomas it prolonged survival.\n\nDeleting viral thymidine kinase makes the virus depend on the host cell's own nucleotide pool, which dividing tumour cells supply and resting brain cells do not. That is the first worked example of the move the whole field now makes: take out a viral gene whose job the cancer cell will do for it.","asOf":"2026-09-25","links":[{"label":"Science 1991","url":"https://doi.org/10.1126/science.1851332"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/1851332/"}],"tags":[],"related":[],"cancers":["glioblastoma"],"sections":["immunotherapy"],"technologies":["oncolytic-virus"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["robert-martuza"],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":1991,"doi":"10.1126/science.1851332","pmid":"1851332","authors":"Martuza RL, Malick A, Markert JM, Ruffner KL, Coen DM","paperType":"basic","findings":["A thymidine-kinase-negative herpes simplex virus type 1 mutant (dlsptk), attenuated for neurovirulence, killed two long-term and three short-term human glioma cell populations in culture.","Injection into subcutaneous and subrenal U87 human gliomas in nude mice inhibited tumour growth.","Injection into intracranial U87 gliomas in nude mice prolonged survival."],"whatItMeans":"This paper turned oncolytic virotherapy from a century of case reports into an engineering discipline. Every approved product descends from the same idea: delete a viral gene that a normal cell would have to supply and a cancer cell already supplies in excess. Talimogene laherparepvec and teserpaturev are both herpes viruses in this line.","caveats":["Thymidine kinase deletion also removes the virus's sensitivity to aciclovir and ganciclovir, which are the safety net if an infection runs away. Later constructs deleted different genes partly for that reason.","Nude mice have no T cells, so the experiment measures direct lysis only.","A human glioma grown in a mouse flank or brain is a poor model of the infiltrating disease in a patient, and three decades later glioblastoma remains almost as lethal."]},{"id":"paper-masai-lancet-oncol-2023","kind":"paper","name":"MASAI: AI-supported mammography screening finds more cancers with half the radiologist workload","aka":[],"tldr":"In the first randomised trial of AI in population mammography, AI-supported reading detected 20% more cancers than standard double reading without increasing false positives, and cut screen-reading work by 44%.","summary":"MASAI randomised 80,033 women aged 40-74 attending screening in Sweden to AI-supported screening (AI risk score used to triage to single or double reading and to flag suspicious findings) or standard double reading. This pre-specified safety analysis compared cancer detection, recall and false positives.\n\nThe cancer detection rate was 6.1 per 1,000 with AI support versus 5.1 per 1,000 with standard reading (ratio 1.2), with recall rates of 2.2% and 2.0% and identical 1.5% false-positive rates. Screen-reading workload fell by 44.3%. The 2025 report on the full cohort (over 105,000 women) confirmed a 29% increase in detection, concentrated in invasive and small cancers.\n\nThis was the first randomised evidence that AI can safely replace one of two human readers in screening.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1016/S1470-2045(23)00298-X"},{"label":"ClinicalTrials.gov NCT04838756","url":"https://clinicaltrials.gov/study/NCT04838756"}],"tags":[],"related":["idea-prev-ai-mammogram-risk-intervals","idea-prev-mammography-ai-stepped-wedge","idea-data-ai-screening-endpoints"],"cancers":["breast-hr-positive","breast-her2-positive","tnbc"],"sections":["early-detection","ai-computation"],"technologies":["radiology-ai-screening","mammography"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ai-validation","b-early-detection","b-overdiagnosis","b-workforce"],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"Lancet Oncology","year":2023,"doi":"10.1016/S1470-2045(23)00298-X","pmid":"37541274","authors":"Lång K, Josefsson V, Larsson AM, et al.","paperType":"rct","findings":["Cancer detection rate 6.1 vs 5.1 per 1,000 screened (ratio 1.2, 95% CI 1.0-1.5; 244 vs 203 cancers)","Recall rate 2.2% vs 2.0%; false-positive rate 1.5% in both arms","Screen-reading workload reduced 44.3%","Final analysis (Lancet Digital Health 2025, 105,934 women): detection 6.4 vs 5.0 per 1,000, a 29% increase, with a 44% workload reduction"],"whatItMeans":"AI can take over one reader's work in double-reading screening programmes while finding more cancers. Whether the extra cancers found are ones that would have harmed women, and whether interval cancers fall, is the question the trial's primary endpoint will answer.","caveats":["Interval cancer rate, the primary endpoint, has not yet been reported; more detection could be overdiagnosis","Single Swedish site with a double-reading culture; generalisation to single-reader systems (as in the US) is uncertain","One commercial AI system; results do not automatically transfer to others","Radiologists were aware of AI output, so the trial cannot separate AI accuracy from its effect on human reading"],"changedPractice":false,"participants":80033},{"id":"paper-masaoka-thymoma-clinical-staging-cancer-1981","kind":"paper","name":"Masaoka staging: follow-up study of thymomas with special reference to their clinical stages","aka":[],"tldr":"The Osaka series that grouped thymomas by how far they had invaded, from fully encapsulated to spread inside the chest or beyond, and showed survival fell with each step. Its stages are still used forty years on.","summary":"Retrospective study of 96 patients with thymoma treated at Osaka University, proposing a four-stage system: stage I encapsulated, stage II invasion into the capsule or surrounding fat, stage III invasion of neighbouring organs, stage IVa pleural or pericardial dissemination and stage IVb lymphatic or haematogenous metastasis.\n\nFive-year survival fell with stage, validating the system, which was later refined by Koga and remained the reference until the TNM classification of 2017 and is still reported alongside it.","asOf":"2026-09-18","links":[{"label":"Cancer 1981","url":"https://doi.org/10.1002/1097-0142(19811201)48:11<2485::AID-CNCR2820481123>3.0.CO;2-R"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/7296496/"}],"tags":[],"related":[],"cancers":["thymoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-wiley"],"dependsOn":[],"notes":[],"journal":"Cancer","year":1981,"doi":"10.1002/1097-0142(19811201)48:11<2485::AID-CNCR2820481123>3.0.CO;2-R","pmid":"7296496","authors":"Masaoka A, Monden Y, Nakahara K, Tanioka T.","paperType":"observational","findings":["Survival fell progressively from encapsulated stage I thymoma to disseminated stage IV disease."],"whatItMeans":"Whether a thymoma is called stage I or stage III, and hence whether radiotherapy follows surgery, still traces back to this scheme.","caveats":["A single-institution series of 96 patients.","Now used alongside the IASLC/ITMIG TNM classification."],"changedPractice":true,"participants":96},{"id":"paper-elad-cancer","kind":"paper","name":"MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy","aka":[],"tldr":"Paper cited by four technology pages, indexed on Europe PMC as PubMed record 32786044 and published in Cancer; the citing pages link this DOI, which is how the record was matched.","summary":"Background: Mucositis is a significant toxicity of cancer therapy with numerous systemic sequelae. The goal of this systematic review was to update the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) Clinical Practice Guidelines for the management of mucositis.\n\nMethods: The literature was reviewed systematically to identify interventions for mucositis. Studies were rated according to the presence of major and minor flaws according to previously published criteria. The body of evidence for each intervention and in each treatment setting was assigned a level of evidence based on previously published criteria. Guidelines were developed based on the level of evidence, with 3 possible guideline determinations: recommendation, suggestion, or no guideline possible.\n\nResults: The guideline covers evidence from 1197 publications related to oral or gastrointestinal mucositis. Thirteen new guidelines were developed for or against the use of various interventions in specific treatment settings, and 11 previous guidelines were confirmed after aa review of new evidence. Thirteen previously established guidelines were carried over because there was no new evidence for these interventions.\n\nConclusions: The updated MASCC/ISOO Clinical Practice Guidelines for mucositis provide professional health caregivers with a clinical setting-specific, evidence-based tool to help with the management of mucositis in patients who have cancer.\n\nIndexed on Europe PMC as PubMed record 32786044 (DOI 10.1002/cncr.33100). Matched by DOI alone: four technology pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer 2020","url":"https://doi.org/10.1002/cncr.33100"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32786044/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32786044"}],"tags":["europepmc-ingest"],"related":["glutamine-mucositis-neuropathy","honey-radiation-mucositis","oral-cryotherapy-mucositis","photobiomodulation-mucositis"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-wiley"],"dependsOn":[],"notes":[],"journal":"Cancer","year":2020,"doi":"10.1002/cncr.33100","pmid":"32786044","authors":"Elad S, Cheng KKF, Lalla RV, et al.","paperType":"review","findings":[],"whatItMeans":"Four technology pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-kutner-ann-intern-med","kind":"paper","name":"Massage therapy versus simple touch to improve pain and mood in patients with advanced cancer: a randomized trial","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 18794556 and published in Annals of Internal Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Background: Small studies of variable quality suggest that massage therapy may relieve pain and other symptoms.\n\nObjective: To evaluate the efficacy of massage for decreasing pain and symptom distress and improving quality of life among persons with advanced cancer.\n\nDesign: Multisite, randomized clinical trial.\n\nSetting: Population-based Palliative Care Research Network.\n\nPatients: 380 adults with advanced cancer who were experiencing moderate-to-severe pain; 90% were enrolled in hospice.\n\nIntervention: Six 30-minute massage or simple-touch sessions over 2 weeks.\n\nMeasurements: Primary outcomes were immediate (Memorial Pain Assessment Card, 0- to 10-point scale) and sustained (Brief Pain Inventory [BPI], 0- to 10-point scale) change in pain. Secondary outcomes were immediate change in mood (Memorial Pain Assessment Card) and 60-second heart and respiratory rates and sustained change in quality of life (McGill Quality of Life Questionnaire, 0- to 10-point scale), symptom distress (Memorial Symptom Assessment Scale, 0- to 4-point scale), and analgesic medication use (parenteral morphine equivalents [mg/d]). Immediate outcomes were obtained just before and after each treatment session. Sustained outcomes were obtained at baseline and weekly for 3 weeks.\n\nResults: 298 persons were included in the immediate outcome analysis and 348 in the sustained outcome analysis. A total of 82 persons did not receive any allocated study treatments (37 massage patients, 45 control participants). Both groups demonstrated immediate improvement in pain (massage, -1.87 points [95% CI, -2.07 to -1.67 points]; control, -0.97 point [CI, -1.18 to -0.76 points]) and mood (massage, 1.58 points [CI, 1.40 to 1.76 points]; control, 0.97 point [CI, 0.78 to 1.16 points]). Massage was superior for both immediate pain and mood (mean difference, 0.90 and 0.61 points, respectively; P < 0.001). No between-group mean differences occurred over time in sustained pain (BPI mean pain, 0.07 point [CI, -0.23 to 0.37 points]; BPI worst pain, -0.14 point [CI, -0.59 to 0.31 points]), quality of life (McGill Quality of Life Questionnaire overall, 0.08 point [CI, -0.37 to 0.53 points]), symptom distress (Memorial Symptom Assessment Scale global distress index, -0.002 point [CI, -0.12 to 0.12 points]), or analgesic medication use (parenteral morphine equivalents, -0.10 mg/d [CI, -0.25 to 0.05 mg/d]).\n\nLimitations: The immediate outcome measures were obtained by unblinded study therapists, possibly leading to reporting bias and the overestimation of a beneficial effect. The generalizability to all patients with advanced cancer is uncertain. The differential beneficial effect of massage therapy over simple touch is not conclusive without a usual care control group.\n\nConclusion: Massage may have immediately beneficial effects on pain and mood among patients with advanced cancer. Given the lack of sustained effects and the observed improvements in both study groups, the potential benefits of attention and simple touch should also be considered in this patient population.\n\nIndexed on Europe PMC as PubMed record 18794556 (DOI 10.7326/0003-4819-149-6-200809160-00003). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Ann Intern Med 2008","url":"https://doi.org/10.7326/0003-4819-149-6-200809160-00003"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/18794556/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/18794556"}],"tags":["europepmc-ingest"],"related":["massage-therapy-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-internal-medicine"],"dependsOn":[],"notes":[],"journal":"Annals of Internal Medicine","year":2008,"doi":"10.7326/0003-4819-149-6-200809160-00003","pmid":"18794556","authors":"Kutner JS, Smith MC, Corbin L, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-shin-cochrane-database-syst-rev","kind":"paper","name":"Massage with or without aromatherapy for symptom relief in people with cancer","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 27258432 and published in The Cochrane database of systematic reviews; the citing page links this DOI, which is how the record was matched.","summary":"Background: Massage and aromatherapy massage are used to relieve cancer-related symptoms. A number of claims have been made for these treatments including reduction of pain, anxiety, depression, and stress. Other studies have not shown these benefits.\n\nObjectives: To evaluate the effects of massage with or without aromatherapy on pain and other symptoms associated with cancer.\n\nSearch methods: We searched the following databases and trials registries up to August 2015: the Cochrane Central Register of Controlled Trials (CENTRAL, 2015, Issue 7), MEDLINE (Ovid), EMBASE (Ovid), PsycINFO (Ovid), CINAHL (EBSCO), PubMed Cancer Subset, SADCCT, and the World Health Organization (WHO) ICTRP. We also searched clinical trial registries for ongoing studies.\n\nSelection criteria: Randomised controlled studies (RCTs) reporting the effects of aromatherapy or massage therapy, or both, in people with cancer of any age. We applied no language restrictions. Comparators were massage (using carrier oil only) versus no massage, massage with aromatherapy (using carrier oil plus essential oils) versus no massage, and massage with aromatherapy (using carrier oil plus essential oils) versus massage without aromatherapy (using carrier oil only).\n\nData collection and analysis: At least two review authors selected studies, assessed the risk of bias, and extracted data relating to pain and other symptoms associated with cancer, using standardised forms. We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and created two 'Summary of findings' tables.\n\nMain results: We included 19 studies (21 reports) of very low quality evidence with a total of 1274 participants. We included 14 studies (16 reports) in a qualitative synthesis and five studies in a quantitative synthesis (meta-analysis). Thirteen studies (14 reports, 596 participants) compared massage with no massage. Six studies (seven reports, 561 participants) compared aromatherapy massage with no massage. Two studies (117 participants) compared massage with aromatherapy and massage without aromatherapy. Fourteen studies had a high risk of bias related to sample size and 15 studies had a low risk of bias for blinding the outcome assessment. We judged the studies to be at unclear risk of bias overall. Our primary outcomes were pain and psychological symptoms. Two studies reported physical distress, rash, and general malaise as adverse events. The remaining 17 studies did not report adverse events. We downgraded the GRADE quality of evidence for all outcomes to very low because of observed imprecision, indirectness, imbalance between groups in many studies, and limitations of study design. Massage versus no-massage groupsWe analysed results for pain and anxiety but the quality of evidence was very low as most studies were small and considered at an unclear or high risk of bias due to poor reporting. Short-term pain (Present Pain Intensity-Visual Analogue Scale) was greater for the massage group compared with the no-massage group (one RCT, n = 72, mean difference (MD) -1.60, 95% confidence interval (CI) -2.67 to -0.53). Data for anxiety (State-Trait Anxiety Inventory-state) relief showed no significant difference in anxiety between the groups (three RCTs, n = 98, combined MD -5.36, 95% CI -16.06 to 5.34). The subgroup analysis for anxiety revealed that the anxiety relief for children was greater for the massage group compared with the no-massage group (one RCT, n = 30, MD -14.70, 95% CI -19.33 to -10.07), but the size of this effect was considered not clinically significant. Furthermore, this review demonstrated no differences in effects of massage on depression, mood disturbance, psychological distress, nausea, fatigue, physical symptom distress, or quality of life when compared with no massage. Massage with aromatherapy versus no-massage groupsWe analysed results for pain, anxiety, symptoms relating to the breast, and quality of life but the quality of evidence was very low as studies were generally at a high risk of bias. There was some indication of benefit in the aromatherapy-massage group but this benefit is unlikely to translate into clinical benefit. The relief of medium- and long-term pain (medium-term: one RCT, n = 86, MD 5.30, 95% CI 1.52 to 9.08; long-term: one RCT, n = 86, MD 3.80, 95% CI 0.19 to 7.41), anxiety (two RCTs, n = 253, combined MD -4.50, 95% CI -7.70 to -1.30), and long-term symptoms relating to the breast in people with breast cancer (one RCT, n = 86, MD -9.80, 95% CI -19.13 to -0.47) was greater for the aromatherapy-massage group, but the results were considered not clinically significant. The medium-term quality of life score was lower (better) for the aromatherapy-massage group compared with the no-massage group (one RCT, n = 30, MD -2.00, 95% CI -3.46 to -0.54). Massage with aromatherapy versus massage without aromatherapy groupsFrom the limited evidence available, we were unable to assess the effect of adding aromatherapy to massage on the relief of pain, psychological symptoms including anxiety and depression, physical symptom distress, or quality of life.\n\nAuthors' conclusions: There was a lack of evidence on the clinical effectiveness of massage for symptom relief in people with cancer. Most studies were too small to be reliable and key outcomes were not reported. Any further studies of aromatherapy and massage will need to address these concerns.\n\nIndexed on Europe PMC as PubMed record 27258432 (DOI 10.1002/14651858.cd009873.pub3). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cochrane Database Syst Rev 2016","url":"https://doi.org/10.1002/14651858.cd009873.pub3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27258432/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27258432"}],"tags":["europepmc-ingest"],"related":["aromatherapy-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Cochrane database of systematic reviews","year":2016,"doi":"10.1002/14651858.cd009873.pub3","pmid":"27258432","authors":"Shin ES, Seo KH, Lee SH, et al.","paperType":"meta-analysis","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-stephens-cell","kind":"paper","name":"Massive genomic rearrangement acquired in a single catastrophic event during cancer development","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 21215367 and published in Cell; the citing page links this DOI, which is how the record was matched.","summary":"Cancer is driven by somatically acquired point mutations and chromosomal rearrangements, conventionally thought to accumulate gradually over time. Using next-generation sequencing, we characterize a phenomenon, which we term chromothripsis, whereby tens to hundreds of genomic rearrangements occur in a one-off cellular crisis. Rearrangements involving one or a few chromosomes crisscross back and forth across involved regions, generating frequent oscillations between two copy number states. These genomic hallmarks are highly improbable if rearrangements accumulate over time and instead imply that nearly all occur during a single cellular catastrophe. The stamp of chromothripsis can be seen in at least 2%-3% of all cancers, across many subtypes, and is present in ∼25% of bone cancers. We find that one, or indeed more than one, cancer-causing lesion can emerge out of the genomic crisis. This phenomenon has important implications for the origins of genomic remodeling and temporal emergence of cancer.\n\nIndexed on Europe PMC as PubMed record 21215367 (DOI 10.1016/j.cell.2010.11.055). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cell 2011","url":"https://doi.org/10.1016/j.cell.2010.11.055"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21215367/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/21215367"}],"tags":["europepmc-ingest"],"related":["aneuploidy-theory-of-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Cell","year":2011,"doi":"10.1016/j.cell.2010.11.055","pmid":"21215367","authors":"Stephens PJ, Greenman CD, Fu B, et al.","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-woodcock-n-engl-j-med","kind":"paper","name":"Master Protocols to Study Multiple Therapies, Multiple Diseases, or Both","aka":[],"tldr":"Paper cited by two term pages, indexed on Europe PMC as PubMed record 28679092 and published in New England Journal of Medicine; the citing pages link this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 28679092 (DOI 10.1056/nejmra1510062). Matched by DOI alone: two term pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2017","url":"https://doi.org/10.1056/nejmra1510062"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28679092/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28679092"}],"tags":["europepmc-ingest"],"related":["basket-trial","umbrella-trial"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2017,"doi":"10.1056/nejmra1510062","pmid":"28679092","authors":"Woodcock J, LaVange LM","paperType":"observational","findings":[],"whatItMeans":"Two term pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-levental-cell","kind":"paper","name":"Matrix crosslinking forces tumor progression by enhancing integrin signaling","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 19931152 and published in Cell; the citing page links this DOI, which is how the record was matched.","summary":"Tumors are characterized by extracellular matrix (ECM) remodeling and stiffening. The importance of ECM remodeling to cancer is appreciated; the relevance of stiffening is less clear. We found that breast tumorigenesis is accompanied by collagen crosslinking, ECM stiffening, and increased focal adhesions. Induction of collagen crosslinking stiffened the ECM, promoted focal adhesions, enhanced PI3 kinase (PI3K) activity, and induced the invasion of an oncogene-initiated epithelium. Inhibition of integrin signaling repressed the invasion of a premalignant epithelium into a stiffened, crosslinked ECM and forced integrin clustering promoted focal adhesions, enhanced PI3K signaling, and induced the invasion of a premalignant epithelium. Consistently, reduction of lysyl oxidase-mediated collagen crosslinking prevented MMTV-Neu-induced fibrosis, decreased focal adhesions and PI3K activity, impeded malignancy, and lowered tumor incidence. These data show how collagen crosslinking can modulate tissue fibrosis and stiffness to force focal adhesions, growth factor signaling and breast malignancy.\n\nIndexed on Europe PMC as PubMed record 19931152 (DOI 10.1016/j.cell.2009.10.027). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cell 2009","url":"https://doi.org/10.1016/j.cell.2009.10.027"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19931152/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/19931152"}],"tags":["europepmc-ingest"],"related":["mechanical-theory-of-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Cell","year":2009,"doi":"10.1016/j.cell.2009.10.027","pmid":"19931152","authors":"Levental KR, Yu H, Kass L, et al.","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-matrix-ielsg43-asct-consolidation-pcnsl-illerhaus-lancet-2026","kind":"paper","name":"MATRix/IELSG43: high-dose chemotherapy and autologous stem cell transplant versus non-myeloablative consolidation in primary CNS lymphoma","aka":[],"tldr":"In the largest trial ever run in lymphoma of the brain, a stem cell transplant after MATRix chemotherapy kept 78 percent of patients free of progression at three years against 51 percent with conventional consolidation chemotherapy, and lengthened survival.","summary":"Randomised phase 3 trial in 368 patients aged 18 to 70 with newly diagnosed primary CNS lymphoma: after four cycles of MATRix, 230 patients with responding or stable disease were randomised to high-dose carmustine and thiotepa with autologous stem cell transplant or two cycles of R-DeVIC; 229 were analysed.\n\nAt a median follow-up of 45.3 months three-year progression-free survival was 78 percent after transplant against 51 percent after R-DeVIC (hazard ratio 0.43, p 0.0003), and overall survival was also improved. Adverse events per patient were 14.6 against 9.3; fatal serious adverse events after consolidation occurred in five transplant patients (infections, pulmonary embolism) and two R-DeVIC patients (acute myeloid leukaemia).","asOf":"2026-09-22","links":[{"label":"Lancet 2026","url":"https://doi.org/10.1016/S0140-6736(26)00917-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42486133/"}],"tags":[],"related":[],"cancers":["primary-cns-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["thiotepa","carmustine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["ielsg43"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2026,"doi":"10.1016/S0140-6736(26)00917-7","pmid":"42486133","authors":"Illerhaus G, Ferreri AJM, Wendler J, et al.","paperType":"rct","findings":["Three-year progression-free survival 78 percent (95% CI 69 to 85) with transplant versus 51 percent (41 to 60) with R-DeVIC; hazard ratio 0.43 (0.27 to 0.68), p 0.0003.","Overall survival significantly improved with transplant.","Mean adverse events per patient 14.6 versus 9.3; five versus two fatal serious adverse events after consolidation."],"whatItMeans":"High-dose chemotherapy with autologous transplant is the preferred consolidation for fit patients with primary CNS lymphoma who complete MATRix induction.","caveats":["Only patients up to 70 who responded to induction and were fit for transplant were randomised; a third of enrolled patients never reached randomisation.","Transplant carried more toxicity, including fatal infections."],"changedPractice":true,"participants":368},{"id":"paper-matterhorn-nejm-2025","kind":"paper","name":"MATTERHORN: perioperative durvalumab with FLOT chemotherapy for resectable gastric and gastro-oesophageal junction cancer","aka":[],"tldr":"Adding durvalumab to perioperative FLOT chemotherapy for operable stomach cancer reduced recurrences and doubled the rate of complete pathological response, the first immunotherapy to improve outcomes in curable gastric cancer.","summary":"Phase 3 placebo-controlled trial of 948 patients with resectable stage II to IVA gastric or gastro-oesophageal junction adenocarcinoma randomised to perioperative FLOT with durvalumab or placebo, followed by durvalumab or placebo maintenance.\n\nEvent-free survival at 24 months was 67.4 versus 58.5 percent (hazard ratio 0.71), pathological complete response 19 versus 7 percent, and an interim overall survival analysis favoured durvalumab; surgery rates and toxicity were similar between arms.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2025","url":"https://doi.org/10.1056/NEJMoa2503701"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40454643/"}],"tags":[],"related":[],"cancers":["gastric-pdl1-high"],"sections":[],"technologies":[],"targets":[],"drugs":["durvalumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["matterhorn"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2025,"doi":"10.1056/NEJMoa2503701","pmid":"40454643","authors":"Janjigian YY, Al-Batran SE, Wainberg ZA, et al.","paperType":"rct","findings":["24-month event-free survival 67.4 percent vs 58.5 percent; hazard ratio 0.71.","Pathological complete response 19 percent vs 7 percent."],"whatItMeans":"Perioperative durvalumab with FLOT is a new standard for resectable gastric and junctional adenocarcinoma irrespective of PD-L1 expression.","caveats":["Overall survival analysis interim.","Applicability to Asian populations receiving adjuvant-only chemotherapy is uncertain."],"changedPractice":true,"participants":948},{"id":"paper-antoine-italiano-nat-cancer-2021","kind":"paper","name":"Mature tertiary lymphoid structures predict immune checkpoint inhibitor efficacy in solid tumors independently of PD-L1 expression","aka":[],"tldr":"Paper by Antoine Italiano indexed on Europe PMC as PubMed record 35118423, in Nature Cancer (2021), one of the most cited records naming an author with this name at Institut Bergonié.","summary":"Only a minority of patients derive long-term clinical benefit from anti-PD1/PD-L1 monoclonal antibodies. The presence of tertiary lymphoid structures (TLS) has been associated with improved survival in several tumor types. Here, using a large-scale retrospective analysis of three independent cohorts of cancer patients treated with anti-PD1/PD-L1 antibodies, we showed that the presence of mature TLS was associated with improved objective response rate, progression-free survival, and overall survival independently of PD-L1 expression status and CD8+ T-cell density. These results pave the way for using TLS detection to select patients who are more likely to benefit from immune checkpoint blockade.\n\nIndexed on Europe PMC as PubMed record 35118423 (DOI 10.1038/s43018-021-00232-6). Its author list gives \"Italiano A\" with the affiliation \"Department of Medicine, Institut Bergonié, Bordeaux, France\", which names Institut Bergonié; that is how the record was matched to Antoine Italiano, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Cancer 2021","url":"https://doi.org/10.1038/s43018-021-00232-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35118423/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35118423"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["antoine-italiano"],"bottlenecks":[],"keyPapers":[],"journals":["nature-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Cancer","year":2021,"doi":"10.1038/s43018-021-00232-6","pmid":"35118423","authors":"Vanhersecke L, Brunet M, Guégan JP, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Antoine Italiano at Institut Bergonié, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-maude-ctl019-all-nejm-2014","kind":"paper","name":"Maude 2014: CD19 CAR-T cells produce complete remission in 27 of 30 children and adults with relapsed ALL","aka":[],"tldr":"The first sizeable series of CD19 CAR-T therapy showed complete remission in 90% of patients with leukaemia that had failed everything else, with persistent engineered cells and a new, treatable toxicity.","summary":"Maude and colleagues reported 30 patients (25 children and 5 adults) with relapsed or refractory ALL, including 18 who had relapsed after allogeneic transplant and 3 refractory to blinatumomab, treated with CTL019, an autologous CD19-directed CAR-T with a 4-1BB costimulatory domain. Complete remission occurred in 27 (90%), including MRD-negative remissions; six-month event-free survival was 67% and overall survival 78%. CAR-T cells persisted for up to two years with ongoing B-cell aplasia. All patients developed cytokine release syndrome, severe in 27%, which was reversed by the IL-6 receptor antibody tocilizumab. Together with the earlier single-patient CLL report (Porter et al., NEJM 2011) and the first two children (Grupp et al., NEJM 2013), it established CAR-T as a realistic therapy and drove the pivotal ELIANA trial.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa1407222"},{"label":"First CLL patient report (Porter 2011)","url":"https://doi.org/10.1056/NEJMoa1103849"},{"label":"ClinicalTrials.gov NCT01626495","url":"https://clinicaltrials.gov/study/NCT01626495"}],"tags":[],"related":["paper-eliana-tisagenlecleucel-nejm-2018"],"cancers":["all-leukemia","cll"],"sections":[],"technologies":["car-t"],"targets":["cd19"],"drugs":["tisagenlecleucel"],"companies":["novartis"],"institutions":["penn-abramson"],"pathways":[],"terms":["crs","mrd-negative-cr"],"trials":[],"people":["carl-june","david-porter","bruce-levine"],"bottlenecks":["b-translational-valley","b-manufacturing-cell-therapy"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2014,"doi":"10.1056/NEJMoa1407222","authors":"Maude SL, Frey N, Shaw PA, et al.","paperType":"translational","findings":["30 patients (25 children, 5 adults) with relapsed/refractory ALL; 18 post-transplant, 3 blinatumomab-refractory.","Complete remission in 27 of 30 (90%); 22 of 27 MRD-negative by flow cytometry.","6-month event-free survival 67%; overall survival 78%; 19 patients in sustained remission at report.","CAR-T persistence and B-cell aplasia for up to 2 years in responders.","CRS in 100%, severe in 27%; reversed with tocilizumab; CD19-negative relapse identified as an escape mechanism."],"whatItMeans":"This paper is the proof-of-concept for a living drug: a single infusion of a patient's own engineered T cells could eradicate leukaemia that had survived chemotherapy, transplant and antibody therapy. It defined cytokine release syndrome and its antidote, tocilizumab, and revealed antigen-loss relapse. It led directly to the first approved gene-modified cell therapy three years later.","caveats":["Single-centre, uncontrolled series with short follow-up.","Selected patients able to wait for manufacturing and tolerate lymphodepletion.","Durability was uncertain; about a third relapsed within months, often with CD19-negative disease.","Toxicity management was still empirical."],"changedPractice":true,"participants":30},{"id":"paper-mavoric-mogamulizumab-lancet-oncol-2018","kind":"paper","name":"MAVORIC: mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma","aka":[],"tldr":"The anti-CCR4 antibody mogamulizumab doubled the time to progression compared with vorinostat in previously treated mycosis fungoides and Sezary syndrome, with particularly strong activity in the blood, and became the first antibody approved for these lymphomas.","summary":"Phase 3 trial of 372 patients with relapsed or refractory mycosis fungoides or Sezary syndrome after at least one systemic therapy randomised to mogamulizumab or vorinostat.\n\nMedian progression-free survival was 7.7 versus 3.1 months (hazard ratio 0.53), global response 28 versus 5 percent, with blood responses in 68 percent of mogamulizumab patients; drug rash was the main toxicity.","asOf":"2026-09-17","links":[{"label":"Lancet Oncol 2018","url":"https://doi.org/10.1016/S1470-2045(18)30379-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30100375/"}],"tags":[],"related":[],"cancers":["cutaneous-t-cell-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["mogamulizumab","vorinostat"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["mavoric"],"people":["youn-kim"],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2018,"doi":"10.1016/S1470-2045(18)30379-6","pmid":"30100375","authors":"Kim YH, Bagot M, Pinter-Brown L, et al.","paperType":"rct","findings":["Median progression-free survival 7.7 vs 3.1 months; hazard ratio 0.53.","Overall response 28 percent vs 5 percent; blood compartment response 68 percent."],"whatItMeans":"Mogamulizumab is a standard for advanced-stage cutaneous T-cell lymphoma with blood involvement, particularly Sezary syndrome.","caveats":["Open-label; vorinostat is a weak comparator.","Mogamulizumab-associated rash can mimic disease progression."],"changedPractice":true,"participants":372},{"id":"paper-catalona-psa-screening-test-nejm-1991","kind":"paper","name":"Measurement of prostate-specific antigen in serum as a screening test for prostate cancer","aka":["Catalona 1991","PSA screening 1991","PSA 4.0 threshold"],"tldr":"This is where the number 4.0 came from. Screening 1,653 healthy men over 50 with a blood test and biopsying those above that level found cancers that a finger examination would have missed, and the threshold entered practice worldwide.","summary":"William Catalona and colleagues measured serum prostate-specific antigen in 1,653 healthy men aged 50 or over, sent those at or above 4.0 micrograms per litre for rectal examination and ultrasonography, and biopsied those with abnormal findings. They compared the results against 300 men biopsied because of symptoms or an abnormal examination.\n\nThe paper is short, clear and enormously consequential. It established the 4.0 threshold, showed that the blood test detected cancers that digital rectal examination alone would have missed, and concluded that the combination of the antigen and examination detected prostate cancer better than examination alone. Within a decade prostate-specific antigen testing had spread through United States primary care without a randomised trial of whether it saved lives, which is why the two trials that followed, ERSPC and PLCO, matter so much and why they disagreed so badly.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 1991","url":"https://doi.org/10.1056/nejm199104253241702"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/1707140/"}],"tags":["prostate-evidence"],"related":["paper-stamey-psa-serum-marker-nejm-1987","paper-schroder-erspc-screening-mortality-nejm-2009","paper-andriole-plco-prostate-screening-nejm-2009","early-detection-roadmap","prostate-roadmap"],"cancers":["prostate","prostate-low-risk","prostate-intermediate-risk"],"sections":["early-detection","diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["psa","screening","number-needed-to-screen","lead-time-bias"],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-overdiagnosis","b-prevention-adoption"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":1991,"doi":"10.1056/nejm199104253241702","pmid":"1707140","authors":"Catalona WJ, Smith DS, Ratliff TL, et al.","paperType":"observational","findings":["Serum prostate-specific antigen was 4.0 to 9.9 micrograms per litre in 107 of the 1,653 men (6.5 percent); of the 85 in that group who had biopsies, 19 (22 percent) had prostate cancer.","Levels were 10.0 micrograms per litre or higher in 30 men (1.8 percent); of the 27 in that group who had biopsies, 18 (67 percent) had cancer.","Rectal examination alone would have missed 12 of the 37 cancers (32 percent); ultrasonography alone would have missed 16 of 37 (43 percent).","Prostate-specific antigen measurement had the lowest error rate of the individual tests, and antigen measurement plus rectal examination the lowest of the two-test combinations.","The authors concluded that antigen measurement plus rectal examination, with ultrasonography in men with abnormal findings, detects prostate cancer better than rectal examination alone."],"whatItMeans":"The paper that made opportunistic prostate-specific antigen testing routine, and the source of the threshold still printed on laboratory reports. Everything in the overdiagnosis literature is, in effect, an audit of what this recommendation did when it was applied to whole populations.","caveats":["A detection study: it measured how many cancers were found, not how many deaths were prevented, and the mortality question needed randomised trials.","The 4.0 micrograms per litre threshold is a convention from this cohort, not a biological boundary; cancer occurs below it and benign enlargement raises it.","1,653 self-selected volunteers aged 50 or over at one United States centre; the yield in other populations differs."],"changedPractice":true,"participants":1653},{"id":"paper-symmans-j-clin-oncol","kind":"paper","name":"Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 17785706 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: To measure residual disease after neoadjuvant chemotherapy in order to improve the prognostic information that can be obtained from evaluating pathologic response.\n\nPatients and methods: Pathologic slides and reports were reviewed from 382 patients in two different treatment cohorts: sequential paclitaxel (T) then fluorouracil, doxorubicin, and cyclophosphamide (FAC) in 241 patients; and a single regimen of FAC in 141 patients. Residual cancer burden (RCB) was calculated as a continuous index combining pathologic measurements of primary tumor (size and cellularity) and nodal metastases (number and size) for prediction of distant relapse-free survival (DRFS) in multivariate Cox regression analyses.\n\nResults: RCB was independently prognostic in a multivariate model that included age, pretreatment clinical stage, hormone receptor status, hormone therapy, and pathologic response (pathologic complete response [pCR] v residual disease [RD]; hazard ratio = 2.50; 95% CI 1.70 to 3.69; P <.001). Minimal RD (RCB-I) in 17% of patients carried the same prognosis as pCR (RCB-0). Extensive RD (RCB-III) in 13% of patients was associated with poor prognosis, regardless of hormone receptor status, adjuvant hormone therapy, or pathologic American Joint Committee on Cancer stage of residual disease. The generalizability of RCB for prognosis of distant relapse was confirmed in the FAC-treated validation cohort.\n\nConclusion: RCB determined from routine pathologic materials represented the distribution of RD, was a significant predictor of DRFS, and can be used to define categories of near-complete response and chemotherapy resistance.\n\nIndexed on Europe PMC as PubMed record 17785706 (DOI 10.1200/jco.2007.10.6823). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2007","url":"https://doi.org/10.1200/jco.2007.10.6823"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/17785706/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/17785706"}],"tags":["europepmc-ingest"],"related":["rcb"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2007,"doi":"10.1200/jco.2007.10.6823","pmid":"17785706","authors":"Symmans WF, Peintinger F, Hatzis C, et al.","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-ren-nat-rev-cancer","kind":"paper","name":"Mechanisms of BCR-ABL in the pathogenesis of chronic myelogenous leukaemia","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 15719031 and published in Nature Reviews Cancer; the citing page links this DOI, which is how the record was matched.","summary":"Imatinib, a potent inhibitor of the oncogenic tyrosine kinase BCR-ABL, has shown remarkable clinical activity in patients with chronic myelogenous leukaemia (CML). However, this drug does not completely eradicate BCR-ABL-expressing cells from the body, and resistance to imatinib emerges. Although BCR-ABL remains an attractive therapeutic target, it is important to identify other components involved in CML pathogenesis to overcome this resistance. What have clinical trials of imatinib and studies using mouse models for BCR-ABL leukaemogenesis taught us about the functions of BCR-ABL beyond its kinase activity, and how these functions contribute to CML pathogenesis?\n\nIndexed on Europe PMC as PubMed record 15719031 (DOI 10.1038/nrc1567). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Cancer 2005","url":"https://doi.org/10.1038/nrc1567"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/15719031/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/15719031"}],"tags":["europepmc-ingest"],"related":["cml-signalling"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Cancer","year":2005,"doi":"10.1038/nrc1567","pmid":"15719031","authors":"Ren R","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-sosa-nat-rev-cancer","kind":"paper","name":"Mechanisms of disseminated cancer cell dormancy: an awakening field","aka":[],"tldr":"Paper cited by one idea page, indexed on Europe PMC as PubMed record 25118602 and published in Nature Reviews Cancer; the citing page links this DOI, which is how the record was matched.","summary":"Metastases arise from residual disseminated tumour cells (DTCs). This can happen years after primary tumour treatment because residual tumour cells can enter dormancy and evade therapies. As the biology of minimal residual disease seems to diverge from that of proliferative lesions, understanding the underpinnings of this new cancer biology is key to prevent metastasis. Analysis of approximately 7 years of literature reveals a growing focus on tumour and normal stem cell quiescence, extracellular and stromal microenvironments, autophagy and epigenetics as mechanisms that dictate tumour cell dormancy. In this Review, we attempt to integrate this information and highlight both the weaknesses and the strengths in the field to provide a framework to understand and target this crucial step in cancer progression.\n\nIndexed on Europe PMC as PubMed record 25118602 (DOI 10.1038/nrc3793). Matched by DOI alone: one idea page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Cancer 2014","url":"https://doi.org/10.1038/nrc3793"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25118602/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25118602"}],"tags":["europepmc-ingest"],"related":["idea-dormancy-maintenance-therapy"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Cancer","year":2014,"doi":"10.1038/nrc3793","pmid":"25118602","authors":"Sosa MS, Bragado P, Aguirre-Ghiso JA","paperType":"review","findings":[],"whatItMeans":"One idea page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-annema-jama","kind":"paper","name":"Mediastinoscopy vs endosonography for mediastinal nodal staging of lung cancer: a randomized trial","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 21098770 and published in JAMA; the citing page links this DOI, which is how the record was matched.","summary":"Context: Mediastinal nodal staging is recommended for patients with resectable non-small cell lung cancer (NSCLC). Surgical staging has limitations, which results in the performance of unnecessary thoracotomies. Current guidelines acknowledge minimally invasive endosonography followed by surgical staging (if no nodal metastases are found by endosonography) as an alternative to immediate surgical staging.\n\nObjective: To compare the 2 recommended lung cancer staging strategies.\n\nDesign, setting, and patients: Randomized controlled multicenter trial (Ghent, Leiden, Leuven, Papworth) conducted between February 2007 and April 2009 in 241 patients with resectable (suspected) NSCLC in whom mediastinal staging was indicated based on computed or positron emission tomography.\n\nIntervention: Either surgical staging or endosonography (combined transesophageal and endobronchial ultrasound [EUS-FNA and EBUS-TBNA]) followed by surgical staging in case no nodal metastases were found at endosonography. Thoracotomy with lymph node dissection was performed when there was no evidence of mediastinal tumor spread.\n\nMain outcome measures: The primary outcome was sensitivity for mediastinal nodal (N2/N3) metastases. The reference standard was surgical pathological staging. Secondary outcomes were rates of unnecessary thoracotomy and complications.\n\nResults: Two hundred forty-one patients were randomized, 118 to surgical staging and 123 to endosonography, of whom 65 also underwent surgical staging. Nodal metastases were found in 41 patients (35%; 95% confidence interval [CI], 27%-44%) by surgical staging vs 56 patients (46%; 95% CI, 37%-54%) by endosonography (P =.11) and in 62 patients (50%; 95% CI, 42%-59%) by endosonography followed by surgical staging (P =.02). This corresponded to sensitivities of 79% (41/52; 95% CI, 66%-88%) vs 85% (56/66; 95% CI, 74%-92%) (P =.47) and 94% (62/66; 95% CI, 85%-98%) (P =.02). Thoracotomy was unnecessary in 21 patients (18%; 95% CI, 12%-26%) in the mediastinoscopy group vs 9 (7%; 95% CI, 4%-13%) in the endosonography group (P =.02). The complication rate was similar in both groups.\n\nConclusions: Among patients with (suspected) NSCLC, a staging strategy combining endosonography and surgical staging compared with surgical staging alone resulted in greater sensitivity for mediastinal nodal metastases and fewer unnecessary thoracotomies.\n\nTrial registration: clinicaltrials.gov Identifier: NCT00432640.\n\nIndexed on Europe PMC as PubMed record 21098770 (DOI 10.1001/jama.2010.1705). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA 2010","url":"https://doi.org/10.1001/jama.2010.1705"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21098770/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/21098770"}],"tags":["europepmc-ingest"],"related":["endoscopic-ultrasound-systems"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2010,"doi":"10.1001/jama.2010.1705","pmid":"21098770","authors":"Annema JT, van Meerbeeck JP, Rintoul RC, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-ajcc-8-melanoma-gershenwald-ca-2017","kind":"paper","name":"Melanoma staging: evidence-based changes in the AJCC eighth edition cancer staging manual","aka":[],"tldr":"The eighth-edition melanoma staging system, derived from over 46,000 patients, refined thickness cut-offs and node categories and created the stage IIIA to IIID subgroups whose very different outlooks now guide adjuvant therapy decisions.","summary":"Description of the American Joint Committee on Cancer eighth-edition staging for melanoma, based on an international database of 46,000 patients, including changes to T1 subcategories, removal of mitotic rate from T1 staging, revised N categories incorporating microsatellites and in-transit disease, new stage III subgroups, and M1 subcategories with lactate dehydrogenase.","asOf":"2026-09-17","links":[{"label":"CA Cancer J Clin 2017","url":"https://doi.org/10.3322/caac.21409"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29028110/"}],"tags":[],"related":[],"cancers":["stage-ii-melanoma","stage-iii-melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["jeffrey-gershenwald"],"bottlenecks":[],"keyPapers":[],"journals":["ca-cancer-journal"],"dependsOn":[],"notes":[],"journal":"CA: A Cancer Journal for Clinicians","year":2017,"doi":"10.3322/caac.21409","pmid":"29028110","authors":"Gershenwald JE, Scolyer RA, Hess KR, et al.","paperType":"guideline","findings":["Five-year melanoma-specific survival ranges from 93 percent in stage IIIA to 32 percent in stage IIID.","Stage IIB and IIC have worse survival than stage IIIA."],"whatItMeans":"Stage IIB, IIC and III on this site's melanoma pages, and the recognition that stage IIIA has a better prognosis than stage IIB or IIC, come from this system.","caveats":["Survival estimates predate modern adjuvant therapy."],"changedPractice":true},{"id":"paper-spranger-nature","kind":"paper","name":"Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 25970248 and published in Nature; the citing page links this DOI, which is how the record was matched.","summary":"Melanoma treatment is being revolutionized by the development of effective immunotherapeutic approaches. These strategies include blockade of immune-inhibitory receptors on activated T cells; for example, using monoclonal antibodies against CTLA-4, PD-1, and PD-L1 (refs 3-5). However, only a subset of patients responds to these treatments, and data suggest that therapeutic benefit is preferentially achieved in patients with a pre-existing T-cell response against their tumour, as evidenced by a baseline CD8(+) T-cell infiltration within the tumour microenvironment. Understanding the molecular mechanisms that underlie the presence or absence of a spontaneous anti-tumour T-cell response in subsets of cases, therefore, should enable the development of therapeutic solutions for patients lacking a T-cell infiltrate. Here we identify a melanoma-cell-intrinsic oncogenic pathway that contributes to a lack of T-cell infiltration in melanoma. Molecular analysis of human metastatic melanoma samples revealed a correlation between activation of the WNT/β-catenin signalling pathway and absence of a T-cell gene expression signature. Using autochthonous mouse melanoma models we identified the mechanism by which tumour-intrinsic active β-catenin signalling results in T-cell exclusion and resistance to anti-PD-L1/anti-CTLA-4 monoclonal antibody therapy. Specific oncogenic signals, therefore, can mediate cancer immune evasion and resistance to immunotherapies, pointing to new candidate targets for immune potentiation.\n\nIndexed on Europe PMC as PubMed record 25970248 (DOI 10.1038/nature14404). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2015","url":"https://doi.org/10.1038/nature14404"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25970248/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25970248"}],"tags":["europepmc-ingest"],"related":["immune-desert-exclusion"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2015,"doi":"10.1038/nature14404","pmid":"25970248","authors":"Spranger S, Bao R, Gajewski TF","paperType":"observational","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-seely-integr-cancer-ther","kind":"paper","name":"Melatonin as adjuvant cancer care with and without chemotherapy: a systematic review and meta-analysis of randomized trials","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 22019490 and published in Integrative cancer therapies; the citing page links this DOI, which is how the record was matched.","summary":"Background: Melatonin (MLT) is known to possess potent antioxidant, antiproliferative, immune-modulating, and hormone-modulating properties. Clinical evidence suggests that MLT may have a possible role in the treatment of cancer. The authors systematically reviewed the effects of MLT in conjunction with chemotherapy, radiotherapy, supportive care, and palliative care on 1-year survival, complete response, partial response, stable disease, and chemotherapy-associated toxicities.\n\nMethods: The authors searched 7 databases: MEDLINE (1966-February 2010), AMED (1985-February 2010), Alt HealthWatch (1995-February 2010), CINAHL (1982-February 2010), Nursing and Allied Health Collection: Basic (1985-February 2010), the Cochrane Database (2009), and the Chinese database CNKI (1979-February 2010). They included all trials that randomized patients to treatment, including MLT or a similar control group without MLT.\n\nResults: The authors included data from 21 clinical trials, all of which dealt with solid tumors. The pooled relative risk (RR) for 1-year mortality was 0.63 (95% confidence interval [CI] = 0.53-0.74; P <.001). Improved effect was found for complete response, partial response, and stable disease with RRs of 2.33 (95% CI = 1.29-4.20), 1.90 (1.43-2.51), and 1.51 (1.08-2.12), respectively. In trials combining MLT with chemotherapy, adjuvant MLT decreased 1-year mortality (RR = 0.60; 95% CI = 0.54-0.67) and improved outcomes of complete response, partial response, and stable disease; pooled RRs were 2.53 (1.36-4.71), 1.70 (1.37-2.12), and 1.15 (1.00-1.33), respectively. In these studies, MLT also significantly reduced asthenia, leucopenia, nausea and vomiting, hypotension, and thrombocytopenia.\n\nConclusion: MLT may benefit cancer patients who are also receiving chemotherapy, radiotherapy, supportive therapy, or palliative therapy by improving survival and ameliorating the side effects of chemotherapy.\n\nIndexed on Europe PMC as PubMed record 22019490 (DOI 10.1177/1534735411425484). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Integr Cancer Ther 2012","url":"https://doi.org/10.1177/1534735411425484"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22019490/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/22019490"}],"tags":["europepmc-ingest"],"related":["melatonin-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["integrative-cancer-therapies"],"dependsOn":[],"notes":[],"journal":"Integrative cancer therapies","year":2012,"doi":"10.1177/1534735411425484","pmid":"22019490","authors":"Seely D, Wu P, Fritz H, et al.","paperType":"meta-analysis","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-mesothelin-mesothelioma-j-clin-oncol-2016","kind":"paper","name":"Mesothelin Immunotherapy for Cancer: Ready for Prime Time?","aka":[],"tldr":"Review on Mesothelin in Mesothelioma, in Journal of Clinical Oncology (2016), one of the most cited Europe PMC records with Mesothelin in its title.","summary":"Mesothelin is a tumor antigen that is highly expressed in many human cancers, including malignant mesothelioma and pancreatic, ovarian, and lung adenocarcinomas. It is an attractive target for cancer immunotherapy because its normal expression is limited to mesothelial cells, which are dispensable. Several antibody-based therapeutic agents as well as vaccine and T-cell therapies directed at mesothelin are undergoing clinical evaluation. These include antimesothelin immunotoxins (SS1P, RG7787/LMB-100), chimeric antimesothelin antibody (amatuximab), mesothelin-directed antibody drug conjugates (anetumab ravtansine, DMOT4039A, BMS-986148), live attenuated Listeria monocytogenes-expressing mesothelin (CRS-207, JNJ-64041757), and chimeric antigen receptor T-cell therapies. Two antimesothelin agents are currently in multicenter clinical registration trials for malignant mesothelioma: amatuximab in the first-line setting and anetumab ravtansine as second-line therapy. Phase II randomized clinical trials of CRS-207 as a boosting agent and in combination with immune checkpoint inhibition for pancreatic cancer are nearing completion. These ongoing studies will define the utility of mesothelin immunotherapy for treating cancer.\n\nIndexed on Europe PMC as PubMed record 27863199 (DOI 10.1200/jco.2016.68.3672). Its title names Mesothelin and its text names Mesothelioma; PubMed types it as a review (research-article, Review). It was matched automatically to the idea \"Treat the body cavity, not the bloodstream, for surface spread\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2016","url":"https://doi.org/10.1200/jco.2016.68.3672"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27863199/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27863199"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2016,"doi":"10.1200/jco.2016.68.3672","pmid":"27863199","authors":"Hassan R, Thomas A, Alewine C, et al.","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for Mesothelin in Mesothelioma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Mesothelin in the title and Mesothelioma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-mesothelin-mesothelioma-cancer-discov-2016","kind":"paper","name":"Mesothelin-Targeted CARs: Driving T Cells to Solid Tumors","aka":[],"tldr":"Review on Mesothelin in Mesothelioma, in Cancer Discovery (2016), one of the most cited Europe PMC records with Mesothelin in its title.","summary":"Unlabelled: Chimeric antigen receptors (CAR) are synthetic receptors that target T cells to cell-surface antigens and augment T-cell function and persistence. Mesothelin is a cell-surface antigen implicated in tumor invasion, which is highly expressed in mesothelioma and lung, pancreas, breast, ovarian, and other cancers. Its low-level expression in mesothelia, however, commands thoughtful therapeutic interventions. Encouragingly, recent clinical trials evaluating active immunization or immunoconjugates in patients with pancreatic adenocarcinoma or mesothelioma have shown responses without toxicity. Altogether, these findings and preclinical CAR therapy models using either systemic or regional T-cell delivery argue favorably for mesothelin CAR therapy in multiple solid tumors.\n\nSignificance: Recent success obtained with adoptive transfer of CAR T cells targeting CD19 in patients with refractory hematologic malignancies has generated much enthusiasm for T-cell engineering and raises the prospect of implementing similar strategies for solid tumors. Mesothelin is expressed in a wide range and a high percentage of solid tumors, which we review here in detail. Mesothelin CAR therapy has the potential to treat multiple solid malignancies.\n\nIndexed on Europe PMC as PubMed record 26503962 (DOI 10.1158/2159-8290.cd-15-0583). Its title names Mesothelin and its text names Mesothelioma; PubMed types it as a review (Research Support, Non-U.S. Gov't, research-article, Review, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural). It was matched automatically to the idea \"Treat the body cavity, not the bloodstream, for surface spread\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer Discov 2016","url":"https://doi.org/10.1158/2159-8290.cd-15-0583"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26503962/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26503962"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-discovery"],"dependsOn":[],"notes":[],"journal":"Cancer Discovery","year":2016,"doi":"10.1158/2159-8290.cd-15-0583","pmid":"26503962","authors":"Morello A, Sadelain M, Adusumilli PS","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for Mesothelin in Mesothelioma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Mesothelin in the title and Mesothelioma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-nct03907852-nat-med-2023","kind":"paper","name":"Mesothelin-targeting T cell receptor fusion construct cell therapy in refractory solid tumors: phase 1/2 trial interim results","aka":[],"tldr":"Published report from the Phase 1 trial registered as NCT03907852, in Nature Medicine (2023), chosen as the most cited paper whose own text cites the registry id.","summary":"The T cell receptor fusion construct (TRuC) gavocabtagene autoleucel (gavo-cel) consists of single-domain anti-mesothelin antibody that integrates into the endogenous T cell receptor (TCR) and engages the signaling capacity of the entire TCR upon mesothelin binding. Here we describe phase 1 results from an ongoing phase1/2 trial of gavo-cel in patients with treatment-refractory mesothelin-expressing solid tumors. The primary objectives were to evaluate safety and determine the recommended phase 2 dose (RP2D). Secondary objectives included efficacy. Thirty-two patients received gavo-cel at increasing doses either as a single agent (n = 3) or after lymphodepletion (LD, n = 29). Dose-limiting toxicities of grade 3 pneumonitis and grade 5 bronchioalveolar hemorrhage were noted. The RP2D was determined as 1 × 10 8 cells per m 2 after LD. Grade 3 or higher pneumonitis was seen in 16% of all patients and in none at the RP2D; grade 3 or higher cytokine release syndrome occurred in 25% of all patients and in 15% at the RP2D. In 30 evaluable patients, the overall response rate and disease control rate were 20% (13% confirmed) and 77%, respectively, and the 6-month overall survival rate was 70%. Gavo-cel warrants further study in patients with mesothelin-expressing cancers given its encouraging anti-tumor activity, but it may have a narrow therapeutic window. ClinicalTrials.gov identifier: NCT03907852.\n\nIndexed on Europe PMC as PubMed record 37501016 (DOI 10.1038/s41591-023-02452-y). Its abstract cites the registry id NCT03907852, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Nat Med 2023","url":"https://doi.org/10.1038/s41591-023-02452-y"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37501016/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37501016"},{"label":"ClinicalTrials.gov NCT03907852","url":"https://clinicaltrials.gov/study/NCT03907852"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct03907852"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2023,"doi":"10.1038/s41591-023-02452-y","pmid":"37501016","authors":"Hassan R, Butler M, O'Cearbhaill RE, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03907852 with the most citations, so it is the natural first reading for anyone following the Phase 1 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-mesothelin-mesothelioma-clin-cancer-res-2004","kind":"paper","name":"Mesothelin: a new target for immunotherapy","aka":[],"tldr":"Review on Mesothelin in Mesothelioma, in Clinical Cancer Research (2004), one of the most cited Europe PMC records with Mesothelin in its title.","summary":"Mesothelin is a differentiation antigen present on normal mesothelial cells and overexpressed in several human tumors, including mesothelioma and ovarian and pancreatic adenocarcinoma. The mesothelin gene encodes a precursor protein that is processed to yield the 40-kDa protein, mesothelin, attached to the cell membrane by a glycosylphosphatidyl inositol linkage and a 31-kDa shed fragment named megakaryocyte-potentiating factor. The biological function of mesothelin is not known. Mesothelin is a promising candidate for tumor-specific therapy, given its limited expression in normal tissues and high expression in several cancers. SS1(dsFv)PE38 is a recombinant anti-mesothelin immunotoxin that is undergoing clinical evaluation in patients with mesothelin-expressing tumors. There is evidence that mesothelin is an immunogenic protein and could be exploited as a therapeutic cancer vaccine. A soluble mesothelin variant has been identified and could be a useful tumor marker for malignant mesotheliomas.\n\nIndexed on Europe PMC as PubMed record 15217923 (DOI 10.1158/1078-0432.ccr-03-0801). Its title names Mesothelin and its text names Mesothelioma; PubMed types it as a review (Research Support, Non-U.S. Gov't, Review). It was matched automatically to the idea \"Treat the body cavity, not the bloodstream, for surface spread\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Clin Cancer Res 2004","url":"https://doi.org/10.1158/1078-0432.ccr-03-0801"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/15217923/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/15217923"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2004,"doi":"10.1158/1078-0432.ccr-03-0801","pmid":"15217923","authors":"Hassan R, Bera T, Pastan I","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for Mesothelin in Mesothelioma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Mesothelin in the title and Mesothelioma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-engelman-met-amplification-gefitinib-resistance-science-2007","kind":"paper","name":"MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling","aka":[],"tldr":"Some lung cancers escape a targeted pill without changing the target at all: they simply make many extra copies of a second receptor that switches the same growth signal back on.","summary":"A gefitinib-sensitive lung cancer cell line that developed resistance was found to carry focal amplification of the MET proto-oncogene, and inhibiting MET signalling restored sensitivity. MET amplification was detected in 4 of 18 lung cancer specimens, 22%, that had developed resistance to gefitinib or erlotinib. Amplification of MET causes resistance by driving ERBB3-dependent activation of PI3K, a pathway previously thought to be specific to the EGFR and ERBB receptor family, so MET amplification may promote drug resistance in other ERBB-driven cancers as well.","asOf":"2026-09-25","links":[{"label":"Engelman et al., Science 2007: MET amplification causes gefitinib resistance by activating ERBB3 signalling","url":"https://doi.org/10.1126/science.1141478"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/17463250/"}],"tags":[],"related":["met-amplification-readout"],"cancers":["nsclc"],"sections":[],"technologies":["kinase-inhibitors"],"targets":["met","egfr"],"drugs":["gefitinib","erlotinib"],"companies":[],"institutions":["mgh","dana-farber"],"pathways":["rtk-activation","pi3k-akt-mtor","resistance-routes-map"],"terms":["met-amplification","resistance","gene-amplification"],"trials":[],"people":["pasi-janne"],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2007,"doi":"10.1126/science.1141478","pmid":"17463250","authors":"Engelman JA, Zejnullahu K, Mitsudomi T, et al.","paperType":"basic","findings":["MET amplification in 4 of 18 specimens with acquired resistance to an EGFR inhibitor, 22%.","Resistance is driven through ERBB3-dependent PI3K activation, not through EGFR.","Inhibiting MET restored sensitivity to gefitinib in the resistant line."],"whatItMeans":"It defined bypass resistance as a category and set the treatment rule that follows from it: keep blocking the original target and add an inhibitor of the bypass, which is the logic of every EGFR plus MET combination since.","caveats":["Eighteen specimens, so the 22% figure is imprecise and larger series have found lower rates at first-generation resistance.","Copy-number thresholds for calling amplification vary.","Cell line work leads the clinical evidence."],"changedPractice":true,"participants":18},{"id":"paper-awad-met-exon-14-mutations-lung-jco-2016","kind":"paper","name":"MET exon 14 mutations in non-small-cell lung cancer are associated with advanced age and stage-dependent MET genomic amplification and c-Met overexpression","aka":[],"tldr":"Mutations that make lung cancer cells skip a single piece of the MET gene define a group of patients who are much older than the rest of lung oncology, mostly women, and often never smokers.","summary":"Next-generation sequencing results from 6,376 cancers were interrogated for MET exon 14 mutations, and the clinical, pathological and genomic characteristics of the positive cases were compared with those of KRAS- and EGFR-mutant lung cancers. MET exon 14 mutations were identified in 28 of 933 non-squamous lung cancers, 3.0%, and in no other cancer type in the series. Patients were significantly older, median 72.5 years, than patients with EGFR-mutant (61 years) or KRAS-mutant (65 years) disease; 68% were women and 36% never smokers. Stage IV MET exon 14 tumours were significantly more likely to carry concurrent MET amplification (mean MET to chromosome 7 ratio 4.3 against 1.4) and strong c-Met immunohistochemical expression (mean H score 253 against 155) than earlier-stage cases. A patient whose tumour carried both an exon 14 mutation and amplification of the mutated allele had a major partial response to crizotinib.","asOf":"2026-09-25","links":[{"label":"Awad et al., J Clin Oncol 2016: MET exon 14 mutations across 6,376 cancers, with age, amplification and c-Met overexpression","url":"https://doi.org/10.1200/JCO.2015.63.4600"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26729443/"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":["cgp","histopathology-ihc"],"targets":["met","egfr","kras"],"drugs":["crizotinib","capmatinib","tepotinib"],"companies":[],"institutions":["dana-farber"],"pathways":["rtk-activation"],"terms":["met-exon-14-skipping","met-amplification","gene-amplification","ihc"],"trials":[],"people":["pasi-janne"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2016,"doi":"10.1200/JCO.2015.63.4600","pmid":"26729443","authors":"Awad MM, Oxnard GR, Jackman DM, et al.","paperType":"observational","findings":["MET exon 14 mutations in 28 of 933 non-squamous lung cancers, 3.0%.","Median age 72.5 years, 68% women, 36% never smokers.","Stage IV cases carry concurrent MET amplification and strong c-Met staining far more often than early-stage cases.","Deep response to crizotinib where the mutated allele was also amplified."],"whatItMeans":"It made MET exon 14 a clinical entity rather than a sequencing curiosity, and identified the patients most likely to be missed: older people whose age would otherwise argue against broad sequencing.","caveats":["Retrospective, from one institution's sequencing stream.","Twenty-eight positive cases.","Treatment evidence is a single response rather than a trial."],"changedPractice":false,"participants":6376},{"id":"paper-frampton-met-exon-14-cancer-discov-2015","kind":"paper","name":"MET exon 14 splicing alterations across tumour types and their sensitivity to MET inhibitors","aka":[],"tldr":"This large sequencing study defined MET exon 14 skipping as a recurrent driver in about 3 percent of lung adenocarcinomas and other cancers, showed the mutations are diverse and easily missed, and reported patients responding to MET inhibitors.","summary":"Analysis of comprehensive genomic profiling from more than 38,000 tumours identifying MET exon 14 splice-site alterations in about 3 percent of lung adenocarcinomas and at lower frequency in other tumours, characterising the wide range of DNA changes involved, and describing responses to crizotinib and capmatinib in patients harbouring them.","asOf":"2026-09-17","links":[{"label":"Cancer Discov 2015","url":"https://doi.org/10.1158/2159-8290.CD-15-0285"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25971938/"}],"tags":[],"related":["met-ex14"],"cancers":["met-altered-nsclc","nsclc"],"sections":[],"technologies":["cgp"],"targets":["met"],"drugs":[],"companies":[],"institutions":[],"pathways":["rtk-activation"],"terms":["met-exon-14-skipping"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-discovery"],"dependsOn":[],"notes":[],"journal":"Cancer Discovery","year":2015,"doi":"10.1158/2159-8290.CD-15-0285","pmid":"25971938","authors":"Frampton GM, Ali SM, Rosenzweig M, et al.","paperType":"translational","findings":["MET exon 14 alterations in about 3 percent of lung adenocarcinomas, more common in older patients and in sarcomatoid histology.","Clinical responses to MET inhibitors in patients with the alteration."],"whatItMeans":"The paper established MET exon 14 skipping as a bona fide lung cancer driver and showed why RNA-based or broad DNA testing is needed to detect it, paving the way for capmatinib and tepotinib.","caveats":["Retrospective sequencing database with case reports of response."],"changedPractice":true},{"id":"paper-chang-cell","kind":"paper","name":"Metabolic Competition in the Tumor Microenvironment Is a Driver of Cancer Progression","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 26321679 and published in Cell; the citing page links this DOI, which is how the record was matched.","summary":"Failure of T cells to protect against cancer is thought to result from lack of antigen recognition, chronic activation, and/or suppression by other cells. Using a mouse sarcoma model, we show that glucose consumption by tumors metabolically restricts T cells, leading to their dampened mTOR activity, glycolytic capacity, and IFN-γ production, thereby allowing tumor progression. We show that enhancing glycolysis in an antigenic \"regressor\" tumor is sufficient to override the protective ability of T cells to control tumor growth. We also show that checkpoint blockade antibodies against CTLA-4, PD-1, and PD-L1, which are used clinically, restore glucose in tumor microenvironment, permitting T cell glycolysis and IFN-γ production. Furthermore, we found that blocking PD-L1 directly on tumors dampens glycolysis by inhibiting mTOR activity and decreasing expression of glycolysis enzymes, reflecting a role for PD-L1 in tumor glucose utilization. Our results establish that tumor-imposed metabolic restrictions can mediate T cell hyporesponsiveness during cancer.\n\nIndexed on Europe PMC as PubMed record 26321679 (DOI 10.1016/j.cell.2015.08.016). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cell 2015","url":"https://doi.org/10.1016/j.cell.2015.08.016"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26321679/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26321679"}],"tags":["europepmc-ingest"],"related":["nutrient-competition-tme"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Cell","year":2015,"doi":"10.1016/j.cell.2015.08.016","pmid":"26321679","authors":"Chang CH, Qiu J, O'Sullivan D, et al.","paperType":"observational","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-gerstberger-cell","kind":"paper","name":"Metastasis","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 37059065 and published in Cell; the citing page links this DOI, which is how the record was matched.","summary":"Most cancer-associated deaths occur due to metastasis, yet our understanding of metastasis as an evolving, heterogeneous, systemic disease and of how to effectively treat it is still emerging. Metastasis requires the acquisition of a succession of traits to disseminate, variably enter and exit dormancy, and colonize distant organs. The success of these events is driven by clonal selection, the potential of metastatic cells to dynamically transition into distinct states, and their ability to co-opt the immune environment. Here, we review the main principles of metastasis and highlight emerging opportunities to develop more effective therapies for metastatic cancer.\n\nIndexed on Europe PMC as PubMed record 37059065 (DOI 10.1016/j.cell.2023.03.003). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cell 2023","url":"https://doi.org/10.1016/j.cell.2023.03.003"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37059065/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37059065"}],"tags":["europepmc-ingest"],"related":["metastatic-cascade"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Cell","year":2023,"doi":"10.1016/j.cell.2023.03.003","pmid":"37059065","authors":"Gerstberger S, Jiang Q, Ganesh K","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-massague-nature","kind":"paper","name":"Metastatic colonization by circulating tumour cells","aka":[],"tldr":"Paper cited by two pathway pages and one idea page, indexed on Europe PMC as PubMed record 26791720 and published in Nature; the citing pages link this DOI, which is how the record was matched.","summary":"Metastasis is the main cause of death in people with cancer. To colonize distant organs, circulating tumour cells must overcome many obstacles through mechanisms that we are only now starting to understand. These include infiltrating distant tissue, evading immune defences, adapting to supportive niches, surviving as latent tumour-initiating seeds and eventually breaking out to replace the host tissue. They make metastasis a highly inefficient process. However, once metastases have been established, current treatments frequently fail to provide durable responses. An improved understanding of the mechanistic determinants of such colonization is needed to better prevent and treat metastatic cancer.\n\nIndexed on Europe PMC as PubMed record 26791720 (DOI 10.1038/nature17038). Matched by DOI alone: two pathway pages and one idea page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2016","url":"https://doi.org/10.1038/nature17038"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26791720/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26791720"}],"tags":["europepmc-ingest"],"related":["intravasation-ctc-survival","metastatic-cascade","idea-dtc-colonisation-determinants"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2016,"doi":"10.1038/nature17038","pmid":"26791720","authors":"Massagué J, Obenauf AC","paperType":"review","findings":[],"whatItMeans":"Two pathway pages and one idea page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-esmo-metastatic-colorectal-cancer-guideline-ann-oncol-2023","kind":"paper","name":"Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","aka":[],"tldr":"The European oncology society's 2023 guideline for bowel cancer that has spread, covering which tests every patient needs, how to choose the first combination of drugs, when to operate on liver secondaries and how to follow patients up.","summary":"ESMO Clinical Practice Guideline for metastatic colorectal cancer, published in Annals of Oncology in 2023 by Cervantes, Adam, Roselló, Arnold, Normanno, Taïeb, Seligmann, De Baere, Osterlund, Yoshino and Martinelli for the ESMO Guidelines Committee. Europe PMC indexes no abstract for this article, so OnCo carries no figures from it; the guideline itself is open on the ESMO website and is maintained as a living document there.\n\nIt is the document that fixes the molecular work-up OnCo's colorectal pages assume: RAS and BRAF status, mismatch repair or microsatellite instability status, and HER2 on every patient with metastatic disease, with primary tumour sidedness used alongside RAS status to choose between an EGFR antibody and bevacizumab.","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2023","url":"https://doi.org/10.1016/j.annonc.2022.10.003"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36307056/"},{"label":"ESMO guidelines: gastrointestinal cancers","url":"https://www.esmo.org/guidelines/esmo-clinical-practice-guidelines-gastrointestinal-cancers"},{"label":"NICE NG151: colorectal cancer (published 29 January 2020)","url":"https://www.nice.org.uk/guidance/ng151"}],"tags":["colorectal-evidence"],"related":["esmo-guidelines"],"cancers":["colorectal"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["esmo"],"pathways":[],"terms":["sidedness","msi"],"trials":["paradigm","keynote-177","beacon-crc"],"people":["andres-cervantes","eric-van-cutsem","josep-tabernero"],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2023,"doi":"10.1016/j.annonc.2022.10.003","pmid":"36307056","authors":"Cervantes A, Adam R, Roselló S, et al.","paperType":"guideline","findings":["No abstract is indexed on Europe PMC; recommendations are read from the guideline itself."],"whatItMeans":"This is the European standard the UK and NHS page for colorectal cancer is compared against; NICE NG151 covers the same ground for England with a narrower set of funded drugs.","caveats":["Published before BREAKWATER moved the BRAF V600E triplet into first line and before the 2024 and 2025 CheckMate 8HW and ATOMIC readouts.","Guideline text, not a trial; each recommendation carries its own level and grade within the document."],"changedPractice":true},{"id":"paper-cheng-melanoma-ctdna-antiparasitic-front-oncol-2026","kind":"paper","name":"Metastatic melanoma with initial ctDNA decline and radiographic response during self-directed antiparasitic use: treatment effect or spontaneous regression?","aka":[],"tldr":"A man with metastatic melanoma who refused standard treatment and took ivermectin and fenbendazole saw his tumour markers and scans improve for a while, then worsen; his oncologists judged spontaneous immune regression at least as likely as any drug effect.","summary":"A 74-year-old man with nodular melanoma and nodal and liver metastases declined guideline-directed therapy and took ivermectin and fenbendazole with lifestyle changes; his disease initially showed reduced metabolic activity and size on imaging and his tumour-informed ctDNA fell from 2.04 to 0.18 MTM/mL, then both worsened, with ctDNA rising to 0.93 MTM/mL and the dominant axillary mass growing (Cheng melanoma case report 2026). The tumour carried at least 50 mutations per megabase, placing it at the extreme immunogenic end of the spectrum, and the authors write that spontaneous immune-mediated regression is at least as plausible as any effect of the patient's interventions, that clinical evidence for efficacy is absent, and that safety counselling is needed given the drugs' reported toxicities (Cheng melanoma case report 2026).","asOf":"2026-09-24","links":[{"label":"Cheng melanoma case report 2026","url":"https://doi.org/10.3389/fonc.2026.1907192"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42745863/"}],"tags":[],"related":[],"cancers":["melanoma"],"sections":[],"technologies":["fenbendazole-ivermectin-repurposing-claims"],"targets":[],"drugs":["ivermectin","fenbendazole"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo agent (Claude Fable 5.1)","editedOn":"2026-09-24","note":"Written from cached ClinicalTrials.gov v2, Europe PMC, DailyMed, Drugs@FDA and WHO eEML responses; no figure appears without its source link."},"journal":"Frontiers in Oncology","year":2026,"doi":"10.3389/fonc.2026.1907192","pmid":"42745863","authors":"Cheng R, Araujo DV.","paperType":"observational","findings":["Transient ctDNA and imaging improvement followed by progression during self-directed ivermectin and fenbendazole.","Very high tumour mutational burden made spontaneous immune regression a plausible explanation."],"whatItMeans":"Shows why single stories cannot settle the question: a melanoma this immunogenic can wax and wane on its own, and the improvement did not last.","caveats":["Single case; the patient declined immunotherapy, which such a tumour would be expected to respond to."],"changedPractice":false,"participants":1},{"id":"paper-asco-metastatic-pancreatic-cancer-guideline-update-jco-2020","kind":"paper","name":"Metastatic Pancreatic Cancer: ASCO Guideline Update","aka":[],"tldr":"The 2020 American guideline update that told doctors to test every treatment-eligible patient with metastatic pancreatic cancer for inherited BRCA changes, mismatch repair deficiency and TRK fusions, because each now had a drug attached.","summary":"ASCO convened an Expert Panel and systematic review to update its metastatic pancreatic cancer guideline for therapy after first-line treatment. One randomised trial of olaparib versus placebo (POLO), one report on phase 1 and 2 studies of larotrectinib and one on entrectinib met the inclusion criteria. New or updated recommendations cover germline and somatic testing for microsatellite instability or mismatch repair deficiency, BRCA mutations and TRK alterations in all treatment-eligible patients, to select patients for pembrolizumab, olaparib, larotrectinib or entrectinib, or for trials. The panel continued to endorse the 2018 recommendations for second-line chemotherapy (gemcitabine plus nab-paclitaxel after FOLFIRINOX; fluorouracil plus nanoliposomal irinotecan after gemcitabine-based therapy) and for palliative care and follow-up.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2020","url":"https://doi.org/10.1200/JCO.20.01364"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32755482/"},{"label":"The 2018 update this built on (J Clin Oncol 2018)","url":"https://doi.org/10.1200/JCO.2018.78.9636"},{"label":"ASCO gastrointestinal cancer guidelines","url":"https://ascopubs.org/topics/asco-guidelines/gastrointestinal-cancer"}],"tags":["pancreatic-evidence"],"related":["paper-polo-olaparib-maintenance-gbrca-pancreatic-nejm-2019"],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":["olaparib","larotrectinib","entrectinib","pembrolizumab","gemcitabine-nab-paclitaxel","liposomal-irinotecan"],"companies":[],"institutions":["asco"],"pathways":[],"terms":["gbrca-mutation","germline-vs-somatic"],"trials":["polo"],"people":["thierry-conroy","eileen-oreilly"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/JCO.20.01364","pmid":"32755482","authors":"Sohal DPS, Kennedy EB, Cinar P, et al.","paperType":"guideline","findings":["Three reports informed the update: POLO (olaparib versus placebo), larotrectinib phase 1 and 2, entrectinib phase 1 and 2.","Germline and somatic testing for mismatch repair deficiency, BRCA mutations and TRK alterations is recommended for all treatment-eligible patients.","Second-line chemotherapy, follow-up and palliative care recommendations from 2018 were carried forward."],"whatItMeans":"The document that made biomarker testing part of routine pancreatic cancer care in the United States; the 2018 version it built on fixed the second-line chemotherapy sequence still used in most guidelines.","caveats":["Predates the KRAS G12C inhibitors, NALIRIFOX and daraxonrasib.","The recommended targeted drugs each apply to a few percent of patients."],"changedPractice":true},{"id":"paper-andrea-decensi-cancer-prev-res-phila-2014","kind":"paper","name":"Metformin and cancer risk and mortality: a systematic review and meta-analysis taking into account biases and confounders","aka":[],"tldr":"Paper by Andrea DeCensi indexed on Europe PMC as PubMed record 24985407, in Cancer prevention research (2014), one of the most cited records naming an author with this name at E.O. Ospedali Galliera.","summary":"Previous meta-analyses have shown that the antidiabetic agent metformin is associated with reduced cancer incidence and mortality. However, this effect has not been consistently demonstrated in animal models and recent epidemiologic studies. We performed a meta-analysis with a focus on confounders and biases, including body mass index (BMI), study type, and time-related biases. We identified 71 articles published between January 1, 1966, and May 31, 2013, through Pubmed, ISI Web of Science (Science Citation Index Expanded), Embase, and the Cochrane library that were related to metformin and cancer incidence or mortality. Study characteristics and outcomes were abstracted for each study that met inclusion criteria. We included estimates from 47 independent studies and 65,540 cancer cases in patients with diabetes. Overall cancer incidence was reduced by 31% [summary relative risk (SRR), 0.69; 95% confidence interval (CI), 0.52-0.90], although between-study heterogeneity was considerable (I(2) = 88%). Cancer mortality was reduced by 34% (SRR, 0.66; 95% CI, 0.54-0.81; I(2) = 21%). BMI-adjusted studies and studies without time-related biases also showed significant reduction in cancer incidence (SRR, 0.82; 95% CI, 0.70-0.96 with I(2) = 76% and SRR, 0.90; 95% CI, 0.89-0.91 with I(2) = 56%, respectively), albeit with lesser magnitude (18% and 10% reduction, respectively). However, studies of cancer mortality and individual organ sites did not consistently show significant reductions across all types of analyses. Although these associations may not be causal, our results show that metformin may reduce cancer incidence and mortality in patients with diabetes However, the reduction seems to be of modest magnitude and not affecting all populations equally. Clinical trials are needed to determine if these observations apply to nondiabetic populations and to specific organ sites.\n\nIndexed on Europe PMC as PubMed record 24985407 (DOI 10.1158/1940-6207.capr-13-0424). Its author list gives \"DeCensi A\" with the affiliation \"Division of Medical Oncology, E.O. Ospedali Galliera, Genoa, Italy\", which names E.O. Ospedali Galliera; that is how the record was matched to Andrea DeCensi, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer Prev Res (Phila) 2014","url":"https://doi.org/10.1158/1940-6207.capr-13-0424"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24985407/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/24985407"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["andrea-decensi"],"bottlenecks":[],"keyPapers":[],"journals":["cancer-prevention-research"],"dependsOn":[],"notes":[],"journal":"Cancer prevention research","year":2014,"doi":"10.1158/1940-6207.capr-13-0424","pmid":"24985407","authors":"Gandini S, Puntoni M, Heckman-Stoddard BM, et al.","paperType":"meta-analysis","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Andrea DeCensi at E.O. Ospedali Galliera, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-authors-nat-methods","kind":"paper","name":"Method of the Year 2012","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 23547284 and published in Nature methods; the citing page links this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 23547284 (DOI 10.1038/nmeth.2329). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Methods 2013","url":"https://doi.org/10.1038/nmeth.2329"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23547284/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/23547284"}],"tags":["europepmc-ingest"],"related":["proteomics-platforms"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature methods","year":2013,"doi":"10.1038/nmeth.2329","pmid":"23547284","authors":"Authors not listed","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-authors-nat-methods-2021","kind":"paper","name":"Method of the Year 2020: spatially resolved transcriptomics","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 33408396 and published in Nature methods; the citing page links this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 33408396 (DOI 10.1038/s41592-020-01042-x). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Methods 2021","url":"https://doi.org/10.1038/s41592-020-01042-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33408396/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33408396"}],"tags":["europepmc-ingest"],"related":["spatial-biology-instruments"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature methods","year":2021,"doi":"10.1038/s41592-020-01042-x","pmid":"33408396","authors":"Authors not listed","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-bielack-j-clin-oncol","kind":"paper","name":"Methotrexate, Doxorubicin, and Cisplatin (MAP) Plus Maintenance Pegylated Interferon Alfa-2b Versus MAP Alone in Patients With Resectable High-Grade Osteosarcoma and Good Histologic Response to Preoperative MAP: First Results of the EURAMOS-1 Good Response Randomized Controlled Trial","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 26033801 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: EURAMOS-1, an international randomized controlled trial, investigated maintenance therapy with pegylated interferon alfa-2b (IFN-α-2b) in patients whose osteosarcoma showed good histologic response (good response) to induction chemotherapy.\n\nPatients and methods: At diagnosis, patients age ≤ 40 years with resectable high-grade osteosarcoma were registered. Eligibility after surgery for good response random assignment included ≥ two cycles of preoperative MAP (methotrexate, doxorubicin, and cisplatin), macroscopically complete surgery of primary tumor, < 10% viable tumor, and no disease progression. These patients were randomly assigned to four additional cycles MAP with or without IFN-α-2b (0.5 to 1.0 μg/kg per week subcutaneously, after chemotherapy until 2 years postregistration). Outcome measures were event-free survival (EFS; primary) and overall survival and toxicity (secondary).\n\nResults: Good response was reported in 1,041 of 2,260 registered patients; 716 consented to random assignment (MAP, n = 359; MAP plus IFN-α-2b, n = 357), with baseline characteristics balanced by arm. A total of 271 of 357 started IFN-α-2b; 105 stopped early, and 38 continued to receive treatment at data freeze. Refusal and toxicity were the main reasons for never starting IFN-α-2b and for stopping prematurely, respectively. Median IFN-α-2b duration, if started, was 67 weeks. A total of 133 of 268 patients who started IFN-α-2b and provided toxicity information reported grade ≥ 3 toxicity during IFN-α-2b treatment. With median follow-up of 44 months, 3-year EFS for all 716 randomly assigned patients was 76% (95% CI, 72% to 79%); 174 EFS events were reported (MAP, n = 93; MAP plus IFN-α-2b, n = 81). Hazard ratio was 0.83 (95% CI, 0.61 to 1.12; P =.214) from an adjusted Cox model.\n\nConclusion: At the preplanned analysis time, MAP plus IFN-α-2b was not statistically different from MAP alone. A considerable proportion of patients never started IFN-α-2b or stopped prematurely. Long-term follow-up for events and survival continues.\n\nIndexed on Europe PMC as PubMed record 26033801 (DOI 10.1200/jco.2014.60.0734). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2015","url":"https://doi.org/10.1200/jco.2014.60.0734"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26033801/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26033801"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["euramos-1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2015,"doi":"10.1200/jco.2014.60.0734","pmid":"26033801","authors":"Bielack SS, Smeland S, Whelan JS, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-mntx-302-thomas-nejm-2008","kind":"paper","name":"Methylnaltrexone for opioid-induced constipation in advanced illness (MNTX 302)","aka":[],"tldr":"In people with advanced illness whose strong painkillers had caused constipation that laxatives could not shift, a methylnaltrexone injection produced a bowel movement within four hours in about half, against about one in seven on placebo, without undoing pain relief.","summary":"Primary publication of MNTX 302 (NCT00402038). A total of 133 patients who had received opioids for two or more weeks, with stable doses of opioids and laxatives for three or more days without relief of opioid-induced constipation, were randomly assigned to subcutaneous methylnaltrexone 0.15 mg per kilogram or placebo every other day for two weeks. Coprimary outcomes were laxation within four hours after the first dose and laxation within four hours after two or more of the first four doses.\n\nLaxation within four hours of the first dose occurred in 48 percent of the methylnaltrexone group and 15 percent of the placebo group; laxation without a rescue laxative after two or more of the first four doses occurred in 52 percent versus 8 percent (P less than 0.001 for both). The response rate held through a three-month open-label extension. Median time to laxation was significantly shorter with methylnaltrexone. No evidence of centrally mediated opioid withdrawal or change in pain scores was seen; abdominal pain and flatulence were the most common adverse events.","asOf":"2026-09-24","links":[{"label":"NEJM 2008","url":"https://doi.org/10.1056/NEJMoa0707377"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/18509120/"},{"label":"ClinicalTrials.gov NCT00402038","url":"https://clinicaltrials.gov/study/NCT00402038"}],"tags":[],"related":[],"cancers":[],"sections":["supportive-care"],"technologies":[],"targets":[],"drugs":["methylnaltrexone"],"companies":["bausch-health"],"institutions":[],"pathways":[],"terms":[],"trials":["mntx-302"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2008,"doi":"10.1056/NEJMoa0707377","pmid":"18509120","authors":"Thomas J, Karver S, Cooney GA, et al.","paperType":"rct","findings":["Laxation within 4 hours of the first dose: 48 percent with methylnaltrexone vs 15 percent with placebo (P<0.001).","Laxation without rescue laxative within 4 hours after two or more of the first four doses: 52 percent vs 8 percent (P<0.001).","No evidence of central opioid withdrawal or change in pain scores; abdominal pain and flatulence were the commonest adverse events."],"whatItMeans":"This trial, with its single-dose companion MNTX 301, is the evidence behind the 2008 US approval of Relistor for opioid-induced constipation in palliative care when laxatives fail. For a patient on strong opioids, it shows that the constipation can be reversed at the gut without touching the pain relief.","caveats":["Two-week double-blind phase; longer-term data come from the open-label extension.","The abstract gives no per-arm patient numbers; the 62 and 71 split is from the Relistor label.","Patients had advanced illness of mixed cause; most, per the label, had incurable cancer, but the trial did not select by cancer type."],"changedPractice":true,"participants":133},{"id":"paper-calin-nat-rev-cancer","kind":"paper","name":"MicroRNA signatures in human cancers","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 17060945 and published in Nature Reviews Cancer; the citing page links this DOI, which is how the record was matched.","summary":"MicroRNA (miRNA) alterations are involved in the initiation and progression of human cancer. The causes of the widespread differential expression of miRNA genes in malignant compared with normal cells can be explained by the location of these genes in cancer-associated genomic regions, by epigenetic mechanisms and by alterations in the miRNA processing machinery. MiRNA-expression profiling of human tumours has identified signatures associated with diagnosis, staging, progression, prognosis and response to treatment. In addition, profiling has been exploited to identify miRNA genes that might represent downstream targets of activated oncogenic pathways, or that target protein-coding genes involved in cancer.\n\nIndexed on Europe PMC as PubMed record 17060945 (DOI 10.1038/nrc1997). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Cancer 2006","url":"https://doi.org/10.1038/nrc1997"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/17060945/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/17060945"}],"tags":["europepmc-ingest"],"related":["micrornas-in-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Cancer","year":2006,"doi":"10.1038/nrc1997","pmid":"17060945","authors":"Calin GA, Croce CM","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-kurata-japanese-tnbc-msi-breast-cancer-2020","kind":"paper","name":"Microsatellite instability in Japanese female patients with triple-negative breast cancer","aka":[],"tldr":"Two of 228 Japanese triple-negative breast cancers, under 1%, were MSI-high; both were aggressive basal-like tumours without BRCA-like features.","summary":"MSI in 228 TNBCs was evaluated with the Promega MSI Analysis System 1.2 (BAT-26, NR-21, BAT-25, MONO-27, NR-24) without normal tissue controls. 222 (97.4%) were stable, 4 (1.7%) MSI-low and 2 (0.9%) MSI-high; the two MSI-high tumours were nuclear grade 3, Ki-67 above 30%, basal-like and non-BRCA-like, with inconsistent TILs, CD8 and PD-L1.","asOf":"2026-09-24","links":[{"label":"Kurata et al., Breast Cancer 2020: MSI in 228 Japanese TNBC patients","url":"https://doi.org/10.1007/s12282-019-01043-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31907878/"}],"tags":[],"related":["msi-high"],"cancers":["tnbc"],"sections":[],"technologies":[],"targets":["mmr"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["msi"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["breast-cancer-jbcs"],"dependsOn":[],"notes":[],"journal":"Breast Cancer","year":2020,"doi":"10.1007/s12282-019-01043-5","pmid":"31907878","authors":"Kurata K, Kubo M, Kai M, et al.","paperType":"observational","findings":["MSI-high 2 of 228 (0.9%); MSI-low 1.7%.","MSI-high tumours were grade 3, Ki-67-high and basal-like."],"whatItMeans":"Rare MSI-high TNBC exists and qualifies for tumour-agnostic pembrolizumab, so comprehensive genomic profiling should report MSI even though dedicated testing is low-yield.","caveats":["No matched normal; small numbers of positives.","Japanese single-region cohort."],"changedPractice":false,"participants":228},{"id":"paper-cillessen-psychooncology","kind":"paper","name":"Mindfulness-based interventions for psychological and physical health outcomes in cancer patients and survivors: A systematic review and meta-analysis of randomized controlled trials","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 31464026 and published in Psycho-oncology; the citing page links this DOI, which is how the record was matched.","summary":"Objective: Mindfulness-based interventions (MBIs) are increasingly used within psycho-oncology. Since the publication of the most recent comprehensive meta-analysis on MBIs in cancer in 2012, the number of published trials has more than doubled. We therefore conducted a systematic review and meta-analysis of randomized controlled trials (RCTs), testing the efficacy of MBIs on measures of psychological distress (primary outcome) and other health outcomes in cancer patients and survivors.\n\nMethods: Two authors conducted independent literature searches in electronic databases from first available date to 10 October 2018, selected eligible studies, extracted data for meta-analysis, and evaluated risk of bias.\n\nResults: Twenty-nine independent RCTs (reported in 38 papers) with 3274 participants were included. Small and statistically significant pooled effects of MBIs on combined measures of psychological distress were found at post-intervention (Hedges's g = 0.32; 95%CI: 0.22-0.41; P <.001) and follow-up (g = 0.19; 95%CI: 0.07-0.30; P <.002). Statistically significant effects were also found at either post-intervention or follow-up for a range of self-reported secondary outcomes, including anxiety, depression, fear of cancer recurrence, fatigue, sleep disturbances, and pain (g: 0.20 to 0.51; p: <.001 to.047). Larger effects of MBIs on psychological distress were found in studies (a) adhering to the original MBI manuals, (b) with younger patients, (c) with passive control conditions, and (d) shorter time to follow-up. Improvements in mindfulness skills were associated with greater reductions in psychological distress at post-intervention.\n\nConclusions: MBIs appear efficacious in reducing psychological distress and other symptoms in cancer patients and survivors. However, many of the effects were of small magnitude, suggesting a need for intervention optimization research.\n\nIndexed on Europe PMC as PubMed record 31464026 (DOI 10.1002/pon.5214). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Psychooncology 2019","url":"https://doi.org/10.1002/pon.5214"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31464026/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31464026"}],"tags":["europepmc-ingest"],"related":["mindfulness-based-interventions"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["psycho-oncology-journal"],"dependsOn":[],"notes":[],"journal":"Psycho-oncology","year":2019,"doi":"10.1002/pon.5214","pmid":"31464026","authors":"Cillessen L, Johannsen M, Speckens AEM, et al.","paperType":"meta-analysis","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-minnesota-fobt-nejm-1993","kind":"paper","name":"Minnesota trial: a yearly stool blood test cuts bowel cancer deaths by a third","aka":[],"tldr":"Annual faecal occult blood testing followed by colonoscopy for positives reduced colorectal cancer deaths by 33% over 13 years, the first proof that bowel cancer screening saves lives.","summary":"The Minnesota Colon Cancer Control Study randomised 46,551 volunteers aged 50-80 to annual guaiac faecal occult blood testing, biennial testing, or no screening. Positive tests led to colonoscopy.\n\nAfter 13 years, colorectal cancer mortality was 33% lower with annual screening (5.88 vs 8.83 deaths per 1,000); the biennial arm showed a smaller, initially non-significant reduction that became significant with longer follow-up. Thirty-year follow-up (Shaukat 2013) confirmed relative reductions of 32% for annual and 22% for biennial screening.\n\nThis trial, with the Nottingham and Funen trials, made stool-based screening the backbone of population bowel cancer programmes, later upgraded to the faecal immunochemical test.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1056/NEJM199305133281901"},{"label":"30-year follow-up (Shaukat 2013)","url":"https://doi.org/10.1056/NEJMoa1300720"}],"tags":[],"related":["paper-nordicc-nejm-2022","idea-prev-fit-risk-adapted-thresholds","colorectal-roadmap","paper-hardcastle-nottingham-faecal-occult-blood-lancet-1996","paper-kronborg-funen-faecal-occult-blood-lancet-1996"],"cancers":["colorectal"],"sections":["early-detection"],"technologies":["colorectal-screening"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["fit-test"],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-prevention-adoption"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":1993,"doi":"10.1056/NEJM199305133281901","pmid":"8474513","authors":"Mandel JS, Bond JH, Church TR, et al.","paperType":"rct","findings":["Colorectal cancer mortality reduced 33% with annual testing at 13 years (5.88 vs 8.83 per 1,000)","Thirty-year follow-up: relative risk of colorectal cancer death 0.68 (annual) and 0.78 (biennial)","Rehydrated slides had a high positivity rate (about 10%), so a large share of participants had colonoscopy","Incidence of colorectal cancer also fell by about 20% at 18 years, attributed to polyp removal"],"whatItMeans":"A cheap home stool test, repeated yearly or every two years and followed by colonoscopy when positive, prevents bowel cancer deaths. This is what national bowel screening programmes do today, with FIT replacing the older guaiac test.","caveats":["Much of the benefit may have come from the colonoscopies triggered by a high false-positive rate","Volunteer population; uptake in real programmes is lower","Guaiac testing has been superseded by more sensitive and specific FIT","No all-cause mortality benefit was shown, as expected for a single cancer site"],"changedPractice":true,"participants":46551},{"id":"paper-tjulandin-prolgolimab-miraculum-ejc-2021","kind":"paper","name":"MIRACULUM: prolgolimab, the first Russian-developed anti-PD-1 antibody, in advanced melanoma","aka":[],"tldr":"The trial behind Russia's own PD-1 antibody: 126 patients with advanced melanoma, an objective response in 38 per cent on the fortnightly dose and 29 per cent on the three-weekly dose, and severe treatment-related side effects in 13 and 3 per cent.","summary":"Prolgolimab is an IgG1 anti-PD-1 monoclonal antibody carrying the Fc-silencing LALA mutation, developed by Biocad in Saint Petersburg. MIRACULUM was a multicentre open-label parallel-arm phase 2 trial in which 126 patients with advanced cutaneous or non-cutaneous melanoma, including stable brain metastases, who had had no previous targeted, anti-PD-(L)1 or anti-CTLA-4 therapy, were randomised one to one to prolgolimab 1 mg/kg every two weeks or 3 mg/kg every three weeks until progression or intolerable toxicity.\n\nRecruitment ran from August 2017 to March 2018. At the one-year data cut-off, with median follow-up of 13.8 and 14.5 months, an objective response by independent central review was seen in 38.1 per cent of the fortnightly arm and 28.6 per cent of the three-weekly arm, and grade 3 to 4 treatment-related adverse events in 12.7 and 3.2 per cent. The trial is registered as NCT03269565.","asOf":"2026-09-25","links":[{"label":"Eur J Cancer 2021","url":"https://doi.org/10.1016/j.ejca.2021.02.030"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33872982/"},{"label":"ClinicalTrials.gov NCT03269565","url":"https://clinicaltrials.gov/study/NCT03269565"}],"tags":[],"related":[],"cancers":["melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":["bcd-100"],"companies":["biocad"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["european-journal-of-cancer"],"dependsOn":[],"notes":[],"journal":"European Journal of Cancer","year":2021,"doi":"10.1016/j.ejca.2021.02.030","pmid":"33872982","authors":"Tjulandin S, Demidov L, Moiseyenko V, et al.","paperType":"rct","findings":["Objective response 38.1 per cent with prolgolimab 1 mg/kg every two weeks and 28.6 per cent with 3 mg/kg every three weeks, by independent central review.","Grade 3 to 4 treatment-related adverse events 12.7 and 3.2 per cent respectively.","126 patients enrolled between August 2017 and March 2018, including patients with stable brain metastases."],"whatItMeans":"This is the evidence on which Russia licensed a PD-1 antibody of its own making, which matters because it is the reason immunotherapy remained available in Russian melanoma clinics on domestic supply. It is a single-country randomised phase 2 with no comparator against an established PD-1 antibody, so it does not establish equivalence with nivolumab or pembrolizumab.","caveats":["Phase 2, open label, with no active comparator: the two arms compare doses of the same drug, not prolgolimab against another PD-1 antibody.","All sites were in Russia and the sponsor is the manufacturer."],"participants":126},{"id":"paper-mirasol-nejm-2023","kind":"paper","name":"MIRASOL: mirvetuximab soravtansine versus chemotherapy in folate receptor alpha-high platinum-resistant ovarian cancer","aka":[],"tldr":"The antibody-drug conjugate mirvetuximab soravtansine lengthened survival compared with chemotherapy in platinum-resistant ovarian cancer with high folate receptor alpha expression, the first drug ever to do so in this setting.","summary":"Phase 3 trial of 453 patients with platinum-resistant high-grade serous ovarian cancer, folate receptor alpha-high tumours and one to three prior regimens, randomised to mirvetuximab soravtansine or investigator's choice chemotherapy (paclitaxel, pegylated liposomal doxorubicin or topotecan).\n\nMedian progression-free survival was 5.62 versus 3.98 months (hazard ratio 0.65), objective response 42.3 versus 15.9 percent and median overall survival 16.46 versus 12.75 months (hazard ratio 0.67); ocular toxicity was frequent but mostly low grade.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2023","url":"https://doi.org/10.1056/NEJMoa2309169"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38055253/"}],"tags":[],"related":[],"cancers":["platinum-resistant-ovarian-cancer","high-grade-serous-ovarian-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["mirvetuximab-soravtansine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["mirasol"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/NEJMoa2309169","pmid":"38055253","authors":"Moore KN, Angelergues A, Konecny GE, et al.","paperType":"rct","findings":["Median overall survival 16.46 vs 12.75 months; hazard ratio 0.67.","Objective response 42.3 percent vs 15.9 percent."],"whatItMeans":"Folate receptor alpha testing is now standard in platinum-resistant ovarian cancer and mirvetuximab is the preferred treatment for high-expressing tumours, with an eye-care protocol.","caveats":["Only about 35 to 40 percent of tumours are folate receptor alpha-high.","Blurred vision and keratopathy require ophthalmic monitoring."],"changedPractice":true,"participants":453},{"id":"paper-ren-tnbc-mmr-msi-440-front-oncol-2021","kind":"paper","name":"Mismatch repair deficiency and microsatellite instability in triple-negative breast cancer: a retrospective study of 440 patients","aka":[],"tldr":"Among 440 Chinese women with triple-negative breast cancer, none had high microsatellite instability by PCR and only one had lost a mismatch repair protein, so the tumour-agnostic immunotherapy route through microsatellite instability almost never applies.","summary":"Tissue microarrays from 440 TNBC patients (median age 49, median follow-up 68 months) were stained for MLH1, MSH2, MSH6 and PMS2; 195 were also tested by MSI PCR. All samples were proficient except one with MSH2 loss and intact MSH6; PCR found no MSI-high case, 14 (7.2%) MSI-low and 181 (92.8%) stable. The dMMR sample had low-frequency instability and a possible EPCAM deletion. MMR and MSI status did not correlate with clinicopathological features, PD-1/PD-L1 expression or survival.","asOf":"2026-09-24","links":[{"label":"Ren et al., Front Oncol 2021: mismatch repair and MSI in 440 Chinese TNBC patients","url":"https://doi.org/10.3389/fonc.2021.570623"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33747906/"}],"tags":[],"related":["msi-high","dmmr-ihc"],"cancers":["tnbc"],"sections":[],"technologies":["msi-mmr-testing"],"targets":["mmr"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["msi"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Frontiers in Oncology","year":2021,"doi":"10.3389/fonc.2021.570623","pmid":"33747906","authors":"Ren XY, Song Y, Wang J, et al.","paperType":"observational","findings":["dMMR by IHC in 1 of 440 (0.2%); MSI-high by PCR in 0 of 195.","MMR/MSI status unrelated to PD-L1 or survival."],"whatItMeans":"MSI testing has a very low yield in TNBC; TMB and PD-L1 are the immunotherapy biomarkers worth pursuing.","caveats":["Single Chinese centre; tissue microarray cores may miss heterogeneous loss.","PCR performed in fewer than half the cohort."],"changedPractice":false,"participants":440},{"id":"paper-goeppert-cholangiocarcinoma-mmr-deficiency-bjc-2019","kind":"paper","name":"Mismatch repair deficiency is a rare but putative therapeutically relevant finding in non-liver fluke associated cholangiocarcinoma","aka":[],"tldr":"Among 308 Western bile duct cancers only about one in 75 was microsatellite unstable, but those few had unusual microscopy, more immune cells and better survival, so testing is still worthwhile because immunotherapy works for them.","summary":"A cohort of 308 Western-world, non-liver-fluke-associated cholangiocarcinomas (159 intrahepatic, 106 perihilar and 43 distal) was analysed with the mononucleotide microsatellite instability marker panel BAT25, BAT26 and CAT25; MSI-high was detected in 4 of 308 (1.3%).\n\nPatients with MSI-high tumours mostly had an atypical histomorphology (P = 0.004), showed longer overall survival despite high tumour stage, and were younger. MSI-high tumours carried higher numbers of CD8-positive T cells, FOXP3-positive regulatory T cells and CD20-positive B cells and high or at least moderate MHC class I expression.","asOf":"2026-09-24","links":[{"label":"Goeppert et al., Br J Cancer 2019: mismatch repair deficiency in 308 Western cholangiocarcinomas","url":"https://doi.org/10.1038/s41416-018-0199-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30377340/"}],"tags":[],"related":[],"cancers":["cholangiocarcinoma","gallbladder"],"sections":[],"technologies":[],"targets":["mmr"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["msi"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["british-journal-of-cancer"],"dependsOn":[],"notes":[],"journal":"British Journal of Cancer","year":2019,"doi":"10.1038/s41416-018-0199-2","pmid":"30377340","authors":"Goeppert B, Roessler S, Renner M, et al.","paperType":"observational","findings":["MSI-high in 4 of 308 cholangiocarcinomas (1.3%).","MSI-high tumours: atypical histomorphology (P = 0.004), younger patients, longer survival despite higher stage.","Higher CD8, FOXP3 and CD20 infiltrates and higher MHC class I in MSI-high tumours."],"whatItMeans":"A Western benchmark for how rare MSI-high is in bile duct cancer; gallbladder cancer was not included, and the MSK gallbladder cohort's 2.5% by MSIsensor and the Indian 0.6% by panel bracket it.","caveats":["Cholangiocarcinoma only, no gallbladder tumours.","Three-marker PCR panel; sequencing-based MSI calls may differ."],"changedPractice":false,"participants":308},{"id":"paper-venderbosch-mmr-braf-metastatic-colorectal-pooled-ccr-2014","kind":"paper","name":"Mismatch repair status and BRAF mutation status in metastatic colorectal cancer: a pooled analysis of the CAIRO, CAIRO2, COIN and FOCUS studies","aka":[],"tldr":"Pooling four large first-line trials, 3,063 patients, showed that broken DNA repair is rare in advanced bowel cancer and that the shorter survival it carries is really the shorter survival of the BRAF mutation that so often comes with it.","summary":"A pooled analysis of four phase 3 first-line studies in metastatic colorectal cancer assessed the prevalence and prognostic value of mismatch repair status and its relation to BRAF mutation, using Cox regression on individual patient data. Of 3,063 primary tumours analysed, 153 (5.0%) showed deficient mismatch repair and 250 (8.2%) a BRAF mutation. BRAF mutation was present in 53 of 153 (34.6%) deficient tumours against 197 of 2,910 (6.8%) proficient tumours. Both markers conferred an inferior prognosis: deficient mismatch repair gave hazard ratios of 1.33 for progression-free and 1.35 for overall survival, and BRAF mutation 1.34 and 1.91. Progression-free and overall survival were significantly worse for BRAF mutation within the proficient group, but BRAF status did not separate outcomes within the deficient group, nor did mismatch repair status within either BRAF group.","asOf":"2026-09-24","links":[{"label":"Venderbosch et al., Clin Cancer Res 2014: mismatch repair and BRAF status pooled across CAIRO, CAIRO2, COIN and FOCUS (3,063 patients)","url":"https://doi.org/10.1158/1078-0432.CCR-14-0332"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25139339/"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["msi-mmr-testing"],"targets":["mmr","braf"],"drugs":[],"companies":[],"institutions":["radboudumc","leeds-cancer-centre"],"pathways":["mismatch-repair-msi","ras-mapk"],"terms":["msi","mss-pmmr"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2014,"doi":"10.1158/1078-0432.CCR-14-0332","pmid":"25139339","authors":"Venderbosch S, Nagtegaal ID, Maughan TS, et al.","paperType":"meta-analysis","findings":["Deficient mismatch repair in 153 of 3,063 (5.0%) and BRAF mutation in 250 (8.2%) first-line metastatic patients.","BRAF mutation in 34.6% of deficient against 6.8% of proficient tumours.","Overall survival hazard ratio 1.35 for deficient mismatch repair and 1.91 for BRAF mutation; the deficient penalty is driven by BRAF."],"whatItMeans":"It fixes the metastatic prevalence figures every subsequent trial design has used, and it separates two biomarkers that travel together: BRAF, not mismatch repair deficiency, is what makes the prognosis bad.","caveats":["Predates checkpoint inhibitors, so the prognosis of deficient patients has since changed completely.","Primary tumour tissue, not metastases.","Immunohistochemistry and MSI methods differed between the four trials."],"changedPractice":false,"participants":3063},{"id":"paper-horneber-cochrane-database-syst-rev","kind":"paper","name":"Mistletoe therapy in oncology","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 18425885 and published in The Cochrane database of systematic reviews; the citing page links this DOI, which is how the record was matched.","summary":"Background: Mistletoe extracts are commonly used in cancer patients. It is claimed that they improve survival and quality of life (QOL) in cancer patients.\n\nObjectives: To determine the effectiveness, tolerability and safety of mistletoe extracts given either as monotherapy or adjunct therapy for patients with cancer.\n\nSearch strategy: Search sources included the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, 2007) Cochrane Complementary Medicine Field Registry of randomized clinical trials (RCTs) and controlled clinical trials, MEDLINE, EMBASE, HEALTHSTAR, INT. HEALTH TECHNOLOGY ASSESSMENT, SOMED, AMED, BIOETHICSLINE, BIOSIS, CancerLit, CATLINE, CISCOM (August 2007). For the search the Standard Operating Procedures of the Information System in Health Economics at the German Institute for Medical Documentation and Information (DIMDI) were utilized. Reference lists of relevant articles and authors extensive files were searched for additional studies. Manufacturers of mistletoe preparations were contacted.\n\nSelection criteria: We included RCTs of adults with cancer of any type. The interventions were mistletoe extracts as sole treatments or given concomitantly with chemo- or radiotherapy. The outcome measures were survival times, tumor response, QOL, psychological distress, adverse effects from antineoplastic treatment and safety of mistletoe extracts.\n\nData collection and analysis: Three review authors independently assessed trials for inclusion in the review. All review authors independently took part in the extraction of data and assessment of study quality and clinical relevance. Disagreements were resolved by consensus. Study authors were contacted where information was unclear. Methodological quality was narratively described and additionally assessed with the Delphi list and the Jadad score. High methodological quality was defined if six out of nine Delphi criteria, or four out of five Jadad criteria were fulfilled. Results were presented qualitatively.\n\nMain results: Eighty studies were identified. Fifty-eight were excluded for various reasons, usually as there was no prospective trial design with randomised treatment allocation. Of the 21 included studies 13 provided data on survival, 7 on tumour response, 16 on measures of QOL or psychological outcomes, or prevalence of chemotherapy-related adverse effects and 12 on side effects of mistletoe treatment; overall comprising 3484 randomised cancer patients. Interventions evaluated were 5 preparations of mistletoe extracts from 5 manufacturers and one commercially not available preparation. The general reporting of RCTs was poor. Of the 13 trials investigating survival, 6 showed some evidence of a benefit, but none of them was of high methodological quality. The results of two trials in patients with melanoma and head and neck cancer gave some evidence that the used mistletoe extracts are not effective for improving survival. Of the 16 trials investigating the efficacy of mistletoe extracts for either improving QOL, psychological measures, performance index, symptom scales or the reduction of adverse effects of chemotherapy, 14 showed some evidence of a benefit, but only 2 of them including breast cancer patients during chemotherapy were of higher methodological quality. Data on side effects indicated that, depending on the dose, mistletoe extracts were usually well tolerated and had few side effects.\n\nAuthors' conclusions: The evidence from RCTs to support the view that the application of mistletoe extracts has impact on survival or leads to an improved ability to fight cancer or to withstand anticancer treatments is weak. Nevertheless, there is some evidence that mistletoe extracts may offer benefits on measures of QOL during chemotherapy for breast cancer, but these results need replication. Overall, more high quality, independent clinical research is needed to truly assess the safety and effectiveness of mistletoe extracts. Patients receiving mistletoe therapy should be encouraged to take part in future trails.\n\nIndexed on Europe PMC as PubMed record 18425885 (DOI 10.1002/14651858.cd003297.pub2). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cochrane Database Syst Rev 2008","url":"https://doi.org/10.1002/14651858.cd003297.pub2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/18425885/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/18425885"}],"tags":["europepmc-ingest"],"related":["mistletoe-extracts"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Cochrane database of systematic reviews","year":2008,"doi":"10.1002/14651858.cd003297.pub2","pmid":"18425885","authors":"Horneber MA, Bueschel G, Huber R, et al.","paperType":"review","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-sharma-endpac-model-new-onset-diabetes-gastroenterology-2018","kind":"paper","name":"Model to Determine Risk of Pancreatic Cancer in Patients With New-Onset Diabetes","aka":[],"tldr":"The 2018 Mayo Clinic score, called ENDPAC, that uses weight change, blood sugar change and age at diabetes onset to pick out the new diabetics whose risk of pancreatic cancer is high enough to scan.","summary":"Sharma, Chari and colleagues built the Enriching New-Onset Diabetes for Pancreatic Cancer (ENDPAC) model from four cohorts (1,561 patients) with glycaemically defined new-onset diabetes in the Rochester Epidemiology Project, 2000 to 2015, weighting three factors, change in weight, change in blood glucose and age at onset, and validated it in an independent cohort of 1,096. In the discovery cohort (64 pancreatic cancer, 192 type 2 diabetes) the area under the curve was 0.87 and a score of 3 or more had 80 percent sensitivity and specificity; in validation a score of 3 or more identified 7 of 9 cancers (78 percent) at 85 percent specificity, with a cancer prevalence of 3.6 percent among high scorers, 4.4-fold that of new-onset diabetes overall. A score of 0 or below (49 percent of patients) meant extremely low risk. A high score identified 75 percent of cases more than six months before diagnosis.","asOf":"2026-09-24","links":[{"label":"Gastroenterology 2018","url":"https://doi.org/10.1053/j.gastro.2018.05.023"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29775599/"},{"label":"ClinicalTrials.gov NCT04164602","url":"https://clinicaltrials.gov/study/NCT04164602"}],"tags":["pancreatic-evidence"],"related":["paper-chari-pancreatic-cancer-following-diabetes-gastroenterology-2005","paper-fahrmann-ca19-9-lead-time-gastroenterology-2021","idea-mced-new-onset-diabetes"],"cancers":["pancreatic"],"sections":[],"technologies":["ct","mri","pancreatic-surveillance","mced"],"targets":[],"drugs":[],"companies":[],"institutions":["mayo-clinic"],"pathways":[],"terms":["ppv"],"trials":[],"people":[],"bottlenecks":["b-early-detection"],"keyPapers":[],"journals":["gastroenterology"],"dependsOn":[],"notes":[],"journal":"Gastroenterology","year":2018,"doi":"10.1053/j.gastro.2018.05.023","pmid":"29775599","authors":"Sharma A, Kandlakunta H, Nagpal SJS, et al.","paperType":"observational","findings":["Three inputs: weight change, glucose change, age at onset; area under the curve 0.87.","Score 3 or more: 78 percent sensitivity, 85 percent specificity in validation; cancer prevalence 3.6 percent.","Score 0 or below in 49 percent of patients, extremely low risk.","75 percent of cases identified more than six months before diagnosis."],"whatItMeans":"A scoring tool that needs no new test and can run in primary care records; it turns the 1 percent of Chari's cohort into a 3.6 percent group in whom imaging or a blood test becomes defensible.","caveats":["Retrospective; the authors call for an independent prospective study, which the US NOD cohort and the Hungarian NODES cohort (NCT04164602) are attempting.","Nine cancers in the validation cohort."],"participants":2657},{"id":"paper-wherry-nat-rev-immunol","kind":"paper","name":"Molecular and cellular insights into T cell exhaustion","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 26205583 and published in Nature reviews. Immunology; the citing page links this DOI, which is how the record was matched.","summary":"In chronic infections and cancer, T cells are exposed to persistent antigen and/or inflammatory signals. This scenario is often associated with the deterioration of T cell function: a state called 'exhaustion'. Exhausted T cells lose robust effector functions, express multiple inhibitory receptors and are defined by an altered transcriptional programme. T cell exhaustion is often associated with inefficient control of persisting infections and tumours, but revitalization of exhausted T cells can reinvigorate immunity. Here, we review recent advances that provide a clearer molecular understanding of T cell exhaustion and reveal new therapeutic targets for persisting infections and cancer.\n\nIndexed on Europe PMC as PubMed record 26205583 (DOI 10.1038/nri3862). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Immunol 2015","url":"https://doi.org/10.1038/nri3862"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26205583/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26205583"}],"tags":["europepmc-ingest"],"related":["t-cell-exhaustion"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature reviews. Immunology","year":2015,"doi":"10.1038/nri3862","pmid":"26205583","authors":"Wherry EJ, Kurachi M","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-cowzer-biliary-targeted-therapy-determinants-ccr-2026","kind":"paper","name":"Molecular and clinical determinants of targeted therapy treatment in biliary tract cancer","aka":[],"tldr":"In 1,254 biliary cancer patients sequenced at one centre, a third had a top-tier druggable change (22% of gallbladder cancers), targeted drugs delayed progression but did not lengthen life, and HER2-driven tumours sometimes lost HER2 at relapse.","summary":"A prospectively maintained cohort of 1,254 patients with histologically confirmed biliary tract cancer underwent molecular profiling with an FDA-authorised targeted next-generation sequencing assay. 59% harboured at least one OncoKB alteration and 32.2% (intrahepatic 40%, extrahepatic 15%, gallbladder 22%) had a level 1 or 2 alteration. Emerging targets included KRAS alterations (17%), MTAP deletions (12.8%), MDM2 amplification (6.5%) and MET amplification (1.5%).\n\nTargeted therapy was associated with improved progression-free survival but not overall survival. Co-occurring TP53/RAS pathway and SMAD4 alterations were associated with inferior outcomes in IDH1/FGFR2-driven and ERBB2-driven tumours respectively. Longitudinal profiling demonstrated ERBB2 loss in ERBB2-driven tumours, whereas IDH-, FGFR-, BRAF- and NTRK-driven tumours retained the primary driver; acquired resistance was associated with alterations in RAS, MEK, MET, MYC and CDKN2A.","asOf":"2026-09-24","links":[{"label":"Cowzer et al., Clin Cancer Res 2026: molecular determinants of targeted therapy in 1,254 biliary tract cancers","url":"https://doi.org/10.1158/1078-0432.ccr-26-0428"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42360806/"},{"label":"cBioPortal study biliary_tract_msk_2026 (Hepatobiliary Cancer, MSK 2026)","url":"https://www.cbioportal.org/study/summary?id=biliary_tract_msk_2026"}],"tags":[],"related":[],"cancers":["gallbladder","cholangiocarcinoma","biliary-tract-cancer"],"sections":[],"technologies":[],"targets":["her2","kras","mdm2","smad4","cdkn2a"],"drugs":[],"companies":[],"institutions":["mskcc"],"pathways":[],"terms":[],"trials":[],"people":["ghassan-abou-alfa"],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2026,"doi":"10.1158/1078-0432.ccr-26-0428","pmid":"42360806","authors":"Cowzer D, Walch H, Atri P, et al.","paperType":"observational","findings":["Level 1 or 2 actionable alteration in 32.2% overall: intrahepatic 40%, extrahepatic 15%, gallbladder 22%.","KRAS 17%, MTAP deletion 12.8%, MDM2 amplification 6.5%, MET amplification 1.5% as emerging targets.","Targeted therapy improved progression-free but not overall survival; ERBB2-driven tumours lost ERBB2 at progression while IDH, FGFR, BRAF and NTRK drivers were retained."],"whatItMeans":"For gallbladder cancer the points that matter are that HER2 can disappear under HER2-directed pressure, that SMAD4 co-mutation predicts a worse response, and that sequencing at progression, not just at diagnosis, may be needed to guide the next line.","caveats":["Single tertiary centre; treatment choice was not randomised, so the PFS gain may reflect selection.","Actionability graded by OncoKB levels."],"changedPractice":false,"participants":1254},{"id":"paper-knowles-nat-rev-cancer","kind":"paper","name":"Molecular biology of bladder cancer: new insights into pathogenesis and clinical diversity","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 25533674 and published in Nature Reviews Cancer; the citing page links this DOI, which is how the record was matched.","summary":"Urothelial carcinoma of the bladder comprises two long-recognized disease entities with distinct molecular features and clinical outcome. Low-grade non-muscle-invasive tumours recur frequently but rarely progress to muscle invasion, whereas muscle-invasive tumours are usually diagnosed de novo and frequently metastasize. Recent genome-wide expression and sequencing studies identify genes and pathways that are key drivers of urothelial cancer and reveal a more complex picture with multiple molecular subclasses that traverse conventional grade and stage groupings. This improved understanding of molecular features, disease pathogenesis and heterogeneity provides new opportunities for prognostic application, disease monitoring and personalized therapy.\n\nIndexed on Europe PMC as PubMed record 25533674 (DOI 10.1038/nrc3817). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Cancer 2015","url":"https://doi.org/10.1038/nrc3817"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25533674/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25533674"}],"tags":["europepmc-ingest"],"related":["bladder-cancer-signalling"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Cancer","year":2015,"doi":"10.1038/nrc3817","pmid":"25533674","authors":"Knowles MA, Hurst CD","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-sepulveda-molecular-biomarkers-colorectal-guideline-jco-2017","kind":"paper","name":"Molecular biomarkers for the evaluation of colorectal cancer: guideline from ASCP, CAP, AMP and ASCO","aka":[],"tldr":"The guideline that says which genes must be tested in every bowel cancer, on what sample, and how quickly: extended RAS and BRAF to decide on EGFR antibodies, and mismatch repair on every tumour.","summary":"The American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology and American Society of Clinical Oncology convened an expert panel to develop evidence-based recommendations for molecular biomarker testing in colorectal cancer, drawing on a systematic review of more than 4,000 articles. Twenty-one guideline statements were established: eight recommendations, ten expert consensus opinions and three areas where no recommendation could be made. The evidence supports mutational testing for genes in the EGFR signalling pathway, since they provide clinically actionable information as negative predictors of benefit from anti-EGFR monoclonal antibody therapy, and several biomarkers carry clear prognostic value. Laboratory recommendations cover assay selection, specimen type, when tests should be ordered and acceptable turnaround times.","asOf":"2026-09-24","links":[{"label":"Sepulveda et al., J Clin Oncol 2017: ASCP, CAP, AMP and ASCO guideline on molecular biomarkers for colorectal cancer","url":"https://doi.org/10.1200/JCO.2016.71.9807"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28165299/"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["msi-mmr-testing","cgp","companion-diagnostic","histopathology-ihc"],"targets":["kras","nras","braf","mmr","egfr"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["wild-type","msi","ngs","ihc"],"trials":[],"people":["scott-kopetz"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2017,"doi":"10.1200/JCO.2016.71.9807","pmid":"28165299","authors":"Sepulveda AR, Hamilton SR, Allegra CJ, et al.","paperType":"guideline","findings":["Extended RAS (KRAS and NRAS exons 2, 3 and 4) testing is required before EGFR antibody therapy.","BRAF V600 testing for prognosis and, with mismatch repair, for Lynch syndrome evaluation.","Mismatch repair status should be determined on all colorectal cancers."],"whatItMeans":"It is the reference for what a colorectal molecular report must contain, and the document that turned extended RAS from a trial finding into a requirement.","caveats":["Published in 2017, so HER2, NTRK, RET and tumour mutational burden are not covered as they would be now.","Recommendations about turnaround time and assay choice are aspirational in many health systems."],"changedPractice":true},{"id":"paper-beltran-nepc-aurka-mycn-cancer-discov-2011","kind":"paper","name":"Molecular characterisation of neuroendocrine prostate cancer and identification of new drug targets","aka":[],"tldr":"Profiling the rare aggressive form of prostate cancer found two genes amplified together in four out of ten cases, and blocking one of them switched off the neuroendocrine programme.","summary":"Using next-generation RNA sequencing and oligonucleotide arrays, 7 neuroendocrine prostate cancers, 30 prostate adenocarcinomas and 5 benign prostate tissues were profiled, with validation on a larger cohort of 37 neuroendocrine cancers, 169 adenocarcinomas and 22 benign tissues using immunohistochemistry and fluorescence in situ hybridisation. Significant overexpression and gene amplification of AURKA and MYCN were found in 40% of neuroendocrine prostate cancers and 5% of adenocarcinomas, with evidence that they cooperate to induce a neuroendocrine phenotype in prostate cells. Neuroendocrine cancers, and MYCN-overexpressing adenocarcinomas, were dramatically sensitive to Aurora kinase inhibitor therapy in vitro and in vivo, with complete suppression of neuroendocrine marker expression after treatment.","asOf":"2026-09-25","links":[{"label":"Beltran et al., Cancer Discov 2011: molecular characterisation of neuroendocrine prostate cancer, with AURKA and MYCN co-amplification in 40%","url":"https://doi.org/10.1158/2159-8290.CD-11-0130"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22389870/"}],"tags":[],"related":[],"cancers":["prostate","prostate-nepc"],"sections":[],"technologies":["rna-seq","cytogenetics-fish","histopathology-ihc"],"targets":["aurka","mycn"],"drugs":[],"companies":[],"institutions":[],"pathways":["lineage-plasticity-neuroendocrine","myc","mitotic-spindle-checkpoint"],"terms":["histologic-transformation","gene-amplification","fish"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-discovery"],"dependsOn":[],"notes":[],"journal":"Cancer Discovery","year":2011,"doi":"10.1158/2159-8290.CD-11-0130","pmid":"22389870","authors":"Beltran H, Rickman DS, Park K, et al.","paperType":"basic","findings":["AURKA and MYCN overexpressed and amplified in 40% of neuroendocrine prostate cancers against 5% of adenocarcinomas.","The two genes cooperate to induce a neuroendocrine phenotype in prostate cells.","Aurora kinase inhibition suppressed neuroendocrine marker expression in models."],"whatItMeans":"It was the first evidence that neuroendocrine prostate cancer is a distinct molecular disease with its own candidate drug target, and it started the programme of Aurora kinase trials in this setting, which have since disappointed.","caveats":["Seven neuroendocrine cancers in the discovery set, which is very few.","Aurora kinase inhibitors have not shown the activity in men that the models predicted.","Forty per cent is enrichment within a rare phenotype, not a prostate-wide frequency."],"changedPractice":false},{"id":"paper-philip-kras-wild-type-pancreatic-ccr-2022","kind":"paper","name":"Molecular characterization of KRAS wild-type tumors in patients with pancreatic adenocarcinoma","aka":[],"tldr":"Among 2,483 pancreatic cancers profiled by one commercial laboratory, the 10.7% without a KRAS mutation more often carried BRAF changes, kinase fusions, microsatellite instability and a high mutation burden, had more immune cells, and lived longer on chemotherapy.","summary":"Tumour tissue underwent next-generation DNA and RNA sequencing with MSI and mismatch repair status. Of 2,483 patients, 266 (10.7%) were KRAS wild-type. The most frequently mutated gene in wild-type tumours was TP53 (44.5%), then BRAF (13.0%), with frequent DNA-damage repair (BRCA2, ATM, BAP1, RAD50, FANCE, PALB2), chromatin remodelling and cell-cycle gene alterations. PD-L1 expression did not differ (15.8% versus 17%), but wild-type tumours were more often MSI-high (4.7% versus 0.7%) and TMB-high (4.5% versus 1%) with more CD8 T cells, NK cells and myeloid dendritic cells. Wild-type tumours carried fusions of BRAF (6.6%), FGFR2 (5.2%), ALK (2.6%), RET (1.3%) and NRG1 (1.3%) and amplification of FGF3 (3%), ERBB2 (2.2%), FGFR3 (1.8%), NTRK (1.8%) and MET (1.3%). Real-world data showed a survival advantage for wild-type patients overall and on gemcitabine/nab-paclitaxel or 5-FU/oxaliplatin.","asOf":"2026-09-24","links":[{"label":"Philip et al., Clin Cancer Res 2022: KRAS wild-type tumours among 2,483 pancreatic adenocarcinomas","url":"https://doi.org/10.1158/1078-0432.CCR-21-3581"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35302596/"}],"tags":[],"related":[],"cancers":["pancreatic","kras-wild-type-pdac","msi-high-pdac"],"sections":[],"technologies":["rna-seq"],"targets":["kras","braf","fgfr2","alk","ret","nrg1","her2","ntrk","met","tp53"],"drugs":[],"companies":["caris"],"institutions":[],"pathways":["rtk-activation","ras-mapk"],"terms":["wild-type","msi","tmb"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2022,"doi":"10.1158/1078-0432.CCR-21-3581","pmid":"35302596","authors":"Philip PA, Azar I, Xiu J, et al.","paperType":"real-world","findings":["KRAS wild-type 10.7%; TP53 44.5% and BRAF 13.0% within it.","Fusions in wild-type tumours: BRAF 6.6%, FGFR2 5.2%, ALK 2.6%, RET 1.3%, NRG1 1.3%.","MSI-high 4.7% versus 0.7% and TMB-high 4.5% versus 1%; survival advantage for wild-type."],"whatItMeans":"This is the fusion and immune-marker table for the wild-type minority, the group in which RNA sequencing pays for itself.","caveats":["Commercial referral cohort (Caris); survival from real-world records.","Fusion percentages rest on 266 tumours."],"changedPractice":false,"participants":2483},{"id":"paper-pajtler-cancer-cell","kind":"paper","name":"Molecular Classification of Ependymal Tumors across All CNS Compartments, Histopathological Grades, and Age Groups","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 25965575 and published in Cancer Cell; the citing page links this DOI, which is how the record was matched.","summary":"Ependymal tumors across age groups are currently classified and graded solely by histopathology. It is, however, commonly accepted that this classification scheme has limited clinical utility based on its lack of reproducibility in predicting patients' outcome. We aimed at establishing a uniform molecular classification using DNA methylation profiling. Nine molecular subgroups were identified in a large cohort of 500 tumors, 3 in each anatomical compartment of the CNS, spine, posterior fossa, supratentorial. Two supratentorial subgroups are characterized by prototypic fusion genes involving RELA and YAP1, respectively. Regarding clinical associations, the molecular classification proposed herein outperforms the current histopathological classification and thus might serve as a basis for the next World Health Organization classification of CNS tumors.\n\nIndexed on Europe PMC as PubMed record 25965575 (DOI 10.1016/j.ccell.2015.04.002). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer Cell 2015","url":"https://doi.org/10.1016/j.ccell.2015.04.002"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25965575/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25965575"}],"tags":["europepmc-ingest"],"related":["ependymoma"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-cell"],"dependsOn":[],"notes":[],"journal":"Cancer Cell","year":2015,"doi":"10.1016/j.ccell.2015.04.002","pmid":"25965575","authors":"Pajtler KW, Witt H, Sill M, et al.","paperType":"observational","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-portec-3-molecular-leon-castillo-jco-2020","kind":"paper","name":"Molecular classification of the PORTEC-3 trial: prognosis and benefit from adjuvant chemotherapy by molecular group","aka":[],"tldr":"Re-analysing the PORTEC-3 trial by molecular class showed that p53-abnormal endometrial cancers gained substantially from adding chemotherapy to radiotherapy, POLE-mutated tumours did well regardless, and the other groups gained little.","summary":"Molecular classification of 410 high-risk endometrial cancers from the PORTEC-3 trial (chemoradiotherapy versus radiotherapy) into p53-abnormal, POLE-mutated, mismatch repair-deficient and no specific molecular profile groups.\n\nFive-year recurrence-free survival for p53-abnormal tumours was 59 percent with chemoradiotherapy against 36 percent with radiotherapy alone; POLE-mutated tumours had 96 to 100 percent recurrence-free survival in both arms; mismatch repair-deficient and no specific molecular profile groups showed no significant benefit from chemotherapy.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2020","url":"https://doi.org/10.1200/JCO.20.00549"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32749941/"}],"tags":[],"related":[],"cancers":["endometrial-mmr-deficient","endometrial-p53-abnormal","endometrial-pole-ultramutated"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["portec-3"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/JCO.20.00549","pmid":"32749941","authors":"León-Castillo A, de Boer SM, Powell ME, et al.","paperType":"translational","findings":["p53-abnormal: five-year recurrence-free survival 59 percent vs 36 percent with chemoradiotherapy vs radiotherapy.","POLE-mutated: recurrence-free survival 96 to 100 percent regardless of treatment."],"whatItMeans":"Molecular class is now a predictive factor for adjuvant therapy: chemotherapy for p53-abnormal disease, de-escalation for POLE-mutated tumours, and trials of immunotherapy for mismatch repair-deficient disease.","caveats":["Retrospective subgroup analysis with small molecular groups.","Confirmation is being sought in the RAINBO programme."],"changedPractice":true,"participants":410},{"id":"paper-chen-androgen-receptor-overexpression-antiandrogen-resistance-nat-med-2004","kind":"paper","name":"Molecular determinants of resistance to antiandrogen therapy","aka":["Chen 2004","AR overexpression antiandrogen resistance","Sawyers 2004 androgen receptor"],"tldr":"This study found the one change that always happened when prostate cancer became resistant to hormone-blocking drugs: the cell made more androgen receptor. With enough of it, the drugs that were meant to block the receptor started switching it on instead.","summary":"Charles Chen and colleagues in Charles Sawyers's laboratory profiled isogenic prostate cancer xenografts before and after they became resistant to antiandrogen therapy. Across the models, a modest increase in androgen receptor messenger RNA was the only change consistently associated with resistance, and it was both necessary and sufficient to convert hormone-sensitive growth into hormone-refractory growth.\n\nThe mechanistic half of the paper matters as much as the observation. At high receptor levels, antagonists behaved as agonists, and the switch tracked a change in which coactivators and corepressors were recruited to the promoters of androgen receptor target genes. That is the biology behind antiandrogen withdrawal response, and it is the design brief that produced enzalutamide, which came out of the same laboratory.","asOf":"2026-09-25","links":[{"label":"Nat Med 2004","url":"https://doi.org/10.1038/nm972"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/14702632/"}],"tags":["prostate-evidence"],"related":["paper-visakorpi-androgen-receptor-amplification-nat-genet-1995","paper-attard-abiraterone-phase-1-cyp17-jco-2008","prostate-roadmap"],"cancers":["prostate","prostate-mcrpc"],"sections":["hormonal","targeted-therapy","drug-discovery"],"technologies":[],"targets":["androgen-receptor"],"drugs":["enzalutamide","bicalutamide"],"companies":[],"institutions":[],"pathways":["ar-signaling","resistance-routes-map","transcription-addiction"],"terms":["castration-resistance","resistance","adt"],"trials":[],"people":["charles-sawyers"],"bottlenecks":["b-resistance","b-preclinical-models"],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2004,"doi":"10.1038/nm972","pmid":"14702632","authors":"Chen CD, Welsbie DS, Tran C, et al.","paperType":"basic","findings":["A modest increase in androgen receptor messenger RNA was the only change consistently associated with the development of resistance to antiandrogen therapy across isogenic xenograft models.","The increase in androgen receptor messenger RNA and protein was both necessary and sufficient to convert growth from hormone-sensitive to hormone-refractory, and depended on a functional ligand-binding domain.","Androgen receptor antagonists showed agonistic activity in cells with increased receptor levels, an antagonist-agonist conversion associated with altered recruitment of coactivators and corepressors."],"whatItMeans":"The design specification for the second-generation antiandrogens. A drug for castration-resistant prostate cancer has to stay an antagonist when the receptor is abundant, which is what enzalutamide, apalutamide and darolutamide were engineered to do and what bicalutamide fails to do.","caveats":["Xenograft models, not patients; the human confirmation came from receptor amplification in recurrent tumours and from the activity of the drugs the paper predicted.","Receptor overexpression is one route to resistance among several; ligand-binding domain mutations, splice variants and loss of androgen receptor dependence altogether are others.","The dependence on a functional ligand-binding domain is exactly what AR-V7 lacks, which is why the drugs that followed do not work in AR-V7-positive disease (paper-antonarakis-ar-v7-resistance-nejm-2014)."],"changedPractice":false},{"id":"paper-rizvi-targeted-ngs-immunotherapy-determinants-jco-2018","kind":"paper","name":"Molecular determinants of response to anti-PD-1 and anti-PD-L1 blockade in patients with non-small-cell lung cancer profiled with targeted next-generation sequencing","aka":[],"tldr":"The routine gene panel used in clinic can estimate how many mutations a lung cancer carries almost as well as sequencing the whole exome can, and tumours with more mutations were more likely to benefit from immunotherapy, independently of the PD-L1 stain.","summary":"Detailed clinical annotation and response data were collected for 240 patients with advanced non-small-cell lung cancer treated with anti-PD-1 or anti-PD-L1 therapy and profiled with a targeted next-generation sequencing panel. Durable clinical benefit was defined as partial response or stable disease lasting more than six months. Panel-based tumour mutation burden correlated well with whole-exome estimates in 49 patients (rho 0.86). Burden was greater in patients with durable benefit than in those without (p = 0.006). Durable benefit was more common and progression-free survival longer above the 50th percentile of burden (38.6% against 25.1%; hazard ratio 1.38). The fraction of copy number-altered genome was highest in patients without durable benefit. Variants in EGFR and STK11 were associated with a lack of benefit. Burden and PD-L1 expression were independent, and a composite of the two enriched further for benefit.","asOf":"2026-09-25","links":[{"label":"Rizvi et al., J Clin Oncol 2018: targeted sequencing of 240 non-small-cell lung cancers treated with PD-(L)1 blockade","url":"https://doi.org/10.1200/JCO.2017.75.3384"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29337640/"},{"label":"cBioPortal study nsclc_pd1_msk_2018 (MSK, J Clin Oncol 2018; 240 non-small-cell lung cancers profiled before PD-(L)1 blockade)","url":"https://www.cbioportal.org/study/summary?id=nsclc_pd1_msk_2018"}],"tags":[],"related":["tmb-high","pd-l1-tps"],"cancers":["nsclc"],"sections":[],"technologies":["cgp","tmb-testing","wes-wgs","checkpoint-inhibitor"],"targets":["pdl1","pd1","egfr","stk11"],"drugs":[],"companies":[],"institutions":["mskcc"],"pathways":["cancer-immunity-cycle","pd1-checkpoint"],"terms":["tmb","ngs","neoantigen","stk11-keap1"],"trials":[],"people":["matthew-hellmann"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2018,"doi":"10.1200/JCO.2017.75.3384","pmid":"29337640","authors":"Rizvi H, Sanchez-Vega F, La K, et al.","paperType":"observational","findings":["Panel-based and exome-based mutation burden correlate at rho 0.86.","Durable benefit 38.6% above against 25.1% below the median burden.","Burden and PD-L1 expression are independent variables with similar predictive power.","EGFR and STK11 alterations predicted a lack of benefit."],"whatItMeans":"It made tumour mutational burden measurable in routine practice and, in the same stroke, showed it is a second axis alongside PD-L1 rather than a replacement for it.","caveats":["Retrospective and single centre.","A percentile cut-off is cohort-dependent and does not transfer to another panel.","Durable clinical benefit is a surrogate endpoint."],"changedPractice":false,"participants":240},{"id":"paper-gebhart-ann-oncol","kind":"paper","name":"Molecular imaging as a tool to investigate heterogeneity of advanced HER2-positive breast cancer and to predict patient outcome under trastuzumab emtansine (T-DM1): the ZEPHIR trial","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 26598545 and published in Annals of Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background: Only human epidermal growth factor receptor (HER)2 status determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) has been validated to predict efficacy of HER2-targeting antibody-drug-conjugate trastuzumab emtansine (T-DM1). We propose molecular imaging to explore intra-/interpatient heterogeneity in HER2 mapping of metastatic disease and to identify patients unlikely to benefit from T-DM1.\n\nPatients and methods: HER2-positive mBC patients with IHC3+ or FISH ≥ 2.2 scheduled for T-DM1 underwent a pretreatment HER2-positron emission tomography (PET)/computed tomography (CT) with (89)Zr-trastuzumab. [(18)F]2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT was performed at baseline and before T-DM1 cycle 2. Patients were grouped into four HER2-PET/CT patterns according to the proportion of FDG-avid tumor load showing relevant (89)Zr-trastuzumab uptake (>blood pool activity): patterns A and B were considered positive (>50% or all of the tumor load 'positive'); patterns C and D were considered negative (>50% or all of the tumor load 'negative'). Early FDG-PET/CT was defined as nonresponding when >50% of the tumor load showed no significant reduction of FDG uptake (<15%). Negative (NPV) and positive predictive values (PPV) of HER2-PET/CT, early FDG response and their combination were assessed to predict morphological response (RECIST 1.1) after three T-DM1 cycles and time-to-treatment failure (TTF).\n\nResults: In the 56 patients analyzed, 29% had negative HER2-PET/CT while intrapatient heterogeneity (patterns B and C) was found in 46% of patients. Compared with RECIST1.1, respective NPV/PPV for HER2-PET/CT were 88%/72% and 83%/96% for early FDG-PET/CT. Combining HER2-PET/CT and FDG-PET/CT accurately predicted morphological response (PPV and NPV: 100%) and discriminated patients with a median TTF of only 2.8 months [n = 12, 95% confidence interval (CI) 1.4-7.6] from those with a TTF of 15 months (n = 25, 95% CI 9.7-not calculable).\n\nConclusions: Pretreatment imaging of HER2 targeting, combined with early metabolic response assessment holds great promise for improving the understanding of tumor heterogeneity in mBC and for selecting patients who will/will not benefit from T-DM1.\n\nClinicaltrialsgov identifier: NCT01565200.\n\nIndexed on Europe PMC as PubMed record 26598545 (DOI 10.1093/annonc/mdv577). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Ann Oncol 2016","url":"https://doi.org/10.1093/annonc/mdv577"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26598545/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26598545"}],"tags":["europepmc-ingest"],"related":["her2-pet"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2016,"doi":"10.1093/annonc/mdv577","pmid":"26598545","authors":"Gebhart G, Lamberts LE, Wimana Z, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-flaherty-j-clin-oncol","kind":"paper","name":"Molecular Landscape and Actionable Alterations in a Genomically Guided Cancer Clinical Trial: National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH)","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 33048619 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: Therapeutically actionable molecular alterations are widely distributed across cancer types. The National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) trial was designed to evaluate targeted therapy antitumor activity in underexplored cancer types. Tumor biopsy specimens were analyzed centrally with next-generation sequencing (NGS) in a master screening protocol. Patients with a tumor molecular alteration addressed by a targeted treatment lacking established efficacy in that tumor type were assigned to 1 of 30 treatments in parallel, single-arm, phase II subprotocols.\n\nPatients and methods: Tumor biopsy specimens from 5,954 patients with refractory malignancies at 1,117 accrual sites were analyzed centrally with NGS and selected immunohistochemistry in a master screening protocol. The treatment-assignment rate to treatment arms was assessed. Molecular alterations in seven tumors profiled in both NCI-MATCH trial and The Cancer Genome Atlas (TCGA) of primary tumors were compared.\n\nResults: Molecular profiling was successful in 93.0% of specimens. An actionable alteration was found in 37.6%. After applying clinical and molecular exclusion criteria, 17.8% were assigned (26.4% could have been assigned if all subprotocols were available simultaneously). Eleven subprotocols reached their accrual goal at this report. Actionability rates differed among histologies (eg, > 35% for urothelial cancers and < 6% for pancreatic and small-cell lung cancer). Multiple actionable or resistance-conferring tumor mutations were seen in 11.9% and 71.3% of specimens, respectively. Known resistance mutations to targeted therapies were numerically more frequent in NCI-MATCH than TCGA tumors, but not markedly so.\n\nConclusion: We demonstrated feasibility of screening large numbers of patients at numerous accruing sites in a complex trial to test investigational therapies for moderately frequent molecular targets. Co-occurring resistance mutations were common and endorse investigation of combination targeted-therapy regimens.\n\nIndexed on Europe PMC as PubMed record 33048619 (DOI 10.1200/jco.19.03010). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2020","url":"https://doi.org/10.1200/jco.19.03010"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33048619/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33048619"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nci-match"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/jco.19.03010","pmid":"33048619","authors":"Flaherty KT, Gray RJ, Chen AP, et al.","paperType":"observational","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-ivey-npm1-mrd-nejm-2016","kind":"paper","name":"Molecular measurable residual disease in NPM1-mutated acute myeloid leukaemia (UK NCRI AML17)","aka":[],"tldr":"Detecting leftover NPM1-mutated leukaemia in the blood after the second course of chemotherapy identified patients very likely to relapse, and proved a better guide than genetics at diagnosis to who needs a transplant.","summary":"Prospective study within the AML17 trial of 346 patients with NPM1-mutated AML monitored by quantitative PCR for NPM1 transcripts in blood and marrow after each course.\n\nPersistence of NPM1 transcripts in peripheral blood after the second chemotherapy course was found in 15 percent and predicted a three-year relapse rate of 82 percent against 30 percent when undetectable, with three-year survival of 24 versus 75 percent. The finding was the strongest independent prognostic factor.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2016","url":"https://doi.org/10.1056/NEJMoa1507471"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26789727/"}],"tags":[],"related":[],"cancers":["aml-npm1-kmt2a"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2016,"doi":"10.1056/NEJMoa1507471","pmid":"26789727","authors":"Ivey A, Hills RK, Simpson MA, et al.","paperType":"observational","findings":["Three-year relapse 82 percent vs 30 percent by blood NPM1 status after course two.","Three-year overall survival 24 percent vs 75 percent."],"whatItMeans":"Molecular monitoring of NPM1 now decides whether a patient with otherwise favourable-risk disease should go to transplant in first remission, and molecular relapse can be treated pre-emptively.","caveats":["Requires a standardised quantitative PCR assay and defined thresholds.","Studied under intensive chemotherapy; thresholds under venetoclax regimens are being established."],"changedPractice":true,"participants":346},{"id":"paper-gainor-alk-resistance-mutations-cancer-discov-2016","kind":"paper","name":"Molecular mechanisms of resistance to first- and second-generation ALK inhibitors in ALK-rearranged lung cancer","aka":[],"tldr":"Rebiopsying 103 patients as each generation of drug failed showed that each drug leaves its own signature of escape mutations, and that whether a mutation is present decides whether the next drug in the sequence will work.","summary":"One hundred and three repeat biopsies from patients with ALK-positive lung cancer progressing on various ALK inhibitors were analysed. Each ALK inhibitor was associated with a distinct spectrum of ALK resistance mutations, and the frequency of ALK G1202R increased significantly after treatment with second-generation agents. Second-generation inhibitors are generally effective after crizotinib even without a crizotinib-resistant ALK mutation, reflecting incomplete inhibition of ALK by crizotinib in many cases. In a series of ceritinib-resistant patient-derived cell lines, the presence of ALK resistance mutations was highly predictive of sensitivity to the third-generation inhibitor lorlatinib, whereas lines without ALK mutations were resistant.","asOf":"2026-09-25","links":[{"label":"Gainor et al., Cancer Discov 2016: 103 repeat biopsies and the resistance mutations of first- and second-generation ALK inhibitors","url":"https://doi.org/10.1158/2159-8290.CD-16-0596"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27432227/"}],"tags":[],"related":["alk-fusion"],"cancers":["nsclc"],"sections":[],"technologies":["kinase-inhibitors","cgp","organoids"],"targets":["alk"],"drugs":["crizotinib","ceritinib","alectinib","brigatinib","lorlatinib"],"companies":[],"institutions":["mgh"],"pathways":["resistance-routes-map","rtk-activation","clonal-evolution"],"terms":["resistance","cross-resistance","gene-fusion","biopsy"],"trials":[],"people":["justin-gainor"],"bottlenecks":[],"keyPapers":[],"journals":["cancer-discovery"],"dependsOn":[],"notes":[],"journal":"Cancer Discovery","year":2016,"doi":"10.1158/2159-8290.CD-16-0596","pmid":"27432227","authors":"Gainor JF, Dardaei L, Yoda S, et al.","paperType":"translational","findings":["Each ALK inhibitor generation leaves a distinct spectrum of resistance mutations.","G1202R rises significantly in frequency after second-generation treatment.","Second-generation drugs work after crizotinib whether or not a resistance mutation is present.","Lorlatinib sensitivity in cell lines tracks the presence of an ALK mutation."],"whatItMeans":"It made repeat biopsy and genotyping at progression the standard in ALK-positive lung cancer, because after a second-generation inhibitor the presence or absence of an ALK mutation is what separates patients who should receive a third-generation inhibitor from those who should not.","caveats":["Biopsies come from patients whose disease could be sampled, which selects for accessible lesions.","Cell line predictions were later confirmed in patients but with weaker separation.","Resistance that is ALK-independent was not characterised in detail."],"changedPractice":true,"participants":103},{"id":"paper-perou-molecular-portraits-breast-tumours-nature-2000","kind":"paper","name":"Molecular portraits of human breast tumours","aka":[],"tldr":"The 2000 study that read the activity of 8,102 genes in 65 breast tumours and found the tumours fell into distinct groups, one of them the basal-like group that most triple-negative cancers belong to.","summary":"Perou, Sørlie, Eisen, van de Rijn and colleagues characterised gene expression in 65 surgical specimens from 42 individuals using complementary DNA microarrays representing 8,102 human genes. Each tumour had a distinctive molecular portrait; 20 tumours sampled before and after 16 weeks of doxorubicin, and two paired with a lymph node metastasis, showed that two samples from the same person were almost always more alike than either was to any other tumour. Sets of co-expressed genes tracked specific features of the tumours, and the tumours could be classified into subtypes distinguished by pervasive differences in expression.","asOf":"2026-09-24","links":[{"label":"Nature 2000","url":"https://doi.org/10.1038/35021093"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/10963602/"}],"tags":["tnbc-evidence"],"related":["paper-sorlie-breast-carcinoma-subclasses-pnas-2001","paper-sorlie-repeated-observation-subtypes-brca1-basal-pnas-2003"],"cancers":["tnbc","breast-hr-positive","breast-her2-positive"],"sections":[],"technologies":["rna-seq"],"targets":[],"drugs":[],"companies":[],"institutions":["unc-lineberger"],"pathways":[],"terms":["pam50"],"trials":[],"people":["charles-perou"],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2000,"doi":"10.1038/35021093","pmid":"10963602","authors":"Perou CM, Sørlie T, Eisen MB, et al.","paperType":"basic","findings":["65 tumours from 42 individuals profiled on 8,102-gene microarrays; paired samples from one person clustered together.","Tumours classified into subtypes by pervasive differences in gene expression, including a basal epithelial-like group."],"whatItMeans":"The origin of the intrinsic subtypes and of the word basal-like; triple-negative breast cancer is the clinical shadow of this molecular group, though the two overlap imperfectly.","caveats":["Small sample; subtype robustness was shown in the follow-up papers of 2001 and 2003.","Basal-like and triple-negative are not synonyms: about a fifth of triple-negative tumours are not basal-like and vice versa."],"changedPractice":true,"participants":42},{"id":"paper-weinberg-biliary-profiling-jgo-2019","kind":"paper","name":"Molecular profiling of biliary cancers reveals distinct molecular alterations and potential therapeutic targets","aka":[],"tldr":"Profiling 1,502 biliary cancers on one commercial platform, gallbladder tumours stood out for HER2 overexpression and amplification and for defects in homologous recombination repair, and, with intrahepatic tumours, for more immunotherapy markers than extrahepatic disease.","summary":"1,502 biliary tract cancers were profiled using next-generation sequencing, immunohistochemistry, in situ hybridisation and RNA sequencing to compare intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma and gallbladder carcinoma, which are frequently grouped together in trials despite differences in tumour biology.\n\nIntrahepatic tumours had higher rates of IDH1, BAP1 and PBRM1 mutations and FGFR2 fusions; extrahepatic tumours higher rates of KRAS, CDKN2A and BRCA1 mutations; and gallbladder carcinomas higher rates of homologous recombination repair deficiency and HER2 overexpression and amplification. Intrahepatic and gallbladder tumours had higher rates of potential positive predictive biomarkers for immune checkpoint inhibition (PD-L1 expression, high microsatellite instability and high tumour mutational burden) than extrahepatic tumours.","asOf":"2026-09-24","links":[{"label":"Weinberg et al., J Gastrointest Oncol 2019: molecular profiling of 1,502 biliary cancers","url":"https://doi.org/10.21037/jgo.2018.08.18"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31392046/"}],"tags":[],"related":[],"cancers":["gallbladder","cholangiocarcinoma"],"sections":[],"technologies":[],"targets":["her2","brca","pdl1","mmr"],"drugs":[],"companies":["caris"],"institutions":[],"pathways":[],"terms":["hrd","msi","tmb"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of Gastrointestinal Oncology","year":2019,"doi":"10.21037/jgo.2018.08.18","pmid":"31392046","authors":"Weinberg BA, Xiu J, Lindberg MR, et al.","paperType":"translational","findings":["Gallbladder carcinoma had the highest rates of HER2 overexpression and amplification and of homologous recombination repair deficiency among the three biliary sites.","Intrahepatic and gallbladder tumours carried more PD-L1 expression, MSI-high and TMB-high than extrahepatic tumours.","Intrahepatic tumours: IDH1, BAP1, PBRM1 and FGFR2 fusions; extrahepatic: KRAS, CDKN2A, BRCA1."],"whatItMeans":"The largest single-platform comparison; the abstract gives directions rather than percentages, so the figures on OnCo come from the other cohorts, but it supports testing gallbladder cancer for HER2, repair defects and immunotherapy markers.","caveats":["Abstract reports relative rates, not frequencies; the full paper holds the numbers.","Referral cohort profiled by Caris Life Sciences."],"changedPractice":false,"participants":1502},{"id":"paper-sicklick-nat-med","kind":"paper","name":"Molecular profiling of cancer patients enables personalized combination therapy: the I-PREDICT study","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 31011206 and published in Nature Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Cancer treatments have evolved from indiscriminate cytotoxic agents to selective genome- and immune-targeted drugs that have transformed the outcomes of some malignancies 1. Tumor complexity and heterogeneity suggest that the 'precision medicine' paradigm of cancer therapy requires treatment to be personalized to the individual patient 2-6. To date, precision oncology trials have been based on molecular matching with predetermined monotherapies 7-14. Several of these trials have been hindered by very low matching rates, often in the 5-10% range 15, and low response rates. Low matching rates may be due to the use of limited gene panels, restrictive molecular matching algorithms, lack of drug availability, or the deterioration and death of end-stage patients before therapy can be implemented. We hypothesized that personalized treatment with combination therapies would improve outcomes in patients with refractory malignancies. As a first test of this concept, we implemented a cross-institutional prospective study (I-PREDICT, NCT02534675) that used tumor DNA sequencing and timely recommendations for individualized treatment with combination therapies. We found that administration of customized multidrug regimens was feasible, with 49% of consented patients receiving personalized treatment. Targeting of a larger fraction of identified molecular alterations, yielding a higher 'matching score', was correlated with significantly improved disease control rates, as well as longer progression-free and overall survival rates, compared to targeting of fewer somatic alterations. Our findings suggest that the current clinical trial paradigm for precision oncology, which pairs one driver mutation with one drug, may be optimized by treating molecularly complex and heterogeneous cancers with combinations of customized agents.\n\nIndexed on Europe PMC as PubMed record 31011206 (DOI 10.1038/s41591-019-0407-5). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Med 2019","url":"https://doi.org/10.1038/s41591-019-0407-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31011206/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31011206"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["i-predict"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2019,"doi":"10.1038/s41591-019-0407-5","pmid":"31011206","authors":"Sicklick JK, Kato S, Okamura R, et al.","paperType":"observational","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-labrecque-mcrpc-phenotypes-jci-2019","kind":"paper","name":"Molecular profiling stratifies diverse phenotypes of treatment-refractory metastatic castration-resistant prostate cancer","aka":[],"tldr":"Deep profiling of treatment-resistant prostate cancers found five distinct kinds rather than the two the field had assumed, and gave a 26-gene signature to tell them apart.","summary":"Deep phenotypic characterisation of castration-resistant prostate cancer metastases and patient-derived xenograft lines was carried out using whole-genome RNA sequencing, gene set enrichment analysis and immunohistochemistry. The analyses revealed five phenotypes based on expression of well-characterised androgen receptor or neuroendocrine genes: androgen receptor-high tumours, androgen receptor-low tumours, amphicrine tumours composed of cells co-expressing androgen receptor and neuroendocrine genes, double-negative tumours, and tumours with small cell or neuroendocrine gene expression without androgen receptor activity. REST activity, which suppresses neuroendocrine gene expression, was lost in the amphicrine and small cell or neuroendocrine xenograft models, and knockdown experiments showed that attenuated REST activity drives the amphicrine phenotype but is not sufficient for conversion to the small cell or neuroendocrine phenotype. A subtype of double-negative tumours with squamous differentiation was identified, and a 26-gene transcriptional signature distinguishing the five phenotypes was generated.","asOf":"2026-09-25","links":[{"label":"Labrecque et al., J Clin Invest 2019: five phenotypes of treatment-refractory metastatic castration-resistant prostate cancer defined by androgen receptor and neuroendocrine gene expression","url":"https://doi.org/10.1172/JCI128212"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31361600/"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc","prostate-nepc"],"sections":[],"technologies":["rna-seq","histopathology-ihc"],"targets":["androgen-receptor","ascl1"],"drugs":[],"companies":[],"institutions":[],"pathways":["lineage-plasticity-neuroendocrine","ar-signaling","transcription-addiction"],"terms":["histologic-transformation","castration-resistance","resistance"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jci"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Investigation","year":2019,"doi":"10.1172/JCI128212","pmid":"31361600","authors":"Labrecque MP, Coleman IM, Brown LG, et al.","paperType":"basic","findings":["Five phenotypes of castration-resistant disease rather than two: androgen receptor-high, androgen receptor-low, amphicrine, double-negative and small cell or neuroendocrine.","Loss of REST activity drives the amphicrine phenotype but is not sufficient for small cell conversion.","A double-negative subtype with squamous differentiation.","A 26-gene transcriptional signature distinguishing the phenotypes."],"whatItMeans":"It gives the field a vocabulary for the states between androgen receptor-driven adenocarcinoma and small cell carcinoma, which matters because those in-between tumours are the ones most likely to be mismanaged as ordinary castration-resistant disease.","caveats":["Research metastases and patient-derived xenografts, not a prospective patient cohort.","The signature needs bulk RNA, which is rarely available from a routine metastatic biopsy.","No treatment is selected by phenotype today."],"changedPractice":false},{"id":"paper-taylor-medulloblastoma-consensus-acta-neuropathol-2012","kind":"paper","name":"Molecular subgroups of medulloblastoma: the current consensus","aka":[],"tldr":"An international consensus divided medulloblastoma into four molecular subgroups, WNT, SHH, group 3 and group 4, with different origins, genetics, ages and survival, a scheme now used in diagnosis and to design risk-adapted trials.","summary":"Consensus paper from medulloblastoma researchers reconciling several transcriptomic classifications into four subgroups (WNT, SHH, group 3, group 4), summarising their demographics, histology, genetics, clinical behaviour and outcomes, and proposing nomenclature for research and clinical use.","asOf":"2026-09-17","links":[{"label":"Acta Neuropathol 2012","url":"https://doi.org/10.1007/s00401-011-0922-z"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22134537/"}],"tags":[],"related":[],"cancers":["medulloblastoma-group-3-4","medulloblastoma-shh","medulloblastoma-wnt"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Acta Neuropathologica","year":2012,"doi":"10.1007/s00401-011-0922-z","pmid":"22134537","authors":"Taylor MD, Northcott PA, Korshunov A, et al.","paperType":"guideline","findings":["WNT tumours have over 90 percent survival, SHH intermediate outcomes dependent on TP53, group 3 the worst outlook and group 4 intermediate."],"whatItMeans":"The medulloblastoma subtype pages on this site follow this scheme, which entered the WHO classification in 2016 and drives current de-escalation and intensification trials.","caveats":["Subgroups have since been split into further subtypes (Cavalli 2017) with prognostic differences."],"changedPractice":true},{"id":"paper-chapuy-molecular-subtypes-dlbcl-nat-med-2018","kind":"paper","name":"Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes","aka":["Chapuy 2018","Five genetic clusters of diffuse large B-cell lymphoma","C1 to C5 clusters"],"tldr":"Reading the whole genetic picture of 304 lymphomas, rather than one gene at a time, sorted them into five groups that arise by different routes and respond differently.","summary":"Chapuy, Shipp and colleagues carried out a comprehensive genetic analysis of 304 primary diffuse large B-cell lymphomas, capturing recurrent mutations, somatic copy-number alterations, structural variants and low-frequency changes together rather than separately, and then clustered the combined signatures.\n\nFive robust subsets came out. One was a previously unrecognised group of low-risk activated B-cell tumours of extrafollicular or marginal zone origin. Two were distinct germinal-centre groups with different outcomes and different targetable alterations. One was independent of the activated and germinal-centre division altogether, defined by biallelic inactivation of TP53, loss of CDKN2A and the genomic instability that follows. The coordinate genetic signatures predicted outcome independently of the clinical International Prognostic Index.\n\nThe paper was published three weeks after Schmitz's from the National Cancer Institute, which used a different algorithm on a different cohort and produced four subtypes rather than five. That the two classifications overlap but do not coincide is the central problem the field then had to solve, and Wright's probabilistic tool in 2020 was the attempt to solve it.","asOf":"2026-10-01","links":[{"label":"Nature Medicine 2018","url":"https://doi.org/10.1038/s41591-018-0016-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29713087/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29713087"}],"tags":["lymphoma-evidence"],"related":["paper-schmitz-genetics-pathogenesis-dlbcl-nejm-2018","paper-wright-lymphgen-genetic-subtypes-dlbcl-cancer-cell-2020","lymphoma-roadmap"],"cancers":["dlbcl","non-hodgkin-lymphoma"],"sections":["diagnostics","drug-discovery"],"technologies":["wes-wgs","ngs"],"targets":["tp53","cdkn2a","bcl2","bcl6","myd88","cd79b","notch2"],"drugs":[],"companies":[],"institutions":["dana-farber"],"pathways":[],"terms":["cell-of-origin","ipi-score","tmb"],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity","b-biomarker-validation","b-translational-valley"],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2018,"doi":"10.1038/s41591-018-0016-8","pmid":"29713087","authors":"Chapuy B, Stewart C, Dunford AJ, et al.","paperType":"basic","findings":["Consensus clustering of integrated mutations, copy-number alterations and structural variants in 304 primary diffuse large B-cell lymphomas identified five robust genetic subsets.","One subset was a previously unrecognised group of low-risk activated B-cell tumours of extrafollicular or marginal zone origin.","Two distinct germinal-centre subsets differed in outcome and in targetable alterations.","One subset was independent of the activated and germinal-centre division and was defined by biallelic TP53 inactivation, CDKN2A loss and associated genomic instability.","The coordinate genetic signatures predicted outcome independently of the clinical International Prognostic Index."],"whatItMeans":"One of the two foundational genetic classifications of diffuse large B-cell lymphoma. Neither has yet changed what a patient receives outside a trial, but together they are the reason precision-medicine trials in this disease now select by genetics rather than by cell of origin.","caveats":["Five clusters from 304 tumours is a discovery result; cluster boundaries move with cohort and method, which is exactly what the comparison with Schmitz showed.","The clusters were derived and their prognostic value assessed in largely the same cohort.","No prospective trial has yet assigned treatment by these clusters, so their therapeutic implications remain hypotheses.","The publisher issued a correction and an author correction to this paper in 2018; both are indexed separately on Europe PMC."],"changedPractice":false,"participants":304},{"id":"paper-rudin-sclc-molecular-subtypes-nat-rev-cancer-2019","kind":"paper","name":"Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data","aka":[],"tldr":"Small-cell lung cancer, treated as one disease for fifty years, is at least four. The subtypes are named after the transcription factor each one leans on: ASCL1, NeuroD1, YAP1 and POU2F3.","summary":"Rudin, Poirier, Byers, Dive and eighteen colleagues proposed a working nomenclature for small-cell lung cancer subtypes defined by the relative expression of four key transcription regulators, ASCL1, NeuroD1, YAP1 and POU2F3, synthesising evidence from primary human tumours, patient-derived xenografts, cell lines and genetically engineered mouse models.\n\nA consensus perspective rather than a study, and it is on this list because of what it enabled: once the subtypes had names, trials could be designed around them, and the therapeutic vulnerabilities that differ between them (DLL3 in ASCL1-high disease, PARP and checkpoint sensitivity elsewhere) became testable propositions rather than post hoc observations.","asOf":"2026-09-25","links":[{"label":"Nat Rev Cancer 2019","url":"https://doi.org/10.1038/s41568-019-0133-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30926931/"},{"label":"Author correction (2019)","url":"https://europepmc.org/article/MED/31175338"},{"label":"Rudin et al., Nat Rev Cancer 2019: the molecular subtypes of small-cell lung cancer, a synthesis of human and mouse data","url":"https://doi.org/10.1038/s41568-019-0133-9"}],"tags":["lung-evidence"],"related":["paper-george-sclc-genomic-profiles-nature-2015","paper-dellphi-301-nejm-2023","idea-sclc-subtype-directed"],"cancers":["lung-cancer","sclc","limited-stage-sclc","extensive-stage-sclc"],"sections":["drug-discovery","diagnostics"],"technologies":["rna-seq","organoids"],"targets":["dll3","ascl1","yap1","myc-gene","mycl"],"drugs":[],"companies":[],"institutions":["mskcc","md-anderson"],"pathways":["sclc-signalling","lineage-plasticity-neuroendocrine","transcription-addiction","myc"],"terms":["histology","driver-mutation"],"trials":[],"people":["charles-rudin"],"bottlenecks":["b-rare-cancers","b-biomarker-validation","b-trial-design"],"keyPapers":[],"journals":["nature-reviews-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Cancer","year":2019,"doi":"10.1038/s41568-019-0133-9","pmid":"30926931","authors":"Rudin CM, Poirier JT, Byers LA, et al.","paperType":"review","findings":["Several independent lines of evidence converge on a model of small-cell lung cancer subtypes defined by differential expression of ASCL1, NeuroD1, YAP1 and POU2F3.","The authors propose a working nomenclature for these subtypes and argue that defining their unique therapeutic vulnerabilities should focus and accelerate therapeutic research.","Four subtypes of small-cell lung cancer defined by ASCL1, NeuroD1, YAP1 and POU2F3 expression.","The subtypes carry different therapeutic vulnerabilities.","A common nomenclature was proposed and has since been adopted."],"whatItMeans":"The organising framework for every small-cell lung cancer trial designed since. It is also why the slow progress in the disease is now attributed to treating four diseases as one rather than to the biology being intractable.","caveats":["A perspective piece proposing a nomenclature, not a validation study; subtype assignment is not a routine clinical test.","Subtypes are transcriptional states, and tumours can shift between them under treatment, so a baseline assignment may not hold.","No randomised trial has yet assigned treatment by subtype and shown benefit.","A synthesis and proposal rather than a primary dataset.","The YAP1 subtype has since been hard to confirm in patient samples.","No assay is approved and no trial has randomised on subtype."],"changedPractice":false},{"id":"paper-momentum-momelotinib-lancet-2023","kind":"paper","name":"MOMENTUM: momelotinib versus danazol for myelofibrosis patients with anaemia after a prior JAK inhibitor","aka":[],"tldr":"A JAK inhibitor that also blocks the anaemia-driving ACVR1 pathway improved symptoms and spleen size without worsening, and often improving, anaemia in previously treated patients.","summary":"MOMENTUM randomised 195 symptomatic, anaemic patients with myelofibrosis previously treated with a JAK inhibitor to momelotinib or danazol (2:1) for 24 weeks, after which danazol patients could cross over. The primary endpoint was a 50% or greater reduction in total symptom score at week 24. This was achieved by 25% versus 9%; transfusion independence at week 24 was 30% versus 20%, meeting non-inferiority, and spleen volume reduction of at least 35% was 22% versus 3%. Momelotinib inhibits JAK1, JAK2 and ACVR1, the last of which lowers hepcidin and improves iron availability. Grade 3 or higher thrombocytopenia and infections were the main toxicities. The drug was approved in 2023 specifically for myelofibrosis with anaemia.","asOf":"2026-09-08","links":[{"label":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=MOMENTUM%20momelotinib%20danazol%20myelofibrosis%20anaemia%20Verstovsek%20Lancet%202023"},{"label":"ClinicalTrials.gov NCT04173494","url":"https://clinicaltrials.gov/study/NCT04173494"}],"tags":[],"related":["paper-comfort-1-ruxolitinib-myelofibrosis-nejm-2012"],"cancers":["myeloproliferative-neoplasms"],"sections":[],"technologies":[],"targets":["jak2"],"drugs":["momelotinib","ruxolitinib","pacritinib"],"companies":["gsk"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2023,"doi":"10.1016/S0140-6736(22)02036-0","pmid":"36709073","authors":"Verstovsek S, Gerds AT, Vannucchi AM, et al.","paperType":"rct","findings":["195 JAK-inhibitor-experienced patients with symptomatic myelofibrosis and anaemia; momelotinib vs danazol (2:1).","Total symptom score reduction of at least 50% at week 24: 25% vs 9%.","Transfusion independence at week 24: 30% vs 20% (non-inferiority met).","Spleen volume reduction of at least 35%: 22% vs 3%.","Mechanism includes ACVR1 inhibition lowering hepcidin, explaining the anaemia benefit."],"whatItMeans":"MOMENTUM addressed the biggest gap left by ruxolitinib: patients whose anaemia makes standard JAK inhibition hard to give. Momelotinib is now the preferred option for anaemic, previously treated myelofibrosis and is being adopted in first line for anaemic patients. The absolute symptom benefit is modest and durable disease modification has not been shown.","caveats":["Danazol is a weak comparator with limited efficacy of its own.","Symptom response rate of 25% is low in absolute terms.","Short (24-week) randomised period before crossover; long-term comparative data are limited.","Peripheral neuropathy signal seen in earlier momelotinib trials."],"changedPractice":true,"participants":195},{"id":"paper-nct02107703-j-clin-oncol-2017","kind":"paper","name":"MONARCH 2: Abemaciclib in Combination With Fulvestrant in Women With HR+/HER2- Advanced Breast Cancer Who Had Progressed While Receiving Endocrine Therapy","aka":[],"tldr":"Published report from the MONARCH 2 trial registered as NCT02107703, in Journal of Clinical Oncology (2017), chosen as the most cited paper whose own text cites the registry id.","summary":"Purpose MONARCH 2 ( ClinicalTrials.gov identifier: NCT02107703) compared the efficacy and safety of abemaciclib, a selective cyclin-dependent kinase 4 and 6 inhibitor, plus fulvestrant with fulvestrant alone in patients with advanced breast cancer (ABC). Patients and Methods MONARCH 2 was a global, double-blind, phase III study of women with hormone receptor-positive and human epidermal growth factor receptor 2-negative ABC who had progressed while receiving neoadjuvant or adjuvant endocrine therapy (ET), ≤ 12 months from the end of adjuvant ET, or while receiving first-line ET for metastatic disease. Patients were randomly assigned 2:1 to receive abemaciclib or placebo (150 mg twice daily) on a continuous schedule and fulvestrant (500 mg, per label). The primary end point was investigator-assessed progression-free survival (PFS), and key secondary end points included overall survival, objective response rate (ORR), duration of response, clinical benefit rate, quality of life, and safety. Results Between August 2014 and December 2015, 669 patients were randomly assigned to receive abemaciclib plus fulvestrant (n = 446) or placebo plus fulvestrant (n = 223). Abemaciclib plus fulvestrant significantly extended PFS versus fulvestrant alone (median, 16.4 v 9.3 months; hazard ratio, 0.553; 95% CI, 0.449 to 0.681; P <.001). In patients with measurable disease, abemaciclib plus fulvestrant achieved an ORR of 48.1% (95% CI, 42.6% to 53.6%) compared with 21.3% (95% CI, 15.1% to 27.6%) in the control arm. The most common adverse events in the abemaciclib versus placebo arms were diarrhea (86.4% v 24.7%), neutropenia (46.0% v 4.0%), nausea (45.1% v 22.9%), and fatigue (39.9% v 26.9%). Conclusions Abemaciclib at 150 mg twice daily plus fulvestrant was effective, significantly improving PFS and ORR and demonstrating a tolerable safety profile in women with hormone receptor-positive and human epidermal growth factor receptor 2-negative ABC who progressed while receiving ET.\n\nIndexed on Europe PMC as PubMed record 28580882 (DOI 10.1200/jco.2017.73.7585). Its abstract cites the registry id NCT02107703, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2017","url":"https://doi.org/10.1200/jco.2017.73.7585"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28580882/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28580882"},{"label":"ClinicalTrials.gov NCT02107703","url":"https://clinicaltrials.gov/study/NCT02107703"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct02107703"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2017,"doi":"10.1200/jco.2017.73.7585","pmid":"28580882","authors":"Sledge GW, Toi M, Neven P, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02107703 with the most citations, so it is the natural first reading for anyone following the MONARCH 2 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-monarche-jco-2020","kind":"paper","name":"monarchE: two years of abemaciclib after surgery in high-risk, hormone-receptor-positive early breast cancer","aka":[],"tldr":"Adding two years of the CDK4/6 inhibitor abemaciclib to standard hormone therapy after surgery cut the risk of the cancer coming back by a quarter in women with node-positive, high-risk disease.","summary":"Open-label phase 3 trial of 5,637 patients with hormone-receptor-positive, HER2-negative early breast cancer at high risk of recurrence (four or more positive nodes, or one to three nodes with grade 3, tumour 5 cm or more, or high Ki-67), randomised to standard endocrine therapy with or without two years of abemaciclib. Primary endpoint was invasive disease-free survival (iDFS).\n\nAt the pre-planned interim analysis, iDFS was improved (HR 0.75; 2-year iDFS 92.2% vs 88.7%). The benefit widened with time: at five years iDFS was 83.6% vs 76.0%, a 7.6-point absolute difference (HR 0.68), well after abemaciclib had stopped. It was the first adjuvant CDK4/6 inhibitor to succeed after palbociclib failed in PALLAS and PENELOPE-B.","asOf":"2026-09-08","links":[{"label":"PubMed search: monarchE JCO 2020","url":"https://pubmed.ncbi.nlm.nih.gov/?term=monarchE+abemaciclib+adjuvant+Johnston+2020"},{"label":"ClinicalTrials.gov NCT03155997","url":"https://clinicaltrials.gov/study/NCT03155997"}],"tags":[],"related":[],"cancers":["breast-hr-positive"],"sections":[],"technologies":["cdk46-inhibitor","endocrine-therapy"],"targets":["cdk4-6","estrogen-receptor"],"drugs":["abemaciclib"],"companies":["eli-lilly"],"institutions":[],"pathways":[],"terms":["neoadjuvant-adjuvant","hazard-ratio"],"trials":["monarche","natalee"],"people":["miguel-martin","shao-zhi-ming","sohn-joohyuk","javier-cortes","andrew-wardley","sara-tolaney"],"bottlenecks":["b-dormancy-mrd","b-drug-pricing","b-toxicity-qol"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/JCO.20.02514","pmid":"32954927","authors":"Johnston SRD, Harbeck N, Hegg R, et al.","paperType":"rct","findings":["Invasive disease-free survival HR 0.75 (95% CI 0.60-0.93) at the interim analysis; 2-year iDFS 92.2% vs 88.7%.","Five-year update (2024): iDFS 83.6% vs 76.0% (HR 0.68) and distant relapse-free survival 86.0% vs 79.2%, with the curves continuing to separate after treatment ended.","Diarrhoea occurred in over 80% of abemaciclib patients (mostly grade 1-2) and roughly one in six discontinued because of adverse events.","Ki-67 of 20% or more identified a higher-risk group but did not predict a larger relative benefit, so the label was later broadened to all high-risk node-positive patients.","Overall survival data remain immature."],"whatItMeans":"Women with hormone-receptor-positive, HER2-negative breast cancer that has spread to lymph nodes and has other high-risk features can now be offered two years of abemaciclib alongside their hormone therapy, with a durable reduction in relapse. It does not apply to node-negative or low-risk disease, and the diarrhoea and cost are real trade-offs to discuss.","caveats":["No overall survival benefit has yet been shown.","Open-label design with an endpoint (iDFS) that includes second primary cancers.","The contrast with the negative PALLAS trial (palbociclib) is not fully explained: differences in drug, dose intensity, or population selection are all possible.","Two years of a costly oral drug for a 7-8 point absolute gain raises access questions in many health systems."],"changedPractice":true,"participants":5637},{"id":"paper-monumental-1-talquetamab-nejm-2022","kind":"paper","name":"MonumenTAL-1: talquetamab, a GPRC5D-directed bispecific antibody for relapsed multiple myeloma","aka":[],"tldr":"Talquetamab, an antibody that pulls T cells onto a new myeloma target called GPRC5D, produced responses in about seven in ten heavily pretreated patients, including those already treated with BCMA-directed therapy.","summary":"Phase 1 dose-escalation and expansion study of 288 patients with relapsed or refractory multiple myeloma treated with subcutaneous talquetamab at 405 micrograms per kilogram weekly or 800 micrograms per kilogram every two weeks.\n\nResponse rates were about 70 percent at both doses with a median duration of response of about 10 months; cytokine release syndrome was common but mostly low grade, and skin, nail and taste changes were characteristic.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2022","url":"https://doi.org/10.1056/NEJMoa2204591"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36507686/"}],"tags":[],"related":[],"cancers":["myeloma-relapsed-refractory"],"sections":[],"technologies":[],"targets":[],"drugs":["mcla-129","talquetamab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["monumental-1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/NEJMoa2204591","pmid":"36507686","authors":"Chari A, Minnema MC, Berdeja JG, et al.","paperType":"observational","findings":["Overall response about 70 percent at the two recommended doses.","Median duration of response roughly 10 months; cytokine release syndrome in about three quarters, mostly grade 1 to 2."],"whatItMeans":"A second bispecific target beyond BCMA gives patients an option after BCMA-directed CAR-T or bispecifics have failed; it was approved in 2023.","caveats":["Single-arm early-phase data.","Dysgeusia, weight loss and skin toxicity affect quality of life and adherence."],"changedPractice":true,"participants":288},{"id":"paper-morpho-gilteritinib-levis-jco-2024","kind":"paper","name":"MORPHO: gilteritinib as post-transplant maintenance for FLT3-ITD acute myeloid leukaemia","aka":[],"tldr":"Two years of the FLT3 blocker gilteritinib after a stem-cell transplant did not significantly reduce relapses across all patients, but it clearly did in the half whose highly sensitive blood tests still found traces of the leukaemia, one of the first results to support choosing post-transplant treatment by residual disease.","summary":"Randomised, double-blind, placebo-controlled phase 3 trial (BMT CTN 1506) in 356 adults with FLT3-ITD acute myeloid leukaemia in first remission after allogeneic transplant, assigned to gilteritinib 120 mg daily or placebo for 24 months. The primary endpoint was relapse-free survival; measurable residual disease for FLT3-ITD was assessed before and after transplant.\n\nRelapse-free survival favoured gilteritinib but was not statistically significant (hazard ratio 0.679, p 0.0518). In the prespecified 50.5 percent of participants with detectable residual disease the hazard ratio was 0.515 (p 0.0065); those without detectable disease showed no benefit (hazard ratio 1.213).","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2024","url":"https://doi.org/10.1200/JCO.23.02474"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38471061/"}],"tags":[],"related":[],"cancers":["aml-flt3","aml"],"sections":[],"technologies":[],"targets":[],"drugs":["gilteritinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["morpho"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2024,"doi":"10.1200/JCO.23.02474","pmid":"38471061","authors":"Levis MJ, Hamadani M, Logan B, et al.","paperType":"rct","findings":["Relapse-free survival hazard ratio 0.679 (95% CI 0.459 to 1.005; two-sided p 0.0518) for gilteritinib versus placebo.","MRD detectable before or after transplant (50.5 percent of participants): hazard ratio 0.515 (95% CI 0.316 to 0.838; p 0.0065).","MRD not detectable: hazard ratio 1.213 (95% CI 0.616 to 2.387; p 0.575)."],"whatItMeans":"Post-transplant FLT3 inhibitor maintenance helps patients with detectable FLT3-ITD residual disease and can probably be spared in those without it; guidelines now describe maintenance for MRD-positive disease on this evidence.","caveats":["The primary endpoint was not met; the MRD finding is a prespecified subgroup analysis.","Conditioning intensity and regional practice differences affected the size of the benefit in later analyses."],"changedPractice":true,"participants":356},{"id":"paper-hanna-bmj","kind":"paper","name":"Mortality due to cancer treatment delay: systematic review and meta-analysis","aka":[],"tldr":"Paper cited by one bottleneck page and 18 idea pages, indexed on Europe PMC as PubMed record 33148535 and published in BMJ; the citing pages link this DOI, which is how the record was matched.","summary":"Objective: To quantify the association of cancer treatment delay and mortality for each four week increase in delay to inform cancer treatment pathways.\n\nDesign: Systematic review and meta-analysis.\n\nData sources: Published studies in Medline from 1 January 2000 to 10 April 2020.\n\nEligibility criteria for selecting studies: Curative, neoadjuvant, and adjuvant indications for surgery, systemic treatment, or radiotherapy for cancers of the bladder, breast, colon, rectum, lung, cervix, and head and neck were included. The main outcome measure was the hazard ratio for overall survival for each four week delay for each indication. Delay was measured from diagnosis to first treatment, or from the completion of one treatment to the start of the next. The primary analysis only included high validity studies controlling for major prognostic factors. Hazard ratios were assumed to be log linear in relation to overall survival and were converted to an effect for each four week delay. Pooled effects were estimated using DerSimonian and Laird random effect models.\n\nResults: The review included 34 studies for 17 indications (n=1 272 681 patients). No high validity data were found for five of the radiotherapy indications or for cervical cancer surgery. The association between delay and increased mortality was significant (P<0.05) for 13 of 17 indications. Surgery findings were consistent, with a mortality risk for each four week delay of 1.06-1.08 (eg, colectomy 1.06, 95% confidence interval 1.01 to 1.12; breast surgery 1.08, 1.03 to 1.13). Estimates for systemic treatment varied (hazard ratio range 1.01-1.28). Radiotherapy estimates were for radical radiotherapy for head and neck cancer (hazard ratio 1.09, 95% confidence interval 1.05 to 1.14), adjuvant radiotherapy after breast conserving surgery (0.98, 0.88 to 1.09), and cervix cancer adjuvant radiotherapy (1.23, 1.00 to 1.50). A sensitivity analysis of studies that had been excluded because of lack of information on comorbidities or functional status did not change the findings.\n\nConclusions: Cancer treatment delay is a problem in health systems worldwide. The impact of delay on mortality can now be quantified for prioritisation and modelling. Even a four week delay of cancer treatment is associated with increased mortality across surgical, systemic treatment, and radiotherapy indications for seven cancers. Policies focused on minimising system level delays to cancer treatment initiation could improve population level survival outcomes.\n\nIndexed on Europe PMC as PubMed record 33148535 (DOI 10.1136/bmj.m4087). Matched by DOI alone: one bottleneck page and 18 idea pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"BMJ 2020","url":"https://doi.org/10.1136/bmj.m4087"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33148535/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33148535"}],"tags":["europepmc-ingest"],"related":["b-care-fragmentation","idea-acc-portable-treatment-summary","idea-acc-funded-navigator-per-diagnosis","idea-acc-transition-handoff-medication-reconciliation","idea-acc-acute-oncology-assessment-units","idea-acc-universal-asynchronous-second-opinion","idea-acc-tumour-board-implementation-audit","idea-acc-episode-payment-tied-to-concordance","idea-acc-embedded-decision-aids","idea-acc-primary-care-shared-care-agreements","idea-acc-guideline-concordance-dashboards","idea-acc-national-virtual-mdt-rare-complex","idea-acc-one-stop-breast-diagnostic-clinic","idea-acc-reflex-genomic-profiling-at-diagnosis","idea-acc-rapid-diagnostic-centres-vague-symptoms","idea-acc-diagnostic-interval-public-registry","idea-acc-financial-toxicity-screening-at-diagnosis","idea-acc-pathway-capacity-simulation","idea-acc-reflex-biomarker-panels-by-tumour"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["bmj"],"dependsOn":[],"notes":[],"journal":"BMJ","year":2020,"doi":"10.1136/bmj.m4087","pmid":"33148535","authors":"Hanna TP, King WD, Thibodeau S, et al.","paperType":"meta-analysis","findings":[],"whatItMeans":"One bottleneck page and 18 idea pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-almoguera-kras-codon-12-pancreatic-cell-1988","kind":"paper","name":"Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes","aka":[],"tldr":"The 1988 paper that found a mutation in the KRAS gene in 21 of 22 pancreatic cancers, establishing the single most common driver in the disease and the target it took 33 more years to hit.","summary":"Almoguera, Shibata, Forrester, Martin, Arnheim and Perucho used polymerase chain reaction amplification and RNAase A mismatch cleavage to examine c-K-ras in human pancreatic carcinomas, in frozen specimens and single 5 micron sections of formalin-fixed tissue from surgery or autopsy. Twenty-one of 22 carcinomas of the exocrine pancreas carried c-K-ras mutations at codon 12; in seven cases tested the mutation was present in both the primary tumour and its metastases; no mutations were found in normal tissue from the same patients or in five gallbladder carcinomas. The authors concluded that somatic activation of c-K-ras is a critical event in the oncogenesis of most, if not all, cancers of the exocrine pancreas.","asOf":"2026-09-24","links":[{"label":"Cell 1988","url":"https://doi.org/10.1016/0092-8674(88)90571-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/2453289/"}],"tags":["pancreatic-evidence"],"related":["kras-roadmap","paper-ostrem-kras-g12c-nature-2013"],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":["kras"],"drugs":[],"companies":[],"institutions":[],"pathways":["ras-mapk"],"terms":["kras-mutation-subtypes"],"trials":[],"people":["frank-mccormick"],"bottlenecks":["b-undruggable-targets"],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Cell","year":1988,"doi":"10.1016/0092-8674(88)90571-5","pmid":"2453289","authors":"Almoguera C, Shibata D, Forrester K, et al.","paperType":"basic","findings":["21 of 22 exocrine pancreatic carcinomas carried c-K-ras codon 12 mutations.","The mutation was present in both primary and metastasis in all seven pairs tested.","No mutations in matched normal tissue or in five gallbladder carcinomas."],"whatItMeans":"The reason pancreatic cancer is the proving ground for RAS drugs: nearly every tumour depends on the same mutant protein, so a drug that works against it works for nearly every patient.","caveats":["22 tumours from one laboratory; later series put the KRAS mutation rate near 90 percent, with G12D, G12V and G12R the common alleles.","Detection method of its time; the codon 12 mutation subtype was not resolved."],"participants":22},{"id":"paper-mpact-nab-paclitaxel-gemcitabine-nejm-2013","kind":"paper","name":"MPACT (Von Hoff 2013): nab-paclitaxel plus gemcitabine for metastatic pancreatic cancer","aka":[],"tldr":"Adding albumin-bound paclitaxel to gemcitabine prolonged survival in metastatic pancreatic cancer in a large international trial, giving patients who are not fit enough for FOLFIRINOX a second effective first-line option.","summary":"MPACT randomised 861 patients with untreated metastatic pancreatic adenocarcinoma to nab-paclitaxel plus gemcitabine or gemcitabine alone. The combination improved overall survival, progression-free survival and response rate, with more neutropenia, fatigue and peripheral neuropathy that was usually reversible on dose reduction. Because it accepted patients up to performance status 2 and was less toxic than FOLFIRINOX, it became the alternative first-line standard and the backbone for many later combination trials.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa1304369"},{"label":"ClinicalTrials.gov NCT00844649","url":"https://clinicaltrials.gov/study/NCT00844649"}],"tags":[],"related":["paper-conroy-folfirinox-pancreatic-nejm-2011"],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":["gemcitabine-nab-paclitaxel","gemcitabine"],"companies":[],"institutions":[],"pathways":[],"terms":["os","pfs"],"trials":[],"people":["daniel-von-hoff"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2013,"doi":"10.1056/NEJMoa1304369","authors":"Von Hoff DD, Ervin T, Arena FP, et al.","paperType":"rct","findings":["861 patients with untreated metastatic pancreatic cancer; nab-paclitaxel plus gemcitabine vs gemcitabine.","Median overall survival 8.5 vs 6.7 months, hazard ratio 0.72.","Median progression-free survival 5.5 vs 3.7 months, hazard ratio 0.69; response rate 23% vs 7%.","Grade 3 or higher neutropenia 38% vs 27% and peripheral neuropathy 17% vs 1%."],"whatItMeans":"With FOLFIRINOX this trial defined the two chemotherapy standards for metastatic pancreatic cancer that still apply, and the gemcitabine and nab-paclitaxel backbone is the comparator in most current first-line pancreatic trials.","caveats":["Open-label design.","The survival gain is measured in months and the disease remains one of the most lethal.","Cross-trial comparison with FOLFIRINOX is unreliable; the populations differed in fitness."],"changedPractice":true,"participants":861},{"id":"paper-mrc-te19-carboplatin-seminoma-oliver-lancet-2005","kind":"paper","name":"MRC TE19/EORTC 30982: radiotherapy versus single-dose carboplatin as adjuvant treatment for stage I seminoma","aka":[],"tldr":"A single dose of carboplatin was as effective as radiotherapy in preventing relapse of stage I seminoma after orchidectomy, with less time off work and fewer second testicular cancers, so it replaced radiotherapy for men who choose adjuvant treatment.","summary":"Phase 3 non-inferiority trial of 1,477 men with stage I seminoma randomised to adjuvant radiotherapy or one cycle of carboplatin (AUC 7).\n\nThree-year relapse-free rates were 94.8 percent with carboplatin and 95.9 percent with radiotherapy (non-inferior), with fewer contralateral germ cell tumours after carboplatin and less acute toxicity; longer follow-up confirmed equivalence.","asOf":"2026-09-17","links":[{"label":"Lancet 2005","url":"https://doi.org/10.1016/S0140-6736(05)66984-X"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/16039331/"}],"tags":[],"related":[],"cancers":["seminoma"],"sections":[],"technologies":[],"targets":[],"drugs":["carboplatin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2005,"doi":"10.1016/S0140-6736(05)66984-X","pmid":"16039331","authors":"Oliver RT, Mason MD, Mead GM, et al.","paperType":"rct","findings":["Three-year relapse-free rate 94.8 percent (carboplatin) vs 95.9 percent (radiotherapy); non-inferior.","Contralateral germ cell tumours 2 vs 10 cases."],"whatItMeans":"Single-dose carboplatin is the adjuvant option for stage I seminoma where surveillance is not chosen; radiotherapy is now rarely used because of second cancer risk.","caveats":["Surveillance alone cures the same proportion of men after salvage and is preferred for most today."],"changedPractice":true,"participants":1477},{"id":"paper-engstrom-cancer-discov","kind":"paper","name":"MRTX1719 Is an MTA-Cooperative PRMT5 Inhibitor That Exhibits Synthetic Lethality in Preclinical Models and Patients with MTAP-Deleted Cancer","aka":[],"tldr":"Paper cited by one target page, indexed on Europe PMC as PubMed record 37552839 and published in Cancer Discovery; the citing page links this DOI, which is how the record was matched.","summary":"Previous studies implicated protein arginine methyltransferase 5 (PRMT5) as a synthetic lethal target for MTAP-deleted (MTAP del) cancers; however, the pharmacologic characterization of small-molecule inhibitors that recapitulate the synthetic lethal phenotype has not been described. MRTX1719 selectively inhibited PRMT5 in the presence of MTA, which is elevated in MTAP del cancers, and inhibited PRMT5-dependent activity and cell viability with >70-fold selecti-vity in HCT116 MTAP del compared with HCT116 MTAP wild-type (WT) cells. MRTX1719 demonstrated dose-dependent antitumor activity and inhibition of PRMT5-dependent SDMA modification in MTAP del tumors. In contrast, MRTX1719 demonstrated minimal effects on SDMA and viability in MTAP WT tumor xenografts or hematopoietic cells. MRTX1719 demonstrated marked antitumor activity across a panel of xenograft models at well-tolerated doses. Early signs of clinical activity were observed including objective responses in patients with MTAP del melanoma, gallbladder adenocarcinoma, mesothelioma, non-small cell lung cancer, and malignant peripheral nerve sheath tumors from the phase I/II study.\n\nSignificance: PRMT5 was identified as a synthetic lethal target for MTAP del cancers; however, previous PRMT5 inhibitors do not selectively target this genotype. The differentiated binding mode of MRTX1719 leverages the elevated MTA in MTAP del cancers and represents a promising therapy for the ∼10% of patients with cancer with this biomarker. See related commentary by Mulvaney, p. 2310. This article is featured in Selected Articles from This Issue, p. 2293.\n\nIndexed on Europe PMC as PubMed record 37552839 (DOI 10.1158/2159-8290.cd-23-0669). Matched by DOI alone: one target page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer Discov 2023","url":"https://doi.org/10.1158/2159-8290.cd-23-0669"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37552839/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37552839"}],"tags":["europepmc-ingest"],"related":["prmt5-mtap"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-discovery"],"dependsOn":[],"notes":[],"journal":"Cancer Discovery","year":2023,"doi":"10.1158/2159-8290.cd-23-0669","pmid":"37552839","authors":"Engstrom LD, Aranda R, Waters L, et al.","paperType":"basic","findings":[],"whatItMeans":"One target page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-guedes-msh2-loss-primary-prostate-ccr-2017","kind":"paper","name":"MSH2 loss in primary prostate cancer","aka":[],"tldr":"Staining more than a thousand prostate tumours found the mismatch repair protein missing in about one in eighty, and twenty times more often in the highest-grade cancers.","summary":"A total of 1,133 primary prostatic adenocarcinomas and 43 prostatic small cell carcinomas were screened by MSH2 immunohistochemistry with confirmation by next-generation sequencing, and microsatellite instability was assessed by PCR and by mSINGS. Of the primary adenocarcinomas and small cell carcinomas together, 14 of 1,176, 1.2%, had MSH2 loss. Eight per cent of adenocarcinomas with primary Gleason pattern 5 (Gleason score 9 to 10), 7 of 91, had MSH2 loss compared with 0.4%, 5 of 1,042, of tumours with any other score, and 2 of 43 small cell carcinomas, 5%. MSH2 loss was generally homogeneous, suggesting an early clonal event. Sequencing confirmed loss-of-function alterations in all 12 samples tested, with biallelic inactivation in 83% and hypermutation in 83%; 61% and 58% had definite microsatellite instability by PCR and mSINGS respectively, and 3 patients, 25%, had germline MSH2 mutations. Tumours with MSH2 loss had a higher density of infiltrating CD8-positive lymphocytes than grade-matched controls, 390 against 76 cells per square millimetre.","asOf":"2026-09-25","links":[{"label":"Guedes et al., Clin Cancer Res 2017: MSH2 loss by immunohistochemistry in 1,133 primary prostatic adenocarcinomas and 43 small-cell carcinomas","url":"https://doi.org/10.1158/1078-0432.CCR-17-0955"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28790115/"}],"tags":[],"related":[],"cancers":["prostate","prostate-nepc"],"sections":[],"technologies":["histopathology-ihc","cgp"],"targets":["msh2","mmr"],"drugs":[],"companies":[],"institutions":[],"pathways":["mismatch-repair-msi","cancer-immunity-cycle"],"terms":["msi","ihc","lynch-syndrome","gleason-grade-group","germline-vs-somatic"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2017,"doi":"10.1158/1078-0432.CCR-17-0955","pmid":"28790115","authors":"Guedes LB, Antonarakis ES, Schweizer MT, et al.","paperType":"observational","findings":["MSH2 protein loss in 14 of 1,176 prostate carcinomas, 1.2%.","Eight per cent of primary Gleason pattern 5 tumours against 0.4% of all others.","Homogeneous loss, biallelic inactivation in 83% and hypermutation in 83% of sequenced cases.","Germline MSH2 mutation in 3 of 12 sequenced patients, 25%; CD8 density 390 against 76 cells per square millimetre."],"whatItMeans":"It gives a cheap way to find the rare men who could benefit from checkpoint blockade: an immunohistochemical stain on the highest-grade primary tumours, where the yield is twenty times higher than average. It also shows the loss is clonal and early, so the diagnostic block is an adequate place to look.","caveats":["MSH2 immunohistochemistry alone, so tumours losing MLH1, MSH6 or PMS2 without MSH2 loss were not counted.","A single-institution series with retrospective case selection.","The immune infiltrate finding is descriptive and was not linked to treatment outcome here."],"changedPractice":false,"participants":1176},{"id":"paper-mslt-ii-faries-nejm-2017","kind":"paper","name":"MSLT-II: completion lymph node dissection or observation for sentinel-node metastasis in melanoma","aka":[],"tldr":"Removing all the remaining lymph nodes after a positive sentinel node did not improve melanoma survival compared with ultrasound surveillance and caused far more lymphoedema, ending routine completion dissection.","summary":"Phase 3 trial of 1,939 patients with sentinel node-positive melanoma randomised to immediate completion lymph node dissection or nodal observation with ultrasound.\n\nThree-year melanoma-specific survival was 86 percent in both groups; dissection improved regional disease control and gave prognostic information but caused lymphoedema in 24 versus 6 percent.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2017","url":"https://doi.org/10.1056/NEJMoa1613210"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28591523/"}],"tags":[],"related":[],"cancers":["stage-iii-melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["mslt-ii"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2017,"doi":"10.1056/NEJMoa1613210","pmid":"28591523","authors":"Faries MB, Thompson JF, Cochran AJ, et al.","paperType":"rct","findings":["Three-year melanoma-specific survival 86 percent in both groups.","Lymphoedema 24.1 percent vs 6.3 percent."],"whatItMeans":"Patients with a positive sentinel node are now managed with surveillance and adjuvant systemic therapy rather than completion dissection.","caveats":["Most patients had low-volume sentinel node disease; the trial was not powered for those with high nodal burden."],"changedPractice":true,"participants":1939},{"id":"paper-morice-mucinous-ovarian-carcinoma-nejm-2019","kind":"paper","name":"Mucinous ovarian carcinoma (review)","aka":[],"tldr":"This review explains how mucinous ovarian cancer differs from other ovarian cancers, why metastases from the bowel must be excluded, and how surgery, fertility preservation and chemotherapy choices are made in a disease with little trial evidence.","summary":"Review covering the epidemiology, pathology and immunohistochemical distinction of primary mucinous ovarian carcinoma from metastatic gastrointestinal tumours, expansile versus infiltrative patterns, molecular features, surgical staging and fertility-sparing surgery, the role of appendicectomy, adjuvant chemotherapy including gastrointestinal-type regimens, and management of advanced disease.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2019","url":"https://doi.org/10.1056/NEJMra1813254"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30917260/"}],"tags":[],"related":[],"cancers":["mucinous-ovarian-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2019,"doi":"10.1056/NEJMra1813254","pmid":"30917260","authors":"Morice P, Gouy S, Leary A.","paperType":"review","findings":[],"whatItMeans":"The mucinous ovarian cancer page's emphasis on excluding a gastrointestinal primary, omitting chemotherapy for early expansile tumours, and considering gastrointestinal-type regimens follows this review.","caveats":["Randomised evidence is minimal because the disease is rare; the mEOC/GOG 0241 trial closed early."],"changedPractice":false},{"id":"paper-hu-nat-genet","kind":"paper","name":"Multi-cancer analysis of clonality and the timing of systemic spread in paired primary tumors and metastases","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 32424352 and published in Nature Genetics; the citing page links this DOI, which is how the record was matched.","summary":"Metastasis is the primary cause of cancer-related deaths, but the natural history, clonal evolution and impact of treatment are poorly understood. We analyzed whole-exome sequencing (WES) data from 457 paired primary tumor and metastatic samples from 136 patients with breast, colorectal and lung cancer, including untreated (n = 99) and treated (n = 100) metastases. Treated metastases often harbored private 'driver' mutations, whereas untreated metastases did not, suggesting that treatment promotes clonal evolution. Polyclonal seeding was common in untreated lymph node metastases (n = 17 out of 29, 59%) and distant metastases (n = 20 out of 70, 29%), but less frequent in treated distant metastases (n = 9 out of 94, 10%). The low number of metastasis-private clonal mutations is consistent with early metastatic seeding, which we estimated occurred 2-4 years before diagnosis across these cancers. Furthermore, these data suggest that the natural course of metastasis is selectively relaxed relative to early tumorigenesis and that metastasis-private mutations are not drivers of cancer spread but instead associated with drug resistance.\n\nIndexed on Europe PMC as PubMed record 32424352 (DOI 10.1038/s41588-020-0628-z). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Genet 2020","url":"https://doi.org/10.1038/s41588-020-0628-z"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32424352/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32424352"}],"tags":["europepmc-ingest"],"related":["metastasis-seeding-models"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":2020,"doi":"10.1038/s41588-020-0628-z","pmid":"32424352","authors":"Hu Z, Li Z, Ma Z, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-lehmann-tnbc-subtype-multiomics-nat-commun-2021","kind":"paper","name":"Multi-omics analysis identifies therapeutic vulnerabilities in triple-negative breast cancer subtypes","aka":[],"tldr":"Mesenchymal triple-negative tumours hide from the immune system by switching off the machinery that displays tumour proteins to T cells; a drug class that blocks the PRC2 epigenetic complex switched it back on in mice and made chemotherapy work better.","summary":"Mutation, copy number, transcriptomic, epigenetic, proteomic and phospho-proteomic patterns were analysed across the TNBC subtypes (BL1, BL2, M, LAR). Mesenchymal tumours displayed high mutation loads, genomic instability, absence of immune cells, low PD-L1 expression, decreased global DNA methylation and transcriptional repression of antigen presentation genes. MHC class I was shown to be suppressed by H3K27me3 laid down by the polycomb repressor complex 2 (PRC2); pharmacological inhibition of the PRC2 subunits EZH2 or EED restored MHC-I expression and enhanced chemotherapy efficacy in murine tumour models.","asOf":"2026-09-24","links":[{"label":"Lehmann et al., Nat Commun 2021: multi-omics vulnerabilities of TNBC subtypes","url":"https://doi.org/10.1038/s41467-021-26502-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34725325/"}],"tags":[],"related":[],"cancers":["tnbc"],"sections":[],"technologies":[],"targets":["ezh2","pdl1"],"drugs":[],"companies":[],"institutions":["vanderbilt-ingram"],"pathways":["antigen-presentation-immunoediting","emt","epigenetic-reprogramming"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-communications"],"dependsOn":[],"notes":[],"journal":"Nature Communications","year":2021,"doi":"10.1038/s41467-021-26502-6","pmid":"34725325","authors":"Lehmann BD, Colaprico A, Silva TC, et al.","paperType":"translational","findings":["Mesenchymal subtype: high mutation load, no immune cells, low PD-L1, repressed antigen presentation.","MHC-I is silenced by PRC2-mediated H3K27me3; EZH2 or EED inhibition restores it and improves chemotherapy in mice."],"whatItMeans":"It gives the PD-L1-negative mesenchymal subtype, the group immunotherapy leaves behind, a mechanistic route back to immune visibility, and explains why immune infiltration and subtype are coupled.","caveats":["Therapeutic evidence is in mouse models only.","Subtype calls on TCGA and METABRIC depend on purity and the classifier version."],"changedPractice":false},{"id":"paper-wagner-j-immunother-cancer","kind":"paper","name":"Multicenter phase II trial (SWOG S1609, cohort 51) of ipilimumab and nivolumab in metastatic or unresectable angiosarcoma: a substudy of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART)","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 34380663 and published in Journal for ImmunoTherapy of Cancer; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: Angiosarcoma is a rare aggressive endothelial cell cancer with high mortality. Isolated reports suggest immune checkpoint inhibition efficacy in angiosarcoma, but no prospective studies have been published. We report results for angiosarcoma treated with ipilimumab and nivolumab as a cohort of an ongoing rare cancer study.\n\nMethods: This is a prospective, open-label, multicenter phase II clinical trial of ipilimumab (1 mg/kg intravenously every 6 weeks) plus nivolumab (240 mg intravenously every 2 weeks) for metastatic or unresectable angiosarcoma. Primary endpoint was objective response rate (ORR) per RECIST 1.1. Secondary endpoints include progression-free (PFS) and overall survival, and toxicity. A two-stage design was used.\n\nResults: Overall, there were 16 evaluable patients. Median age was 68 years (range, 25-81); median number of prior lines of therapy, 2. Nine patients had cutaneous and seven non-cutaneous primary tumors. ORR was 25% (4/16). Sixty per cent of patients (3/5) with primary cutaneous scalp or face tumors attained a confirmed response. Six-month PFS was 38%. Altogether, 75% of patients experienced an adverse event (AE) (at least possibly related to drug) (25% grade 3-4 AE); 68.8%, an immune-related AE (irAE) (2 (12.5%), grade 3 or 4 irAEs (alanine aminotransferase/aspartate aminotransferase increase and diarrhea)). There were no grade 5 toxicities. One of seven patients in whom tumor mutation burden (TMB) was assessed showed a high TMB (24 mutations/mb); that patient achieved a partial response (PR). Two of three patients with PDL1 immunohistochemistry assessed had high PDL1 expression; one achieved a PR.\n\nConclusion: The combination of ipilimumab and nivolumab demonstrated an ORR of 25% in angiosarcoma, with three of five patients with cutaneous tumors of the scalp or face responding. Ipilimumab and nivolumab warrant further investigation in angiosarcoma.\n\nTrial registration number: NCT02834013.\n\nIndexed on Europe PMC as PubMed record 34380663 (DOI 10.1136/jitc-2021-002990). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Immunother Cancer 2021","url":"https://doi.org/10.1136/jitc-2021-002990"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34380663/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34380663"}],"tags":["europepmc-ingest"],"related":["vascular-tumours"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jitc"],"dependsOn":[],"notes":[],"journal":"Journal for ImmunoTherapy of Cancer","year":2021,"doi":"10.1136/jitc-2021-002990","pmid":"34380663","authors":"Wagner MJ, Othus M, Patel SP, et al.","paperType":"observational","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-taylor-bmj","kind":"paper","name":"Multidisciplinary team working in cancer: what is the evidence?","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 20332315 and published in BMJ; the citing page links this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 20332315 (DOI 10.1136/bmj.c951). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"BMJ 2010","url":"https://doi.org/10.1136/bmj.c951"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20332315/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/20332315"}],"tags":["europepmc-ingest"],"related":["multidisciplinary-tumour-board"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["bmj"],"dependsOn":[],"notes":[],"journal":"BMJ","year":2010,"doi":"10.1136/bmj.c951","pmid":"20332315","authors":"Taylor C, Munro AJ, Glynne-Jones R, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-imperiale-multitarget-stool-dna-screening-nejm-2014","kind":"paper","name":"Multitarget stool DNA testing for colorectal-cancer screening","aka":[],"tldr":"A stool test that looks for cancer DNA as well as blood found 92 percent of cancers against 74 percent for the blood-only test, at the price of more false alarms. It is the trial behind Cologuard.","summary":"Imperiale, Ransohoff, Itzkowitz and colleagues compared a non-invasive multitarget stool DNA test with a faecal immunochemical test in people at average risk of colorectal cancer, all of whom also had a colonoscopy. The DNA test includes quantitative molecular assays for KRAS mutations, aberrant NDRG4 and BMP3 methylation and beta-actin, plus a haemoglobin immunoassay, with results generated by a logistic-regression algorithm; values of 183 or more counted as positive, and faecal immunochemical test values above 100 ng of haemoglobin per millilitre of buffer counted as positive. Tests were processed independently of the colonoscopy findings.\n\nOf 9,989 evaluable participants, 65 (0.7 percent) had colorectal cancer and 757 (7.6 percent) had advanced precancerous lesions.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2014","url":"https://doi.org/10.1056/NEJMoa1311194"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24645800/"},{"label":"N Engl J Med 2014","url":"https://doi.org/10.1056/nejmoa1311194"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/24645800"},{"label":"ClinicalTrials.gov NCT01397747","url":"https://clinicaltrials.gov/study/NCT01397747"}],"tags":["colorectal-evidence"],"related":["paper-hardcastle-nottingham-faecal-occult-blood-lancet-1996","paper-nordicc-nejm-2022"],"cancers":["colorectal"],"sections":["early-detection"],"technologies":["colorectal-screening","cologuard","liquid-biopsy","mced"],"targets":[],"drugs":[],"companies":["exact-sciences"],"institutions":[],"pathways":[],"terms":["fit-test","ppv"],"trials":["deep-c"],"people":[],"bottlenecks":["b-early-detection","b-biomarker-validation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2014,"doi":"10.1056/NEJMoa1311194","pmid":"24645800","authors":"Imperiale TF, Ransohoff DF, Itzkowitz SH, et al.","paperType":"methods","findings":["Sensitivity for colorectal cancer 92.3 percent with the DNA test against 73.8 percent with the faecal immunochemical test (p=0.002).","Sensitivity for advanced precancerous lesions 42.4 percent against 23.8 percent (p<0.001).","Specificity 86.6 percent against 94.9 percent among those with non-advanced or negative findings (p<0.001).","Numbers needed to screen to detect one cancer: 154 with colonoscopy, 166 with the DNA test, 208 with the faecal immunochemical test."],"whatItMeans":"The first molecular stool test to reach approval, and the template for the blood tests that followed: more sensitive for cancer, much less specific, and still poor at the precancerous lesions that screening is supposed to remove.","caveats":["Cross-sectional accuracy against colonoscopy in one round; no trial has shown that stool DNA testing reduces colorectal cancer mortality.","Lower specificity means more colonoscopies per cancer found, which matters where endoscopy capacity is the constraint.","Funded by the test's manufacturer."],"changedPractice":true,"participants":9989},{"id":"paper-murano-venetoclax-rituximab-nejm-2018","kind":"paper","name":"MURANO: two years of venetoclax plus rituximab versus chemo-immunotherapy in relapsed CLL","aka":[],"tldr":"In relapsed CLL, a time-limited venetoclax-rituximab course cut progression risk by more than 80% compared with bendamustine-rituximab and later improved survival.","summary":"MURANO randomised 389 patients with relapsed or refractory CLL to venetoclax for two years plus six months of rituximab, or six cycles of bendamustine-rituximab. The primary endpoint was investigator-assessed PFS. At 24 months PFS was 84.9% versus 36.3% (hazard ratio 0.17), with benefit across del(17p) and other high-risk subgroups. Rates of undetectable MRD were much higher with venetoclax-rituximab. With five years of follow-up the overall survival advantage held (about 82% versus 62%), and most patients who reached undetectable MRD at end of therapy stayed in remission for years off treatment.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa1713976"},{"label":"ClinicalTrials.gov NCT02005471","url":"https://clinicaltrials.gov/study/NCT02005471"}],"tags":[],"related":["paper-cll14-venetoclax-obinutuzumab-nejm-2019"],"cancers":["cll"],"sections":[],"technologies":[],"targets":["bcl2","cd20"],"drugs":["venetoclax","rituximab","bendamustine"],"companies":["abbvie","roche-genentech"],"institutions":[],"pathways":[],"terms":["mrd","pfs","os","del17p-tp53"],"trials":[],"people":[],"bottlenecks":["b-dormancy-mrd","b-resistance"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2018,"doi":"10.1056/NEJMoa1713976","authors":"Seymour JF, Kipps TJ, Eichhorst B, et al.","paperType":"rct","findings":["389 patients with relapsed/refractory CLL; venetoclax (2 years) + rituximab vs bendamustine-rituximab.","24-month PFS 84.9% vs 36.3%; hazard ratio 0.17.","Benefit preserved in del(17p), TP53-mutated and IGHV-unmutated disease.","Peripheral-blood undetectable MRD at end of combination treatment was far more frequent with venetoclax-rituximab.","Five-year overall survival roughly 82% vs 62%; end-of-treatment MRD status predicted subsequent PFS."],"whatItMeans":"MURANO made fixed-duration venetoclax the standard for relapsed CLL and showed that stopping therapy after a deep response is safe for most patients. It also established MRD at end of treatment as a practical guide to who is likely to stay in remission. Retreatment with venetoclax at relapse appears feasible.","caveats":["Bendamustine-rituximab is a weak comparator by today's standards; there is no head-to-head against BTK inhibitors in this setting.","Few patients had prior BTK inhibitor exposure, so results may not apply after BTKi failure.","Open-label design with investigator-assessed endpoints.","Tumour-lysis prophylaxis and ramp-up add complexity."],"changedPractice":true,"participants":389},{"id":"paper-bradt-cochrane-database-syst-rev-2021","kind":"paper","name":"Music interventions for improving psychological and physical outcomes in people with cancer","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 34637527 and published in The Cochrane database of systematic reviews; the citing page links this DOI, which is how the record was matched.","summary":"Background: This is an update of the review published on the Cochrane Library in 2016, Issue 8. Having cancer may result in extensive emotional, physical and social suffering. Music interventions have been used to alleviate symptoms and treatment side effects in people with cancer. This review includes music interventions defined as music therapy offered by trained music therapists, as well as music medicine, which was defined as listening to pre-recorded music offered by medical staff.\n\nObjectives: To assess and compare the effects of music therapy and music medicine interventions for psychological and physical outcomes in people with cancer.\n\nSearch methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 3) in the Cochrane Library, MEDLINE via Ovid, Embase via Ovid, CINAHL, PsycINFO, LILACS, Science Citation Index, CancerLit, CAIRSS, Proquest Digital Dissertations, ClinicalTrials.gov, Current Controlled Trials, the RILM Abstracts of Music Literature, http://www.wfmt.info/Musictherapyworld/ and the National Research Register. We searched all databases, except for the last two, from their inception to April 2020; the other two are no longer functional, so we searched them until their termination date. We handsearched music therapy journals, reviewed reference lists and contacted experts. There was no language restriction.\n\nSelection criteria: We included all randomized and quasi-randomized controlled trials of music interventions for improving psychological and physical outcomes in adults and pediatric patients with cancer. We excluded patients undergoing biopsy and aspiration for diagnostic purposes.\n\nData collection and analysis: Two review authors independently extracted the data and assessed the risk of bias. Where possible, we presented results in meta-analyses using mean differences and standardized mean differences. We used post-test scores. In cases of significant baseline difference, we used change scores. We conducted separate meta-analyses for studies with adult participants and those with pediatric participants. Primary outcomes of interest included psychological outcomes and physical symptoms and secondary outcomes included physiological responses, physical functioning, anesthetic and analgesic intake, length of hospitalization, social and spiritual support, communication, and quality of life (QoL). We used GRADE to assess the certainty of the evidence.\n\nMain results: We identified 29 new trials for inclusion in this update. In total, the evidence of this review rests on 81 trials with a total of 5576 participants. Of the 81 trials, 74 trials included adult (N = 5306) and seven trials included pediatric (N = 270) oncology patients. We categorized 38 trials as music therapy trials and 43 as music medicine trials. The interventions were compared to standard care. Psychological outcomes The results suggest that music interventions may have a large anxiety-reducing effect in adults with cancer, with a reported average anxiety reduction of 7.73 units (17 studies, 1381 participants; 95% confidence interval (CI) -10.02 to -5.44; very low-certainty evidence) on the Spielberger State Anxiety Inventory scale (range 20 to 80; lower values reflect lower anxiety). Results also suggested a moderately strong, positive impact of music interventions on depression in adults (12 studies, 1021 participants; standardized mean difference (SMD): -0.41, 95% CI -0.67 to -0.15; very low-certainty evidence). We found no support for an effect of music interventions on mood (SMD 0.47, 95% CI -0.02 to 0.97; 5 studies, 236 participants; very low-certainty evidence). Music interventions may increase hope in adults with cancer, with a reported average increase of 3.19 units (95% CI 0.12 to 6.25) on the Herth Hope Index (range 12 to 48; higher scores reflect greater hope), but this finding was based on only two studies (N = 53 participants; very low-certainty evidence). Physical outcomes We found a moderate pain-reducing effect of music interventions (SMD -0.67, 95% CI -1.07 to -0.26; 12 studies, 632 adult participants; very low-certainty evidence). In addition, music interventions had a small treatment effect on fatigue (SMD -0.28, 95% CI -0.46 to -0.10; 10 studies, 498 adult participants; low-certainty evidence). The results suggest a large effect of music interventions on adult participants' QoL, but the results were highly inconsistent across studies, and the pooled effect size was accompanied by a large confidence interval (SMD 0.88, 95% CI -0.31 to 2.08; 7 studies, 573 participants; evidence is very uncertain). Removal of studies that used improper randomization methods resulted in a moderate effect size that was less heterogeneous (SMD 0.47, 95% CI 0.06 to 0.88, P = 0.02, I 2 = 56%). A small number of trials included pediatric oncology participants. The findings suggest that music interventions may reduce anxiety but this finding was based on only two studies (SMD -0.94, 95% CI -1.9 to 0.03; very low-certainty evidence). Due to the small number of studies, we could not draw conclusions regarding the effects of music interventions on mood, depression, QoL, fatigue or pain in pediatric participants with cancer. The majority of studies included in this review update presented a high risk of bias, and therefore the overall certainty of the evidence is low. For several outcomes (i.e. anxiety, depression, pain, fatigue, and QoL) the beneficial treatment effects were consistent across studies for music therapy interventions delivered by music therapists. In contrast, music medicine interventions resulted in inconsistent treatment effects across studies for these outcomes.\n\nAuthors' conclusions: This systematic review indicates that music interventions compared to standard care may have beneficial effects on anxiety, depression, hope, pain, and fatigue in adults with cancer. The results of two trials suggest that music interventions may have a beneficial effect on anxiety in children with cancer. Too few trials with pediatric participants were included to draw conclusions about the treatment benefits of music for other outcomes. For several outcomes, music therapy interventions delivered by a trained music therapist led to consistent results across studies and this was not the case for music medicine interventions. Moreover, evidence of effect was found for music therapy interventions for QoL and fatigue but not for music medicine interventions. Most trials were at high risk of bias and low or very low certainty of evidence; therefore, these results need to be interpreted with caution.\n\nIndexed on Europe PMC as PubMed record 34637527 (DOI 10.1002/14651858.cd006911.pub4). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cochrane Database Syst Rev 2021","url":"https://doi.org/10.1002/14651858.cd006911.pub4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34637527/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34637527"}],"tags":["europepmc-ingest"],"related":["music-therapy-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Cochrane database of systematic reviews","year":2021,"doi":"10.1002/14651858.cd006911.pub4","pmid":"34637527","authors":"Bradt J, Dileo C, Myers-Coffman K, et al.","paperType":"review","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-amer-zeidan-j-clin-oncol-2021","kind":"paper","name":"Mutant Isocitrate Dehydrogenase 1 Inhibitor Ivosidenib in Combination With Azacitidine for Newly Diagnosed Acute Myeloid Leukemia","aka":[],"tldr":"Paper by Amer M. Zeidan indexed on Europe PMC as PubMed record 33119479, in Journal of Clinical Oncology (2021), one of the most cited records naming an author with this name at Yale Cancer Center / Smilow Cancer Hospital.","summary":"Purpose: Ivosidenib is an oral inhibitor of the mutant isocitrate dehydrogenase 1 (IDH1) enzyme, approved for treatment of IDH1 -mutant (m IDH1) acute myeloid leukemia (AML). Preclinical work suggested that addition of azacitidine to ivosidenib enhances mIDH1 inhibition-related differentiation and apoptosis.\n\nPatients and methods: This was an open-label, multicenter, phase Ib trial comprising dose-finding and expansion stages to evaluate safety and efficacy of combining oral ivosidenib 500 mg once daily continuously with subcutaneous azacitidine 75 mg/m 2 on days 1-7 in 28-day cycles in patients with newly diagnosed m IDH1 AML ineligible for intensive induction chemotherapy (ClinicalTrials.gov identifier: NCT02677922).\n\nResults: Twenty-three patients received ivosidenib plus azacitidine (median age, 76 years; range, 61-88 years). Treatment-related grade ≥ 3 adverse events occurring in > 10% of patients were neutropenia (22%), anemia (13%), thrombocytopenia (13%), and electrocardiogram QT prolongation (13%). Adverse events of special interest included all-grade IDH differentiation syndrome (17%), all-grade electrocardiogram QT prolongation (26%), and grade ≥ 3 leukocytosis (9%). Median treatment duration was 15.1 months (range, 0.3-32.2 months); 10 patients remained on treatment at February 19, 2019. The overall response rate was 78.3% (18/23 patients; 95% CI, 56.3% to 92.5%), and the complete remission rate was 60.9% (14/23 patients; 95% CI, 38.5% to 80.3%). With median follow-up of 16 months, median duration of response in responders had not been reached. The 12-month survival estimate was 82.0% (95% CI, 58.8% to 92.8%). m IDH1 clearance in bone marrow mononuclear cells by BEAMing (beads, emulsion, amplification, magnetics) digital polymerase chain reaction was seen in 10/14 patients (71.4%) achieving complete remission.\n\nConclusion: Ivosidenib plus azacitidine was well tolerated, with an expected safety profile consistent with monotherapy with each agent. Responses were deep and durable, with most complete responders achieving m IDH1 mutation clearance.\n\nIndexed on Europe PMC as PubMed record 33119479 (DOI 10.1200/jco.20.01632). Its author list gives \"Zeidan AM\" with the affiliation \"Yale Cancer Center, New Haven, CT\", which names Yale Cancer Center / Smilow Cancer Hospital; that is how the record was matched to Amer M. Zeidan, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2021","url":"https://doi.org/10.1200/jco.20.01632"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33119479/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33119479"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["amer-zeidan"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2021,"doi":"10.1200/jco.20.01632","pmid":"33119479","authors":"DiNardo CD, Stein AS, Stein EM, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Amer M. Zeidan at Yale Cancer Center / Smilow Cancer Hospital, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-knudson-proc-natl-acad-sci-u-s-a","kind":"paper","name":"Mutation and cancer: statistical study of retinoblastoma","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 5279523 and published in Proceedings of the National Academy of Sciences; the citing page links this DOI, which is how the record was matched.","summary":"Based upon observations on 48 cases of retinoblastoma and published reports, the hypothesis is developed that retinoblastoma is a cancer caused by two mutational events. In the dominantly inherited form, one mutation is inherited via the germinal cells and the second occurs in somatic cells. In the nonhereditary form, both mutations occur in somatic cells. The second mutation produces an average of three retinoblastomas per individual inheriting the first mutation. Using Poisson statistics, one can calculate that this number (three) can explain the occasional gene carrier who gets no tumor, those who develop only unilateral tumors, and those who develop bilateral tumors, as well as explaining instances of multiple tumors in one eye. This value for the mean number of tumors occurring in genetic carriers may be used to estimate the mutation rate for each mutation. The germinal and somatic rates for the first, and the somatic rate for the second, mutation, are approximately equal. The germinal mutation may arise in some instances from a delayed mutation.\n\nIndexed on Europe PMC as PubMed record 5279523 (DOI 10.1073/pnas.68.4.820). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Proc Natl Acad Sci U S A 1971","url":"https://doi.org/10.1073/pnas.68.4.820"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/5279523/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/5279523"}],"tags":["europepmc-ingest"],"related":["somatic-mutation-theory"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["pnas"],"dependsOn":[],"notes":[],"journal":"Proceedings of the National Academy of Sciences","year":1971,"doi":"10.1073/pnas.68.4.820","pmid":"5279523","authors":"Knudson AG","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-shah-foxl2-granulosa-nejm-2009","kind":"paper","name":"Mutation of FOXL2 in granulosa cell tumours of the ovary","aka":[],"tldr":"Sequencing of adult granulosa cell tumours found a single recurrent mutation in the FOXL2 gene in almost every case, giving this rare ovarian cancer a defining molecular marker and a diagnostic test.","summary":"Whole-transcriptome sequencing of four adult granulosa cell tumours followed by targeted validation in 89 additional adult tumours and other ovarian tumours, identifying the FOXL2 c.402C>G (C134W) mutation in 97 percent of adult granulosa cell tumours and rarely in other tumour types.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2009","url":"https://doi.org/10.1056/NEJMoa0902542"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19516027/"}],"tags":[],"related":[],"cancers":["granulosa-cell-tumour"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2009,"doi":"10.1056/NEJMoa0902542","pmid":"19516027","authors":"Shah SP, Köbel M, Senz J, et al.","paperType":"translational","findings":["FOXL2 C134W mutation in 86 of 89 adult granulosa cell tumours (97 percent).","Absent from most other ovarian tumour types and from juvenile granulosa cell tumours."],"whatItMeans":"FOXL2 mutation testing is now used to confirm the diagnosis of adult granulosa cell tumour, and the mutation is central to understanding and treating the disease.","caveats":["Discovery study; no FOXL2-directed therapy exists yet."],"changedPractice":true},{"id":"paper-taplin-ar-mutation-androgen-independent-prostate-nejm-1995","kind":"paper","name":"Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer","aka":[],"tldr":"In half of ten men whose prostate cancer had stopped responding to hormone treatment, the receptor had changed shape so that other hormones, including oestrogen, could switch it on.","summary":"Complementary DNA was made from metastatic prostate cancers in 10 men with androgen-independent disease and the androgen receptor gene was amplified, cloned across exons B to H and sequenced. All the androgen-independent tumours expressed high levels of androgen receptor transcripts relative to the androgen-independent LNCaP cell line. Point mutations were identified in metastatic cells from 5 of the 10 men, one of them in the same codon as a mutation previously found in LNCaP. The mutations were not detectable in the primary tumours of two of those men. Functional studies of two of the mutant receptors in transfected cells showed that they could be activated by progesterone and by oestrogen.","asOf":"2026-09-25","links":[{"label":"Taplin et al., N Engl J Med 1995: androgen-receptor gene mutation in metastatic androgen-independent prostate cancer (10 patients)","url":"https://doi.org/10.1056/NEJM199505253322101"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/7723794/"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["cgp"],"targets":["androgen-receptor"],"drugs":[],"companies":[],"institutions":[],"pathways":["ar-signaling","resistance-routes-map"],"terms":["castration-resistance","resistance","driver-mutation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":1995,"doi":"10.1056/NEJM199505253322101","pmid":"7723794","authors":"Taplin ME, Bubley GJ, Shuster TD, et al.","paperType":"translational","findings":["Point mutations in the androgen receptor in 5 of 10 men with androgen-independent metastatic disease.","High androgen receptor transcript levels in all of the androgen-independent tumours.","Two mutant receptors activated by progesterone and by oestrogen in transfected cells.","Mutations absent from the primary tumours of two men, so they were selected rather than founder events."],"whatItMeans":"It established that the receptor in resistant prostate cancer is not silent but promiscuous, which is why the specific allele matters clinically: a receptor that will accept a glucocorticoid or a progestogen changes what should and should not be prescribed alongside the hormonal agent.","caveats":["Ten men, and the assay could only read the exons cloned.","Androgen-independent was a clinical description in 1995, not a defined state with a testosterone threshold.","The allele-specific consequences, including F877L and enzalutamide, were worked out much later."],"changedPractice":false,"participants":10},{"id":"paper-garcia-murillas-ctdna-mutation-tracking-stm-2015","kind":"paper","name":"Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer","aka":[],"tldr":"Tracking a tumour's own mutations in blood after surgery for early breast cancer predicted relapse with a 25-fold hazard and a median lead of nearly eight months, and the DNA in the blood foretold the genetics of the eventual metastases better than the primary did.","summary":"In a prospective cohort of 55 early breast cancer patients receiving neoadjuvant chemotherapy, detection of ctDNA after apparently curative treatment, at a single post-surgical time point or with serial samples, predicted metastatic relapse (HR 25.1 and 12.0). Serial mutation tracking increased sensitivity with a median lead time of 7.9 months over clinical relapse. Targeted capture sequencing of ctDNA defined the genetic events of minimal residual disease and predicted the metastatic genotype more accurately than sequencing of the primary.","asOf":"2026-09-24","links":[{"label":"Garcia-Murillas et al., Sci Transl Med 2015: mutation tracking in ctDNA predicts relapse in 55 early breast cancer patients","url":"https://doi.org/10.1126/scitranslmed.aab0021"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26311728/"}],"tags":[],"related":["ctdna-mrd-positive"],"cancers":["tnbc","breast-cancer"],"sections":[],"technologies":["mrd-testing","liquid-biopsy"],"targets":[],"drugs":[],"companies":[],"institutions":["icr-london","royal-marsden"],"pathways":[],"terms":["ctdna","mrd"],"trials":[],"people":["nicholas-turner"],"bottlenecks":[],"keyPapers":[],"journals":["science-translational-medicine"],"dependsOn":[],"notes":[],"journal":"Science Translational Medicine","year":2015,"doi":"10.1126/scitranslmed.aab0021","pmid":"26311728","authors":"Garcia-Murillas I, Schiavon G, Weigelt B, et al.","paperType":"translational","findings":["Post-treatment ctDNA detection: relapse HR 25.1 (single time point) and 12.0 (serial).","Median lead time 7.9 months; MRD sequencing predicted the metastatic genotype."],"whatItMeans":"The proof-of-principle paper for molecular residual disease in breast cancer, and the origin of the personalised digital PCR approach that c-TRAK TN later tested prospectively in TNBC.","caveats":["55 patients of all subtypes.","Digital PCR of one or two mutations per patient."],"changedPractice":false,"participants":55},{"id":"paper-alexandrov-tobacco-smoking-mutational-signatures-science-2016","kind":"paper","name":"Mutational signatures associated with tobacco smoking in human cancer","aka":[],"tldr":"Comparing more than five thousand cancers of the types smoking causes showed exactly how tobacco does its damage: in the tissues smoke touches directly it leaves a chemical fingerprint in the DNA, and elsewhere it acts more indirectly.","summary":"Somatic mutations and DNA methylation were analysed in 5,243 cancers of types for which tobacco smoking confers an elevated risk. Smoking is associated with increased mutation burdens of multiple distinct mutational signatures, contributing to different extents in different cancers. One of these, found mainly in cancers derived from tissues directly exposed to tobacco smoke, is attributable to misreplication of DNA damage caused by tobacco carcinogens. Others likely reflect indirect activation of DNA editing by APOBEC cytidine deaminases and of an endogenous clock-like mutational process. Smoking is associated with only limited differences in methylation. The results support the proposition that smoking increases cancer risk by increasing the somatic mutation load, although direct evidence is lacking for some smoking-related cancer types.","asOf":"2026-09-25","links":[{"label":"Alexandrov et al., Science 2016: mutational signatures associated with tobacco smoking in 5,243 cancers","url":"https://doi.org/10.1126/science.aag0299"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27811275/"}],"tags":[],"related":[],"cancers":["nsclc","sclc"],"sections":[],"technologies":["wes-wgs"],"targets":["kras","tp53"],"drugs":[],"companies":[],"institutions":[],"pathways":["mutagenesis-signatures","chemical-carcinogenesis-receptor-activation","theories-of-cancer"],"terms":["mutational-signature","tmb","kras-mutation-subtypes"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2016,"doi":"10.1126/science.aag0299","pmid":"27811275","authors":"Alexandrov LB, Ju YS, Haase K, et al.","paperType":"basic","findings":["Smoking raises mutation burden through several distinct signatures at once.","The carcinogen-adduct signature is confined to directly exposed tissues, lung among them.","APOBEC and clock-like processes are also elevated, indirectly.","Methylation differences associated with smoking are limited."],"whatItMeans":"It supplies the chemistry behind the allele spectrum of lung cancer: the G to T transversion that the tobacco signature generates is why KRAS G12C dominates in lung and G12D dominates in bowel and pancreatic cancer.","caveats":["Cross-sectional genomes, so the causal chain from exposure to mutation to cancer is inferred.","Smoking history is recorded at cohort level with varying quality.","Signature attribution depends on the extraction method used."],"changedPractice":false,"participants":5243},{"id":"paper-zaretsky-n-engl-j-med","kind":"paper","name":"Mutations Associated with Acquired Resistance to PD-1 Blockade in Melanoma","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 27433843 and published in New England Journal of Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Background: Approximately 75% of objective responses to anti-programmed death 1 (PD-1) therapy in patients with melanoma are durable, lasting for years, but delayed relapses have been noted long after initial objective tumor regression despite continuous therapy. Mechanisms of immune escape in this context are unknown.\n\nMethods: We analyzed biopsy samples from paired baseline and relapsing lesions in four patients with metastatic melanoma who had had an initial objective tumor regression in response to anti-PD-1 therapy (pembrolizumab) followed by disease progression months to years later.\n\nResults: Whole-exome sequencing detected clonal selection and outgrowth of the acquired resistant tumors and, in two of the four patients, revealed resistance-associated loss-of-function mutations in the genes encoding interferon-receptor-associated Janus kinase 1 (JAK1) or Janus kinase 2 (JAK2), concurrent with deletion of the wild-type allele. A truncating mutation in the gene encoding the antigen-presenting protein beta-2-microglobulin (B2M) was identified in a third patient. JAK1 and JAK2 truncating mutations resulted in a lack of response to interferon gamma, including insensitivity to its antiproliferative effects on cancer cells. The B2M truncating mutation led to loss of surface expression of major histocompatibility complex class I.\n\nConclusions: In this study, acquired resistance to PD-1 blockade immunotherapy in patients with melanoma was associated with defects in the pathways involved in interferon-receptor signaling and in antigen presentation. (Funded by the National Institutes of Health and others.).\n\nIndexed on Europe PMC as PubMed record 27433843 (DOI 10.1056/nejmoa1604958). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2016","url":"https://doi.org/10.1056/nejmoa1604958"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27433843/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27433843"}],"tags":["europepmc-ingest"],"related":["antigen-presentation-immunoediting"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2016,"doi":"10.1056/nejmoa1604958","pmid":"27433843","authors":"Zaretsky JM, Garcia-Diaz A, Shin DS, et al.","paperType":"observational","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-kras-nsclc-j-clin-oncol-2005","kind":"paper","name":"Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib","aka":[],"tldr":"Phase 2 or 3 results paper on KRAS in Non-small-cell lung cancer, in Journal of Clinical Oncology (2005), one of the most cited Europe PMC records with KRAS in its title.","summary":"Purpose: Epidermal growth factor receptor (EGFR) mutations have been associated with tumor response to treatment with single-agent EGFR inhibitors in patients with relapsed non-small-cell lung cancer (NSCLC). The implications of EGFR mutations in patients treated with EGFR inhibitors plus first-line chemotherapy are unknown. KRAS is frequently activated in NSCLC. The relationship of KRAS mutations to outcome after EGFR inhibitor treatment has not been described.\n\nPatients and methods: Previously untreated patients with advanced NSCLC in the phase III TRIBUTE study who were randomly assigned to carboplatin and paclitaxel with erlotinib or placebo were assessed for survival, response, and time to progression (TTP). EGFR exons 18 through 21 and KRAS exon 2 were sequenced in tumors from 274 patients. Outcomes were correlated with EGFR and KRAS mutations in retrospective subset analyses.\n\nResults: EGFR mutations were detected in 13% of tumors and were associated with longer survival, irrespective of treatment (P <.001). Among erlotinib-treated patients, EGFR mutations were associated with improved response rate (P <.05) and there was a trend toward an erlotinib benefit on TTP (P =.092), but not improved survival (P =.96). KRAS mutations (21% of tumors) were associated with significantly decreased TTP and survival in erlotinib plus chemotherapy-treated patients.\n\nConclusion: EGFR mutations may be a positive prognostic factor for survival in advanced NSCLC patients treated with chemotherapy with or without erlotinib, and may predict greater likelihood of response. Patients with KRAS-mutant NSCLC showed poorer clinical outcomes when treated with erlotinib and chemotherapy. Further studies are needed to confirm the findings of this retrospective subset analysis.\n\nIndexed on Europe PMC as PubMed record 16043828 (DOI 10.1200/jco.2005.02.857). Its title names KRAS and its text names Non-small-cell lung cancer; PubMed types it as a clinical trial report (Clinical Trial, Phase III, Clinical Trial, Research Support, Non-U.S. Gov't, Multicenter Study, Randomized Controlled Trial). It was matched automatically to the idea \"Turn a brake back on: drugs that reactivate the PP2A phosphatase\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2005","url":"https://doi.org/10.1200/jco.2005.02.857"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/16043828/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/16043828"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2005,"doi":"10.1200/jco.2005.02.857","pmid":"16043828","authors":"Eberhard DA, Johnson BE, Amler LC, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for KRAS in Non-small-cell lung cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by KRAS in the title and Non-small-cell lung cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-horiuchi-myc-tnbc-cdk-synthetic-lethal-jem-2012","kind":"paper","name":"MYC pathway activation in triple-negative breast cancer is synthetic lethal with CDK inhibition","aka":[],"tldr":"Triple-negative tumours run high on the MYC oncogene, which predicts shorter survival, and that dependence makes them vulnerable to CDK inhibitors, which shrank MYC-high tumours in mice.","summary":"Triple-negative tumours exhibited elevated MYC expression and altered expression of MYC regulatory genes, resulting in increased MYC pathway activity. In primary tumours MYC signalling did not predict response to neoadjuvant chemotherapy but was associated with shorter survival. A synthetic-lethal approach dependent on cyclin-dependent kinase inhibition induced regression of triple-negative xenografts; the pro-apoptotic BCL-2 family member BIM was up-regulated after CDK inhibition and contributed to the mechanism.","asOf":"2026-09-24","links":[{"label":"Horiuchi et al., J Exp Med 2012: MYC pathway activation in TNBC is synthetic lethal with CDK inhibition","url":"https://doi.org/10.1084/jem.20111512"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22430491/"}],"tags":[],"related":[],"cancers":["tnbc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["ucsf"],"pathways":["myc","cell-cycle-engine-cdks","synthetic-lethality-map"],"terms":["synthetic-lethality"],"trials":[],"people":["laura-esserman"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of Experimental Medicine","year":2012,"doi":"10.1084/jem.20111512","pmid":"22430491","authors":"Horiuchi D, Kusdra L, Huskey NE, et al.","paperType":"basic","findings":["Elevated MYC expression and pathway activity in TNBC; MYC signalling associated with shorter survival.","CDK inhibition regressed MYC-high xenografts through BIM up-regulation."],"whatItMeans":"MYC amplification, present in a fifth to a third of TNBC, is undruggable directly; this is the synthetic-lethal logic behind CDK (especially CDK9 and CDK1/2) inhibitor trials in the disease.","caveats":["Preclinical; the pan-CDK inhibitor used is not a clinical agent.","MYC pathway activity was scored by expression signatures rather than amplification alone."],"changedPractice":false},{"id":"paper-garralda-nat-med","kind":"paper","name":"MYC targeting by OMO-103 in solid tumors: a phase 1 trial","aka":[],"tldr":"Paper cited by one idea page, indexed on Europe PMC as PubMed record 38321218 and published in Nature Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Among the 'most wanted' targets in cancer therapy is the oncogene MYC, which coordinates key transcriptional programs in tumor development and maintenance. It has, however, long been considered undruggable. OMO-103 is a MYC inhibitor consisting of a 91-amino acid miniprotein. Here we present results from a phase 1 study of OMO-103 in advanced solid tumors, established to examine safety and tolerability as primary outcomes and pharmacokinetics, recommended phase 2 dose and preliminary signs of activity as secondary ones. A classical 3 + 3 design was used for dose escalation of weekly intravenous, single-agent OMO-103 administration in 21-day cycles, encompassing six dose levels (DLs). A total of 22 patients were enrolled, with treatment maintained until disease progression. The most common adverse events were grade 1 infusion-related reactions, occurring in ten patients. One dose-limiting toxicity occurred at DL5. Pharmacokinetics showed nonlinearity, with tissue saturation signs at DL5 and a terminal half-life in serum of 40 h. Of the 19 patients evaluable for response, 12 reached the predefined 9-week time point for assessment of drug antitumor activity, eight of those showing stable disease by computed tomography. One patient defined as stable disease by response evaluation criteria in solid tumors showed a 49% reduction in total tumor volume at best response. Transcriptomic analysis supported target engagement in tumor biopsies. In addition, we identified soluble factors that are potential pharmacodynamic and predictive response markers. Based on all these data, the recommended phase 2 dose was determined as DL5 (6.48 mg kg -1).ClinicalTrials.gov identifier: NCT04808362.\n\nIndexed on Europe PMC as PubMed record 38321218 (DOI 10.1038/s41591-024-02805-1). Matched by DOI alone: one idea page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Med 2024","url":"https://doi.org/10.1038/s41591-024-02805-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38321218/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38321218"}],"tags":["europepmc-ingest"],"related":["idea-drugging-myc"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2024,"doi":"10.1038/s41591-024-02805-1","pmid":"38321218","authors":"Garralda E, Beaulieu ME, Moreno V, et al.","paperType":"observational","findings":[],"whatItMeans":"One idea page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-myxofibrosarcoma-mentzel-ajsp-1996","kind":"paper","name":"Myxofibrosarcoma: clinicopathological analysis of 75 cases with emphasis on the low-grade variant","aka":[],"tldr":"This series defined myxofibrosarcoma as a distinct sarcoma of elderly limbs with characteristic curvilinear blood vessels and a strong tendency to recur locally and progress in grade, features that still guide its wide excision.","summary":"Clinicopathological study of 75 cases of myxofibrosarcoma establishing diagnostic criteria (multinodular growth, myxoid stroma, curvilinear vessels, pleomorphic cells), a grading spectrum from low to high grade, a local recurrence rate of about 50 to 60 percent often with grade progression, and metastasis mainly from high-grade tumours.","asOf":"2026-09-17","links":[{"label":"Am J Surg Pathol 1996","url":"https://doi.org/10.1097/00000478-199604000-00001"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/8604805/"}],"tags":[],"related":[],"cancers":["myxofibrosarcoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"American Journal of Surgical Pathology","year":1996,"doi":"10.1097/00000478-199604000-00001","pmid":"8604805","authors":"Mentzel T, Calonje E, Wadden C, et al.","paperType":"observational","findings":["Local recurrence in over half of cases regardless of grade, with progression to higher grade in a proportion.","Metastasis mostly from intermediate- and high-grade tumours."],"whatItMeans":"The recognition that myxofibrosarcoma infiltrates along tissue planes far beyond the visible mass underlies the wide, MRI-planned excision and adjuvant radiotherapy recommended today.","caveats":["Retrospective pathology series."],"changedPractice":true,"participants":75},{"id":"paper-n107c-brown-lancet-oncol-2017","kind":"paper","name":"N107C/CEC.3: postoperative radiosurgery versus whole-brain radiotherapy after resection of a brain metastasis","aka":[],"tldr":"After surgery to remove a brain metastasis, focused radiosurgery to the cavity preserved thinking and memory far better than whole-brain radiotherapy and gave the same survival, so it became the standard.","summary":"Phase 3 trial of 194 patients with one resected brain metastasis (and up to three unresected) randomised to stereotactic radiosurgery to the surgical cavity or whole-brain radiotherapy.\n\nCognitive deterioration-free survival was 3.7 versus 3.0 months (hazard ratio 0.47) and cognitive decline at six months was 52 versus 85 percent; overall survival was similar (12.2 versus 11.6 months) although whole-brain radiotherapy gave better intracranial control.","asOf":"2026-09-17","links":[{"label":"Lancet Oncol 2017","url":"https://doi.org/10.1016/S1470-2045(17)30441-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28687377/"}],"tags":[],"related":[],"cancers":["secondary-brain-tumours"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["paul-brown"],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2017,"doi":"10.1016/S1470-2045(17)30441-2","pmid":"28687377","authors":"Brown PD, Ballman KV, Cerhan JH, et al.","paperType":"rct","findings":["Cognitive deterioration at six months 52 percent vs 85 percent.","Median overall survival 12.2 vs 11.6 months (no difference)."],"whatItMeans":"Surgical cavity radiosurgery, rather than whole-brain radiotherapy, follows resection of a brain metastasis in fit patients, part of the broader move away from whole-brain treatment.","caveats":["Surgical bed control was lower with radiosurgery than with whole-brain radiotherapy (about 61 vs 81 percent at one year).","Leptomeningeal relapse is a concern after cavity radiosurgery."],"changedPractice":true,"participants":194},{"id":"paper-nadina-nejm-2024","kind":"paper","name":"NADINA: two doses of ipilimumab plus nivolumab before surgery beat a year of nivolumab after surgery in stage III melanoma","aka":[],"tldr":"Giving just two cycles of combination immunotherapy before removing melanoma lymph nodes cut relapses by more than two-thirds compared with a year of standard immunotherapy after surgery, and most patients needed no further treatment.","summary":"Open-label phase 3 trial of 423 patients with resectable, macroscopic stage III melanoma randomised to two cycles of neoadjuvant ipilimumab (80 mg) plus nivolumab (240 mg) followed by lymph node dissection, with adjuvant therapy only for those without a major pathological response, or to upfront surgery followed by 12 cycles of adjuvant nivolumab. Primary endpoint was event-free survival.\n\n12-month EFS was 83.7% vs 57.2% (HR 0.32). A major pathological response occurred in 59% of neoadjuvant patients, and 95% of those were event-free at 12 months without any adjuvant therapy. It established neoadjuvant immunotherapy as the standard for macroscopic stage III melanoma and showed that the pathological response can be used to stop treatment early in most patients.","asOf":"2026-09-08","links":[{"label":"NEJM 2024","url":"https://doi.org/10.1056/NEJMoa2402604"},{"label":"ClinicalTrials.gov NCT04949113","url":"https://clinicaltrials.gov/study/NCT04949113"}],"tags":[],"related":[],"cancers":["melanoma"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["pd1","ctla4"],"drugs":["nivolumab","ipilimumab"],"companies":["bms"],"institutions":["nki"],"pathways":[],"terms":["efs","neoadjuvant-adjuvant","pcr","irae"],"trials":[],"people":["christian-blank","john-haanen"],"bottlenecks":["b-trial-design","b-dose-optimisation","b-toxicity-qol","b-surgery-radiation-innovation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2024,"doi":"10.1056/NEJMoa2402604","authors":"Blank CU, Lucas MW, Scolyer RA, et al.","paperType":"rct","findings":["12-month event-free survival 83.7% vs 57.2%; HR 0.32 (99.9% CI 0.15-0.66).","Major pathological response (10% or less viable tumour) in 59.0% of neoadjuvant patients; 12-month recurrence-free survival 95.1% in those patients with no adjuvant therapy.","Partial pathological responders (12-month RFS 76%) and non-responders (57%) fared progressively worse and received adjuvant nivolumab or BRAF/MEK therapy.","Grade 3 or higher systemic treatment-related adverse events 29.7% vs 14.7%.","Patients in the neoadjuvant arm received a median of two immunotherapy cycles instead of twelve."],"whatItMeans":"Patients with melanoma that has spread to palpable lymph nodes should now be offered immunotherapy before rather than only after surgery: two cycles of low-dose ipilimumab with nivolumab, then surgery, with the pathology result deciding whether any more treatment is needed. Most patients respond well and are spared a year of adjuvant therapy. Serious side effects are more common than with nivolumab alone, mostly endocrine, and the approach requires close coordination between oncologists, surgeons and pathologists.","caveats":["Open-label; follow-up is short and overall survival is not yet reported.","Higher rate of serious immune-related toxicity in the neoadjuvant arm, including permanent endocrinopathies.","Requires expert pathological assessment of response to guide de-escalation, which not all centres can provide.","Patients with in-transit-only disease or BRAF-mutated tumours preferring targeted therapy were handled differently, limiting generalisability."],"changedPractice":true,"participants":423},{"id":"paper-nadofaragene-firadenovec-lancet-oncol-2021","kind":"paper","name":"Nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer","aka":[],"tldr":"A single instillation of a virus carrying the interferon gene into the bladder every three months cleared carcinoma in situ in about half of patients who had failed BCG, and became the first gene therapy approved for bladder cancer.","summary":"Single-arm phase 3 study of 157 patients with BCG-unresponsive high-grade non-muscle-invasive bladder cancer treated with intravesical nadofaragene firadenovec, a non-replicating adenovirus vector expressing interferon alfa-2b, every three months.\n\nAmong patients with carcinoma in situ, 53.4 percent had a complete response within 12 months and about a quarter remained free of high-grade recurrence at one year. Treatment was well tolerated with mostly transient bladder symptoms.","asOf":"2026-09-17","links":[{"label":"Lancet Oncol 2021","url":"https://doi.org/10.1016/S1470-2045(20)30540-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33253641/"}],"tags":[],"related":[],"cancers":["non-muscle-invasive-bladder-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["nadofaragene-firadenovec"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["stephen-boorjian"],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2021,"doi":"10.1016/S1470-2045(20)30540-4","pmid":"33253641","authors":"Boorjian SA, Alemozaffar M, Konety BR, et al.","paperType":"observational","findings":["Complete response in 53.4 percent of patients with carcinoma in situ within 12 months.","45.5 percent of responders remained in complete response at 12 months."],"whatItMeans":"Bladder-sparing gene therapy is a realistic option for BCG-unresponsive disease, given four times a year in clinic. Durability is limited and cystoscopic follow-up continues.","caveats":["Single-arm design with no cystectomy or chemotherapy comparator.","Approval in the United States came in 2022; access outside the United States remains limited."],"changedPractice":true,"participants":157},{"id":"paper-naliricc-lancet-gastroenterol-hepatol-2024","kind":"paper","name":"Nanoliposomal irinotecan and fluorouracil plus leucovorin versus fluorouracil plus leucovorin in patients with cholangiocarcinoma and gallbladder carcinoma previously treated with gemcitabine-based therapies (AIO NALIRICC): a multicentre, open-label, randomised, phase 2 trial","aka":[],"tldr":"Published report from the NALIRICC trial registered as NCT03043547, in The lancet. Gastroenterology & hepatology (2024), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: There is an unmet need for effective therapies in pretreated advanced biliary tract cancer. We aimed to evaluate the efficacy of nanoliposomal irinotecan and fluorouracil plus leucovorin compared with fluorouracil plus leucovorin as second-line treatment for biliary tract cancer.\n\nMethods: NALIRICC was a multicentre, open-label, randomised, phase 2 trial done in 17 German centres for patients aged 18 years or older, with an Eastern Cooperative Oncology Group performance status of 0-1, metastatic biliary tract cancer, and progression on gemcitabine-based therapy. Patients were randomly assigned (1:1) to receive intravenous infusions of nanoliposomal irinotecan (70 mg/m 2), fluorouracil (2400 mg/m 2), and leucovorin (400 mg/m 2) every 2 weeks (nanoliposomal irinotecan group) or fluorouracil (2400 mg/m 2) plus leucovorin (400 mg/m 2) every 2 weeks (control group). Randomisation was by permutated block randomisation in block sizes of four, stratified by primary tumour site. Investigator-assessed progression-free survival was the primary endpoint, which was evaluated in all randomly assigned patients. Secondary efficacy outcomes were overall survival, objective response rate, and quality of life. Safety was assessed in all randomly assigned patients who received at least one dose of the study treatment. Enrolment for this trial has been completed, and it is registered with ClinicalTrials.gov, NCT03043547.\n\nFinding: Between Dec 4, 2017, and Aug 2, 2021, 49 patients were randomly assigned to the nanoliposomal irinotecan group and 51 patients to the control group. Median age was 65 years (IQR 59-71); 45 (45%) of 100 patients were female. Median progression-free survival was 2·6 months (95% CI 1·7-3·6) in the nanoliposomal irinotecan group and 2·3 months (1·6-3·4) in the control group (hazard ratio [HR] 0·87 [0·56-1·35]). Median overall survival was 6·9 months (95% CI 5·3-10·6) in the nanoliposomal irinotecan group and 8·2 months (5·4-11·9) in the control group (HR 1·08 [0·68-1·72]). The objective response rate was 14% (95% CI 6-27; seven patients) in the nanoliposomal irinotecan group and 4% (1-14; two patients) in the control group. The most common grade 3 or worse adverse events in the nanoliposomal irinotecan group were neutropenia (eight [17%] of 48 vs none in the control group), diarrhoea (seven [15%] vs one [2%]), and nausea (four [8%] vs none). In the control group, the most common grade 3 or worse adverse events were cholangitis (four [8%] patients vs none in the nanoliposomal irinotecan group) and bile duct stenosis (four [8%] vs three [6%]). Treatment-related serious adverse events occurred in 16 (33%) patients in the nanoliposomal irinotecan group (grade 2-3 diarrhoea in five patients; one case each of abdominal infection, acute kidney injury, pancytopenia, increased blood bilirubin, colitis, dehydration, dyspnoea, infectious enterocolitis, ileus, oral mucositis, and nausea). One (2%) treatment-related serious adverse event occurred in the control group (worsening of general condition). Median duration until deterioration of global health status, characterised by the time from randomisation to the initial observation of a score decline exceeding 10 points, was 4·0 months (95% CI 2·2-not reached) in the nanoliposomal irinotecan group and 3·7 months (2·7-not reached) in the control group.\n\nInterpretation: The addition of nanoliposomal irinotecan to fluorouracil plus leucovorin did not improve progression-free survival or overall survival and was associated with higher toxicity compared with fluorouracil plus leucovorin. Further research is necessary to define the role of irinotecan-based combinations in second-line treatment of biliary tract cancer.\n\nFunding: Servier and AIO-Studien.\n\nIndexed on Europe PMC as PubMed record 38870977 (DOI 10.1016/s2468-1253(24)00119-5). Its abstract cites the registry id NCT03043547, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Gastroenterol Hepatol 2024","url":"https://doi.org/10.1016/s2468-1253(24)00119-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38870977/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38870977"},{"label":"ClinicalTrials.gov NCT03043547","url":"https://clinicaltrials.gov/study/NCT03043547"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["naliricc"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The lancet. Gastroenterology & hepatology","year":2024,"doi":"10.1016/s2468-1253(24)00119-5","pmid":"38870977","authors":"Vogel A, Saborowski A, Wenzel P, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03043547 with the most citations, so it is the natural first reading for anyone following the NALIRICC trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-napoli-1-nanoliposomal-irinotecan-lancet-2016","kind":"paper","name":"Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial","aka":[],"tldr":"The 2016 trial that gave patients whose pancreatic cancer had grown through gemcitabine a proven second treatment: liposomal irinotecan with fluorouracil lengthened survival from about four to six months.","summary":"NAPOLI-1 randomised 417 patients with metastatic pancreatic ductal adenocarcinoma previously treated with gemcitabine-based therapy at 76 sites in 14 countries between January 2012 and September 2013 to nanoliposomal irinotecan plus fluorouracil and folinic acid (117, an arm added by amendment), nanoliposomal irinotecan alone (151) or fluorouracil and folinic acid (149). After 313 events, median overall survival was 6.1 months with the combination against 4.2 months with fluorouracil and folinic acid (hazard ratio 0.67, 95 percent confidence interval 0.49 to 0.92, p = 0.012); monotherapy did not differ from control (4.9 versus 4.2 months, hazard ratio 0.99). The commonest grade 3 or 4 events with the combination were neutropenia (27 percent), fatigue (14 percent), diarrhoea (13 percent) and vomiting (11 percent). Funded by Merrimack Pharmaceuticals; the drug is now marketed by Ipsen.","asOf":"2026-09-24","links":[{"label":"Lancet 2016","url":"https://doi.org/10.1016/S0140-6736(15)00986-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26615328/"},{"label":"ClinicalTrials.gov NCT01494506","url":"https://clinicaltrials.gov/study/NCT01494506"}],"tags":["pancreatic-evidence"],"related":["paper-napoli-3-lancet-2023","paper-asco-metastatic-pancreatic-cancer-guideline-update-jco-2020"],"cancers":["pancreatic","metastatic-pdac"],"sections":[],"technologies":["topoisomerase-inhibitors","cytotoxic-chemotherapy"],"targets":[],"drugs":["liposomal-irinotecan","fluorouracil","nalirifox"],"companies":["ipsen"],"institutions":[],"pathways":[],"terms":["os","hazard-ratio"],"trials":["napoli-3"],"people":["daniel-von-hoff"],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2016,"doi":"10.1016/S0140-6736(15)00986-1","pmid":"26615328","authors":"Wang-Gillam A, Li CP, Bodoky G, et al.","paperType":"rct","findings":["417 patients after gemcitabine-based therapy; three arms.","Median overall survival 6.1 versus 4.2 months for the combination against fluorouracil and folinic acid (hazard ratio 0.67).","Nanoliposomal irinotecan alone gave no benefit (4.9 versus 4.2 months, hazard ratio 0.99).","Grade 3 or 4 neutropenia 27 percent, fatigue 14 percent, diarrhoea 13 percent."],"whatItMeans":"The first approved second-line regimen and the basis of NALIRIFOX, which NAPOLI 3 later moved to first line; it fixed the sequence (gemcitabine-based first, then liposomal irinotecan with fluorouracil) written into the 2018 ASCO guideline.","caveats":["Open-label; the combination arm was added mid-trial by protocol amendment.","A gain of about two months in a population with a median survival under six."],"changedPractice":true,"participants":417},{"id":"paper-napoli-3-lancet-2023","kind":"paper","name":"NAPOLI-3: NALIRIFOX versus gemcitabine plus nab-paclitaxel as first treatment for metastatic pancreatic cancer","aka":[],"tldr":"NAPOLI-3 randomised 770 patients with untreated metastatic pancreatic cancer to NALIRIFOX, a four-drug regimen built on liposomal irinotecan, or to gemcitabine plus nab-paclitaxel, the doublet most patients receive. NALIRIFOX lengthened life and delayed progression, the first positive first-line trial in a decade, though conventional FOLFIRINOX remains the usual choice where affordable.","summary":"Open-label phase 3 trial of 770 patients with untreated metastatic pancreatic adenocarcinoma randomised to NALIRIFOX (liposomal irinotecan, oxaliplatin, fluorouracil, leucovorin) or gemcitabine plus nab-paclitaxel. Primary endpoint was overall survival.\n\nMedian OS was 11.1 vs 9.2 months (HR 0.83) and median PFS 7.4 vs 5.6 months (HR 0.69). It was the first randomised evidence that a FOLFIRINOX-type regimen beats gemcitabine plus nab-paclitaxel, and led to FDA approval of NALIRIFOX in 2024, though conventional FOLFIRINOX remains the usual choice where it is affordable.","asOf":"2026-09-08","links":[{"label":"PubMed search: NAPOLI-3 Lancet 2023","url":"https://pubmed.ncbi.nlm.nih.gov/?term=NAPOLI-3+NALIRIFOX+Wainberg+Lancet"},{"label":"ClinicalTrials.gov NCT04083235","url":"https://clinicaltrials.gov/study/NCT04083235"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":["cytotoxic-chemotherapy","topoisomerase-inhibitors","platinum"],"targets":[],"drugs":[],"companies":["servier"],"institutions":[],"pathways":[],"terms":["os","pfs","first-line","standard-of-care"],"trials":[],"people":["tanios-bekaii-saab"],"bottlenecks":["b-undruggable-targets","b-drug-pricing","b-tme-immunosuppression"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2023,"doi":"10.1016/S0140-6736(23)01366-1","pmid":"37708904","authors":"Wainberg ZA, Melisi D, Macarulla T, et al.","paperType":"rct","findings":["Median overall survival 11.1 vs 9.2 months; HR 0.83 (95% CI 0.70-0.99).","Median PFS 7.4 vs 5.6 months; HR 0.69 (95% CI 0.58-0.83).","Objective response 41.8% vs 36.2%.","Grade 3-4 diarrhoea 20% vs 5% and grade 3-4 neutropenia lower with NALIRIFOX (14% vs 25%); peripheral neuropathy less frequent with NALIRIFOX.","Benefit was consistent across age groups but the trial enrolled fit patients (ECOG 0-1)."],"whatItMeans":"For fit patients with newly diagnosed metastatic pancreatic cancer, a FOLFIRINOX-type regimen is now proven to be better than gemcitabine plus nab-paclitaxel, settling a long-standing debate. The absolute gain is about two months of median survival, and the regimen is more toxic for the gut. Whether liposomal irinotecan adds anything over conventional irinotecan (standard FOLFIRINOX) has never been tested head-to-head.","caveats":["No direct comparison with standard FOLFIRINOX, which is much cheaper; the benefit of the liposomal formulation is inferred, not shown.","Absolute survival gain is modest and the population was fit and relatively young (median 65).","Open-label design.","Highlights how little progress systemic therapy has made in pancreatic cancer: median survival remains under a year."],"changedPractice":true,"participants":770},{"id":"paper-jean-pascal-machiels-ann-oncol-2021","kind":"paper","name":"Nasopharyngeal carcinoma: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up †","aka":[],"tldr":"Paper by Jean-Pascal Machiels indexed on Europe PMC as PubMed record 33358989, in Annals of Oncology (2021), one of the most cited records naming an author with this name at King Albert II Cancer Institute, Cliniques universitaires Saint-Luc.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 33358989 (DOI 10.1016/j.annonc.2020.12.007). Its author list gives \"Machiels JP\" with the affiliation \"Institut Roi Albert II, Service d'Oncologie Médicale, Cliniques Universitaires Saint-Luc, Brussels, Belgium; Institut de Recherche Clinique et Expérimentale (POLE MIRO), Université Catholique de Louvain, Brussels, Belgium\", which names King Albert II Cancer Institute, Cliniques universitaires Saint-Luc; that is how the record was matched to Jean-Pascal Machiels, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Ann Oncol 2021","url":"https://doi.org/10.1016/j.annonc.2020.12.007"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33358989/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33358989"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["jean-pascal-machiels"],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2021,"doi":"10.1016/j.annonc.2020.12.007","pmid":"33358989","authors":"Bossi P, Chan AT, Licitra L, et al.","paperType":"guideline","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Jean-Pascal Machiels at King Albert II Cancer Institute, Cliniques universitaires Saint-Luc, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-natalee-nejm-2024","kind":"paper","name":"NATALEE: three years of ribociclib after surgery in a broad population of hormone-receptor-positive early breast cancer","aka":[],"tldr":"Three years of the CDK4/6 inhibitor ribociclib added to hormone therapy reduced relapses in stage II-III hormone-receptor-positive breast cancer, including some node-negative patients.","summary":"Open-label phase 3 trial of 5,101 patients with hormone-receptor-positive, HER2-negative stage II or III early breast cancer, including node-negative patients with high-risk features, randomised to a non-steroidal aromatase inhibitor with or without three years of ribociclib at a reduced dose (400 mg daily). Primary endpoint was invasive disease-free survival.\n\nThree-year iDFS was 90.4% vs 87.1% (HR 0.75). Together with monarchE it established adjuvant CDK4/6 inhibition, but in a broader, lower-risk population and with a longer, lower-dose schedule.","asOf":"2026-09-08","links":[{"label":"NEJM 2024","url":"https://doi.org/10.1056/NEJMoa2305488"},{"label":"ClinicalTrials.gov NCT03701334","url":"https://clinicaltrials.gov/study/NCT03701334"}],"tags":[],"related":[],"cancers":["breast-hr-positive"],"sections":[],"technologies":["cdk46-inhibitor","endocrine-therapy"],"targets":["cdk4-6","estrogen-receptor"],"drugs":["ribociclib"],"companies":["novartis"],"institutions":[],"pathways":[],"terms":["neoadjuvant-adjuvant","hazard-ratio"],"trials":["natalee","monarche"],"people":["dennis-slamon","im-seock-ah","miguel-martin","loi-sherene","xu-binghe","sara-hurvitz","barrios-carlos"],"bottlenecks":["b-dormancy-mrd","b-drug-pricing","b-dose-optimisation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2024,"doi":"10.1056/NEJMoa2305488","authors":"Slamon D, Lipatov O, Nowecki Z, et al.","paperType":"rct","findings":["Three-year invasive disease-free survival 90.4% vs 87.1%; HR 0.75 (95% CI 0.62-0.91).","Benefit was consistent across stage II and III and in node-negative and node-positive subgroups.","Distant disease-free survival HR 0.74.","Grade 3 or higher neutropenia in roughly 44% and liver enzyme elevation in roughly 8% of ribociclib patients; about one in five discontinued for adverse events.","Overall survival immature at the primary analysis."],"whatItMeans":"Ribociclib is a second adjuvant CDK4/6 option, and the only one with data in node-negative stage II disease. Roughly 3 in 100 patients avoid a relapse or death at three years, so the decision depends heavily on individual risk, tolerance of a three-year oral drug, and cost. Whether the benefit persists after treatment ends, as it did with abemaciclib, needs longer follow-up.","caveats":["Absolute benefit at three years is about 3 percentage points and the trial included many patients whose baseline risk was modest.","Follow-up beyond the three years of treatment is limited, so durability is not yet established.","Open-label; a large proportion of patients stopped ribociclib early.","Cost of three years of therapy is substantial; cost-effectiveness has been questioned in several health systems."],"changedPractice":true,"participants":5101},{"id":"paper-pramesh-bull-world-health-organ","kind":"paper","name":"National Cancer Grid initiative for electronic medical records, India","aka":[],"tldr":"Paper cited by one institution page, indexed on Europe PMC as PubMed record 40342845 and published in Bulletin of the World Health Organization; the citing page links this DOI, which is how the record was matched.","summary":"Problem: Inefficient workflows, incomplete data and lack of interoperability can hinder the uptake of electronic records systems, challenges particularly relevant in cancer treatment with its complex longitudinal and multidisciplinary nature. Further, products developed in high-income countries are not designed for compatibility with the workflows of low- and middle-income countries, which face additional issues of cost.\n\nApproach: We evaluated centres with different resources and geographical locations to develop the requirements of our product. We published an invitation to potential vendors, evaluated submitted product development bids and enlisted six vendors. Our subcommittees developed workflow modules and templates, ensured interoperability and developed key performance indicators.\n\nSetting: The National Cancer Grid, a network of more than 360 cancer centres in India, assembled a team of experienced oncologists and digital health experts to develop electronic medical records products with specialized oncology capabilities.\n\nRelevant changes: Our collaboration between clinical and technical experts led to the development of six new, high-quality and interoperable products, compliant with the varying needs and resources of hospitals. We supported more than 20 centres with procurement and adoption through partial funding and technical assistance.\n\nLessons learnt: In developing product requirements, we gained an understanding of the challenges faced by hospitals in implementing such systems; by inviting vendors to submit a product development bid, we ensured that the product development cost was borne by the vendor and not hospitals; and by monitoring user feedback, we can continue to address issues raised by health workers and encourage the adoption of electronic medical records.\n\nIndexed on Europe PMC as PubMed record 40342845 (DOI 10.2471/blt.24.292230). Matched by DOI alone: one institution page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Bull World Health Organ 2025","url":"https://doi.org/10.2471/blt.24.292230"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40342845/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40342845"}],"tags":["europepmc-ingest"],"related":["national-cancer-grid"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Bulletin of the World Health Organization","year":2025,"doi":"10.2471/blt.24.292230","pmid":"40342845","authors":"Pramesh CS, Koita R, Sengar M, et al.","paperType":"observational","findings":[],"whatItMeans":"One institution page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-childers-j-clin-oncol","kind":"paper","name":"National Estimates of Genetic Testing in Women With a History of Breast or Ovarian Cancer","aka":[],"tldr":"Paper cited by one bottleneck page and 15 idea pages, indexed on Europe PMC as PubMed record 28820644 and published in Journal of Clinical Oncology; the citing pages link this DOI, which is how the record was matched.","summary":"Purpose In the United States, 3.8 million women have a history of breast (BC) or ovarian cancer (OC). Up to 15% of cases are attributable to heritable mutations, which, if identified, provide critical knowledge for treatment and preventive care. It is unknown how many patients who are at high risk for these mutations have not been tested and how rates vary by risk criteria. Methods We used pooled cross-sectional data from three Cancer Control Modules (2005, 2010, 2015) of the National Health Interview Survey, a national in-person household interview survey. Eligible patients were adult females with a history of BC and/or OC meeting select 2017 National Comprehensive Cancer Network eligibility criteria on the basis of age of diagnosis and family history. Outcomes included the proportion of individuals reporting a history of discussing genetic testing with a health professional, being advised to undergo genetic testing, or undergoing genetic testing for BC or OC. Results Of 47,218 women, 2.7% had a BC history and 0.4% had an OC history. For BC, 35.6% met one or more select eligibility criteria; of those, 29.0% discussed, 20.2% were advised to undergo, and 15.3% underwent genetic testing. Testing rates for individual eligibility criteria ranged from 6.2% (relative with OC) to 18.2% (diagnosis ≤ 45 years of age). For OC, 15.1% discussed, 13.1% were advised to undergo, and 10.5% underwent testing. Using only four BC eligibility criteria and all patients with OC, an estimated 1.2 to 1.3 million individuals failed to receive testing. Conclusion Fewer than one in five individuals with a history of BC or OC meeting select National Cancer Comprehensive Network criteria have undergone genetic testing. Most have never discussed testing with a health care provider. Large national efforts are warranted to address this unmet need.\n\nIndexed on Europe PMC as PubMed record 28820644 (DOI 10.1200/jco.2017.73.6314). Matched by DOI alone: one bottleneck page and 15 idea pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2017","url":"https://doi.org/10.1200/jco.2017.73.6314"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28820644/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28820644"}],"tags":["europepmc-ingest"],"related":["b-hereditary-risk","idea-prev-brca1-denosumab-prevention","idea-prev-genetic-counselling-chatbot","idea-moon-lynch-vaccine-phase3","idea-prev-lynch-frameshift-vaccine-rct","idea-prev-reflex-germline-testing","idea-prev-genetic-non-discrimination-insurance","idea-prev-prs-ancestry-portability-standard","idea-prev-family-history-auto-match","idea-prev-lynch-aspirin-implementation","idea-prev-traceback-deceased-probands","idea-prev-cascade-direct-contact-relatives","idea-moon-population-germline-screening","idea-prev-vus-saturation-editing-consortium","idea-prev-prs-screening-start-age","idea-prev-li-fraumeni-mri-plus-cfdna"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2017,"doi":"10.1200/jco.2017.73.6314","pmid":"28820644","authors":"Childers CP, Childers KK, Maggard-Gibbons M, et al.","paperType":"observational","findings":[],"whatItMeans":"One bottleneck page and 15 idea pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-navigator-avapritinib-heinrich-lancet-oncol-2020","kind":"paper","name":"NAVIGATOR: avapritinib in advanced PDGFRA D842V-mutant gastrointestinal stromal tumour","aka":[],"tldr":"Avapritinib shrank tumours in almost nine in ten patients with PDGFRA D842V-mutant gastrointestinal stromal tumour, a subtype completely resistant to imatinib and every other kinase inhibitor, and became its first effective treatment.","summary":"Phase 1 dose-escalation and expansion study; this analysis covers 56 patients with PDGFRA D842V-mutant advanced GIST treated with avapritinib at 300 or 400 mg daily.\n\nObjective response was 88 percent (9 percent complete), median duration of response not reached, and 12-month progression-free survival 81 percent; cognitive effects, periorbital oedema and anaemia were the characteristic toxicities, with rare intracranial bleeding.","asOf":"2026-09-17","links":[{"label":"Lancet Oncol 2020","url":"https://doi.org/10.1016/S1470-2045(20)30269-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32615108/"}],"tags":[],"related":[],"cancers":["gist-pdgfra-d842v"],"sections":[],"technologies":[],"targets":[],"drugs":["avapritinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["navigator"],"people":["michael-heinrich"],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2020,"doi":"10.1016/S1470-2045(20)30269-2","pmid":"32615108","authors":"Heinrich MC, Jones RL, von Mehren M, et al.","paperType":"observational","findings":["Objective response 88 percent in PDGFRA D842V-mutant GIST.","Twelve-month progression-free survival 81 percent."],"whatItMeans":"Avapritinib 300 mg is the standard first-line treatment for advanced PDGFRA D842V GIST, and mutation testing before starting imatinib is essential to identify these patients.","caveats":["Single-arm; cognitive side effects need monitoring and dose adjustment.","In non-D842V GIST avapritinib was not superior to regorafenib (VOYAGER)."],"changedPractice":true,"participants":56},{"id":"paper-act-in-sarc-lancet-oncol-2019","kind":"paper","name":"NBTXR3, a first-in-class radioenhancer hafnium oxide nanoparticle, plus radiotherapy versus radiotherapy alone in patients with locally advanced soft-tissue sarcoma (Act.In.Sarc): a multicentre, phase 2-3, randomised, controlled trial","aka":[],"tldr":"The primary report of Act.In.Sarc: a single injection of hafnium oxide nanoparticles before preoperative radiotherapy doubled the share of sarcomas with a pathological complete response, from 8 to 16 percent.","summary":"Phase 2-3 randomised, multicentre, international, open-label trial in adults with locally advanced soft-tissue sarcoma of the extremity or trunk wall requiring preoperative radiotherapy. Patients were randomised 1:1, stratified by histological subtype (myxoid liposarcoma versus others), to a single intratumoural administration of NBTXR3 (volume 10 percent of baseline tumour volume at 53.3 g/L) before external-beam radiotherapy of 50 Gy in 25 fractions, or radiotherapy alone, followed by surgery. The primary endpoint was pathological complete response by a central pathology review board under EORTC guidelines in the intention-to-treat full analysis set.\n\nBetween March 2015 and November 2017, 180 eligible patients were randomised and 179 started treatment (89 NBTXR3, 90 radiotherapy alone); 176 were analysed for the primary endpoint after three were found ineligible. Pathological complete response was noted in 14 of 87 (16 percent) in the NBTXR3 group and 7 of 89 (8 percent) with radiotherapy alone (p=0.044). Postoperative wound complication was the most common grade 3 to 4 event in both groups (9 percent each); serious adverse events occurred in 39 versus 30 percent, with no treatment-related deaths.","asOf":"2026-09-24","links":[{"label":"The Lancet Oncology 2019","url":"https://doi.org/10.1016/S1470-2045(19)30326-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31296491/"},{"label":"ClinicalTrials.gov NCT02379845","url":"https://clinicaltrials.gov/study/NCT02379845"}],"tags":[],"related":[],"cancers":["sarcoma"],"sections":[],"technologies":["radiosensitisers"],"targets":[],"drugs":["nbtxr3"],"companies":["nanobiotix"],"institutions":[],"pathways":[],"terms":[],"trials":["act-in-sarc"],"people":["sylvie-bonvalot"],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2019,"doi":"10.1016/S1470-2045(19)30326-2","pmid":"31296491","authors":"Bonvalot S, Rutkowski PL, Thariat J, et al.","paperType":"rct","findings":["Pathological complete response 14 of 87 (16%) with NBTXR3 plus radiotherapy vs 7 of 89 (8%) with radiotherapy alone (p=0.044).","180 patients randomised at international centres between March 2015 and November 2017; 176 analysed for the primary endpoint.","Grade 3 to 4 events related to NBTXR3 administration: injection site pain 4%, hypotension 4%; serious adverse events 39% vs 30%; no treatment-related deaths."],"whatItMeans":"This trial validated the radioenhancer mode of action and supported the 2019 European CE mark for NBTXR3 (Hensify) in soft-tissue sarcoma. Whether more pathological complete responses translate into fewer recurrences or longer survival was not shown here; the 2022 follow-up paper reported more R0 resections and no harm to quality of life.","caveats":["Open-label; pathological complete response is a surrogate, and the trial was not powered for recurrence or survival.","The absolute difference is 8 percentage points with a p value of 0.044.","Serious adverse events were more frequent with NBTXR3 (39% vs 30%)."],"changedPractice":true,"participants":180},{"id":"paper-nci9673-part-b-nivolumab-ipilimumab-anal-cancer-morris-jco-2026","kind":"paper","name":"NCI9673 part B: randomised phase 2 study of nivolumab with or without ipilimumab in refractory metastatic anal cancer","aka":[],"tldr":"Adding ipilimumab to nivolumab for metastatic anal cancer after chemotherapy did not improve response, progression-free survival or overall survival and doubled severe side effects.","summary":"Randomised phase 2 part of the ETCTN trial NCI9673: patients with refractory metastatic squamous cell carcinoma of the anal canal were randomised to nivolumab alone or nivolumab with ipilimumab.\n\nMedian progression-free survival was 2.9 months with nivolumab and 3.7 months with the combination (hazard ratio 0.86, p 0.25); response rates were 17.4 and 21.5 percent and median overall survival 15.9 and 20.0 months (hazard ratio 0.98). Grade 3 or worse treatment-related adverse events occurred in 12 percent with nivolumab and 25 percent with the combination. Circulating TIGIT-positive CD8 T cells rose with dual blockade.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2026","url":"https://doi.org/10.1200/JCO-25-00929"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41499716/"}],"tags":[],"related":[],"cancers":["metastatic-anal-cancer","anal"],"sections":[],"technologies":[],"targets":[],"drugs":["nivolumab","ipilimumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nci9673"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2026,"doi":"10.1200/JCO-25-00929","pmid":"41499716","authors":"Morris VK, Ciombor KK, Xiao L, et al.","paperType":"rct","findings":["Median progression-free survival 2.9 months (90% CI 1.9 to 3.8) with nivolumab versus 3.7 months (2.0 to 5.6) with nivolumab plus ipilimumab; hazard ratio 0.86 (0.60 to 1.23), p 0.25.","Response rates 17.4 versus 21.5 percent (p 0.89); median overall survival 15.9 versus 20.0 months (hazard ratio 0.98).","Grade 3 or worse treatment-related adverse events 12 versus 25 percent."],"whatItMeans":"Single-agent PD-1 blockade remains the immunotherapy standard after chemotherapy in metastatic anal cancer; CTLA-4 blockade adds toxicity without benefit.","caveats":["Phase 2 powered for progression-free survival with wide confidence intervals."],"changedPractice":false,"participants":106},{"id":"paper-nci9673-nivolumab-metastatic-anal-cancer-morris-lancet-oncol-2017","kind":"paper","name":"NCI9673: nivolumab for previously treated unresectable metastatic anal cancer","aka":[],"tldr":"In the first completed immunotherapy trial for anal cancer, the PD-1 antibody nivolumab shrank tumours in a quarter of heavily pretreated patients with few side effects.","summary":"Multicentre single-arm phase 2 trial: 37 patients with previously treated metastatic squamous cell carcinoma of the anal canal received nivolumab 3 mg/kg every two weeks.\n\nNine patients (24 percent, 95% CI 15 to 33) responded, two completely and seven partially. Grade 3 adverse events were anaemia (2), fatigue, rash and hypothyroidism (1 each); there were no serious adverse events.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2017","url":"https://doi.org/10.1016/S1470-2045(17)30104-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28223062/"}],"tags":[],"related":[],"cancers":["metastatic-anal-cancer","anal"],"sections":[],"technologies":[],"targets":[],"drugs":["nivolumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nci9673"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2017,"doi":"10.1016/S1470-2045(17)30104-3","pmid":"28223062","authors":"Morris VK, Salem ME, Nimeiri H, et al.","paperType":"observational","findings":["Objective response 24 percent (95% CI 15 to 33): 2 complete and 7 partial responses in 37 patients.","Grade 3 adverse events in 5 patients; no serious adverse events."],"whatItMeans":"PD-1 blockade is an option for metastatic anal cancer after chemotherapy, and the basis for later immunotherapy combinations in the disease.","caveats":["Single-arm design with 37 patients."],"changedPractice":true,"participants":37},{"id":"paper-ncic-sr2-preoperative-vs-postoperative-radiotherapy-osullivan-lancet-2002","kind":"paper","name":"NCIC SR2: preoperative versus postoperative radiotherapy in soft tissue sarcoma of the limbs","aka":[],"tldr":"Radiotherapy before surgery for limb sarcoma doubled the rate of wound complications compared with radiotherapy after surgery, but gave the same tumour control with lower doses and less late fibrosis, leaving the timing as a trade between early and late side effects.","summary":"Phase 3 trial of 190 patients with extremity soft tissue sarcoma randomised to preoperative radiotherapy (50 Gy) or postoperative radiotherapy (66 Gy).\n\nMajor wound complications occurred in 35 percent after preoperative radiotherapy versus 17 percent after postoperative; local control and survival were similar (with a small non-significant survival advantage for preoperative), and later reports showed less fibrosis, oedema and joint stiffness with preoperative treatment.","asOf":"2026-09-17","links":[{"label":"Lancet 2002","url":"https://doi.org/10.1016/S0140-6736(02)09292-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/12103287/"}],"tags":[],"related":[],"cancers":["extremity-soft-tissue-sarcoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2002,"doi":"10.1016/S0140-6736(02)09292-9","pmid":"12103287","authors":"O'Sullivan B, Davis AM, Turcotte R, et al.","paperType":"rct","findings":["Major wound complications 35 percent (preoperative) vs 17 percent (postoperative).","Local control and overall survival equivalent."],"whatItMeans":"Both sequences are standard; preoperative radiotherapy is favoured for large deep tumours because of better long-term function, with postoperative radiotherapy where wound risk is high.","caveats":["Small trial; the late toxicity comparison came from secondary analysis."],"changedPractice":true,"participants":190},{"id":"paper-nelson-nejm-2020","kind":"paper","name":"NELSON: volume-based CT screening reduces lung cancer deaths with fewer false alarms","aka":[],"tldr":"In a Dutch-Belgian trial, CT screening using nodule volume rather than diameter cut lung cancer deaths in men by about a quarter at 10 years, with a far lower false-positive rate than NLST.","summary":"NELSON randomised 15,789 current or former smokers (13,195 men and 2,594 women) aged 50-74 to CT screening at baseline, 1, 3 and 5.5 years or to no screening. Nodules were managed by volume and volume-doubling time, with an indeterminate category that triggered a repeat scan rather than a biopsy.\n\nThe primary analysis in men showed a lung cancer mortality rate ratio of 0.76 at 10 years. Screen-detected cancers were much more often stage I. The positive-screen rate was around 2%, far below NLST's, because the indeterminate category absorbed most small nodules.\n\nNELSON confirmed NLST against a no-screening control and gave European programmes a workable protocol.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1056/NEJMoa1911793"},{"label":"NEJM full text","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa1911793"}],"tags":[],"related":["paper-nlst-nejm-2011","idea-prev-lung-screening-risk-model-eligibility","lung-cancer-evidence-roadmap","paper-uspstf-lung-cancer-screening-jama-2021","idea-lung-screening-eligibility-by-risk-not-pack-years"],"cancers":["nsclc","lung-cancer"],"sections":["early-detection"],"technologies":["low-dose-ct-screening","ct","radiology-ai-screening"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["stage-shift","ppv"],"trials":["nlst-nelson"],"people":[],"bottlenecks":["b-early-detection","b-overdiagnosis"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2020,"doi":"10.1056/NEJMoa1911793","pmid":"31995683","authors":"de Koning HJ, van der Aalst CM, de Jong PA, et al.","paperType":"rct","findings":["Lung cancer mortality rate ratio in men 0.76 (95% CI 0.61-0.94) at 10 years","In the smaller female cohort the rate ratio was 0.67 (95% CI 0.38-1.14), not statistically significant but consistent with benefit","Overall positive-screen rate about 2%, with the majority of screen-detected cancers at stage IA-IB","Comparator was no screening, removing the concern that chest X-ray in NLST masked part of the effect"],"whatItMeans":"Lung screening works when it uses volumetric nodule management, and it works against a no-screening control. The protocol underpins the UK Targeted Lung Health Check programme and European recommendations. Benefit in women remains less precisely estimated.","caveats":["Women were under-represented, so the female estimate is imprecise","Screening intervals lengthened to 2.5 years in the final round; the optimal interval is still debated","Some overdiagnosis is likely; the authors estimated a modest excess of cancers in the screened arm at 10 years","Participants were volunteers responding to a population mailing, which may not reflect routine uptake"],"changedPractice":true,"participants":15789},{"id":"paper-issels-lancet-oncol","kind":"paper","name":"Neo-adjuvant chemotherapy alone or with regional hyperthermia for localised high-risk soft-tissue sarcoma: a randomised phase 3 multicentre study","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 20434400 and published in The Lancet Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background: The optimum treatment for high-risk soft-tissue sarcoma (STS) in adults is unclear. Regional hyperthermia concentrates the action of chemotherapy within the heated tumour region. Phase 2 studies have shown that chemotherapy with regional hyperthermia improves local control compared with chemotherapy alone. We designed a parallel-group randomised controlled trial to assess the safety and efficacy of regional hyperthermia with chemotherapy.\n\nMethods: Patients were recruited to the trial between July 21, 1997, and November 30, 2006, at nine centres in Europe and North America. Patients with localised high-risk STS (> or = 5 cm, Fédération Nationale des Centres de Lutte Contre le Cancer [FNCLCC] grade 2 or 3, deep to the fascia) were randomly assigned to receive either neo-adjuvant chemotherapy consisting of etoposide, ifosfamide, and doxorubicin (EIA) alone, or combined with regional hyperthermia (EIA plus regional hyperthermia) in addition to local therapy. Local progression-free survival (LPFS) was the primary endpoint. Efficacy analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT 00003052.\n\nFindings: 341 patients were enrolled, with 169 randomly assigned to EIA plus regional hyperthermia and 172 to EIA alone. All patients were included in the analysis of the primary endpoint, and 332 patients who received at least one cycle of chemotherapy were included in the safety analysis. After a median follow-up of 34 months (IQR 20-67), 132 patients had local progression (56 EIA plus regional hyperthermia vs 76 EIA). Patients were more likely to experience local progression or death in the EIA-alone group compared with the EIA plus regional hyperthermia group (relative hazard [RH] 0.58, 95% CI 0.41-0.83; p=0.003), with an absolute difference in LPFS at 2 years of 15% (95% CI 6-26; 76% EIA plus regional hyperthermia vs 61% EIA). For disease-free survival the relative hazard was 0.70 (95% CI 0.54-0.92, p=0.011) for EIA plus regional hyperthermia compared with EIA alone. The treatment response rate in the group that received regional hyperthermia was 28.8%, compared with 12.7% in the group who received chemotherapy alone (p=0.002). In a pre-specified per-protocol analysis of patients who completed EIA plus regional hyperthermia induction therapy compared with those who completed EIA alone, overall survival was better in the combined therapy group (HR 0.66, 95% CI 0.45-0.98, p=0.038). Leucopenia (grade 3 or 4) was more frequent in the EIA plus regional hyperthermia group compared with the EIA-alone group (128 of 165 vs 106 of 167, p=0.005). Hyperthermia-related adverse events were pain, bolus pressure, and skin burn, which were mild to moderate in 66 (40.5%), 43 (26.4%), and 29 patients (17.8%), and severe in seven (4.3%), eight (4.9%), and one patient (0.6%), respectively. Two deaths were attributable to treatment in the combined treatment group, and one death was attributable to treatment in the EIA-alone group.\n\nInterpretation: To our knowledge, this is the first randomised phase 3 trial to show that regional hyperthermia increases the benefit of chemotherapy. Adding regional hyperthermia to chemotherapy is a new effective treatment strategy for patients with high-risk STS, including STS with an abdominal or retroperitoneal location.\n\nFunding: Deutsche Krebshilfe, Helmholtz Association (HGF), European Organisation of Research and Treatment of Cancer (EORTC), European Society for Hyperthermic Oncology (ESHO), and US National Institute of Health (NIH).\n\nIndexed on Europe PMC as PubMed record 20434400 (DOI 10.1016/s1470-2045(10)70071-1). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2010","url":"https://doi.org/10.1016/s1470-2045(10)70071-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20434400/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/20434400"}],"tags":["europepmc-ingest"],"related":["hyperthermia-systems"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2010,"doi":"10.1016/s1470-2045(10)70071-1","pmid":"20434400","authors":"Issels RD, Lindner LH, Verweij J, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nct06747338-jama-oncol-2026","kind":"paper","name":"Neoadjuvant Anbenitamab and HB1801 in ERBB2-Positive Breast Cancer: A Phase 3 Randomized Clinical Trial","aka":[],"tldr":"Published report from the trial registered as NCT06747338, in JAMA Oncology (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Importance: The combination of neoadjuvant taxanes with trastuzumab and pertuzumab remains the cornerstone treatment strategy in ERBB2-positive breast cancer. Anbenitamab (a ERBB2-biparatopic antibody that induces profound receptor clustering) and HB1801 (a solvent-free albumin-bound docetaxel), have shown promising antitumor activity and an acceptable safety profile in patients with breast cancer.\n\nObjective: To evaluate whether neoadjuvant anbenitamab combined with HB1801 could improve efficacy without increasing toxic effects for patients with early ERBB2-positive breast cancer.\n\nDesign, setting, and participants: This multicenter, phase 3 registrational randomized clinical trial enrolled patients with stage II or III ERBB2-positive breast cancer from 61 hospitals in China between December 19, 2024, and August 29, 2025 (data cutoff: January 28, 2026). Data were analyzed from February 1 to March 20, 2026.\n\nInterventions: Patients were randomly assigned (1:1) to receive 6 cycles of neoadjuvant anbenitamab plus HB1801, with or without carboplatin (investigational group), or trastuzumab, pertuzumab, and docetaxel, with or without carboplatin (control group).\n\nMain outcomes and measures: The primary end point was total pathological complete response (tpCR) assessed by a blinded independent review committee.\n\nResults: Among 521 included patients (median [IQR] age, 52.0 [23-79] years), 263 were randomized to the investigational group and 258 to the control group. The tpCR rate was significantly higher in the investigational group than the control group (164 patients [62.4%] vs 132 patients [51.2%]; absolute difference, 11.4 [95% CI, 3.2 to 19.6] percentage points; P =.004). Benefit was consistent across subgroups, including subgroups with hormone receptor-positive disease (77 patients [51.7%] vs 63 patients [44.4%]), hormone receptor-negative disease (87 patients [76.3%] vs 69 patients [59.5%]), early-stage disease (111 patients [63.8%] vs 87 patients [51.8%]), locally advanced disease (53 patients [59.6%] vs 45 patients [50.0%]), with carboplatin treatment (74 patients [66.7%] vs 61 patients [54.5%]), and without carboplatin treatment (90 patients [59.2%] vs 71 patients [48.6%]). Grade 3 or 4 treatment-related adverse events occurred in 77 patients (29.3%) in the investigational group and 73 patients (28.3%) of the control group. No treatment-related deaths occurred.\n\nConclusions and relevance: This randomized clinical trial found that neoadjuvant anbenitamab and HB1801 in patients with breast cancer significantly improved the tpCR rate compared with standard therapy with a highly manageable safety profile. This new combination may offer an improved treatment option, although long-term survival follow-up analyses are warranted.\n\nTrial registration: ClinicalTrials.gov Identifier: NCT06747338.\n\nIndexed on Europe PMC as PubMed record 42690668 (DOI 10.1001/jamaoncol.2026.3329). Its abstract cites the registry id NCT06747338, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"JAMA Oncol 2026","url":"https://doi.org/10.1001/jamaoncol.2026.3329"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42690668/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42690668"},{"label":"ClinicalTrials.gov NCT06747338","url":"https://clinicaltrials.gov/study/NCT06747338"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct06747338"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2026,"doi":"10.1001/jamaoncol.2026.3329","pmid":"42690668","authors":"Li J, Liu T, Yu KD, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT06747338 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-impassion031-lancet-2020","kind":"paper","name":"Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial","aka":[],"tldr":"Published report from the IMpassion031 trial registered as NCT03197935, in The Lancet (2020), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Preferred neoadjuvant regimens for early-stage triple-negative breast cancer (TNBC) include anthracycline-cyclophosphamide and taxane-based chemotherapy. IMpassion031 compared efficacy and safety of atezolizumab versus placebo combined with nab-paclitaxel followed by doxorubicin plus cyclophosphamide as neoadjuvant treatment for early-stage TNBC.\n\nMethods: This double-blind, randomised, phase 3 study enrolled patients in 75 academic and community sites in 13 countries. Patients aged 18 years or older with previously untreated stage II-III histologically documented TNBC were randomly assigned (1:1) to receive chemotherapy plus intravenous atezolizumab at 840 mg or placebo every 2 weeks. Chemotherapy comprised of nab-paclitaxel at 125 mg/m 2 every week for 12 weeks followed by doxorubicin at 60 mg/m 2 and cyclophosphamide at 600 mg/m 2 every 2 weeks for 8 weeks, which was then followed by surgery. Stratification was by clinical breast cancer stage and programmed cell death ligand 1 (PD-L1) status. Co-primary endpoints were pathological complete response in all-randomised (ie, all randomly assigned patients in the intention-to-treat population) and PD-L1-positive (ie, patients with PD-L1-expressing tumour infiltrating immune cells covering ≥1% of tumour area) populations. This study is registered with ClinicalTrials.gov (NCT03197935), Eudra (CT2016-004734-22), and the Japan Pharmaceutical Information Center (JapicCTI-173630), and is ongoing.\n\nFindings: Between July 7, 2017, and Sept 24, 2019, 455 patients were recruited and assessed for eligibility. Of the 333 eligible patients, 165 were randomly assigned to receive atezolizumab plus chemotherapy and 168 to placebo plus chemotherapy. At data cutoff (April 3, 2020), median follow-up was 20·6 months (IQR 8·7-24·9) in the atezolizumab plus chemotherapy group and 19·8 months (8·1-24·5) in the placebo plus chemotherapy group. Pathological complete response was documented in 95 (58%, 95% CI 50-65) patients in the atezolizumab plus chemotherapy group and 69 (41%, 34-49) patients in the placebo plus chemotherapy group (rate difference 17%, 95% CI 6-27; one-sided p=0·0044 [significance boundary 0·0184]). In the PD-L1-positive population, pathological complete response was documented in 53 (69%, 95% CI 57-79) of 77 patients in the atezolizumab plus chemotherapy group versus 37 (49%, 38-61) of 75 patients in the placebo plus chemotherapy group (rate difference 20%, 95% CI 4-35; one-sided p=0·021 [significance boundary 0·0184]). In the neoadjuvant phase, grade 3-4 adverse events were balanced and treatment-related serious adverse events occurred in 37 (23%) and 26 (16%) patients, with one patient per group experiencing an unrelated grade 5 adverse event (traffic accident in the atezolizumab plus chemotherapy group and pneumonia in the placebo plus chemotherapy group).\n\nInterpretation: In patients with early-stage TNBC, neoadjuvant treatment with atezolizumab in combination with nab-paclitaxel and anthracycline-based chemotherapy significantly improved pathological complete response rates with an acceptable safety profile.\n\nFunding: F Hoffmann-La Roche/Genentech.\n\nIndexed on Europe PMC as PubMed record 32966830 (DOI 10.1016/s0140-6736(20)31953-x). Its abstract cites the registry id NCT03197935, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet 2020","url":"https://doi.org/10.1016/s0140-6736(20)31953-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32966830/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32966830"},{"label":"ClinicalTrials.gov NCT03197935","url":"https://clinicaltrials.gov/study/NCT03197935"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["impassion031"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2020,"doi":"10.1016/s0140-6736(20)31953-x","pmid":"32966830","authors":"Mittendorf EA, Zhang H, Barrios CH, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03197935 with the most citations, so it is the natural first reading for anyone following the IMpassion031 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-geparsixto-lancet-oncol-2014","kind":"paper","name":"Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial","aka":[],"tldr":"Published report from the GeparSixto trial registered as NCT01426880, in The Lancet Oncology (2014), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Preclinical data suggest that triple-negative breast cancers are sensitive to interstrand crosslinking agents, and that synergy may exist for the combination of a taxane, trastuzumab, and a platinum salt for HER2-positive breast cancer. We therefore aimed to assess the efficacy of the addition of carboplatin to neoadjuvant therapy for triple-negative and HER2-positive breast cancer.\n\nMethods: Patients with previously untreated, non-metastatic, stage II-III, triple-negative breast cancer and HER2-positive breast cancer were enrolled. Patients were treated for 18 weeks with paclitaxel (80 mg/m(2) once a week) and non-pegylated liposomal doxorubicin (20 mg/m(2) once a week). Patients with triple-negative breast cancer received simultaneous bevacizumab (15 mg/kg intravenously every 3 weeks). Patients with HER2-positive disease received simultaneous trastuzumab (8 mg/kg initial dose with subsequent doses of 6 mg/kg intravenously every 3 weeks) and lapatinib (750 mg daily). Patients were randomly assigned in a 1:1 ratio with dynamic allocation and minimisation, stratified by biological subtype and Ki-67 level to receive, at the same time as the backbone regimens, either carboplatin (AUC 1·5 [2·0 for the first 329 patients] once a week) or no carboplatin. The primary endpoint the proportion of patients who achieved a pathological complete response (defined as ypT0 ypN0), analysed for all patients who started treatment; a p value of less than 0·2 was deemed significant for the primary endpoint. This trial is registered with ClinicalTrials.gov, number NCT01426880.\n\nFindings: 296 patients were randomly assigned to receive carboplatin and 299 to no additional carboplatin, of whom 295 and 293 started treatment, respectively. In this final analysis, 129 patients (43·7%, 95% CI 38·1-49·4) in the carboplatin group achieved a pathological complete response, compared with 108 patients (36·9%, 31·3-42·4) without carboplatin (odds ratio 1·33, 95% CI 0·96-1·85; p=0·107). Of the patients with triple-negative breast cancer, 84 (53·2%, 54·4-60·9) of 158 patients achieved a pathological complete response with carboplatin, compared with 58 (36·9%, 29·4-44·5) of 157 without (p=0·005). Of the patients with HER2-positive tumours, 45 (32·8%, 25·0-40·7) of 137 patients achieved a pathological complete response with carboplatin compared with 50 (36·8%, 28·7-44·9) of 136 without (p=0·581; test for interaction p=0·015). Haematological and non-haematological toxic effects that were significantly more common in the carboplatin group than in the no-carboplatin group included grade 3 or 4 neutropenia (192 [65%] vs 79 [27%]), grade 3 or 4 anaemia (45 [15%] vs one [<1%]), grade 3 or 4 thrombocytopenia (42 [14%] vs one [<1%]), and grade 3 or 4 diarrhoea (51 [17%] vs 32 [11%]); carboplatin was more often associated with dose discontinuations (141 [48%] with carboplatin and 114 [39%] without carboplatin; p=0·031). The frequency of grade 3 or 4 haematological events decreased from 82% (n=135) to 70% (n=92) and grade 3 or 4 non-haematological events from 78% (n=128) to 59% (n=77) in the carboplatin arm when the dose of carboplatin was reduced from AUC 2·0 to 1·5.\n\nInterpretation: The addition of neoadjuvant carboplatin to a regimen of a taxane, an anthracycline, and targeted therapy significantly increases the proportion of patients achieving a pathological complete response. This regimen seems to increase responses in patients with triple-negative breast cancer, but not in those with HER2-positive breast cancer.\n\nFunding: GlaxoSmithKline, Roche, and Teva.\n\nIndexed on Europe PMC as PubMed record 24794243 (DOI 10.1016/s1470-2045(14)70160-3). Its abstract cites the registry id NCT01426880, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2014","url":"https://doi.org/10.1016/s1470-2045(14)70160-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24794243/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/24794243"},{"label":"ClinicalTrials.gov NCT01426880","url":"https://clinicaltrials.gov/study/NCT01426880"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["geparsixto"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2014,"doi":"10.1016/s1470-2045(14)70160-3","pmid":"24794243","authors":"von Minckwitz G, Schneeweiss A, Loibl S, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT01426880 with the most citations, so it is the natural first reading for anyone following the GeparSixto trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-nct03916627-lancet-gastroenterol-hepatol-2022","kind":"paper","name":"Neoadjuvant cemiplimab for resectable hepatocellular carcinoma: a single-arm, open-label, phase 2 trial","aka":[],"tldr":"Published report from the trial registered as NCT03916627, in The lancet. Gastroenterology & hepatology (2022), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Surgical resection of early stage hepatocellular carcinoma is standard clinical practice; however, most tumours recur despite surgery, and no perioperative intervention has shown a survival benefit. Neoadjuvant immunotherapy has induced pathological responses in multiple tumour types and might decrease the risk of postoperative recurrence in hepatocellular carcinoma. We aimed to evaluate the clinical activity of neoadjuvant cemiplimab (an anti-PD-1) in patients with resectable hepatocellular carcinoma.\n\nMethods: For this single-arm, open-label, phase 2 trial, patients with resectable hepatocellular carcinoma (stage Ib, II, and IIIb) were enrolled and received two cycles of neoadjuvant cemiplimab 350 mg intravenously every 3 weeks followed by surgical resection. Eligible patients were aged 18 years or older, had confirmed resectable hepatocellular carcinoma, an Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate liver function. Patients were excluded if they had metastatic disease, if the surgery was not expected to be curative, if they had a known additional malignancy requiring active treatment, or if they required systemic steroid treatment or any other immunosuppressive therapy. After resection, patients received an additional eight cycles of cemiplimab 350 mg intravenously every 3 weeks in the adjuvant setting. The primary endpoint was significant tumour necrosis on pathological examination (defined as >70% necrosis of the resected tumour). Secondary endpoints included delay of surgery, the proportion of patients with an overall response, change in CD8 + T-cell density, and adverse events. Tumour necrosis and response were analysed in all patients who received at least one dose of cemiplimab and completed surgical resection; safety and other endpoints were analysed in the intention-to-treat population. Patients underwent pre-treatment biopsies and blood collection throughout treatment. This trial is registered with ClinicalTrials.gov (NCT03916627, Cohort B) and is ongoing.\n\nFindings: Between Aug 5, 2019, and Nov 25, 2020, 21 patients were enrolled. All patients received neoadjuvant cemiplimab, and 20 patients underwent successful resection. Of the 20 patients with resected tumours, four (20%) had significant tumour necrosis. Three (15%) of 20 patients had a partial response, and all other patients maintained stable disease. 20 (95%) patients had a treatment-emergent adverse event of any grade during the neoadjuvant treatment period. The most common adverse events of any grade were increased aspartate aminotransferase (in four patients), increased blood creatine phosphokinase (in three), constipation (in three), and fatigue (in three). Seven patients had grade 3 adverse events, including increased blood creatine phosphokinase (in two patients) and hypoalbuminaemia (in one). No grade 4 or 5 events were observed. One patient developed pneumonitis, which led to a delay in surgery by 2 weeks.\n\nInterpretation: This report is, to our knowledge, the largest clinical trial of a neoadjuvant anti-PD-1 monotherapy reported to date in hepatocellular carcinoma. The observed pathological responses to cemiplimab in this cohort support the design of larger trials to identify the optimal treatment duration and definitively establish the clinical benefit of preoperative PD-1 blockade in patients with hepatocellular carcinoma.\n\nFunding: Regeneron Pharmaceuticals.\n\nIndexed on Europe PMC as PubMed record 35065058 (DOI 10.1016/s2468-1253(21)00385-x). Its abstract cites the registry id NCT03916627, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Gastroenterol Hepatol 2022","url":"https://doi.org/10.1016/s2468-1253(21)00385-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35065058/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35065058"},{"label":"ClinicalTrials.gov NCT03916627","url":"https://clinicaltrials.gov/study/NCT03916627"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct03916627"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The lancet. Gastroenterology & hepatology","year":2022,"doi":"10.1016/s2468-1253(21)00385-x","pmid":"35065058","authors":"Marron TU, Fiel MI, Hamon P, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03916627 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-gross-neoadjuvant-cemiplimab-cscc-nejm-2022","kind":"paper","name":"Neoadjuvant cemiplimab for stage II to IV cutaneous squamous cell carcinoma","aka":[],"tldr":"Giving four doses of cemiplimab before surgery for resectable cutaneous squamous cell carcinoma eliminated all viable tumour in half of patients and left only minimal residual disease in another 13 percent, opening the way to smaller operations and less radiotherapy.","summary":"Phase 2 study of 79 patients with resectable stage II to IV (M0) cutaneous squamous cell carcinoma treated with up to four doses of neoadjuvant cemiplimab followed by surgery.\n\nPathological complete response was 50.6 percent and major pathological response (10 percent or less viable tumour) a further 12.7 percent; radiological response underestimated pathological response, and adverse events were consistent with PD-1 blockade.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2022","url":"https://doi.org/10.1056/NEJMoa2209813"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36094839/"}],"tags":[],"related":[],"cancers":["advanced-cutaneous-scc"],"sections":[],"technologies":[],"targets":[],"drugs":["cemiplimab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["neil-gross"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/NEJMoa2209813","pmid":"36094839","authors":"Gross ND, Miller DM, Khushalani NI, et al.","paperType":"observational","findings":["Pathological complete response 50.6 percent; major pathological response 12.7 percent.","Objective radiological response 68.4 percent."],"whatItMeans":"Neoadjuvant cemiplimab is now used to shrink large or function-threatening cutaneous squamous cell carcinomas before surgery, and pathological response is being studied as a guide to omitting adjuvant radiotherapy.","caveats":["Single-arm; long-term recurrence-free survival data are maturing.","Surgical de-escalation after complete response is not yet standard."],"changedPractice":true,"participants":79},{"id":"paper-conroy-prodige-23-neoadjuvant-folfirinox-rectal-lancet-oncol-2021","kind":"paper","name":"Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23)","aka":[],"tldr":"Six cycles of a three-drug chemotherapy before the usual chemoradiotherapy raised three-year disease-free survival from 69 to 76 percent, and left patients with less nerve damage than giving the chemotherapy afterwards.","summary":"Conroy, Bosset, Etienne and colleagues ran a phase 3 open-label randomised trial at 35 French hospitals in adults aged 18 to 75 with newly diagnosed biopsy-proven cT3 or cT4 M0 rectal adenocarcinoma and WHO performance status 0 to 1. The neoadjuvant chemotherapy group received six cycles of FOLFIRINOX, then chemoradiotherapy (50 Gy over five weeks with concurrent capecitabine), total mesorectal excision and three months of adjuvant chemotherapy; the standard-of-care group received chemoradiotherapy, total mesorectal excision and six months of adjuvant chemotherapy. The primary endpoint was three-year disease-free survival in the intention-to-treat population.\n\nSerious adverse events during adjuvant therapy were markedly fewer in the neoadjuvant group, which is the tolerability argument for moving chemotherapy forward.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2021","url":"https://doi.org/10.1016/S1470-2045(21)00079-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33862000/"}],"tags":["colorectal-evidence"],"related":["paper-bahadoer-rapido-short-course-radiotherapy-lancet-oncol-2021"],"cancers":["colorectal","rectal-cancer"],"sections":["chemotherapy","radiation"],"technologies":["radiotherapy","imrt-igrt"],"targets":[],"drugs":["folfirinox","folfox","capecitabine","oxaliplatin","irinotecan"],"companies":["unicancer"],"institutions":[],"pathways":[],"terms":["total-neoadjuvant-therapy","chemoradiation","total-mesorectal-excision"],"trials":["prodige-23"],"people":["thierry-conroy"],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2021,"doi":"10.1016/S1470-2045(21)00079-6","pmid":"33862000","authors":"Conroy T, Bosset JF, Etienne PL, et al.","paperType":"rct","findings":["At a median 46.5 months, three-year disease-free survival 76 percent (95 percent CI 69 to 81) against 69 percent (62 to 74): stratified hazard ratio 0.69 (0.49 to 0.97, p=0.034).","During neoadjuvant FOLFIRINOX the commonest grade 3-4 events were neutropenia (38 of 225, 17 percent) and diarrhoea (25 of 226, 11 percent).","During adjuvant chemotherapy, grade 3-4 peripheral sensory neuropathy occurred in 19 of 162 (12 percent) against 32 of 155 (21 percent).","Serious adverse events during adjuvant therapy in 18 of 163 (11 percent) against 36 of 158 (23 percent), p=0.0049.","Treatment-related deaths: one of 226 against two of 227."],"whatItMeans":"The second total neoadjuvant therapy schedule to change practice, and the one that shows the advantage is partly deliverability: chemotherapy given before an operation is completed by far more patients than chemotherapy given after one.","caveats":["FOLFIRINOX before chemoradiotherapy is demanding, and the trial enrolled patients up to 75 with good performance status.","No direct randomised comparison with the RAPIDO schedule exists.","Disease-free survival at three years, not overall survival, is the primary endpoint."],"changedPractice":true,"participants":461},{"id":"paper-gain-trial-protocol-bmc-cancer-2020","kind":"paper","name":"Neoadjuvant chemotherapy with gemcitabine plus cisplatin followed by radical liver resection versus immediate radical liver resection alone with or without adjuvant chemotherapy in incidentally detected gallbladder carcinoma after simple cholecystectomy or in front of radical resection of BTC (ICC/ECC) - a phase III study of the German registry of incidental gallbladder carcinoma platform (GR)- the AIO/ CALGP/ ACO- GAIN-trial","aka":[],"tldr":"The design of the German GAIN trial: chemotherapy before and after the second operation for gallbladder cancer found by chance, against surgery first.","summary":"Protocol for GAIN, a multicentre randomised open-label phase 3 built on the German Registry of Incidental Gallbladder Carcinoma. Patients with incidentally discovered gallbladder cancer before radical re-resection, or with resectable or borderline resectable cholangiocarcinoma, were to receive three cycles of gemcitabine plus cisplatin before and after surgery, or surgery alone followed by therapy of the investigator's choice. Primary endpoint overall survival; planned 333 patients; recruitment started August 2019. The authors note that gallbladder cancer is suspected before surgery in only about 30 percent of patients and that five-year survival after curative resection is 20 to 40 percent.","asOf":"2026-09-24","links":[{"label":"BMC Cancer 2020","url":"https://doi.org/10.1186/s12885-020-6610-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32059704/"},{"label":"ClinicalTrials.gov NCT03673072","url":"https://clinicaltrials.gov/study/NCT03673072"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder","cholangiocarcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["krankenhaus-nordwest"],"pathways":[],"terms":["incidental-gallbladder-cancer","neoadjuvant-adjuvant"],"trials":["gain-igbc"],"people":[],"bottlenecks":["b-trial-enrolment"],"keyPapers":[],"journals":["bmc-cancer"],"dependsOn":[],"notes":[],"journal":"BMC Cancer","year":2020,"doi":"10.1186/s12885-020-6610-4","pmid":"32059704","authors":"Goetze TO, Bechstein WO, Bankstahl US, et al.","paperType":"methods","findings":["Planned 333 patients; three cycles of gemcitabine-cisplatin before and after radical surgery vs surgery first; primary endpoint overall survival.","Gallbladder cancer is suspected preoperatively in only about 30 percent of patients (authors' background)."],"whatItMeans":"GAIN closed in October 2024 with 68 participants according to ClinicalTrials.gov, one fifth of its target: the clearest example of how hard it is to run a randomised surgical trial in incidental gallbladder cancer, and why OPT-IN's result matters.","caveats":["Protocol paper; the trial closed far short of its target.","Mixed population of incidental gallbladder cancer and cholangiocarcinoma."],"changedPractice":false,"participants":333},{"id":"paper-asco-neoadjuvant-therapy-breast-guideline-jco-2021","kind":"paper","name":"Neoadjuvant Chemotherapy, Endocrine Therapy, and Targeted Therapy for Breast Cancer: ASCO Guideline","aka":[],"tldr":"The US oncology society's 2021 rules for treatment before surgery: triple-negative tumours of 1 cm or more, or with involved nodes, should get anthracycline and taxane chemotherapy, carboplatin may be added, and at that date the evidence for adding immunotherapy was judged insufficient.","summary":"ASCO guideline by Korde, Somerfield, Carey, Crews and colleagues, based on a systematic review of 41 articles. Patients on neoadjuvant therapy should be managed by a multidisciplinary team; candidates include inflammatory breast cancer and cases where residual disease would change therapy, and neoadjuvant treatment can reduce the extent of local therapy. Tumour histology, grade, stage and receptor status should guide decisions; other markers and genomic profiles lack evidence. Triple-negative patients with clinically node-positive or at least T1c disease should be offered an anthracycline- and taxane-containing regimen; cT1a or cT1bN0 disease should not routinely be offered neoadjuvant therapy; carboplatin may be offered to increase pathological complete response; evidence was insufficient to add immune checkpoint inhibitors. Hormone receptor-positive and HER2-positive recommendations are also given.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2021","url":"https://doi.org/10.1200/JCO.20.03399"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33507815/"},{"label":"ASCO breast cancer guidelines","url":"https://ascopubs.org/topics/asco-guidelines/breast-cancer"},{"label":"J Clin Oncol 2021","url":"https://doi.org/10.1200/jco.20.03399"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33507815"}],"tags":["tnbc-evidence"],"related":["paper-asco-pembrolizumab-early-tnbc-rapid-update-jco-2022"],"cancers":["tnbc"],"sections":[],"technologies":[],"targets":[],"drugs":["carboplatin"],"companies":[],"institutions":["asco"],"pathways":[],"terms":["neoadjuvant-adjuvant","pcr","anthracycline","taxane"],"trials":[],"people":["shelley-hwang"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2021,"doi":"10.1200/JCO.20.03399","pmid":"33507815","authors":"Korde LA, Somerfield MR, Carey LA, et al.","paperType":"guideline","findings":["Triple-negative, node-positive or at least T1c: offer anthracycline- and taxane-containing neoadjuvant chemotherapy; cT1a or cT1bN0: not routinely.","Carboplatin may be offered to increase pathological complete response.","Insufficient evidence in 2021 to add immune checkpoint inhibitors to neoadjuvant chemotherapy."],"whatItMeans":"The last major guideline written before KEYNOTE-522 changed the standard; the 2022 rapid update reversed the immunotherapy line within a year.","caveats":["Superseded on immunotherapy by the 2022 rapid recommendation update.","Systematic review closed before the KEYNOTE-522 event-free survival data."],"changedPractice":true},{"id":"paper-preopanc-2-neoadjuvant-folfirinox-vs-chemoradiotherapy-lancet-oncol-2025","kind":"paper","name":"Neoadjuvant FOLFIRINOX versus neoadjuvant gemcitabine-based chemoradiotherapy in resectable and borderline resectable pancreatic cancer (PREOPANC-2): a multicentre, open-label, phase 3 randomised trial","aka":[],"tldr":"The 2025 Dutch trial in which eight cycles of FOLFIRINOX before surgery, with no treatment afterwards, gave the same survival (about 22 months) as the older gemcitabine chemoradiotherapy schedule, so either can be used but neither is clearly better.","summary":"PREOPANC-2 enrolled 375 patients with resectable or borderline resectable pancreatic ductal adenocarcinoma and WHO performance status 0 or 1 at 19 Dutch centres between June 2018 and January 2021, randomised 1:1 to eight cycles of neoadjuvant FOLFIRINOX followed by surgery without adjuvant treatment (188) or three cycles of neoadjuvant gemcitabine with hypofractionated radiotherapy (36 Gy in 15 fractions) during the second cycle, then surgery and four cycles of adjuvant gemcitabine (187). In the modified intention-to-treat population of 369, after a median follow-up of 42.3 months, median overall survival was 21.9 months with FOLFIRINOX versus 21.3 months with chemoradiotherapy (hazard ratio 0.88, 95 percent confidence interval 0.69 to 1.13, p = 0.32). Grade 3 to 4 neutropenia occurred in 25 versus 22 percent, diarrhoea in 23 versus 1 percent, leukopenia in 8 versus 15 percent; serious adverse events in 49 versus 43 percent; treatment-related deaths two versus one. Registered with EudraCT 2017-002036-17; funded by the Dutch Cancer Society and ZonMw.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2025","url":"https://doi.org/10.1016/S1470-2045(25)00363-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40945523/"},{"label":"Protocol (BMC Cancer 2021)","url":"https://doi.org/10.1186/s12885-021-08031-z"},{"label":"Letter: Neoptolemos and colleagues (Lancet Oncol 2026)","url":"https://doi.org/10.1016/S1470-2045(25)00601-1"}],"tags":["pancreatic-evidence"],"related":["paper-preopanc-preoperative-chemoradiotherapy-jco-2020","paper-norpact-1-neoadjuvant-folfirinox-labori-lancet-gastroenterol-hepatol-2024","paper-prodige-24-five-year-outcomes-jama-oncol-2022"],"cancers":["pancreatic","resectable-pdac","borderline-resectable-pdac"],"sections":[],"technologies":["cytotoxic-chemotherapy","imrt-igrt"],"targets":[],"drugs":["folfirinox","gemcitabine"],"companies":[],"institutions":["erasmus-mc","amsterdam-umc"],"pathways":[],"terms":["total-neoadjuvant-therapy","neoadjuvant-adjuvant","resectability"],"trials":["preopanc"],"people":["marc-besselink"],"bottlenecks":["b-trial-design"],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2025,"doi":"10.1016/S1470-2045(25)00363-8","pmid":"40945523","authors":"Janssen QP, van Dam JL, van Bekkum ML, et al.","paperType":"rct","findings":["375 randomised, 369 analysed; neoadjuvant FOLFIRINOX versus neoadjuvant gemcitabine chemoradiotherapy plus adjuvant gemcitabine.","Median overall survival 21.9 versus 21.3 months (hazard ratio 0.88, p = 0.32).","Grade 3 to 4 diarrhoea 23 versus 1 percent; serious adverse events 49 versus 43 percent."],"whatItMeans":"Together with NORPACT-1 this left the neoadjuvant question for resectable disease open: FOLFIRINOX before surgery is not proven superior to alternatives, and the comparison against upfront surgery with adjuvant modified FOLFIRINOX is what PREOPANC-3 and Alliance A021806 are running.","caveats":["No upfront-surgery arm; the comparator was the PREOPANC-1 regimen, not the current adjuvant standard.","The FOLFIRINOX arm received no adjuvant treatment by design.","Letters in the January 2026 issue (Neoptolemos and colleagues; Sherry and colleagues) disputed the design and interpretation."],"participants":375},{"id":"paper-niche-2-nat-med-2020","kind":"paper","name":"Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers","aka":[],"tldr":"Published report from the NICHE-2 trial registered as NCT03026140, in Nature Medicine (2020), chosen as the most cited paper whose own text cites the registry id.","summary":"PD-1 plus CTLA-4 blockade is highly effective in advanced-stage, mismatch repair (MMR)-deficient (dMMR) colorectal cancers, yet not in MMR-proficient (pMMR) tumors. We postulated a higher efficacy of neoadjuvant immunotherapy in early-stage colon cancers. In the exploratory NICHE study (ClinicalTrials.gov: NCT03026140), patients with dMMR or pMMR tumors received a single dose of ipilimumab and two doses of nivolumab before surgery, the pMMR group with or without celecoxib. The primary objective was safety and feasibility; 40 patients with 21 dMMR and 20 pMMR tumors were treated, and 3 patients received nivolumab monotherapy in the safety run-in. Treatment was well tolerated and all patients underwent radical resections without delays, meeting the primary endpoint. Of the patients who received ipilimumab + nivolumab (20 dMMR and 15 pMMR tumors), 35 were evaluable for efficacy and translational endpoints. Pathological response was observed in 20/20 (100%; 95% exact confidence interval (CI): 86-100%) dMMR tumors, with 19 major pathological responses (MPRs, ≤10% residual viable tumor) and 12 pathological complete responses. In pMMR tumors, 4/15 (27%; 95% exact CI: 8-55%) showed pathological responses, with 3 MPRs and 1 partial response. CD8 + PD-1 + T cell infiltration was predictive of response in pMMR tumors. These data indicate that neoadjuvant immunotherapy may have the potential to become the standard of care for a defined group of colon cancer patients when validated in larger studies with at least 3 years of disease-free survival data.\n\nIndexed on Europe PMC as PubMed record 32251400 (DOI 10.1038/s41591-020-0805-8). Its abstract cites the registry id NCT03026140, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Nat Med 2020","url":"https://doi.org/10.1038/s41591-020-0805-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32251400/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32251400"},{"label":"ClinicalTrials.gov NCT03026140","url":"https://clinicaltrials.gov/study/NCT03026140"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["niche-2"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2020,"doi":"10.1038/s41591-020-0805-8","pmid":"32251400","authors":"Chalabi M, Fanchi LF, Dijkstra KK, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03026140 with the most citations, so it is the natural first reading for anyone following the NICHE-2 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-nct02938299-j-clin-oncol-2026-update","kind":"paper","name":"Neoadjuvant Intralesional Daromun (L19IL2/L19TNF) in Resectable Locally Advanced Melanoma: An Update on the Efficacy and Safety Results of the PIVOTAL Phase III Trial","aka":[],"tldr":"Later report from the Neoadjuvant L19IL2 trial registered as NCT02938299, in Journal of Clinical Oncology (2026); its title describes an updated or longer-term analysis.","summary":"Daromun (L19IL2/L19TNF) was investigated as a neoadjuvant, intralesional therapy for patients with fully resectable stage III melanoma in the phase III PIVOTAL trial (ClinicalTrials.gov identifier: NCT02938299). The trial enrolled 256 patients in the European Union and met its primary end point, demonstrating a statistically significant improvement in recurrence-free survival (RFS; hazard ratio, 0.59; P =.005) for daromun followed by surgery versus up-front surgery, at a median follow-up (FU) of 21 months from random assignment. PIVOTAL included two clinically distinct subgroups, namely, patients with de novo diagnosed metastatic disease (n = 34; 13%) and patients with recurrence(s) after surgery with or without radiotherapy and/or adjuvant systemic therapies (n = 222; 87%). Here, we present an updated analysis of the primary and secondary end points, including safety data, at a median FU of 36.8 months from random assignment (database cutoff: November 28, 2025), alongside new sensitivity analyses of event-free survival (EFS). The updated analysis confirms the clinically and statistically meaningful improvements in RFS and distant metastasis-free survival recorded in the neoadjuvant daromun versus control arm. The EFS post hoc analysis, conducted in both the overall population and the recurrent patient subgroups (with or without prior systemic therapies), provides consistency and robustness to the benefit of neoadjuvant daromun observed for the primary efficacy end point. No new safety signals of concern were recorded.\n\nIndexed on Europe PMC as PubMed record 42579833 (DOI 10.1200/jco-26-00852). Its abstract cites the registry id NCT02938299, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2026","url":"https://doi.org/10.1200/jco-26-00852"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42579833/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42579833"},{"label":"ClinicalTrials.gov NCT02938299","url":"https://clinicaltrials.gov/study/NCT02938299"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct02938299"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2026,"doi":"10.1200/jco-26-00852","pmid":"42579833","authors":"Hauschild A, Hassel JC, Ziemer M, et al.","paperType":"observational","findings":[],"whatItMeans":"A second publication from the Neoadjuvant L19IL2 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-nct02938299-ann-oncol-2025","kind":"paper","name":"Neoadjuvant intralesional targeted immunocytokines (daromun) in stage III melanoma","aka":[],"tldr":"Published report from the Neoadjuvant L19IL2 trial registered as NCT02938299, in Annals of Oncology (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: This phase III trial assessed daromun, a combination of two fibronectin-targeting immunocytokines (L19IL2 and L19TNF), as a neoadjuvant treatment for patients with clinically detectable stage IIIB/C melanoma [American Joint Committee on Cancer (AJCC) version 7].\n\nPatients and methods: Patients were randomized to weekly intralesional daromun administrations (13 million IU of L19IL2 and 400 μg of L19TNF) for 4 weeks followed by surgery, or upfront surgery. Pretreatment with approved adjuvant agents was allowed. The primary endpoint was recurrence-free survival (RFS): events were disease recurrence or death from any cause after complete surgical tumor resection (ClinicalTrials.gov NCT02938299).\n\nResults: A total of 246 patients were randomized and included in the intention-to-treat analysis: 74% had undergone two or more prior surgical resections and 35% had received prior systemic therapy. At a median follow-up of 21 months, the neoadjuvant group (n = 122) had a significantly longer RFS than the upfront surgery group (n = 124), with a median RFS of 16.7 months and 6.8 months, respectively [hazard ratio (HR) 0.59, 95% confidence interval (CI 0.41-0.86), P = 0.005, log-rank test]. The risk of distant recurrence was reduced by 40% in the neoadjuvant arm (HR 0.60, 95% CI 0.37-0.95, P = 0.029). Grade ≥3 treatment-related adverse events (TRAEs) were 6.7% in the surgery-alone arm and 27.1% in the daromun arm, mostly injection site reactions.\n\nConclusions: Neoadjuvant daromun resulted in a significantly longer RFS than upfront surgery in patients with locally advanced melanoma. TRAEs were transient and manageable. Neoadjuvant daromun is a new therapeutic option for patients with stage III melanoma, including those with locoregional recurrence after surgery and previous adjuvant therapy.\n\nIndexed on Europe PMC as PubMed record 40633690 (DOI 10.1016/j.annonc.2025.06.014). Its abstract cites the registry id NCT02938299, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2025","url":"https://doi.org/10.1016/j.annonc.2025.06.014"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40633690/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40633690"},{"label":"ClinicalTrials.gov NCT02938299","url":"https://clinicaltrials.gov/study/NCT02938299"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct02938299"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2025,"doi":"10.1016/j.annonc.2025.06.014","pmid":"40633690","authors":"Kähler KC, Hassel JC, Ziemer M, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02938299 with the most citations, so it is the natural first reading for anyone following the Neoadjuvant L19IL2 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-pagliaro-neoadjuvant-tip-penile-cancer-jco-2010","kind":"paper","name":"Neoadjuvant paclitaxel, ifosfamide and cisplatin (TIP) for penile cancer with bulky lymph node metastases","aka":[],"tldr":"Giving three drugs before surgery to men with penile cancer that had spread to bulky groin or pelvic nodes shrank the cancer in half of them and allowed some to be cured, and TIP became the standard chemotherapy for node-positive penile cancer.","summary":"Single-centre phase 2 study of 30 men with penile squamous cell carcinoma and bulky regional lymph node metastases (N2 to N3) treated with four cycles of paclitaxel, ifosfamide and cisplatin followed by lymphadenectomy where feasible.\n\nHalf of the patients had an objective response, 22 went on to surgery and three had no viable tumour in the resected nodes. Response to chemotherapy and absence of extranodal extension or bilateral disease at surgery predicted survival.","asOf":"2026-09-18","links":[{"label":"J Clin Oncol 2010","url":"https://doi.org/10.1200/JCO.2010.29.5477"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20625118/"}],"tags":[],"related":[],"cancers":["node-positive-penile-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["paclitaxel","ifosfamide","cisplatin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2010,"doi":"10.1200/JCO.2010.29.5477","pmid":"20625118","authors":"Pagliaro LC, Williams DL, Daliani D, et al.","paperType":"observational","findings":["Objective response in 15 of 30 patients (50 percent) to neoadjuvant TIP.","22 patients proceeded to lymphadenectomy; three had a complete pathological response."],"whatItMeans":"Neoadjuvant TIP followed by surgery is the standard approach to bulky node-positive penile cancer in guidelines, though its randomised test against surgery first is the InPACT trial.","caveats":["Single-arm study of 30 patients at one centre.","Most patients still relapsed; long-term survival remained poor."],"changedPractice":true,"participants":30},{"id":"paper-trastuzumab-deruxtecan-breast-hr-positive-ann-oncol-2026","kind":"paper","name":"Neoadjuvant trastuzumab deruxtecan alone or followed by paclitaxel, trastuzumab, and pertuzumab for high-risk HER2-positive early breast cancer (DESTINY-Breast11): a randomised, open-label, multicentre, phase III trial","aka":[],"tldr":"Phase 2 or 3 results paper on Trastuzumab deruxtecan in HR-positive / HER2-negative breast cancer, in Annals of Oncology (2026), one of the most cited Europe PMC records with Trastuzumab deruxtecan in its title.","summary":"Background: Neoadjuvant standard-of-care for HER2-positive early-stage breast cancer is trastuzumab + pertuzumab with polychemotherapy; however, existing regimens have high toxicity burdens and suboptimal outcomes. DESTINY-Breast11 assessed efficacy and safety of neoadjuvant trastuzumab deruxtecan (T-DXd) alone or followed by paclitaxel + trastuzumab + pertuzumab (THP) versus dose-dense doxorubicin + cyclophosphamide (ddAC) followed by THP for high-risk (≥cT3cN0 or cT0-4cN1-3) HER2-positive disease.\n\nPatients and methods: This open-label, phase III trial (147 sites, 18 countries) randomised adults 1: 1: 1 to T-DXd (×8 cycles), T-DXd-THP (4 + 4 cycles), or ddAC-THP (4 + 4 cycles). T-DXd-alone arm enrolment closed early following the Independent Data Monitoring Committee recommendation. The primary endpoint was pathological complete response (pCR; ypT0/is ypN0; intent-to-treat population). Secondary endpoints included event-free survival (EFS; intent-to-treat population) and safety (safety analysis set).\n\nResults: Between 25 October 2021 and 12 March 2025, 286 (T-DXd), 321 (T-DXd-THP), and 320 (ddAC-THP) female patients were randomised. pCR rates were 43.0% (T-DXd, n = 123), 67.3% (T-DXd-THP, n = 216), and 56.3% (ddAC-THP, n = 180). T-DXd-THP versus ddAC-THP absolute pCR rate difference was 11.2% [95% confidence interval (CI), 4.0% to 18.3%, P = 0.003], with benefit in hormone receptor (HR)-positive [61.4% (n/N = 145/236) versus 52.3% (n/N = 123/235); difference in pCR (ΔpCR) 9.1% (95% CI 0.2% to 17.9%)] and HR-negative [83.1% (n/N = 69/83) versus 67.1% (n/N = 57/85); ΔpCR 16.1% (95% CI 3.0% to 28.8%)] subgroups. Median EFS (T-DXd-THP versus ddAC-THP, maturity 4.5%) hazard ratio was 0.56 (95% CI 0.26 to 1.17). Grade ≥3 adverse events (AE; T-DXd, 22.6% (n = 64); T-DXd-THP, 37.5% (n = 120); ddAC-THP, 55.8% (n = 174)], serious AE [T-DXd, 10.2% (n = 29); T-DXd-THP, 10.6% (n = 34); ddAC-THP, 20.2% (n = 63)], and all-grade left-ventricular dysfunction [T-DXd, 0.7% (n = 2); T-DXd-THP, 1.3% (n = 4); ddAC-THP, 6.1% (n = 19)] rates were lower for T-DXd and T-DXd-THP than ddAC-THP. All-grade adjudicated drug-related interstitial lung disease/pneumonitis rates were low and similar across arms [T-DXd, 4.9% (n = 14); T-DXd-THP, 4.4% (n = 14); ddAC-THP, 5.1% (n = 16)]. Three treatment-related deaths occurred [T-DXd-THP, 0.3% (n = 1); ddAC-THP, 0.6% (n = 2)].\n\nConclusions: Neoadjuvant T-DXd-THP demonstrated statistically significant and clinically meaningful pCR benefit and improved safety versus ddAC-THP.\n\nIndexed on Europe PMC as PubMed record 41130363 (DOI 10.1016/j.annonc.2025.10.019). Its title names Trastuzumab deruxtecan and its text names HR-positive / HER2-negative breast cancer; PubMed types it as a clinical trial report (Clinical Trial, Phase III, Multicenter Study, Randomized Controlled Trial). It was matched automatically to the idea \"AI quantification of HER2-low and HER2-ultralow\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Ann Oncol 2026","url":"https://doi.org/10.1016/j.annonc.2025.10.019"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41130363/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41130363"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2026,"doi":"10.1016/j.annonc.2025.10.019","pmid":"41130363","authors":"Harbeck N, Modi S, Pusztai L, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Trastuzumab deruxtecan in HR-positive / HER2-negative breast cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Trastuzumab deruxtecan in the title and HR-positive / HER2-negative breast cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-kristine-lancet-oncol-2018","kind":"paper","name":"Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE): a randomised, open-label, multicentre, phase 3 trial","aka":[],"tldr":"Published report from the KRISTINE trial registered as NCT02131064, in The Lancet Oncology (2018), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: HER2-targeted treatments have improved outcomes in patients with HER2-positive breast cancer in the neoadjuvant, adjuvant, and metastatic settings; however, some patients remain at risk of relapse or death for many years after treatment of early-stage disease. Therefore, new strategies are needed. We did a phase 3 trial to assess a neoadjuvant regimen for HER2-positive breast cancer that replaces traditional systemic chemotherapy with targeted treatment.\n\nMethods: We did a randomised, open-label phase 3 KRISTINE trial in 68 Translational Research In Oncology centres (hospitals and specialty cancer centres in Asia, Europe, USA, and Canada). Eligible participants were aged 18 years or older with centrally confirmed HER2-positive stage II-III operable breast cancer (>2 cm tumour size), an Eastern Cooperative Oncology Group performance status of 0-1, and a baseline left ventricular ejection fraction of at least 55% (by echocardiogram or multiple-gated acquisition scan). We randomly assigned participants (1:1) to receive either trastuzumab emtansine plus pertuzumab or docetaxel, carboplatin, and trastuzumab plus pertuzumab. We did the randomisation via an interactive response system under a permuted block randomisation scheme (block size of four), stratified by hormone receptor status, stage at diagnosis, and geographical location. Patients received six cycles (every 3 weeks) of neoadjuvant trastuzumab emtansine plus pertuzumab (trastuzumab emtansine 3·6 mg/kg; pertuzumab 840 mg loading dose, 420 mg maintenance doses) or docetaxel, carboplatin, and trastuzumab plus pertuzumab (docetaxel 75 mg/m 2; carboplatin area under the concentration-time curve 6 mg/mL × min; trastuzumab 8 mg/kg loading dose, 6 mg/kg maintenance doses) plus pertuzumab [same dosing as in the other group]). All treatments were administered intravenously. The primary objective was to compare the number of patients who achieved a pathological complete response (ypT0/is, ypN0), between groups in the intention-to-treat population (two-sided assessment), based on local evaluation of tumour samples taken at breast cancer surgery done between 14 days and 6 weeks after completion of neoadjuvant therapy. Safety was analysed in patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov, number NCT02131064, and follow-up of the adjuvant phase is ongoing.\n\nFindings: Between June 25, 2014, and June 15, 2015, we randomly assigned 444 patients to neoadjuvant treatment with trastuzumab emtansine plus pertuzumab (n=223) or docetaxel, carboplatin, and trastuzumab plus pertuzumab (n=221). A pathological complete response was achieved by 99 (44·4%) of 223 patients in the trastuzumab emtansine plus pertuzumab group and 123 (55·7%) of 221 patients in the docetaxel, carboplatin, and trastuzumab plus pertuzumab group (absolute difference -11·3 percentage points, 95% CI -20·5 to -2·0; p=0·016). During neoadjuvant treatment, compared with patients receiving docetaxel, carboplatin, and trastuzumab plus pertuzumab, fewer patients receiving trastuzumab emtansine plus pertuzumab had a grade 3-4 adverse event (29 [13%] of 223 vs 141 [64%] of 219) or a serious adverse event (11 [5%] of 223 vs 63 [29%] of 219). The most common grade 3-4 adverse events in the trastuzumab emtansine plus pertuzumab group were decreased platelet count (three [1%] of 223 patients vs 11 [5%] of 219 with docetaxel, carboplatin, and trastuzumab plus pertuzumab), fatigue (three [1%] vs seven [3%]), alanine aminotransferase increase (three [1%] vs four [2%]), and hypokalaemia (three [1%] vs five [2%]). The most common grade 3-4 adverse events in the docetaxel, carboplatin, and trastuzumab plus pertuzumab group were neutropenia (55 [25%] of 219 vs one [<1%] of 223 with trastuzumab emtansine plus pertuzumab), diarrhoea (33 [15%] vs 2 [<1%]), and febrile neutropenia (33 [15%] vs 0). No deaths were reported during neoadjuvant treatment.\n\nInterpretation: Traditional neoadjuvant systemic chemotherapy plus dual HER2-targeted blockade (docetaxel, carboplatin, and trastuzumab plus pertuzumab) resulted in significantly more patients achieving a pathological complete response than HER2-targeted chemotherapy plus HER2-targeted blockade (trastuzumab emtansine plus pertuzumab); however, numerically more grade 3-4 and serious adverse events occurred in the chemotherapy plus trastuzumab and pertuzumab group. Further efforts to improve the efficacy of chemotherapy without imparting more toxicity are warranted.\n\nFunding: F Hoffmann-La Roche and Genentech.\n\nIndexed on Europe PMC as PubMed record 29175149 (DOI 10.1016/s1470-2045(17)30716-7). Its abstract cites the registry id NCT02131064, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2018","url":"https://doi.org/10.1016/s1470-2045(17)30716-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29175149/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29175149"},{"label":"ClinicalTrials.gov NCT02131064","url":"https://clinicaltrials.gov/study/NCT02131064"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["kristine"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2018,"doi":"10.1016/s1470-2045(17)30716-7","pmid":"29175149","authors":"Hurvitz SA, Martin M, Symmans WF, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02131064 with the most citations, so it is the natural first reading for anyone following the KRISTINE trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-varshney-neoadjuvant-incidental-gallbladder-cancer-systematic-review-ahbps-2025","kind":"paper","name":"Neoadjuvant treatment for incidental gallbladder cancer: A systematic review","aka":[],"tldr":"A review of whether chemotherapy should come before the second operation for gallbladder cancer found by chance: recurrences after that operation are early and distant, so treating the whole body first makes sense, and the limited evidence favours three to four cycles of gemcitabine-based chemotherapy in higher-risk cases.","summary":"Systematic review by an international group including the GAIN and Indian investigators. Incidental gallbladder cancer is usually early stage, yet a high proportion recur within six months of radical re-resection, mostly at distant sites, which points to systemic disease. The review examines evidence for and against neoadjuvant systemic therapy before reoperation, proposes selection criteria and a regimen, and notes improved outcomes reported for reoperation 4 to 14 weeks after cholecystectomy compared with immediate reoperation. It concludes that limited but promising evidence supports 3 to 4 cycles of gemcitabine-based neoadjuvant chemotherapy in selected high-risk cases.","asOf":"2026-09-24","links":[{"label":"Ann Hepatobiliary Pancreat Surg 2025","url":"https://doi.org/10.14701/ahbps.24-223"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40064481/"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":["gemcitabine-cisplatin"],"companies":[],"institutions":[],"pathways":[],"terms":["incidental-gallbladder-cancer","neoadjuvant-adjuvant"],"trials":["opt-in","gain-igbc"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Annals of Hepato-Biliary-Pancreatic Surgery","year":2025,"doi":"10.14701/ahbps.24-223","pmid":"40064481","authors":"Varshney P, Baghmar S, Sirohi B, et al.","paperType":"review","findings":["Most recurrences after radical re-resection of incidental gallbladder cancer are distant and early (within six months).","Limited evidence supports 3 to 4 cycles of gemcitabine-based neoadjuvant chemotherapy in selected high-risk incidental cases; reoperation at 4 to 14 weeks is associated with better outcomes than immediate reoperation."],"whatItMeans":"The rationale for OPT-IN and GAIN in one place. Until OPT-IN reports in 2028 the neoadjuvant approach for incidental cancer remains a reasoned choice rather than a proven one.","caveats":["Narrative synthesis of small retrospective series.","Authors include investigators of the trials under review."],"changedPractice":false},{"id":"paper-nct05890742-cancer-cell-2025","kind":"paper","name":"Neoadjuvant treatment of IBI310 plus sintilimab in locally advanced MSI-H/dMMR colon cancer: A randomized phase 1b study","aka":[],"tldr":"Published report from the dMMR Resectable Colon Cancer trial registered as NCT05890742, in Cancer Cell (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Although neoadjuvant immunotherapy showed promising efficacy in locally advanced microsatellite instability-high or mismatch repair-deficient (MSI-H/dMMR) colon cancer, whether dual immune checkpoint inhibition provides additional benefit over anti-PD-1 monotherapy remains unclear. This randomized phase 1b trial (NCT05890742) evaluated a neoadjuvant regimen of IBI310 (anti-cytotoxic T lymphocyte-associated antigen 4 [CTLA-4]) plus sintilimab (n = 52) versus sintilimab monotherapy (n = 49). Surgery was performed in 51 and 45 patients, respectively. The primary endpoint, pathological complete response (pCR) rate, was significantly higher in the combination compared to the monotherapy arm within the modified intent-to-treat (mITT) population (78.4% versus 46.7%, p = 0.0015), with consistent results in the intent-to-treat (ITT) population (76.9% versus 42.9%). Safety in both arms was comparable and manageable without new safety signals. After a median follow-up of 21.4 months, no disease recurrences occurred. One death occurred in each arm due to postoperative complication and adverse events. These findings demonstrate the added benefit of neoadjuvant IBI310 plus sintilimab over sintilimab monotherapy for locally advanced MSI-H/dMMR colon cancer.\n\nIndexed on Europe PMC as PubMed record 41043438 (DOI 10.1016/j.ccell.2025.09.004). Its abstract cites the registry id NCT05890742, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Cancer Cell 2025","url":"https://doi.org/10.1016/j.ccell.2025.09.004"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41043438/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41043438"},{"label":"ClinicalTrials.gov NCT05890742","url":"https://clinicaltrials.gov/study/NCT05890742"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05890742"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-cell"],"dependsOn":[],"notes":[],"journal":"Cancer Cell","year":2025,"doi":"10.1016/j.ccell.2025.09.004","pmid":"41043438","authors":"Wang F, Chen G, Qiu M, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05890742 with the most citations, so it is the natural first reading for anyone following the dMMR Resectable Colon Cancer trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-swog-s1801-n-engl-j-med-2023","kind":"paper","name":"Neoadjuvant-Adjuvant or Adjuvant-Only Pembrolizumab in Advanced Melanoma","aka":[],"tldr":"Published report from the SWOG S1801 trial registered as NCT03698019, in New England Journal of Medicine (2023), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Whether pembrolizumab given both before surgery (neoadjuvant therapy) and after surgery (adjuvant therapy), as compared with pembrolizumab given as adjuvant therapy alone, would increase event-free survival among patients with resectable stage III or IV melanoma is unknown.\n\nMethods: In a phase 2 trial, we randomly assigned patients with clinically detectable, measurable stage IIIB to IVC melanoma that was amenable to surgical resection to three doses of neoadjuvant pembrolizumab, surgery, and 15 doses of adjuvant pembrolizumab (neoadjuvant-adjuvant group) or to surgery followed by pembrolizumab (200 mg intravenously every 3 weeks for a total of 18 doses) for approximately 1 year or until disease recurred or unacceptable toxic effects developed (adjuvant-only group). The primary end point was event-free survival in the intention-to-treat population. Events were defined as disease progression or toxic effects that precluded surgery; the inability to resect all gross disease; disease progression, surgical complications, or toxic effects of treatment that precluded the initiation of adjuvant therapy within 84 days after surgery; recurrence of melanoma after surgery; or death from any cause. Safety was also evaluated.\n\nResults: At a median follow-up of 14.7 months, the neoadjuvant-adjuvant group (154 patients) had significantly longer event-free survival than the adjuvant-only group (159 patients) (P = 0.004 by the log-rank test). In a landmark analysis, event-free survival at 2 years was 72% (95% confidence interval [CI], 64 to 80) in the neoadjuvant-adjuvant group and 49% (95% CI, 41 to 59) in the adjuvant-only group. The percentage of patients with treatment-related adverse events of grades 3 or higher during therapy was 12% in the neoadjuvant-adjuvant group and 14% in the adjuvant-only group.\n\nConclusions: Among patients with resectable stage III or IV melanoma, event-free survival was significantly longer among those who received pembrolizumab both before and after surgery than among those who received adjuvant pembrolizumab alone. No new toxic effects were identified. (Funded by the National Cancer Institute and Merck Sharp and Dohme; S1801 ClinicalTrials.gov number, NCT03698019.).\n\nIndexed on Europe PMC as PubMed record 36856617 (DOI 10.1056/nejmoa2211437). Its abstract cites the registry id NCT03698019, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2023","url":"https://doi.org/10.1056/nejmoa2211437"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36856617/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36856617"},{"label":"ClinicalTrials.gov NCT03698019","url":"https://clinicaltrials.gov/study/NCT03698019"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["swog-s1801"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/nejmoa2211437","pmid":"36856617","authors":"Patel SP, Othus M, Chen Y, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03698019 with the most citations, so it is the natural first reading for anyone following the SWOG S1801 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-nala-j-clin-oncol-2020","kind":"paper","name":"Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated With ≥ 2 HER2-Directed Regimens: Phase III NALA Trial","aka":[],"tldr":"Published report from the NALA trial registered as NCT01808573, in Journal of Clinical Oncology (2020), chosen as the most cited paper whose own text cites the registry id.","summary":"Purpose: NALA (ClinicalTrials.gov identifier: NCT01808573) is a randomized, active-controlled, phase III trial comparing neratinib, an irreversible pan-HER tyrosine kinase inhibitor (TKI), plus capecitabine (N+C) against lapatinib, a reversible dual TKI, plus capecitabine (L+C) in patients with centrally confirmed HER2-positive, metastatic breast cancer (MBC) with ≥ 2 previous HER2-directed MBC regimens.\n\nMethods: Patients, including those with stable, asymptomatic CNS disease, were randomly assigned 1:1 to neratinib (240 mg once every day) plus capecitabine (750 mg/m 2 twice a day 14 d/21 d) with loperamide prophylaxis, or to lapatinib (1,250 mg once every day) plus capecitabine (1,000 mg/m 2 twice a day 14 d/21 d). Coprimary end points were centrally confirmed progression-free survival (PFS) and overall survival (OS). NALA was considered positive if either primary end point was met (α split between end points). Secondary end points were time to CNS disease intervention, investigator-assessed PFS, objective response rate (ORR), duration of response (DoR), clinical benefit rate, safety, and health-related quality of life (HRQoL).\n\nResults: A total of 621 patients from 28 countries were randomly assigned (N+C, n = 307; L+C, n = 314). Centrally reviewed PFS was improved with N+C (hazard ratio [HR], 0.76; 95% CI, 0.63 to 0.93; stratified log-rank P =. 0059). The OS HR was 0.88 (95% CI, 0.72 to 1.07; P =. 2098). Fewer interventions for CNS disease occurred with N+C versus L+C (cumulative incidence, 22.8% v 29.2%; P =. 043). ORRs were N+C 32.8% (95% CI, 27.1 to 38.9) and L+C 26.7% (95% CI, 21.5 to 32.4; P =. 1201); median DoR was 8.5 versus 5.6 months, respectively (HR, 0.50; 95% CI, 0.33 to 0.74; P =.0004). The most common all-grade adverse events were diarrhea (N+C 83% v L+C 66%) and nausea (53% v 42%). Discontinuation rates and HRQoL were similar between groups.\n\nConclusion: N+C significantly improved PFS and time to intervention for CNS disease versus L+C. No new N+C safety signals were observed.\n\nIndexed on Europe PMC as PubMed record 32678716 (DOI 10.1200/jco.20.00147). Its abstract cites the registry id NCT01808573, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2020","url":"https://doi.org/10.1200/jco.20.00147"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32678716/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32678716"},{"label":"ClinicalTrials.gov NCT01808573","url":"https://clinicaltrials.gov/study/NCT01808573"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nala"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/jco.20.00147","pmid":"32678716","authors":"Saura C, Oliveira M, Feng YH, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT01808573 with the most citations, so it is the natural first reading for anyone following the NALA trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-netter-1-nejm-2017","kind":"paper","name":"NETTER-1: 177Lu-Dotatate for midgut neuroendocrine tumours progressing on octreotide","aka":[],"tldr":"Radioligand therapy with lutetium-177 dotatate reduced the risk of progression or death by nearly 80 percent compared with high-dose octreotide in midgut neuroendocrine tumours, the first randomised proof that targeted radiation works in these cancers.","summary":"Phase 3 trial of 229 patients with advanced, progressive, somatostatin receptor-positive midgut neuroendocrine tumours randomised to four cycles of 177Lu-Dotatate plus octreotide LAR 30 mg or high-dose octreotide LAR 60 mg.\n\nProgression-free survival at 20 months was 65.2 versus 10.8 percent (hazard ratio 0.21), response 18 versus 3 percent, and an interim analysis suggested improved overall survival; myelosuppression was modest.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2017","url":"https://doi.org/10.1056/NEJMoa1607427"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28076709/"}],"tags":[],"related":[],"cancers":["small-intestinal-net"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["netter-1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2017,"doi":"10.1056/NEJMoa1607427","pmid":"28076709","authors":"Strosberg J, El-Haddad G, Wolin E, et al.","paperType":"rct","findings":["Progression-free survival hazard ratio 0.21; 20-month rate 65.2 percent vs 10.8 percent.","Objective response 18 percent vs 3 percent."],"whatItMeans":"Lutetium-177 dotatate is a standard treatment for progressive small bowel neuroendocrine tumours after somatostatin analogues, and NETTER-2 has since moved it into first-line use for higher-grade tumours.","caveats":["Final overall survival difference (48.0 vs 36.3 months) did not reach significance, partly because of crossover.","Rare late myelodysplasia and leukaemia."],"changedPractice":true,"participants":229},{"id":"paper-netter-2-lancet-2024","kind":"paper","name":"NETTER-2: lutetium-177 dotatate as first treatment for higher-grade gastroenteropancreatic neuroendocrine tumours","aka":[],"tldr":"Using the radioactive drug lutetium dotatate as the first treatment for faster-growing neuroendocrine tumours, rather than saving it for later, nearly tripled the time without progression compared with high-dose octreotide.","summary":"Open-label phase 3 trial of 226 patients with newly diagnosed, somatostatin-receptor-positive grade 2-3 (Ki-67 10-55%) advanced gastroenteropancreatic neuroendocrine tumours randomised 2:1 to four cycles of 177Lu-dotatate plus octreotide LAR 30 mg or high-dose octreotide LAR (60 mg). Primary endpoint was PFS by blinded review.\n\nMedian PFS was 22.8 vs 8.5 months (HR 0.28) with an objective response rate of 43% vs 9%. Following NETTER-1 (which established lutetium dotatate in progressive midgut tumours), it moved radioligand therapy to the first line for higher-grade disease, where somatostatin analogues alone are weak.","asOf":"2026-09-08","links":[{"label":"PubMed search: NETTER-2 Lancet 2024","url":"https://pubmed.ncbi.nlm.nih.gov/?term=NETTER-2+lutetium+dotatate+first-line+Singh+Lancet"},{"label":"ClinicalTrials.gov NCT03972488","url":"https://clinicaltrials.gov/study/NCT03972488"}],"tags":[],"related":[],"cancers":["neuroendocrine"],"sections":[],"technologies":["radioligand-therapy","pet-ct"],"targets":["sstr2"],"drugs":["lutathera"],"companies":["novartis"],"institutions":[],"pathways":[],"terms":["theranostics","pfs","orr","first-line","dosimetry"],"trials":[],"people":["oh-do-youn"],"bottlenecks":["b-rare-cancers","b-global-access","b-trial-design"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2024,"doi":"10.1016/S0140-6736(24)00701-3","pmid":"38851203","authors":"Singh S, Halperin D, Myrehaug S, et al.","paperType":"rct","findings":["Median PFS 22.8 vs 8.5 months; HR 0.28 (95% CI 0.18-0.42).","Objective response 43.0% vs 9.3%.","Benefit consistent in grade 2 and grade 3 tumours and in pancreatic and small-bowel primaries.","Grade 3 or higher adverse events about 35% vs 28%; no cases of treatment-related myelodysplasia or leukaemia at the primary analysis.","Overall survival data immature; crossover to lutetium dotatate was permitted at progression."],"whatItMeans":"Patients newly diagnosed with an advanced grade 2 or 3 neuroendocrine tumour of the gut or pancreas that shows somatostatin receptors on imaging can now receive lutetium dotatate as their first treatment, gaining more than a year of additional disease control and a much higher chance of tumour shrinkage. It does not settle whether radioligand therapy is better than other first-line options such as capecitabine-temozolomide or everolimus, and long-term marrow safety with earlier use needs surveillance.","caveats":["Comparator was high-dose octreotide, which has limited anti-proliferative activity in grade 2-3 tumours.","Overall survival not yet shown; crossover will make it hard to demonstrate.","Long-term risks of earlier radioligand exposure (marrow, kidney, secondary leukaemia) require follow-up.","Requires somatostatin-receptor PET and nuclear medicine capacity; grade 3 tumours with Ki-67 above 55% were excluded."],"changedPractice":true,"participants":226},{"id":"paper-albrengues-science","kind":"paper","name":"Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 30262472 and published in Science; the citing page links this DOI, which is how the record was matched.","summary":"Cancer cells from a primary tumor can disseminate to other tissues, remaining dormant and clinically undetectable for many years. Little is known about the cues that cause these dormant cells to awaken, resume proliferating, and develop into metastases. Studying mouse models, we found that sustained lung inflammation caused by tobacco smoke exposure or nasal instillation of lipopolysaccharide converted disseminated, dormant cancer cells to aggressively growing metastases. Sustained inflammation induced the formation of neutrophil extracellular traps (NETs), and these were required for awakening dormant cancer. Mechanistic analysis revealed that two NET-associated proteases, neutrophil elastase and matrix metalloproteinase 9, sequentially cleaved laminin. The proteolytically remodeled laminin induced proliferation of dormant cancer cells by activating integrin α3β1 signaling. Antibodies against NET-remodeled laminin prevented awakening of dormant cells. Therapies aimed at preventing dormant cell awakening could potentially prolong the survival of cancer patients.\n\nIndexed on Europe PMC as PubMed record 30262472 (DOI 10.1126/science.aao4227). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Science 2018","url":"https://doi.org/10.1126/science.aao4227"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30262472/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30262472"}],"tags":["europepmc-ingest"],"related":["tumor-dormancy"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2018,"doi":"10.1126/science.aao4227","pmid":"30262472","authors":"Albrengues J, Shields MA, Ng D, et al.","paperType":"observational","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-jacques-grill-cell-2016","kind":"paper","name":"New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs","aka":[],"tldr":"Paper by Jacques Grill indexed on Europe PMC as PubMed record 26919435, in Cell (2016), one of the most cited records naming an author with this name at Gustave Roussy.","summary":"Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well-defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors. From the remaining fraction of CNS-PNETs, we identify four new CNS tumor entities, each associated with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated \"CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2),\" \"CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT-CIC),\" \"CNS high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1),\" and \"CNS high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR),\" will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by poorly differentiated CNS tumors.\n\nIndexed on Europe PMC as PubMed record 26919435 (DOI 10.1016/j.cell.2016.01.015). Its author list gives \"Grill J\" with the affiliation \"Brain Tumor Program, Department of Pediatric and Adolescent Oncology, Gustave Roussy Cancer Institute, University Paris Sud, 94805, Villejuif, France\", which names Gustave Roussy; that is how the record was matched to Jacques Grill, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cell 2016","url":"https://doi.org/10.1016/j.cell.2016.01.015"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26919435/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26919435"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["jacques-grill"],"bottlenecks":[],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Cell","year":2016,"doi":"10.1016/j.cell.2016.01.015","pmid":"26919435","authors":"Sturm D, Orr BA, Toprak UH, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Jacques Grill at Gustave Roussy, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-akgor-vaccines-basel","kind":"paper","name":"New HPV Vaccines on the Market and Future Trends: A State-of-the-Art Review","aka":[],"tldr":"Paper cited by one treatment page, indexed on Europe PMC as PubMed record 41746062 and published in Vaccines; the citing page links this DOI, which is how the record was matched.","summary":"Next-generation human papillomavirus (HPV) vaccines encompass newly licensed and emerging formulations that employ alternative production platforms, expanded valency, or novel antigenic targets beyond conventional L1-based vaccines. These vaccines aim to address affordability challenges, supply limitations, and suboptimal vaccination coverage, particularly in low- and middle-income countries. This review aggregates current clinical, immunological, and programme-related evidence on newly licensed vaccines, including the World Health Organization (WHO)-prequalified bivalent formulations (Cecolin ® and Walrinvax ®), the quadrivalent Cervavac ®, and the Escherichia coli -derived nonavalent Cecolin 9 ®, which received national licensure in 2025. Additionally, emerging high-valency candidates in Phase I-III trials-9-valent, 11-valent, and 14-valent formulations-are critically assessed. Clinical trials demonstrate that next-generation HPV vaccines provide robust protection; for example, Cecolin ® showed 100% efficacy against HPV-16/18-associated high-grade squamous intraepithelial lesions (HSIL) and up to 97.8% efficacy against persistent HPV infection, while Walrinvax ® demonstrated 78.6% protection against CIN2+ lesions. Cervavac ® showed non-inferior immunogenicity compared with established vaccines. While comparative analyses of efficacy, immunogenicity, and safety indicate that these vaccines are strong alternatives to established products, robust long-term effectiveness and real-world impact data remain essential before full clinical equivalence can be definitively established. Advances in L2-based platforms further aim to broaden cross-type protection, simplify manufacturing, and enable thermostable formulations, thereby enhancing applicability in resource-limited settings. Economic evaluations demonstrating favorable cost-effectiveness emphasize the essential role of next-generation vaccines in improving access and reducing inequity. Overall, innovations in valency, technology, and delivery strategies have the potential to significantly expand global HPV prevention coverage and accelerate progress toward cervical cancer elimination.\n\nIndexed on Europe PMC as PubMed record 41746062 (DOI 10.3390/vaccines14020140). Matched by DOI alone: one treatment page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Vaccines (Basel) 2026","url":"https://doi.org/10.3390/vaccines14020140"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41746062/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41746062"}],"tags":["europepmc-ingest"],"related":["cervavac"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Vaccines","year":2026,"doi":"10.3390/vaccines14020140","pmid":"41746062","authors":"Akgör U, Temiz BE, Cengiz M, et al.","paperType":"review","findings":[],"whatItMeans":"One treatment page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-blue-c-n-engl-j-med-2024","kind":"paper","name":"Next-Generation Multitarget Stool DNA Test for Colorectal Cancer Screening","aka":[],"tldr":"Published report from the BLUE-C trial registered as NCT04144738, in New England Journal of Medicine (2024), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: A next-generation multitarget stool DNA test, including assessments of DNA molecular markers and hemoglobin level, was developed to improve the performance of colorectal cancer screening, primarily with regard to specificity.\n\nMethods: In a prospective study, we evaluated a next-generation multitarget stool DNA test in asymptomatic adults 40 years of age or older who were undergoing screening colonoscopy. The primary outcomes were sensitivity of the test for colorectal cancer and specificity for advanced neoplasia (colorectal cancer or advanced precancerous lesions). Advanced precancerous lesions included one or more adenomas or sessile serrated lesions measuring at least 1 cm in the longest dimension, lesions with villous histologic features, and high-grade dysplasia. Secondary objectives included the quantification of sensitivity for advanced precancerous lesions and specificity for nonneoplastic findings or negative colonoscopy and comparison of sensitivities for colorectal cancer and advanced precancerous lesions between the multitarget stool DNA test and a commercially available fecal immunochemical test (FIT).\n\nResults: Of 20,176 participants, 98 had colorectal cancer, 2144 had advanced precancerous lesions, 6973 had nonadvanced adenomas, and 10,961 had nonneoplastic findings or negative colonoscopy. With the next-generation test, sensitivity for colorectal cancer was 93.9% (95% confidence interval [CI], 87.1 to 97.7), and specificity for advanced neoplasia was 90.6% (95% CI, 90.1 to 91.0). Sensitivity for advanced precancerous lesions was 43.4% (95% CI, 41.3 to 45.6), and specificity for nonneoplastic findings or negative colonoscopy was 92.7% (95% CI, 92.2 to 93.1). With the FIT, sensitivity was 67.3% (95% CI, 57.1 to 76.5) for colorectal cancer and 23.3% (95% CI, 21.5 to 25.2) for advanced precancerous lesions; specificity was 94.8% (95% CI, 94.4 to 95.1) for advanced neoplasia and 95.7% (95% CI, 95.3 to 96.1) for nonneoplastic findings or negative colonoscopy. As compared with FIT, the next-generation test had superior sensitivity for colorectal cancer (P<0.001) and for advanced precancerous lesions (P<0.001) but had lower specificity for advanced neoplasia (P<0.001). No adverse events occurred.\n\nConclusions: The next-generation multitarget stool DNA test showed higher sensitivity for colorectal cancer and advanced precancerous lesions than FIT but also showed lower specificity. (Funded by Exact Sciences; BLUE-C ClinicalTrials.gov number, NCT04144738.).\n\nIndexed on Europe PMC as PubMed record 38477986 (DOI 10.1056/nejmoa2310336). Its abstract cites the registry id NCT04144738, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2024","url":"https://doi.org/10.1056/nejmoa2310336"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38477986/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38477986"},{"label":"ClinicalTrials.gov NCT04144738","url":"https://clinicaltrials.gov/study/NCT04144738"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["blue-c"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2024,"doi":"10.1056/nejmoa2310336","pmid":"38477986","authors":"Imperiale TF, Porter K, Zella J, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04144738 with the most citations, so it is the natural first reading for anyone following the BLUE-C trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-nhs-galleri-design-cancers-2022","kind":"paper","name":"NHS-Galleri: design of the largest randomised trial of a multi-cancer blood test","aka":[],"tldr":"The NHS-Galleri design paper is the protocol for a 140,000-person randomised trial in England testing whether three annual Galleri blood tests reduce late-stage (III-IV) cancer diagnoses, the first MCED trial powered for a stage-shift endpoint.","summary":"NHS-Galleri (ISRCTN91431511) enrolled about 140,000 asymptomatic adults aged 50-77 through NHS England, randomised 1:1 to annual Galleri testing for three years with results returned, or to blood draws stored without testing. The design paper set out the primary endpoint of a reduction in stage III-IV cancer incidence between arms, with secondary endpoints including stage IV incidence, cancer-specific mortality and test performance.\n\nThe trial deliberately over-sampled deprived and ethnically diverse communities using mobile clinics. Results were reported in 2026; the trial record in this corpus tracks the primary and secondary outcomes and the regulatory response.\n\nThe design is important in its own right: it established stage shift as a pragmatic proxy endpoint for screening trials of multi-cancer tests, a choice that remains contested.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.3390/cancers14194818"},{"label":"NHS-Galleri trial site","url":"https://www.nhs-galleri.org"}],"tags":[],"related":["early-detection-roadmap","idea-prev-mced-stage-endpoint-surrogate","idea-prev-mced-registry-randomised"],"cancers":[],"sections":["early-detection"],"technologies":["mced","liquid-biopsy"],"targets":[],"drugs":["galleri"],"companies":[],"institutions":[],"pathways":[],"terms":["stage-shift","ppv"],"trials":["nhs-galleri","pathfinder-2"],"people":[],"bottlenecks":["b-early-detection","b-trial-design","b-overdiagnosis"],"keyPapers":[],"journals":["cancers-mdpi"],"dependsOn":[],"notes":[],"journal":"Cancers","year":2022,"doi":"10.3390/cancers14194818","authors":"Neal RD, Johnson P, Clarke CA, et al.","paperType":"methods","findings":["About 140,000 participants randomised, recruited through mobile clinics across NHS regions in England","Primary endpoint: absolute reduction in stage III-IV cancers in the intervention arm; key secondary endpoint: stage IV incidence","Test results were not returned in the control arm, preserving blinding of the population and clinicians","Population enriched for deprived and minority communities, unusual for a screening trial"],"whatItMeans":"NHS-Galleri is the trial that will decide whether a blood test for many cancers at once should be offered by a health system. Its endpoint is a reduction in late-stage cancer rather than deaths, so even a positive result leaves the mortality question to be settled by longer follow-up.","caveats":["Stage shift is a surrogate: fewer late-stage cancers does not guarantee fewer deaths, and lead-time and overdiagnosis can distort it","Three annual rounds is short for detecting slow-growing cancers","A single commercial test; results may not generalise to other MCED assays","Sponsor involvement in design and analysis (GRAIL) was substantial"],"changedPractice":false,"participants":140000},{"id":"paper-niagara-nejm-2024","kind":"paper","name":"NIAGARA: durvalumab before and after cystectomy for muscle-invasive bladder cancer","aka":[],"tldr":"Adding the immunotherapy durvalumab to chemotherapy before bladder removal, and continuing it afterwards, reduced relapse and death in muscle-invasive bladder cancer, the first improvement on neoadjuvant chemotherapy in two decades.","summary":"Open-label phase 3 trial of 1,063 patients with cisplatin-eligible muscle-invasive bladder cancer randomised to neoadjuvant gemcitabine-cisplatin with or without durvalumab, followed by radical cystectomy and, in the durvalumab arm, eight cycles of adjuvant durvalumab. Primary endpoints were event-free survival and pathological complete response.\n\n24-month EFS was 67.8% vs 59.8% (HR 0.68) and 24-month OS 82.2% vs 75.2% (HR 0.75); pCR was 37.3% vs 27.5%. It made perioperative durvalumab a new standard for cisplatin-eligible patients and, following CheckMate 274 (adjuvant nivolumab), completed the move of checkpoint inhibitors into curative-intent bladder cancer treatment.","asOf":"2026-09-08","links":[{"label":"NEJM 2024","url":"https://doi.org/10.1056/NEJMoa2408154"},{"label":"ClinicalTrials.gov NCT03732677","url":"https://clinicaltrials.gov/study/NCT03732677"}],"tags":[],"related":[],"cancers":["urothelial"],"sections":[],"technologies":["checkpoint-inhibitor","cytotoxic-chemotherapy","platinum"],"targets":["pdl1"],"drugs":["durvalumab"],"companies":["astrazeneca"],"institutions":["mount-sinai"],"pathways":[],"terms":["efs","pcr","neoadjuvant-adjuvant"],"trials":[],"people":["matthew-galsky"],"bottlenecks":["b-immunotherapy-response","b-trial-design","b-dormancy-mrd"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2024,"doi":"10.1056/NEJMoa2408154","authors":"Powles T, Catto JWF, Galsky MD, et al.","paperType":"rct","findings":["24-month event-free survival 67.8% vs 59.8%; HR 0.68 (95% CI 0.56-0.82).","24-month overall survival 82.2% vs 75.2%; HR 0.75 (95% CI 0.59-0.93).","Pathological complete response 37.3% vs 27.5% (the pCR endpoint narrowly missed statistical significance in the initial analysis but was significant on re-analysis of all patients).","Cystectomy was performed in 88% of both arms; durvalumab did not delay surgery or increase surgical complications.","Grade 3-4 treatment-related adverse events about 41% in both arms."],"whatItMeans":"Patients fit enough for cisplatin whose bladder cancer has invaded the muscle wall should now be offered durvalumab with their pre-operative chemotherapy and for about a year after surgery, which improves the chance of cure without compromising the operation. The trial cannot say whether the adjuvant phase is necessary, or how to treat cisplatin-ineligible patients, for whom other trials are ongoing.","caveats":["Open-label; the contribution of the adjuvant phase versus the neoadjuvant phase is not separable.","Cisplatin-ineligible patients (about half of real-world patients) were excluded.","Absolute EFS gain of about 8 points at two years; longer follow-up is needed.","Overlaps with adjuvant nivolumab (CheckMate 274) for patients with residual disease; sequencing is undefined."],"changedPractice":true,"participants":1063},{"id":"paper-niche-2-nejm-2024","kind":"paper","name":"NICHE-2: a month of nivolumab and ipilimumab before surgery clears mismatch-repair-deficient colon cancer in most patients","aka":[],"tldr":"Two doses of immunotherapy over four weeks before surgery left little or no living tumour in 95% of patients with mismatch-repair-deficient colon cancer, and none had relapsed at three years.","summary":"Single-arm phase 2 trial of 115 patients with non-metastatic, mismatch-repair-deficient colon cancer (mostly stage III, including bulky T4 and node-positive tumours) treated with one dose of ipilimumab (1 mg/kg) and two doses of nivolumab (3 mg/kg) over four weeks, followed by surgery within six weeks. Primary endpoints were safety and three-year disease-free survival.\n\nOf 111 patients evaluable, 109 (98%) had a pathological response, 105 (95%) a major pathological response (10% or less residual tumour), and 75 (68%) a complete response. At three years no patient had relapsed. The result challenges the need for adjuvant chemotherapy in dMMR colon cancer and raises the possibility of avoiding surgery altogether in some patients.","asOf":"2026-09-08","links":[{"label":"NEJM 2024","url":"https://doi.org/10.1056/NEJMoa2400634"},{"label":"ClinicalTrials.gov NCT03026140","url":"https://clinicaltrials.gov/study/NCT03026140"},{"label":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=NICHE-2%20neoadjuvant%20nivolumab%20ipilimumab%20dMMR%20colon%20cancer%20Chalabi%20NEJM%202024"}],"tags":[],"related":["msi-high","dmmr-ihc","colorectal-roadmap","paper-andre-checkmate-8hw-nivolumab-ipilimumab-nejm-2024","paper-cercek-nonoperative-management-mismatch-repair-deficient-tumours-nejm-2025","paper-cercek-dostarlimab-rectal-nejm-2022","paper-le-mmr-deficiency-science-2017"],"cancers":["colorectal"],"sections":[],"technologies":["checkpoint-inhibitor","msi-mmr-testing"],"targets":["pd1","ctla4","mmr"],"drugs":["nivolumab","ipilimumab"],"companies":["bms"],"institutions":["nki"],"pathways":["mismatch-repair-msi","pd1-checkpoint","cancer-immunity-cycle"],"terms":["msi","pcr","neoadjuvant-adjuvant","irae"],"trials":["niche-2"],"people":["myriam-chalabi","emile-voest","ton-schumacher","john-haanen"],"bottlenecks":["b-immunotherapy-response","b-surgery-radiation-innovation","b-trial-design"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2024,"doi":"10.1056/NEJMoa2400634","pmid":"38838311","authors":"Chalabi M, Verschoor YL, Tan PB, et al.","paperType":"rct","findings":["Pathological response in 109 of 111 evaluable patients (98%); major pathological response 95%; pathological complete response 68%.","Three-year disease-free survival 100% at a median follow-up of about 26 months.","Grade 3-4 immune-related adverse events in 4% of patients; 98% underwent surgery on time.","Responses were independent of PD-L1, tumour mutational burden or Lynch syndrome status.","Radiological response underestimated pathological response, as in other neoadjuvant immunotherapy studies."],"whatItMeans":"For colon cancer that is mismatch-repair deficient (about 10-15% of colon cancers, more in older patients), a single short course of immunotherapy before surgery is now a reasonable standard and is far more effective than chemotherapy, which has little effect in this subtype. It requires testing every colon cancer for mismatch repair at diagnosis, before surgery. Whether some patients can safely skip surgery, as in dMMR rectal cancer, is the next question.","caveats":["Single-arm phase 2 without a control; the 100% disease-free survival is remarkable but from a single-centre network with limited follow-up.","Surgery was still performed in all patients, so organ preservation is not yet demonstrated in colon cancer.","Requires reliable pre-operative mismatch repair testing and rapid access to immunotherapy, which many systems lack.","Two-drug regimen with ipilimumab; whether nivolumab alone would suffice is untested."],"changedPractice":true,"participants":115},{"id":"paper-leighl-nile-cfdna-tissue-genotyping-ccr-2019","kind":"paper","name":"NILE: clinical utility of comprehensive cell-free DNA analysis to identify genomic biomarkers in patients with newly diagnosed metastatic non-small cell lung cancer","aka":[],"tldr":"Testing a blood sample found at least as many treatable mutations as testing the tumour did, found them six days sooner, and when both were done together found half as many again.","summary":"Prospectively enrolled patients with previously untreated metastatic non-small-cell lung cancer undergoing physician-discretion standard-of-care tissue genotyping also submitted a pretreatment blood sample for comprehensive cell-free DNA analysis. Among 282 patients, tissue genotyping identified a guideline-recommended biomarker in 60 patients against 77 identified by cell-free DNA, 21.3% against 27.3%, meeting non-inferiority. In tissue-positive patients the biomarker was identified by tissue alone in 12 of 60 and concordantly in 48 of 60, an 80% clinical sensitivity for cell-free DNA. For the alterations with approved drugs, EGFR, ALK, ROS1 and BRAF, concordance exceeded 98% with 100% positive predictive value for cell-free DNA against tissue in 34 positive patients. Using cell-free DNA in addition to tissue increased detection by 48%, from 60 to 89 patients. Median turnaround was 9 days against 15 days for tissue, and guideline-complete genotyping was far more likely.","asOf":"2026-09-25","links":[{"label":"Leighl et al., Clin Cancer Res 2019: NILE, cell-free DNA against tissue genotyping in 282 newly diagnosed metastatic lung cancers","url":"https://doi.org/10.1158/1078-0432.CCR-19-0624"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30988079/"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":["liquid-biopsy","cgp"],"targets":["egfr","alk","ros1","braf","ret","met","her2","kras"],"drugs":["guardant360-cdx"],"companies":[],"institutions":[],"pathways":["rtk-activation"],"terms":["ctdna","cfdna","ngs","biopsy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2019,"doi":"10.1158/1078-0432.CCR-19-0624","pmid":"30988079","authors":"Leighl NB, Page RD, Raymond VM, et al.","paperType":"observational","findings":["Cell-free DNA found a guideline biomarker in 27.3% of patients against 21.3% by tissue, meeting non-inferiority.","Clinical sensitivity of plasma against tissue was 80% for any guideline biomarker.","Positive predictive value was 100% for EGFR, ALK and BRAF positives.","Adding plasma to tissue raised detection by 48% and cut turnaround from 15 to 9 days."],"whatItMeans":"It is the evidence behind running plasma and tissue together at diagnosis rather than in sequence, and the 80% sensitivity figure is the reason a negative plasma result never ends the work-up.","caveats":["Tissue genotyping was at physician discretion, so the comparator is real-world practice rather than complete sequencing.","Cell-free DNA detection depends on tumour shedding, which varies with disease site and burden.","One commercial assay was tested."],"changedPractice":true,"participants":282},{"id":"paper-qin-j-clin-oncol","kind":"paper","name":"Nimotuzumab Plus Gemcitabine for K-Ras Wild-Type Locally Advanced or Metastatic Pancreatic Cancer","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 37647576 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: In a phase IIb trial of nimotuzumab plus gemcitabine, substantial clinical benefits were observed in patients with locally advanced or metastatic pancreatic cancer (PC). Therefore, we conducted a phase III clinical study to verify the efficacy and safety of this combination regimen in patients with K-Ras wild-type tumors (ClinicalTrials.gov identifier: NCT02395016).\n\nPatients and methods: Eligible patients were randomly assigned to receive nimotuzumab (400 mg once per week) or placebo followed by gemcitabine (1,000 mg/m 2 on days 1, 8, and 15, once every 4 weeks) until disease progression or unacceptable toxicity. The primary end point was overall survival (OS) and the secondary end points were progression-free survival (PFS), response rates, and safety.\n\nResults: A total of 480 patients were screened; 92 patients were enrolled and 82 patients with K-Ras wild-type tumors were eligible. In the full analysis set, the median OS was 10.9 versus 8.5 months, while the restricted mean survival time (RMST) was 18.05 versus 11.14 months for the investigational versus control arm (ratio of control v investigation = 0.62 [0.40-0.97]; P =.036). Median PFS was 4.2 versus 3.6 months in the investigational versus control arm (log-rank P =.04; hazard ratio, 0.60 [0.37-0.99]) and the restricted mean PFS time was 8.08 versus 4.76 months (RMST ratio, 0.58 [0.38-0.90]; P =.036). Both OS and PFS were longer in the nimotuzumab group than in the placebo group. The objective response rates and disease control rates were 7% versus 10% and 68% versus 63% for the investigational and control groups, respectively. The incidence of adverse events were comparable between the two groups.\n\nConclusion: In patients with locally advanced or metastatic K-Ras wild-type PC, nimotuzumab plus gemcitabine significantly improved OS and PFS with a good safety profile.\n\nIndexed on Europe PMC as PubMed record 37647576 (DOI 10.1200/jco.22.02630). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2023","url":"https://doi.org/10.1200/jco.22.02630"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37647576/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37647576"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["notable-trial"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2023,"doi":"10.1200/jco.22.02630","pmid":"37647576","authors":"Qin S, Li J, Bai Y, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-magnitude-j-clin-oncol-2023","kind":"paper","name":"Niraparib and Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer","aka":[],"tldr":"Published report from the MAGNITUDE trial registered as NCT03748641, in Journal of Clinical Oncology (2023), chosen as the most cited paper whose own text cites the registry id.","summary":"Purpose: Metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease with current standard-of-care therapies. Homologous recombination repair (HRR) gene alterations, including BRCA1/2 alterations, can sensitize cancer cells to poly (ADP-ribose) polymerase inhibition, which may improve outcomes in treatment-naïve mCRPC when combined with androgen receptor signaling inhibition.\n\nMethods: MAGNITUDE (ClinicalTrials.gov identifier: NCT03748641) is a phase III, randomized, double-blinded study that evaluates niraparib and abiraterone acetate plus prednisone (niraparib + AAP) in patients with (HRR+, n = 423) or without (HRR-, n = 247) HRR-associated gene alterations, as prospectively determined by tissue/plasma-based assays. Patients were assigned 1:1 to receive niraparib + AAP or placebo + AAP. The primary end point, radiographic progression-free survival (rPFS) assessed by central review, was evaluated first in the BRCA1/2 subgroup and then in the full HRR+ cohort, with secondary end points analyzed for the full HRR+ cohort if rPFS was statistically significant. A futility analysis was preplanned in the HRR- cohort.\n\nResults: Median rPFS in the BRCA1/2 subgroup was significantly longer in the niraparib + AAP group compared with the placebo + AAP group (16.6 v 10.9 months; hazard ratio [HR], 0.53; 95% CI, 0.36 to 0.79; P =.001). In the overall HRR+ cohort, rPFS was significantly longer in the niraparib + AAP group compared with the placebo + AAP group (16.5 v 13.7 months; HR, 0.73; 95% CI, 0.56 to 0.96; P =.022). These findings were supported by improvement in the secondary end points of time to symptomatic progression and time to initiation of cytotoxic chemotherapy. In the HRR- cohort, futility was declared per the prespecified criteria. Treatment with niraparib + AAP was tolerable, with anemia and hypertension as the most reported grade ≥ 3 adverse events.\n\nConclusion: Combination treatment with niraparib + AAP significantly lengthened rPFS in patients with HRR+ mCRPC compared with standard-of-care AAP.[Media: see text].\n\nIndexed on Europe PMC as PubMed record 36952634 (DOI 10.1200/jco.22.01649). Its abstract cites the registry id NCT03748641, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2023","url":"https://doi.org/10.1200/jco.22.01649"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36952634/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36952634"},{"label":"ClinicalTrials.gov NCT03748641","url":"https://clinicaltrials.gov/study/NCT03748641"}],"tags":["europepmc-ingest"],"related":["prostate-roadmap","paper-chung-comprehensive-genomic-profiling-prostate-jco-po-2019","idea-prostate-hrr-testing-at-metastatic-diagnosis"],"cancers":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["magnitude"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2023,"doi":"10.1200/jco.22.01649","pmid":"36952634","authors":"Chi KN, Rathkopf D, Smith MR, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03748641 with the most citations, so it is the natural first reading for anyone following the MAGNITUDE trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-nct04497844-nat-med-2025","kind":"paper","name":"Niraparib and abiraterone acetate plus prednisone for HRR-deficient metastatic castration-sensitive prostate cancer: a randomized phase 3 trial","aka":[],"tldr":"Published report from the AMPLITUDE trial registered as NCT04497844, in Nature Medicine (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Inhibition of poly(ADP-ribose) polymerase (PARP) after relapse on hormone therapy is well established for patients with prostate cancer with homologous recombination repair (HRR) gene alterations, but resistance often develops. We hypothesized that PARP inhibition within 6 months of starting androgen deprivation therapy for metastatic castration-sensitive prostate cancer (mCSPC) could be effective and improve radiographic progression-free survival when added to standard-of-care treatments. The double-blind AMPLITUDE trial evaluated combining niraparib, a potent and specific PARP inhibitor, with abiraterone acetate and prednisone (AAP) versus placebo and AAP in mCSPC with HRR gene alterations. Patients (n = 696) were randomized in a 1:1 ratio (348 per group). Median age was 68 years; 56% had BRCA1 or BRCA2 alterations; 78% had high-volume metastases; and 16% had received docetaxel. The primary endpoint was met, with a significant improvement in radiographic progression-free survival observed first in the BRCA subgroup (median not reached at the time of analysis for the niraparib and AAP group versus 26 months for the AAP group; hazard ratio = 0.52; 95% confidence interval: 0.37-0.72; P < 0.0001) and then in the intention-to-treat population (hazard ratio = 0.63; 95% confidence interval: 0.49-0.80; P = 0.0001). The data for overall survival, a key secondary endpoint, are immature (193/389 events) but favor niraparib (hazard ratio = 0.79 (95% confidence interval: 0.59-1.04); BRCA subgroup: hazard ratio = 0.75 (95% confidence interval: 0.51-1.11)). Incidence of grade 3 or 4 adverse events was 75% in the niraparib and AAP group and 59% in the AAP group; most frequent in the niraparib and AAP group were anemia (29%), with 25% of patients requiring a blood transfusion, and hypertension (27%). There were 14 treatment-emergent adverse events leading to deaths in the niraparib group and seven in the placebo group. Combining niraparib with AAP significantly improved radiographic progression-free survival in patients with mCSPC harboring BRCA1/BRCA2 or other HRR gene alterations, suggesting clinical benefit with this combination for these patients. ClinicalTrials.gov identifier: NCT04497844.\n\nIndexed on Europe PMC as PubMed record 41057655 (DOI 10.1038/s41591-025-03961-8). Its abstract cites the registry id NCT04497844, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Nat Med 2025","url":"https://doi.org/10.1038/s41591-025-03961-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41057655/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41057655"},{"label":"ClinicalTrials.gov NCT04497844","url":"https://clinicaltrials.gov/study/NCT04497844"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04497844"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2025,"doi":"10.1038/s41591-025-03961-8","pmid":"41057655","authors":"Attard G, Agarwal N, Graff JN, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04497844 with the most citations, so it is the natural first reading for anyone following the AMPLITUDE trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-niraparib-ovarian-n-engl-j-med-2016","kind":"paper","name":"Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer","aka":[],"tldr":"Phase 2 or 3 results paper on Niraparib in Ovarian cancer, in New England Journal of Medicine (2016), one of the most cited Europe PMC records with Niraparib in its title.","summary":"Background: Niraparib is an oral poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) 1/2 inhibitor that has shown clinical activity in patients with ovarian cancer. We sought to evaluate the efficacy of niraparib versus placebo as maintenance treatment for patients with platinum-sensitive, recurrent ovarian cancer.\n\nMethods: In this randomized, double-blind, phase 3 trial, patients were categorized according to the presence or absence of a germline BRCA mutation (gBRCA cohort and non-gBRCA cohort) and the type of non-gBRCA mutation and were randomly assigned in a 2:1 ratio to receive niraparib (300 mg) or placebo once daily. The primary end point was progression-free survival.\n\nResults: Of 553 enrolled patients, 203 were in the gBRCA cohort (with 138 assigned to niraparib and 65 to placebo), and 350 patients were in the non-gBRCA cohort (with 234 assigned to niraparib and 116 to placebo). Patients in the niraparib group had a significantly longer median duration of progression-free survival than did those in the placebo group, including 21.0 vs. 5.5 months in the gBRCA cohort (hazard ratio, 0.27; 95% confidence interval [CI], 0.17 to 0.41), as compared with 12.9 months vs. 3.8 months in the non-gBRCA cohort for patients who had tumors with homologous recombination deficiency (HRD) (hazard ratio, 0.38; 95% CI, 0.24 to 0.59) and 9.3 months vs. 3.9 months in the overall non-gBRCA cohort (hazard ratio, 0.45; 95% CI, 0.34 to 0.61; P<0.001 for all three comparisons). The most common grade 3 or 4 adverse events that were reported in the niraparib group were thrombocytopenia (in 33.8%), anemia (in 25.3%), and neutropenia (in 19.6%), which were managed with dose modifications.\n\nConclusions: Among patients with platinum-sensitive, recurrent ovarian cancer, the median duration of progression-free survival was significantly longer among those receiving niraparib than among those receiving placebo, regardless of the presence or absence of gBRCA mutations or HRD status, with moderate bone marrow toxicity. (Funded by Tesaro; ClinicalTrials.gov number, NCT01847274.).\n\nIndexed on Europe PMC as PubMed record 27717299 (DOI 10.1056/nejmoa1611310). Its title names Niraparib and its text names Ovarian cancer; PubMed types it as a clinical trial report (Clinical Trial, Phase III, Multicenter Study, Randomized Controlled Trial). It was matched automatically to the idea \"ctDNA-guided duration of PARP maintenance\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2016","url":"https://doi.org/10.1056/nejmoa1611310"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27717299/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27717299"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2016,"doi":"10.1056/nejmoa1611310","pmid":"27717299","authors":"Mirza MR, Monk BJ, Herrstedt J, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Niraparib in Ovarian cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Niraparib in the title and Ovarian cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-gounder-n-engl-j-med","kind":"paper","name":"Nirogacestat, a γ-Secretase Inhibitor for Desmoid Tumors","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 36884323 and published in New England Journal of Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Background: Desmoid tumors are rare, locally aggressive, highly recurrent soft-tissue tumors without approved treatments.\n\nMethods: We conducted a phase 3, international, double-blind, randomized, placebo-controlled trial of nirogacestat in adults with progressing desmoid tumors according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Patients were assigned in a 1:1 ratio to receive the oral γ-secretase inhibitor nirogacestat (150 mg) or placebo twice daily. The primary end point was progression-free survival.\n\nResults: From May 2019 through August 2020, a total of 70 patients were assigned to receive nirogacestat and 72 to receive placebo. Nirogacestat had a significant progression-free survival benefit over placebo (hazard ratio for disease progression or death, 0.29; 95% confidence interval, 0.15 to 0.55; P<0.001); the likelihood of being event-free at 2 years was 76% with nirogacestat and 44% with placebo. Between-group differences in progression-free survival were consistent across prespecified subgroups. The percentage of patients who had an objective response was significantly higher with nirogacestat than with placebo (41% vs. 8%; P<0.001), with a median time to response of 5.6 months and 11.1 months, respectively; the percentage of patients with a complete response was 7% and 0%, respectively. Significant between-group differences in secondary patient-reported outcomes, including pain, symptom burden, physical or role functioning, and health-related quality of life, were observed (P≤0.01). Frequent adverse events with nirogacestat included diarrhea (in 84% of the patients), nausea (in 54%), fatigue (in 51%), hypophosphatemia (in 42%), and maculopapular rash (in 32%); 95% of adverse events were of grade 1 or 2. Among women of childbearing potential receiving nirogacestat, 27 of 36 (75%) had adverse events consistent with ovarian dysfunction, which resolved in 20 women (74%).\n\nConclusions: Nirogacestat was associated with significant benefits with respect to progression-free survival, objective response, pain, symptom burden, physical functioning, role functioning, and health-related quality of life in adults with progressing desmoid tumors. Adverse events with nirogacestat were frequent but mostly low grade. (Funded by SpringWorks Therapeutics; DeFi ClinicalTrials.gov number, NCT03785964.).\n\nIndexed on Europe PMC as PubMed record 36884323 (DOI 10.1056/nejmoa2210140). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2023","url":"https://doi.org/10.1056/nejmoa2210140"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36884323/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36884323"}],"tags":["europepmc-ingest"],"related":["desmoid-tumour"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/nejmoa2210140","pmid":"36884323","authors":"Gounder M, Ratan R, Alcindor T, et al.","paperType":"rct","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-dangelo-mucosal-melanoma-pooled-jco-2017","kind":"paper","name":"Nivolumab alone or with ipilimumab in mucosal melanoma: pooled analysis","aka":[],"tldr":"Pooling several trials showed that mucosal melanoma responds to nivolumab less often than skin melanoma, but that adding ipilimumab raised the response rate from about a quarter to more than a third, supporting combination immunotherapy first.","summary":"Pooled analysis of 889 patients from six nivolumab trials, including 86 with mucosal melanoma treated with nivolumab monotherapy and 35 with nivolumab plus ipilimumab, compared with 665 and 326 cutaneous melanoma patients.\n\nIn mucosal melanoma, objective response was 23.3 percent with nivolumab and 37.1 percent with the combination (versus 40.9 and 60.4 percent in cutaneous melanoma), with median progression-free survival 3.0 versus 5.9 months.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2017","url":"https://doi.org/10.1200/JCO.2016.67.9258"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28056206/"}],"tags":[],"related":[],"cancers":["mucosal-melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":["ipilimumab","nivolumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2017,"doi":"10.1200/JCO.2016.67.9258","pmid":"28056206","authors":"D'Angelo SP, Larkin J, Sosman JA, et al.","paperType":"observational","findings":["Mucosal melanoma objective response 23.3 percent (nivolumab) vs 37.1 percent (nivolumab plus ipilimumab).","Median progression-free survival 3.0 vs 5.9 months."],"whatItMeans":"Nivolumab plus ipilimumab is the preferred first-line immunotherapy for mucosal melanoma where tolerated, given its lower intrinsic sensitivity to single-agent PD-1 blockade.","caveats":["Retrospective pooled analysis with small mucosal cohorts."],"changedPractice":true,"participants":889},{"id":"paper-nct04969887-jama-oncol-2025","kind":"paper","name":"Nivolumab and Ipilimumab Combination Treatment in Advanced Ovarian and Endometrial Clear Cell Cancers: A Nonrandomized Clinical Trial","aka":[],"tldr":"Published report from the MOST-CIRCUIT trial registered as NCT04969887, in JAMA Oncology (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Importance: Gynecological clear cell cancers (CCCs) are aggressive malignant neoplasms with low response rate to chemotherapy. The treatment of patients with metastatic disease remains an area of significant unmet need.\n\nObjective: To evaluate the efficacy of combined anti-programmed cell death 1 protein (PD-1)/cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) blockade using nivolumab and ipilimumab in advanced gynecological CCCs.\n\nDesign, setting, and participants: The MoST-CIRCUIT prospective multicenter phase 2 nonrandomized clinical trial included patients with advanced selected rare cancers. Patients with advanced clear cell ovarian cancer (CCOC)/clear cell endometrial cancer (CCEC) with a maximum of 1 course of prior systemic therapy were enrolled from August 2021 to February 2024 across 17 Australian and New Zealand sites.\n\nInterventions: Patients received nivolumab, 3 mg/kg, and ipilimumab, 1 mg/kg, every 3 weeks for 4 doses followed by nivolumab, 480 mg, every 4 weeks for 96 weeks until disease progression or the development of unacceptable toxic effects.\n\nMain outcomes and measures: Coprimary end points were objective response rate (ORR) and 6-month progression-free survival (PFS) as assessed by RECIST version 1.1 criteria, with the secondary end points being median overall survival, PFS, and treatment-related toxic effects.\n\nResults: Of 28 included patients, the median (range) age was 55 (34-77) years. A total of 24 had CCOC and 4 had CCEC; 19 (68%) had a previous course of therapy. Overall ORR was 54% (95% CI, 35-71), with 3 (12%) with complete response and 12 (42%) with partial response; the ORR was 55% (95% CI, 35-73) in the CCOC group and 50% (95% CI, 9-91) in the CCEC group. The median duration of response has not been reached, with all responses ongoing. The 6-month PFS was 58% (95% CI, 39-74), and the median overall survival has not been reached. A total of 9 patients (35%) experienced a grade 3 or 4 immune-related adverse event, and a grade 5 myocarditis occurred in 1 patient.\n\nConclusions and relevance: In this nonrandomized clinical trial, immunotherapy using combined anti-PD-1/CTLA-4 blockade demonstrated encouraging activity with a high rate of durable responses in patients with advanced gynecological CCCs. This regimen should be further investigated in this patient population with unmet medical need.\n\nTrial registration: ClinicalTrials.gov Identifier: NCT04969887.\n\nIndexed on Europe PMC as PubMed record 40608313 (DOI 10.1001/jamaoncol.2025.1916). Its abstract cites the registry id NCT04969887, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"JAMA Oncol 2025","url":"https://doi.org/10.1001/jamaoncol.2025.1916"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40608313/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40608313"},{"label":"ClinicalTrials.gov NCT04969887","url":"https://clinicaltrials.gov/study/NCT04969887"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04969887"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2025,"doi":"10.1001/jamaoncol.2025.1916","pmid":"40608313","authors":"Gao B, Carlino MS, Michael M, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04969887 with the most citations, so it is the natural first reading for anyone following the MOST-CIRCUIT trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-brentuximab-vedotin-hodgkin-lymphoma-lancet-oncol-2016","kind":"paper","name":"Nivolumab for classical Hodgkin's lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single-arm phase 2 trial","aka":[],"tldr":"Phase 2 or 3 results paper on Brentuximab vedotin in Hodgkin lymphoma, in The Lancet Oncology (2016), one of the most cited Europe PMC records with Brentuximab vedotin in its title.","summary":"Background: Malignant cells of classical Hodgkin's lymphoma are characterised by genetic alterations at the 9p24.1 locus, leading to overexpression of PD-1 ligands and evasion of immune surveillance. In a phase 1b study, nivolumab, a PD-1-blocking antibody, produced a high response in patients with relapsed and refractory classical Hodgkin's lymphoma, with an acceptable safety profile. We aimed to assess the clinical benefit and safety of nivolumab monotherapy in patients with classical Hodgkin's lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin.\n\nMethods: In this ongoing, single-arm phase 2 study, adult patients (aged ≥18 years) with recurrent classical Hodgkin's lymphoma who had failed to respond to autologous stem-cell transplantation and had either relapsed after or failed to respond to brentuximab vedotin, and with an Eastern Cooperative Oncology Group performance status score of 0 or 1, were enrolled from 34 hospitals and academic centres across Europe and North America. Patients were given nivolumab intravenously over 60 min at 3 mg/kg every 2 weeks until progression, death, unacceptable toxicity, or withdrawal from study. The primary endpoint was objective response following a prespecified minimum follow-up period of 6 months, assessed by an independent radiological review committee (IRRC). All patients who received at least one dose of nivolumab were included in the primary and safety analyses. This trial is registered with ClinicalTrials.gov, number NCT02181738.\n\nFindings: Among 80 treated patients recruited between Aug 26, 2014, and Feb 20, 2015, the median number of previous therapies was four (IQR 4-7). At a median follow-up of 8·9 months (IQR 7·8-9·9), 53 (66·3%, 95% CI 54·8-76·4) of 80 patients achieved an IRRC-assessed objective response. The most common drug-related adverse events (those that occurred in ≥15% of patients) included fatigue (20 [25%] patients), infusion-related reaction (16 [20%]), and rash (13 [16%]). The most common drug-related grade 3 or 4 adverse events were neutropenia (four [5%] patients) and increased lipase concentrations (four [5%]). The most common serious adverse event (any grade) was pyrexia (three [4%] patients). Three patients died during the study; none of these deaths were judged to be treatment related.\n\nInterpretation: Nivolumab resulted in frequent responses with an acceptable safety profile in patients with classical Hodgkin's lymphoma who progressed after autologous stem-cell transplantation and brentuximab vedotin. Therefore, nivolumab might be a new treatment option for a patient population with a high unmet need. Ongoing follow-up will help to assess the durability of response.\n\nFunding: Bristol-Myers Squibb.\n\nIndexed on Europe PMC as PubMed record 27451390 (DOI 10.1016/s1470-2045(16)30167-x). Its title names Brentuximab vedotin and its text names Hodgkin lymphoma; PubMed types it as a clinical trial report (Clinical Trial, Phase II, research-article, Multicenter Study). It was matched automatically to the idea \"Chemotherapy-free Hodgkin lymphoma: brentuximab + PD-1 in early stage\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2016","url":"https://doi.org/10.1016/s1470-2045(16)30167-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27451390/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27451390"},{"label":"ClinicalTrials.gov NCT02181738","url":"https://clinicaltrials.gov/study/NCT02181738"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-205"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2016,"doi":"10.1016/s1470-2045(16)30167-x","pmid":"27451390","authors":"Younes A, Santoro A, Shipp M, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Brentuximab vedotin in Hodgkin lymphoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Brentuximab vedotin in the title and Hodgkin lymphoma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-overman-checkmate-142-nivolumab-dmmr-colorectal-lancet-oncol-2017","kind":"paper","name":"Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142)","aka":[],"tldr":"Seventy-four heavily pre-treated patients whose bowel cancers had lost DNA mismatch repair were given nivolumab; nearly a third responded and most of those responses were still going a year later.","summary":"In this multicentre, open-label, phase 2 trial, adults with histologically confirmed mismatch repair deficient or microsatellite instability-high metastatic colorectal cancer received nivolumab, with investigator-assessed objective response by RECIST 1.1 as the primary endpoint. Of the 74 patients enrolled between March 2014 and March 2016, 40 (54%) had received three or more previous treatments. At a median follow-up of 12.0 months, 23 patients (31.1%) achieved an objective response and 51 (69%) had disease control for 12 weeks or longer. Median duration of response was not reached, all responders were alive, and 8 had responses lasting 12 months or longer. The most common grade 3 or 4 drug-related adverse events were raised lipase (8%) and amylase (3%), and none of the 23 deaths during the study was considered treatment related.","asOf":"2026-09-24","links":[{"label":"Overman et al., Lancet Oncol 2017: CheckMate 142, nivolumab in 74 patients with dMMR/MSI-high metastatic colorectal cancer","url":"https://doi.org/10.1016/S1470-2045(17)30422-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28734759/"}],"tags":[],"related":["msi-high","dmmr-ihc"],"cancers":["colorectal"],"sections":[],"technologies":["checkpoint-inhibitor","msi-mmr-testing"],"targets":["pd1","mmr"],"drugs":["nivolumab"],"companies":[],"institutions":["md-anderson"],"pathways":["pd1-checkpoint","mismatch-repair-msi"],"terms":["msi","tumour-agnostic"],"trials":["checkmate-8hw"],"people":["scott-kopetz","thierry-andre"],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"Lancet Oncology","year":2017,"doi":"10.1016/S1470-2045(17)30422-9","pmid":"28734759","authors":"Overman MJ, McDermott R, Leach JL, et al.","paperType":"rct","findings":["Objective response in 23 of 74 patients (31.1%); disease control for 12 weeks or longer in 69%.","Median duration of response not reached; all responders alive at a median 12 months' follow-up.","Grade 3 or 4 drug-related events uncommon (raised lipase 8%)."],"whatItMeans":"It gave the second PD-1 antibody a colorectal indication in mismatch repair deficient disease and, with the ipilimumab cohort that followed, set up CheckMate 8HW and the first-line combination.","caveats":["Single-arm phase 2 with no control.","Investigator-assessed response.","Mismatch repair status was determined locally by several methods."],"changedPractice":true,"participants":74},{"id":"paper-braf-melanoma-n-engl-j-med-2015","kind":"paper","name":"Nivolumab in previously untreated melanoma without BRAF mutation","aka":[],"tldr":"Phase 2 or 3 results paper on BRAF in Melanoma, in New England Journal of Medicine (2015), one of the most cited Europe PMC records with BRAF in its title.","summary":"Background: Nivolumab was associated with higher rates of objective response than chemotherapy in a phase 3 study involving patients with ipilimumab-refractory metastatic melanoma. The use of nivolumab in previously untreated patients with advanced melanoma has not been tested in a phase 3 controlled study.\n\nMethods: We randomly assigned 418 previously untreated patients who had metastatic melanoma without a BRAF mutation to receive nivolumab (at a dose of 3 mg per kilogram of body weight every 2 weeks and dacarbazine-matched placebo every 3 weeks) or dacarbazine (at a dose of 1000 mg per square meter of body-surface area every 3 weeks and nivolumab-matched placebo every 2 weeks). The primary end point was overall survival.\n\nResults: At 1 year, the overall rate of survival was 72.9% (95% confidence interval [CI], 65.5 to 78.9) in the nivolumab group, as compared with 42.1% (95% CI, 33.0 to 50.9) in the dacarbazine group (hazard ratio for death, 0.42; 99.79% CI, 0.25 to 0.73; P<0.001). The median progression-free survival was 5.1 months in the nivolumab group versus 2.2 months in the dacarbazine group (hazard ratio for death or progression of disease, 0.43; 95% CI, 0.34 to 0.56; P<0.001). The objective response rate was 40.0% (95% CI, 33.3 to 47.0) in the nivolumab group versus 13.9% (95% CI, 9.5 to 19.4) in the dacarbazine group (odds ratio, 4.06; P<0.001). The survival benefit with nivolumab versus dacarbazine was observed across prespecified subgroups, including subgroups defined by status regarding the programmed death ligand 1 (PD-L1). Common adverse events associated with nivolumab included fatigue, pruritus, and nausea. Drug-related adverse events of grade 3 or 4 occurred in 11.7% of the patients treated with nivolumab and 17.6% of those treated with dacarbazine.\n\nConclusions: Nivolumab was associated with significant improvements in overall survival and progression-free survival, as compared with dacarbazine, among previously untreated patients who had metastatic melanoma without a BRAF mutation. (Funded by Bristol-Myers Squibb; CheckMate 066 ClinicalTrials.gov number, NCT01721772.).\n\nIndexed on Europe PMC as PubMed record 25399552 (DOI 10.1056/nejmoa1412082). Its title names BRAF and its text names Melanoma; PubMed types it as a clinical trial report (Clinical Trial, Phase III, Comparative Study, Research Support, Non-U.S. Gov't, Randomized Controlled Trial). It was matched automatically to the idea \"Test intermittent dosing of targeted drugs to delay resistance, with honest priors\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2015","url":"https://doi.org/10.1056/nejmoa1412082"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25399552/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25399552"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2015,"doi":"10.1056/nejmoa1412082","pmid":"25399552","authors":"Robert C, Long GV, Brady B, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for BRAF in Melanoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by BRAF in the title and Melanoma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-azad-j-clin-oncol","kind":"paper","name":"Nivolumab Is Effective in Mismatch Repair-Deficient Noncolorectal Cancers: Results From Arm Z1D-A Subprotocol of the NCI-MATCH (EAY131) Study","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 31765263 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: The National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) trial, the largest national precision oncology study to date (> 1,100 sites) of patients with relapsed or refractory malignancies, assigned patients to targeted therapy in parallel phase II studies based on tumor molecular alterations. The anti-programmed death receptor 1 inhibitor nivolumab previously showed activity in mismatch repair (MMR)-deficient colon cancer. We hypothesized that nivolumab would have activity in patients with MMR-deficient, noncolorectal tumors.\n\nPatients and methods: Eligible patients with relapsed or refractory tumors, good end-organ function, and Eastern Cooperative Oncology Group performance status of ≤ 1 underwent tumor biopsy for centralized screening of molecular alterations. MMR deficiency was defined by complete loss of nuclear expression of MLH1 or MSH2 MMR gene products by immunohistochemistry (IHC). Patients with MMR-deficient colorectal cancer were excluded. Nivolumab, 3 mg/kg every 2 weeks (28-day cycles) and 480 mg every 4 weeks after cycle 4, was administered intravenously. Disease reassessment was performed every 2 cycles. The primary end point was RECIST 1.1 objective response rate (ORR).\n\nResults: Two percent of 4,902 screened patients had an MMR-deficient cancer by IHC. Forty-two evaluable patients were enrolled, with a median age of 60 years and a median of 3 prior therapies. The most common histologies were endometrioid endometrial adenocarcinoma (n = 13), prostate adenocarcinoma (n = 5), and uterine carcinosarcoma (n = 4). ORR was 36% (15 of 42 patients). An additional 21% of patients had stable disease. The estimated 6-, 12-, and 18-month progression-free survival rates were 51.3% (90% CI, 38.2% to 64.5%), 46.2% (90% CI, 33.1% to 59.3%), and 31.4% (90% CI, 18.7% to 44.2%), respectively. Median overall survival was 17.3 months. Toxicity was predominantly low grade.\n\nConclusion: A variety of refractory cancers (2.0% of those screened) had MMR deficiency as defined in NCI-MATCH. Nivolumab has promising activity in MMR-deficient noncolorectal cancers of a wide variety of histopathologic types.\n\nIndexed on Europe PMC as PubMed record 31765263 (DOI 10.1200/jco.19.00818). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2020","url":"https://doi.org/10.1200/jco.19.00818"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31765263/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31765263"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nci-match"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/jco.19.00818","pmid":"31765263","authors":"Azad NS, Gray RJ, Overman MJ, et al.","paperType":"observational","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-keunchil-park-n-engl-j-med-2019","kind":"paper","name":"Nivolumab plus Ipilimumab in Advanced Non-Small-Cell Lung Cancer","aka":[],"tldr":"Paper by Keunchil Park indexed on Europe PMC as PubMed record 31562796, in New England Journal of Medicine (2019), one of the most cited records naming an author with this name at Samsung Medical Center.","summary":"Background: In an early-phase study involving patients with advanced non-small-cell lung cancer (NSCLC), the response rate was better with nivolumab plus ipilimumab than with nivolumab monotherapy, particularly among patients with tumors that expressed programmed death ligand 1 (PD-L1). Data are needed to assess the long-term benefit of nivolumab plus ipilimumab in patients with NSCLC.\n\nMethods: In this open-label, phase 3 trial, we randomly assigned patients with stage IV or recurrent NSCLC and a PD-L1 expression level of 1% or more in a 1:1:1 ratio to receive nivolumab plus ipilimumab, nivolumab alone, or chemotherapy. The patients who had a PD-L1 expression level of less than 1% were randomly assigned in a 1:1:1 ratio to receive nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy alone. All the patients had received no previous chemotherapy. The primary end point reported here was overall survival with nivolumab plus ipilimumab as compared with chemotherapy in patients with a PD-L1 expression level of 1% or more.\n\nResults: Among the patients with a PD-L1 expression level of 1% or more, the median duration of overall survival was 17.1 months (95% confidence interval [CI], 15.0 to 20.1) with nivolumab plus ipilimumab and 14.9 months (95% CI, 12.7 to 16.7) with chemotherapy (P = 0.007), with 2-year overall survival rates of 40.0% and 32.8%, respectively. The median duration of response was 23.2 months with nivolumab plus ipilimumab and 6.2 months with chemotherapy. The overall survival benefit was also observed in patients with a PD-L1 expression level of less than 1%, with a median duration of 17.2 months (95% CI, 12.8 to 22.0) with nivolumab plus ipilimumab and 12.2 months (95% CI, 9.2 to 14.3) with chemotherapy. Among all the patients in the trial, the median duration of overall survival was 17.1 months (95% CI, 15.2 to 19.9) with nivolumab plus ipilimumab and 13.9 months (95% CI, 12.2 to 15.1) with chemotherapy. The percentage of patients with grade 3 or 4 treatment-related adverse events in the overall population was 32.8% with nivolumab plus ipilimumab and 36.0% with chemotherapy.\n\nConclusions: First-line treatment with nivolumab plus ipilimumab resulted in a longer duration of overall survival than did chemotherapy in patients with NSCLC, independent of the PD-L1 expression level. No new safety concerns emerged with longer follow-up. (Funded by Bristol-Myers Squibb and Ono Pharmaceutical; CheckMate 227 ClinicalTrials.gov number, NCT02477826.).\n\nIndexed on Europe PMC as PubMed record 31562796 (DOI 10.1056/nejmoa1910231). Its author list gives \"Park K\" with the affiliation \"From the Memorial Sloan Kettering Cancer Center, New York (M.D.H.); Hospital Universitario Doce de Octubre, Centro Nacional de Investigaciones Oncológicas, Universidad Complutense, and Centro de Investigación Biomédica en Red de Cáncer, Madrid (L.P.-A.), Hospital Universitario Virgen Del Rocio, Seville (R.B.C.), and the Catalan Institute of Oncology-Germans Trias i Pujol Hospital, Badalona (E.C.C.) - all in Spain; Ambulatorium Chemioterapii, Bydgoszcz, Poland (B.Z.); the Asan Medical Center (S.-W.K.) and the Samsung Medical Center at Sungkyunkwan University School of Medicine (K.P.) - both in Seoul, South Korea; the Institute of Oncology Prof. Dr. Alexandru Trestioreanu, Bucharest, Romania (A.A.); the Hospital Italiano de Buenos Aires, Buenos Aires (L.L.); Instituto Jalisciense de Cancerologia, Guadalajara, Mexico (E.M.J.); the Saitama Cancer Center, Saitama, Japan (H.S.); Matrai Gyogyintezet, Matrahaza, Hungary (I.A.); Limoges University Hospital, Limoges (A.V.), and Aix-Marseille University, National Center for Scientific Research, INSERM, Centre de Recherche en Cancérologie de Marseille, Assistance Publique-Hôpitaux de Marseille, Marseille (F.B.) - all in France; Centre Hospitalier Universitaire Vaudois, Lausanne University, Lausanne, Switzerland (S.P.); Sotiria General Hospital, National and Kapodistrian University of Athens, Athens (K.S.); Lung Clinic Grosshansdorf, Airway Research Center North, German Center of Lung Research, Grosshansdorf, Germany (M.R.); Fox Chase Cancer Center, Philadelphia (H.B.); Johns Hopkins Kimmel Cancer Center, Baltimore (J.R.B.); Princess Alexandra Hospital, Brisbane, QLD, Australia (K.J.O.); Bristol-Myers Squibb, Princeton, NJ (W.J.G., P.B., S.K.R., R.S.K., F.E.N.); and Winship Cancer Institute, Emory University, Atlanta (S.S.R.)\", which names Samsung Medical Center; that is how the record was matched to Keunchil Park, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2019","url":"https://doi.org/10.1056/nejmoa1910231"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31562796/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31562796"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["keunchil-park"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2019,"doi":"10.1056/nejmoa1910231","pmid":"31562796","authors":"Hellmann MD, Paz-Ares L, Bernabe Caro R, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Keunchil Park at Samsung Medical Center, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-checkmate-227-n-engl-j-med-2018","kind":"paper","name":"Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden","aka":[],"tldr":"Published report from the CheckMate 227 trial registered as NCT02477826, in New England Journal of Medicine (2018), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Nivolumab plus ipilimumab showed promising efficacy for the treatment of non-small-cell lung cancer (NSCLC) in a phase 1 trial, and tumor mutational burden has emerged as a potential biomarker of benefit. In this part of an open-label, multipart, phase 3 trial, we examined progression-free survival with nivolumab plus ipilimumab versus chemotherapy among patients with a high tumor mutational burden (≥10 mutations per megabase).\n\nMethods: We enrolled patients with stage IV or recurrent NSCLC that was not previously treated with chemotherapy. Those with a level of tumor programmed death ligand 1 (PD-L1) expression of at least 1% were randomly assigned, in a 1:1:1 ratio, to receive nivolumab plus ipilimumab, nivolumab monotherapy, or chemotherapy; those with a tumor PD-L1 expression level of less than 1% were randomly assigned, in a 1:1:1 ratio, to receive nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy. Tumor mutational burden was determined by the FoundationOne CDx assay.\n\nResults: Progression-free survival among patients with a high tumor mutational burden was significantly longer with nivolumab plus ipilimumab than with chemotherapy. The 1-year progression-free survival rate was 42.6% with nivolumab plus ipilimumab versus 13.2% with chemotherapy, and the median progression-free survival was 7.2 months (95% confidence interval [CI], 5.5 to 13.2) versus 5.5 months (95% CI, 4.4 to 5.8) (hazard ratio for disease progression or death, 0.58; 97.5% CI, 0.41 to 0.81; P<0.001). The objective response rate was 45.3% with nivolumab plus ipilimumab and 26.9% with chemotherapy. The benefit of nivolumab plus ipilimumab over chemotherapy was broadly consistent within subgroups, including patients with a PD-L1 expression level of at least 1% and those with a level of less than 1%. The rate of grade 3 or 4 treatment-related adverse events was 31.2% with nivolumab plus ipilimumab and 36.1% with chemotherapy. ical; CheckMate 227 ClinicalTrials.gov number, NCT02477826.).\n\nConclusions: Progression-free survival was significantly longer with first-line nivolumab plus ipilimumab than with chemotherapy among patients with NSCLC and a high tumor mutational burden, irrespective of PD-L1 expression level. The results validate the benefit of nivolumab plus ipilimumab in NSCLC and the role of tumor mutational burden as a biomarker for patient selection. (Funded by Bristol-Myers Squibb and Ono Pharmaceut\n\nIndexed on Europe PMC as PubMed record 29658845 (DOI 10.1056/nejmoa1801946). Its abstract cites the registry id NCT02477826, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2018","url":"https://doi.org/10.1056/nejmoa1801946"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29658845/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29658845"},{"label":"ClinicalTrials.gov NCT02477826","url":"https://clinicaltrials.gov/study/NCT02477826"}],"tags":["europepmc-ingest"],"related":["tmb-high","pd-l1-tc-score"],"cancers":[],"sections":[],"technologies":["tmb-testing","checkpoint-inhibitor"],"targets":["pdl1","pd1","ctla4"],"drugs":[],"companies":[],"institutions":[],"pathways":["pd1-checkpoint","cancer-immunity-cycle"],"terms":["tmb"],"trials":["checkmate-227"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2018,"doi":"10.1056/nejmoa1801946","pmid":"29658845","authors":"Hellmann MD, Ciuleanu TE, Pluzanski A, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02477826 with the most citations, so it is the natural first reading for anyone following the CheckMate 227 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-andre-checkmate-8hw-nivolumab-ipilimumab-nejm-2024","kind":"paper","name":"Nivolumab plus ipilimumab in microsatellite-instability-high metastatic colorectal cancer (CheckMate 8HW)","aka":[],"tldr":"Two immunotherapy drugs together kept 72 percent of patients progression-free at two years against 14 percent on chemotherapy, the largest effect size of any first-line trial in colorectal cancer.","summary":"André, Elez, Van Cutsem and colleagues randomly assigned patients with unresectable or metastatic colorectal cancer and locally determined microsatellite-instability-high or mismatch repair-deficient status 2:2:1 to nivolumab plus ipilimumab, nivolumab alone, or chemotherapy with or without targeted therapies. The dual primary end points, assessed in patients with centrally confirmed status, were progression-free survival with the combination against chemotherapy in the first line and against nivolumab alone regardless of previous treatment; this prespecified interim analysis reports the first.\n\nA total of 303 previously untreated patients were randomised to the combination or chemotherapy, and 255 had centrally confirmed microsatellite-instability-high or mismatch repair-deficient tumours.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2024","url":"https://doi.org/10.1056/NEJMoa2402141"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39602630/"},{"label":"N Engl J Med 2024","url":"https://doi.org/10.1056/nejmoa2402141"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39602630"},{"label":"ClinicalTrials.gov NCT04008030","url":"https://clinicaltrials.gov/study/NCT04008030"}],"tags":["colorectal-evidence"],"related":["paper-keynote-177-nejm-2020","paper-niche-2-nejm-2024"],"cancers":["colorectal","msi-high-colorectal"],"sections":["immunotherapy"],"technologies":["checkpoint-inhibitor"],"targets":["pd1","ctla4"],"drugs":["nivolumab","ipilimumab"],"companies":["bms"],"institutions":[],"pathways":[],"terms":["msi","mmr"],"trials":["checkmate-8hw"],"people":["thierry-andre","eric-van-cutsem","heinz-josef-lenz","myriam-chalabi","yoshino-takayuki"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2024,"doi":"10.1056/NEJMoa2402141","pmid":"39602630","authors":"André T, Elez E, Van Cutsem E, et al.","paperType":"rct","findings":["At a median 31.5 months, 24-month progression-free survival 72 percent (95 percent CI 64 to 79) with nivolumab plus ipilimumab against 14 percent (6 to 25) with chemotherapy (p<0.001).","At 24 months, restricted mean survival time was 10.6 months (8.4 to 12.9) longer with the combination.","Grade 3 or 4 treatment-related adverse events in 23 percent of the combination group against 48 percent of the chemotherapy group."],"whatItMeans":"Combination checkpoint blockade became a first-line standard for mismatch repair-deficient metastatic colorectal cancer in 2025; the later all-lines comparison against nivolumab alone showed the CTLA-4 antibody adds to the PD-1 antibody, the first phase 3 to prove that in this disease.","caveats":["Interim analysis of the first of two primary endpoints; overall survival is not mature.","Eligibility used local testing, and 48 of 303 randomised patients did not have centrally confirmed status.","No randomised comparison against pembrolizumab, so the choice between single and dual checkpoint blockade rests on cross-trial comparison."],"changedPractice":true,"participants":303},{"id":"paper-lung-map-s1400i-jama-oncol-2021","kind":"paper","name":"Nivolumab Plus Ipilimumab vs Nivolumab for Previously Treated Patients With Stage IV Squamous Cell Lung Cancer: The Lung-MAP S1400I Phase 3 Randomized Clinical Trial","aka":[],"tldr":"Published report from the S1400I trial registered as NCT02785952, in JAMA Oncology (2021), chosen as the most cited paper whose own text cites the registry id.","summary":"Importance: Nivolumab plus ipilimumab is superior to platinum-based chemotherapy in treatment-naive advanced non-small cell lung cancer (NSCLC). Nivolumab is superior to docetaxel in advanced pretreated NSCLC.\n\nObjective: To determine whether the addition of ipilimumab to nivolumab improves survival in patients with advanced, pretreated, immunotherapy-naive squamous (Sq) NSCLC.\n\nDesign, setting, and participants: The Lung Cancer Master Protocol (Lung-MAP) S1400I phase 3, open-label randomized clinical trial was conducted from December 18, 2015, to April 23, 2018, randomizing patients in a 1:1 ratio to nivolumab alone or combined with ipilimumab. The median follow-up in surviving patients was 29.5 months. The trial was conducted through the National Clinical Trials Network and included patients with advanced immunotherapy-naive SqNSCLC and a Zubrod score of 0 (asymptomatic) to 1 (symptomatic but completely ambulatory) with disease progression after standard platinum-based chemotherapy. Randomization was stratified by sex and number of prior therapies (1 vs 2 or more). Data were analyzed from May 3, 2018, to February 1, 2021.\n\nInterventions: Nivolumab, 3 mg/kg intravenously every 2 weeks, with or without ipilimumab, 1 mg/kg intravenously every 6 weeks, until disease progression or intolerable toxic effects.\n\nMain outcomes and measures: The primary end point was overall survival (OS). Secondary end points included investigator-assessed progression-free survival (IA-PFS) and response per Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, version 1.1.\n\nResults: Of 275 enrolled patients, 252 (mean age, 67.5 years [range 41.8-90.3 years]; 169 men [67%]; 206 White patients [82%]) were deemed eligible (125 randomized to nivolumab/ipilimumab and 127 to nivolumab). The study was closed for futility at a planned interim analysis. Overall survival was not significantly different between the groups (hazard ratio [HR], 0.87; 95% CI, 0.66-1.16; P =.34). Median survival was 10 months (95% CI, 8.0-14.4 months) in the nivolumab/ipilimumab group and 11 months (95% CI, 8.6-13.7 months) in the nivolumab group. The IA-PFS HR was 0.80 (95% CI, 0.61-1.03; P =.09); median IA-PFS was 3.8 months (95% CI, 2.7-4.4 months) in the nivolumab/ipilimumab group and 2.9 months (95% CI, 1.8-4.0 months) in the nivolumab alone group. Response rates were 18% (95% CI, 12%-25%) with nivolumab/ipilimumab and 17% (95% CI, 10%-23%) with nivolumab. Median response duration was 28.4 months (95% CI, 4.9 months to not reached) with nivolumab/ipilimumab and 9.7 months with nivolumab (95% CI, 4.2-23.1 months). Grade 3 or higher treatment-related adverse events occurred in 49 of 124 patients (39.5%) who received nivolumab/ipilimumab and in 41 of 123 (33.3%) who received nivolumab alone. Toxic effects led to discontinuation in 31 of 124 patients (25%) on nivolumab/ipilimumab and in 19 of 123 (15%) on nivolumab.\n\nConclusions and relevance: In this phase 3 randomized clinical trial, ipilimumab added to nivolumab did not improve outcomes in patients with advanced, pretreated, immune checkpoint inhibitor-naive SqNSCLC.\n\nTrial registration: ClinicalTrials.gov Identifier: NCT02785952.\n\nIndexed on Europe PMC as PubMed record 34264316 (DOI 10.1001/jamaoncol.2021.2209). Its abstract cites the registry id NCT02785952, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"JAMA Oncol 2021","url":"https://doi.org/10.1001/jamaoncol.2021.2209"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34264316/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34264316"},{"label":"ClinicalTrials.gov NCT02785952","url":"https://clinicaltrials.gov/study/NCT02785952"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["lung-map-s1400i"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2021,"doi":"10.1001/jamaoncol.2021.2209","pmid":"34264316","authors":"Gettinger SN, Redman MW, Bazhenova L, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02785952 with the most citations, so it is the natural first reading for anyone following the S1400I trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-dizman-nat-med","kind":"paper","name":"Nivolumab plus ipilimumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 35228755 and published in Nature Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Previous studies have suggested that the gut microbiome influences the response to checkpoint inhibitors (CPIs) in patients with cancer. CBM588 is a bifidogenic live bacterial product that we postulated could augment CPI response through modulation of the gut microbiome. In this open-label, single-center study (NCT03829111), 30 treatment-naive patients with metastatic renal cell carcinoma with clear cell and/or sarcomatoid histology and intermediate- or poor-risk disease were randomized 2:1 to receive nivolumab and ipilimumab with or without daily oral CBM588, respectively. Stool metagenomic sequencing was performed at multiple timepoints. The primary endpoint to compare the relative abundance of Bifidobacterium spp. at baseline and at 12 weeks was not met, and no significant differences in Bifidobacterium spp. or Shannon index associated with the addition of CBM588 to nivolumab-ipilimumab were detected. Secondary endpoints included response rate, progression-free survival (PFS) and toxicity. PFS was significantly longer in patients receiving nivolumab-ipilimumab with CBM588 than without (12.7 months versus 2.5 months, hazard ratio 0.15, 95% confidence interval 0.05-0.47, P = 0.001). Although not statistically significant, the response rate was also higher in patients receiving CBM588 (58% versus 20%, P = 0.06). No significant difference in toxicity was observed between the study arms. The data suggest that CBM588 appears to enhance the clinical outcome in patients with metastatic renal cell carcinoma treated with nivolumab-ipilimumab. Larger studies are warranted to confirm this clinical observation and elucidate the mechanism of action and the effects on microbiome and immune compartments.\n\nIndexed on Europe PMC as PubMed record 35228755 (DOI 10.1038/s41591-022-01694-6). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Med 2022","url":"https://doi.org/10.1038/s41591-022-01694-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35228755/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35228755"}],"tags":["europepmc-ingest"],"related":["probiotics-antibiotic-stewardship-io"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2022,"doi":"10.1038/s41591-022-01694-6","pmid":"35228755","authors":"Dizman N, Meza L, Bergerot P, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-morvan-nat-rev-cancer","kind":"paper","name":"NK cells and cancer: you can teach innate cells new tricks","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 26694935 and published in Nature Reviews Cancer; the citing page links this DOI, which is how the record was matched.","summary":"Natural killer (NK) cells are the prototype innate lymphoid cells endowed with potent cytolytic function that provide host defence against microbial infection and tumours. Here, we review evidence for the role of NK cells in immune surveillance against cancer and highlight new therapeutic approaches for targeting NK cells in the treatment of cancer.\n\nIndexed on Europe PMC as PubMed record 26694935 (DOI 10.1038/nrc.2015.5). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Cancer 2016","url":"https://doi.org/10.1038/nrc.2015.5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26694935/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26694935"}],"tags":["europepmc-ingest"],"related":["nk-cell-recognition"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Cancer","year":2016,"doi":"10.1038/nrc.2015.5","pmid":"26694935","authors":"Morvan MG, Lanier LL","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nlst-nejm-2011","kind":"paper","name":"NLST: yearly low-dose CT scans cut lung cancer deaths in heavy smokers","aka":[],"tldr":"Three annual low-dose CT scans reduced lung cancer deaths by a fifth compared with chest X-rays in current and former heavy smokers.","summary":"The National Lung Screening Trial randomised 53,454 current or former smokers aged 55-74 with at least 30 pack-years to three annual screens with low-dose helical CT or chest radiography at 33 US centres.\n\nThe primary endpoint was lung cancer mortality. After a median 6.5 years of follow-up there were 247 lung cancer deaths per 100,000 person-years in the CT arm and 309 in the radiography arm, a 20% relative reduction; all-cause mortality also fell by 6.7%. The trial was stopped early for benefit.\n\nNLST is the evidence base for US Preventive Services Task Force lung screening recommendations and for national programmes that followed.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1056/NEJMoa1102873"},{"label":"ClinicalTrials.gov NCT00047385","url":"https://clinicaltrials.gov/study/NCT00047385"}],"tags":[],"related":["cdas-nlst-plco","idea-prev-lung-screening-risk-model-eligibility","idea-prev-mobile-lung-screening-deprived-areas","lung-cancer-evidence-roadmap","paper-plco-chest-radiograph-lung-cancer-mortality-jama-2011","paper-uspstf-lung-cancer-screening-jama-2021","idea-lung-screening-eligibility-by-risk-not-pack-years"],"cancers":["nsclc","sclc","lung-cancer"],"sections":["early-detection","prevention"],"technologies":["low-dose-ct-screening","ct"],"targets":[],"drugs":[],"companies":[],"institutions":["nci"],"pathways":[],"terms":["ppv","stage-shift"],"trials":["nlst-nelson"],"people":[],"bottlenecks":["b-early-detection","b-overdiagnosis","b-prevention-adoption"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2011,"doi":"10.1056/NEJMoa1102873","pmid":"21714641","authors":"Aberle DR, Adams AM, Berg CD, et al. (National Lung Screening Trial Research Team)","paperType":"rct","findings":["Lung cancer mortality reduced by 20.0% (95% CI 6.8-26.7) with low-dose CT versus chest radiography","All-cause mortality reduced by 6.7% (95% CI 1.2-13.6)","24.2% of CT screens were positive, and 96.4% of positive screens were false positives","Roughly 320 people had to be screened to prevent one lung cancer death over the trial period"],"whatItMeans":"For people with a heavy smoking history, an annual low-dose CT scan is one of the few screening tests proven to reduce cancer deaths. Most abnormal scans are not cancer, so screening must be paired with careful nodule management. It does not apply to never-smokers or light smokers.","caveats":["High false-positive rate with the 4 mm nodule threshold used in 2002-2004; modern Lung-RADS criteria reduce this","Comparator was chest X-ray, itself of no proven benefit, so the effect versus no screening may differ","Participants were younger, better educated and more often former smokers than the US smoking population","Uptake of screening among eligible people remains low in most countries"],"changedPractice":true,"participants":53454},{"id":"paper-mcculloch-lancet","kind":"paper","name":"No surgical innovation without evaluation: the IDEAL recommendations","aka":[],"tldr":"Paper cited by one bottleneck page, indexed on Europe PMC as PubMed record 19782876 and published in The Lancet; the citing page links this DOI, which is how the record was matched.","summary":"Surgery and other invasive therapies are complex interventions, the assessment of which is challenged by factors that depend on operator, team, and setting, such as learning curves, quality variations, and perception of equipoise. We propose recommendations for the assessment of surgery based on a five-stage description of the surgical development process. We also encourage the widespread use of prospective databases and registries. Reports of new techniques should be registered as a professional duty, anonymously if necessary when outcomes are adverse. Case series studies should be replaced by prospective development studies for early technical modifications and by prospective research databases for later pre-trial evaluation. Protocols for these studies should be registered publicly. Statistical process control techniques can be useful in both early and late assessment. Randomised trials should be used whenever possible to investigate efficacy, but adequate pre-trial data are essential to allow power calculations, clarify the definition and indications of the intervention, and develop quality measures. Difficulties in doing randomised clinical trials should be addressed by measures to evaluate learning curves and alleviate equipoise problems. Alternative prospective designs, such as interrupted time series studies, should be used when randomised trials are not feasible. Established procedures should be monitored with prospective databases to analyse outcome variations and to identify late and rare events. Achievement of improved design, conduct, and reporting of surgical research will need concerted action by editors, funders of health care and research, regulatory bodies, and professional societies.\n\nIndexed on Europe PMC as PubMed record 19782876 (DOI 10.1016/s0140-6736(09)61116-8). Matched by DOI alone: one bottleneck page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet 2009","url":"https://doi.org/10.1016/s0140-6736(09)61116-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19782876/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/19782876"}],"tags":["europepmc-ingest"],"related":["b-surgery-radiation-innovation"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2009,"doi":"10.1016/s0140-6736(09)61116-8","pmid":"19782876","authors":"McCulloch P, Altman DG, Campbell WB, et al.","paperType":"rct","findings":[],"whatItMeans":"One bottleneck page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-noa-08-temozolomide-vs-radiotherapy-elderly-wick-lancet-oncol-2012","kind":"paper","name":"NOA-08: temozolomide alone versus radiotherapy alone for malignant astrocytoma in the elderly","aka":[],"tldr":"Older people with glioblastoma lived as long on temozolomide tablets as on radiotherapy, and the MGMT test showed who should get which: methylated tumours did better with the chemotherapy and unmethylated tumours with radiotherapy.","summary":"Randomised phase 3 non-inferiority trial of the German Neuro-oncology Working Group in 412 patients over 65 with anaplastic astrocytoma or glioblastoma, comparing dose-dense temozolomide (one week on, one week off) with radiotherapy of 60 Gy; 373 patients were treated and analysed.\n\nMedian overall survival was 8.6 months with temozolomide against 9.6 months with radiotherapy (hazard ratio 1.09), meeting non-inferiority, and event-free survival did not differ. MGMT promoter methylation was associated with longer survival and predicted benefit from temozolomide (event-free survival 8.4 against 4.6 months), while unmethylated tumours did better with radiotherapy (3.3 against 4.6 months).","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2012","url":"https://doi.org/10.1016/S1470-2045(12)70164-X"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22578793/"}],"tags":[],"related":[],"cancers":["glioblastoma"],"sections":[],"technologies":[],"targets":[],"drugs":["temozolomide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["noa-08"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2012,"doi":"10.1016/S1470-2045(12)70164-X","pmid":"22578793","authors":"Wick W, Platten M, Meisner C, et al.","paperType":"rct","findings":["Median overall survival 8.6 months (95% CI 7.3 to 10.2) with temozolomide versus 9.6 months (8.2 to 10.8) with radiotherapy; hazard ratio 1.09 (0.84 to 1.42), non-inferior.","MGMT promoter methylation: event-free survival 8.4 months with temozolomide versus 4.6 with radiotherapy; unmethylated: 3.3 versus 4.6 months.","More grade 3 to 4 haematological toxicity, infections and thromboembolic events with temozolomide."],"whatItMeans":"With the Nordic trial, NOA-08 made MGMT testing the way to choose between temozolomide alone and radiotherapy alone for older patients with glioblastoma who are not offered combined treatment.","caveats":["Non-inferiority design with a dose-dense temozolomide schedule that is no longer standard.","The combined short-course radiotherapy plus temozolomide approach was tested separately (CE.6) and is preferred for fit older patients."],"changedPractice":true,"participants":412},{"id":"paper-wang-adjuvant-chemoradiotherapy-nomogram-gallbladder-cancer-jco-2011","kind":"paper","name":"Nomogram for predicting the benefit of adjuvant chemoradiotherapy for resected gallbladder cancer","aka":[],"tldr":"Using US Medicare records from 1,137 older patients, a calculator was built to estimate who might gain from radiotherapy with chemotherapy after gallbladder cancer surgery; it points to those whose tumour had reached the muscle layer or the nodes.","summary":"SEER-Medicare analysis of patients with resected gallbladder cancer diagnosed 1995 to 2005 (1,137 met inclusion criteria), with propensity score weighting to balance covariates between those who did and did not receive adjuvant chemotherapy or chemoradiotherapy. Several parametric survival models were compared; a lognormal model performed best and was built into a web-based nomogram for individualised survival estimates. The model predicts that certain subsets with at least T2 or N1 disease gain a survival benefit from adjuvant chemoradiotherapy, with the size of benefit varying between individuals.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2011","url":"https://doi.org/10.1200/JCO.2010.33.8020"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22067404/"}],"tags":["gallbladder-evidence"],"related":["paper-swog-s0809-adjuvant-chemoradiation-jco-2015"],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["chemoradiation","radiotherapy","neoadjuvant-adjuvant"],"trials":[],"people":[],"bottlenecks":["b-surgery-radiation-innovation"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2011,"doi":"10.1200/JCO.2010.33.8020","pmid":"22067404","authors":"Wang SJ, Lemieux A, Kalpathy-Cramer J, et al.","paperType":"observational","findings":["1,137 SEER-Medicare patients with resected gallbladder cancer, 1995 to 2005.","Model predicts adjuvant chemoradiotherapy benefit for subsets with at least T2 or N1 disease."],"whatItMeans":"The observational basis, with SWOG S0809, for offering chemoradiation after node-positive or margin-positive resection in the United States. UK practice rarely does so; a randomised trial has never been run.","caveats":["Registry data on patients over 65 with treatment selection bias that weighting cannot fully remove.","Pre-dates modern chemotherapy and staging."],"changedPractice":false,"participants":1137},{"id":"paper-esmo-non-epithelial-ovarian-ray-coquard-ann-oncol-2018","kind":"paper","name":"Non-epithelial ovarian cancer: ESMO clinical practice guidelines","aka":[],"tldr":"The ESMO guideline on the rarer ovarian cancers, including granulosa cell and other sex cord-stromal tumours and germ cell tumours, sets out surgery, when chemotherapy is needed, fertility preservation and long-term follow-up.","summary":"Evidence-based guideline covering diagnosis, staging, surgical management including fertility-sparing surgery, adjuvant and recurrent-disease chemotherapy, hormonal therapy and follow-up for malignant germ cell tumours and sex cord-stromal tumours of the ovary.","asOf":"2026-09-17","links":[{"label":"Ann Oncol 2018","url":"https://doi.org/10.1093/annonc/mdy001"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29697741/"}],"tags":[],"related":[],"cancers":["granulosa-cell-tumour"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2018,"doi":"10.1093/annonc/mdy001","pmid":"29697741","authors":"Ray-Coquard I, Morice P, Lorusso D, et al.","paperType":"guideline","findings":[],"whatItMeans":"The observation after complete surgery for stage I granulosa cell tumour, lifelong inhibin monitoring and endocrine or bevacizumab-based options at relapse follow this guideline.","caveats":["Evidence in sex cord-stromal tumours is largely retrospective."],"changedPractice":true},{"id":"paper-chang-nat-rev-mol-cell-biol","kind":"paper","name":"Non-homologous DNA end joining and alternative pathways to double-strand break repair","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 28512351 and published in Nature reviews. Molecular cell biology; the citing page links this DOI, which is how the record was matched.","summary":"DNA double-strand breaks (DSBs) are the most dangerous type of DNA damage because they can result in the loss of large chromosomal regions. In all mammalian cells, DSBs that occur throughout the cell cycle are repaired predominantly by the non-homologous DNA end joining (NHEJ) pathway. Defects in NHEJ result in sensitivity to ionizing radiation and the ablation of lymphocytes. The NHEJ pathway utilizes proteins that recognize, resect, polymerize and ligate the DNA ends in a flexible manner. This flexibility permits NHEJ to function on a wide range of DNA-end configurations, with the resulting repaired DNA junctions often containing mutations. In this Review, we discuss the most recent findings regarding the relative involvement of the different NHEJ proteins in the repair of various DNA-end configurations. We also discuss the shunting of DNA-end repair to the auxiliary pathways of alternative end joining (a-EJ) or single-strand annealing (SSA) and the relevance of these different pathways to human disease.\n\nIndexed on Europe PMC as PubMed record 28512351 (DOI 10.1038/nrm.2017.48). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Mol Cell Biol 2017","url":"https://doi.org/10.1038/nrm.2017.48"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28512351/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28512351"}],"tags":["europepmc-ingest"],"related":["homologous-recombination-repair"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature reviews. Molecular cell biology","year":2017,"doi":"10.1038/nrm.2017.48","pmid":"28512351","authors":"Chang HHY, Pannunzio NR, Adachi N, et al.","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-jones-non-v600-braf-colorectal-jco-2017","kind":"paper","name":"Non-V600 BRAF mutations define a clinically distinct molecular subtype of metastatic colorectal cancer","aka":[],"tldr":"Not every BRAF mutation is the notorious one. The other 22% of BRAF-mutant bowel cancers occur in younger patients, on the left, and live five times longer than the V600E group.","summary":"A multicentre retrospective cohort study pooled patients with non-V600 BRAF mutations from next-generation sequencing databases at three large molecular genetics reference laboratories. Of 9,643 patients with metastatic colorectal cancer tested, 208 had non-V600 BRAF mutations, 2.2% of all patients and 22% of all BRAF mutations identified. Compared with V600E BRAF-mutant cancers, non-V600 cancers occurred in significantly younger patients (58 against 68 years), fewer female patients (46% against 65%), fewer high-grade tumours (13% against 64%) and fewer right-sided primaries (36% against 81%). Median overall survival was 60.7 months for non-V600 BRAF against 11.4 months for V600E and 43.0 months for BRAF wild-type disease, and in multivariable analysis non-V600 BRAF mutation was independently associated with improved overall survival (hazard ratio 0.18).","asOf":"2026-09-24","links":[{"label":"Jones et al., J Clin Oncol 2017: non-V600 BRAF mutations in 9,643 sequenced metastatic colorectal cancers","url":"https://doi.org/10.1200/JCO.2016.71.4394"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28486044/"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":[],"targets":["braf"],"drugs":[],"companies":[],"institutions":["mayo-clinic","md-anderson"],"pathways":["ras-mapk"],"terms":["sidedness","ngs"],"trials":[],"people":["scott-kopetz"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2017,"doi":"10.1200/JCO.2016.71.4394","pmid":"28486044","authors":"Jones JC, Renfro LA, Al-Shamsi HO, et al.","paperType":"observational","findings":["Non-V600 BRAF mutations in 208 of 9,643 patients (2.2%), 22% of all BRAF mutations.","Median overall survival 60.7 months against 11.4 for V600E and 43.0 for BRAF wild-type.","Younger, more often left-sided and lower grade than V600E."],"whatItMeans":"It stops a BRAF-mutant report being read as one uniform outlook, and it separates the class II and III mutations, which signal differently and are not covered by the encorafenib plus cetuximab label, from V600E.","caveats":["Retrospective across three commercial sequencing databases, so ascertainment and follow-up are uneven.","Non-V600 is a heterogeneous group of class II and class III alleles with different biology.","No approved therapy follows from a non-V600 BRAF result."],"changedPractice":false,"participants":9643},{"id":"paper-kuznetsov-bull-math-biol","kind":"paper","name":"Nonlinear dynamics of immunogenic tumors: parameter estimation and global bifurcation analysis","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 8186756 and published in Bulletin of mathematical biology; the citing page links this DOI, which is how the record was matched.","summary":"We present a mathematical model of the cytotoxic T lymphocyte response to the growth of an immunogenic tumor. The model exhibits a number of phenomena that are seen in vivo, including immunostimulation of tumor growth, \"sneaking through\" of the tumor, and formation of a tumor \"dormant state\". The model is used to describe the kinetics of growth and regression of the B-lymphoma BCL1 in the spleen of mice. By comparing the model with experimental data, numerical estimates of parameters describing processes that cannot be measured in vivo are derived. Local and global bifurcations are calculated for realistic values of the parameters. For a large set of parameters we predict that the course of tumor growth and its clinical manifestation have a recurrent profile with a 3- to 4-month cycle, similar to patterns seen in certain leukemias.\n\nIndexed on Europe PMC as PubMed record 8186756 (DOI 10.1007/bf02460644). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Bull Math Biol 1994","url":"https://doi.org/10.1007/bf02460644"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/8186756/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/8186756"}],"tags":["europepmc-ingest"],"related":["immune-tumour-dynamics-models"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Bulletin of mathematical biology","year":1994,"doi":"10.1007/bf02460644","pmid":"8186756","authors":"Kuznetsov VA, Makalkin IA, Taylor MA, et al.","paperType":"basic","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-cercek-nonoperative-management-mismatch-repair-deficient-tumours-nejm-2025","kind":"paper","name":"Nonoperative management of mismatch repair-deficient tumors","aka":[],"tldr":"The extension of the rectal dostarlimab result to every organ: 49 of 49 rectal cancers and 35 of 54 other early-stage mismatch repair-deficient cancers disappeared on six months of one drug, and 82 patients avoided surgery altogether.","summary":"Cercek, Foote, Rousseau and colleagues conducted a phase 2 study in which patients with stage I, II or III mismatch repair-deficient solid tumours amenable to curative-intent surgery were treated with neoadjuvant dostarlimab, a PD-1 blocking agent, for six months. Response was assessed in two cohorts: cohort 1 had mismatch repair-deficient locally advanced rectal cancer and cohort 2 had mismatch repair-deficient non-rectal solid tumours. Patients with a clinical complete response could elect non-operative management; those with residual disease were to undergo resection. The primary end point, assessed in cohort 1, was a sustained clinical complete response at 12 months.\n\nThe option of curative resection was not compromised during or after treatment in any patient, which is the safety claim that makes the strategy defensible outside a trial.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2025","url":"https://doi.org/10.1056/NEJMoa2404512"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40293177/"},{"label":"Europe PMC full text (PMC12661660)","url":"https://europepmc.org/article/MED/40293177"}],"tags":["colorectal-evidence"],"related":["paper-cercek-dostarlimab-rectal-nejm-2022","paper-niche-2-nejm-2024","paper-garcia-aguilar-opra-organ-preservation-jco-2022"],"cancers":["colorectal","rectal-cancer","msi-high-colorectal"],"sections":["immunotherapy","surgery"],"technologies":["checkpoint-inhibitor"],"targets":["pd1"],"drugs":["dostarlimab"],"companies":["gsk"],"institutions":["mskcc"],"pathways":[],"terms":["msi","mmr","organ-preservation","clinical-complete-response","complete-response"],"trials":["azur-1"],"people":["andrea-cercek"],"bottlenecks":["b-surgery-radiation-innovation","b-toxicity-qol"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2025,"doi":"10.1056/NEJMoa2404512","pmid":"40293177","authors":"Cercek A, Foote MB, Rousseau B, et al.","paperType":"rct","findings":["All 49 patients in cohort 1 who completed treatment had a clinical complete response and elected non-operative management; 37 had a sustained clinical complete response at 12 months, meeting the efficacy criterion.","In cohort 2, 35 of 54 patients who completed treatment had a clinical complete response and 33 elected non-operative management.","Across both cohorts, 84 of 103 patients who completed treatment had a clinical complete response and 82 did not undergo surgery.","Recurrence-free survival at two years 92 percent (95 percent CI 86 to 99) among all 117 patients, at a median 20.0 months of follow-up for recurrence.","95 percent of patients had reversible grade 1 or 2 adverse events (60 percent) or none (35 percent)."],"whatItMeans":"For mismatch repair-deficient rectal cancer, six months of a single antibody now replaces chemotherapy, radiotherapy and an operation, and the same appears to be true for early-stage mismatch repair-deficient cancers of other organs.","caveats":["Single-arm phase 2 with no randomised comparison against chemoradiotherapy and surgery; AZUR-1 is the registrational multicentre version.","Median follow-up for recurrence is 20 months, short for an organ-preservation strategy.","Applies only to the mismatch repair-deficient minority, and depends on high-quality restaging by endoscopy and MRI that not every centre can provide."],"changedPractice":true,"participants":117},{"id":"paper-nordic-nec-sorbye-ann-oncol-2013","kind":"paper","name":"NORDIC NEC: predictive and prognostic factors in 305 patients with advanced gastrointestinal neuroendocrine carcinoma","aka":[],"tldr":"This large Nordic series showed that gastrointestinal neuroendocrine carcinomas with a Ki-67 below 55 percent respond poorly to platinum-etoposide yet live longer than those above it, which led to the separation of grade 3 neuroendocrine tumours from carcinomas.","summary":"Retrospective analysis of 305 patients with advanced gastrointestinal high-grade (grade 3) neuroendocrine carcinoma treated at Nordic centres, examining response to first-line platinum-based chemotherapy and survival by clinical and pathological features.\n\nResponse to platinum chemotherapy was 42 percent for Ki-67 of 55 percent or more but 15 percent below it, while survival was longer in the lower Ki-67 group (median 14 versus 10 months); performance status, primary site and lactate dehydrogenase were also prognostic.","asOf":"2026-09-17","links":[{"label":"Ann Oncol 2013","url":"https://doi.org/10.1093/annonc/mds276"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22967994/"}],"tags":[],"related":[],"cancers":["extrapulmonary-nec"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2013,"doi":"10.1093/annonc/mds276","pmid":"22967994","authors":"Sorbye H, Welin S, Langer SW, et al.","paperType":"observational","findings":["Response to platinum chemotherapy 42 percent with Ki-67 of 55 percent or more vs 15 percent below.","Median survival 14 months with Ki-67 under 55 percent vs 10 months above."],"whatItMeans":"The 55 percent Ki-67 threshold and the recognition that well-differentiated grade 3 tumours behave differently from carcinomas, now embedded in the WHO classification, came from this analysis.","caveats":["Retrospective; morphology (well versus poorly differentiated) was not systematically recorded."],"changedPractice":true,"participants":305},{"id":"paper-nordicc-nejm-2022","kind":"paper","name":"NordICC: inviting people to a screening colonoscopy reduced bowel cancer, but less than expected","aka":[],"tldr":"NordICC, the first randomised trial of colonoscopy screening, invited 84,585 people aged 55 to 64 to a single colonoscopy or to no screening. Bowel cancer incidence fell 18% over ten years among those invited, but only 42% attended, and the fall in bowel cancer deaths did not reach statistical significance, fuelling debate over colonoscopy versus stool-test programmes.","summary":"NordICC randomised 84,585 people aged 55-64 in Poland, Norway and Sweden to an invitation to a single screening colonoscopy or to usual care with no screening. The primary endpoints were colorectal cancer incidence and death at 10 years, analysed by intention to screen.\n\nThe 10-year risk of colorectal cancer was 0.98% in the invited group and 1.20% in usual care (risk ratio 0.82). Colorectal cancer death was 0.28% versus 0.31%, not significantly different. In the adjusted per-protocol analysis, assuming everyone invited had attended, incidence fell 31% and death 50%.\n\nThe trial prompted a wide debate about the real-world effect of colonoscopy programmes versus stool-test programmes.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1056/NEJMoa2208375"},{"label":"ClinicalTrials.gov NCT00883792","url":"https://clinicaltrials.gov/study/NCT00883792"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36214590/"}],"tags":[],"related":["paper-minnesota-fobt-nejm-1993","idea-prev-fit-risk-adapted-thresholds","idea-prev-screening-default-appointments","paper-zauber-national-polyp-study-colonoscopic-polypectomy-nejm-2012","paper-kaminski-adenoma-detection-rate-interval-cancer-nejm-2010"],"cancers":["colorectal"],"sections":["early-detection","prevention"],"technologies":["colorectal-screening","colonoscopy","endoscopy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["fit-test"],"trials":["nordicc"],"people":["michael-bretthauer"],"bottlenecks":["b-early-detection","b-prevention-adoption","b-overdiagnosis"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/NEJMoa2208375","pmid":"36214590","authors":"Bretthauer M, Løberg M, Wieszczy P, et al.","paperType":"rct","findings":["Colorectal cancer incidence at 10 years: 0.98% vs 1.20% (RR 0.82, 95% CI 0.70-0.93) by intention to screen","Colorectal cancer death: 0.28% vs 0.31% (RR 0.90, 95% CI 0.64-1.16)","Only 42% of those invited underwent colonoscopy","Adjusted per-protocol estimate: incidence RR 0.69, death RR 0.50 among those who attended","Number needed to invite to prevent one cancer over 10 years: 455"],"whatItMeans":"A colonoscopy probably does reduce bowel cancer risk for the person who has it, but a programme that offers colonoscopy achieves much less if most people decline. Programmes based on stool tests with high uptake may deliver as much population benefit at lower cost and risk.","caveats":["Low participation dilutes the intention-to-screen effect; the per-protocol estimate relies on modelling assumptions","Ten years is short for a mortality endpoint after polyp removal; a 15-year analysis is planned","Adenoma detection rates varied between endoscopists and some were below quality thresholds","Results apply to a one-off colonoscopy at 55-64, not to repeated colonoscopy programmes as practised in the US"],"changedPractice":false,"participants":84585},{"id":"paper-mintz-proc-natl-acad-sci-u-s-a","kind":"paper","name":"Normal genetically mosaic mice produced from malignant teratocarcinoma cells","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 1059147 and published in Proceedings of the National Academy of Sciences; the citing page links this DOI, which is how the record was matched.","summary":"Malignant mouse teratocarcinoma (or embryonal carcinoma) cells with a normal modal chromosome number were taken from the \"cores\" of embryoid bodies grown only in vivo as an ascites tumor for 8 years, and were injected into blastocysts bearing many genetic markers, in order to test the developmental capacities, genetic constitution, and reversibility of malignancy of the core cells. Ninety-three live normal pre- and postnatal animals were obtained. Of 14 thus far analyzed, three were cellular genetic mosaics with substantial contributions of tumor-derived cells in many developmentally unrelated tissues, including some never seen in the solid tumors that form in transplant hosts. The tissues functioned normally and synthesized their specific products (e.g., immunoglobulins, adult hemoglobin, liver proteins) coded for by strain-type alleles at known loci. In addition, a tumor-contributed color gene, steel, not previously known to be present in the carcinoma cells, was detected from the coat phenotype. Cells derived from the carcinoma, which is of X/Y sex chromosome constitution, also contributed to the germ line and formed reproductively functional sperms, some of which transmitted the steel gene to the progeny. Thus, after almost 200 transplant generations as a highly malignant tumor, embryoid body core cells appear to be developmentally totipotent and able to express, in an orderly sequence in differentiation of somatic and germ-line tissues, many genes hitherto silent in the tumor of origin. This experimental system of \"cycling\" teratocarcinoma core cells through mice, in conjunction with experimental mutagenesis of those cells, may therefore provide a new and useful tool for biochemical, developmental, and genetic analyses of mammalian differentiation. The results also furnish an unequivocal example in animals of a non-mutational basis for transformation to malignancy and of reversal to normalcy. The origin of this tumor from a disorganized embryo suggests that malignancies of some other, more specialized, stem cells might arise comparably through tissue disorganization, leading to developmental aberrations of gene expression rather than changes in gene structure.\n\nIndexed on Europe PMC as PubMed record 1059147 (DOI 10.1073/pnas.72.9.3585). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Proc Natl Acad Sci U S A 1975","url":"https://doi.org/10.1073/pnas.72.9.3585"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/1059147/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/1059147"}],"tags":["europepmc-ingest"],"related":["somatic-mutation-theory"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["pnas"],"dependsOn":[],"notes":[],"journal":"Proceedings of the National Academy of Sciences","year":1975,"doi":"10.1073/pnas.72.9.3585","pmid":"1059147","authors":"Mintz B, Illmensee K","paperType":"basic","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-jain-science","kind":"paper","name":"Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 15637262 and published in Science; the citing page links this DOI, which is how the record was matched.","summary":"Solid tumors require blood vessels for growth, and many new cancer therapies are directed against the tumor vasculature. The widely held view is that these antiangiogenic therapies should destroy the tumor vasculature, thereby depriving the tumor of oxygen and nutrients. Here, I review emerging evidence supporting an alternative hypothesis-that certain antiangiogenic agents can also transiently \"normalize\" the abnormal structure and function of tumor vasculature to make it more efficient for oxygen and drug delivery. Drugs that induce vascular normalization can alleviate hypoxia and increase the efficacy of conventional therapies if both are carefully scheduled. A better understanding of the molecular and cellular underpinnings of vascular normalization may ultimately lead to more effective therapies not only for cancer but also for diseases with abnormal vasculature, as well as regenerative medicine, in which the goal is to create and maintain a functionally normal vasculature.\n\nIndexed on Europe PMC as PubMed record 15637262 (DOI 10.1126/science.1104819). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Science 2005","url":"https://doi.org/10.1126/science.1104819"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/15637262/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/15637262"}],"tags":["europepmc-ingest"],"related":["angiogenesis-models"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2005,"doi":"10.1126/science.1104819","pmid":"15637262","authors":"Jain RK","paperType":"review","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-norpact-1-neoadjuvant-folfirinox-labori-lancet-gastroenterol-hepatol-2024","kind":"paper","name":"NORPACT-1: neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer","aka":[],"tldr":"Giving FOLFIRINOX before surgery did not help people with clearly resectable pancreatic head cancer: fewer were alive at 18 months than those who went straight to surgery.","summary":"Nordic multicentre randomised phase 2 trial: 140 patients with resectable pancreatic head cancer were assigned to four cycles of neoadjuvant FOLFIRINOX then surgery and adjuvant chemotherapy (77) or upfront surgery and adjuvant chemotherapy (63). The primary endpoint was survival at 18 months by intention to treat.\n\n60 percent of the neoadjuvant group were alive at 18 months against 73 percent of the upfront surgery group (p 0.032); median overall survival was 25.1 against 38.5 months (hazard ratio 1.52). Resection rates were 82 and 89 percent; grade 3 or worse adverse events occurred in 58 and 40 percent.","asOf":"2026-09-22","links":[{"label":"Lancet Gastroenterol Hepatol 2024","url":"https://doi.org/10.1016/S2468-1253(23)00405-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38237621/"}],"tags":[],"related":[],"cancers":["resectable-pdac","pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":["folfirinox"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["norpact-1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Lancet Gastroenterology and Hepatology","year":2024,"doi":"10.1016/S2468-1253(23)00405-3","pmid":"38237621","authors":"Labori KJ, Bratlie SO, Andersson B, et al.","paperType":"rct","findings":["Alive at 18 months: 60 percent (95% CI 49 to 71) versus 73 percent (62 to 84), p 0.032.","Median overall survival 25.1 versus 38.5 months; hazard ratio 1.52 (1.00 to 2.33), p 0.050.","Only 61 of 77 (79 percent) neoadjuvant patients received neoadjuvant therapy."],"whatItMeans":"Upfront surgery followed by adjuvant chemotherapy remains standard for clearly resectable pancreatic cancer; neoadjuvant treatment belongs in trials or borderline disease.","caveats":["Phase 2 with a small sample; a fifth of the neoadjuvant arm never received the assigned treatment."],"changedPractice":false,"participants":140},{"id":"paper-tallman-atra-apl-nejm-1997","kind":"paper","name":"North American Intergroup: all-trans retinoic acid in acute promyelocytic leukaemia","aka":[],"tldr":"This randomised trial showed that the vitamin A derivative retinoic acid, used in induction and as maintenance, sharply improved survival in acute promyelocytic leukaemia compared with chemotherapy alone.","summary":"Phase 3 trial of 346 patients with newly diagnosed APL randomised to induction with all-trans retinoic acid or with daunorubicin plus cytarabine, and then to maintenance retinoic acid or observation.\n\nThree-year disease-free survival was 67 percent after retinoic acid induction against 32 percent after chemotherapy, and maintenance retinoic acid further reduced relapse. The trial established retinoic acid as essential to APL therapy.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 1997","url":"https://doi.org/10.1056/NEJM199710093371501"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/9321529/"}],"tags":[],"related":[],"cancers":["apl"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":1997,"doi":"10.1056/NEJM199710093371501","pmid":"9321529","authors":"Tallman MS, Andersen JW, Schiffer CA, et al.","paperType":"rct","findings":["Three-year disease-free survival 67 percent with retinoic acid induction vs 32 percent with chemotherapy induction.","Maintenance retinoic acid improved disease-free survival compared with observation."],"whatItMeans":"Differentiation therapy, making leukaemic cells mature rather than killing them, became the first targeted treatment in leukaemia. Every modern APL regimen starts with retinoic acid on suspicion of the diagnosis.","caveats":["Retinoic acid syndrome caused deaths before steroid prophylaxis became routine.","Modern regimens combine retinoic acid with arsenic trioxide, which was not available at the time."],"changedPractice":true,"participants":346},{"id":"paper-jak2-myeloproliferative-neoplasms-leukemia-2010","kind":"paper","name":"Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1","aka":[],"tldr":"Review on JAK2 in Myeloproliferative neoplasms, in Leukemia (2010), one of the most cited Europe PMC records with JAK2 in its title.","summary":"Myeloproliferative neoplasms (MPNs) originate from genetically transformed hematopoietic stem cells that retain the capacity for multilineage differentiation and effective myelopoiesis. Beginning in early 2005, a number of novel mutations involving Janus kinase 2 (JAK2), Myeloproliferative Leukemia Virus (MPL), TET oncogene family member 2 (TET2), Additional Sex Combs-Like 1 (ASXL1), Casitas B-lineage lymphoma proto-oncogene (CBL), Isocitrate dehydrogenase (IDH) and IKAROS family zinc finger 1 (IKZF1) have been described in BCR-ABL1-negative MPNs. However, none of these mutations were MPN specific, displayed mutual exclusivity or could be traced back to a common ancestral clone. JAK2 and MPL mutations appear to exert a phenotype-modifying effect and are distinctly associated with polycythemia vera, essential thrombocythemia and primary myelofibrosis; the corresponding mutational frequencies are approximately 99, 55 and 65% for JAK2 and 0, 3 and 10% for MPL mutations. The incidence of TET2, ASXL1, CBL, IDH or IKZF1 mutations in these disorders ranges from 0 to 17%; these latter mutations are more common in chronic (TET2, ASXL1, CBL) or juvenile (CBL) myelomonocytic leukemias, mastocytosis (TET2), myelodysplastic syndromes (TET2, ASXL1) and secondary acute myeloid leukemia, including blast-phase MPN (IDH, ASXL1, IKZF1). The functional consequences of MPN-associated mutations include unregulated JAK-STAT (Janus kinase/signal transducer and activator of transcription) signaling, epigenetic modulation of transcription and abnormal accumulation of oncoproteins. However, it is not clear as to whether and how these abnormalities contribute to disease initiation, clonal evolution or blastic transformation.\n\nIndexed on Europe PMC as PubMed record 20428194 (DOI 10.1038/leu.2010.69). Its title names JAK2 and its text names Myeloproliferative neoplasms; PubMed types it as a review (review-article, Review). It was matched automatically to the idea \"Clearing the JAK2 clone in polycythaemia vera: interferon plus mutant-selective inhibitors as a route to treatment-free remission\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Leukemia 2010","url":"https://doi.org/10.1038/leu.2010.69"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20428194/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/20428194"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["leukemia"],"dependsOn":[],"notes":[],"journal":"Leukemia","year":2010,"doi":"10.1038/leu.2010.69","pmid":"20428194","authors":"Tefferi A","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for JAK2 in Myeloproliferative neoplasms, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by JAK2 in the title and Myeloproliferative neoplasms in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-nrg-cc001-brown-jco-2020","kind":"paper","name":"NRG CC001: hippocampal-avoidance whole-brain radiotherapy plus memantine for brain metastases","aka":[],"tldr":"When whole-brain radiotherapy is needed, shaping the beams to spare the hippocampus and adding memantine reduced the memory and thinking decline that the treatment causes, with no loss of tumour control.","summary":"Phase 3 trial of 518 patients with brain metastases randomised to whole-brain radiotherapy with memantine, with or without hippocampal avoidance using intensity-modulated techniques.\n\nCognitive failure was less frequent with hippocampal avoidance (hazard ratio 0.74), driven by less decline in executive function and memory, with no difference in overall survival, intracranial progression or toxicity.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2020","url":"https://doi.org/10.1200/JCO.19.02767"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32058845/"}],"tags":[],"related":[],"cancers":["secondary-brain-tumours"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nrg-cc001"],"people":["paul-brown"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/JCO.19.02767","pmid":"32058845","authors":"Brown PD, Gondi V, Pugh S, et al.","paperType":"rct","findings":["Risk of cognitive failure reduced by 26 percent with hippocampal avoidance.","No difference in survival or intracranial progression."],"whatItMeans":"Where whole-brain radiotherapy is still chosen, for many metastases or leptomeningeal disease, hippocampal avoidance with memantine is the recommended technique.","caveats":["Excluded patients with metastases within 5 mm of the hippocampus.","Requires intensity-modulated planning capability."],"changedPractice":true,"participants":518},{"id":"paper-rtog-1016-lancet-2019","kind":"paper","name":"NRG Oncology RTOG 1016: radiotherapy plus cetuximab versus cisplatin in HPV-positive oropharyngeal cancer","aka":[],"tldr":"Trying to reduce toxicity by swapping cisplatin for cetuximab during radiotherapy in HPV-positive oropharyngeal cancer backfired: cetuximab gave worse survival and more recurrences with no reduction in toxicity, so cisplatin remains standard.","summary":"Phase 3 non-inferiority trial of 849 patients with HPV-positive (p16-positive) oropharyngeal cancer randomised to accelerated intensity-modulated radiotherapy with cisplatin or with cetuximab.\n\nFive-year overall survival was 77.9 percent with cetuximab against 84.6 percent with cisplatin (hazard ratio 1.45, non-inferiority not met) and five-year locoregional failure 17.3 versus 9.9 percent; acute and late toxicity rates were similar.","asOf":"2026-09-17","links":[{"label":"Lancet 2019","url":"https://doi.org/10.1016/S0140-6736(18)32779-X"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30449625/"}],"tags":[],"related":[],"cancers":["hpv-positive-oropharyngeal-cancer","oropharyngeal-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["cetuximab","cisplatin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["rtog-1016"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2019,"doi":"10.1016/S0140-6736(18)32779-X","pmid":"30449625","authors":"Gillison ML, Trotti AM, Harris J, et al.","paperType":"rct","findings":["Five-year overall survival 77.9 percent (cetuximab) vs 84.6 percent (cisplatin); hazard ratio 1.45.","Five-year locoregional failure 17.3 percent vs 9.9 percent."],"whatItMeans":"Cisplatin chemoradiation is the standard for HPV-positive oropharyngeal cancer; cetuximab is reserved for patients who cannot receive cisplatin.","caveats":["Accelerated radiotherapy fractionation differs from standard practice in some countries."],"changedPractice":true,"participants":849},{"id":"paper-nrg-gy018-nejm-2023","kind":"paper","name":"NRG-GY018: pembrolizumab plus chemotherapy in advanced or recurrent endometrial cancer","aka":[],"tldr":"Adding pembrolizumab to carboplatin-paclitaxel and continuing it as maintenance cut the risk of progression by 70 percent in mismatch repair-deficient endometrial cancer and by 46 percent in mismatch repair-proficient disease.","summary":"Phase 3 placebo-controlled trial of 816 patients with measurable stage III to IVA, stage IVB or recurrent endometrial cancer randomised to pembrolizumab or placebo with carboplatin-paclitaxel followed by up to 14 maintenance cycles, analysed separately by mismatch repair status.\n\nIn mismatch repair-deficient disease, 12-month progression-free survival was 74 versus 38 percent (hazard ratio 0.30); in proficient disease median progression-free survival was 13.1 versus 8.7 months (hazard ratio 0.54).","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2023","url":"https://doi.org/10.1056/NEJMoa2302312"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36972022/"}],"tags":[],"related":[],"cancers":["advanced-recurrent-endometrial-cancer","endometrial-mmr-deficient","endometrial-nsmp"],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/NEJMoa2302312","pmid":"36972022","authors":"Eskander RN, Sill MW, Beffa L, et al.","paperType":"rct","findings":["Mismatch repair-deficient: progression-free survival hazard ratio 0.30.","Mismatch repair-proficient: median progression-free survival 13.1 vs 8.7 months; hazard ratio 0.54."],"whatItMeans":"Together with RUBY, this trial made chemo-immunotherapy the first-line standard for advanced endometrial cancer in both molecular groups, with the largest effect in mismatch repair-deficient tumours.","caveats":["Overall survival data were immature at first report.","Excluded carcinosarcoma, unlike RUBY."],"changedPractice":true,"participants":816},{"id":"paper-navigate-j-clin-invest-2021","kind":"paper","name":"NTRK and RET fusion-directed therapy in pediatric thyroid cancer yields a tumor response and radioiodine uptake","aka":[],"tldr":"Published report from the NAVIGATE trial registered as NCT02576431, in Journal of Clinical Investigation (2021), chosen as the most cited paper whose own text cites the registry id.","summary":"BACKGROUNDMolecular characterization in pediatric papillary thyroid cancer (PTC), distinct from adult PTC, is important for developing molecularly targeted therapies for progressive radioiodine-refractory (131I-refractory) PTC.METHODSPTC samples from 106 pediatric patients (age range: 4.3-19.8 years; n = 84 girls, n = 22 boys) who were admitted to SNUH (January 1983-March 2020) were available for genomic profiling. Previous transcriptomic data from 125 adult PTC samples were used for comparison.RESULTSWe identified genetic drivers in 80 tumors: 31 with fusion oncogenes (RET in 21 patients, ALK in 6 patients, and NTRK1/3 in 4 patients); 47 with point mutations (BRAFV600E in 41 patients, TERTC228T in 2 patients [1 of whom had a coexisting BRAFV600E], and DICER1 variants in 5 patients); and 2 with amplifications. Fusion oncogene PTCs, which are predominantly detected in younger patients, were at a more advanced stage and showed more recurrent or persistent disease compared with BRAFV600E PTCs, which are detected mostly in adolescents. Pediatric fusion PTCs (in patients <10 years of age) had lower expression of thyroid differentiation genes, including SLC5A5, than did adult fusion PTCs. Two girls with progressive 131I-refractory lung metastases harboring a TPR-NTRK1 or CCDC6-RET fusion oncogene received fusion-targeted therapy; larotrectinib and selpercatinib decreased the size of the tumor and restored 125I radioiodine uptake. The girl with the CCDC6-RET fusion oncogene received 131I therapy combined with selpercatinib, resulting in a tumor response. In vitro 125I uptake and 131I clonogenic assays showed that larotrectinib inhibited tumor growth and restored radioiodine avidity.CONCLUSIONSIn pediatric patients with fusion oncogene PTC who have 131I-refractory advanced disease, selective fusion-directed therapy may restore radioiodine avidity and lead to a dramatic tumor response, underscoring the importance of molecular testing in pediatric patients with PTC.FUNDINGThe Ministry of Science, ICT and Future Planning (NRF-2016R1A2B4012417 and 2019R1A2C2084332); the Korean Ministry of Health and Welfare (H14C1277); the Ministry of Education (2020R1A6A1A03047972); and the SNUH Research Fund (04-2015-0830).TRIAL REGISTRATIONTwo patients received fusion-targeted therapy with larotrectinib (NCT02576431; NAVIGATE) or selpercatinib (LOXO-RET-18018).\n\nIndexed on Europe PMC as PubMed record 34237031 (DOI 10.1172/jci144847). Its abstract cites the registry id NCT02576431, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Clin Invest 2021","url":"https://doi.org/10.1172/jci144847"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34237031/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34237031"},{"label":"ClinicalTrials.gov NCT02576431","url":"https://clinicaltrials.gov/study/NCT02576431"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["navigate"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jci"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Investigation","year":2021,"doi":"10.1172/jci144847","pmid":"34237031","authors":"Lee YA, Lee H, Im SW, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02576431 with the most citations, so it is the natural first reading for anyone following the NAVIGATE trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-scher-nuclear-arv7-taxane-vs-arsi-jama-oncol-2018","kind":"paper","name":"Nuclear-localised androgen receptor splice variant 7 in circulating tumour cells as a predictive biomarker in castration-resistant prostate cancer","aka":[],"tldr":"A blinded three-hospital study found that men with the shortened receptor in their circulating tumour cells lived roughly twice as long on chemotherapy as on another hormone tablet, and that men without it did better the other way round.","summary":"A blinded correlative study conducted between December 2012 and September 2016 included 142 men with histologically confirmed metastatic castration-resistant prostate cancer treated at Memorial Sloan Kettering Cancer Center, the Royal Marsden or the London Health Sciences Centre. Blood samples were taken before an androgen receptor signalling inhibitor or a taxane given as second-line or later therapy for progressing disease, and nuclear-localised AR-V7 protein in circulating tumour cells was measured on a validated assay. Among the 70 men designated high risk by conventional prognostic factors, AR-V7-positive men treated with taxanes had a median overall survival of 14.3 months against 7.3 months for those treated with receptor signalling inhibitors (hazard ratio 0.62), while AR-V7-negative men treated with receptor signalling inhibitors had a median overall survival of 19.8 months against 12.8 months on taxanes (hazard ratio 1.67).","asOf":"2026-09-25","links":[{"label":"Scher et al., JAMA Oncol 2018: nuclear-localised AR-V7 protein in circulating tumour cells and the taxane against androgen receptor signalling inhibitor choice (142 patients)","url":"https://doi.org/10.1001/jamaoncol.2018.1621"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29955787/"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["liquid-biopsy"],"targets":["androgen-receptor"],"drugs":[],"companies":[],"institutions":[],"pathways":["ar-signaling","rna-splicing","intravasation-ctc-survival"],"terms":["ar-v7","liquid-biopsy","castration-resistance","resistance"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2018,"doi":"10.1001/jamaoncol.2018.1621","pmid":"29955787","authors":"Scher HI, Graf RP, Schreiber NA, et al.","paperType":"observational","findings":["AR-V7-positive high-risk men: median overall survival 14.3 months on a taxane against 7.3 months on a receptor signalling inhibitor.","AR-V7-negative men: 19.8 months on a receptor signalling inhibitor against 12.8 months on a taxane (hazard ratio 1.67).","The treatment-selection effect was confined to the conventionally high-risk group of 70 men."],"whatItMeans":"It is the clearest evidence in prostate cancer that a blood biomarker can point to one treatment class over another, and the reason AR-V7 is discussed in guidelines despite being in no label.","caveats":["Not randomised: treatment was chosen by clinicians, so confounding by indication cannot be excluded.","The confidence interval for the positive group crossed one (hazard ratio 0.62, 0.28 to 1.39).","One hundred and forty-two men across three centres with a laboratory-developed test."],"changedPractice":false,"participants":142},{"id":"paper-dalla-torre-nat-methods","kind":"paper","name":"Nucleotide Transformer: building and evaluating robust foundation models for human genomics","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 39609566 and published in Nature methods; the citing page links this DOI, which is how the record was matched.","summary":"The prediction of molecular phenotypes from DNA sequences remains a longstanding challenge in genomics, often driven by limited annotated data and the inability to transfer learnings between tasks. Here, we present an extensive study of foundation models pre-trained on DNA sequences, named Nucleotide Transformer, ranging from 50 million up to 2.5 billion parameters and integrating information from 3,202 human genomes and 850 genomes from diverse species. These transformer models yield context-specific representations of nucleotide sequences, which allow for accurate predictions even in low-data settings. We show that the developed models can be fine-tuned at low cost to solve a variety of genomics applications. Despite no supervision, the models learned to focus attention on key genomic elements and can be used to improve the prioritization of genetic variants. The training and application of foundational models in genomics provides a widely applicable approach for accurate molecular phenotype prediction from DNA sequence.\n\nIndexed on Europe PMC as PubMed record 39609566 (DOI 10.1038/s41592-024-02523-z). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Methods 2025","url":"https://doi.org/10.1038/s41592-024-02523-z"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39609566/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39609566"}],"tags":["europepmc-ingest"],"related":["nucleotide-transformer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature methods","year":2025,"doi":"10.1038/s41592-024-02523-z","pmid":"39609566","authors":"Dalla-Torre H, Gonzalez L, Mendoza-Revilla J, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-dangelo-ny-eso-1-tcr-synovial-sarcoma-cancer-discov-2018","kind":"paper","name":"NY-ESO-1 c259 T-cell receptor therapy in synovial sarcoma: prolonged persistence and antitumour activity","aka":[],"tldr":"Engineering patients' own T cells with a receptor recognising the NY-ESO-1 antigen shrank tumours in half of a small group with advanced synovial sarcoma, the first convincing evidence that T-cell receptor therapy can work in a solid tumour.","summary":"Pilot study of 12 patients with HLA-A*02-positive, NY-ESO-1-expressing advanced synovial sarcoma treated with autologous T cells transduced with an affinity-enhanced NY-ESO-1 c259 T-cell receptor after lymphodepleting chemotherapy.\n\nObjective response was 50 percent including one complete response, with responses associated with T-cell persistence and higher lymphodepletion intensity; toxicity included cytokine release syndrome and cytopenias.","asOf":"2026-09-17","links":[{"label":"Cancer Discov 2018","url":"https://doi.org/10.1158/2159-8290.CD-17-1417"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29891538/"}],"tags":[],"related":[],"cancers":["synovial-sarcoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-discovery"],"dependsOn":[],"notes":[],"journal":"Cancer Discovery","year":2018,"doi":"10.1158/2159-8290.CD-17-1417","pmid":"29891538","authors":"D'Angelo SP, Melchiori L, Merchant MS, et al.","paperType":"observational","findings":["Objective response 6 of 12 patients (50 percent), one complete response.","Response correlated with T-cell persistence and lymphodepletion dose."],"whatItMeans":"This study opened the path to engineered T-cell receptor therapy in synovial sarcoma, leading to afamitresgene autoleucel targeting MAGE-A4 (SPEARHEAD-1) and its approval in 2024.","caveats":["Twelve patients; requires HLA-A*02 and antigen expression."],"changedPractice":true,"participants":12},{"id":"paper-oreilly-gemcitabine-cisplatin-veliparib-gbrca-palb2-pancreatic-jco-2020","kind":"paper","name":"O'Reilly 2020: gemcitabine and cisplatin with or without veliparib in pancreatic cancer with a germline BRCA or PALB2 mutation","aka":[],"tldr":"In the first randomised trial restricted to pancreatic cancer patients with inherited BRCA or PALB2 mutations, platinum chemotherapy shrank tumours in about two-thirds and gave unusually long survival, while adding the PARP inhibitor veliparib to the chemotherapy did not help and added toxicity.","summary":"Randomised multicentre phase 2 trial in 50 patients with untreated locally advanced or metastatic pancreatic adenocarcinoma and a germline BRCA1, BRCA2 or PALB2 mutation, assigned to gemcitabine plus cisplatin with or without veliparib.\n\nObjective response rates were about 74 percent with veliparib and 65 percent without, not significantly different, and median overall survival was 15.5 against 16.4 months. Haematological toxicity was greater with veliparib. Across both arms, two-year survival was about 31 percent and three-year survival about 18 percent, far above unselected pancreatic cancer.","asOf":"2026-09-21","links":[{"label":"J Clin Oncol 2020","url":"https://doi.org/10.1200/JCO.19.02931"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31976786/"}],"tags":[],"related":[],"cancers":["brca-palb2-pdac","pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":["gemcitabine","cisplatin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["eileen-oreilly"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/JCO.19.02931","pmid":"31976786","authors":"O'Reilly EM, Lee JW, Zalupski M, et al.","paperType":"rct","findings":["Objective response about 74 percent with veliparib versus 65 percent with gemcitabine and cisplatin alone; median overall survival 15.5 versus 16.4 months.","Two-year survival about 31 percent and three-year about 18 percent across both arms.","More haematological toxicity with veliparib."],"whatItMeans":"Gemcitabine plus cisplatin is a validated platinum doublet for BRCA or PALB2 carriers, and the trial explains why PARP inhibitors are used as maintenance after platinum rather than concurrently with it.","caveats":["A 50-patient phase 2 without a non-platinum comparator, so the platinum benefit is inferred from historical controls.","PALB2 carriers were few."],"changedPractice":true,"participants":50},{"id":"paper-goya-obinutuzumab-vs-rituximab-chop-dlbcl-jco-2017","kind":"paper","name":"Obinutuzumab or rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in previously untreated diffuse large B-cell lymphoma","aka":["GOYA","Vitolo 2017"],"tldr":"A newer antibody against the same target did not improve first-line treatment of the commonest aggressive lymphoma, although it had improved treatment of two other B-cell cancers.","summary":"A randomised phase 3 trial in which 1,418 patients with previously untreated advanced diffuse large B-cell lymphoma received eight 21-day cycles of obinutuzumab (706) or rituximab (712) with six or eight cycles of CHOP. The primary endpoint was investigator-assessed progression-free survival.\n\nAfter a median observation of 29 months there were 201 progression-free survival events (28.5 per cent) with obinutuzumab and 215 (30.2 per cent) with rituximab, a stratified hazard ratio of 0.92 (95 per cent confidence interval 0.76 to 1.11, p = 0.39), with three-year rates of 70 and 67 per cent. Independently reviewed progression-free survival, other time-to-event endpoints and response rates were similar. Grade 3 to 5 adverse events occurred in 73.7 against 64.7 per cent, serious adverse events in 42.6 against 37.6 per cent and fatal adverse events in 5.8 against 4.3 per cent. In exploratory analysis, patients with germinal-centre B-cell subtype disease had better progression-free survival than those with activated B-cell subtype disease irrespective of treatment.","asOf":"2026-10-01","links":[{"label":"Journal of Clinical Oncology 2017","url":"https://doi.org/10.1200/JCO.2017.73.3402"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28796588/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28796588"}],"tags":["lymphoma-evidence"],"related":["lymphoma-roadmap"],"cancers":["dlbcl","non-hodgkin-lymphoma"],"sections":["immunotherapy","chemotherapy"],"technologies":[],"targets":["cd20"],"drugs":["obinutuzumab","rituximab","cyclophosphamide","doxorubicin","vincristine","prednisone"],"companies":["roche-genentech"],"institutions":[],"pathways":[],"terms":["r-chop","cell-of-origin"],"trials":["goya","gallium"],"people":["laurie-sehn"],"bottlenecks":["b-negative-results","b-biomarker-validation"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2017,"doi":"10.1200/JCO.2017.73.3402","pmid":"28796588","authors":"Vitolo U, Trněný M, Belada D, et al.","paperType":"rct","findings":["Obinutuzumab with CHOP did not improve progression-free survival over rituximab with CHOP (stratified hazard ratio 0.92, 95 per cent confidence interval 0.76 to 1.11, p = 0.39).","Three-year progression-free survival was 70 per cent with obinutuzumab and 67 per cent with rituximab.","Grade 3 to 5 adverse events occurred in 73.7 per cent with obinutuzumab against 64.7 per cent with rituximab; fatal adverse events in 5.8 against 4.3 per cent.","Infusion-related reactions occurred in 36.1 per cent with obinutuzumab against 23.5 per cent with rituximab.","In exploratory subgroup analysis, germinal-centre B-cell subtype disease had better progression-free survival than activated B-cell subtype disease irrespective of treatment."],"whatItMeans":"Rituximab remains the CD20 antibody used in first-line diffuse large B-cell lymphoma. The result is a warning against assuming an antibody improvement carries from one B-cell malignancy to another: the same substitution improved progression-free survival in chronic lymphocytic leukaemia and in follicular lymphoma.","caveats":["Median observation of 29 months is short for a disease in which most relapses occur within two years but survival differences take longer to emerge.","The cell-of-origin subgroup analysis was exploratory and described prognosis, not a treatment interaction.","The registry lists the study as terminated, reflecting the end of the development programme rather than a safety stop."],"changedPractice":false,"participants":1418},{"id":"paper-kelly-jama-oncol","kind":"paper","name":"Objective Response Rate Among Patients With Locally Advanced or Metastatic Sarcoma Treated With Talimogene Laherparepvec in Combination With Pembrolizumab: A Phase 2 Clinical Trial","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 31971541 and published in JAMA Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Importance: Patients with advanced sarcoma have limited treatment options. Talimogene laherparepvec (T-VEC) has been shown to increase tumor-specific immune activation via augmenting antigen presentation and T-cell priming.\n\nObjective: To examine whether T-VEC in combination with pembrolizumab is associated with increased tumor-infiltrating lymphocyte infiltration and programmed death-ligand 1 expression and thus with increased antitumor activity in patients with locally advanced or metastatic sarcoma.\n\nDesign, setting, and participants: This open-label, single-institution phase 2 interventional trial of T-VEC plus pembrolizumab enrolled 20 patients with locally advanced or metastatic sarcoma between March 16 and December 4, 2017, for whom at least 1 standard systemic therapy had failed. The median duration of therapy was 16 weeks (range, 7-67 weeks). Reported analyses include data through December 14, 2018.\n\nIntervention: Patients received pembrolizumab (200-mg flat dose) intravenously and T-VEC (first dose, ≤4 mL × 106 plaque-forming units [PFU]/mL; second and subsequent doses, ≤4 mL × 108 PFU/mL) injected into palpable tumor site(s) on day 1 of each 21-day cycle.\n\nMain outcomes and measures: The primary end point was objective response rate (ORR; complete response and partial response) at 24 weeks determined by Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1, criteria. Secondary end points included best ORR by immune-related RECIST criteria, progression-free survival rate at 24 weeks, overall survival, and safety.\n\nResults: All 20 patients (12 women [60%]; median age, 63.5 years [range, 24-90 years]) were evaluable for response. The study met its primary end point of evaluating the best ORR at 24 weeks determined by RECIST, version 1.1, criteria; the best ORR was 30% (95% CI, 12%-54%; n = 6). The ORR overall was 35% (95% CI, 15%-59%; n = 7). The incidence of grade 3 treatment-related adverse events was low (4 patients [20%]). There were no grade 4 treatment-related adverse events or treatment-related deaths.\n\nConclusions and relevance: In this phase 2 clinical trial, treatment with T-VEC plus pembrolizumab was associated with antitumor activity in advanced sarcoma across a range of sarcoma histologic subtypes, with a manageable safety profile. This combination therapy met its predefined primary study end point; further evaluation of T-VEC in combination with pembrolizumab for patients with select sarcoma subtypes is planned.\n\nTrial registration: ClinicalTrials.gov identifier: NCT03069378.\n\nIndexed on Europe PMC as PubMed record 31971541 (DOI 10.1001/jamaoncol.2019.6152). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA Oncol 2020","url":"https://doi.org/10.1001/jamaoncol.2019.6152"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31971541/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31971541"}],"tags":["europepmc-ingest"],"related":["epithelioid-sarcoma"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2020,"doi":"10.1001/jamaoncol.2019.6152","pmid":"31971541","authors":"Kelly CM, Antonescu CR, Bowler T, et al.","paperType":"observational","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-navari-n-engl-j-med","kind":"paper","name":"Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 27410922 and published in New England Journal of Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Background: We examined the efficacy of olanzapine for the prevention of nausea and vomiting in patients receiving highly emetogenic chemotherapy.\n\nMethods: In a randomized, double-blind, phase 3 trial, we compared olanzapine with placebo, in combination with dexamethasone, aprepitant or fosaprepitant, and a 5-hydroxytryptamine type 3-receptor antagonist, in patients with no previous chemotherapy who were receiving cisplatin (≥70 mg per square meter of body-surface area) or cyclophosphamide-doxorubicin. The doses of the three concomitant drugs administered before and after chemotherapy were similar in the two groups. The two groups received either 10 mg of olanzapine orally or matching placebo daily on days 1 through 4. Nausea prevention was the primary end point; a complete response (no emesis and no use of rescue medication) was a secondary end point.\n\nResults: In the analysis, we included 380 patients who could be evaluated (192 assigned to olanzapine, and 188 to placebo). The proportion of patients with no chemotherapy-induced nausea was significantly greater with olanzapine than with placebo in the first 24 hours after chemotherapy (74% vs. 45%, P=0.002), the period from 25 to 120 hours after chemotherapy (42% vs. 25%, P=0.002), and the overall 120-hour period (37% vs. 22%, P=0.002). The complete-response rate was also significantly increased with olanzapine during the three periods: 86% versus 65% (P<0.001), 67% versus 52% (P=0.007), and 64% versus 41% (P<0.001), respectively. Although there were no grade 5 toxic effects, some patients receiving olanzapine had increased sedation (severe in 5%) on day 2.\n\nConclusions: Olanzapine, as compared with placebo, significantly improved nausea prevention, as well as the complete-response rate, among previously untreated patients who were receiving highly emetogenic chemotherapy. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02116530.).\n\nIndexed on Europe PMC as PubMed record 27410922 (DOI 10.1056/nejmoa1515725). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2016","url":"https://doi.org/10.1056/nejmoa1515725"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27410922/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27410922"}],"tags":["europepmc-ingest"],"related":["antiemetic-therapy"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2016,"doi":"10.1056/nejmoa1515725","pmid":"27410922","authors":"Navari RM, Qin R, Ruddy KJ, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-ring-clin-cancer-res","kind":"paper","name":"Olaparib and Ceralasertib (AZD6738) in Patients with Triple-Negative Advanced Breast Cancer: Results from Cohort E of the plasmaMATCH Trial (CRUK/15/010)","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 37773077 and published in Clinical Cancer Research; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: Approximately 10% to 15% of triple-negative breast cancers (TNBC) have deleterious mutations in BRCA1 and BRCA2 and may benefit from PARP inhibitor treatment. PARP inhibitors may also increase exogenous replication stress and thereby increase sensitivity to inhibitors of ataxia telangiectasia and Rad3-related (ATR) protein. This phase II study examined the activity of the combination of PARP inhibitor, olaparib, and ATR inhibitor, ceralasertib (AZD6738), in patients with advanced TNBC.\n\nPatients and methods: Patients with TNBC on most recent biopsy who had received 1 or 2 lines of chemotherapy for advanced disease or had relapsed within 12 months of (neo)adjuvant chemotherapy were eligible. Treatment was olaparib 300 mg twice a day continuously and celarasertib 160 mg on days 1-7 on a 28-day cycle until disease progression. The primary endpoint was confirmed objective response rate (ORR). Tissue and plasma biomarker analyses were preplanned to identify predictors of response.\n\nResults: 70 evaluable patients were enrolled. Germline BRCA1/2 mutations were present in 10 (14%) patients and 3 (4%) patients had somatic BRCA mutations. The confirmed ORR was 12/70; 17.1% (95% confidence interval, 10.4-25.5). Responses were observed in patients without germline or somatic BRCA1/2 mutations, including patients with mutations in other homologous recombination repair genes and tumors with functional homologous recombination deficiency by RAD51 foci.\n\nConclusions: The response rate to olaparib and ceralasertib did not meet prespecified criteria for activity in the overall evaluable population, but responses were observed in patients who would not be expected to respond to olaparib monotherapy.\n\nIndexed on Europe PMC as PubMed record 37773077 (DOI 10.1158/1078-0432.ccr-23-1696). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Clin Cancer Res 2023","url":"https://doi.org/10.1158/1078-0432.ccr-23-1696"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37773077/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37773077"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["plasmamatch"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2023,"doi":"10.1158/1078-0432.ccr-23-1696","pmid":"37773077","authors":"Ring A, Kilburn LS, Pearson A, et al.","paperType":"observational","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nct02734004-lancet-oncol-2020","kind":"paper","name":"Olaparib and durvalumab in patients with germline BRCA-mutated metastatic breast cancer (MEDIOLA): an open-label, multicentre, phase 1/2, basket study","aka":[],"tldr":"Published report from the MEDIOLA trial registered as NCT02734004, in The Lancet Oncology (2020), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Poly (ADP-ribose) polymerase inhibitors combined with immunotherapy have shown antitumour activity in preclinical studies. We aimed to assess the safety and activity of olaparib in combination with the PD-L1-inhibitor, durvalumab, in patients with germline BRCA1-mutated or BRCA2-mutated metastatic breast cancer.\n\nMethods: The MEDIOLA trial is a multicentre, open-label, phase 1/2, basket trial of durvalumab and olaparib in solid tumours. Patients were enrolled into four initial cohorts: germline BRCA-mutated, metastatic breast cancer; germline BRCA-mutated, metastatic ovarian cancer; metastatic gastric cancer; and relapsed small-cell lung cancer. Here, we report on the cohort of patients with breast cancer. Patients who were aged 18 years or older (or aged 19 years or older in South Korea) with germline BRCA1-mutated or BRCA2-mutated or both and histologically confirmed, progressive, HER2-negative, metastatic breast cancer were enrolled from 14 health centres in the UK, the USA, Israel, France, Switzerland, and South Korea. Patients should not have received more than two previous lines of chemotherapy for metastatic breast cancer. Patients received 300 mg olaparib in tablet form orally twice daily for 4 weeks and thereafter a combination of olaparib 300 mg twice daily and durvalumab 1·5 g via intravenous infusion every 4 weeks until disease progression. Primary endpoints were safety and tolerability, and 12-week disease control rate. Safety was analysed in patients who received at least one dose of study treatment, and activity analyses were done in the full-analysis set (patients who received at least one dose of study treatment and were not excluded from the study). Recruitment has completed and the study is ongoing. This trial is registered with ClinicalTrials.gov, NCT02734004.\n\nFindings: Between June 14, 2016, and May 2, 2017, 34 patients were enrolled and received both study drugs and were included in the safety analysis. 11 (32%) patients experienced grade 3 or worse adverse events, of which the most common were anaemia (four [12%]), neutropenia (three [9%]), and pancreatitis (two [6%]). Three (9%) patients discontinued due to adverse events and four (12%) patients experienced a total of six serious adverse events. There were no treatment-related deaths. 24 (80%; 90% CI 64·3-90·9) of 30 patients eligible for activity analysis had disease control at 12 weeks.\n\nInterpretation: Combination of olaparib and durvalumab showed promising antitumour activity and safety similar to that previously observed in olaparib and durvalumab monotherapy studies. Further research in a randomised setting is needed to determine predictors of therapeutic benefit and whether addition of durvalumab improves long-term clinical outcomes compared with olaparib monotherapy.\n\nFunding: AstraZeneca.\n\nIndexed on Europe PMC as PubMed record 32771088 (DOI 10.1016/s1470-2045(20)30324-7). Its abstract cites the registry id NCT02734004, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2020","url":"https://doi.org/10.1016/s1470-2045(20)30324-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32771088/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32771088"},{"label":"ClinicalTrials.gov NCT02734004","url":"https://clinicaltrials.gov/study/NCT02734004"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct02734004"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2020,"doi":"10.1016/s1470-2045(20)30324-7","pmid":"32771088","authors":"Domchek SM, Postel-Vinay S, Im SA, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02734004 with the most citations, so it is the natural first reading for anyone following the MEDIOLA trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-propel-lancet-oncol-2023","kind":"paper","name":"Olaparib plus abiraterone versus placebo plus abiraterone in metastatic castration-resistant prostate cancer (PROpel): final prespecified overall survival results of a randomised, double-blind, phase 3 trial","aka":[],"tldr":"Published report from the PROpel trial registered as NCT03732820, in The Lancet Oncology (2023), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: PROpel met its primary endpoint showing statistically significant improvement in radiographic progression-free survival with olaparib plus abiraterone versus placebo plus abiraterone in patients with first-line metastatic castration-resistant prostate cancer (mCRPC) unselected by homologous recombination repair mutation (HRRm) status, with benefit observed in all prespecified subgroups. Here we report the final prespecified overall survival analysis.\n\nMethods: This was a randomised, double-blind, phase 3 trial done at 126 centres in 17 countries worldwide. Patients with mCRPC aged at least 18 years, Eastern Cooperative Oncology Group performance status 0-1, a life expectancy of at least 6 months, with no previous systemic treatment for mCRPC and unselected by HRRm status were randomly assigned (1:1) centrally by means of an interactive voice response system-interactive web response system to abiraterone acetate (orally, 1000 mg once daily) plus prednisone or prednisolone with either olaparib (orally, 300 mg twice daily) or placebo. The patients, the investigator, and study centre staff were masked to drug allocation. Stratification factors were site of metastases and previous docetaxel at metastatic hormone-sensitive cancer stage. Radiographic progression-free survival was the primary endpoint and overall survival was a key secondary endpoint with alpha-control (alpha-threshold at prespecified final analysis: 0·0377 [two-sided]), evaluated in the intention-to-treat population. Safety was evaluated in all patients who received at least one dose of a study drug. This study is registered with ClinicalTrials.gov, NCT03732820, and is completed and no longer recruiting.\n\nFindings: Between Oct 31, 2018 and March 11, 2020, 1103 patients were screened, of whom 399 were randomly assigned to olaparib plus abiraterone and 397 to placebo plus abiraterone. Median follow-up for overall survival in patients with censored data was 36·6 months (IQR 34·1-40·3) for olaparib plus abiraterone and 36·5 months (33·8-40·3) for placebo plus abiraterone. Median overall survival was 42·1 months (95% CI 38·4-not reached) with olaparib plus abiraterone and 34·7 months (31·0-39·3) with placebo plus abiraterone (hazard ratio 0·81, 95% CI 0·67-1·00; p=0·054). The most common grade 3-4 adverse event was anaemia reported in 64 (16%) of 398 patients in the olaparib plus abiraterone and 13 (3%) of 396 patients in the placebo plus abiraterone group. Serious adverse events were reported in 161 (40%) in the olaparib plus abiraterone group and 126 (32%) in the placebo plus abiraterone group. One death in the placebo plus abiraterone group, from interstitial lung disease, was considered treatment related.\n\nInterpretation: Overall survival was not significantly different between treatment groups at this final prespecified analysis.\n\nFunding: Supported by AstraZeneca and Merck Sharp & Dohme.\n\nIndexed on Europe PMC as PubMed record 37714168 (DOI 10.1016/s1470-2045(23)00382-0). Its abstract cites the registry id NCT03732820, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2023","url":"https://doi.org/10.1016/s1470-2045(23)00382-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37714168/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37714168"},{"label":"ClinicalTrials.gov NCT03732820","url":"https://clinicaltrials.gov/study/NCT03732820"}],"tags":["europepmc-ingest"],"related":["prostate-roadmap","paper-mateo-toparp-a-olaparib-dna-repair-nejm-2015","idea-prostate-hrr-testing-at-metastatic-diagnosis"],"cancers":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["propel"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2023,"doi":"10.1016/s1470-2045(23)00382-0","pmid":"37714168","authors":"Saad F, Clarke NW, Oya M, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03732820 with the most citations, so it is the natural first reading for anyone following the PROpel trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-robin-jones-lancet-2016","kind":"paper","name":"Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial","aka":[],"tldr":"Paper by Robin L. Jones indexed on Europe PMC as PubMed record 27291997, in The Lancet (2016), one of the most cited records naming an author with this name at The Royal Marsden.","summary":"Background: Treatment with doxorubicin is a present standard of care for patients with metastatic soft-tissue sarcoma and median overall survival for those treated is 12-16 months, but few, if any, novel treatments or chemotherapy combinations have been able to improve these poor outcomes. Olaratumab is a human antiplatelet-derived growth factor receptor α monoclonal antibody that has antitumour activity in human sarcoma xenografts. We aimed to assess the efficacy of olaratumab plus doxorubicin in patients with advanced or metastatic soft-tissue sarcoma.\n\nMethods: We did an open-label phase 1b and randomised phase 2 study of doxorubicin plus olaratumab treatment in patients with unresectable or metastatic soft-tissue sarcoma at 16 clinical sites in the USA. For both the phase 1b and phase 2 parts of the study, eligible patients were aged 18 years or older and had a histologically confirmed diagnosis of locally advanced or metastatic soft-tissue sarcoma not previously treated with an anthracycline, an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, and available tumour tissue to determine PDGFRα expression by immunohistochemistry. In the phase 2 part of the study, patients were randomly assigned in a 1:1 ratio to receive either olaratumab (15 mg/kg) intravenously on day 1 and day 8 plus doxorubicin (75 mg/m(2)) or doxorubicin alone (75 mg/m(2)) on day 1 of each 21-day cycle for up to eight cycles. Randomisation was dynamic and used the minimisation randomisation technique. The phase 1b primary endpoint was safety and the phase 2 primary endpoint was progression-free survival using a two-sided α level of 0.2 and statistical power of 0.8. This study was registered with ClinicalTrials.gov, number NCT01185964.\n\nFindings: 15 patients were enrolled and treated with olaratumab plus doxorubicin in the phase 1b study, and 133 patients were randomised (66 to olaratumab plus doxorubicin; 67 to doxorubicin alone) in the phase 2 trial, 129 (97%) of whom received at least one dose of study treatment (64 received olaratumab plus doxorubicin, 65 received doxorubicin). Median progression-free survival in phase 2 was 6.6 months (95% CI 4.1-8.3) with olaratumab plus doxorubicin and 4.1 months (2.8-5.4) with doxorubicin (stratified hazard ratio [HR] 0.67; 0.44-1.02, p=0.0615). Median overall survival was 26.5 months (20.9-31.7) with olaratumab plus doxorubicin and 14.7 months (9.2-17.1) with doxorubicin (stratified HR 0.46, 0.30-0.71, p=0.0003). The objective response rate was 18.2% (9.8-29.6) with olaratumab plus doxorubicin and 11.9% (5.3-22.2) with doxorubicin (p=0.3421). Steady state olaratumab serum concentrations were reached during cycle 3 with mean maximum and trough concentrations ranging from 419 μg/mL (geometric coefficient of variation in percentage [CV%] 26.2) to 487 μg/mL (CV% 33.0) and from 123 μg/mL (CV% 31.2) to 156 μg/mL (CV% 38.0), respectively. Adverse events that were more frequent with olaratumab plus doxorubicin versus doxorubicin alone included neutropenia (37 [58%] vs 23 [35%]), mucositis (34 [53%] vs 23 [35%]), nausea (47 [73%] vs 34 [52%]), vomiting (29 [45%] vs 12 [18%]), and diarrhoea (22 [34%] vs 15 [23%]). Febrile neutropenia of grade 3 or higher was similar in both groups (olaratumab plus doxorubicin: eight [13%] of 64 patients vs doxorubicin: nine [14%] of 65 patients).\n\nInterpretation: This study of olaratumab with doxorubicin in patients with advanced soft-tissue sarcoma met its predefined primary endpoint for progression-free survival and achieved a highly significant improvement of 11.8 months in median overall survival, suggesting a potential shift in the treatment of soft-tissue sarcoma.\n\nFunding: Eli Lilly and Company.\n\nIndexed on Europe PMC as PubMed record 27291997 (DOI 10.1016/s0140-6736(16)30587-6). Its author list gives \"Jones RL\" with the affiliation \"University Washington, Seattle, WA, USA; The Royal Marsden Hospital, London, UK\", which names The Royal Marsden; that is how the record was matched to Robin L. Jones, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet 2016","url":"https://doi.org/10.1016/s0140-6736(16)30587-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27291997/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27291997"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["robin-jones"],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2016,"doi":"10.1016/s0140-6736(16)30587-6","pmid":"27291997","authors":"Tap WD, Jones RL, Van Tine BA, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Robin L. Jones at The Royal Marsden, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-sedrak-ca-cancer-j-clin","kind":"paper","name":"Older adult participation in cancer clinical trials: A systematic review of barriers and interventions","aka":[],"tldr":"Paper cited by one bottleneck page, indexed on Europe PMC as PubMed record 33002206 and published in CA: A Cancer Journal for Clinicians; the citing page links this DOI, which is how the record was matched.","summary":"Cancer is a disease of aging and, as the world's population ages, the number of older persons with cancer is increasing and will make up a growing share of the oncology population in virtually every country. Despite this, older patients remain vastly underrepresented in research that sets the standards for cancer treatments. Consequently, most of what we know about cancer therapeutics is based on clinical trials conducted in younger, healthier patients, and effective strategies to improve clinical trial participation of older adults with cancer remain sparse. For this systematic review, the authors evaluated published studies regarding barriers to participation and interventions to improve participation of older adults in cancer trials. The quality of the available evidence was low and, despite a literature describing multifaceted barriers, only one intervention study aimed to increase enrollment of older adults in trials. The findings starkly amplify the paucity of evidence-based, effective strategies to improve participation of this underrepresented population in cancer trials. Within these limitations, the authors provide their opinion on how the current cancer research infrastructure must be modified to accommodate the needs of older patients. Several underused solutions are offered to expand clinical trials to include older adults with cancer. However, as currently constructed, these recommendations alone will not solve the evidence gap in geriatric oncology, and efforts are needed to meet older and frail adults where they are by expanding clinical trials designed specifically for this population and leveraging real-world data.\n\nIndexed on Europe PMC as PubMed record 33002206 (DOI 10.3322/caac.21638). Matched by DOI alone: one bottleneck page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"CA Cancer J Clin 2021","url":"https://doi.org/10.3322/caac.21638"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33002206/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33002206"}],"tags":["europepmc-ingest"],"related":["b-aging-comorbidity"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["ca-cancer-journal"],"dependsOn":[],"notes":[],"journal":"CA: A Cancer Journal for Clinicians","year":2021,"doi":"10.3322/caac.21638","pmid":"33002206","authors":"Sedrak MS, Freedman RA, Cohen HJ, et al.","paperType":"review","findings":[],"whatItMeans":"One bottleneck page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-olympia-nejm-2021","kind":"paper","name":"OlympiA: a year of olaparib after surgery for BRCA-mutated, high-risk early breast cancer","aka":[],"tldr":"In women born with a BRCA1 or BRCA2 mutation whose early breast cancer was high risk, a year of the PARP inhibitor olaparib after standard treatment cut relapses by more than 40% and later improved survival.","summary":"Double-blind, placebo-controlled phase 3 trial of 1,836 patients with germline BRCA1/2 mutations and HER2-negative early breast cancer at high risk of recurrence, randomised to one year of olaparib or placebo after completing local therapy and chemotherapy. Primary endpoint was invasive disease-free survival.\n\nThree-year iDFS was 85.9% vs 77.1% (HR 0.58) and distant disease-free survival 87.5% vs 80.4%. A 2022 update showed improved overall survival (HR 0.68). It was the first adjuvant PARP inhibitor and made germline testing part of treatment planning rather than only risk counselling.","asOf":"2026-09-08","links":[{"label":"NEJM 2021","url":"https://doi.org/10.1056/NEJMoa2105215"},{"label":"ClinicalTrials.gov NCT02032823","url":"https://clinicaltrials.gov/study/NCT02032823"}],"tags":[],"related":[],"cancers":["tnbc","breast-hr-positive"],"sections":[],"technologies":["parp-inhibitor","germline-testing","synthetic-lethality-approaches"],"targets":["parp","brca"],"drugs":["olaparib"],"companies":["astrazeneca","merck"],"institutions":[],"pathways":[],"terms":["germline-vs-somatic","synthetic-lethality","neoadjuvant-adjuvant","rcb"],"trials":["olympia"],"people":["andrew-tutt","judy-garber","evandro-de-azambuja","susan-domchek","shao-zhi-ming","sibylle-loibl","martine-piccart","charles-geyer"],"bottlenecks":["b-hereditary-risk","b-dormancy-mrd"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2021,"doi":"10.1056/NEJMoa2105215","authors":"Tutt ANJ, Garber JE, Kaufman B, et al.","paperType":"rct","findings":["Three-year invasive disease-free survival 85.9% vs 77.1%, an 8.8-point gain; HR 0.58 (99.5% CI 0.41-0.82).","Three-year distant disease-free survival 87.5% vs 80.4%; HR 0.57.","Overall survival HR 0.68 at the second interim analysis (2022), with 4-year OS 89.8% vs 86.4%.","Fewer new primary cancers, including ovarian, in the olaparib arm.","Olaparib was generally well tolerated; anaemia was the main grade 3 toxicity and no excess of myelodysplasia or leukaemia was seen at this follow-up."],"whatItMeans":"Everyone with HER2-negative early breast cancer that meets high-risk criteria should be offered germline BRCA testing, because a positive result now changes treatment: a year of olaparib after chemotherapy reduces relapse and death. It does not apply to low-risk tumours, HER2-positive disease, or somatic-only BRCA mutations.","caveats":["Most patients had not received platinum chemotherapy or pembrolizumab, so the benefit alongside the current KEYNOTE-522 regimen is extrapolated.","Long-term risk of second haematological malignancies with PARP inhibitors needs continued surveillance.","The hormone-receptor-positive subgroup was small (under a fifth of patients) and its benefit is less certain.","Access to germline testing is uneven, particularly in lower-income settings."],"changedPractice":true,"participants":1836},{"id":"paper-olympiad-ann-oncol-2019-update","kind":"paper","name":"OlympiAD final overall survival and tolerability results: Olaparib versus chemotherapy treatment of physician's choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer","aka":[],"tldr":"Later report from the OlympiAD trial registered as NCT02000622, in Annals of Oncology (2019); its title describes an updated or longer-term analysis.","summary":"Background: In the OlympiAD study, olaparib was shown to improve progression-free survival compared with chemotherapy treatment of physician's choice (TPC) in patients with a germline BRCA1 and/or BRCA2 mutation (BRCAm) and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (mBC). We now report the planned final overall survival (OS) results, and describe the most common adverse events (AEs) to better understand olaparib tolerability in this population.\n\nPatients and methods: OlympiAD, a Phase III, randomized, controlled, open-label study (NCT02000622), enrolled patients with a germline BRCAm and HER2-negative mBC who had received ≤2 lines of chemotherapy for mBC. Patients were randomized to olaparib tablets (300 mg bid) or predeclared TPC (capecitabine, vinorelbine, or eribulin). OS and safety were secondary end points.\n\nResults: A total of 205 patients were randomized to olaparib and 97 to TPC. At 64% data maturity, median OS was 19.3 months with olaparib versus 17.1 months with TPC (HR 0.90, 95% CI 0.66-1.23; P = 0.513); median follow-up was 25.3 and 26.3 months, respectively. HR for OS with olaparib versus TPC in prespecified subgroups were: prior chemotherapy for mBC [no (first-line setting): 0.51, 95% CI 0.29-0.90; yes (second/third-line): 1.13, 0.79-1.64]; receptor status (triple negative: 0.93, 0.62-1.43; hormone receptor positive: 0.86, 0.55-1.36); prior platinum (yes: 0.83, 0.49-1.45; no: 0.91, 0.64-1.33). Adverse events during olaparib treatment were generally low grade and manageable by supportive treatment or dose modification. There was a low rate of treatment discontinuation (4.9%), and the risk of developing anemia did not increase with extended olaparib exposure.\n\nConclusions: While there was no statistically significant improvement in OS with olaparib compared to TPC, there was the possibility of meaningful OS benefit among patients who had not received chemotherapy for metastatic disease. Olaparib was generally well-tolerated, with no evidence of cumulative toxicity during extended exposure. Please see the article online for additional video content.\n\nIndexed on Europe PMC as PubMed record 30689707 (DOI 10.1093/annonc/mdz012). Its abstract cites the registry id NCT02000622, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2019","url":"https://doi.org/10.1093/annonc/mdz012"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30689707/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30689707"},{"label":"ClinicalTrials.gov NCT02000622","url":"https://clinicaltrials.gov/study/NCT02000622"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["olympiad"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2019,"doi":"10.1093/annonc/mdz012","pmid":"30689707","authors":"Robson ME, Tung N, Conte P, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the OlympiAD trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-olympiad-nejm-2017","kind":"paper","name":"OlympiAD: olaparib versus chemotherapy in metastatic breast cancer with a germline BRCA mutation","aka":[],"tldr":"In women with metastatic HER2-negative breast cancer and an inherited BRCA mutation, the PARP inhibitor tablet olaparib delayed progression by almost three months compared with chemotherapy and caused fewer severe side effects.","summary":"Phase 3 trial of 302 patients with HER2-negative metastatic breast cancer and a germline BRCA1 or BRCA2 mutation, previously treated with up to two chemotherapy lines, randomised 2:1 to olaparib or single-agent chemotherapy of physician's choice.\n\nMedian progression-free survival was 7.0 versus 4.2 months (hazard ratio 0.58) with a response rate of 59.9 versus 28.8 percent; overall survival was not significantly different, though a benefit appeared in patients who had not received chemotherapy for metastatic disease.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2017","url":"https://doi.org/10.1056/NEJMoa1706450"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28578601/"}],"tags":[],"related":[],"cancers":["tnbc-metastatic"],"sections":[],"technologies":[],"targets":[],"drugs":["olaparib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["olympiad"],"people":["mark-robson"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2017,"doi":"10.1056/NEJMoa1706450","pmid":"28578601","authors":"Robson M, Im SA, Senkus E, et al.","paperType":"rct","findings":["Median progression-free survival 7.0 vs 4.2 months; hazard ratio 0.58.","Objective response 59.9 percent vs 28.8 percent; grade 3 or worse adverse events 36.6 percent vs 50.5 percent."],"whatItMeans":"Germline BRCA testing became part of metastatic breast cancer work-up, and olaparib (with talazoparib after EMBRACA) is a standard option, especially for triple-negative disease.","caveats":["No overall survival benefit in the whole population.","Platinum chemotherapy was not in the comparator arm."],"changedPractice":true,"participants":302},{"id":"paper-lumina-n-engl-j-med-2023","kind":"paper","name":"Omitting Radiotherapy after Breast-Conserving Surgery in Luminal A Breast Cancer","aka":[],"tldr":"Published report from the LUMINA trial registered as NCT01791829, in New England Journal of Medicine (2023), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Adjuvant radiotherapy is prescribed after breast-conserving surgery to reduce the risk of local recurrence. However, radiotherapy is inconvenient, costly, and associated with both short-term and long-term side effects. Clinicopathologic factors alone are of limited use in the identification of women at low risk for local recurrence in whom radiotherapy can be omitted. Molecularly defined intrinsic subtypes of breast cancer can provide additional prognostic information.\n\nMethods: We performed a prospective cohort study involving women who were at least 55 years of age, had undergone breast-conserving surgery for T1N0 (tumor size <2 cm and node negative), grade 1 or 2, luminal A-subtype breast cancer (defined as estrogen receptor positivity of ≥1%, progesterone receptor positivity of >20%, negative human epidermal growth factor receptor 2, and Ki67 index of ≤13.25%), and had received adjuvant endocrine therapy. Patients who met the clinical eligibility criteria were registered, and Ki67 immunohistochemical analysis was performed centrally. Patients with a Ki67 index of 13.25% or less were enrolled and did not receive radiotherapy. The primary outcome was local recurrence in the ipsilateral breast. In consultation with radiation oncologists and patients with breast cancer, we determined that if the upper boundary of the two-sided 90% confidence interval for the cumulative incidence at 5 years was less than 5%, this would represent an acceptable risk of local recurrence at 5 years.\n\nResults: Of 740 registered patients, 500 eligible patients were enrolled. At 5 years after enrollment, recurrence was reported in 2.3% of the patients (90% confidence interval [CI], 1.3 to 3.8; 95% CI, 1.2 to 4.1), a result that met the prespecified boundary. Breast cancer occurred in the contralateral breast in 1.9% of the patients (90% CI, 1.1 to 3.2), and recurrence of any type was observed in 2.7% (90% CI, 1.6 to 4.1).\n\nConclusions: Among women who were at least 55 years of age and had T1N0, grade 1 or 2, luminal A breast cancer that were treated with breast-conserving surgery and endocrine therapy alone, the incidence of local recurrence at 5 years was low with the omission of radiotherapy. (Funded by the Canadian Cancer Society and the Canadian Breast Cancer Foundation; LUMINA ClinicalTrials.gov number, NCT01791829.).\n\nIndexed on Europe PMC as PubMed record 37585627 (DOI 10.1056/nejmoa2302344). Its abstract cites the registry id NCT01791829, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2023","url":"https://doi.org/10.1056/nejmoa2302344"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37585627/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37585627"},{"label":"ClinicalTrials.gov NCT01791829","url":"https://clinicaltrials.gov/study/NCT01791829"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["lumina"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/nejmoa2302344","pmid":"37585627","authors":"Whelan TJ, Smith S, Parpia S, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT01791829 with the most citations, so it is the natural first reading for anyone following the LUMINA trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-warburg-science","kind":"paper","name":"On the origin of cancer cells","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 13298683 and published in Science; the citing page links this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 13298683 (DOI 10.1126/science.123.3191.309). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Science 1956","url":"https://doi.org/10.1126/science.123.3191.309"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/13298683/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/13298683"}],"tags":["europepmc-ingest"],"related":["metabolic-theory-of-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":1956,"doi":"10.1126/science.123.3191.309","pmid":"13298683","authors":"WARBURG O","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-arrillaga-romany-j-clin-oncol","kind":"paper","name":"ONC201 (Dordaviprone) in Recurrent H3 K27M-Mutant Diffuse Midline Glioma","aka":[],"tldr":"Paper cited by one treatment page, indexed on Europe PMC as PubMed record 38335473 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: Histone 3 (H3) K27M-mutant diffuse midline glioma (DMG) has a dismal prognosis with no established effective therapy beyond radiation. This integrated analysis evaluated single-agent ONC201 (dordaviprone), a first-in-class imipridone, in recurrent H3 K27M-mutant DMG.\n\nMethods: Fifty patients (pediatric, n = 4; adult, n = 46) with recurrent H3 K27M-mutant DMG who received oral ONC201 monotherapy in four clinical trials or one expanded access protocol were included. Eligible patients had measurable disease by Response Assessment in Neuro-Oncology (RANO) high-grade glioma (HGG) criteria and performance score (PS) ≥60 and were ≥90 days from radiation; pontine and spinal tumors were ineligible. The primary end point was overall response rate (ORR) by RANO-HGG criteria. Secondary end points included duration of response (DOR), time to response (TTR), corticosteroid response, PS response, and ORR by RANO low-grade glioma (LGG) criteria. Radiographic end points were assessed by dual-reader, blinded independent central review.\n\nResults: The ORR (RANO-HGG) was 20.0% (95% CI, 10.0 to 33.7). The median TTR was 8.3 months (range, 1.9-15.9); the median DOR was 11.2 months (95% CI, 3.8 to not reached). The ORR by combined RANO-HGG/LGG criteria was 30.0% (95% CI, 17.9 to 44.6). A ≥50% corticosteroid dose reduction occurred in 7 of 15 evaluable patients (46.7% [95% CI, 21.3 to 73.4]); PS improvement occurred in 6 of 34 evaluable patients (20.6% [95% CI, 8.7 to 37.9]). Grade 3 treatment-related treatment-emergent adverse events (TR-TEAEs) occurred in 20.0% of patients; the most common was fatigue (n = 5; 10%); no grade 4 TR-TEAEs, deaths, or discontinuations occurred.\n\nConclusion: ONC201 monotherapy was well tolerated and exhibited durable and clinically meaningful efficacy in recurrent H3 K27M-mutant DMG.\n\nIndexed on Europe PMC as PubMed record 38335473 (DOI 10.1200/jco.23.01134). Matched by DOI alone: one treatment page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2024","url":"https://doi.org/10.1200/jco.23.01134"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38335473/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38335473"}],"tags":["europepmc-ingest"],"related":["dordaviprone"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2024,"doi":"10.1200/jco.23.01134","pmid":"38335473","authors":"Arrillaga-Romany I, Gardner SL, Odia Y, et al.","paperType":"observational","findings":[],"whatItMeans":"One treatment page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-atkin-once-only-flexible-sigmoidoscopy-lancet-2010","kind":"paper","name":"Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicentre randomised controlled trial","aka":[],"tldr":"One look at the lower bowel with a short scope, offered once between 55 and 64, cut bowel cancer cases by a quarter and deaths by a third in a UK trial of 170,432 people.","summary":"The UK Flexible Sigmoidoscopy Trial, run in 14 UK centres by Atkin, Edwards, Kralj-Hans and colleagues, randomly allocated 170,432 men and women who had said on a previous questionnaire that they would accept screening to be offered one flexible sigmoidoscopy or not to be contacted at all. Randomisation was in blocks of 12, stratified by trial centre, general practice and household type. The primary outcomes were colorectal cancer incidence, including cases found at screening, and colorectal cancer mortality.\n\n40,674 of the 57,099 people in the intervention group (71 percent) underwent the test. Over a median 11.2 years, 2,524 participants were diagnosed with colorectal cancer and 727 deaths were certified from it.","asOf":"2026-09-24","links":[{"label":"Lancet 2010","url":"https://doi.org/10.1016/S0140-6736(10)60551-X"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20430429/"}],"tags":["colorectal-evidence"],"related":["paper-atkin-flexible-sigmoidoscopy-17-year-follow-up-lancet-2017"],"cancers":["colorectal"],"sections":["early-detection","prevention"],"technologies":["colorectal-screening","endoscopy"],"targets":[],"drugs":[],"companies":[],"institutions":["cruk"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-prevention-adoption"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2010,"doi":"10.1016/S0140-6736(10)60551-X","pmid":"20430429","authors":"Atkin WS, Edwards R, Kralj-Hans I, et al.","paperType":"rct","findings":["Intention to treat: colorectal cancer incidence reduced by 23 percent (hazard ratio 0.77, 95 percent CI 0.70 to 0.84) and mortality by 31 percent (0.69, 0.59 to 0.82).","Per protocol, adjusted for self-selection: incidence reduced 33 percent (0.67, 0.60 to 0.76) and mortality 43 percent (0.57, 0.45 to 0.72).","Distal colorectal cancer incidence halved (0.50, 0.42 to 0.59).","Numbers needed to screen to prevent one diagnosis 191 (145 to 277) and one death 489 (343 to 852)."],"whatItMeans":"The trial behind England's short-lived bowel scope screening programme, and the clearest demonstration that one endoscopic look, by removing adenomas, prevents cancer rather than only advancing its diagnosis.","caveats":["Participants had already said they would probably attend, so the trial population is more willing than a whole population.","Flexible sigmoidoscopy sees only the left colon, and the benefit was confined to distal cancers; right-sided disease, which is rising, is untouched.","England's bowel scope programme was discontinued and replaced by extending faecal immunochemical testing to younger ages."],"changedPractice":true,"participants":170432},{"id":"paper-egfr-glioblastoma-sci-signal-2009","kind":"paper","name":"Oncogenic EGFR signaling networks in glioma","aka":[],"tldr":"Review on EGFR in Glioma & glioblastoma, in Science signaling (2009), one of the most cited Europe PMC records with EGFR in its title.","summary":"The epidermal growth factor receptor (EGFR) is a primary contributor to glioblastoma (GBM) initiation and progression. Here, we examine how EGFR and key downstream signaling networks contribute to the hallmark characteristics of GBM such as rapid cancer cell proliferation and diffused invasion. Additionally, we discuss current therapeutic options for GBM patients and elaborate on the mechanisms through which EGFR promotes chemoresistance. We conclude by offering a perspective on how the potential of integrative systems biology may be harnessed to develop safe and effective treatment strategies for this disease.\n\nIndexed on Europe PMC as PubMed record 19738203 (DOI 10.1126/scisignal.287re6). Its title names EGFR and its text names Glioma & glioblastoma; PubMed types it as a review (Review). It was matched automatically to the idea \"Attack extrachromosomal DNA, the engine of oncogene amplification\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Sci Signal 2009","url":"https://doi.org/10.1126/scisignal.287re6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19738203/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/19738203"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Science signaling","year":2009,"doi":"10.1126/scisignal.287re6","pmid":"19738203","authors":"Huang PH, Xu AM, White FM","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for EGFR in Glioma & glioblastoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by EGFR in the title and Glioma & glioblastoma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-stopsack-mcspc-genomic-alterations-outcomes-ccr-2020","kind":"paper","name":"Oncogenic genomic alterations, clinical phenotypes and outcomes in metastatic castration-sensitive prostate cancer","aka":[],"tldr":"Sequencing 424 men at the point their cancer had spread but before hormone treatment failed showed which genetic changes make castration resistance come sooner, and which make it come later.","summary":"Clinical-grade targeted tumour sequencing was performed in men with metastatic castration-sensitive prostate cancer at a tertiary referral centre, quantifying copy-number alterations and alterations in predefined oncogenic signalling pathways. Among 424 men, 213 had high-volume disease and 211 low-volume disease, 275 had de novo metastatic disease and 149 metastatic recurrence of earlier non-metastatic disease. Rates of castration resistance and of death were higher in high-volume disease, and high-volume tumours carried more copy-number alterations, with the NOTCH, cell-cycle and epigenetic modifier pathways ranking highest. De novo metastatic disease differed from metastatic recurrence in the prevalence of CDK12 alterations but had similar prognosis. Rates of castration resistance differed 1.5-fold to 5-fold according to alterations in AR, SPOP (in the inverse direction) and TP53 and to the cell-cycle, WNT (inverse) and MYC pathways, adjusting for disease volume; overall survival differed 2-fold to 4-fold by AR, SPOP (inverse), WNT (inverse) and cell-cycle alterations. PI3K pathway alterations carried no independent prognostic weight.","asOf":"2026-09-25","links":[{"label":"Stopsack et al., Clin Cancer Res 2020: oncogenic alterations, phenotypes and outcomes in 424 men with metastatic castration-sensitive prostate cancer","url":"https://doi.org/10.1158/1078-0432.CCR-20-0168"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32220891/"},{"label":"cBioPortal study prad_mcspc_mskcc_2020 (MSK, Clin Cancer Res 2020; 424 metastatic castration-sensitive prostate cancers)","url":"https://www.cbioportal.org/study/summary?id=prad_mcspc_mskcc_2020"}],"tags":[],"related":[],"cancers":["prostate","prostate-mhspc"],"sections":[],"technologies":["cgp"],"targets":["androgen-receptor","spop","tp53","cdk12","apc"],"drugs":[],"companies":[],"institutions":[],"pathways":["ar-signaling","p53-cell-cycle","wnt","myc","cell-cycle-engine-cdks"],"terms":["castration-resistance","mcrpc-mhspc","driver-mutation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2020,"doi":"10.1158/1078-0432.CCR-20-0168","pmid":"32220891","authors":"Stopsack KH, Nandakumar S, Wibmer AG, et al.","paperType":"observational","findings":["AR and TP53 alterations and cell-cycle and MYC pathway alterations associated with faster castration resistance.","SPOP and WNT alterations associated with slower castration resistance and longer survival.","CDK12 alterations differed between de novo metastatic disease and metastatic recurrence.","PI3K pathway alterations carried no independent prognostic weight after adjustment."],"whatItMeans":"It fills the gap between the primary-tumour atlases and the castration-resistant series by describing the disease at the moment most treatment decisions are actually made, and it identifies SPOP as a favourable marker rather than a neutral one.","caveats":["Eighty-eight per cent of the men were White, at a single tertiary centre.","Targeted panel sequencing, so structural and non-coding events are invisible.","Prognostic associations, not a basis for withholding or intensifying treatment."],"changedPractice":false,"participants":424},{"id":"paper-chakravarty-jco-precis-oncol","kind":"paper","name":"OncoKB: A Precision Oncology Knowledge Base","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 28890946 and published in JCO Precision Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: With prospective clinical sequencing of tumors emerging as a mainstay in cancer care, there is an urgent need for a clinical support tool that distills the clinical implications associated with specific mutation events into a standardized and easily interpretable format. To this end, we developed OncoKB, an expert-guided precision oncology knowledge base.\n\nMethods: OncoKB annotates the biological and oncogenic effect and the prognostic and predictive significance of somatic molecular alterations. Potential treatment implications are stratified by the level of evidence that a specific molecular alteration is predictive of drug response based on US Food and Drug Administration (FDA) labeling, National Comprehensive Cancer Network (NCCN) guidelines, disease-focused expert group recommendations and the scientific literature.\n\nResults: To date, over 3000 unique mutations, fusions, and copy number alterations in 418 cancer-associated genes have been annotated. To test the utility of OncoKB, we annotated all genomic events in 5983 primary tumor samples in 19 cancer types. Forty-one percent of samples harbored at least one potentially actionable alteration, of which 7.5% were predictive of clinical benefit from a standard treatment. OncoKB annotations are available through a public web resource (http://oncokb.org/) and are also incorporated into the cBioPortal for Cancer Genomics to facilitate the interpretation of genomic alterations by physicians and researchers.\n\nConclusion: OncoKB, a comprehensive and curated precision oncology knowledge base, offers oncologists detailed, evidence-based information about individual somatic mutations and structural alterations present in patient tumors with the goal of supporting optimal treatment decisions.\n\nIndexed on Europe PMC as PubMed record 28890946 (DOI 10.1200/po.17.00011). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JCO Precis Oncol 2017","url":"https://doi.org/10.1200/po.17.00011"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28890946/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28890946"}],"tags":["europepmc-ingest"],"related":["variant-knowledgebases"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco-precision-oncology"],"dependsOn":[],"notes":[],"journal":"JCO Precision Oncology","year":2017,"doi":"10.1200/po.17.00011","pmid":"28890946","authors":"Chakravarty D, Gao J, Phillips SM, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nct06106308-j-clin-oncol-2025","kind":"paper","name":"Onvansertib in Combination With Chemotherapy and Bevacizumab in Second-Line Treatment of KRAS -Mutant Metastatic Colorectal Cancer: A Single-Arm, Phase II Trial","aka":[],"tldr":"Published report from the trial registered as NCT06106308, in Journal of Clinical Oncology (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Purpose: This phase II study evaluated the efficacy and tolerability of onvansertib, a polo-like kinase 1 (PLK1) inhibitor, in combination with fluorouracil, leucovorin, and irinotecan (FOLFIRI) + bevacizumab for the second-line treatment of KRAS -mutant metastatic colorectal cancer (mCRC).\n\nPatients and methods: This multicenter, open-label, single-arm study enrolled patients with KRAS -mutated mCRC previously treated with oxaliplatin and fluorouracil with or without bevacizumab. Patients received onvansertib (15 mg/m 2 once daily on days 1-5 and 15-19 of a 28-day cycle) and FOLFIRI + bevacizumab (days 1 and 15). The primary end point was the objective response rate (ORR), and secondary endpoints included progression-free survival (PFS), duration of response (DOR), and tolerability. Translational and preclinical studies were conducted in KRAS -mutant CRC.\n\nResults: Among the 53 patients treated, the confirmed ORR was 26.4% (95% CI, 15.3 to 40.3). The median DOR was 11.7 months (95% CI, 9.4 to not reached). Grade 3/4 adverse events were reported in 62% of patients. A post hoc analysis revealed that patients with no prior bevacizumab treatment had a significantly higher ORR and longer PFS compared with patients with prior bevacizumab treatment: ORR of 76.9% versus 10.0% (odds ratio of 30.0, P <.001) and median PFS of 14.9 months versus 6.6 months (hazard ratio of 0.16, P <.001). Our translational findings support that prior bevacizumab exposure contributes to onvansertib resistance. Preclinically, we showed that onvansertib inhibited the hypoxia pathway and exhibited robust antitumor activity in combination with bevacizumab through the inhibition of angiogenesis.\n\nConclusion: Onvansertib in combination with FOLFIRI + bevacizumab showed significant activity in the second-line treatment of patients with KRAS -mutant mCRC, particularly in patients with no prior bevacizumab treatment. These findings led to the evaluation of the combination in the first-line setting (ClinicalTrails.gov identifier: NCT06106308).\n\nIndexed on Europe PMC as PubMed record 39475591 (DOI 10.1200/jco-24-01266). Its abstract cites the registry id NCT06106308, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2025","url":"https://doi.org/10.1200/jco-24-01266"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39475591/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39475591"},{"label":"ClinicalTrials.gov NCT06106308","url":"https://clinicaltrials.gov/study/NCT06106308"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct06106308"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2025,"doi":"10.1200/jco-24-01266","pmid":"39475591","authors":"Ahn DH, Ridinger M, Cannon TL, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT06106308 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-habr-gama-nonoperative-stage-0-rectal-ann-surg-2004","kind":"paper","name":"Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results","aka":[],"tldr":"In São Paulo, Angelita Habr-Gama simply watched the patients whose rectal cancers had disappeared after chemoradiotherapy instead of operating. Ten-year survival was 98 percent, and she had invented watch and wait.","summary":"Habr-Gama, Perez, Nadalin and colleagues treated 265 patients with resectable distal rectal adenocarcinoma with neoadjuvant chemoradiation using fluorouracil, leucovorin and 5,040 cGy. Patients with an incomplete clinical response were referred for radical surgical resection. Those with a complete clinical response treated without operation (the observation group) were compared with those whose incomplete clinical response was treated surgically and whose specimens proved to be stage p0 (the resection group).\n\nIn the resection group nine definitive colostomies and seven diverting temporary ileostomies were performed, which is the morbidity the observation strategy avoids.","asOf":"2026-09-24","links":[{"label":"Ann Surg 2004","url":"https://doi.org/10.1097/01.sla.0000141194.27992.32"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/15383798/"}],"tags":["colorectal-evidence"],"related":["paper-garcia-aguilar-opra-organ-preservation-jco-2022","paper-cercek-dostarlimab-rectal-nejm-2022"],"cancers":["colorectal","rectal-cancer"],"sections":["surgery","radiation"],"technologies":["radiotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["organ-preservation","clinical-complete-response","chemoradiation","complete-response"],"trials":[],"people":["angelita-habr-gama"],"bottlenecks":["b-surgery-radiation-innovation","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Annals of Surgery","year":2004,"doi":"10.1097/01.sla.0000141194.27992.32","pmid":"15383798","authors":"Habr-Gama A, Perez RO, Nadalin W, et al.","paperType":"observational","findings":["Overall and disease-free ten-year survival across the series 97.7 percent and 84 percent.","Complete clinical response after chemoradiation in 71 of 265 patients (26.8 percent), managed without operation.","Twenty-two patients (8.3 percent) had an incomplete clinical response and pT0N0M0 resected specimens.","Five-year overall and disease-free survival 100 percent and 92 percent in the observation group against 88 percent and 83 percent in the resection group.","Three systemic recurrences in each group and two endorectal recurrences in the observation group."],"whatItMeans":"The origin of organ preservation in rectal cancer. Twenty years later OPRA made it a planned strategy and the dostarlimab series made it the expected outcome in mismatch repair-deficient disease.","caveats":["A single-centre non-randomised comparison of two groups defined by their response, so the comparison is confounded by prognosis.","Clinical complete response was assessed without modern MRI restaging, and local regrowth rates in later series are higher than reported here.","Long follow-up but no central review."],"changedPractice":true,"participants":265},{"id":"paper-andtbacka-optim-talimogene-jco-2015","kind":"paper","name":"OPTiM: the trial that made talimogene laherparepvec the first approved oncolytic virus","aka":[],"tldr":"Injecting an engineered herpes virus into melanoma lesions produced lasting shrinkage in about one patient in six, compared with one in fifty on the control drug, but it did not clearly help people live longer.","summary":"Open-label phase 3 trial randomising 436 patients with unresectable stage IIIB to IV melanoma 2:1 to talimogene laherparepvec injected into lesions or subcutaneous granulocyte-macrophage colony-stimulating factor. The primary endpoint was durable response rate, defined as an objective response lasting continuously for at least six months, judged by independent assessment.\n\nDurable response rate was 16.3 per cent with talimogene laherparepvec against 2.1 per cent with the control, odds ratio 8.9. Overall response rate was 26.4 per cent against 5.7 per cent. Median overall survival was 23.3 months against 18.9 months, hazard ratio 0.79, p = 0.051, which did not meet significance. Benefit concentrated in stage IIIB, IIIC and IVM1a disease and in patients who had not been treated before. The commonest adverse events were fatigue, chills and fever; the only grade 3 or 4 event in at least 2 per cent of treated patients was cellulitis.\n\nThe gap between the response result and the survival result is the single most important fact about this field. It is a licensing trial built on a response endpoint whose survival comparison did not reach significance, against a comparator that is not a modern melanoma treatment.","asOf":"2026-09-25","links":[{"label":"JCO 2015","url":"https://doi.org/10.1200/JCO.2014.58.3377"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26014293/"}],"tags":[],"related":["paper-chesney-j-clin-oncol"],"cancers":["melanoma","advanced-melanoma"],"sections":["immunotherapy"],"technologies":["oncolytic-virus"],"targets":[],"drugs":["talimogene-laherparepvec"],"companies":["amgen"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["howard-kaufman"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2015,"doi":"10.1200/JCO.2014.58.3377","pmid":"26014293","authors":"Andtbacka RH, Kaufman HL, Collichio F, et al.","paperType":"rct","findings":["Durable response rate 16.3 per cent (95% CI 12.1 to 20.5) with talimogene laherparepvec versus 2.1 per cent (95% CI 0 to 4.5) with granulocyte-macrophage colony-stimulating factor; odds ratio 8.9, p < 0.001.","Overall response rate 26.4 per cent versus 5.7 per cent.","Median overall survival 23.3 months versus 18.9 months; hazard ratio 0.79 (95% CI 0.62 to 1.00), p = 0.051, not statistically significant.","Effect was largest in stage IIIB, IIIC and IVM1a disease and in treatment-naive patients.","Cellulitis was the only grade 3 or 4 adverse event occurring in at least 2 per cent of treated patients, at 2.1 per cent; no fatal treatment-related events."],"whatItMeans":"This is the approval that created the class, and it is also the clearest example of how the class is oversold. A durable response rate eight times the comparator is a real local effect on injectable lesions. The survival comparison did not reach significance, and the comparator was granulocyte-macrophage colony-stimulating factor rather than a checkpoint inhibitor, which by 2015 was already the standard. A reader told that a virus improves survival in melanoma is being told something this trial did not show.","caveats":["The comparator arm received granulocyte-macrophage colony-stimulating factor, which is not a standard melanoma treatment; the trial predates the routine use of anti-PD-1 therapy.","Overall survival did not reach statistical significance (p = 0.051).","Open-label, and response assessment in injected lesions is hard to blind.","Requires lesions that can be injected, which restricts use to accessible skin, subcutaneous and nodal disease."],"changedPractice":true,"participants":436},{"id":"paper-kim-t1b-gallbladder-cancer-international-jhbps-2018","kind":"paper","name":"Optimal surgical treatment in patients with T1b gallbladder cancer: An international multicenter study","aka":[],"tldr":"Across 14 specialist centres in Korea, Japan, Chile and the United States, people with a gallbladder cancer that had just reached the muscle layer did equally well whether or not they had a second, bigger operation: about 95 in 100 were alive and free of the disease at five years either way.","summary":"Retrospective study of 272 patients with T1b gallbladder cancer resected at 14 centres with specialised hepatobiliary surgeons and pathologists; 237 qualified for analysis (90 men, 147 women). Simple cholecystectomy was performed in 116 (48.9 percent) and extended cholecystectomy in 121 (51.1 percent). Five-year disease-specific survival was 94.6 percent overall and did not differ between simple and extended cholecystectomy (93.7 versus 95.5 percent, p=0.496), in America (82.3 versus 100 percent, p=0.249) or Asia (98.6 versus 95.2 percent, p=0.690), nor by lymph node metastasis (p=0.688) or tumour location (p=0.474).","asOf":"2026-09-24","links":[{"label":"J Hepatobiliary Pancreat Sci 2018","url":"https://doi.org/10.1002/jhbp.593"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30562839/"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["radical-cholecystectomy","incidental-gallbladder-cancer","tnm-staging"],"trials":[],"people":[],"bottlenecks":["b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of Hepato-Biliary-Pancreatic Sciences","year":2018,"doi":"10.1002/jhbp.593","pmid":"30562839","authors":"Kim HS, Park JW, Kim H, et al.","paperType":"observational","findings":["Five-year disease-specific survival 93.7 percent after simple cholecystectomy vs 95.5 percent after extended cholecystectomy (p=0.496) in 237 T1b patients.","No difference by region, nodal status or tumour location."],"whatItMeans":"The strongest data against routine re-resection for T1b tumours, which guidelines still recommend. A prospective study or registry with standardised pathology is the missing step; the authors' own conclusion is that extended cholecystectomy is not needed for T1b.","caveats":["Retrospective; patients offered simple cholecystectomy may have had favourable features.","Pathological standardisation of T1b across centres is itself difficult, as the authors note."],"changedPractice":false,"participants":237},{"id":"paper-nct03944772-jco-precis-oncol-2025","kind":"paper","name":"ORCHARD: Osimertinib Plus Necitumumab in Patients With Epidermal Growth Factor Receptor-Mutated Advanced Non-Small Cell Lung Cancer With a Secondary Epidermal Growth Factor Receptor Alteration Whose Disease Had Progressed on First-Line Osimertinib","aka":[],"tldr":"Published report from the ORCHARD trial registered as NCT03944772, in JCO Precision Oncology (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Purpose: ORCHARD (ClinicalTrials.gov identifier: NCT03944772) is a phase II, biomarker-directed platform study designed to characterize resistance mechanisms and evaluate novel drug combinations in patients with epidermal growth factor receptor ( EGFR)-mutated advanced non-small cell lung cancer who have progressed on first-line osimertinib. We report final results of the module assessing the efficacy and safety of osimertinib plus necitumumab (a monoclonal antibody that blocks EGFR) in patients with ≥one of the following: EGFR amplification or select secondary EGFR alterations (L718 or G724 mutation, or exon 20 insertion).\n\nMaterials and methods: Patients received osimertinib (80 mg orally once daily) plus necitumumab (800 mg intravenously, days 1 and 8 of a 3-week cycle) until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR) per RECIST 1.1 by investigator assessment.\n\nResults: Overall, 19 patients received osimertinib plus necitumumab; at data cutoff (April 18, 2023), all patients had discontinued treatment. The ORR was 11% (80% CI, 3 to 26); two patients had a confirmed partial response, with duration of response of 10.4 and 6.0 months; both patients had EGFR amplification. The median progression-free survival was 4.0 months (95% CI, 1.3 to 5.4) and the overall survival was 11.4 months (95% CI, 6.6 to 15.5). Ten patients (53%) had grade ≥3 adverse events, most commonly embolism (not otherwise specified, pulmonary embolism or deep vein thrombosis, reported in four patients; 21%). The safety profile of the combination was consistent with the known profiles of the two individual drugs, and no new signals were identified.\n\nConclusion: Osimertinib plus necitumumab demonstrated modest clinical benefit, and the overall risk-benefit analysis indicates that further evaluation of the regimen is not warranted in these molecularly defined subsets of osimertinib resistance.\n\nIndexed on Europe PMC as PubMed record 40466026 (DOI 10.1200/po-24-00818). Its abstract cites the registry id NCT03944772, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"JCO Precis Oncol 2025","url":"https://doi.org/10.1200/po-24-00818"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40466026/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40466026"},{"label":"ClinicalTrials.gov NCT03944772","url":"https://clinicaltrials.gov/study/NCT03944772"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct03944772"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco-precision-oncology"],"dependsOn":[],"notes":[],"journal":"JCO Precision Oncology","year":2025,"doi":"10.1200/po-24-00818","pmid":"40466026","authors":"Riess JW, de Langen AJ, Ponce S, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03944772 with the most citations, so it is the natural first reading for anyone following the ORCHARD trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-garcia-aguilar-opra-organ-preservation-jco-2022","kind":"paper","name":"Organ preservation in patients with rectal adenocarcinoma treated with total neoadjuvant therapy (OPRA)","aka":[],"tldr":"Planning for watch and wait from the start, rather than stumbling into it, let half of 324 rectal cancer patients keep their rectum with no loss of disease-free survival.","summary":"Garcia-Aguilar, Patil, Gollub and colleagues randomised 324 patients with stage II or III rectal adenocarcinoma to induction chemotherapy followed by chemoradiotherapy, or chemoradiotherapy followed by consolidation chemotherapy, and then to total mesorectal excision or watch and wait on the basis of tumour response. Both groups received four months of infusional fluorouracil-leucovorin-oxaliplatin or capecitabine-oxaliplatin and 5,000 to 5,600 cGy of radiation with concurrent fluorouracil or capecitabine. The trial was designed as two stand-alone studies with disease-free survival as the primary endpoint for each, compared against a null hypothesis based on historical data; the secondary endpoint was survival free of total mesorectal excision.\n\nPatients who underwent total mesorectal excision after restaging and those who underwent it after regrowth had similar disease-free survival, which is the finding that makes a trial of watch and wait ethically defensible.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2022","url":"https://doi.org/10.1200/JCO.22.00032"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35483010/"},{"label":"Europe PMC full text (PMC9362876)","url":"https://europepmc.org/article/MED/35483010"},{"label":"J Clin Oncol 2022","url":"https://doi.org/10.1200/jco.22.00032"}],"tags":["colorectal-evidence"],"related":["paper-habr-gama-nonoperative-stage-0-rectal-ann-surg-2004","paper-bahadoer-rapido-short-course-radiotherapy-lancet-oncol-2021","organ-preservation"],"cancers":["colorectal","rectal-cancer"],"sections":["surgery","radiation"],"technologies":["radiotherapy","mri"],"targets":[],"drugs":["folfox","capox","capecitabine","fluorouracil"],"companies":[],"institutions":["mskcc"],"pathways":[],"terms":["organ-preservation","clinical-complete-response","total-neoadjuvant-therapy","total-mesorectal-excision"],"trials":["opra"],"people":["julio-garcia-aguilar","andrea-cercek"],"bottlenecks":["b-surgery-radiation-innovation","b-toxicity-qol"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2022,"doi":"10.1200/JCO.22.00032","pmid":"35483010","authors":"Garcia-Aguilar J, Patil S, Gollub MJ, et al.","paperType":"rct","findings":["Three-year disease-free survival 76 percent (95 percent CI 69 to 84) after induction chemotherapy then chemoradiotherapy and 76 percent (69 to 83) after chemoradiotherapy then consolidation chemotherapy, matching the 75 percent historical rate.","Three-year survival free of total mesorectal excision 41 percent (33 to 50) and 53 percent (45 to 62) respectively.","No differences between groups in local recurrence-free, distant metastasis-free or overall survival.","Disease-free survival was similar whether total mesorectal excision followed restaging or followed regrowth."],"whatItMeans":"Organ preservation became a plan rather than an accident: consolidation chemotherapy after chemoradiotherapy gives the best chance of keeping the rectum, and salvage surgery after regrowth does not appear to cost survival.","caveats":["The disease-free survival comparison is against historical controls, not a randomised surgical arm.","Median follow-up three years; regrowth continues after that and the durability of organ preservation is not settled.","Quality of life and bowel function after watch and wait against surgery are reported separately and are not uniformly better."],"changedPractice":true,"participants":324},{"id":"paper-tiriac-cancer-discov","kind":"paper","name":"Organoid Profiling Identifies Common Responders to Chemotherapy in Pancreatic Cancer","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 29853643 and published in Cancer Discovery; the citing page links this DOI, which is how the record was matched.","summary":"Pancreatic cancer is the most lethal common solid malignancy. Systemic therapies are often ineffective, and predictive biomarkers to guide treatment are urgently needed. We generated a pancreatic cancer patient-derived organoid (PDO) library that recapitulates the mutational spectrum and transcriptional subtypes of primary pancreatic cancer. New driver oncogenes were nominated and transcriptomic analyses revealed unique clusters. PDOs exhibited heterogeneous responses to standard-of-care chemotherapeutics and investigational agents. In a case study manner, we found that PDO therapeutic profiles paralleled patient outcomes and that PDOs enabled longitudinal assessment of chemosensitivity and evaluation of synchronous metastases. We derived organoid-based gene expression signatures of chemosensitivity that predicted improved responses for many patients to chemotherapy in both the adjuvant and advanced disease settings. Finally, we nominated alternative treatment strategies for chemorefractory PDOs using targeted agent therapeutic profiling. We propose that combined molecular and therapeutic profiling of PDOs may predict clinical response and enable prospective therapeutic selection. Significance: New approaches to prioritize treatment strategies are urgently needed to improve survival and quality of life for patients with pancreatic cancer. Combined genomic, transcriptomic, and therapeutic profiling of PDOs can identify molecular and functional subtypes of pancreatic cancer, predict therapeutic responses, and facilitate precision medicine for patients with pancreatic cancer. Cancer Discov; 8(9); 1112-29. ©2018 AACR. See related commentary by Collisson, p. 1062 This article is highlighted in the In This Issue feature, p. 1047.\n\nIndexed on Europe PMC as PubMed record 29853643 (DOI 10.1158/2159-8290.cd-18-0349). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer Discov 2018","url":"https://doi.org/10.1158/2159-8290.cd-18-0349"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29853643/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29853643"}],"tags":["europepmc-ingest"],"related":["pdac-organoid-pharmacotyping"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-discovery"],"dependsOn":[],"notes":[],"journal":"Cancer Discovery","year":2018,"doi":"10.1158/2159-8290.cd-18-0349","pmid":"29853643","authors":"Tiriac H, Belleau P, Engle DD, et al.","paperType":"basic","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-lu-laura-osimertinib-stage-iii-nejm-2024","kind":"paper","name":"Osimertinib after chemoradiotherapy in stage III EGFR-mutated NSCLC","aka":[],"tldr":"For stage III lung cancer with an EGFR mutation, the standard consolidation immunotherapy works poorly. LAURA gave the EGFR tablet instead and pushed median time to progression from 5.6 months to 39.1.","summary":"The LAURA trial investigators, reported by Lu, Kato, Dong and colleagues with Ramalingam as senior author, randomised 216 patients with unresectable EGFR-mutated stage III non-small-cell lung cancer who had not progressed during or after chemoradiotherapy to osimertinib (143) or placebo (73), in a double-blind, placebo-controlled phase 3 design.\n\nIt closes a hole the PACIFIC regimen left open. Durvalumab consolidation after chemoradiotherapy became standard for stage III disease, but EGFR-mutant tumours respond poorly to checkpoint blockade, so the patients with the most treatable biology in the metastatic setting had the least to gain in the curative one.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2024","url":"https://doi.org/10.1056/NEJMoa2402614"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38828946/"},{"label":"ClinicalTrials.gov NCT03521154","url":"https://clinicaltrials.gov/study/NCT03521154"},{"label":"N Engl J Med 2024","url":"https://doi.org/10.1056/nejmoa2402614"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38828946"}],"tags":["lung-evidence"],"related":["paper-pacific-nejm-2017","paper-adaura-nejm-2020","paper-flaura-nejm-2018"],"cancers":["lung-cancer","nsclc","egfr-mutant-nsclc","stage-iii-unresectable-nsclc"],"sections":["targeted-therapy","radiation"],"technologies":["radiotherapy","imrt-igrt"],"targets":["egfr"],"drugs":["osimertinib","durvalumab"],"companies":["astrazeneca"],"institutions":[],"pathways":[],"terms":["chemoradiation","driver-mutation"],"trials":["laura"],"people":["suresh-ramalingam"],"bottlenecks":["b-resistance","b-biomarker-validation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2024,"doi":"10.1056/NEJMoa2402614","pmid":"38828946","authors":"Lu S, Kato T, Dong X, et al.","paperType":"rct","findings":["Median progression-free survival by blinded independent central review 39.1 months with osimertinib against 5.6 months with placebo: hazard ratio for progression or death 0.16 (95 percent confidence interval 0.10 to 0.24).","216 patients who had undergone chemoradiotherapy were randomised, 143 to osimertinib and 73 to placebo.","Treatment continued until disease progression or discontinuation of the regimen."],"whatItMeans":"Stage III lung cancer is now treated by genotype as well as by stage: an EGFR mutation moves a patient from durvalumab consolidation to osimertinib consolidation. It is also the strongest hazard ratio in the lung cancer literature, which is a reason to read the overall survival data carefully when they arrive.","caveats":["A hazard ratio of 0.16 on progression-free survival in a setting where the aim is cure; overall survival was immature and the placebo arm could cross over.","Small trial, 216 patients, in a population that has to be found by molecular testing of stage III disease, which is not universal.","Optimal duration of osimertinib, and whether it is deferring recurrence or preventing it, are unanswered."],"changedPractice":true,"participants":216},{"id":"paper-osimertinib-nsclc-n-engl-j-med-2017","kind":"paper","name":"Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer","aka":[],"tldr":"Phase 2 or 3 results paper on Osimertinib in Non-small-cell lung cancer, in New England Journal of Medicine (2017), one of the most cited Europe PMC records with Osimertinib in its title.","summary":"Background: Osimertinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that is selective for both EGFR-TKI sensitizing and T790M resistance mutations in patients with non-small-cell lung cancer. The efficacy of osimertinib as compared with platinum-based therapy plus pemetrexed in such patients is unknown.\n\nMethods: In this randomized, international, open-label, phase 3 trial, we assigned 419 patients with T790M-positive advanced non-small-cell lung cancer, who had disease progression after first-line EGFR-TKI therapy, in a 2:1 ratio to receive either oral osimertinib (at a dose of 80 mg once daily) or intravenous pemetrexed (500 mg per square meter of body-surface area) plus either carboplatin (target area under the curve, 5 [AUC5]) or cisplatin (75 mg per square meter) every 3 weeks for up to six cycles; maintenance pemetrexed was allowed. In all the patients, disease had progressed during receipt of first-line EGFR-TKI therapy. The primary end point was investigator-assessed progression-free survival.\n\nResults: The median duration of progression-free survival was significantly longer with osimertinib than with platinum therapy plus pemetrexed (10.1 months vs. 4.4 months; hazard ratio; 0.30; 95% confidence interval [CI], 0.23 to 0.41; P<0.001). The objective response rate was significantly better with osimertinib (71%; 95% CI, 65 to 76) than with platinum therapy plus pemetrexed (31%; 95% CI, 24 to 40) (odds ratio for objective response, 5.39; 95% CI, 3.47 to 8.48; P<0.001). Among 144 patients with metastases to the central nervous system (CNS), the median duration of progression-free survival was longer among patients receiving osimertinib than among those receiving platinum therapy plus pemetrexed (8.5 months vs. 4.2 months; hazard ratio, 0.32; 95% CI, 0.21 to 0.49). The proportion of patients with adverse events of grade 3 or higher was lower with osimertinib (23%) than with platinum therapy plus pemetrexed (47%).\n\nConclusions: Osimertinib had significantly greater efficacy than platinum therapy plus pemetrexed in patients with T790M-positive advanced non-small-cell lung cancer (including those with CNS metastases) in whom disease had progressed during first-line EGFR-TKI therapy. (Funded by AstraZeneca; AURA3 ClinicalTrials.gov number, NCT02151981.).\n\nIndexed on Europe PMC as PubMed record 27959700 (DOI 10.1056/nejmoa1612674). Its title names Osimertinib and its text names Non-small-cell lung cancer; PubMed types it as a clinical trial report (Clinical Trial, Phase III, Comparative Study, Research Support, Non-U.S. Gov't, research-article, Multicenter Study, Randomized Controlled Trial). It was matched automatically to the idea \"Treat brain metastases as a disease with its own trials programme\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2017","url":"https://doi.org/10.1056/nejmoa1612674"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27959700/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27959700"}],"tags":["europepmc-ingest"],"related":["lung-cancer-evidence-roadmap","paper-kobayashi-egfr-t790m-gefitinib-resistance-nejm-2005"],"cancers":["lung-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2017,"doi":"10.1056/nejmoa1612674","pmid":"27959700","authors":"Mok TS, Wu Y-L, Ahn M-J, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Osimertinib in Non-small-cell lung cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Osimertinib in the title and Non-small-cell lung cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-planchard-flaura2-osimertinib-chemotherapy-nejm-2023","kind":"paper","name":"Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC","aka":[],"tldr":"FLAURA2 added chemotherapy to the standard EGFR tablet in 557 patients and cut the risk of the cancer growing by 38 percent, at the cost of chemotherapy's side effects for everybody.","summary":"The FLAURA2 investigators, reported by Planchard, Jänne, Cheng and colleagues, randomised 557 patients with previously untreated EGFR-mutated (exon 19 deletion or L858R) advanced non-small-cell lung cancer 1 to 1 between osimertinib 80 mg daily with pemetrexed and platinum chemotherapy, and osimertinib alone. The primary endpoint was investigator-assessed progression-free survival.\n\nIt is one of two 2023 and 2024 trials that beat osimertinib monotherapy, the other being MARIPOSA with amivantamab and lazertinib. Both ask the same unresolved question: whether intensifying first-line treatment for everybody is better than keeping a second option in reserve, and for which patients.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2023","url":"https://doi.org/10.1056/NEJMoa2306434"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37937763/"},{"label":"ClinicalTrials.gov NCT04035486","url":"https://clinicaltrials.gov/study/NCT04035486"}],"tags":["lung-evidence"],"related":["paper-flaura-nejm-2018","paper-mariposa-nejm-2024","paper-osimertinib-nsclc-n-engl-j-med-2020"],"cancers":["lung-cancer","nsclc","egfr-mutant-nsclc"],"sections":["targeted-therapy"],"technologies":[],"targets":["egfr"],"drugs":["osimertinib","pemetrexed","cisplatin","carboplatin"],"companies":["astrazeneca"],"institutions":[],"pathways":[],"terms":["driver-mutation","oncogene-addiction"],"trials":["flaura2"],"people":["david-planchard","pasi-janne"],"bottlenecks":["b-combination-space","b-resistance","b-toxicity-qol"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/NEJMoa2306434","pmid":"37937763","authors":"Planchard D, Jänne PA, Cheng Y, et al.","paperType":"rct","findings":["Investigator-assessed progression-free survival was significantly longer with osimertinib plus chemotherapy: hazard ratio for progression or death 0.62 (95 percent confidence interval 0.49 to 0.79).","557 patients underwent randomisation, 1 to 1, with exon 19 deletion or L858R mutations.","Europe PMC truncates the abstract after the P value for the primary endpoint, so the median progression-free survival figures and the safety numbers are not quoted here."],"whatItMeans":"Adding chemotherapy to osimertinib delays progression. Whether it extends life, and whether the same benefit could be had by giving the chemotherapy later to the patients who need it, is what the overall survival analysis and the registry watch on this roadmap are for.","caveats":["Progression-free survival by investigator assessment as the primary endpoint; overall survival was immature at this report.","Everyone in the combination arm receives platinum chemotherapy, including the substantial fraction who would have done well on osimertinib alone for years.","No direct comparison against MARIPOSA's amivantamab and lazertinib combination exists."],"changedPractice":true,"participants":557},{"id":"paper-ostrem-kras-g12c-nature-2013","kind":"paper","name":"Ostrem and Shokat: the hidden pocket that made KRAS G12C druggable","aka":[],"tldr":"Using disulfide-tethering screens, Shokat's laboratory found small molecules that bind covalently to the mutant cysteine of KRAS G12C in a previously unknown pocket beneath switch II, locking the oncoprotein in its inactive GDP-bound state.","summary":"KRAS had been considered undruggable for three decades because it binds GTP with picomolar affinity and has no obvious deep pocket. Ostrem and colleagues exploited the cysteine introduced by the G12C mutation, present in about 13% of lung adenocarcinomas, screening a library of cysteine-reactive fragments by tethering.\n\nCrystal structures revealed that the hits bound in a cryptic pocket (switch-II pocket, S-IIP) that exists only in the GDP-bound state. The compounds impaired SOS-catalysed nucleotide exchange, shifted KRAS towards GDP binding, and reduced Raf effector binding, selectively killing G12C-mutant cells. The compounds were weak but demonstrated mechanism.\n\nThis work led directly to ARS-853, ARS-1620 and then sotorasib (approved 2021) and adagrasib (2022), the first KRAS inhibitors, and inspired covalent and non-covalent approaches to other RAS mutants.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1038/nature12796"}],"tags":[],"related":["paper-drug-dosing-conundrum-nejm-2021","kras-roadmap","paper-codebreak-100-sotorasib-kras-g12c-pancreatic-nejm-2023","paper-almoguera-kras-codon-12-pancreatic-cell-1988"],"cancers":["nsclc","colorectal","pancreatic"],"sections":["targeted-therapy","drug-discovery"],"technologies":["kras-inhibitors","kinase-inhibitors"],"targets":["kras"],"drugs":["sotorasib","adagrasib","daraxonrasib"],"companies":[],"institutions":["ucsf"],"pathways":["ras-mapk"],"terms":[],"trials":[],"people":["kevan-shokat"],"bottlenecks":["b-undruggable-targets","b-resistance"],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2013,"doi":"10.1038/nature12796","pmid":"24256730","authors":"Ostrem JM, Peters U, Sos ML, Wells JA, Shokat KM","paperType":"basic","findings":["Identified covalent compounds binding cysteine 12 of KRAS G12C in a cryptic switch-II pocket visible only in the GDP-bound state","Compounds impaired SOS-mediated nucleotide exchange and shifted the nucleotide preference from GTP to GDP","Effector (Raf) binding was decreased and G12C-mutant cell viability selectively reduced","Mutant-specific mechanism: wild-type KRAS was unaffected, giving a therapeutic window"],"whatItMeans":"The most frequently mutated oncogene in cancer stopped being undruggable, and patients with KRAS G12C lung and bowel cancers now have targeted pills. The approach, exploiting a mutation-created chemical handle and an inactive-state pocket, has become a template for other hard targets.","caveats":["The original compounds were micromolar tools, not drugs; a decade of medicinal chemistry was required","Applies only to G12C; other KRAS mutants lack a reactive cysteine, though pan-RAS(ON) inhibitors are now emerging","Clinical responses to G12C inhibitors are shorter than for EGFR or ALK inhibitors, and resistance is rapid","Tumour-type dependence: colorectal G12C cancers respond poorly to monotherapy"],"changedPractice":false},{"id":"paper-outback-lancet-oncol-2023","kind":"paper","name":"OUTBACK: adjuvant carboplatin-paclitaxel after chemoradiotherapy for locally advanced cervical cancer","aka":[],"tldr":"Adding four cycles of carboplatin-paclitaxel chemotherapy after standard chemoradiation did not improve survival in locally advanced cervical cancer and caused more side effects, so adjuvant chemotherapy is not recommended.","summary":"Phase 3 trial of 919 women with locally advanced cervical cancer randomised to cisplatin chemoradiotherapy alone or followed by four cycles of adjuvant carboplatin and paclitaxel.\n\nFive-year overall survival was 72 versus 71 percent and progression-free survival 63 versus 61 percent, with more grade 3 to 5 adverse events with adjuvant chemotherapy (81 versus 62 percent) and a fifth of patients never starting it.","asOf":"2026-09-17","links":[{"label":"Lancet Oncol 2023","url":"https://doi.org/10.1016/S1470-2045(23)00147-X"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37080223/"}],"tags":[],"related":[],"cancers":["locally-advanced-cervical-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["outback"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2023,"doi":"10.1016/S1470-2045(23)00147-X","pmid":"37080223","authors":"Mileshkin LR, Moore KN, Barnes EH, et al.","paperType":"rct","findings":["Five-year overall survival 72 percent vs 71 percent.","Grade 3 to 5 adverse events 81 percent vs 62 percent."],"whatItMeans":"Chemotherapy after chemoradiation adds toxicity without benefit; the search for improvement has moved to induction chemotherapy (INTERLACE) and immunotherapy (KEYNOTE-A18).","caveats":["Compliance with adjuvant chemotherapy was incomplete, which may have diluted any effect."],"changedPractice":true,"participants":919},{"id":"paper-jimenez-gaona-ivermectin-loja-ecuador-2023","kind":"paper","name":"Outcome of ivermectin in cancer treatment: an experience in Loja, Ecuador","aka":[],"tldr":"A survey in rural Ecuador found that about one in five people with cancer were taking cattle ivermectin alongside their treatment, while the specialists interviewed said there was no evidence and did not recommend it.","summary":"Using observation, surveys and interviews in the rural Loja province, the study found that 19 percent of participants diagnosed with cancer took ivermectin-based medicines, commonly used in cattle, as an alternative therapy without leaving chemotherapy, radiotherapy or immunotherapy, while 81 percent used it for other diseases (Loja survey 2023). Participants said they felt better after the third dose; the specialists interviewed said there was no authorisation to prescribe it, no scientific knowledge of its use in humans for cancer, and that they did not recommend it (Loja survey 2023).","asOf":"2026-09-24","links":[{"label":"Loja survey 2023","url":"https://doi.org/10.3390/nursrep13010030"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36976682/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["ivermectin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct07487805"],"people":[],"bottlenecks":["b-misinformation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo agent (Claude Fable 5.1)","editedOn":"2026-09-24","note":"Written from cached ClinicalTrials.gov v2, Europe PMC, DailyMed, Drugs@FDA and WHO eEML responses; no figure appears without its source link."},"journal":"Nursing Reports","year":2023,"doi":"10.3390/nursrep13010030","pmid":"36976682","authors":"Jiménez-Gaona Y, Vivanco-Galván O, Morales-Larreategui G, Cabrera-Bejarano A, Lakshminarayanan V.","paperType":"observational","findings":["19 percent of surveyed cancer patients used ivermectin as an add-on to their treatment.","Self-reported improvement only; specialists interviewed did not recommend it."],"whatItMeans":"Shows how widespread use already is where cancer care is expensive, and why the ICONIC investigators cite it as a reason to run a proper trial.","caveats":["Small mixed-methods survey; no clinical outcomes measured."],"changedPractice":false},{"id":"paper-szpakowski-gallbladder-polyps-20-year-cohort-jama-netw-open-2020","kind":"paper","name":"Outcomes of Gallbladder Polyps and Their Association With Gallbladder Cancer in a 20-Year Cohort","aka":[],"tldr":"Following more than 600,000 people for two decades, those with gallbladder polyps on ultrasound were no more likely to get gallbladder cancer than those without, though the risk did climb for polyps of a centimetre or more; the authors question whether watching polyps finds cancer at all.","summary":"Kaiser Permanente Northern California cohort of 622,227 adults with abdominal ultrasonography between 1995 and 2014. Polyps were present in 5.8 percent of scans (35,870 people) and in 6.0 percent (22 of 365) of people later diagnosed with gallbladder cancer. Among 35,856 people with polyps, 19 (0.053 percent) developed gallbladder cancer, the same as those without polyps (316 of 586,357; 0.054 percent). The cancer rate was 11.3 per 100,000 person-years overall, 1.3 for polyps under 6 mm and 128.2 for polyps of 10 mm or more; among those followed for at least a year it was 3.6. Growth of 2 mm or more at 10 years occurred in 66.2 percent of polyps initially under 6 mm and 52.9 percent of those 6 to under 10 mm, so growth is part of natural history.","asOf":"2026-09-24","links":[{"label":"JAMA Netw Open 2020","url":"https://doi.org/10.1001/jamanetworkopen.2020.5143"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32421183/"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":["ultrasound"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["gallbladder-polyp","overdiagnosis","screening"],"trials":[],"people":[],"bottlenecks":["b-overdiagnosis"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"JAMA Network Open","year":2020,"doi":"10.1001/jamanetworkopen.2020.5143","pmid":"32421183","authors":"Szpakowski JL, Tucker LY.","paperType":"observational","findings":["Gallbladder cancer in 0.053 percent of 35,856 people with polyps vs 0.054 percent of 586,357 without.","Cancer rate 11.3 per 100,000 person-years overall; 1.3 for polyps under 6 mm and 128.2 for 10 mm or more.","Growth of 2 mm or more at 10 years in 66.2 percent of polyps under 6 mm and 52.9 percent of 6 to under 10 mm polyps."],"whatItMeans":"The largest natural history study of gallbladder polyps undermines the surveillance half of the 2022 European guideline: small polyps grow as a matter of course and almost never become cancer, while size at first scan carries most of the risk.","caveats":["US insured population with low gallbladder cancer incidence; findings may not transfer to Chile or northern India.","Polyps removed at cholecystectomy during follow-up are censored, which could understate progression."],"changedPractice":false,"participants":622227},{"id":"paper-phillips-jama-oncol","kind":"paper","name":"Outcomes of Observation vs Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer: The ORIOLE Phase 2 Randomized Clinical Trial","aka":[],"tldr":"Paper cited by one idea page, indexed on Europe PMC as PubMed record 32215577 and published in JAMA Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Importance: Complete metastatic ablation of oligometastatic prostate cancer may provide an alternative to early initiation of androgen deprivation therapy (ADT).\n\nObjective: To determine if stereotactic ablative radiotherapy (SABR) improves oncologic outcomes in men with oligometastatic prostate cancer.\n\nDesign, setting, and participants: The Observation vs Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer (ORIOLE) phase 2 randomized study accrued participants from 3 US radiation treatment facilities affiliated with a university hospital from May 2016 to March 2018 with a data cutoff date of May 20, 2019, for analysis. Of 80 men screened, 54 men with recurrent hormone-sensitive prostate cancer and 1 to 3 metastases detectable by conventional imaging who had not received ADT within 6 months of enrollment or 3 or more years total were randomized.\n\nInterventions: Patients were randomized in a 2:1 ratio to receive SABR or observation.\n\nMain outcomes and measures: The primary outcome was progression at 6 months by prostate-specific antigen level increase, progression detected by conventional imaging, symptomatic progression, ADT initiation for any reason, or death. Predefined secondary outcomes were toxic effects of SABR, local control at 6 months with SABR, progression-free survival, Brief Pain Inventory (Short Form)-measured quality of life, and concordance between conventional imaging and prostate-specific membrane antigen (PSMA)-targeted positron emission tomography in the identification of metastatic disease.\n\nResults: In the 54 men randomized, the median (range) age was 68 (61-70) years for patients allocated to SABR and 68 (64-76) years for those allocated to observation. Progression at 6 months occurred in 7 of 36 patients (19%) receiving SABR and 11 of 18 patients (61%) undergoing observation (P =.005). Treatment with SABR improved median progression-free survival (not reached vs 5.8 months; hazard ratio, 0.30; 95% CI, 0.11-0.81; P =.002). Total consolidation of PSMA radiotracer-avid disease decreased the risk of new lesions at 6 months (16% vs 63%; P =.006). No toxic effects of grade 3 or greater were observed. T-cell receptor sequencing identified significant increased clonotypic expansion following SABR and correlation between baseline clonality and progression with SABR only (0.082085 vs 0.026051; P =.03).\n\nConclusions and relevance: Treatment with SABR for oligometastatic prostate cancer improved outcomes and was enhanced by total consolidation of disease identified by PSMA-targeted positron emission tomography. SABR induced a systemic immune response, and baseline immune phenotype and tumor mutation status may predict the benefit from SABR. These results underline the importance of prospective randomized investigation of the oligometastatic state with integrated imaging and biological correlates.\n\nTrial registration: ClinicalTrials.gov Identifier: NCT02680587.\n\nIndexed on Europe PMC as PubMed record 32215577 (DOI 10.1001/jamaoncol.2020.0147). Matched by DOI alone: one idea page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA Oncol 2020","url":"https://doi.org/10.1001/jamaoncol.2020.0147"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32215577/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32215577"}],"tags":["europepmc-ingest"],"related":["idea-psma-pet-guided-mdt"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2020,"doi":"10.1001/jamaoncol.2020.0147","pmid":"32215577","authors":"Phillips R, Shi WY, Deek M, et al.","paperType":"rct","findings":[],"whatItMeans":"One idea page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-menon-lancet","kind":"paper","name":"Ovarian cancer population screening and mortality after long-term follow-up in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial","aka":[],"tldr":"Paper cited by one bottleneck page, indexed on Europe PMC as PubMed record 33991479 and published in The Lancet; the citing page links this DOI, which is how the record was matched.","summary":"Background: Ovarian cancer continues to have a poor prognosis with the majority of women diagnosed with advanced disease. Therefore, we undertook the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) to determine if population screening can reduce deaths due to the disease. We report on ovarian cancer mortality after long-term follow-up in UKCTOCS.\n\nMethods: In this randomised controlled trial, postmenopausal women aged 50-74 years were recruited from 13 centres in National Health Service trusts in England, Wales, and Northern Ireland. Exclusion criteria were bilateral oophorectomy, previous ovarian or active non-ovarian malignancy, or increased familial ovarian cancer risk. The trial management system confirmed eligibility and randomly allocated participants in blocks of 32 using computer generated random numbers to annual multimodal screening (MMS), annual transvaginal ultrasound screening (USS), or no screening, in a 1:1:2 ratio. Follow-up was through national registries. The primary outcome was death due to ovarian or tubal cancer (WHO 2014 criteria) by June 30, 2020. Analyses were by intention to screen, comparing MMS and USS separately with no screening using the versatile test. Investigators and participants were aware of screening type, whereas the outcomes review committee were masked to randomisation group. This study is registered with ISRCTN, 22488978, and ClinicalTrials.gov, NCT00058032.\n\nFindings: Between April 17, 2001, and Sept 29, 2005, of 1 243 282 women invited, 202 638 were recruited and randomly assigned, and 202 562 were included in the analysis: 50 625 (25·0%) in the MMS group, 50 623 (25·0%) in the USS group, and 101 314 (50·0%) in the no screening group. At a median follow-up of 16·3 years (IQR 15·1-17·3), 2055 women were diagnosed with tubal or ovarian cancer: 522 (1·0%) of 50 625 in the MMS group, 517 (1·0%) of 50 623 in the USS group, and 1016 (1·0%) of 101 314 in the no screening group. Compared with no screening, there was a 47·2% (95% CI 19·7 to 81·1) increase in stage I and 24·5% (-41·8 to -2·0) decrease in stage IV disease incidence in the MMS group. Overall the incidence of stage I or II disease was 39·2% (95% CI 16·1 to 66·9) higher in the MMS group than in the no screening group, whereas the incidence of stage III or IV disease was 10·2% (-21·3 to 2·4) lower. 1206 women died of the disease: 296 (0·6%) of 50 625 in the MMS group, 291 (0·6%) of 50 623 in the USS group, and 619 (0·6%) of 101 314 in the no screening group. No significant reduction in ovarian and tubal cancer deaths was observed in the MMS (p=0·58) or USS (p=0·36) groups compared with the no screening group.\n\nInterpretation: The reduction in stage III or IV disease incidence in the MMS group was not sufficient to translate into lives saved, illustrating the importance of specifying cancer mortality as the primary outcome in screening trials. Given that screening did not significantly reduce ovarian and tubal cancer deaths, general population screening cannot be recommended.\n\nFunding: National Institute for Health Research, Cancer Research UK, and The Eve Appeal.\n\nIndexed on Europe PMC as PubMed record 33991479 (DOI 10.1016/s0140-6736(21)00731-5). Matched by DOI alone: one bottleneck page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet 2021","url":"https://doi.org/10.1016/s0140-6736(21)00731-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33991479/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33991479"}],"tags":["europepmc-ingest"],"related":["b-early-detection"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2021,"doi":"10.1016/s0140-6736(21)00731-5","pmid":"33991479","authors":"Menon U, Gentry-Maharaj A, Burnell M, et al.","paperType":"rct","findings":[],"whatItMeans":"One bottleneck page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-golan-brca-pancreatic-platinum-survival-bjc-2014","kind":"paper","name":"Overall survival and clinical characteristics of pancreatic cancer in BRCA mutation carriers","aka":[],"tldr":"Among 71 people with pancreatic cancer and an inherited BRCA mutation, those with advanced disease lived 22 months on platinum chemotherapy against 9 months on other drugs, the clinical hint that led to the POLO trial.","summary":"Patients with BRCA1/2-associated pancreatic ductal adenocarcinoma diagnosed 1994 to 2012 were identified at three institutions: 71 patients (BRCA1 21, BRCA2 49, both 1), mean age 60.3, 81.7% with a family history of malignancy, 30% resected. Median overall survival for 58 analysable patients was 14 months; not reached for stage 1/2 (52% alive at 60 months) and 12 months for stage 3/4. Superior overall survival was observed for stage 3/4 patients treated with platinum against non-platinum chemotherapy (22 versus 9 months; P = 0.039).","asOf":"2026-09-24","links":[{"label":"Golan et al., Br J Cancer 2014: 71 BRCA carriers with pancreatic cancer, platinum and survival","url":"https://doi.org/10.1038/bjc.2014.418"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25072261/"}],"tags":[],"related":["brca-germline"],"cancers":["pancreatic","brca-palb2-pdac","metastatic-pdac"],"sections":[],"technologies":[],"targets":["brca"],"drugs":["folfirinox","gemcitabine-cisplatin"],"companies":[],"institutions":["sheba","princess-margaret"],"pathways":[],"terms":["gbrca-mutation"],"trials":[],"people":["talia-golan"],"bottlenecks":[],"keyPapers":[],"journals":["british-journal-of-cancer"],"dependsOn":[],"notes":[],"journal":"British Journal of Cancer","year":2014,"doi":"10.1038/bjc.2014.418","pmid":"25072261","authors":"Golan T, Kanji ZS, Epelbaum R, et al.","paperType":"observational","findings":["71 BRCA carriers: BRCA2 49, BRCA1 21.","Advanced disease: 22 months on platinum versus 9 on non-platinum."],"whatItMeans":"The retrospective platinum signal that made platinum-based first-line chemotherapy the standard for BRCA carriers and set POLO's design of olaparib after platinum.","caveats":["Retrospective, 58 analysable, three centres.","Treatment selection bias."],"changedPractice":false,"participants":71},{"id":"paper-relativity-047-nejm-evid-2023-update","kind":"paper","name":"Overall Survival and Response with Nivolumab and Relatlimab in Advanced Melanoma","aka":[],"tldr":"Later report from the RELATIVITY-047 trial registered as NCT03470922, in NEJM Evidence (2023); its title describes an updated or longer-term analysis.","summary":"BACKGROUND: A phase 2/3 trial, A Study of Relatlimab Plus Nivolumab Versus Nivolumab Alone in Participants With Advanced Melanoma (RELATIVITY-047), evaluated nivolumab + relatlimab as a fixed-dose combination and found a significant progression-free survival (PFS) benefit over nivolumab monotherapy in previously untreated unresectable or metastatic melanoma. We now report updated PFS and safety data and the first results for overall survival (OS) and objective response rate (ORR). METHODS: Patients were randomly assigned 1:1 to receive nivolumab 480 mg and relatlimab 160 mg fixed-dose combination or nivolumab 480 mg alone, given intravenously every 4 weeks. PFS (primary end point) according to the Response Evaluation Criteria in Solid Tumors, version 1.1, was assessed by blinded independent central review (BICR). Secondary end points, tested hierarchically, were OS and then ORR per Response Evaluation Criteria in Solid Tumors, version 1.1, per BICR. RESULTS: At a median follow-up of 19.3 months, median PFS according to BICR was 10.2 months (95% confidence interval [CI], 6.5 to 14.8) with nivolumab + relatlimab versus 4.6 months (95% CI, 3.5 to 6.4) with nivolumab (hazard ratio, 0.78; 95% CI, 0.64 to 0.94). Median OS was not reached (NR) (95% CI, 34.2 to NR) with nivolumab + relatlimab versus 34.1 months (95% CI, 25.2 to NR) with nivolumab (hazard ratio, 0.80; 95% CI, 0.64 to 1.01; P=0.059) (prespecified value for statistical significance, P≤0.043). ORRs per BICR were 43.1% (95% CI, 37.9 to 48.4) versus 32.6% (95% CI, 27.8 to 37.7), respectively. Grade 3/4 treatment-related adverse events were observed in 21.1% of patients treated with nivolumab + relatlimab versus 11.1% treated with nivolumab. CONCLUSIONS: The fixed-dose combination of nivolumab + relatlimab showed consistent PFS benefit versus nivolumab with approximately 6 months of additional median follow-up. The combination treatment did not reach the preplanned statistical threshold for OS, with a 10.3 percentage-point difference in ORR. Grade 3/4 treatment-related adverse events were more frequent with nivolumab + relatlimab versus nivolumab. (Funded by Bristol Myers Squibb; ClinicalTrials.gov number, NCT03470922.)\n\nIndexed on Europe PMC as PubMed record 38320023 (DOI 10.1056/evidoa2200239). Its abstract cites the registry id NCT03470922, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"NEJM Evid 2023","url":"https://doi.org/10.1056/evidoa2200239"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38320023/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38320023"},{"label":"ClinicalTrials.gov NCT03470922","url":"https://clinicaltrials.gov/study/NCT03470922"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["relativity-047"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm-evidence"],"dependsOn":[],"notes":[],"journal":"NEJM Evidence","year":2023,"doi":"10.1056/evidoa2200239","pmid":"38320023","authors":"Long GV, Stephen Hodi F, Lipson EJ, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the RELATIVITY-047 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-imcgp100-202-n-engl-j-med-2021","kind":"paper","name":"Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma","aka":[],"tldr":"Published report from the IMCgp100-202 trial registered as NCT03070392, in New England Journal of Medicine (2021), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Uveal melanoma is a disease that is distinct from cutaneous melanoma, with a low tumor mutational burden and a 1-year overall survival of approximately 50% in patients with metastatic uveal melanoma. Data showing a proven overall survival benefit with a systemic treatment are lacking. Tebentafusp is a bispecific protein consisting of an affinity-enhanced T-cell receptor fused to an anti-CD3 effector that can redirect T cells to target glycoprotein 100-positive cells.\n\nMethods: In this open-label, phase 3 trial, we randomly assigned previously untreated HLA-A*02:01-positive patients with metastatic uveal melanoma in a 2:1 ratio to receive tebentafusp (tebentafusp group) or the investigator's choice of therapy with single-agent pembrolizumab, ipilimumab, or dacarbazine (control group), stratified according to the lactate dehydrogenase level. The primary end point was overall survival.\n\nResults: A total of 378 patients were randomly assigned to either the tebentafusp group (252 patients) or the control group (126 patients). Overall survival at 1 year was 73% in the tebentafusp group and 59% in the control group (hazard ratio for death, 0.51; 95% confidence interval [CI], 0.37 to 0.71; P<0.001) in the intention-to-treat population. Progression-free survival was also significantly higher in the tebentafusp group than in the control group (31% vs. 19% at 6 months; hazard ratio for disease progression or death, 0.73; 95% CI, 0.58 to 0.94; P = 0.01). The most common treatment-related adverse events in the tebentafusp group were cytokine-mediated events (due to T-cell activation) and skin-related events (due to glycoprotein 100-positive melanocytes), including rash (83%), pyrexia (76%), and pruritus (69%). These adverse events decreased in incidence and severity after the first three or four doses and infrequently led to discontinuation of the trial treatment (2%). No treatment-related deaths were reported.\n\nConclusions: Treatment with tebentafusp resulted in longer overall survival than the control therapy among previously untreated patients with metastatic uveal melanoma. (Funded by Immunocore; ClinicalTrials.gov number, NCT03070392; EudraCT number, 2015-003153-18.).\n\nIndexed on Europe PMC as PubMed record 34551229 (DOI 10.1056/nejmoa2103485). Its abstract cites the registry id NCT03070392, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2021","url":"https://doi.org/10.1056/nejmoa2103485"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34551229/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34551229"},{"label":"ClinicalTrials.gov NCT03070392","url":"https://clinicaltrials.gov/study/NCT03070392"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["imcgp100-202"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2021,"doi":"10.1056/nejmoa2103485","pmid":"34551229","authors":"Nathan P, Hassel JC, Rutkowski P, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03070392 with the most citations, so it is the natural first reading for anyone following the IMCgp100-202 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-maniakas-neoadjuvant-braf-atc-jama-oncol-2020","kind":"paper","name":"Overall survival in anaplastic thyroid carcinoma 2000 to 2019: impact of targeted therapy and neoadjuvant BRAF-MEK inhibition","aka":[],"tldr":"At MD Anderson, survival in anaplastic thyroid cancer improved dramatically over two decades as BRAF testing, targeted therapy and neoadjuvant BRAF-MEK inhibition followed by surgery were introduced, with one-year survival rising from 35 to 59 percent.","summary":"Retrospective cohort study of 479 patients with anaplastic thyroid carcinoma treated at a single centre between 2000 and 2019, divided into three eras, examining the association of targeted therapy, immunotherapy and neoadjuvant BRAF-MEK inhibitor therapy with survival.\n\nOne-year overall survival rose from 35 percent (2000 to 2013) to 47 percent (2014 to 2016) and 59 percent (2017 to 2019); BRAF-mutant patients treated with neoadjuvant BRAF-directed therapy and surgery had 94 percent one-year survival.","asOf":"2026-09-17","links":[{"label":"JAMA Oncol 2020","url":"https://doi.org/10.1001/jamaoncol.2020.3362"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32761153/"}],"tags":[],"related":[],"cancers":["anaplastic-thyroid-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2020,"doi":"10.1001/jamaoncol.2020.3362","pmid":"32761153","authors":"Maniakas A, Dadu R, Busaidy NL, et al.","paperType":"observational","findings":["One-year overall survival 35 percent, 47 percent and 59 percent across three eras.","Neoadjuvant BRAF-directed therapy with surgery: one-year survival 94 percent."],"whatItMeans":"Neoadjuvant dabrafenib-trametinib to convert unresectable BRAF-mutant anaplastic thyroid cancer into operable disease is now a guideline-endorsed strategy.","caveats":["Single-centre retrospective data with era and selection effects."],"changedPractice":true,"participants":479},{"id":"paper-columbus-lancet-oncol-2018-update","kind":"paper","name":"Overall survival in patients with BRAF-mutant melanoma receiving encorafenib plus binimetinib versus vemurafenib or encorafenib (COLUMBUS): a multicentre, open-label, randomised, phase 3 trial","aka":[],"tldr":"Later report from the COLUMBUS trial registered as NCT01909453, in The Lancet Oncology (2018); its title describes an updated or longer-term analysis.","summary":"Background: Encorafenib plus binimetinib and encorafenib alone improved progression-free survival compared with vemurafenib in patients with BRAF V600 -mutant melanoma in the COLUMBUS trial. Here, we report the results of the secondary endpoint of overall survival.\n\nMethods: COLUMBUS was a two-part, randomised, open-label, phase 3 study done at 162 hospitals in 28 countries. Eligible patients were aged at least 18 years with histologically confirmed, locally advanced, unresectable, or metastatic cutaneous melanoma, or unknown primary melanoma, BRAF V600E or BRAF V600K mutation, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and were treatment naive or had progressed on or after first-line immunotherapy. In part 1 of the study, patients were randomly assigned (1:1:1) by use of interactive response technology to receive oral encorafenib 450 mg once daily plus oral binimetinib 45 mg twice daily (encorafenib plus binimetinib group), oral encorafenib 300 mg once daily (encorafenib group), or oral vemurafenib 960 mg twice daily (vemurafenib group). Randomisation was stratified by the American Joint Committee on Cancer stage, ECOG performance status, and BRAF mutation status. The primary outcome of the trial, progression-free survival with encorafenib plus binimetinib versus vemurafenib, was reported previously. Here we present the prespecified interim overall survival analysis. Efficacy analyses were by intent to treat. Safety was analysed in patients who received at least one dose of study drug. Part 2 of the study was initiated at the request of the US Food and Drug Administration to better understand the contribution of binimetinib to the combination therapy by comparing encorafenib 300 mg once daily plus binimetinib 45 mg twice daily with encorafenib 300 mg once daily alone. Results of part 2 will be published separately. This trial is ongoing and is registered with ClinicalTrials.gov, number NCT01909453, and EudraCT, number 2013-001176-38.\n\nFindings: Between Dec 30, 2013, and April 10, 2015, 577 of 1345 screened patients were randomly assigned to receive encorafenib plus binimetinib (n=192), encorafenib (n=194), or vemurafenib (n=191). Median follow-up for overall survival was 36·8 months (95% CI 35·9-37·5). Median overall survival was 33·6 months (95% CI 24·4-39·2) with encorafenib plus binimetinib and 16·9 months (14·0-24·5) with vemurafenib (hazard ratio 0·61 [95% CI 0·47-0·79]; two-sided p<0·0001). The most common grade 3 or 4 adverse events did not change substantially from the first report; those seen in more than 5% of patients treated with encorafenib plus binimetinib were increased γ-glutamyltransferase (18 [9%] of 192 patients), increased blood creatine phosphokinase (14 [7%]), and hypertension (12 [6%]); those seen with encorafenib alone were palmar-plantar erythrodysaesthesia syndrome (26 [14%] of 192 patients), myalgia (19 [10%]), and arthralgia (18 [9%]); and with vemurafenib the most common grade 3 or 4 adverse event was arthralgia (11 [6%] of 186 patients). One death in the combination treatment group was considered by the investigator to be possibly related to treatment.\n\nInterpretation: The combination of encorafenib plus binimetinib provided clinically meaningful efficacy with good tolerability as shown by improvements in both progression-free survival and overall survival compared with vemurafenib. These data suggest that the combination of encorafenib plus binimetinib is likely to become an important therapeutic option in patients with BRAF V600 -mutant melanoma.\n\nFunding: Array BioPharma, Novartis.\n\nIndexed on Europe PMC as PubMed record 30219628 (DOI 10.1016/s1470-2045(18)30497-2). Its abstract cites the registry id NCT01909453, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2018","url":"https://doi.org/10.1016/s1470-2045(18)30497-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30219628/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30219628"},{"label":"ClinicalTrials.gov NCT01909453","url":"https://clinicaltrials.gov/study/NCT01909453"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["columbus"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2018,"doi":"10.1016/s1470-2045(18)30497-2","pmid":"30219628","authors":"Dummer R, Ascierto PA, Gogas HJ, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the COLUMBUS trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-pishvaian-lancet-oncol","kind":"paper","name":"Overall survival in patients with pancreatic cancer receiving matched therapies following molecular profiling: a retrospective analysis of the Know Your Tumor registry trial","aka":[],"tldr":"Paper cited by one collection page, indexed on Europe PMC as PubMed record 32135080 and published in The Lancet Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background: About 25% of pancreatic cancers harbour actionable molecular alterations, defined as molecular alterations for which there is clinical or strong preclinical evidence of a predictive benefit from a specific therapy. The Know Your Tumor (KYT) programme includes US patients with pancreatic cancer and enables patients to undergo commercially available multi-omic profiling to provide molecularly tailored therapy options and clinical trial recommendations. We sought to determine whether patients with pancreatic cancer whose tumours harboured such actionable molecular alterations and who received molecularly matched therapy had a longer median overall survival than similar patients who did not receive molecularly matched therapy.\n\nMethods: In this retrospective analysis, treatment history and longitudinal survival outcomes were analysed in patients aged 18 years or older with biopsy-confirmed pancreatic cancer of any stage, enrolled in the KYT programme and who received molecular testing results. Since the timing of KYT enrolment varied for each patient, the primary outcome measurement of median overall survival was calculated from the initial diagnosis of advanced disease until death. We compared median overall survival in patients with actionable mutations who were treated with a matched therapy versus those who were not treated with a matched therapy.\n\nFindings: Of 1856 patients with pancreatic cancer who were referred to the KYT programme between June 16, 2014, and March 31, 2019, 1082 (58%) patients received personalised reports based on their molecular testing results. Actionable molecular alterations were identified in 282 (26%) of 1082 samples. Among 677 patients for whom outcomes were available, 189 had actionable molecular alterations. With a median follow-up of 383 days (IQR 214-588), those patients with actionable molecular alterations who received a matched therapy (n=46) had significantly longer median overall survival than did those patients who only received unmatched therapies (n=143; 2·58 years [95% CI 2·39 to not reached] vs 1·51 years [1·33-1·87]; hazard ratio 0·42 [95% CI 0·26-0·68], p=0·0004). The 46 patients who received a matched therapy also had significantly longer overall survival than the 488 patients who did not have an actionable molecular alteration (2·58 years [95% CI 2·39 to not reached] vs 1·32 years [1·25-1·47]; HR 0·34 [95% CI 0·22-0·53], p<0·0001). However, median overall survival did not differ between the patients who received unmatched therapy and those without an actionable molecular alteration (HR 0·82 [95% CI 0·64-1·04], p=0·10).\n\nInterpretation: These real-world outcomes suggest that the adoption of precision medicine can have a substantial effect on survival in patients with pancreatic cancer, and that molecularly guided treatments targeting oncogenic drivers and the DNA damage response and repair pathway warrant further prospective evaluation.\n\nFunding: Pancreatic Cancer Action Network and Perthera.\n\nIndexed on Europe PMC as PubMed record 32135080 (DOI 10.1016/s1470-2045(20)30074-7). Matched by DOI alone: one collection page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2020","url":"https://doi.org/10.1016/s1470-2045(20)30074-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32135080/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32135080"}],"tags":["europepmc-ingest"],"related":["pancan"],"cancers":["pancreatic","metastatic-pdac"],"sections":[],"technologies":["wes-wgs","germline-testing"],"targets":["brca","kras","mmr"],"drugs":[],"companies":[],"institutions":["lustgarten-foundation"],"pathways":[],"terms":["ngs"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2020,"doi":"10.1016/s1470-2045(20)30074-7","pmid":"32135080","authors":"Pishvaian MJ, Blais EM, Brody JR, et al.","paperType":"observational","findings":[],"whatItMeans":"One collection page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-olympia-overall-survival-ann-oncol-2022","kind":"paper","name":"Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer","aka":[],"tldr":"The second planned analysis of OlympiA, at 3.5 years, in which a year of olaparib tablets after standard treatment cut deaths by 32 percent in women with an inherited BRCA fault, the first time a PARP inhibitor had lengthened life in early breast cancer.","summary":"Geyer, Garber, Gelber, Yothers and colleagues report the pre-specified second interim analysis of overall survival in OlympiA, which randomised 1,836 patients with germline BRCA1 or BRCA2 pathogenic variants and high-risk HER2-negative early breast cancer to a year of olaparib or placebo after neoadjuvant or adjuvant chemotherapy, surgery and radiotherapy. With a median follow-up of 3.5 years overall survival improved (hazard ratio 0.68, 98.5 percent confidence interval 0.47 to 0.97, p=0.009); four-year overall survival was 89.8 versus 86.4 percent (difference 3.4 percentage points), four-year invasive disease-free survival 82.7 versus 75.4 percent (7.3 points) and distant disease-free survival 86.5 versus 79.1 percent (7.4 points), with benefit across major subgroups and no new safety signals, including no new acute myeloid leukaemia or myelodysplastic syndrome.","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2022","url":"https://doi.org/10.1016/j.annonc.2022.09.159"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36228963/"},{"label":"ClinicalTrials.gov NCT02032823","url":"https://clinicaltrials.gov/study/NCT02032823"}],"tags":["tnbc-evidence"],"related":["paper-olympia-nejm-2021","paper-olympia-6-year-update-ann-oncol-2026"],"cancers":["tnbc","breast-hr-positive"],"sections":[],"technologies":["parp-inhibitor","germline-testing"],"targets":["brca"],"drugs":["olaparib"],"companies":["astrazeneca","merck"],"institutions":[],"pathways":[],"terms":["os","germline-testing","hazard-ratio"],"trials":["olympia"],"people":["charles-geyer","judy-garber","andrew-tutt"],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2022,"doi":"10.1016/j.annonc.2022.09.159","pmid":"36228963","authors":"Geyer CE, Garber JE, Gelber RD, et al.","paperType":"rct","findings":["Overall survival hazard ratio 0.68 (98.5 percent CI 0.47 to 0.97), p=0.009, at 3.5 years median follow-up.","Four-year overall survival 89.8 vs 86.4 percent; invasive disease-free survival 82.7 vs 75.4 percent; distant disease-free survival 86.5 vs 79.1 percent.","No new cases of acute myeloid leukaemia or myelodysplastic syndrome."],"whatItMeans":"The survival result that moved adjuvant olaparib from a disease-free survival approval to an undisputed standard, and the reason germline testing at diagnosis of triple-negative breast cancer is now a treatment decision rather than a family history exercise.","caveats":["About 82 percent of participants had triple-negative disease; hormone receptor-positive carriers were a minority.","Interim analysis with a stricter alpha; the six-year update is the mature result."],"changedPractice":true,"participants":1836},{"id":"paper-therap-lancet-oncol-2024-update","kind":"paper","name":"Overall survival with [ 177 Lu]Lu-PSMA-617 versus cabazitaxel in metastatic castration-resistant prostate cancer (TheraP): secondary outcomes of a randomised, open-label, phase 2 trial","aka":[],"tldr":"Later report from the TheraP trial registered as NCT03392428, in The Lancet Oncology (2024); its title describes an updated or longer-term analysis.","summary":"Background: The TheraP study reported improved prostate-specific antigen responses with lutetium-177 [ 177 Lu]Lu-PSMA-617 versus cabazitaxel in men with metastatic castration-resistant prostate cancer progressing after docetaxel. In this Article, we report the secondary outcome of overall survival with mature follow-up, and an updated imaging biomarker analysis. We also report the outcomes of participants excluded due to ineligibility on gallium-68 [ 68 Ga]Ga-PSMA-11 and 2-[ 18 F]fluoro-2-deoxy-D-glucose (2-[ 18 F]FDG) PET-CT.\n\nMethods: TheraP was an open-label, randomised phase 2 trial at 11 centres in Australia. Eligible participants had metastatic castration-resistant prostate cancer progressing after docetaxel, and PET imaging with [ 68 Ga]Ga-PSMA-11 and 2-[ 18 F]FDG that showed prostate-specific membrane antigen (PSMA)-positive disease and no sites of metastatic disease with discordant 2-[ 18 F]FDG-positive and PSMA-negative findings. Participants were randomly assigned (1:1) to treatment with [ 177 Lu]Lu-PSMA-617 (every 6 weeks for a maximum of six cycles; starting at 8·5 GBq, decreasing by 0.5 GBq to 6·0 GBq for the sixth cycle) versus cabazitaxel (20 mg/m 2 every 3 weeks, maximum of ten cycles). Overall survival was analysed by intention-to-treat and summarised as restricted mean survival time (RMST) to account for non-proportional hazards, with a 36-month restriction time corresponding to median follow-up. This trial is registered with ClinicalTrials.gov, NCT03392428, and is complete.\n\nFindings: 291 men were registered from Feb 6, 2018, to Sept 3, 2019; after study imaging, 200 were eligible and randomly assigned to treatment with [ 177 Lu]Lu-PSMA-617 (n=99) or cabazitaxel (n=101). After completing study treatment, 20 (20%) participants assigned to cabazitaxel and 32 (32%) assigned to [ 177 Lu]Lu-PSMA-617 were subsequently treated with the alternative regimen. After a median follow-up of 35·7 months (IQR 31·1 to 39·2), 77 (78%) participants had died in the [ 177 Lu]Lu-PSMA-617 group and 70 (69%) participants had died in the cabazitaxel group. Overall survival was similar among those assigned to [ 177 Lu]Lu-PSMA-617 versus those assigned to cabazitaxel (RMST 19·1 months [95% CI 16·9 to 21·4] vs 19·6 months [17·4 to 21·8]; difference -0·5 months [95% CI -3·7 to 2·7]; p=0·77). No additional safety signals were identified with the longer follow-up in this analysis. 80 (27%) of 291 men who were registered after initial eligibility screening were excluded after [ 68 Ga]Ga-PSMA-11 and 2-[ 18 F]FDG PET. In the 61 of these men with follow-up available, RMST was 11·0 months (95% CI 9·0 to 13·1).\n\nInterpretation: These results support the use of [ 177 Lu]Lu-PSMA-617 as an alternative to cabazitaxel for PSMA-positive metastatic castration-resistant prostate cancer progressing after docetaxel. We did not find evidence that overall survival differed between the randomised groups. Median overall survival was shorter for men who were excluded because of low PSMA expression or 2-[ 18 F]FDG-discordant disease.\n\nFunding: Australian and New Zealand Urogenital and Prostate Cancer Trials Group, Prostate Cancer Foundation of Australia, Endocyte (a Novartis company), Australian Nuclear Science and Technology Organization, Movember, It's a Bloke Thing, CAN4CANCER, and The Distinguished Gentleman's Ride.\n\nIndexed on Europe PMC as PubMed record 38043558 (DOI 10.1016/s1470-2045(23)00529-6). Its abstract cites the registry id NCT03392428, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2024","url":"https://doi.org/10.1016/s1470-2045(23)00529-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38043558/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38043558"},{"label":"ClinicalTrials.gov NCT03392428","url":"https://clinicaltrials.gov/study/NCT03392428"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["therap"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2024,"doi":"10.1016/s1470-2045(23)00529-6","pmid":"38043558","authors":"Hofman MS, Emmett L, Sandhu S, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the TheraP trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-monarche-ann-oncol-2026-update","kind":"paper","name":"Overall survival with abemaciclib in early breast cancer","aka":[],"tldr":"Later report from the monarchE trial registered as NCT03155997, in Annals of Oncology (2026); its title describes an updated or longer-term analysis.","summary":"Background: Adjuvant abemaciclib combined with endocrine therapy (ET) significantly improved invasive disease-free survival (IDFS) in patients with hormone receptor (HR)-positive, human epidermal growth factor 2 (HER2)-negative, node-positive, high-risk early breast cancer (EBC). The impact on overall survival (OS) remained unknown.\n\nPatients and methods: In the phase III monarchE trial (NCT03155997), patients received ET for at least 5 years with or without abemaciclib for 2 years. In this article, we report the primary OS results, a key secondary endpoint, and updated estimates of IDFS and distant relapse-free survival (DRFS).\n\nResults: Overall, 5637 patients underwent randomization, with 2808 assigned to abemaciclib-ET, and 2829 to ET. In the intent-to-treat population, with a median follow-up of 76.2 months, abemaciclib-ET resulted in a 15.8% lower risk of death than ET [661 deaths; hazard ratio 0.842, 95% confidence interval (CI) 0.722-0.981, P = 0.027], meeting the prespecified boundary for significance. The 7-year OS was 86.8% with abemaciclib-ET and 85.0% with ET (absolute difference, 1.8%). OS benefit was consistent across prespecified subgroups. In addition to patients who had already died of metastatic disease, fewer patients in the abemaciclib-ET arm were living with metastatic disease compared with the ET arm (6.4% versus 9.4%). Sustained improvement was demonstrated in IDFS and DRFS (hazard ratio 0.734, 95% CI 0.657-0.820 and hazard ratio 0.746, 95% CI 0.662-0.840, respectively). Seven-year IDFS was 77.4% with abemaciclib-ET and 70.9% with ET (absolute difference, 6.5%) and 7-year DRFS were 80.0% and 74.9% (absolute difference, 5.1%). The long-term safety data compiled did not support any concerns of delayed toxicities.\n\nConclusions: Adjuvant abemaciclib-ET resulted in a statistically significant and clinically meaningful improvement in OS compared with ET in patients with HR-positive, HER2-negative, node-positive, high-risk EBC. At 7 years, abemaciclib-ET continued to demonstrate a sustained IDFS and DRFS benefit.\n\nIndexed on Europe PMC as PubMed record 41110697 (DOI 10.1016/j.annonc.2025.10.005). Its abstract cites the registry id NCT03155997, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2026","url":"https://doi.org/10.1016/j.annonc.2025.10.005"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41110697/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41110697"},{"label":"ClinicalTrials.gov NCT03155997","url":"https://clinicaltrials.gov/study/NCT03155997"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["monarche"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2026,"doi":"10.1016/j.annonc.2025.10.005","pmid":"41110697","authors":"Johnston S, Martin M, O'Shaughnessy J, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the monarchE trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-nct02486718-ann-oncol-2023-update","kind":"paper","name":"Overall survival with adjuvant atezolizumab after chemotherapy in resected stage II-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase III trial","aka":[],"tldr":"Later report from the trial registered as NCT02486718, in Annals of Oncology (2023); its title describes an updated or longer-term analysis.","summary":"Background: IMpower010 (NCT02486718) demonstrated significantly improved disease-free survival (DFS) with adjuvant atezolizumab versus best supportive care (BSC) following platinum-based chemotherapy in the programmed death-ligand 1 (PD-L1)-positive and all stage II-IIIA non-small-cell lung cancer (NSCLC) populations, at the DFS interim analysis. Results of the first interim analysis of overall survival (OS) are reported here.\n\nPatient and methods: The design, participants, and primary-endpoint DFS outcomes have been reported for this phase III, open-label, 1: 1 randomised study of atezolizumab (1200 mg q3w; 16 cycles) versus BSC after adjuvant platinum-based chemotherapy (1-4 cycles) in adults with completely resected stage IB (≥4 cm)-IIIA NSCLC (per the Union Internationale Contre le Cancer and American Joint Committee on Cancer staging system, 7th edition). Key secondary endpoints included OS in the stage IB-IIIA intent-to-treat (ITT) population and safety in randomised treated patients. The first pre-specified interim analysis of OS was conducted after 251 deaths in the ITT population. Exploratory analyses included OS by baseline PD-L1 expression level (SP263 assay).\n\nResults: At a median of 45.3 months' follow-up on 18 April 2022, 127 of 507 patients (25%) in the atezolizumab arm and 124 of 498 (24.9%) in the BSC arm had died. The median OS in the ITT population was not estimable; the stratified hazard ratio (HR) was 0.995 [95% confidence interval (CI) 0.78-1.28]. The stratified OS HRs (95% CI) were 0.95 (0.74-1.24) in the stage II-IIIA (n = 882), 0.71 (0.49-1.03) in the stage II-IIIA PD-L1 tumour cell (TC) ≥1% (n = 476), and 0.43 (95% CI 0.24-0.78) in the stage II-IIIA PD-L1 TC ≥50% (n = 229) populations. Atezolizumab-related adverse event incidences remained unchanged since the previous analysis [grade 3/4 in 53 (10.7%) and grade 5 in 4 (0.8%) of 495 patients, respectively].\n\nConclusions: Although OS remains immature for the ITT population, these data indicate a positive trend favouring atezolizumab in PD-L1 subgroup analyses, primarily driven by the PD-L1 TC ≥50% stage II-IIIA subgroup. No new safety signals were observed after 13 months' additional follow-up. Together, these findings support the positive benefit-risk profile of adjuvant atezolizumab in this setting.\n\nIndexed on Europe PMC as PubMed record 37467930 (DOI 10.1016/j.annonc.2023.07.001). Its abstract cites the registry id NCT02486718, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2023","url":"https://doi.org/10.1016/j.annonc.2023.07.001"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37467930/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37467930"},{"label":"ClinicalTrials.gov NCT02486718","url":"https://clinicaltrials.gov/study/NCT02486718"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct02486718"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2023,"doi":"10.1016/j.annonc.2023.07.001","pmid":"37467930","authors":"Felip E, Altorki N, Zhou C, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-pacific-n-engl-j-med-2018-update","kind":"paper","name":"Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC","aka":[],"tldr":"Later report from the PACIFIC trial registered as NCT02125461, in New England Journal of Medicine (2018); its title describes an updated or longer-term analysis.","summary":"Background: An earlier analysis in this phase 3 trial showed that durvalumab significantly prolonged progression-free survival, as compared with placebo, among patients with stage III, unresectable non-small-cell lung cancer (NSCLC) who did not have disease progression after concurrent chemoradiotherapy. Here we report the results for the second primary end point of overall survival.\n\nMethods: We randomly assigned patients, in a 2:1 ratio, to receive durvalumab intravenously, at a dose of 10 mg per kilogram of body weight, or matching placebo every 2 weeks for up to 12 months. Randomization occurred 1 to 42 days after the patients had received chemoradiotherapy and was stratified according to age, sex, and smoking history. The primary end points were progression-free survival (as assessed by blinded independent central review) and overall survival. Secondary end points included the time to death or distant metastasis, the time to second progression, and safety.\n\nResults: Of the 713 patients who underwent randomization, 709 received the assigned intervention (473 patients received durvalumab and 236 received placebo). at March 22, 2018, the median follow-up was 25.2 months. The 24-month overall survival rate was 66.3% (95% confidence interval [CI], 61.7 to 70.4) in the durvalumab group, as compared with 55.6% (95% CI, 48.9 to 61.8) in the placebo group (two-sided P=0.005). Durvalumab significantly prolonged overall survival, as compared with placebo (stratified hazard ratio for death, 0.68; 99.73% CI, 0.47 to 0.997; P=0.0025). Updated analyses regarding progression-free survival were similar to those previously reported, with a median duration of 17.2 months in the durvalumab group and 5.6 months in the placebo group (stratified hazard ratio for disease progression or death, 0.51; 95% CI, 0.41 to 0.63). The median time to death or distant metastasis was 28.3 months in the durvalumab group and 16.2 months in the placebo group (stratified hazard ratio, 0.53; 95% CI, 0.41 to 0.68). A total of 30.5% of the patients in the durvalumab group and 26.1% of those in the placebo group had grade 3 or 4 adverse events of any cause; 15.4% and 9.8% of the patients, respectively, discontinued the trial regimen because of adverse events.\n\nConclusions: Durvalumab therapy resulted in significantly longer overall survival than placebo. No new safety signals were identified. (Funded by AstraZeneca; PACIFIC ClinicalTrials.gov number, NCT02125461.).\n\nIndexed on Europe PMC as PubMed record 30280658 (DOI 10.1056/nejmoa1809697). Its abstract cites the registry id NCT02125461, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2018","url":"https://doi.org/10.1056/nejmoa1809697"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30280658/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30280658"},{"label":"ClinicalTrials.gov NCT02125461","url":"https://clinicaltrials.gov/study/NCT02125461"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["pacific"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2018,"doi":"10.1056/nejmoa1809697","pmid":"30280658","authors":"Antonia SJ, Villegas A, Daniel D, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the PACIFIC trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-imspire150-lancet-oncol-2023-update","kind":"paper","name":"Overall survival with first-line atezolizumab in combination with vemurafenib and cobimetinib in BRAF V600 mutation-positive advanced melanoma (IMspire150): second interim analysis of a multicentre, randomised, phase 3 study","aka":[],"tldr":"Later report from the IMspire150 trial registered as NCT02908672, in The Lancet Oncology (2023); its title describes an updated or longer-term analysis.","summary":"Background: Primary analysis of the phase 3 IMspire150 study showed improved investigator-assessed progression-free survival with first-line atezolizumab, vemurafenib, and cobimetinib (atezolizumab group) versus placebo, vemurafenib, and cobimetinib (control group) in patients with BRAF V600 mutation-positive melanoma. With a median follow-up of 18·9 months (IQR 10·4-23·8) at the primary analysis, overall survival data were immature. Here, we report the results from the second, prespecified, interim overall survival analysis.\n\nMethods: The multicentre, double-blind, placebo-controlled, randomised, phase 3 IMspire150 study was done at 108 academic and community hospitals in 20 countries. Patients aged 18 years or older with previously untreated unresectable stage IIIc or stage IV melanoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible for inclusion. Patients were randomly assigned (1:1) to receive either atezolizumab (840 mg intravenously on day 1 and 15) or placebo plus vemurafenib (960 mg or 720 mg twice daily orally) and cobimetinib (60 mg once daily orally; 21 days on and 7 days off) in 28-day cycles. Atezolizumab and placebo were added to treatment regimens from cycle two onwards. Randomisation was done centrally (Durham, NC, USA) based on a permuted block randomisation scheme (block size of 4) using an interactive web-based response system and was stratified by geographical region and baseline lactate dehydrogenase concentration. Overall survival was analysed in the intention-to-treat population and safety was analysed in all patients who received at least one dose of study drug according to actual treatment received. The primary endpoint was investigator-assessed progression-free survival, which was previously reported. Here, we report the second, prespecified, interim overall survival analysis, which was planned after about 270 overall survival events had occurred. The trial is ongoing, but is no longer enrolling patients, and it is registered with ClinicalTrials.gov, NCT02908672.\n\nFindings: Between Jan 13, 2017, and April 26, 2018, 514 patients (median age 54 years [IQR 43-63]; 299 [58%] men and 215 [42%] women) were enrolled in the trial and randomly assigned to the atezolizumab group (256 [50%] patients) or the control group (258 [50%] patients). At the data cutoff (Sept 8, 2021), 273 patients had died (126 in the atezolizumab group and 147 in the control group). Median follow-up was 29·1 months (IQR 10·1-45·4) for the atezolizumab group versus 22·8 months (10·6-44·1) for the control group. Median overall survival was 39·0 months (95% CI 29·9-not estimable) in the atezolizumab group versus 25·8 months (22·0-34·6) in the control group (HR 0·84 [95% CI 0·66-1·06]; p=0·14). The most common adverse events of any grade in the atezolizumab group were blood creatine phosphokinase increased (123 [53%] of 231 patients), diarrhoea (116 [50%]), and pyrexia (115 [50%]). The most common adverse events of any grade in the control group were diarrhoea (157 [56%] of 280 patients), blood creatine phosphokinase increased (135 [48%]), and rash (119 [43%]). The most common grade 3-4 adverse events were increased lipase (54 [23%] of 231 patients in the atezolizumab group vs 62 [22%] of 280 patients in the control group), increased blood creatine phosphokinase (51 [22%] vs 50 [18%]), and increased alanine aminotransferase (32 [14%] vs 26 [9%]). Serious adverse events were reported in 112 (48%) patients in the atezolizumab group and 117 (42%) patients in the control group. Grade 5 adverse events were reported in eight (3%) patients in the atezolizumab group versus six (2%) patients in the control group. Two grade 5 adverse events (hepatitis fulminant and hepatic failure) in the atezolizumab group were considered to be associated with the triplet combination, and one event in the control group (pulmonary haemorrhage) was considered to be associated with cobimetinib.\n\nInterpretation: Additional follow-up of the IMspire150 trial showed that overall survival was not significantly improved with atezolizumab, vemurafenib, and cobimetinib compared with placebo, vemurafenib, and cobimetinib in patients with BRAF V600 mutation-positive advanced melanoma. Results of the final analysis are awaited to establish whether a significant improvement in overall survival can be achieved with long-term treatment with this triplet combination versus vemurafenib plus cobimetinib.\n\nFunding: F Hoffmann-La Roche.\n\nIndexed on Europe PMC as PubMed record 36460017 (DOI 10.1016/s1470-2045(22)00687-8). Its abstract cites the registry id NCT02908672, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2023","url":"https://doi.org/10.1016/s1470-2045(22)00687-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36460017/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36460017"},{"label":"ClinicalTrials.gov NCT02908672","url":"https://clinicaltrials.gov/study/NCT02908672"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["imspire150"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2023,"doi":"10.1016/s1470-2045(22)00687-8","pmid":"36460017","authors":"Ascierto PA, Stroyakovskiy D, Gogas H, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the IMspire150 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-inavo120-n-engl-j-med-2025-update","kind":"paper","name":"Overall Survival with Inavolisib in PIK3CA -Mutated Advanced Breast Cancer","aka":[],"tldr":"Later report from the INAVO120 trial registered as NCT04191499, in New England Journal of Medicine (2025); its title describes an updated or longer-term analysis.","summary":"Background: In the phase 3, double-blind, randomized INAVO120 trial, treatment with inavolisib plus palbociclib-fulvestrant led to a significant progression-free survival benefit, as compared with placebo plus palbociclib-fulvestrant, among patients with PIK3CA -mutated, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer who had had relapse during or within 12 months after completion of adjuvant endocrine therapy.\n\nMethods: We randomly assigned patients with PIK3CA -mutated, hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer who had had disease recurrence or progression during or within 12 months after completion of adjuvant endocrine therapy to receive inavolisib plus palbociclib-fulvestrant (inavolisib group) or placebo plus palbociclib-fulvestrant (placebo group). In the current report, we provide the results of the final analysis of overall survival, including updated data on efficacy and safety.\n\nResults: A total of 161 patients were assigned to the inavolisib group, and 164 to the placebo group. After a median follow-up of 34.2 months in the inavolisib group and 32.3 months in the placebo group, the median overall survival was 34.0 months (95% confidence interval [CI], 28.4 to 44.8) with inavolisib and 27.0 months (95% CI, 22.8 to 38.7) with placebo (hazard ratio for death, 0.67; 95% CI, 0.48 to 0.94; P = 0.02 [prespecified boundary for statistical significance, P<0.0469]). An objective response occurred in 62.7% (95% CI, 54.8 to 70.2) of patients in the inavolisib group and 28.0% (95% CI, 21.3 to 35.6) of those in the placebo group (P<0.001). The updated hazard ratio for disease progression or death was 0.42 (95% CI, 0.32 to 0.55). Adverse events led to discontinuation of inavolisib in 6.8% of patients and discontinuation of placebo in 0.6%. The incidence of hyperglycemia, stomatitis or mucosal inflammation, gastrointestinal toxic effects (e.g., diarrhea), and ocular toxic effects (e.g., dry eye and blurred vision) was higher with inavolisib than with placebo.\n\nConclusions: Treatment with inavolisib plus palbociclib-fulvestrant led to a significant overall survival benefit, as compared with placebo plus palbociclib-fulvestrant. Hyperglycemia, stomatitis or mucosal inflammation, gastrointestinal toxic effects, and ocular toxic effects were reported more frequently with inavolisib than with placebo. (Funded by F. Hoffmann-La Roche; INAVO120 ClinicalTrials.gov number, NCT04191499.).\n\nIndexed on Europe PMC as PubMed record 40454641 (DOI 10.1056/nejmoa2501796). Its abstract cites the registry id NCT04191499, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2025","url":"https://doi.org/10.1056/nejmoa2501796"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40454641/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40454641"},{"label":"ClinicalTrials.gov NCT04191499","url":"https://clinicaltrials.gov/study/NCT04191499"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["inavo120"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2025,"doi":"10.1056/nejmoa2501796","pmid":"40454641","authors":"Jhaveri KL, Im SA, Saura C, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the INAVO120 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-checkmate-816-n-engl-j-med-2025-update","kind":"paper","name":"Overall Survival with Neoadjuvant Nivolumab plus Chemotherapy in Lung Cancer","aka":[],"tldr":"Later report from the CheckMate 816 trial registered as NCT02998528, in New England Journal of Medicine (2025); its title describes an updated or longer-term analysis.","summary":"Background: Neoadjuvant nivolumab plus chemotherapy significantly improved pathological complete response and event-free survival in patients with resectable non-small-cell lung cancer (NSCLC) in a phase 3 trial. Data are needed on overall survival.\n\nMethods: In this open-label, phase 3 trial, patients with stage IB to IIIA resectable NSCLC were randomly assigned to receive nivolumab plus chemotherapy or chemotherapy alone for three cycles, followed by surgery. The primary end points were event-free survival and pathological complete response. Here, we report the results of the planned analysis of overall survival.\n\nResults: A total of 358 patients were concurrently assigned to receive nivolumab plus chemotherapy (179 patients) or chemotherapy alone (179 patients). The final analysis of overall survival significantly favored neoadjuvant nivolumab plus chemotherapy over chemotherapy (hazard ratio for death, 0.72; 95% confidence interval [CI], 0.523 to 0.998; P = 0.048). At a median follow-up of 68.4 months, the 5-year overall survival was 65.4% with nivolumab plus chemotherapy and 55.0% with chemotherapy alone, with consistency across most subgroups. In exploratory analyses, the 5-year overall survival in the nivolumab-plus-chemotherapy group was 95.3% (95% CI, 82.7 to 98.8) among the patients with a pathological complete response and 55.7% (95% CI, 46.9 to 63.7) among those without such a response; survival was 75.0% among the patients with presurgery clearance of circulating tumor DNA (ctDNA) and 52.6% among those without such clearance. No new safety signals were observed.\n\nConclusions: Three cycles of neoadjuvant nivolumab plus chemotherapy significantly improved overall survival among patients with resectable NSCLC as compared with chemotherapy alone. (Funded by Bristol Myers Squibb; CheckMate 816 ClinicalTrials.gov number, NCT02998528.).\n\nIndexed on Europe PMC as PubMed record 40454642 (DOI 10.1056/nejmoa2502931). Its abstract cites the registry id NCT02998528, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2025","url":"https://doi.org/10.1056/nejmoa2502931"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40454642/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40454642"},{"label":"ClinicalTrials.gov NCT02998528","url":"https://clinicaltrials.gov/study/NCT02998528"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-816"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2025,"doi":"10.1056/nejmoa2502931","pmid":"40454642","authors":"Forde PM, Spicer JD, Provencio M, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the CheckMate 816 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-osimertinib-nsclc-n-engl-j-med-2020","kind":"paper","name":"Overall Survival with Osimertinib in Untreated, EGFR -Mutated Advanced NSCLC","aka":[],"tldr":"Phase 2 or 3 results paper on Osimertinib in Non-small-cell lung cancer, in New England Journal of Medicine (2020), one of the most cited Europe PMC records with Osimertinib in its title.","summary":"Background: Osimertinib is a third-generation, irreversible tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR-TKI) that selectively inhibits both EGFR-TKI-sensitizing and EGFR T790M resistance mutations. A phase 3 trial compared first-line osimertinib with other EGFR-TKIs in patients with EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC). The trial showed longer progression-free survival with osimertinib than with the comparator EGFR-TKIs (hazard ratio for disease progression or death, 0.46). Data from the final analysis of overall survival have not been reported.\n\nMethods: In this trial, we randomly assigned 556 patients with previously untreated advanced NSCLC with an EGFR mutation (exon 19 deletion or L858R allele) in a 1:1 ratio to receive either osimertinib (80 mg once daily) or one of two other EGFR-TKIs (gefitinib at a dose of 250 mg once daily or erlotinib at a dose of 150 mg once daily, with patients receiving these drugs combined in a single comparator group). Overall survival was a secondary end point.\n\nResults: The median overall survival was 38.6 months (95% confidence interval [CI], 34.5 to 41.8) in the osimertinib group and 31.8 months (95% CI, 26.6 to 36.0) in the comparator group (hazard ratio for death, 0.80; 95.05% CI, 0.64 to 1.00; P = 0.046). At 3 years, 79 of 279 patients (28%) in the osimertinib group and 26 of 277 (9%) in the comparator group were continuing to receive a trial regimen; the median exposure was 20.7 months and 11.5 months, respectively. Adverse events of grade 3 or higher were reported in 42% of the patients in the osimertinib group and in 47% of those in the comparator group.\n\nConclusions: Among patients with previously untreated advanced NSCLC with an EGFR mutation, those who received osimertinib had longer overall survival than those who received a comparator EGFR-TKI. The safety profile for osimertinib was similar to that of the comparator EGFR-TKIs, despite a longer duration of exposure in the osimertinib group. (Funded by AstraZeneca; FLAURA ClinicalTrials.gov number, NCT02296125.).\n\nIndexed on Europe PMC as PubMed record 31751012 (DOI 10.1056/nejmoa1913662). Its title names Osimertinib and its text names Non-small-cell lung cancer; PubMed types it as a clinical trial report (Clinical Trial, Phase III, Comparative Study, Research Support, Non-U.S. Gov't, Multicenter Study, Randomized Controlled Trial). It was matched automatically to the idea \"Treat brain metastases as a disease with its own trials programme\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2020","url":"https://doi.org/10.1056/nejmoa1913662"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31751012/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31751012"},{"label":"ClinicalTrials.gov NCT02296125","url":"https://clinicaltrials.gov/study/NCT02296125"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["flaura"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2020,"doi":"10.1056/nejmoa1913662","pmid":"31751012","authors":"Ramalingam SS, Vansteenkiste J, Planchard D, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Osimertinib in Non-small-cell lung cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Osimertinib in the title and Non-small-cell lung cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-keynote-522-n-engl-j-med-2024-update","kind":"paper","name":"Overall Survival with Pembrolizumab in Early-Stage Triple-Negative Breast Cancer","aka":[],"tldr":"Later report from the KEYNOTE-522 trial registered as NCT03036488, in New England Journal of Medicine (2024); its title describes an updated or longer-term analysis.","summary":"Background: In patients with early-stage triple-negative breast cancer, the phase 3 KEYNOTE-522 trial showed significant improvements in pathological complete response and event-free survival with the addition of pembrolizumab to platinum-containing chemotherapy. Here we report the final results for overall survival.\n\nMethods: We randomly assigned, in a 2:1 ratio, patients with previously untreated stage II or III triple-negative breast cancer to receive neoadjuvant therapy with four cycles of pembrolizumab (at a dose of 200 mg) or placebo every 3 weeks plus paclitaxel and carboplatin, followed by four cycles of pembrolizumab or placebo plus doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide. After definitive surgery, patients received adjuvant pembrolizumab (pembrolizumab-chemotherapy group) or placebo (placebo-chemotherapy group) every 3 weeks for up to nine cycles. The primary end points were pathological complete response and event-free survival. Overall survival was a secondary end point.\n\nResults: Of the 1174 patients who underwent randomization, 784 were assigned to the pembrolizumab-chemotherapy group and 390 to the placebo-chemotherapy group. At the data-cutoff date (March 22, 2024), the median follow-up was 75.1 months (range, 65.9 to 84.0). The estimated overall survival at 60 months was 86.6% (95% confidence interval [CI], 84.0 to 88.8) in the pembrolizumab-chemotherapy group, as compared with 81.7% (95% CI, 77.5 to 85.2) in the placebo-chemotherapy group (P = 0.002). Adverse events were consistent with the established safety profiles of pembrolizumab and chemotherapy.\n\nConclusions: Neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab resulted in a significant improvement, as compared with neoadjuvant chemotherapy alone, in overall survival among patients with early-stage triple-negative breast cancer. (Funded by Merck Sharp and Dohme, a subsidiary of Merck [Rahway, NJ]; KEYNOTE-522 ClinicalTrials.gov number, NCT03036488.).\n\nIndexed on Europe PMC as PubMed record 39282906 (DOI 10.1056/nejmoa2409932). Its abstract cites the registry id NCT03036488, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2024","url":"https://doi.org/10.1056/nejmoa2409932"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39282906/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39282906"},{"label":"ClinicalTrials.gov NCT03036488","url":"https://clinicaltrials.gov/study/NCT03036488"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-522"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2024,"doi":"10.1056/nejmoa2409932","pmid":"39282906","authors":"Schmid P, Cortes J, Dent R, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the KEYNOTE-522 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-monaleesa-2-n-engl-j-med-2022-update","kind":"paper","name":"Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer","aka":[],"tldr":"Later report from the MONALEESA-2 trial registered as NCT01958021, in New England Journal of Medicine (2022); its title describes an updated or longer-term analysis.","summary":"Background: In a previous analysis of this phase 3 trial, first-line ribociclib plus letrozole resulted in significantly longer progression-free survival than letrozole alone among postmenopausal patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Whether overall survival would also be longer with ribociclib was not known.\n\nMethods: Here we report the results of the protocol-specified final analysis of overall survival, a key secondary end point. Patients were randomly assigned in a 1:1 ratio to receive either ribociclib or placebo in combination with letrozole. Overall survival was assessed with the use of a stratified log-rank test and summarized with the use of Kaplan-Meier methods after 400 deaths had occurred. A hierarchical testing strategy was used for the analysis of progression-free survival and overall survival to ensure the validity of the findings.\n\nResults: After a median follow-up of 6.6 years, 181 deaths had occurred among 334 patients (54.2%) in the ribociclib group and 219 among 334 (65.6%) in the placebo group. Ribociclib plus letrozole showed a significant overall survival benefit as compared with placebo plus letrozole. Median overall survival was 63.9 months (95% confidence interval [CI], 52.4 to 71.0) with ribociclib plus letrozole and 51.4 months (95% CI, 47.2 to 59.7) with placebo plus letrozole (hazard ratio for death, 0.76; 95% CI, 0.63 to 0.93; two-sided P = 0.008). No new safety signals were observed.\n\nConclusions: First-line therapy with ribociclib plus letrozole showed a significant overall survival benefit as compared with placebo plus letrozole in patients with HR-positive, HER2-negative advanced breast cancer. Median overall survival was more than 12 months longer with ribociclib than with placebo. (Funded by Novartis; MONALEESA-2 ClinicalTrials.gov number, NCT01958021.).\n\nIndexed on Europe PMC as PubMed record 35263519 (DOI 10.1056/nejmoa2114663). Its abstract cites the registry id NCT01958021, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2022","url":"https://doi.org/10.1056/nejmoa2114663"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35263519/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35263519"},{"label":"ClinicalTrials.gov NCT01958021","url":"https://clinicaltrials.gov/study/NCT01958021"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["monaleesa-2"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/nejmoa2114663","pmid":"35263519","authors":"Hortobagyi GN, Stemmer SM, Burris HA, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the MONALEESA-2 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-tropics-02-lancet-2023","kind":"paper","name":"Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): a randomised, open-label, multicentre, phase 3 trial","aka":[],"tldr":"Published report from the TROPiCS-02 trial registered as NCT03901339, in The Lancet (2023), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Sacituzumab govitecan demonstrated significant progression-free survival benefit over chemotherapy in the phase 3 TROPiCS-02 trial in patients with pretreated, endocrine-resistant hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+ and HER2-) metastatic breast cancer with limited treatment options. Here, we report the protocol-specified final analysis of overall survival and endpoints by trophoblast cell-surface antigen 2 (Trop-2) expression and other variables.\n\nMethods: In this randomised, open-label, multicentre, phase 3 trial, which took place in 91 centres across North America (the USA and Canada) and Europe (Belgium, France, Germany, Italy, the Netherlands, Spain, and the UK), patients were randomly assigned (1:1) to receive sacituzumab govitecan or chemotherapy (eribulin, vinorelbine, capecitabine, or gemcitabine). Patients had confirmed HR+ and HER2- locally recurrent inoperable or metastatic breast cancer and had received at least one previous endocrine therapy, a taxane, and a CDK4/6 inhibitor in any setting and two to four previous chemotherapy regimens for metastatic disease. The primary endpoint was progression-free survival (previously reported and not included in this analysis), and secondary endpoints included overall survival, objective response rate (ORR), and patient-reported outcomes. Overall survival was assessed using stratified log-rank tests and Cox regression. Trop-2 expression was assessed in tumour tissue by immunohistochemistry. In the statistical testing hierarchy, ORR and patient-reported outcomes were tested sequentially if overall survival was significant. This study is registered with ClinicalTrials.gov, NCT03901339.\n\nFindings: At the data cutoff date of July 1, 2022, 543 of 776 screened patients were randomly assigned between May 30, 2019, and April 5, 2021, with 272 patients in the sacituzumab govitecan group and 271 patients in the chemotherapy group. With a 12·5-month (IQR 6·4-18·8) median follow-up, 390 deaths occurred among 543 patients. Overall survival was significantly improved with sacituzumab govitecan versus chemotherapy (median 14·4 months [95% CI 13·0-15·7] vs 11·2 months [10·1-12·7]; hazard ratio [HR] 0·79, 95% CI 0·65-0·96; p=0·020); survival benefit was consistent across Trop-2 expression-level subgroups. ORR was significantly improved with sacituzumab govitecan compared with chemotherapy (57 [21%] patients vs 38 [14%]; odds ratio 1·63 [95% CI 1·03-2·56]; p=0·035), as was time to deterioration of global health status and quality of life (median 4·3 months vs 3·0 months; HR 0·75 [0·61-0·92]; p=0·0059) and fatigue (median 2·2 months vs 1·4 months; HR 0·73 [0·60-0·89]; p=0·0021). The safety profile of sacituzumab govitecan was consistent with previous studies (including the TROPiCS-02 primary analysis and the ASCENT trial). One fatal adverse event (septic shock caused by neutropenic colitis) was determined to be related to sacituzumab govitecan treatment.\n\nInterpretation: Sacituzumab govitecan demonstrated statistically significant and clinically meaningful benefit over chemotherapy, with a 3·2-month median overall survival improvement and a manageable safety profile. These data support sacituzumab govitecan as a new treatment option for patients with pretreated, endocrine-resistant HR+ and HER2- metastatic breast cancer.\n\nFunding: Gilead Sciences.\n\nIndexed on Europe PMC as PubMed record 37633306 (DOI 10.1016/s0140-6736(23)01245-x). Its abstract cites the registry id NCT03901339, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet 2023","url":"https://doi.org/10.1016/s0140-6736(23)01245-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37633306/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37633306"},{"label":"ClinicalTrials.gov NCT03901339","url":"https://clinicaltrials.gov/study/NCT03901339"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["tropics-02"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2023,"doi":"10.1016/s0140-6736(23)01245-x","pmid":"37633306","authors":"Rugo HS, Bardia A, Marmé F, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03901339 with the most citations, so it is the natural first reading for anyone following the TROPiCS-02 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-cd47-pancreatic-pharmacol-res-2022","kind":"paper","name":"Overcoming immunotherapeutic resistance in PDAC: SIRPα-CD47 blockade","aka":[],"tldr":"Review on CD47 in Pancreatic ductal adenocarcinoma, in Pharmacological research (2022), one of the most cited Europe PMC records with CD47 in its title.","summary":"A daily increase in the number of new cases of pancreatic ductal adenocarcinoma remains an issue of contention in cancer research. The data revealed that a global cumulated case of about 500, 000 have been reported. This has made PDAC the fourteenth most occurring tumor case in cancer research. Furthermore, PDAC is responsible for about 466,003 deaths annually, representing the seventh prevalent type of cancer mortality. PDAC has no salient symptoms in its early stages. This has exasperated several attempts to produce a perfect therapeutic agent against PDAC. Recently, immunotherapeutic research has shifted focus to the blockade of checkpoint proteins in the management and of some cancers. Investigations have centrally focused on developing therapeutic agents that could at least to a significant extent block the SIRPα-CD47 signaling cascade (a cascade which prevent phagocytosis of tumors by dendritic cells, via the deactivation of innate immunity and subsequently resulting in tumor regression) with minimal side effects. The concept on the blockade of this interaction as a possible mechanism for inhibiting the progression of PDAC is currently being debated. This review examined the structure--function activity of SIRPα-CD47 interaction while discussing in detail the mechanism of tumor resistance in PDAC. Further, this review details how the blockade of SIRPα-CD47 interaction serve as a therapeutic option in the management of PDAC.\n\nIndexed on Europe PMC as PubMed record 35597384 (DOI 10.1016/j.phrs.2022.106264). Its title names CD47 and its text names Pancreatic ductal adenocarcinoma; PubMed types it as a review (Review). It was matched automatically to the idea \"Can MYC be drugged directly, and will patients tolerate it?\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Pharmacol Res 2022","url":"https://doi.org/10.1016/j.phrs.2022.106264"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35597384/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35597384"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Pharmacological research","year":2022,"doi":"10.1016/j.phrs.2022.106264","pmid":"35597384","authors":"Alausa A, Lawal KA, Babatunde OA, et al.","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for CD47 in Pancreatic ductal adenocarcinoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by CD47 in the title and Pancreatic ductal adenocarcinoma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-loeb-overdiagnosis-overtreatment-prostate-eur-urol-2014","kind":"paper","name":"Overdiagnosis and overtreatment of prostate cancer","aka":["Loeb 2014 overdiagnosis review","prostate overdiagnosis 1.7 to 67 percent"],"tldr":"A review that gathered every way overdiagnosis in prostate cancer has been measured and found estimates from under two percent to two thirds, depending entirely on the method. The one figure everyone can agree on is that autopsy studies find prostate cancer in around a fifth to two fifths of men who died of something else.","summary":"Stacy Loeb, Ruth Etzioni and colleagues reviewed the primary data on prostate cancer overdiagnosis and overtreatment from epidemiological, clinical and autopsy studies. Overdiagnosis has been estimated by lead-time modelling, by excess incidence, by the frequency of low-grade minimal tumours in prostatectomy specimens and by finding cancer in men who died of other causes, and each method gives a different answer.\n\nThe review is the right citation for the open problem rather than any single number, because it demonstrates that the number is not a property of the disease but of the study design and the background incidence. It also records the direction of travel on the treatment side: contemporary international studies show increasing use of conservative management, which is the only lever that turns overdiagnosis from a harm into a statistic.","asOf":"2026-09-25","links":[{"label":"Eur Urol 2014","url":"https://doi.org/10.1016/j.eururo.2013.12.062"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24439788/"}],"tags":["prostate-evidence"],"related":["paper-draisma-lead-time-overdiagnosis-psa-jnci-2009","paper-welch-albertsen-psa-era-diagnosis-treatment-jnci-2009","paper-klotz-active-surveillance-jco-2015","idea-prev-gleason6-terminology-rct","prostate-roadmap"],"cancers":["prostate","prostate-low-risk"],"sections":["early-detection","prevention"],"technologies":["active-surveillance"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["overdiagnosis","screening","psa","gleason-grade-group","overtreatment","lead-time-bias"],"trials":[],"people":[],"bottlenecks":["b-overdiagnosis","b-early-detection","b-toxicity-qol","b-patient-voice"],"keyPapers":[],"journals":["european-urology"],"dependsOn":[],"notes":[],"journal":"European Urology","year":2014,"doi":"10.1016/j.eururo.2013.12.062","pmid":"24439788","authors":"Loeb S, Bjurlin MA, Nicholson J, et al.","paperType":"review","findings":["Estimates of overdiagnosis across epidemiological, clinical and autopsy studies ranged from 1.7 percent to 67 percent.","The estimated number of prostate cancers needing to be diagnosed to save one life ranged from 48 down to 5 with increasing follow-up.","In clinical studies based on the frequency of low-grade minimal tumours at radical prostatectomy, reported overdiagnosis rates were 1.7 to 46.8 percent.","Autopsy studies reported prostate cancer in 18.5 to 38.5 percent of men, although not all of it was low grade or low volume.","Reported rates of overtreatment vary widely and contemporary international studies suggest increasing use of conservative management."],"whatItMeans":"The honest state of the overdiagnosis question. Prostate cancer is common in the prostates of men who die of something else, screening finds a proportion of it, and how much of that is harm depends on what is done next. The fix is not a better estimate but fewer treatments for the cancers that do not need them.","caveats":["A narrative review with a systematic search rather than a pooled quantitative analysis, so it summarises heterogeneity rather than resolving it.","Autopsy prevalence is not the same as overdiagnosis: some autopsy-detected cancer is high grade and would have surfaced.","Published in 2014, before magnetic resonance imaging triage and before active surveillance reached its current share of low-risk management, so the overtreatment figures are historical."],"changedPractice":false},{"id":"paper-welch-j-natl-cancer-inst","kind":"paper","name":"Overdiagnosis in cancer","aka":[],"tldr":"Paper cited by one bottleneck page and 21 idea pages, indexed on Europe PMC as PubMed record 20413742 and published in JNCI: Journal of the National Cancer Institute; the citing pages link this DOI, which is how the record was matched.","summary":"This article summarizes the phenomenon of cancer overdiagnosis-the diagnosis of a \"cancer\" that would otherwise not go on to cause symptoms or death. We describe the two prerequisites for cancer overdiagnosis to occur: the existence of a silent disease reservoir and activities leading to its detection (particularly cancer screening). We estimated the magnitude of overdiagnosis from randomized trials: about 25% of mammographically detected breast cancers, 50% of chest x-ray and/or sputum-detected lung cancers, and 60% of prostate-specific antigen-detected prostate cancers. We also review data from observational studies and population-based cancer statistics suggesting overdiagnosis in computed tomography-detected lung cancer, neuroblastoma, thyroid cancer, melanoma, and kidney cancer. To address the problem, patients must be adequately informed of the nature and the magnitude of the trade-off involved with early cancer detection. Equally important, researchers need to work to develop better estimates of the magnitude of overdiagnosis and develop clinical strategies to help minimize it.\n\nIndexed on Europe PMC as PubMed record 20413742 (DOI 10.1093/jnci/djq099). Matched by DOI alone: one bottleneck page and 21 idea pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Natl Cancer Inst 2010","url":"https://doi.org/10.1093/jnci/djq099"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20413742/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/20413742"}],"tags":["europepmc-ingest"],"related":["b-overdiagnosis","idea-prev-mced-pretest-decision-aid","idea-prev-incidentaloma-natural-history-cohort","idea-prev-blood-precursor-watch-registry","idea-prev-ptmc-active-surveillance-default","idea-prev-low-risk-dcis-surveillance-pathway","idea-prev-lung-nodule-ai-discharge","idea-prev-pathology-ai-borderline-anchor","idea-prev-indolent-lesion-nomenclature-body","idea-prev-annual-overdiagnosis-reporting","idea-prev-frail-elderly-primary-endocrine-breast","idea-prev-melanoma-ai-thick-melanoma-metric","idea-prev-omit-radiotherapy-low-risk-breast-default","idea-prev-modern-autopsy-reservoir-studies","idea-moon-indolence-classifiers-with-screening","idea-prev-prostate-as-triggered-biopsy","idea-prev-thyroid-no-screening-no-small-biopsy","idea-prev-barrett-surveillance-deescalation","idea-prev-screening-stop-by-life-expectancy","idea-prev-ipmn-surveillance-stop-rule","idea-prev-gleason6-terminology-rct","idea-prev-small-renal-mass-surveillance"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jnci"],"dependsOn":[],"notes":[],"journal":"JNCI: Journal of the National Cancer Institute","year":2010,"doi":"10.1093/jnci/djq099","pmid":"20413742","authors":"Welch HG, Black WC","paperType":"review","findings":[],"whatItMeans":"One bottleneck page and 21 idea pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-roa-her2-overexpression-gallbladder-gcr-2014","kind":"paper","name":"Overexpression of the HER2/neu gene: a new therapeutic possibility for patients with advanced gallbladder cancer","aka":[],"tldr":"In 187 Chilean gallbladder cancers stained with breast cancer rules, about one in eight overexpressed HER2, one in five was borderline, and the HER2-positive patients did slightly worse, an early argument for HER2 drugs in this disease.","summary":"187 patients with gallbladder cancer (165 women, 22 men) with at least five years of follow-up and 75 controls were studied with an automated immunohistochemical technique using an anti-ErbB2 antibody, scored by the CAP/ASCO criteria for breast cancer.\n\nOverexpression of HER2/neu was observed in 12.8% of cases (0% mucosal, 14.3% muscular, 12.8% subserosal and 10.6% serosal tumours) and equivocal staining in 20%. Overexpression was more frequent in advanced and in better-differentiated tumours (13.8% and 17.4%), not significantly. Patients with overexpression had worse five-year survival than those without (34% versus 41%). The authors concluded that overexpression occurred in 14% of advanced cases and that this subgroup might benefit from HER2 pathway inhibitors.","asOf":"2026-09-24","links":[{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24799970/"}],"tags":[],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":["her2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ihc","her2-testing-in-biliary-cancer"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Gastrointestinal Cancer Research","year":2014,"pmid":"24799970","authors":"Roa I, de Toro G, Schalper K, et al.","paperType":"observational","findings":["HER2 overexpression in 12.8% of 187 Chilean gallbladder cancers; equivocal staining in 20%.","Overexpression absent in mucosal tumours, 14.3% in muscular, 12.8% in subserosal, 10.6% in serosal.","Five-year survival 34% with overexpression versus 41% without."],"whatItMeans":"The largest Chilean HER2 series and the reason HER2 rates in the highest-incidence country are quoted at around 13%; scoring by breast rather than gastric rules explains part of the gap to the Japanese 31%.","caveats":["Immunohistochemistry only, no in situ hybridisation, so the 20% equivocal group is unresolved.","No DOI; PubMed record only."],"changedPractice":false,"participants":187},{"id":"paper-mosaic-oxaliplatin-adjuvant-colon-nejm-2004","kind":"paper","name":"Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer (MOSAIC)","aka":[],"tldr":"Adding oxaliplatin to chemotherapy after a colon cancer operation cut recurrences by 23 percent. It made FOLFOX the standard, and gave a generation of patients the numb fingers that go with it.","summary":"The Multicenter International Study of Oxaliplatin, Fluorouracil and Leucovorin in the Adjuvant Treatment of Colon Cancer randomly assigned 2,246 patients who had undergone curative resection for stage II or III colon cancer to fluorouracil and leucovorin alone or with oxaliplatin for six months, with disease-free survival as the primary end point; 1,123 patients were assigned to each group.\n\nGrade 3 sensory neuropathy occurred in 12.4 percent during treatment and fell to 1.1 percent at one year, the trade-off that the IDEA collaboration later tried to reduce by shortening treatment.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2004","url":"https://doi.org/10.1056/NEJMoa032709"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/15175436/"},{"label":"N Engl J Med 2004","url":"https://doi.org/10.1056/nejmoa032709"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/15175436"}],"tags":["colorectal-evidence"],"related":["paper-idea-duration-adjuvant-stage-iii-colon-nejm-2018","paper-quasar-adjuvant-chemotherapy-vs-observation-lancet-2007","oxaliplatin"],"cancers":["colorectal","colon-cancer"],"sections":["chemotherapy"],"technologies":["cytotoxic-chemotherapy"],"targets":[],"drugs":["folfox","oxaliplatin","fluorouracil","leucovorin"],"companies":[],"institutions":[],"pathways":[],"terms":["neoadjuvant-adjuvant"],"trials":[],"people":["thierry-andre","josep-tabernero","aimery-de-gramont"],"bottlenecks":["b-toxicity-qol"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2004,"doi":"10.1056/NEJMoa032709","pmid":"15175436","authors":"André T, Boni C, Mounedji-Boudiaf L, et al.","paperType":"rct","findings":["After a median 37.9 months, 237 cancer-related events with oxaliplatin against 293 without (21.1 against 26.1 percent; hazard ratio for recurrence 0.77, p=0.002).","Three-year disease-free survival 78.2 percent (95 percent CI 75.6 to 80.7) against 72.9 percent (70.2 to 75.7), p=0.002.","Febrile neutropenia 1.8 percent; grade 3 sensory neuropathy 12.4 percent during treatment, 1.1 percent at one year.","Six patients in each group died during treatment (death rate 0.5 percent)."],"whatItMeans":"FOLFOX after surgery for stage III colon cancer, still the standard 22 years later, and the reason every later adjuvant trial in this disease is an oxaliplatin trial.","caveats":["The stage II subgroup did not show a clear benefit, and later analyses confined any benefit to high-risk stage II disease.","Persistent neuropathy is the dominant long-term harm and was the motivation for the duration trials.","Predates mismatch repair testing, ctDNA and the knowledge that mismatch repair-deficient stage II disease does not benefit from fluoropyrimidines."],"changedPractice":true,"participants":2246},{"id":"paper-pace-ponatinib-nejm-2013","kind":"paper","name":"PACE: ponatinib in Philadelphia chromosome-positive leukaemias resistant to earlier tyrosine kinase inhibitors","aka":[],"tldr":"Ponatinib produced deep responses in patients with chronic myeloid leukaemia or Philadelphia-positive acute lymphoblastic leukaemia whose disease had resisted other kinase inhibitors, including the T315I mutation that no other drug could reach.","summary":"Phase 2 study of 449 heavily pretreated patients with chronic, accelerated or blast-phase CML or Ph-positive ALL, including 128 with the T315I gatekeeper mutation, treated with ponatinib 45 mg daily.\n\nIn chronic phase, 56 percent achieved a major cytogenetic response (70 percent of those with T315I); responses in accelerated and blast phase were lower and shorter. Arterial occlusive events emerged as the defining toxicity, later prompting dose reduction strategies.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2013","url":"https://doi.org/10.1056/NEJMoa1306494"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24180494/"}],"tags":[],"related":[],"cancers":["cml-advanced-phase"],"sections":[],"technologies":[],"targets":[],"drugs":["ponatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2013,"doi":"10.1056/NEJMoa1306494","pmid":"24180494","authors":"Cortes JE, Kim DW, Pinilla-Ibarz J, et al.","paperType":"observational","findings":["Major cytogenetic response in 56 percent of chronic-phase patients and 70 percent of those with T315I.","Major haematological response in 55 percent of accelerated-phase and 31 percent of blast-phase or Ph-positive ALL patients."],"whatItMeans":"Ponatinib is the drug for T315I-mutated disease and for patients who have failed several inhibitors, including in accelerated and blast phase as a bridge to transplant. Cardiovascular risk must be managed actively.","caveats":["Serious arterial thrombotic events in a substantial minority, increasing with time on treatment.","Single-arm design; response-based dose reduction (OPTIC) came later."],"changedPractice":true,"participants":449},{"id":"paper-nct03706690-j-hematol-oncol-2025","kind":"paper","name":"PACIFIC-5: a phase III clinical trial of consolidation durvalumab in patients with unresectable stage III NSCLC and no progression after concurrent or sequential chemoradiotherapy","aka":[],"tldr":"Published report from the PACIFIC-5 trial registered as NCT03706690, in Journal of hematology & oncology (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Consolidation durvalumab following no progression on concurrent chemoradiotherapy (cCRT) is standard of care for unresectable stage III non-small-cell lung cancer (NSCLC). However, in clinical practice many patients receive sequential CRT (sCRT). The PACIFIC-5 trial aimed to evaluate the efficacy and safety of consolidation durvalumab for unresectable stage III NSCLC following no progression on cCRT or sCRT.\n\nMethods: This randomised, double-blind, placebo-controlled, phase III trial enrolled patients aged ≥ 18 years with unresectable stage III NSCLC, regardless of PD-L1 expression or sensitising EGFR or ALK aberrations, without disease progression after cCRT or sCRT. Patients were randomised (2:1) to durvalumab 1500 mg or placebo intravenously every 4 weeks (stratified by tumour PD-L1 expression and prior treatment) until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was progression-free survival (PFS) by blinded independent central review in the modified intention-to-treat population (mITT). Secondary endpoints included overall survival (OS) in the mITT and safety. The safety analysis set include patients who received at least one dose of study treatment.\n\nResults: Of 407 patients randomised to receive durvalumab (n = 272) or placebo (n = 135), 405 received at least one dose of durvalumab (n = 271) or placebo (n = 134). The mITT comprised 381 patients randomised to durvalumab (n = 252) or placebo (n = 129). Durvalumab showed statistically significant improvement in PFS versus placebo in the mITT (median [95% confidence interval {CI}], 14.0 [10.9-18.0] vs. 6.5 [5.4-13.8] months; hazard ratio [95% CI], 0.75 [0.58-0.99]; p = 0.038). There was a trend toward improved OS with durvalumab versus placebo in the mITT (median [95% CI], 38.3 [28.9-42.8] vs. 32.5 [20.6-40.4] months; hazard ratio [95% CI], 0.87 [0.66-1.17]; p = 0.346 [interim analysis]). Among the safety analysis set, maximum grade 3 or 4 adverse events of any cause occurred in 26.9% (73/271) and 23.9% (32/134) and 1.5% (4/271) and 0% (0/134) had treatment-related adverse events leading to death for durvalumab and placebo, respectively.\n\nConclusions: PACIFIC-5 met its primary endpoint of improved PFS after either cCRT or sCRT. Follow-up for overall survival is ongoing.\n\nTrial registration: NCT03706690.\n\nIndexed on Europe PMC as PubMed record 41354932 (DOI 10.1186/s13045-025-01768-1). Its abstract cites the registry id NCT03706690, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Hematol Oncol 2025","url":"https://doi.org/10.1186/s13045-025-01768-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41354932/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41354932"},{"label":"ClinicalTrials.gov NCT03706690","url":"https://clinicaltrials.gov/study/NCT03706690"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct03706690"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-hematology-and-oncology"],"dependsOn":[],"notes":[],"journal":"Journal of hematology & oncology","year":2025,"doi":"10.1186/s13045-025-01768-1","pmid":"41354932","authors":"Wu YL, Wu L, Bi N, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03706690 with the most citations, so it is the natural first reading for anyone following the PACIFIC-5 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-pacific-nejm-2017","kind":"paper","name":"PACIFIC: a year of durvalumab after chemoradiotherapy for stage III lung cancer","aka":[],"tldr":"Giving the immunotherapy durvalumab for a year after chemoradiotherapy for unresectable stage III lung cancer tripled the time to progression and raised five-year survival from about a third to over 40%.","summary":"Double-blind, placebo-controlled phase 3 trial of 713 patients with unresectable stage III NSCLC who had not progressed after concurrent platinum-based chemoradiotherapy, randomised 2:1 to up to 12 months of durvalumab or placebo. Co-primary endpoints were PFS and overall survival.\n\nMedian PFS was 16.8 vs 5.6 months (HR 0.52) and overall survival was significantly improved (HR 0.68 in the 2018 report). Five-year OS was 42.9% vs 33.4%. It was the first change in stage III standard of care in two decades and the model for consolidation immunotherapy in small-cell lung cancer (ADRIATIC) and other tumours.","asOf":"2026-09-08","links":[{"label":"NEJM 2017","url":"https://doi.org/10.1056/NEJMoa1709937"},{"label":"NEJM 2018 (OS)","url":"https://doi.org/10.1056/NEJMoa1809697"},{"label":"ClinicalTrials.gov NCT02125461","url":"https://clinicaltrials.gov/study/NCT02125461"}],"tags":[],"related":["lung-cancer-evidence-roadmap","paper-spigel-pacific-five-year-survival-jco-2022","paper-lu-laura-osimertinib-stage-iii-nejm-2024"],"cancers":["nsclc","lung-cancer"],"sections":[],"technologies":["checkpoint-inhibitor","imrt-igrt","platinum"],"targets":["pdl1"],"drugs":["durvalumab"],"companies":["astrazeneca"],"institutions":[],"pathways":[],"terms":["pfs","os","standard-of-care","irae"],"trials":[],"people":["cho-byoung-chul"],"bottlenecks":["b-immunotherapy-response","b-surgery-radiation-innovation","b-biomarker-validation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2017,"doi":"10.1056/NEJMoa1709937","authors":"Antonia SJ, Villegas A, Daniel D, et al.","paperType":"rct","findings":["Median PFS 16.8 vs 5.6 months; HR 0.52 (95% CI 0.42-0.65).","Overall survival (2018): HR 0.68; 24-month OS 66.3% vs 55.6%.","Five-year update (JCO 2022): OS 42.9% vs 33.4%; PFS 33.1% vs 19.0%.","Grade 3-4 pneumonitis or radiation pneumonitis 3.4% vs 2.6%; any-grade pneumonitis about 34% vs 25%.","Post hoc analysis suggested little benefit in PD-L1 below 1%, leading the EMA (but not FDA) to restrict the label to PD-L1 of 1% or more."],"whatItMeans":"Patients with stage III lung cancer that cannot be removed surgically should receive a year of durvalumab after completing chemoradiotherapy, provided they have not progressed. This roughly doubles the chance of being alive without progression at five years. Whether the benefit extends to PD-L1-negative tumours is contested, and the EGFR-mutated subgroup is better served by osimertinib (LAURA).","caveats":["PD-L1 status was not required for enrolment and the subgroup analysis by PD-L1 below 1% was unplanned and post hoc.","Patients had to have completed chemoradiotherapy without progression, a selected fitter population.","Combined radiation and immune pneumonitis requires careful monitoring, especially in Asian populations where rates were higher.","The trial did not test whether concurrent immunotherapy during radiotherapy is better; PACIFIC-2 was negative."],"changedPractice":true,"participants":713},{"id":"paper-sandler-ecog-4599-bevacizumab-nsclc-nejm-2006","kind":"paper","name":"Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer","aka":[],"tldr":"Adding an antibody against the tumour's blood supply to chemotherapy pushed median survival past a year for the first time in advanced lung cancer, at the cost of more treatment-related deaths.","summary":"The Eastern Cooperative Oncology Group's E4599 trial, reported by Sandler, Gray, Perry, Brahmer, Schiller, Dowlati, Lilenbaum and Johnson: 878 patients with recurrent or advanced stage IIIB or IV non-small-cell lung cancer randomised between July 2001 and April 2004 to paclitaxel and carboplatin alone (444) or with bevacizumab continued until progression (434).\n\nPatients with squamous tumours, brain metastases, clinically significant haemoptysis, inadequate organ function or a performance status above 1 were excluded, because of fatal pulmonary haemorrhage seen in earlier studies. That exclusion list is part of the result: it is the first modern lung cancer trial in which a biological feature of the tumour decided who could receive the drug.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2006","url":"https://doi.org/10.1056/NEJMoa061884"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/17167137/"},{"label":"ClinicalTrials.gov NCT00021060","url":"https://clinicaltrials.gov/study/NCT00021060"}],"tags":["lung-evidence"],"related":["paper-scagliotti-cisplatin-pemetrexed-histology-jco-2008","targeted-therapy-roadmap"],"cancers":["lung-cancer","nsclc","lung-adenocarcinoma"],"sections":[],"technologies":[],"targets":["vegf"],"drugs":["bevacizumab","paclitaxel","carboplatin"],"companies":["ecog-acrin"],"institutions":[],"pathways":["angiogenesis"],"terms":["brain-metastases","performance-status","histology"],"trials":[],"people":["julie-brahmer"],"bottlenecks":["b-biomarker-validation","b-toxicity-qol","b-trial-enrolment"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2006,"doi":"10.1056/NEJMoa061884","pmid":"17167137","authors":"Sandler A, Gray R, Perry MC, et al.","paperType":"rct","findings":["Median survival 12.3 months with bevacizumab against 10.3 months with chemotherapy alone (hazard ratio for death 0.79; P equals 0.003).","Median progression-free survival 6.2 against 4.5 months (hazard ratio 0.66).","The survival benefit came with a risk of increased treatment-related deaths.","Patients with squamous tumours, brain metastases, significant haemoptysis, inadequate organ function or performance status above 1 were excluded from the trial."],"whatItMeans":"The first time a targeted biological agent extended survival in lung cancer, and the first time median survival in the advanced setting crossed twelve months. It also set the pattern that a drug's exclusion criteria can matter as much as its mechanism.","caveats":["Non-squamous histology only, with brain metastases excluded; the result does not transfer to the patients who were kept out.","Treatment-related deaths were higher with bevacizumab, and the abstract does not quantify them.","No predictive biomarker for benefit was ever validated, so bevacizumab is given to a histologically rather than molecularly defined group."],"changedPractice":true,"participants":878},{"id":"paper-paganetti-proton-rbe-ijrobp-2014","kind":"paper","name":"Paganetti 2014: proton RBE is not a fixed 1.1","aka":[],"tldr":"The number used to convert proton gray into X-ray gray (1.1) is a convention. The true relative effect is higher where the beam stops, and it depends on the tissue and the size of each dose.","summary":"Paganetti reviewed laboratory and clinical estimates of proton relative biological effectiveness and showed systematic variation with linear energy transfer, dose per fraction, and biological endpoint. The distal edge is the region of concern. The paper is why variable-RBE planning exists and why constant 1.1 remains a reporting rule rather than a measurement.","asOf":"2026-09-17","links":[{"label":"DOI","url":"https://doi.org/10.1016/j.ijrobp.2014.07.001"}],"tags":["radiation-wave5"],"related":[],"cancers":[],"sections":["radiation"],"technologies":["proton-therapy","intensity-modulated-proton-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["relative-biological-effectiveness","linear-energy-transfer","alpha-beta-ratio","bragg-peak"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"International Journal of Radiation Oncology, Biology, Physics","year":2014,"doi":"10.1016/j.ijrobp.2014.07.001","authors":"Paganetti H","paperType":"review","findings":["Clinical proton dose is reported at a constant RBE of 1.1.","RBE increases with LET toward the distal edge of the spread-out Bragg peak.","RBE is larger at lower dose per fraction and for late-responding (low alpha/beta) endpoints."],"whatItMeans":"A proton plan that looks safe on a 1.1 RBE map can still over-dose a late-responding organ sitting on the distal edge. Comparing protons with IMRT without an LET-weighted view asks the wrong physical question.","caveats":["In vivo human RBE remains inferred, not measured lesion by lesion.","No single variable-RBE model is standard in the clinic.","This is a review of estimates, not a randomised comparison of RBE models."],"changedPractice":false},{"id":"paper-kothari-paget-disease-nipple-multifocal-cancer-2002","kind":"paper","name":"Paget disease of the nipple as a marker of multifocal, higher-risk underlying breast cancer","aka":[],"tldr":"This pathological study found that the cancer underlying Paget disease of the nipple is often multifocal and spread away from the nipple, which is why full imaging and careful surgical planning are needed rather than simple nipple excision.","summary":"Review of 70 mastectomy specimens with Paget disease of the nipple, mapping the extent and location of the underlying in situ and invasive carcinoma.\n\nMost cases had underlying carcinoma, frequently multifocal and often distant from the nipple, with a high proportion of high-grade and HER2-positive tumours, arguing that Paget disease marks a higher-risk breast.","asOf":"2026-09-17","links":[{"label":"Cancer 2002","url":"https://doi.org/10.1002/cncr.10638"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/12115309/"}],"tags":[],"related":[],"cancers":["paget-disease-of-the-nipple"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-wiley"],"dependsOn":[],"notes":[],"journal":"Cancer","year":2002,"doi":"10.1002/cncr.10638","pmid":"12115309","authors":"Kothari AS, Beechey-Newman N, Hamed H, et al.","paperType":"observational","findings":[],"whatItMeans":"Breast MRI to map disease and central excision with clear margins or mastectomy, rather than removing the nipple alone, follow from findings like these.","caveats":["Single-institution mastectomy series, which selects for more extensive disease."],"changedPractice":false,"participants":70},{"id":"paper-paloma-2-n-engl-j-med-2016","kind":"paper","name":"Palbociclib and Letrozole in Advanced Breast Cancer","aka":[],"tldr":"Published report from the PALOMA-2 trial registered as NCT01740427, in New England Journal of Medicine (2016), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: A phase 2 study showed that progression-free survival was longer with palbociclib plus letrozole than with letrozole alone in the initial treatment of postmenopausal women with estrogen-receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. We performed a phase 3 study that was designed to confirm and expand the efficacy and safety data for palbociclib plus letrozole for this indication.\n\nMethods: In this double-blind study, we randomly assigned, in a 2:1 ratio, 666 postmenopausal women with ER-positive, HER2-negative breast cancer, who had not had prior treatment for advanced disease, to receive palbociclib plus letrozole or placebo plus letrozole. The primary end point was progression-free survival, as assessed by the investigators; secondary end points were overall survival, objective response, clinical benefit response, patient-reported outcomes, pharmacokinetic effects, and safety.\n\nResults: The median progression-free survival was 24.8 months (95% confidence interval [CI], 22.1 to not estimable) in the palbociclib-letrozole group, as compared with 14.5 months (95% CI, 12.9 to 17.1) in the placebo-letrozole group (hazard ratio for disease progression or death, 0.58; 95% CI, 0.46 to 0.72; P<0.001). The most common grade 3 or 4 adverse events were neutropenia (occurring in 66.4% of the patients in the palbociclib-letrozole group vs. 1.4% in the placebo-letrozole group), leukopenia (24.8% vs. 0%), anemia (5.4% vs. 1.8%), and fatigue (1.8% vs. 0.5%). Febrile neutropenia was reported in 1.8% of patients in the palbociclib-letrozole group and in none of the patients in the placebo-letrozole group. Permanent discontinuation of any study treatment as a result of adverse events occurred in 43 patients (9.7%) in the palbociclib-letrozole group and in 13 patients (5.9%) in the placebo-letrozole group.\n\nConclusions: Among patients with previously untreated ER-positive, HER2-negative advanced breast cancer, palbociclib combined with letrozole resulted in significantly longer progression-free survival than that with letrozole alone, although the rates of myelotoxic effects were higher with palbociclib-letrozole. (Funded by Pfizer; PALOMA-2 ClinicalTrials.gov number, NCT01740427.).\n\nIndexed on Europe PMC as PubMed record 27959613 (DOI 10.1056/nejmoa1607303). Its abstract cites the registry id NCT01740427, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2016","url":"https://doi.org/10.1056/nejmoa1607303"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27959613/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27959613"},{"label":"ClinicalTrials.gov NCT01740427","url":"https://clinicaltrials.gov/study/NCT01740427"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["paloma-2"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2016,"doi":"10.1056/nejmoa1607303","pmid":"27959613","authors":"Finn RS, Martin M, Rugo HS, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT01740427 with the most citations, so it is the natural first reading for anyone following the PALOMA-2 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-patina-n-engl-j-med-2026","kind":"paper","name":"Palbociclib for Hormone-Receptor-Positive, HER2-Positive Advanced Breast Cancer","aka":[],"tldr":"Published report from the PATINA trial registered as NCT02947685, in New England Journal of Medicine (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Dual anti-human epidermal growth factor receptor 2 (HER2) therapy plus chemotherapy followed by maintenance treatment with HER2-targeted and endocrine therapies is standard first-line treatment for hormone-receptor-positive, HER2-positive metastatic breast cancer. On the basis of preclinical and clinical data, the addition of palbociclib (a selective inhibitor of cyclin-dependent kinases 4 and 6) may overcome resistance to both endocrine and HER2-directed therapies.\n\nMethods: In this phase 3, open-label, randomized trial, we enrolled patients with hormone-receptor-positive, HER2-positive metastatic breast cancer who did not have disease progression after four to eight cycles of chemotherapy plus HER2-targeted therapy. Patients were randomly assigned in a 1:1 ratio to receive maintenance HER2-targeted and endocrine therapies with or without palbociclib. The primary end point was investigator-assessed progression-free survival. Secondary end points included the objective response, clinical benefit, safety, and overall survival.\n\nResults: A total of 518 patients underwent randomization: 261 were assigned to receive palbociclib and 257 to receive standard therapy. At a median follow-up of 53.5 months, patients in the palbociclib group had significantly longer progression-free survival than those in the standard-therapy group (median duration, 44.3 months vs. 29.1 months; hazard ratio for disease progression or death, 0.75; 95% confidence interval, 0.59 to 0.96; two-sided P = 0.02). Grade 3 and 4 adverse events, predominantly from neutropenia, occurred in 79.7% and 10.0% of the patients, respectively, in the palbociclib group, as compared with 30.6% and 3.6% of the patients, respectively, in the standard-therapy group.\n\nConclusions: The addition of palbociclib to maintenance anti-HER2 and endocrine therapies led to a significant improvement in progression-free survival over standard therapy, with increased toxic effects, mainly neutropenia. (Funded by Pfizer and others; PATINA ClinicalTrials.gov number, NCT02947685.).\n\nIndexed on Europe PMC as PubMed record 41604639 (DOI 10.1056/nejmoa2511218). Its abstract cites the registry id NCT02947685, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2026","url":"https://doi.org/10.1056/nejmoa2511218"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41604639/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41604639"},{"label":"ClinicalTrials.gov NCT02947685","url":"https://clinicaltrials.gov/study/NCT02947685"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["patina"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2026,"doi":"10.1056/nejmoa2511218","pmid":"41604639","authors":"Metzger O, Mandrekar S, Goel S, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02947685 with the most citations, so it is the natural first reading for anyone following the PATINA trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-penelope-b-j-clin-oncol-2021","kind":"paper","name":"Palbociclib for Residual High-Risk Invasive HR-Positive and HER2-Negative Early Breast Cancer-The Penelope-B Trial","aka":[],"tldr":"Published report from the PENELOPE-B trial registered as NCT01864746, in Journal of Clinical Oncology (2021), chosen as the most cited paper whose own text cites the registry id.","summary":"Purpose: About one third of patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer who have residual invasive disease after neoadjuvant chemotherapy (NACT) will relapse. Thus, additional therapy is needed. Palbociclib is a cyclin-dependent kinase 4 and 6 inhibitor demonstrating efficacy in the metastatic setting.\n\nPatients and methods: PENELOPE-B (NCT01864746) is a double-blind, placebo-controlled, phase III study in women with hormone receptor-positive, human epidermal growth factor receptor 2-negative primary breast cancer without a pathological complete response after taxane-containing NACT and at high risk of relapse (clinical pathological staging-estrogen receptor grading score ≥ 3 or 2 and ypN+). Patients were randomly assigned (1:1) to receive 13 cycles of palbociclib 125 mg once daily or placebo on days 1-21 in a 28-day cycle in addition to endocrine therapy (ET). Primary end point is invasive disease-free survival (iDFS). Final analysis was planned after 290 iDFS events with a two-sided efficacy boundary P <.0463 because of two interim analyses.\n\nResults: One thousand two hundred fifty patients were randomly assigned. The median age was 49.0 years (range, 19-79), and the majority were ypN+ with Ki-67 ≤ 15%; 59.4% of patients had a clinical pathological staging-estrogen receptor grading score ≥ 3. 50.1% received aromatase inhibitor, and 33% of premenopausal women received a luteinizing hormone releasing hormone analog in addition to either tamoxifen or an aromatase inhibitor. After a median follow-up of 42.8 months (92% complete), 308 events were confirmed. Palbociclib did not improve iDFS versus placebo added to ET-stratified hazard ratio, 0.93 (95% repeated CI, 0.74 to 1.17) and two-sided weighted log-rank test (Cui, Hung, and Wang) P =.525. There was no difference among the subgroups. Most common related serious adverse events were infections and vascular disorders in 113 (9.1%) patients with no difference between the treatment arms. Eight fatal serious adverse events (two palbociclib and six placebo) were reported.\n\nConclusion: Palbociclib for 1 year in addition to ET did not improve iDFS in women with residual invasive disease after NACT.\n\nIndexed on Europe PMC as PubMed record 33793299 (DOI 10.1200/jco.20.03639). Its abstract cites the registry id NCT01864746, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2021","url":"https://doi.org/10.1200/jco.20.03639"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33793299/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33793299"},{"label":"ClinicalTrials.gov NCT01864746","url":"https://clinicaltrials.gov/study/NCT01864746"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["penelope-b"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2021,"doi":"10.1200/jco.20.03639","pmid":"33793299","authors":"Loibl S, Marmé F, Martin M, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT01864746 with the most citations, so it is the natural first reading for anyone following the PENELOPE-B trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-ahn-jco-precis-oncol","kind":"paper","name":"Palbociclib in Patients With Non-Small-Cell Lung Cancer With CDKN2A Alterations: Results From the Targeted Agent and Profiling Utilization Registry Study","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 35050752 and published in JCO Precision Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: The Targeted Agent and Profiling Utilization Registry (TAPUR) Study is a phase II pragmatic basket trial evaluating antitumor activity of commercially available targeted agents in patients with advanced cancer with genomic alterations known to be drug targets. Results in a cohort of patients with non-small-cell lung cancer (NSCLC) with CDKN2A alterations treated with palbociclib are reported.\n\nMethods: Eligible patients were ≥ 18 years old with advanced NSCLC, no remaining standard treatment options, measurable disease, Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate organ function. Patients with NSCLC with CDKN2A alterations and no Rb mutations received palbociclib 125 mg orally once daily for 21 days, followed by 7 days off. Simon's two-stage design was used with a primary study end point of objective response or stable disease (SD) of at least 16 weeks in duration. Secondary end points are progression-free survival (PFS), overall survival (OS), and safety.\n\nResults: Twenty-nine patients were enrolled from January 2017 to June 2018; two patients were not evaluable for response but were included in safety analyses. One patient with partial response and six patients with SD were observed, for a disease control rate of 31% (90% CI, 19% to 40%). Median PFS was 8.1 weeks (95% CI, 7.1 to 16.0 weeks), and median OS was 21.6 weeks (95% CI, 14.1 to 41.1 weeks). Eleven patients had at least 1 grade 3 or 4 adverse event (AE) or serious AE (SAE) possibly related to palbociclib (most common, cytopenias). Other AEs or SAEs possibly related to the treatment included anorexia, fatigue, febrile neutropenia, hypophosphatemia, sepsis, and vomiting.\n\nConclusion: Palbociclib monotherapy demonstrated evidence of modest antitumor activity in heavily pretreated patients with NSCLC with CDKN2A alterations. Additional investigation is necessary to confirm efficacy and utility of palbociclib in this population.\n\nIndexed on Europe PMC as PubMed record 35050752 (DOI 10.1200/po.20.00037). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JCO Precis Oncol 2020","url":"https://doi.org/10.1200/po.20.00037"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35050752/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35050752"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["tapur"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco-precision-oncology"],"dependsOn":[],"notes":[],"journal":"JCO Precision Oncology","year":2020,"doi":"10.1200/po.20.00037","pmid":"35050752","authors":"Ahn ER, Mangat PK, Garrett-Mayer E, et al.","paperType":"observational","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-paloma-2-breast-cancer-res-treat-2019-update","kind":"paper","name":"Palbociclib plus letrozole as first-line therapy in estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up","aka":[],"tldr":"Later report from the PALOMA-2 trial registered as NCT01740427, in Breast cancer research and treatment (2019); its title describes an updated or longer-term analysis.","summary":"Purpose: In the initial PALOMA-2 (NCT01740427) analysis with median follow-up of 23 months, palbociclib plus letrozole significantly prolonged progression-free survival (PFS) in women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) [hazard ratio (HR) 0.58; P < 0.001]. Herein, we report results overall and by subgroups with extended follow-up.\n\nMethods: In this double-blind, phase 3 study, post-menopausal women with ER+/HER2- ABC who had not received prior systemic therapy for their advanced disease were randomized 2:1 to palbociclib-letrozole or placebo-letrozole. Endpoints include investigator-assessed PFS (primary), safety, and patient-reported outcomes (PROs).\n\nResults: After a median follow-up of approximately 38 months, median PFS was 27.6 months for palbociclib-letrozole (n = 444) and 14.5 months for placebo-letrozole (n = 222) (HR 0.563; 1-sided P < 0.0001). All subgroups benefited from palbociclib treatment. The improvement of PFS with palbociclib-letrozole was maintained in the next 2 subsequent lines of therapy and delayed the use of chemotherapy (40.4 vs. 29.9 months for palbociclib-letrozole vs. placebo-letrozole). Safety data were consistent with the known profile. Patients' quality of life was maintained.\n\nConclusions: With approximately 15 months of additional follow-up, palbociclib plus letrozole continued to demonstrate improved PFS compared with placebo plus letrozole in the overall population and across all patient subgroups, while the safety profile remained favorable and quality of life was maintained. These data confirm that palbociclib-letrozole should be considered the standard of care for first-line therapy in patients with ER+/HER2- ABC, including those with low disease burden or long disease-free interval. Sponsored by Pfizer; ClinicalTrials.gov: NCT01740427.\n\nIndexed on Europe PMC as PubMed record 30632023 (DOI 10.1007/s10549-018-05125-4). Its abstract cites the registry id NCT01740427, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Breast Cancer Res Treat 2019","url":"https://doi.org/10.1007/s10549-018-05125-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30632023/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30632023"},{"label":"ClinicalTrials.gov NCT01740427","url":"https://clinicaltrials.gov/study/NCT01740427"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["paloma-2"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["breast-cancer-research-and-treatment"],"dependsOn":[],"notes":[],"journal":"Breast cancer research and treatment","year":2019,"doi":"10.1007/s10549-018-05125-4","pmid":"30632023","authors":"Rugo HS, Finn RS, Diéras V, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the PALOMA-2 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-pallas-penelope-b-lancet-oncol-2021","kind":"paper","name":"Palbociclib with adjuvant endocrine therapy in early breast cancer (PALLAS): interim analysis of a multicentre, open-label, randomised, phase 3 study","aka":[],"tldr":"Published report from the PALLAS trial registered as NCT02513394, in The Lancet Oncology (2021), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Palbociclib added to endocrine therapy improves progression-free survival in hormone-receptor-positive, HER2-negative, metastatic breast cancer. The PALLAS trial aimed to investigate whether the addition of 2 years of palbociclib to adjuvant endocrine therapy improves invasive disease-free survival over endocrine therapy alone in patients with hormone-receptor-positive, HER2-negative, early-stage breast cancer.\n\nMethods: PALLAS is an ongoing multicentre, open-label, randomised, phase 3 study that enrolled patients at 406 cancer centres in 21 countries worldwide with stage II-III histologically confirmed hormone-receptor-positive, HER2-negative breast cancer, within 12 months of initial diagnosis. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance score of 0 or 1. Patients were randomly assigned (1:1) in permuted blocks of random size (4 or 6), stratified by anatomic stage, previous chemotherapy, age, and geographical region, by use of central telephone-based and web-based interactive response technology, to receive either 2 years of palbociclib (125 mg orally once daily on days 1-21 of a 28-day cycle) with ongoing standard provider or patient-choice adjuvant endocrine therapy (tamoxifen or aromatase inhibitor, with or without concurrent luteinising hormone-releasing hormone agonist), or endocrine therapy alone, without masking. The primary endpoint of the study was invasive disease-free survival in the intention-to-treat population. Safety was assessed in all randomly assigned patients who started palbociclib or endocrine therapy. This report presents results from the second pre-planned interim analysis triggered on Jan 9, 2020, when 67% of the total number of expected invasive disease-free survival events had been observed. The trial is registered with ClinicalTrials.gov (NCT02513394) and EudraCT (2014-005181-30).\n\nFindings: Between Sept 1, 2015, and Nov 30, 2018, 5760 patients were randomly assigned to receive palbociclib plus endocrine therapy (n=2883) or endocrine therapy alone (n=2877). At the time of the planned second interim analysis, at a median follow-up of 23·7 months (IQR 16·9-29·2), 170 of 2883 patients assigned to palbociclib plus endocrine therapy and 181 of 2877 assigned to endocrine therapy alone had invasive disease-free survival events. 3-year invasive disease-free survival was 88·2% (95% CI 85·2-90·6) for palbociclib plus endocrine therapy and 88·5% (85·8-90·7) for endocrine therapy alone (hazard ratio 0·93 [95% CI 0·76-1·15]; log-rank p=0·51). As the test statistic comparing invasive disease-free survival between groups crossed the prespecified futility boundary, the independent data monitoring committee recommended discontinuation of palbociclib in patients still receiving palbociclib and endocrine therapy. The most common grade 3-4 adverse events were neutropenia (1742 [61·3%] of 2840 patients on palbociclib and endocrine therapy vs 11 [0·3%] of 2903 on endocrine therapy alone), leucopenia (857 [30·2%] vs three [0·1%]), and fatigue (60 [2·1%] vs ten [0·3%]). Serious adverse events occurred in 351 (12·4%) of 2840 patients on palbociclib plus endocrine therapy versus 220 (7·6%) of 2903 patients on endocrine therapy alone. There were no treatment-related deaths.\n\nInterpretation: At the planned second interim analysis, addition of 2 years of adjuvant palbociclib to adjuvant endocrine therapy did not improve invasive disease-free survival compared with adjuvant endocrine therapy alone. On the basis of these findings, this regimen cannot be recommended in the adjuvant setting. Long-term follow-up of the PALLAS population and correlative studies are ongoing.\n\nFunding: Pfizer.\n\nIndexed on Europe PMC as PubMed record 33460574 (DOI 10.1016/s1470-2045(20)30642-2). Its abstract cites the registry id NCT02513394, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2021","url":"https://doi.org/10.1016/s1470-2045(20)30642-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33460574/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33460574"},{"label":"ClinicalTrials.gov NCT02513394","url":"https://clinicaltrials.gov/study/NCT02513394"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["pallas-penelope-b"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2021,"doi":"10.1016/s1470-2045(20)30642-2","pmid":"33460574","authors":"Mayer EL, Dueck AC, Martin M, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02513394 with the most citations, so it is the natural first reading for anyone following the PALLAS trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-sanders-j-clin-oncol","kind":"paper","name":"Palliative Care for Patients With Cancer: ASCO Guideline Update","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 38748941 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: To provide evidence-based guidance to oncology clinicians, patients, nonprofessional caregivers, and palliative care clinicians to update the 2016 ASCO guideline on the integration of palliative care into standard oncology for all patients diagnosed with cancer.\n\nMethods: ASCO convened an Expert Panel of medical, radiation, hematology-oncology, oncology nursing, palliative care, social work, ethics, advocacy, and psycho-oncology experts. The Panel conducted a literature search, including systematic reviews, meta-analyses, and randomized controlled trials published from 2015-2023. Outcomes of interest included quality of life (QOL), patient satisfaction, physical and psychological symptoms, survival, and caregiver burden. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations.\n\nResults: The literature search identified 52 relevant studies to inform the evidence base for this guideline.\n\nRecommendations: Evidence-based recommendations address the integration of palliative care in oncology. Oncology clinicians should refer patients with advanced solid tumors and hematologic malignancies to specialized interdisciplinary palliative care teams that provide outpatient and inpatient care beginning early in the course of the disease, alongside active treatment of their cancer. For patients with cancer with unaddressed physical, psychosocial, or spiritual distress, cancer care programs should provide dedicated specialist palliative care services complementing existing or emerging supportive care interventions. Oncology clinicians from across the interdisciplinary cancer care team may refer the caregivers (eg, family, chosen family, and friends) of patients with cancer to palliative care teams for additional support. The Expert Panel suggests early palliative care involvement, especially for patients with uncontrolled symptoms and QOL concerns. Clinicians caring for patients with solid tumors on phase I cancer trials may also refer them to specialist palliative care.Additional information is available at www.asco.org/supportive-care-guidelines.\n\nIndexed on Europe PMC as PubMed record 38748941 (DOI 10.1200/jco.24.00542). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2024","url":"https://doi.org/10.1200/jco.24.00542"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38748941/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38748941"}],"tags":["europepmc-ingest"],"related":["palliative-care"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2024,"doi":"10.1200/jco.24.00542","pmid":"38748941","authors":"Sanders JJ, Temin S, Ghoshal A, et al.","paperType":"guideline","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-lutz-pract-radiat-oncol","kind":"paper","name":"Palliative radiation therapy for bone metastases: Update of an ASTRO Evidence-Based Guideline","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 27663933 and published in Practical radiation oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: The purpose is to provide an update the Bone Metastases Guideline published in 2011 based on evidence complemented by expert opinion. The update will discuss new high-quality literature for the 8 key questions from the original guideline and implications for practice.\n\nMethods and materials: A systematic PubMed search from the last date included in the original Guideline yielded 414 relevant articles. Ultimately, 20 randomized controlled trials, 32 prospective nonrandomized studies, and 4 meta-analyses/pooled analyses were selected and abstracted into evidence tables. The authors synthesized the evidence and reached consensus on the included recommendations.\n\nResults: Available literature continues to support pain relief equivalency between single and multiple fraction regimens for bone metastases. High-quality data confirm single fraction radiation therapy may be delivered to spine lesions with acceptable late toxicity. One prospective, randomized trial confirms both peripheral and spine-based painful metastases can be successfully and safely palliated with retreatment for recurrence pain with adherence to published dosing constraints. Advanced radiation therapy techniques such as stereotactic body radiation therapy lack high-quality data, leading the panel to favor its use on a clinical trial or when results will be collected in a registry. The panel's conclusion remains that surgery, radionuclides, bisphosphonates, and kyphoplasty/vertebroplasty do not obviate the need for external beam radiation therapy.\n\nConclusion: Updated data analysis confirms that radiation therapy provides excellent palliation for painful bone metastases and that retreatment is safe and effective. Although adherence to evidence-based medicine is critical, thorough expert radiation oncology physician judgment and discretion regarding number of fractions and advanced techniques are also essential to optimize outcomes when considering the patient's overall health, life expectancy, comorbidities, tumor biology, anatomy, previous treatment including prior radiation at or near current site of treatment, tumor and normal tissue response history to local and systemic therapies, and other factors related to the patient, tumor characteristics, or treatment.\n\nIndexed on Europe PMC as PubMed record 27663933 (DOI 10.1016/j.prro.2016.08.001). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Pract Radiat Oncol 2017","url":"https://doi.org/10.1016/j.prro.2016.08.001"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27663933/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27663933"}],"tags":["europepmc-ingest"],"related":["palliative-radiotherapy"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["practical-radiation-oncology"],"dependsOn":[],"notes":[],"journal":"Practical radiation oncology","year":2017,"doi":"10.1016/j.prro.2016.08.001","pmid":"27663933","authors":"Lutz S, Balboni T, Jones J, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nct04956640-nat-commun-2026","kind":"paper","name":"Pan-tumor activity of olomorasib, a next-generation KRAS G12C inhibitor in KRAS G12C-mutant advanced solid tumors: a first-in-human study","aka":[],"tldr":"Published report from the trial registered as NCT04956640, in Nature Communications (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"This multicenter, first-in-human Phase 1 study (NCT04956640) evaluated olomorasib (LY3537982), a next-generation KRAS G12C inhibitor designed to enhance target occupancy at low absolute exposures. In total, data from 195 patients are reported: Phase 1a dose escalation (n = 112) assessed olomorasib monotherapy at 50, 100, 150 or 200 mg BID across KRAS G12C-mutant advanced solid tumors; the primary objective was to determine the recommended Phase 2 dose (RP2D) based on dose-limiting toxicities (DLTs). No DLTs occurred, and 150 mg BID was selected as the RP2D. The primary objective for the Phase 1b dose expansion (n = 83) was to evaluate the safety and tolerability of olomorasib in specific KRAS G12C-mutant tumor types. Olomorasib was well tolerated, with predominantly grade 1-2 treatment-related adverse events (TRAEs) and infrequent grade 3 TRAEs; no grade 4/5 TRAEs occurred. Secondary objectives evaluated the antitumor activity of olomorasib. Among 168 efficacy-evaluable patients, the ORR and median PFS were both higher in non-CRC solid tumors compared to CRC, including in patients with NSCLC who previously received a KRAS G12C inhibitor. Intracranial responses were observed in patients with untreated, active brain metastases. This may support the potential of next-generation KRAS G12C inhibitors to overcome limitations of earlier agents and justify further investigation of combination therapy.\n\nIndexed on Europe PMC as PubMed record 41820335 (DOI 10.1038/s41467-026-69943-7). Its abstract cites the registry id NCT04956640, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Nat Commun 2026","url":"https://doi.org/10.1038/s41467-026-69943-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41820335/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41820335"},{"label":"ClinicalTrials.gov NCT04956640","url":"https://clinicaltrials.gov/study/NCT04956640"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04956640"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-communications"],"dependsOn":[],"notes":[],"journal":"Nature Communications","year":2026,"doi":"10.1038/s41467-026-69943-7","pmid":"41820335","authors":"Murciano-Goroff YR, Hollebecque A, Heist RS, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04956640 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-cristescu-science","kind":"paper","name":"Pan-tumor genomic biomarkers for PD-1 checkpoint blockade-based immunotherapy","aka":[],"tldr":"Paper cited by one bottleneck page, indexed on Europe PMC as PubMed record 30309915 and published in Science; the citing page links this DOI, which is how the record was matched.","summary":"Programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) checkpoint blockade immunotherapy elicits durable antitumor effects in multiple cancers, yet not all patients respond. We report the evaluation of >300 patient samples across 22 tumor types from four KEYNOTE clinical trials. Tumor mutational burden (TMB) and a T cell-inflamed gene expression profile (GEP) exhibited joint predictive utility in identifying responders and nonresponders to the PD-1 antibody pembrolizumab. TMB and GEP were independently predictive of response and demonstrated low correlation, suggesting that they capture distinct features of neoantigenicity and T cell activation. Analysis of The Cancer Genome Atlas database showed TMB and GEP to have a low correlation, and analysis by joint stratification revealed biomarker-defined patterns of targetable-resistance biology. These biomarkers may have utility in clinical trial design by guiding rational selection of anti-PD-1 monotherapy and combination immunotherapy regimens.\n\nIndexed on Europe PMC as PubMed record 30309915 (DOI 10.1126/science.aar3593). Matched by DOI alone: one bottleneck page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Science 2018","url":"https://doi.org/10.1126/science.aar3593"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30309915/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30309915"}],"tags":["europepmc-ingest"],"related":["b-immunotherapy-response"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2018,"doi":"10.1126/science.aar3593","pmid":"30309915","authors":"Cristescu R, Mogg R, Ayers M, et al.","paperType":"observational","findings":[],"whatItMeans":"One bottleneck page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nccn-pancreatic-adenocarcinoma-v2-2021-jnccn-2021","kind":"paper","name":"Pancreatic Adenocarcinoma, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology","aka":[],"tldr":"The 2021 journal summary of the US NCCN pancreatic cancer guideline, focused on drug treatment for disease that has spread locally or to other organs.","summary":"Journal summary of the NCCN Clinical Practice Guidelines for Pancreatic Adenocarcinoma, version 2.2021, by Tempero, Malafa, Al-Hawary and colleagues. The abstract notes that pancreatic cancer is the fourth leading cause of cancer-related death among men and women in the United States, that advanced disease at diagnosis remains the major challenge, and that survival rates remain relatively unchanged although newer modalities including targeted therapies provide hope. This manuscript focuses on the available systemic therapy approaches for locally advanced and metastatic disease. Earlier summaries (version 2.2017, version 1.2019 on adjuvant treatment) are on Europe PMC under the same title stem.","asOf":"2026-09-24","links":[{"label":"JNCCN 2021","url":"https://doi.org/10.6004/jnccn.2021.0017"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33845462/"},{"label":"NCCN Guidelines: Pancreatic Adenocarcinoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1455"}],"tags":["pancreatic-evidence"],"related":["nccn"],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jnccn"],"dependsOn":[],"notes":[],"journal":"Journal of the National Comprehensive Cancer Network","year":2021,"doi":"10.6004/jnccn.2021.0017","pmid":"33845462","authors":"Tempero MA, Malafa MP, Al-Hawary M, et al.","paperType":"guideline","findings":["Pancreatic cancer is the fourth leading cause of cancer-related death among men and women in the United States.","The summary concentrates on systemic therapy for locally advanced and metastatic disease."],"whatItMeans":"NCCN is the source of the category grades on the pancreatic cancer page and the guideline that first placed germline testing for every patient and universal tumour profiling in routine care.","caveats":["The full guideline requires free registration on nccn.org; the JNCCN article is a summary and the live guideline has moved on several versions since.","US practice and payer context; not all listed options are funded in the UK."],"changedPractice":true},{"id":"paper-hidalgo-pancreatic-cancer-review-nejm-2010","kind":"paper","name":"Pancreatic cancer","aka":[],"tldr":"The 2010 New England Journal review that summarised what was known about pancreatic cancer at the end of the gemcitabine era, a year before FOLFIRINOX changed treatment.","summary":"Manuel Hidalgo's review in the New England Journal of Medicine, 29 April 2010, pages 1605 to 1617. Europe PMC indexes no abstract for this article, so OnCo carries no figures from it. It is used on this roadmap as the marker of where the field stood before combination chemotherapy (2011, 2013), genomic subtyping (2015, 2016), PARP inhibition for germline BRCA carriers (2019) and KRAS inhibition (2021 onward).","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2010","url":"https://doi.org/10.1056/NEJMra0901557"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20427809/"}],"tags":["pancreatic-evidence"],"related":["paper-burris-gemcitabine-pancreatic-jco-1997","paper-conroy-folfirinox-pancreatic-nejm-2011"],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2010,"doi":"10.1056/NEJMra0901557","pmid":"20427809","authors":"Hidalgo M.","paperType":"review","findings":["No abstract is indexed on Europe PMC; the review is read from the journal."],"whatItMeans":"A fixed point for readers who want to see how much, and how little, has changed since 2010.","caveats":["A review, not primary evidence; superseded on treatment by every guideline on this page."]},{"id":"paper-kleeff-nat-rev-dis-primers","kind":"paper","name":"Pancreatic cancer","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 27158978 and published in Nature reviews. Disease primers; the citing page links this DOI, which is how the record was matched.","summary":"Pancreatic cancer is a major cause of cancer-associated mortality, with a dismal overall prognosis that has remained virtually unchanged for many decades. Currently, prevention or early diagnosis at a curable stage is exceedingly difficult; patients rarely exhibit symptoms and tumours do not display sensitive and specific markers to aid detection. Pancreatic cancers also have few prevalent genetic mutations; the most commonly mutated genes are KRAS, CDKN2A (encoding p16), TP53 and SMAD4 - none of which are currently druggable. Indeed, therapeutic options are limited and progress in drug development is impeded because most pancreatic cancers are complex at the genomic, epigenetic and metabolic levels, with multiple activated pathways and crosstalk evident. Furthermore, the multilayered interplay between neoplastic and stromal cells in the tumour microenvironment challenges medical treatment. Fewer than 20% of patients have surgically resectable disease; however, neoadjuvant therapies might shift tumours towards resectability. Although newer drug combinations and multimodal regimens in this setting, as well as the adjuvant setting, appreciably extend survival, ∼80% of patients will relapse after surgery and ultimately die of their disease. Thus, consideration of quality of life and overall survival is important. In this Primer, we summarize the current understanding of the salient pathophysiological, molecular, translational and clinical aspects of this disease. In addition, we present an outline of potential future directions for pancreatic cancer research and patient management.\n\nIndexed on Europe PMC as PubMed record 27158978 (DOI 10.1038/nrdp.2016.22). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Dis Primers 2016","url":"https://doi.org/10.1038/nrdp.2016.22"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27158978/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27158978"}],"tags":["europepmc-ingest"],"related":["pancreatic-cancer-signalling"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature reviews. Disease primers","year":2016,"doi":"10.1038/nrdp.2016.22","pmid":"27158978","authors":"Kleeff J, Korc M, Apte M, et al.","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-worthington-precede-early-detection-biomarkers-ijc-2026","kind":"paper","name":"Pancreatic cancer early detection biomarkers for high-risk individuals: insights from the PRECEDE consortium","aka":[],"tldr":"A review from the PRECEDE consortium of what might catch pancreatic cancer early in people at high risk: imaging remains the backbone, cyst fluid and pancreatic juice add specificity, and blood, microbiome and multi-omic markers are still research because early lesions shed too little to measure.","summary":"Efforts in early detection have centred on imaging features and liquid biopsy biomarkers able to detect pancreatic ductal adenocarcinoma and its high-grade precursors before symptoms in people at elevated risk. Classical imaging-based surveillance aligned with current guidelines forms the foundation, while organ-specific fluid analyses such as cyst fluid and pancreatic juice offer complementary tools with enhanced specificity. Advances in radiomics, liquid biopsy, microbiome and multi-omics profiling are expanding the field, but precursor lesions are difficult to diagnose non-invasively, are often not visible radiologically or endosonographically and cannot be definitively graded before resection; early-stage neoplasias release low levels of many biomarkers and thresholds defining malignant transformation remain poorly established. The PRECEDE international cohort study of high-risk individuals was designed to discover and validate diagnostic biomarkers under the PROBE study design.","asOf":"2026-09-24","links":[{"label":"Worthington et al., Int J Cancer 2026: early detection biomarkers for high-risk individuals, PRECEDE","url":"https://doi.org/10.1002/ijc.70592"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42298760/"}],"tags":[],"related":[],"cancers":["pancreatic","ipmn-cystic-precursors"],"sections":[],"technologies":["pancreatic-surveillance","liquid-biopsy","mced","proteomics","methylation-profiling"],"targets":[],"drugs":[],"companies":[],"institutions":["nyu-perlmutter","sheba"],"pathways":[],"terms":["ca19-9","cfdna"],"trials":["precede"],"people":["diane-simeone","talia-golan"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"International Journal of Cancer","year":2026,"doi":"10.1002/ijc.70592","pmid":"42298760","authors":"Worthington C, Raitses-Gurevich M, Innamorati G, et al.","paperType":"review","findings":["Imaging surveillance remains the foundation; cyst fluid and pancreatic juice add specificity.","Early lesions shed too little for current blood markers and transformation thresholds are unestablished."],"whatItMeans":"The current honest statement of where early detection stands: no blood test is ready, and the research is about finding the threshold at which to operate.","caveats":["Review; the PRECEDE cohort's own biomarker results are not yet reported.","High-risk individuals only, not population screening."],"changedPractice":false},{"id":"paper-biankin-pancreatic-exomes-axon-guidance-nature-2012","kind":"paper","name":"Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes","aka":[],"tldr":"Exome sequencing of 99 early-stage pancreatic cancers from the Australian genome initiative confirmed the four known drivers, added ATM and chromatin genes to the list, and found unexpected damage to nerve-guidance genes.","summary":"Exome sequencing and copy-number analysis were performed on a prospectively accrued clinical cohort of 142 early (stage I and II) sporadic pancreatic ductal adenocarcinomas; 99 informative tumours carried 2,016 non-silent mutations and 1,628 copy-number variations. Sixteen significantly mutated genes reaffirmed KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1 and uncovered EPC1, ARID2, ATM, ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6. Frequent and diverse somatic aberrations were found in axon guidance genes, particularly SLIT/ROBO signalling, also seen in Sleeping Beauty transposon mouse models.\n\nDeposited as paad_icgc on cBioPortal (KRAS mutated in 94 of 99).","asOf":"2026-09-24","links":[{"label":"Biankin et al., Nature 2012: exomes of 99 early pancreatic cancers (APGI/ICGC)","url":"https://doi.org/10.1038/nature11547"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23103869/"},{"label":"cBioPortal study paad_icgc (ICGC/APGI, Nature 2012; 99 exomes)","url":"https://www.cbioportal.org/study/summary?id=paad_icgc"}],"tags":[],"related":[],"cancers":["pancreatic","resectable-pdac"],"sections":[],"technologies":["wes-wgs"],"targets":["kras","tp53","cdkn2a","smad4","atm","arid1a","tgfbr2"],"drugs":[],"companies":[],"institutions":["garvan-institute"],"pathways":["pancreatic-cancer-signalling","tgf-beta","swi-snf-chromatin"],"terms":["somatic-mutations-wxs-wgs"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2012,"doi":"10.1038/nature11547","pmid":"23103869","authors":"Biankin AV, Waddell N, Kassahn KS, et al.","paperType":"translational","findings":["16 significantly mutated genes in 99 informative exomes, including ATM, ARID2 and EPC1 as new entries.","Recurrent somatic aberrations in SLIT/ROBO axon guidance genes."],"whatItMeans":"The APGI cohort became the backbone of the QCMG whole-genome and subtype papers; ATM's entry here is the origin of its place on today's germline panels.","caveats":["Early-stage resected tumours only; bulk tissue at 2012 exome depth under-called TP53 and CDKN2A (33 and 2 of 99 on cBioPortal).","Axon guidance gene function in the disease is still unproven."],"changedPractice":false,"participants":142},{"id":"paper-esmo-pancreatic-cancer-guideline-ann-oncol-2023","kind":"paper","name":"Pancreatic cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","aka":[],"tldr":"The European oncology society's 2023 guideline for pancreatic cancer, covering diagnosis, staging, surgery, chemotherapy before and after surgery, treatment of advanced disease and follow-up; the reference standard European and UK care is compared against.","summary":"ESMO Clinical Practice Guideline for pancreatic cancer, published in Annals of Oncology in 2023 by Conroy, Pfeiffer, Vilgrain, Lamarca, Seufferlein, O'Reilly, Hackert, Golan, Prager, Haustermans, Vogel and Ducreux for the ESMO Guidelines Committee. Europe PMC indexes no abstract for this article, so OnCo carries no figures from it; the guideline itself is open on the ESMO website. A 2024 letter from radiation oncologists (Huguet and colleagues) argued that radiotherapy for locally advanced disease had been given too little weight, and the authors replied in the same issue.","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2023","url":"https://doi.org/10.1016/j.annonc.2023.08.009"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37678671/"},{"label":"ESMO guidelines: pancreatic cancer","url":"https://www.esmo.org/guidelines/esmo-clinical-practice-guidelines-gastrointestinal-cancers"},{"label":"NICE NG85: pancreatic cancer in adults, diagnosis and management (2018)","url":"https://www.nice.org.uk/guidance/ng85"}],"tags":["pancreatic-evidence"],"related":["esmo-guidelines"],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["esmo"],"pathways":[],"terms":[],"trials":["prodige-24","napoli-3","polo"],"people":["thierry-conroy","eileen-oreilly","talia-golan"],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2023,"doi":"10.1016/j.annonc.2023.08.009","pmid":"37678671","authors":"Conroy T, Pfeiffer P, Vilgrain V, et al.","paperType":"guideline","findings":["No abstract is indexed on Europe PMC; recommendations are read from the guideline itself."],"whatItMeans":"This is the European standard the UK and NHS page for pancreatic cancer is compared against; NICE guideline NG85 (2018) covers the same ground with an older evidence base and a narrower set of funded drugs.","caveats":["Published before the 2026 daraxonrasib result and approval, and before PREOPANC-2 and NORPACT-1 were in print.","Guideline text, not a trial; the strength of each recommendation is graded within the document."],"changedPractice":true},{"id":"paper-hruban-panin-nomenclature-ajsp-2001","kind":"paper","name":"Pancreatic intraepithelial neoplasia: a new nomenclature and classification system for pancreatic duct lesions","aka":[],"tldr":"Eight expert pathologists given the same 35 slides used more than 70 different names for the lesions, so they agreed on one system, PanIN grades 1 to 3, which is still the language of pancreatic precursor pathology.","summary":"Thirty-five microscopic slides with representative duct lesions were sent to eight expert pathologists from the United States, Canada and Europe. Interobserver kappa values could not be calculated initially because more than 70 different diagnostic terms were used, with single lesions called hyperplasia, metaplasia, dysplasia or carcinoma in situ. A working group adopted the term pancreatic intraepithelial neoplasia (PanIN) with diagnostic criteria for each grade; on re-review only seven diagnoses were used, with kappa 0.43, 0.14 and 0.42 for PanIN 1, 2 and 3.","asOf":"2026-09-24","links":[{"label":"Hruban et al., Am J Surg Pathol 2001: the PanIN nomenclature","url":"https://doi.org/10.1097/00000478-200105000-00003"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/11342768/"}],"tags":[],"related":[],"cancers":["pancreatic","ipmn-cystic-precursors"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":[],"terms":["biopsy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"American Journal of Surgical Pathology","year":2001,"doi":"10.1097/00000478-200105000-00003","pmid":"11342768","authors":"Hruban RH, Adsay NV, Albores-Saavedra J, et al.","paperType":"guideline","findings":["More than 70 terms were in use for the same duct lesions before the system.","PanIN 1 to 3 defined; agreement kappa 0.43, 0.14 and 0.42."],"whatItMeans":"It created the vocabulary that made precursor research possible, and its poor agreement on the middle grade is why the grading later collapsed to two tiers.","caveats":["Agreement on PanIN-2 was poor (kappa 0.14).","Superseded in grading by the 2015 Baltimore consensus."],"changedPractice":true},{"id":"paper-bien-pediatr-blood-cancer","kind":"paper","name":"Pancreatoblastoma in children: EXPeRT/PARTNER diagnostic and therapeutic recommendations","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 34174157 and published in Pediatric Blood & Cancer; the citing page links this DOI, which is how the record was matched.","summary":"Pancreatoblastoma (PBL) is a rare malignant epithelial neoplasm that affects typically young children. Signs related to advanced upper-abdominal tumor accompanied by elevated serum α-fetoprotein levels in a young child suggest PBL, however histopathological confirmation is mandatory. The mainstay of the treatment is a complete surgical resection. Unresectable and/or metastatic PBL may become amenable to complete delayed surgery after neoadjuvant chemotherapy. This manuscript presents the international consensus recommendations for the diagnosis and treatment of children with PBL, established by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) within the EU-funded PARTNER (Paediatric Rare Tumors Network - European Registry) project.\n\nIndexed on Europe PMC as PubMed record 34174157 (DOI 10.1002/pbc.29112). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Pediatr Blood Cancer 2021","url":"https://doi.org/10.1002/pbc.29112"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34174157/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34174157"}],"tags":["europepmc-ingest"],"related":["pancreatoblastoma"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["pediatric-blood-and-cancer"],"dependsOn":[],"notes":[],"journal":"Pediatric Blood & Cancer","year":2021,"doi":"10.1002/pbc.29112","pmid":"34174157","authors":"Bien E, Roganovic J, Krawczyk MA, et al.","paperType":"observational","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-paradigm-jama-2023","kind":"paper","name":"Panitumumab vs Bevacizumab Added to Standard First-line Chemotherapy and Overall Survival Among Patients With RAS Wild-type, Left-Sided Metastatic Colorectal Cancer: A Randomized Clinical Trial","aka":[],"tldr":"Published report from the PARADIGM trial registered as NCT02394795, in JAMA (2023), chosen as the most cited paper whose own text cites the registry id.","summary":"Importance: For patients with RAS wild-type metastatic colorectal cancer, adding anti-epidermal growth factor receptor (anti-EGFR) or anti-vascular endothelial growth factor (anti-VEGF) monoclonal antibodies to first-line doublet chemotherapy is routine, but the optimal targeted therapy has not been defined.\n\nObjective: To evaluate the effect of adding panitumumab (an anti-EGFR monoclonal antibody) vs bevacizumab (an anti-VEGF monoclonal antibody) to standard first-line chemotherapy for treatment of RAS wild-type, left-sided, metastatic colorectal cancer.\n\nDesign, setting, and participants: Randomized, open-label, phase 3 clinical trial at 197 sites in Japan in May 2015-January 2022 among 823 patients with chemotherapy-naive RAS wild-type, unresectable metastatic colorectal cancer (final follow-up, January 14, 2022).\n\nInterventions: Panitumumab (n = 411) or bevacizumab (n = 412) plus modified fluorouracil, l-leucovorin, and oxaliplatin (mFOLFOX6) every 14 days.\n\nMain outcomes and measures: The primary end point, overall survival, was tested first in participants with left-sided tumors, then in the overall population. Secondary end points were progression-free survival, response rate, duration of response, and curative (defined as R0 status) resection rate.\n\nResults: In the as-treated population (n = 802; median age, 66 years; 282 [35.2%] women), 604 (75.3%) had left-sided tumors. Median follow-up was 61 months. Median overall survival was 37.9 months with panitumumab vs 34.3 months with bevacizumab in participants with left-sided tumors (hazard ratio [HR] for death, 0.82; 95.798% CI, 0.68-0.99; P =.03) and 36.2 vs 31.3 months, respectively, in the overall population (HR, 0.84; 95% CI, 0.72-0.98; P =.03). Median progression-free survival for panitumumab vs bevacizumab was 13.1 vs 11.9 months, respectively, for those with left-sided tumors (HR, 1.00; 95% CI, 0.83-1.20) and 12.2 vs 11.4 months overall (HR, 1.05; 95% CI, 0.90-1.24). Response rates with panitumumab vs bevacizumab were 80.2% vs 68.6%, respectively, for left-sided tumors (difference, 11.2%; 95% CI, 4.4%-17.9%) and 74.9% vs 67.3% overall (difference, 7.7%; 95% CI, 1.5%-13.8%). Median duration of response with panitumumab vs bevacizumab was 13.1 vs 11.2 months for left-sided tumors (HR, 0.86; 95% CI, 0.70-1.10) and 11.9 vs 10.7 months overall (HR, 0.89; 95% CI, 0.74-1.06). Curative resection rates with panitumumab vs bevacizumab were 18.3% vs 11.6% for left-sided tumors; (difference, 6.6%; 95% CI, 1.0%-12.3%) and 16.5% vs 10.9% overall (difference, 5.6%; 95% CI, 1.0%-10.3%). Common treatment-emergent adverse events were acneiform rash (panitumumab: 74.8%; bevacizumab: 3.2%), peripheral sensory neuropathy (panitumumab: 70.8%; bevacizumab: 73.7%), and stomatitis (panitumumab: 61.6%; bevacizumab: 40.5%).\n\nConclusions and relevance: Among patients with RAS wild-type metastatic colorectal cancer, adding panitumumab, compared with bevacizumab, to standard first-line chemotherapy significantly improved overall survival in those with left-sided tumors and in the overall population.\n\nTrial registration: ClinicalTrials.gov Identifier: NCT02394795.\n\nIndexed on Europe PMC as PubMed record 37071094 (DOI 10.1001/jama.2023.4428). Its abstract cites the registry id NCT02394795, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"JAMA 2023","url":"https://doi.org/10.1001/jama.2023.4428"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37071094/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37071094"},{"label":"ClinicalTrials.gov NCT02394795","url":"https://clinicaltrials.gov/study/NCT02394795"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":["egfr","kras","nras","vegf"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["sidedness","wild-type"],"trials":["paradigm"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2023,"doi":"10.1001/jama.2023.4428","pmid":"37071094","authors":"Watanabe J, Muro K, Shitara K, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02394795 with the most citations, so it is the natural first reading for anyone following the PARADIGM trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-douillard-prime-panitumumab-ras-nejm-2013","kind":"paper","name":"Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer (PRIME)","aka":[],"tldr":"Looking beyond the one KRAS exon everyone tested found that a further 17 percent of patients carried a RAS mutation and were harmed rather than helped by the antibody. Testing widened overnight.","summary":"Douillard, Oliner, Siena and colleagues assessed the efficacy and safety of panitumumab plus FOLFOX4 against FOLFOX4 alone by RAS (KRAS or NRAS) and BRAF mutation status, in a prospective-retrospective analysis of PRIME. Six hundred and thirty-nine patients whose tumours had no KRAS exon 2 mutation had results for at least one of KRAS exon 3 or 4, NRAS exon 2, 3 or 4, or BRAF exon 15; the overall rate of RAS status ascertainment was 90 percent.\n\nNo new safety signals were identified, and BRAF mutation was a negative prognostic factor rather than a predictor of antibody benefit.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2013","url":"https://doi.org/10.1056/NEJMoa1305275"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24024839/"}],"tags":["colorectal-evidence"],"related":["paper-van-cutsem-crystal-cetuximab-folfiri-nejm-2009","paper-arnold-primary-tumour-side-ras-wild-type-ann-oncol-2017"],"cancers":["colorectal"],"sections":["targeted-therapy"],"technologies":["monoclonal-antibody"],"targets":["egfr","kras","braf","nras"],"drugs":["panitumumab","folfox","oxaliplatin"],"companies":["amgen"],"institutions":[],"pathways":["ras-mapk"],"terms":["sidedness","wild-type","ngs"],"trials":[],"people":["salvatore-siena","josep-tabernero"],"bottlenecks":["b-biomarker-validation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2013,"doi":"10.1056/NEJMoa1305275","pmid":"24024839","authors":"Douillard JY, Oliner KS, Siena S, et al.","paperType":"rct","findings":["Among 512 patients without any RAS mutation, progression-free survival 10.1 against 7.9 months (hazard ratio 0.72, 95 percent CI 0.58 to 0.90, p=0.004).","Overall survival 26.0 against 20.2 months (hazard ratio 0.78, 0.62 to 0.99, p=0.04).","108 of 639 patients (17 percent) with non-mutated KRAS exon 2 had other RAS mutations, and these were associated with inferior outcomes on panitumumab-FOLFOX4.","BRAF mutation was a negative prognostic factor."],"whatItMeans":"Extended RAS testing (KRAS and NRAS exons 2, 3 and 4) became the standard before any EGFR antibody, and about one in six patients who would previously have been treated is now spared a drug that would have made things worse.","caveats":["Prospective-retrospective: the RAS analysis was planned but performed after the trial read out, on 90 percent of samples.","The harm signal in the additional RAS-mutant group rests on 108 patients.","Sidedness was analysed only later, in the pooled analysis of six trials."],"changedPractice":true,"participants":639},{"id":"paper-paola-1-nejm-2019","kind":"paper","name":"PAOLA-1: olaparib added to bevacizumab maintenance in newly diagnosed ovarian cancer, with benefit confined to HRD-positive tumours","aka":[],"tldr":"Adding the PARP inhibitor olaparib to bevacizumab after first-line chemotherapy for advanced ovarian cancer roughly doubled the time without progression in women whose tumours had defective DNA repair, but did nothing for those without it.","summary":"Double-blind, placebo-controlled phase 3 trial of 806 patients with newly diagnosed advanced high-grade ovarian cancer who had responded to platinum-taxane chemotherapy with bevacizumab, randomised 2:1 to two years of olaparib or placebo added to bevacizumab maintenance. Primary endpoint was investigator-assessed PFS.\n\nMedian PFS was 22.1 vs 16.6 months overall (HR 0.59), but 37.2 vs 17.7 months (HR 0.33) in homologous-recombination-deficient (HRD) tumours and no different in HRD-negative tumours (HR 1.00). The 2023 OS analysis showed a survival benefit in HRD-positive disease (5-year OS 65.5% vs 48.4%, HR 0.62). It established HRD testing as a decision tool and olaparib plus bevacizumab as a first-line maintenance standard for HRD-positive ovarian cancer.","asOf":"2026-09-08","links":[{"label":"NEJM 2019","url":"https://doi.org/10.1056/NEJMoa1911361"},{"label":"ClinicalTrials.gov NCT02477644","url":"https://clinicaltrials.gov/study/NCT02477644"}],"tags":[],"related":[],"cancers":["ovarian"],"sections":[],"technologies":["parp-inhibitor","hrd-testing","antiangiogenic","synthetic-lethality-approaches"],"targets":["parp","brca","vegf"],"drugs":["olaparib"],"companies":["astrazeneca","merck"],"institutions":["gemelli"],"pathways":[],"terms":["hrd","synthetic-lethality","pfs","os","germline-vs-somatic"],"trials":[],"people":["giovanni-scambia"],"bottlenecks":["b-biomarker-validation","b-dormancy-mrd","b-drug-pricing"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2019,"doi":"10.1056/NEJMoa1911361","authors":"Ray-Coquard I, Pautier P, Pignata S, et al.","paperType":"rct","findings":["Overall population: median PFS 22.1 vs 16.6 months; HR 0.59 (95% CI 0.49-0.72).","HRD-positive (including BRCA-mutated): median PFS 37.2 vs 17.7 months; HR 0.33.","HRD-positive without BRCA mutation: median PFS 28.1 vs 16.6 months; HR 0.43.","HRD-negative or unknown: no benefit (HR about 1.0).","Overall survival (Annals of Oncology 2023): HRD-positive 5-year OS 65.5% vs 48.4%, HR 0.62; no OS benefit in the ITT population (HR 0.92)."],"whatItMeans":"Women with newly diagnosed advanced ovarian cancer should have their tumour tested for BRCA mutations and homologous recombination deficiency, because those who are HRD-positive gain years of additional disease control and better survival from adding olaparib to bevacizumab maintenance. Those who are HRD-negative gain nothing from olaparib in this combination and should not be exposed to its toxicity and cost. HRD testing has become a routine part of ovarian cancer care as a result.","caveats":["HRD assays (Myriad myChoice and alternatives) have imperfect concordance and a substantial proportion of tests are inconclusive.","All patients received bevacizumab, so the trial cannot say whether olaparib alone would be as good in HRD-positive non-BRCA tumours (PRIMA suggests niraparib alone works).","No ITT overall survival benefit; the HRD-positive OS result is from a prespecified subgroup.","Two years of olaparib plus bevacizumab is expensive and adds anaemia, fatigue and nausea."],"changedPractice":true,"participants":806},{"id":"paper-papmet-pal-lancet-2021","kind":"paper","name":"PAPMET (SWOG 1500): cabozantinib versus sunitinib for metastatic papillary renal cell carcinoma","aka":[],"tldr":"In the first randomised trial to show a benefit in papillary kidney cancer, the MET-targeting kinase inhibitor cabozantinib delayed progression and tripled the response rate compared with sunitinib, while two other MET inhibitors did not.","summary":"Randomised phase 2 trial of 147 patients with metastatic papillary renal cell carcinoma randomised to sunitinib, cabozantinib, crizotinib or savolitinib; the crizotinib and savolitinib arms closed early for futility.\n\nMedian progression-free survival was 9.0 months with cabozantinib against 5.6 months with sunitinib (hazard ratio 0.60) and response 23 versus 4 percent.","asOf":"2026-09-17","links":[{"label":"Lancet 2021","url":"https://doi.org/10.1016/S0140-6736(21)00152-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33592176/"}],"tags":[],"related":[],"cancers":["papillary-rcc"],"sections":[],"technologies":[],"targets":[],"drugs":["cabozantinib","crizotinib","savolitinib","sunitinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["papmet"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2021,"doi":"10.1016/S0140-6736(21)00152-5","pmid":"33592176","authors":"Pal SK, Tangen C, Thompson IM, et al.","paperType":"rct","findings":["Median progression-free survival 9.0 vs 5.6 months; hazard ratio 0.60.","Objective response 23 percent vs 4 percent."],"whatItMeans":"Cabozantinib is the preferred first-line targeted therapy for metastatic papillary renal cell carcinoma; immunotherapy combinations are being tested on top of it.","caveats":["Small phase 2 with unselected MET status.","Savolitinib may still have a role in MET-driven tumours."],"changedPractice":true,"participants":147},{"id":"paper-pardoll-immune-checkpoint-blockade-nrc-2012","kind":"paper","name":"Pardoll 2012: the blockade of immune checkpoints in cancer immunotherapy","aka":[],"tldr":"The review that named and organised the field of checkpoint blockade: tumours switch off attacking T cells through brakes such as CTLA-4 and PD-1, and antibodies that release those brakes can produce lasting responses.","summary":"Written as the first PD-1 antibody results appeared, Pardoll's review explained how immune checkpoints, receptors that normally protect tissues from autoimmunity, are exploited by tumours, and why blocking them is a fundamentally different approach from vaccines or cytokines. It contrasted CTLA-4, which acts early in lymph nodes, with PD-1 and its ligand PD-L1, which act in the tumour itself, catalogued further checkpoints such as LAG-3 and TIM-3, and set out the questions that have shaped the decade since: biomarkers, combinations, and the autoimmune side effects that come with releasing the brakes.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1038/nrc3239"}],"tags":[],"related":["paper-hodi-ipilimumab-melanoma-nejm-2010","paper-topalian-anti-pd1-nejm-2012"],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["ctla4","pd1","pdl1","lag3","tim3"],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":[],"terms":["immune-checkpoint","irae"],"trials":[],"people":["drew-pardoll"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature Reviews Cancer","year":2012,"doi":"10.1038/nrc3239","authors":"Pardoll DM.","paperType":"review","findings":["Immune checkpoints are inhibitory receptors on T cells that tumours co-opt; CTLA-4 acts mainly during T cell priming and PD-1 during the effector phase in tissues.","PD-L1 expression by tumour cells offers a mechanism-based biomarker and a rationale for anti-PD-1 and anti-PD-L1 antibodies.","Multiple additional checkpoints (LAG-3, TIM-3, BTLA, adenosine and others) offer combination targets."],"whatItMeans":"This is the most cited map of the immunotherapy revolution and a good first read before the trials. Its predictions largely held: PD-1 pathway antibodies became the most widely used cancer drugs, PD-L1 testing entered practice, and LAG-3 blockade was approved in melanoma a decade later.","caveats":["A review written before most phase 3 evidence existed.","Biomarkers for checkpoint blockade remain imperfect despite the mechanistic case for PD-L1."],"changedPractice":false},{"id":"paper-parkin-global-cancer-statistics-2002-cacancer-2005","kind":"paper","name":"Parkin 2005: Global cancer statistics, 2002","aka":[],"tldr":"The world cancer count for 2002: about 10.9 million new cases and about 24.6 million people living within three years of a cancer diagnosis, with lung, breast and colorectal cancers the three most common.","summary":"Parkin, Bray, Ferlay and Pisani presented the GLOBOCAN 2002 estimates of incidence, mortality and prevalence for 26 cancers worldwide. They estimated 10.9 million new cases, 6.7 million deaths and 24.6 million people alive within three years of diagnosis. Lung cancer was the most common cancer and the leading cause of cancer death, followed by breast and colorectal cancers for incidence, and the paper documented the contrasting patterns of developed and developing regions, including the large burden of stomach, liver and cervical cancers in the latter.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.3322/canjclin.55.2.74"},{"label":"IARC Global Cancer Observatory","url":"https://gco.iarc.who.int/today"}],"tags":[],"related":["paper-jemal-global-cancer-statistics-2011-cacancer"],"cancers":["nsclc","breast-hr-positive","colorectal"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["iarc"],"pathways":[],"terms":["incidence-vs-prevalence","mortality"],"trials":[],"people":["bray-freddie"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"CA: A Cancer Journal for Clinicians","year":2005,"doi":"10.3322/canjclin.55.2.74","authors":"Parkin DM, Bray F, Ferlay J, Pisani P.","paperType":"observational","findings":["About 10.9 million new cancer cases, 6.7 million cancer deaths and 24.6 million people living with cancer within three years of diagnosis in 2002.","Lung cancer the most common cancer (about 1.35 million cases) and leading cause of cancer death; breast (1.15 million) and colorectal (1 million) cancers next.","Stomach, liver and cervical cancers made up a much larger share of the burden in developing countries."],"whatItMeans":"The first of the modern GLOBOCAN summaries in CA, it set the template that Jemal, Torre, Bray and Sung later followed and provides the 2002 baseline for tracking how the global burden has grown and shifted.","caveats":["Registry coverage in 2002 was far thinner than today, so many estimates were rough.","Superseded by later GLOBOCAN releases."],"changedPractice":false},{"id":"paper-nct04821622-n-engl-j-med-2026","kind":"paper","name":"PARP and Androgen-Signaling Inhibition plus ADT in Metastatic Prostate Cancer","aka":[],"tldr":"Published report from the TALAPRO-3 trial registered as NCT04821622, in New England Journal of Medicine (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: A previous trial involving patients with metastatic prostate cancer that was resistant to androgen pathway modulation (formerly referred to as castration-resistant) showed that adding talazoparib to enzalutamide significantly improved imaging-based progression-free survival and overall survival, with the greatest benefit observed in the cohort with alterations in homologous recombination repair genes.\n\nMethods: In this ongoing, phase 3, double-blind trial assessing talazoparib in patients with metastatic androgen pathway modulation-sensitive [APMS] prostate cancer harboring alterations in homologous recombination repair genes, we randomly assigned patients in a 1:1 ratio to receive talazoparib at a dose of 0.5 mg plus enzalutamide at a dose of 160 mg once daily (talazoparib group) or placebo plus enzalutamide at a dose of 160 mg once daily (control group). Randomization was stratified according to disease status (new or relapsed), disease volume (high or low), and BRCA (vs. non- BRCA) mutation status. The primary end point was investigator-assessed imaging-based progression-free survival. The key secondary end point was overall survival.\n\nResults: A total of 300 patients were assigned to the talazoparib group and 299 to the control group. At 3 years, progression-free survival was 77% in the talazoparib group and 56% in the control group (hazard ratio for disease progression or death, 0.48; 95% confidence interval [CI], 0.36 to 0.65; P<0.001). In this interim analysis, overall survival at 3 years was 78% in the talazoparib group and 72% in the control group (hazard ratio for death, 0.77; 95% CI, 0.56 to 1.04). Serious adverse events were reported in 42% and 32% of the patients in the talazoparib group and the control group, respectively. In the talazoparib group, the most common adverse events were anemia, fatigue, and decreased neutrophil count, and the most common event of grade 3 or higher was anemia, reported in 51% of the patients; two treatment-related deaths occurred.\n\nConclusions: Talazoparib added to enzalutamide led to significantly better imaging-based progression-free survival than placebo plus enzalutamide among patients with metastatic APMS prostate cancer harboring alterations in homologous recombination repair genes. Serious adverse events were more common with talazoparib plus enzalutamide than with placebo plus enzalutamide. (Funded by Pfizer; TALAPRO-3 ClinicalTrials.gov number, NCT04821622.).\n\nIndexed on Europe PMC as PubMed record 42223064 (DOI 10.1056/nejmoa2604126). Its abstract cites the registry id NCT04821622, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2026","url":"https://doi.org/10.1056/nejmoa2604126"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42223064/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42223064"},{"label":"ClinicalTrials.gov NCT04821622","url":"https://clinicaltrials.gov/study/NCT04821622"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04821622"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2026,"doi":"10.1056/nejmoa2604126","pmid":"42223064","authors":"Agarwal N, Matsubara N, Azad AA, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04821622 with the most citations, so it is the natural first reading for anyone following the TALAPRO-3 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-lord-science","kind":"paper","name":"PARP inhibitors: Synthetic lethality in the clinic","aka":[],"tldr":"Paper cited by three pathway pages, indexed on Europe PMC as PubMed record 28302823 and published in Science; the citing pages link this DOI, which is how the record was matched.","summary":"PARP inhibitors (PARPi), a cancer therapy targeting poly(ADP-ribose) polymerase, are the first clinically approved drugs designed to exploit synthetic lethality, a genetic concept proposed nearly a century ago. Tumors arising in patients who carry germline mutations in either BRCA1 or BRCA2 are sensitive to PARPi because they have a specific type of DNA repair defect. PARPi also show promising activity in more common cancers that share this repair defect. However, as with other targeted therapies, resistance to PARPi arises in advanced disease. In addition, determining the optimal use of PARPi within drug combination approaches has been challenging. Nevertheless, the preclinical discovery of PARPi synthetic lethality and the route to clinical approval provide interesting lessons for the development of other therapies. Here, we discuss current knowledge of PARP inhibitors and potential ways to maximize their clinical effectiveness.\n\nIndexed on Europe PMC as PubMed record 28302823 (DOI 10.1126/science.aam7344). Matched by DOI alone: three pathway pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Science 2017","url":"https://doi.org/10.1126/science.aam7344"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28302823/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28302823"}],"tags":["europepmc-ingest"],"related":["base-excision-repair-parp","homologous-recombination-repair","synthetic-lethality-map"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2017,"doi":"10.1126/science.aam7344","pmid":"28302823","authors":"Lord CJ, Ashworth A","paperType":"review","findings":[],"whatItMeans":"Three pathway pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-coles-lancet","kind":"paper","name":"Partial-breast radiotherapy after breast conservation surgery for patients with early breast cancer (UK IMPORT LOW trial): 5-year results from a multicentre, randomised, controlled, phase 3, non-inferiority trial","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 28779963 and published in The Lancet; the citing page links this DOI, which is how the record was matched.","summary":"Background: Local cancer relapse risk after breast conservation surgery followed by radiotherapy has fallen sharply in many countries, and is influenced by patient age and clinicopathological factors. We hypothesise that partial-breast radiotherapy restricted to the vicinity of the original tumour in women at lower than average risk of local relapse will improve the balance of beneficial versus adverse effects compared with whole-breast radiotherapy.\n\nMethods: IMPORT LOW is a multicentre, randomised, controlled, phase 3, non-inferiority trial done in 30 radiotherapy centres in the UK. Women aged 50 years or older who had undergone breast-conserving surgery for unifocal invasive ductal adenocarcinoma of grade 1-3, with a tumour size of 3 cm or less (pT1-2), none to three positive axillary nodes (pN0-1), and minimum microscopic margins of non-cancerous tissue of 2 mm or more, were recruited. Patients were randomly assigned (1:1:1) to receive 40 Gy whole-breast radiotherapy (control), 36 Gy whole-breast radiotherapy and 40 Gy to the partial breast (reduced-dose group), or 40 Gy to the partial breast only (partial-breast group) in 15 daily treatment fractions. Computer-generated random permuted blocks (mixed sizes of six and nine) were used to assign patients to groups, stratifying patients by radiotherapy treatment centre. Patients and clinicians were not masked to treatment allocation. Field-in-field intensity-modulated radiotherapy was delivered using standard tangential beams that were simply reduced in length for the partial-breast group. The primary endpoint was ipsilateral local relapse (80% power to exclude a 2·5% increase [non-inferiority margin] at 5 years for each experimental group; non-inferiority was shown if the upper limit of the two-sided 95% CI for the local relapse hazard ratio [HR] was less than 2·03), analysed by intention to treat. Safety analyses were done in all patients for whom data was available (ie, a modified intention-to-treat population). This study is registered in the ISRCTN registry, number ISRCTN12852634.\n\nFindings: Between May 3, 2007, and Oct 5, 2010, 2018 women were recruited. Two women withdrew consent for use of their data in the analysis. 674 patients were analysed in the whole-breast radiotherapy (control) group, 673 in the reduced-dose group, and 669 in the partial-breast group. Median follow-up was 72·2 months (IQR 61·7-83·2), and 5-year estimates of local relapse cumulative incidence were 1·1% (95% CI 0·5-2·3) of patients in the control group, 0·2% (0·02-1·2) in the reduced-dose group, and 0·5% (0·2-1·4) in the partial-breast group. Estimated 5-year absolute differences in local relapse compared with the control group were -0·73% (-0·99 to 0·22) for the reduced-dose and -0·38% (-0·84 to 0·90) for the partial-breast groups. Non-inferiority can be claimed for both reduced-dose and partial-breast radiotherapy, and was confirmed by the test against the critical HR being more than 2·03 (p=0·003 for the reduced-dose group and p=0·016 for the partial-breast group, compared with the whole-breast radiotherapy group). Photographic, patient, and clinical assessments recorded similar adverse effects after reduced-dose or partial-breast radiotherapy, including two patient domains achieving statistically significantly lower adverse effects (change in breast appearance [p=0·007 for partial-breast] and breast harder or firmer [p=0·002 for reduced-dose and p<0·0001 for partial-breast]) compared with whole-breast radiotherapy.\n\nInterpretation: We showed non-inferiority of partial-breast and reduced-dose radiotherapy compared with the standard whole-breast radiotherapy in terms of local relapse in a cohort of patients with early breast cancer, and equivalent or fewer late normal-tissue adverse effects were seen. This simple radiotherapy technique is implementable in radiotherapy centres worldwide.\n\nFunding: Cancer Research UK.\n\nIndexed on Europe PMC as PubMed record 28779963 (DOI 10.1016/s0140-6736(17)31145-5). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet 2017","url":"https://doi.org/10.1016/s0140-6736(17)31145-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28779963/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28779963"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["import-low"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2017,"doi":"10.1016/s0140-6736(17)31145-5","pmid":"28779963","authors":"Coles CE, Griffin CL, Kirby AM, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nct06099782-jco-oncol-pract-2026","kind":"paper","name":"Participant-Reported Preference for Pembrolizumab Administered Subcutaneously or Intravenously: A Randomized, Open-Label, Phase II Study","aka":[],"tldr":"Published report from the trial registered as NCT06099782, in JCO Oncology Practice (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Purpose: Pembrolizumab with berahyaluronidase alfa, a human hyaluronidase variant, is for subcutaneous (SC) injection. The phase II, open-label, crossover study 3475A-F11 (ClinicalTrials.gov identifier: NCT06099782) assessed participant preference for SC or intravenous (IV) pembrolizumab.\n\nMethods: Participants with resected melanoma, resected renal cell carcinoma, or metastatic non-small cell lung cancer (PD-L1 tumor proportion score ≥50%) were randomly assigned 1:1 to pembrolizumab SC 395 mg (arm A) or pembrolizumab IV 200 mg (arm B) once every 3 weeks for three cycles before crossover to the other administration route for three cycles. The primary objective was participant preference for SC pembrolizumab as assessed by the Patient Preference Questionnaire. Secondary objectives included reasons for participant preference, participant satisfaction with administration route, participant choice of treatment (SC or IV) to continue after cycle 6, and safety and tolerability.\n\nResults: Overall, 147 participants were randomly assigned (arm A = 71, arm B = 76). The participant preference rate for pembrolizumab SC was 65% (95% CI, 56 to 74). The most common reason for this preference was less time in clinic (64%). Altogether, 64%/25% of participants were very satisfied/satisfied with pembrolizumab SC; 54%/31% were very satisfied/satisfied with pembrolizumab IV. More participants chose to continue treatment after cycle 6 with pembrolizumab SC than pembrolizumab IV (68% v 32%). Grade 3-4 treatment-related adverse events (AEs) in cycles 1-3 occurred in one (1%; arm A) and five (7%; arm B) participants. Injection-site AEs during SC administration cycles of the crossover period occurred in nine (13%; arm A) and 11 (16%; arm B) participants (mostly grade 1).\n\nConclusion: More participants preferred pembrolizumab SC over pembrolizumab IV and chose to continue with pembrolizumab SC. The results of this study suggest that pembrolizumab SC improves convenience compared with pembrolizumab IV in cancer treatment.\n\nIndexed on Europe PMC as PubMed record 42234938 (DOI 10.1200/op-25-01248). Its abstract cites the registry id NCT06099782, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"JCO Oncol Pract 2026","url":"https://doi.org/10.1200/op-25-01248"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42234938/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42234938"},{"label":"ClinicalTrials.gov NCT06099782","url":"https://clinicaltrials.gov/study/NCT06099782"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct06099782"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco-oncology-practice"],"dependsOn":[],"notes":[],"journal":"JCO Oncology Practice","year":2026,"doi":"10.1200/op-25-01248","pmid":"42234938","authors":"Casarini IA, Kowalski DM, Caglevic C, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT06099782 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-partiqol-astro-2024","kind":"paper","name":"PARTIQoL: phase 3 randomised trial of proton therapy versus IMRT for localised prostate cancer (ASTRO 2024 late-breaking abstract)","aka":[],"tldr":"In the first multicentre randomised comparison of protons and IMRT for localised prostate cancer, bowel, urinary and sexual quality of life and five-year cancer control were the same with either technique.","summary":"Late-breaking abstract LBA01 at the 2024 ASTRO Annual Meeting, published in the meeting supplement of the International Journal of Radiation Oncology, Biology, Physics. PARTIQoL (NCT01617161) randomised 450 men with low- or intermediate-risk localised prostate cancer at 29 centres between June 2012 and November 2021 to proton beam therapy or intensity-modulated radiotherapy, without hormone therapy, stratified by institution, age, rectal spacer use and fractionation. The primary endpoint was the change in EPIC bowel quality of life at 24 months.\n\nWith a median follow-up of 60.3 months, bowel scores declined only slightly in both arms: from 93.7 to 91.8 with protons and from 93.5 to 91.9 with IMRT at 24 months (p=0.836), a difference that was neither statistically significant nor clinically meaningful. Urinary incontinence, urinary irritation and sexual function did not differ at any time point, and there were no sustained differences in subgroups by risk group, age, rectal spacer or fractionation. Five-year progression-free survival was 93.4% with protons and 93.7% with IMRT (p=0.706). This record carries the abstract's figures only.","asOf":"2026-09-21","links":[{"label":"IJROBP 2024 supplement (LBA01)","url":"https://doi.org/10.1016/j.ijrobp.2024.08.012"},{"label":"ClinicalTrials.gov NCT01617161","url":"https://clinicaltrials.gov/study/NCT01617161"}],"tags":["radiation-wave5"],"related":[],"cancers":["prostate"],"sections":[],"technologies":["proton-therapy","imrt-igrt"],"targets":[],"drugs":[],"companies":[],"institutions":["mgh"],"pathways":[],"terms":["relative-biological-effectiveness","linear-energy-transfer","bragg-peak"],"trials":["partiqol"],"people":["anthony-zietman"],"bottlenecks":[],"keyPapers":[],"journals":["ijrobp"],"dependsOn":[],"notes":[],"journal":"International Journal of Radiation Oncology, Biology, Physics","year":2024,"doi":"10.1016/j.ijrobp.2024.08.012","authors":"Efstathiou JA, Yeap BY, Michalski JM, et al.","paperType":"rct","findings":["EPIC bowel quality of life at 24 months 91.8 with protons vs 91.9 with IMRT (baseline 93.7 and 93.5); p=0.836 for the primary endpoint.","No significant differences in urinary incontinence, urinary irritation or sexual function at any time point over 60 months.","Five-year progression-free survival 93.4% with protons vs 93.7% with IMRT (p=0.706).","Median follow-up 60.3 months; 450 men randomised at 29 centres, median age 68."],"whatItMeans":"For men with low- or intermediate-risk prostate cancer, protons and modern IMRT give the same excellent quality of life and cancer control, so the choice can rest on access, cost and convenience rather than on an expected sparing of bowel or bladder. The result removes prostate cancer from the list of adult indications where a proton advantage was assumed but untested.","caveats":["Abstract figures only; the peer-reviewed full paper carries the definitive numbers.","Patient-reported quality of life was the primary endpoint, not toxicity graded by clinicians or long-term second cancers.","Low- and intermediate-risk disease without hormone therapy; high-risk and node-positive disease were not studied.","Rectal spacers and hypofractionation were allowed in both arms, which may have narrowed any difference."],"changedPractice":false,"participants":450},{"id":"paper-pathfinder-avapritinib-advanced-systemic-mastocytosis-nat-med-2021","kind":"paper","name":"PATHFINDER: efficacy and safety of avapritinib in advanced systemic mastocytosis (phase 2 interim analysis)","aka":[],"tldr":"The confirmatory trial of avapritinib in advanced systemic mastocytosis again showed responses in three quarters of patients, with the drug clearing marrow mast cells and normalising tryptase in many, and it became the standard first-line targeted therapy.","summary":"Open-label single-arm phase 2 trial of avapritinib 200 mg daily in adults with advanced systemic mastocytosis; the pre-specified interim analysis included 62 patients, 32 evaluable for response.\n\nThe overall response rate was 75 percent, with complete remission with full or partial haematological recovery in 19 percent, and rapid reductions in marrow mast cells, serum tryptase and KIT D816V allele fraction; quality of life improved. Patients with platelets under 50,000 per microlitre were excluded to avoid intracranial bleeding.","asOf":"2026-09-18","links":[{"label":"Nat Med 2021","url":"https://doi.org/10.1038/s41591-021-01539-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34873345/"}],"tags":[],"related":[],"cancers":["advanced-systemic-mastocytosis"],"sections":[],"technologies":[],"targets":[],"drugs":["avapritinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2021,"doi":"10.1038/s41591-021-01539-8","pmid":"34873345","authors":"Gotlib J, Reiter A, Radia DH, et al.","paperType":"observational","findings":["Overall response 75 percent in evaluable patients at the interim analysis, with complete remission with full or partial haematological recovery in 19 percent.","Marrow mast cell burden and serum tryptase fell in most patients."],"whatItMeans":"Avapritinib is the preferred first targeted therapy for advanced systemic mastocytosis in patients with adequate platelet counts.","caveats":["Interim analysis of a single-arm trial.","Excluded patients with severe thrombocytopenia, who are common in mast cell leukaemia and have few options."],"changedPractice":true,"participants":62},{"id":"paper-pathfinder-lancet-2023","kind":"paper","name":"PATHFINDER: the first prospective test of a multi-cancer blood test in people without symptoms","aka":[],"tldr":"In 6,621 adults over 50, the Galleri test flagged a cancer signal in 1.4%, of whom 38% turned out to have cancer; diagnostic work-up took about two months for true positives and over five months for false positives.","summary":"PATHFINDER was a single-arm prospective study in which 6,621 adults aged 50 or over at seven US health systems had the Galleri methylation-based multi-cancer early detection (MCED) test in addition to standard screening. A cancer signal triggered clinician-directed diagnostic evaluation guided by the predicted cancer signal origin.\n\nA signal was detected in 92 participants (1.4%); 35 had cancer confirmed, giving a positive predictive value of 38%. Specificity was 99.1% and the cancer signal origin prediction was correct in the large majority of true positives. Median time to diagnostic resolution was 79 days: 57 days for true positives and 162 days for false positives. Almost half of the cancers detected were early stage, and several were in organs without standard screening.\n\nThe study established feasibility and the diagnostic pathway and set the stage for the randomised NHS-Galleri trial and the larger PATHFINDER 2.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1016/S0140-6736(23)01700-2"},{"label":"ClinicalTrials.gov NCT04241796","url":"https://clinicaltrials.gov/study/NCT04241796"}],"tags":[],"related":["idea-prev-mced-positive-resolution-pathway","idea-prev-mced-pretest-decision-aid"],"cancers":[],"sections":["early-detection"],"technologies":["mced","liquid-biopsy","methylation-profiling"],"targets":[],"drugs":["galleri"],"companies":[],"institutions":["dana-farber"],"pathways":[],"terms":["ppv","stage-shift"],"trials":["pathfinder-2","nhs-galleri"],"people":[],"bottlenecks":["b-early-detection","b-overdiagnosis","b-biomarker-validation"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2023,"doi":"10.1016/S0140-6736(23)01700-2","pmid":"37805216","authors":"Schrag D, Beer TM, McDonnell CH, et al.","paperType":"observational","findings":["Cancer signal detected in 92 of 6,621 (1.4%); 35 true positives, PPV 38%","Specificity 99.1%; negative predictive value 98.6%","Median time to diagnostic resolution 79 days (57 for true positives, 162 for false positives)","Most participants with a false-positive signal underwent imaging and a substantial minority an invasive procedure"],"whatItMeans":"A multi-cancer blood test can be run in ordinary clinics, and most positive results can be resolved with imaging. But six in ten positives are false alarms that take months to resolve, and the test misses most cancers. Whether it reduces late-stage cancer or deaths is unknown; that requires randomised trials.","caveats":["Single-arm; no control group and no mortality or stage-shift endpoint","Sensitivity for incident cancers was low because many cancers arose after a negative test","Participants were largely white, insured and health-literate","Harm from false positives (anxiety, procedures, cost) was documented but not weighed against benefit"],"changedPractice":false,"participants":6621},{"id":"paper-tetzlaff-ann-oncol","kind":"paper","name":"Pathological assessment of resection specimens after neoadjuvant therapy for metastatic melanoma","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 29945191 and published in Annals of Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background: Clinical trials have recently evaluated safety and efficacy of neoadjuvant therapy among patients with surgically resectable regional melanoma metastases. To capture informative prognostic data connected to pathological response in such trials, it is critical to standardize pathologic assessment and reporting of tumor response after this treatment.\n\nMethods: The International Neoadjuvant Melanoma Consortium meetings in 2016 and 2017 assembled pathologists from academic centers to develop consensus guidelines for pathologic examination and reporting of surgical specimens from AJCC (8th edition) stage IIIB/C/D or oligometastatic stage IV melanoma patients treated with neoadjuvant-targeted or immune therapy. Patterns of pathologic response are provided context to inform these guidelines.\n\nResults: Based on our collective experience and guided by efforts in well-established neoadjuvant settings like breast cancer, procedures directing handling of pre- and post-neoadjuvant therapy-treated melanoma specimens are provided to facilitate comparison of findings across different trials and centers. Definitions of pathologic response are provided together with guidelines for reporting and quantifying the extent of pathologic response. Finally, the spectrum of histopathologic responses observed following neoadjuvant-targeted and immune-checkpoint therapy is described and illustrated.\n\nConclusions: Standardizing pathologic evaluation of resected melanoma metastases following neoadjuvant-targeted or immune-checkpoint therapy allows more robust stratification of patient outcomes. This includes recognizing the spectrum of histopathologic response patterns to neoadjuvant therapy and a standard approach to grading pathologic responses. Such an approach will facilitate comparison of results across clinical trials and inform ongoing correlative studies into the mechanisms of response and resistance to agents applied in the neoadjuvant setting.\n\nIndexed on Europe PMC as PubMed record 29945191 (DOI 10.1093/annonc/mdy226). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Ann Oncol 2018","url":"https://doi.org/10.1093/annonc/mdy226"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29945191/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29945191"}],"tags":["europepmc-ingest"],"related":["major-pathological-response"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2018,"doi":"10.1093/annonc/mdy226","pmid":"29945191","authors":"Tetzlaff MT, Messina JL, Stein JE, et al.","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-cortazar-ctneobc-pcr-pooled-analysis-lancet-2014","kind":"paper","name":"Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis","aka":[],"tldr":"The US regulator's pooled analysis of 11,955 patients in 12 trials that found complete disappearance of the tumour before surgery predicts survival most strongly in triple-negative disease, but that a trial raising the complete response rate does not reliably improve survival.","summary":"Cortazar, Zhang, Untch, Mehta and colleagues pooled 12 international neoadjuvant trials with at least 200 patients, response and survival data and three years of follow-up (11,955 patients), comparing three definitions of pathological complete response and testing trial-level surrogacy. Eradication from breast and nodes (ypT0 ypN0, or ypT0/is ypN0) associated better with event-free survival (hazard ratios 0.44 and 0.48) and overall survival (0.36 for both) than eradication from the breast alone (0.60 and 0.51). The association was strongest in triple-negative breast cancer (event-free survival hazard ratio 0.24, 95 percent confidence interval 0.18 to 0.33; overall survival 0.16, 0.11 to 0.25) and in HER2-positive, hormone receptor-negative disease treated with trastuzumab. At trial level there was little association between increases in pathological complete response and event-free (R squared 0.03) or overall survival (0.24), so the analysis could not validate pathological complete response as a surrogate endpoint.","asOf":"2026-09-24","links":[{"label":"Lancet 2014","url":"https://doi.org/10.1016/S0140-6736(13)62422-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24529560/"}],"tags":["tnbc-evidence"],"related":["paper-liedtke-neoadjuvant-response-survival-tnbc-jco-2008"],"cancers":["tnbc","breast-her2-positive"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["pcr","efs","os","hazard-ratio"],"trials":[],"people":[],"bottlenecks":["b-trial-design"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2014,"doi":"10.1016/S0140-6736(13)62422-8","pmid":"24529560","authors":"Cortazar P, Zhang L, Untch M, et al.","paperType":"meta-analysis","findings":["Pathological complete response (ypT0/is ypN0) in triple-negative disease: event-free survival hazard ratio 0.24 (95 percent CI 0.18 to 0.33); overall survival 0.16 (0.11 to 0.25).","Trial-level association between pathological complete response gains and survival weak: R squared 0.03 (event-free) and 0.24 (overall)."],"whatItMeans":"The basis of the US accelerated approval pathway on pathological complete response that KEYNOTE-522 and neoadjuvant trials since have used, together with the warning that a higher response rate in a trial is a promise, not a proof, of longer life.","caveats":["Pooled trials used varied regimens and definitions.","Trial-level surrogacy tested across only 12 trials."],"changedPractice":true,"participants":11955},{"id":"paper-omori-ipmn-progression-pathways-gastroenterology-2019","kind":"paper","name":"Pathways of progression from intraductal papillary mucinous neoplasm to pancreatic ductal adenocarcinoma based on molecular features","aka":[],"tldr":"Mapping 168 microscopic lesions from 30 pancreata that held both a cyst and a cancer showed three different relationships: the cancer grew out of the cyst, branched off it early, or arose independently, and the branch-off patients lived longest without recurrence.","summary":"Thirty pancreatic tissues with concurrent ductal adenocarcinoma and IPMN yielded 168 mapped, microdissected lesions analysed for mutations in 18 pancreatic cancer genes and tumour suppressor expression. Twelve cancers shared driver mutations with all concurrent IPMNs (sequential subtype, less diverse incipient foci and frequent GNAS mutations); eleven shared some (branch-off subtype, identical KRAS but different GNAS mutations despite adjacency, with whole-exome and methylation analysis indicating clonal origin and later divergence); ten had drivers not found in the IPMNs (de novo subtype). TP53 and SMAD4 expression improved subtype discrimination. Branch-off patients had longer disease-free survival than de novo or sequential patients.","asOf":"2026-09-24","links":[{"label":"Omori et al., Gastroenterology 2019: sequential, branch-off and de novo pathways from IPMN to cancer","url":"https://doi.org/10.1053/j.gastro.2018.10.029"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30342036/"}],"tags":[],"related":[],"cancers":["pancreatic","ipmn-cystic-precursors"],"sections":[],"technologies":[],"targets":["kras","gnas","tp53","smad4"],"drugs":[],"companies":[],"institutions":[],"pathways":["clonal-evolution"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["gastroenterology"],"dependsOn":[],"notes":[],"journal":"Gastroenterology","year":2019,"doi":"10.1053/j.gastro.2018.10.029","pmid":"30342036","authors":"Omori Y, Ono Y, Tanino M, et al.","paperType":"translational","findings":["Three IPMN-to-cancer pathways: sequential (12), branch-off (11), de novo (10).","Branch-off cancers had the longest disease-free survival."],"whatItMeans":"A cancer next to a cyst is not necessarily from the cyst, so removing the cyst does not always remove the risk, and surveillance must cover the whole gland.","caveats":["Thirty pancreata from one programme.","Subtype assignment needs extensive microdissection not available in practice."],"changedPractice":false,"participants":30},{"id":"paper-paskett-ca-cancer-j-clin","kind":"paper","name":"Patient navigation: an update on the state of the science","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 21659419 and published in CA: A Cancer Journal for Clinicians; the citing page links this DOI, which is how the record was matched.","summary":"Although patient navigation was introduced 2 decades ago, there remains a lack of consensus regarding its definition, the necessary qualifications of patient navigators, and its impact on the continuum of cancer care. This review provides an update to the 2008 review by Wells et al on patient navigation. Since then, there has been a significant increase in the number of published studies dealing with cancer patient navigation. The authors of the current review conducted a search by using the keywords \"navigation\" or \"navigator\" and \"cancer.\" Thirty-three articles published from November 2007 through July 2010 met the search criteria. Consistent with the prior review, there is building evidence of some degree of efficacy of patient navigation in terms of increasing cancer screening rates. However, there is less recent evidence concerning the benefit of patient navigation with regard to diagnostic follow-up and in the treatment setting, and a paucity of research focusing on patient navigation in cancer survivorship remains. Methodological limitations were noted in many studies, including small sample sizes and a lack of control groups. As patient navigation programs continue to develop across North America and beyond, further research will be required to determine the efficacy of cancer patient navigation across all aspects of the cancer care continuum.\n\nIndexed on Europe PMC as PubMed record 21659419 (DOI 10.3322/caac.20111). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"CA Cancer J Clin 2011","url":"https://doi.org/10.3322/caac.20111"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21659419/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/21659419"}],"tags":["europepmc-ingest"],"related":["oncology-nursing"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["ca-cancer-journal"],"dependsOn":[],"notes":[],"journal":"CA: A Cancer Journal for Clinicians","year":2011,"doi":"10.3322/caac.20111","pmid":"21659419","authors":"Paskett ED, Harrop JP, Wells KJ","paperType":"review","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-gay-sclc-subtypes-inflamed-cancer-cell-2021","kind":"paper","name":"Patterns of transcription factor programs and immune pathway activation define four major subtypes of SCLC with distinct therapeutic vulnerabilities","aka":[],"tldr":"Reanalysing gene activity in small-cell lung cancer tumours found that the fourth kind is not defined by a control protein at all but by inflammation, and it is the one kind that clearly gains from adding immunotherapy.","summary":"Using tumour expression data and non-negative matrix factorisation, four subtypes of small-cell lung cancer were identified, defined largely by differential expression of the transcription factors ASCL1, NEUROD1 and POU2F3, or by low expression of all three signatures accompanied by an inflamed gene signature (SCLC-A, N, P and I respectively). SCLC-I experienced the greatest benefit from the addition of immunotherapy to chemotherapy, while the other subtypes each had distinct vulnerabilities, including to inhibitors of PARP, Aurora kinases or BCL-2. Cisplatin treatment of SCLC-A patient-derived xenografts induced intratumoral shifts towards SCLC-I, supporting subtype switching as a mechanism of acquired platinum resistance.","asOf":"2026-09-25","links":[{"label":"Gay et al., Cancer Cell 2021: four transcriptional subtypes of small-cell lung cancer with distinct vulnerabilities, including the inflamed subtype","url":"https://doi.org/10.1016/j.ccell.2020.12.014"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33482121/"}],"tags":[],"related":[],"cancers":["sclc"],"sections":[],"technologies":["rna-seq","checkpoint-inhibitor","organoids"],"targets":["ascl1","yap1","aurka","dll3"],"drugs":[],"companies":[],"institutions":["md-anderson"],"pathways":["sclc-signalling","lineage-plasticity-neuroendocrine","pd1-checkpoint","cancer-immunity-cycle","transcription-addiction"],"terms":["cold-vs-hot","resistance"],"trials":[],"people":["john-heymach"],"bottlenecks":[],"keyPapers":[],"journals":["cancer-cell"],"dependsOn":[],"notes":[],"journal":"Cancer Cell","year":2021,"doi":"10.1016/j.ccell.2020.12.014","pmid":"33482121","authors":"Gay CM, Stewart CA, Park EM, et al.","paperType":"translational","findings":["Four subtypes, with the fourth defined by an inflamed signature rather than by a transcription factor.","The inflamed subtype gained most from adding immunotherapy to chemotherapy.","Distinct vulnerabilities to PARP, Aurora kinase and BCL-2 inhibition across the other subtypes.","Platinum shifts tumours towards the inflamed subtype, a mechanism of acquired resistance."],"whatItMeans":"It offers the first credible explanation for why only a minority of small-cell patients get a durable benefit from checkpoint blockade, and it introduces subtype switching, which would mean retesting at relapse rather than typing once.","caveats":["Derived from trial expression data and models rather than from a prospective biomarker-driven trial.","Subtype calls need bulk RNA, which is rarely available from a small-cell biopsy.","Switching under platinum is shown in xenografts and inferred in patients."],"changedPractice":false},{"id":"paper-empower-cscc-1-cemiplimab-migden-nejm-2018","kind":"paper","name":"PD-1 blockade with cemiplimab in advanced cutaneous squamous cell carcinoma (EMPOWER-CSCC-1)","aka":[],"tldr":"Cemiplimab shrank tumours in about half of patients with metastatic or locally advanced cutaneous squamous cell carcinoma, a highly mutated skin cancer with almost no previous treatment options, leading to the first approval for the disease.","summary":"Phase 1 expansion cohort (26 patients) and phase 2 study (59 patients) of cemiplimab in patients with metastatic or locally advanced cutaneous squamous cell carcinoma not amenable to curative surgery or radiotherapy.\n\nObjective response was 50 percent in the phase 1 cohort and 47 percent in the phase 2 metastatic cohort, with most responses durable beyond six months and typical immune-related toxicity.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2018","url":"https://doi.org/10.1056/NEJMoa1805131"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29863979/"}],"tags":[],"related":[],"cancers":["lip-cancer","advanced-cutaneous-scc"],"sections":[],"technologies":[],"targets":[],"drugs":["cemiplimab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["empower-cscc-1"],"people":["michael-migden"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2018,"doi":"10.1056/NEJMoa1805131","pmid":"29863979","authors":"Migden MR, Rischin D, Schmults CD, et al.","paperType":"observational","findings":["Objective response 50 percent (phase 1) and 47 percent (phase 2 metastatic cohort).","Durable responses exceeding six months in the majority of responders."],"whatItMeans":"PD-1 blockade is the first-line systemic treatment for advanced cutaneous squamous cell carcinoma, including on the lip, and cemiplimab has since moved into neoadjuvant and adjuvant use.","caveats":["Single-arm; transplant recipients and immunosuppressed patients were excluded."],"changedPractice":true,"participants":85},{"id":"paper-keynote-017-n-engl-j-med-2016","kind":"paper","name":"PD-1 Blockade with Pembrolizumab in Advanced Merkel-Cell Carcinoma","aka":[],"tldr":"Published report from the KEYNOTE-017 trial registered as NCT02267603, in New England Journal of Medicine (2016), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Merkel-cell carcinoma is an aggressive skin cancer that is linked to exposure to ultraviolet light and the Merkel-cell polyomavirus (MCPyV). Advanced Merkel-cell carcinoma often responds to chemotherapy, but responses are transient. Blocking the programmed death 1 (PD-1) immune inhibitory pathway is of interest, because these tumors often express PD-L1, and MCPyV-specific T cells express PD-1.\n\nMethods: In this multicenter, phase 2, noncontrolled study, we assigned adults with advanced Merkel-cell carcinoma who had received no previous systemic therapy to receive pembrolizumab (anti-PD-1) at a dose of 2 mg per kilogram of body weight every 3 weeks. The primary end point was the objective response rate according to Response Evaluation Criteria in Solid Tumors, version 1.1. Efficacy was correlated with tumor viral status, as assessed by serologic and immunohistochemical testing.\n\nResults: A total of 26 patients received at least one dose of pembrolizumab. The objective response rate among the 25 patients with at least one evaluation during treatment was 56% (95% confidence interval [CI], 35 to 76); 4 patients had a complete response, and 10 had a partial response. With a median follow-up of 33 weeks (range, 7 to 53), relapses occurred in 2 of the 14 patients who had had a response (14%). The response duration ranged from at least 2.2 months to at least 9.7 months. The rate of progression-free survival at 6 months was 67% (95% CI, 49 to 86). A total of 17 of the 26 patients (65%) had virus-positive tumors. The response rate was 62% among patients with MCPyV-positive tumors (10 of 16 patients) and 44% among those with virus-negative tumors (4 of 9 patients). Drug-related grade 3 or 4 adverse events occurred in 15% of the patients.\n\nConclusions: In this study, first-line therapy with pembrolizumab in patients with advanced Merkel-cell carcinoma was associated with an objective response rate of 56%. Responses were observed in patients with virus-positive tumors and those with virus-negative tumors. (Funded by the National Cancer Institute and Merck; ClinicalTrials.gov number, NCT02267603.).\n\nIndexed on Europe PMC as PubMed record 27093365 (DOI 10.1056/nejmoa1603702). Its abstract cites the registry id NCT02267603, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2016","url":"https://doi.org/10.1056/nejmoa1603702"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27093365/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27093365"},{"label":"ClinicalTrials.gov NCT02267603","url":"https://clinicaltrials.gov/study/NCT02267603"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-017"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2016,"doi":"10.1056/nejmoa1603702","pmid":"27093365","authors":"Nghiem PT, Bhatia S, Lipson EJ, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02267603 with the most citations, so it is the natural first reading for anyone following the KEYNOTE-017 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-tabrizian-am-j-transplant","kind":"paper","name":"PD-1 inhibitor as bridge therapy to liver transplantation?","aka":[],"tldr":"Paper cited by one idea page, indexed on Europe PMC as PubMed record 33316117 and published in American journal of transplantation; the citing page links this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 33316117 (DOI 10.1111/ajt.16448). Matched by DOI alone: one idea page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Am J Transplant 2021","url":"https://doi.org/10.1111/ajt.16448"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33316117/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33316117"}],"tags":["europepmc-ingest"],"related":["idea-hcc-io-before-transplant"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"American journal of transplantation","year":2021,"doi":"10.1111/ajt.16448","pmid":"33316117","authors":"Tabrizian P, Florman SS, Schwartz ME","paperType":"observational","findings":[],"whatItMeans":"One idea page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-pd-l1-urothelial-mol-cancer-ther-2015","kind":"paper","name":"PD-L1 Expression as a Predictive Biomarker in Cancer Immunotherapy","aka":[],"tldr":"Review on PD-L1 in Bladder & urothelial cancer, in Molecular Cancer Therapeutics (2015), one of the most cited Europe PMC records with PD-L1 in its title.","summary":"The resurgence of cancer immunotherapy stems from an improved understanding of the tumor microenvironment. The PD-1/PD-L1 axis is of particular interest, in light of promising data demonstrating a restoration of host immunity against tumors, with the prospect of durable remissions. Indeed, remarkable clinical responses have been seen in several different malignancies including, but not limited to, melanoma, lung, kidney, and bladder cancers. Even so, determining which patients derive benefit from PD-1/PD-L1-directed immunotherapy remains an important clinical question, particularly in light of the autoimmune toxicity of these agents. The use of PD-L1 (B7-H1) immunohistochemistry (IHC) as a predictive biomarker is confounded by multiple unresolved issues: variable detection antibodies, differing IHC cutoffs, tissue preparation, processing variability, primary versus metastatic biopsies, oncogenic versus induced PD-L1 expression, and staining of tumor versus immune cells. Emerging data suggest that patients whose tumors overexpress PD-L1 by IHC have improved clinical outcomes with anti-PD-1-directed therapy, but the presence of robust responses in some patients with low levels of expression of these markers complicates the issue of PD-L1 as an exclusionary predictive biomarker. An improved understanding of the host immune system and tumor microenvironment will better elucidate which patients derive benefit from these promising agents.\n\nIndexed on Europe PMC as PubMed record 25695955 (DOI 10.1158/1535-7163.mct-14-0983). Its title names PD-L1 and its text names Bladder & urothelial cancer; PubMed types it as a review (Research Support, Non-U.S. Gov't, Review). It was matched automatically to the idea \"Anchor a TGF-beta trap in the tumour stroma so it cannot act everywhere\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Mol Cancer Ther 2015","url":"https://doi.org/10.1158/1535-7163.mct-14-0983"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25695955/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25695955"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["molecular-cancer-therapeutics"],"dependsOn":[],"notes":[],"journal":"Molecular Cancer Therapeutics","year":2015,"doi":"10.1158/1535-7163.mct-14-0983","pmid":"25695955","authors":"Patel SP, Kurzrock R","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for PD-L1 in Bladder & urothelial cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by PD-L1 in the title and Bladder & urothelial cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-pd-l1-urothelial-onco-targets-ther-2016","kind":"paper","name":"PD-L1 expression in human cancers and its association with clinical outcomes","aka":[],"tldr":"Review on PD-L1 in Bladder & urothelial cancer, in OncoTargets and therapy (2016), one of the most cited Europe PMC records with PD-L1 in its title.","summary":"PD-L1 is an immunoinhibitory molecule that suppresses the activation of T cells, leading to the progression of tumors. Overexpression of PD-L1 in cancers such as gastric cancer, hepatocellular carcinoma, renal cell carcinoma, esophageal cancer, pancreatic cancer, ovarian cancer, and bladder cancer is associated with poor clinical outcomes. In contrast, PD-L1 expression correlates with better clinical outcomes in breast cancer and merkel cell carcinoma. The prognostic value of PD-L1 expression in lung cancer, colorectal cancer, and melanoma is controversial. Blocking antibodies that target PD-1 and PD-L1 have achieved remarkable response rates in cancer patients who have PD-L1-overexpressing tumors. However, using PD-L1 as an exclusive predictive biomarker for cancer immunotherapy is questionable due to the low accuracy of PD-L1 immunohistochemistry staining. Factors that affect the accuracy of PD-L1 immunohistochemistry staining are as follows. First, antibodies used in different studies have different sensitivity. Second, in different studies, the cut-off value of PD-L1 staining positivity is different. Third, PD-L1 expression in tumors is not uniform, and sampling time and location may affect the results of PD-L1 staining. Therefore, better understanding of tumor microenvironment and use of other biomarkers such as gene marker and combined index are necessary to better identify patients who will benefit from PD-1/PD-L1 checkpoint blockade therapy.\n\nIndexed on Europe PMC as PubMed record 27574444 (DOI 10.2147/ott.s105862). Its title names PD-L1 and its text names Bladder & urothelial cancer; PubMed types it as a review (review-article, Review). It was matched automatically to the idea \"Anchor a TGF-beta trap in the tumour stroma so it cannot act everywhere\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Onco Targets Ther 2016","url":"https://doi.org/10.2147/ott.s105862"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27574444/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27574444"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"OncoTargets and therapy","year":2016,"doi":"10.2147/ott.s105862","pmid":"27574444","authors":"Wang X, Teng F, Kong L, et al.","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for PD-L1 in Bladder & urothelial cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by PD-L1 in the title and Bladder & urothelial cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-rugo-pd-l1-assay-comparison-impassion130-jnci-2021","kind":"paper","name":"PD-L1 Immunohistochemistry Assay Comparison in Atezolizumab Plus nab-Paclitaxel-Treated Advanced Triple-Negative Breast Cancer","aka":[],"tldr":"Three different PD-L1 tests run on the same 614 IMpassion130 tumours called 46, 75 and 73 percent of them positive and agreed with each other only about 69 percent of the time; the benefit of atezolizumab was concentrated in the tumours all three called positive.","summary":"Rugo, Loi, Adams, Schmid and colleagues centrally tested samples from 614 patients (68.1 percent of the IMpassion130 population) for PD-L1 on immune cells by VENTANA SP142, SP263 and Dako 22C3, and as 22C3 combined positive score. Prevalence of immune cell PD-L1 of 1 percent or more was 46.4 percent (SP142), 74.9 percent (SP263) and 73.1 percent (22C3); 80.9 percent had 22C3 combined positive score of 1 or more. Analytical concordance of SP263 and 22C3 with SP142 was 69.2 and 68.7 percent; almost all SP142-positive cases were positive on the others, but 29.6 percent of SP263-positive and 29.0 percent of 22C3-positive cases were SP142-negative. Atezolizumab benefit in SP263- and 22C3-positive patients (progression-free survival hazard ratios 0.64 to 0.68; overall survival 0.75 to 0.79) was driven by double-positive cases (0.60 to 0.61; 0.71 to 0.75) rather than single-positive cases (0.68 to 0.81; 0.87 to 0.95). Harmonised cut-offs (SP263 immune cells 4 percent or more; 22C3 combined positive score 10 or more) reached only about 75 percent concordance with SP142.","asOf":"2026-09-24","links":[{"label":"J Natl Cancer Inst 2021","url":"https://doi.org/10.1093/jnci/djab108"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34097070/"},{"label":"ClinicalTrials.gov NCT02425891","url":"https://clinicaltrials.gov/study/NCT02425891"}],"tags":["tnbc-evidence"],"related":["pd-l1-ic-score","pd-l1-cps"],"cancers":["tnbc","tnbc-metastatic"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["pdl1"],"drugs":["atezolizumab","nab-paclitaxel","ventana-pd-l1-sp142","ventana-pd-l1-sp263","dako-pd-l1-22c3-pharmdx"],"companies":["roche-genentech"],"institutions":[],"pathways":[],"terms":["cps","ihc","hazard-ratio"],"trials":["impassion130","keynote-355"],"people":["hope-rugo","peter-schmid","loi-sherene","eric-winer"],"bottlenecks":["b-biomarker-validation","b-regulatory-fragmentation"],"keyPapers":[],"journals":["jnci"],"dependsOn":[],"notes":[],"journal":"Journal of the National Cancer Institute","year":2021,"doi":"10.1093/jnci/djab108","pmid":"34097070","authors":"Rugo HS, Loi S, Adams S, et al.","paperType":"translational","findings":["PD-L1 positivity (immune cells 1 percent or more): SP142 46.4 percent, SP263 74.9 percent, 22C3 73.1 percent; 22C3 combined positive score 1 or more 80.9 percent.","Concordance with SP142: SP263 69.2 percent, 22C3 68.7 percent; harmonised cut-offs about 75 percent.","Benefit concentrated in double-positive cases; single-positive cases showed overall survival hazard ratios of 0.87 to 0.95."],"whatItMeans":"The clearest demonstration that PD-L1 positive in triple-negative breast cancer means different things depending on the kit; with atezolizumab withdrawn, pembrolizumab's 22C3 combined positive score of 10 is the surviving standard, and roughly a quarter of patients get a different answer depending on which assay their laboratory runs.","caveats":["Retrospective, in 68 percent of the trial population.","Atezolizumab's breast cancer indication has since been withdrawn in the United States, so the clinical anchor is historical."],"changedPractice":false,"participants":614},{"id":"paper-hirsch-j-thorac-oncol","kind":"paper","name":"PD-L1 Immunohistochemistry Assays for Lung Cancer: Results from Phase 1 of the Blueprint PD-L1 IHC Assay Comparison Project","aka":[],"tldr":"Paper cited by two bottleneck pages, indexed on Europe PMC as PubMed record 27913228 and published in Journal of Thoracic Oncology; the citing pages link this DOI, which is how the record was matched.","summary":"Introduction: The Blueprint Programmed Death Ligand 1 (PD-L1) Immunohistochemistry (IHC) Assay Comparison Project is an industrial-academic collaborative partnership to provide information on the analytical and clinical comparability of four PD-L1 IHC assays used in clinical trials.\n\nMethods: A total of 39 NSCLC tumors were stained with four PD-L1 IHC assays (22C3, 28-8, SP142, and SP263), as used in the clinical trials. Three experts in interpreting their respective assays independently evaluated the percentages of tumor and immune cells staining positive at any intensity. Clinical diagnostic performance was assessed through comparisons of patient classification above and below a selected expression cutoff and by agreement using various combinations of assays and cutoffs.\n\nResults: Analytical comparison demonstrated that the percentage of PD-L1-stained tumor cells was comparable when the 22C3, 28-8, and SP263 assays were used, whereas the SP142 assay exhibited fewer stained tumor cells overall. The variability of immune cell staining across the four assays appears to be higher than for tumor cell staining. Of the 38 cases, 19 (50.0%) were classified above and five (13%) were classified below the selected cutoffs of all assays. For 14 of the 38 cases (37%), a different PD-L1 classification would be made depending on which assay/scoring system was used.\n\nConclusions: The Blueprint PD-L1 IHC Assay Comparison Project revealed that three of the four assays were closely aligned on tumor cell staining whereas the fourth showed consistently fewer tumor cells stained. All of the assays demonstrated immune cell staining, but with greater variability than with tumor cell staining. By comparing assays and cutoffs, the study indicated that despite similar analytical performance of PD-L1 expression for three assays, interchanging assays and cutoffs would lead to \"misclassification\" of PD-L1 status for some patients. More data are required to inform on the use of alternative staining assays upon which to read different specific therapy-related PD-L1 cutoffs.\n\nIndexed on Europe PMC as PubMed record 27913228 (DOI 10.1016/j.jtho.2016.11.2228). Matched by DOI alone: two bottleneck pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Thorac Oncol 2017","url":"https://doi.org/10.1016/j.jtho.2016.11.2228"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27913228/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27913228"}],"tags":["europepmc-ingest"],"related":["b-biomarker-validation","b-immunotherapy-response","pd-l1-tps","pd-l1-tc-score","pd-l1-ic-score"],"cancers":["nsclc"],"sections":[],"technologies":["histopathology-ihc"],"targets":["pdl1"],"drugs":[],"companies":[],"institutions":[],"pathways":["pd1-checkpoint"],"terms":["ihc"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-thoracic-oncology"],"dependsOn":[],"notes":[],"journal":"Journal of Thoracic Oncology","year":2017,"doi":"10.1016/j.jtho.2016.11.2228","pmid":"27913228","authors":"Hirsch FR, McElhinny A, Stanforth D, et al.","paperType":"observational","findings":[],"whatItMeans":"Two bottleneck pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-blueprint-phase-2-pd-l1-assays-jto-2018","kind":"paper","name":"PD-L1 immunohistochemistry comparability study in real-life clinical samples: results of Blueprint phase 2 project","aka":[],"tldr":"Five different stains for the same protein were run on 81 real lung cancer samples and read by pathologists from thirteen countries. Three of the five agree closely on tumour cells, one stains less and one stains more, and none of them can be read reliably on immune cells.","summary":"Eighty-one lung cancer specimens of various histological and sample types were stained with all five trial-validated PD-L1 assays (22C3, 28-8, SP142, SP263 and 73-10) and evaluated by an international panel of pathologists, with parallel assessment of digital images and of cytology cell blocks. The 22C3, 28-8 and SP263 assays gave highly comparable staining of tumour cells; SP142 was less sensitive and 73-10 more sensitive. Glass slide and digital scoring were highly concordant, with correlation above 0.96. Reliability between pathologists was very strong for tumour-cell scoring, with overall intraclass correlation 0.86 to 0.93, poor for immune-cell scoring at 0.18 to 0.19, and good for scoring on cytological cell block material at 0.78 to 0.85.","asOf":"2026-09-25","links":[{"label":"Tsao et al., J Thorac Oncol 2018: Blueprint phase 2, five PD-L1 assays on 81 real-world lung cancer specimens","url":"https://doi.org/10.1016/j.jtho.2018.05.013"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29800747/"}],"tags":[],"related":["pd-l1-tps","pd-l1-tc-score","pd-l1-ic-score"],"cancers":["nsclc"],"sections":[],"technologies":["histopathology-ihc","checkpoint-inhibitor"],"targets":["pdl1"],"drugs":[],"companies":[],"institutions":[],"pathways":["pd1-checkpoint"],"terms":["ihc","biopsy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-thoracic-oncology"],"dependsOn":[],"notes":[],"journal":"Journal of Thoracic Oncology","year":2018,"doi":"10.1016/j.jtho.2018.05.013","pmid":"29800747","authors":"Tsao MS, Kerr KM, Kockx M, et al.","paperType":"methods","findings":["22C3, 28-8 and SP263 are interchangeable for tumour-cell scoring; SP142 is less sensitive and 73-10 more sensitive.","Agreement between pathologists on tumour cells is excellent (0.86 to 0.93) and on immune cells is poor (0.18 to 0.19).","Cytology cell blocks are an acceptable substrate (0.78 to 0.85).","Digital images can be scored in place of glass slides."],"whatItMeans":"It is the reason a laboratory can run one stain and report against several drug labels, and the reason any decision resting on an immune-cell score rests on the least reproducible number in lung pathology.","caveats":["Eighty-one specimens, chosen to span sample types rather than to represent a consecutive series.","Comparability is analytical: it shows the stains agree, not that the thresholds predict benefit equally.","The SP142 immune-cell score used for atezolizumab was not made reliable by this work."],"changedPractice":true,"participants":81},{"id":"paper-heinrich-pdgfra-gist-science-2003","kind":"paper","name":"PDGFRA activating mutations in gastrointestinal stromal tumours","aka":[],"tldr":"This study found that most gastrointestinal stromal tumours without KIT mutations instead carry activating mutations in the related receptor PDGFRA, including the D842V mutation that resists imatinib, completing the genetic definition of the disease.","summary":"Mutation analysis of KIT-wild-type gastrointestinal stromal tumours identifying activating PDGFRA mutations in about a third, mutually exclusive with KIT mutations, with the mutant receptors showing constitutive activation and, for D842V, resistance to imatinib in vitro, while other PDGFRA mutants were sensitive.","asOf":"2026-09-17","links":[{"label":"Science 2003","url":"https://doi.org/10.1126/science.1079666"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/12522257/"}],"tags":[],"related":[],"cancers":["gist-pdgfra-d842v"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["michael-heinrich"],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2003,"doi":"10.1126/science.1079666","pmid":"12522257","authors":"Heinrich MC, Corless CL, Duensing A, et al.","paperType":"basic","findings":["PDGFRA mutations in about 35 percent of KIT wild-type GISTs.","D842V mutant resistant to imatinib; other PDGFRA mutants sensitive."],"whatItMeans":"PDGFRA testing is part of standard GIST genotyping, and the imatinib resistance of D842V predicted here led to the development of avapritinib.","caveats":["Discovery study; clinical resistance of D842V was confirmed in later trials."],"changedPractice":true},{"id":"paper-amant-n-engl-j-med","kind":"paper","name":"Pediatric Outcome after Maternal Cancer Diagnosed during Pregnancy","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 26415085 and published in New England Journal of Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Background: Data on the long-term outcome of children who are exposed to maternal cancer with or without treatment during pregnancy are lacking.\n\nMethods: In this multicenter case-control study, we compared children whose mothers received a diagnosis of cancer during the pregnancy with matched children of women without a cancer diagnosis. We used a health questionnaire and medical files to collect data regarding neonatal and general health. All children were prospectively assessed (by means of a neurologic examination and the Bayley Scales of Infant Development) at 18 months, 36 months, or both. A cardiac assessment was performed at 36 months.\n\nResults: A total of 129 children (median age, 22 months; range, 12 to 42) were included in the group whose mother had cancer (prenatal-exposure group) with a matching number in the control group. During pregnancy, 96 children (74.4%) were exposed to chemotherapy (alone or in combination with other treatments), 11 (8.5%) to radiotherapy (alone or in combination), 13 (10.1%) to surgery alone, 2 (1.6%) to other drug treatments, and 14 (10.9%) to no treatment. Birth weight was below the 10th percentile in 28 of 127 children (22.0%) in the prenatal-exposure group and in 19 of 125 children (15.2%) in the control group (P=0.16). There was no significant between-group difference in cognitive development on the basis of the Bayley score (P=0.08) or in subgroup analyses. The gestational age at birth was correlated with the cognitive outcome in the two study groups. Cardiologic evaluation among 47 children at 36 months of age showed normal cardiac findings.\n\nConclusions: Prenatal exposure to maternal cancer with or without treatment did not impair the cognitive, cardiac, or general development of children in early childhood. Prematurity was correlated with a worse cognitive outcome, but this effect was independent of cancer treatment. (Funded by Research Foundation-Flanders and others; ClinicalTrials.gov number, NCT00330447.).\n\nIndexed on Europe PMC as PubMed record 26415085 (DOI 10.1056/nejmoa1508913). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2015","url":"https://doi.org/10.1056/nejmoa1508913"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26415085/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26415085"}],"tags":["europepmc-ingest"],"related":["cancer-in-pregnancy"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2015,"doi":"10.1056/nejmoa1508913","pmid":"26415085","authors":"Amant F, Vandenbroucke T, Verheecke M, et al.","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nct03725059-nat-med-2025","kind":"paper","name":"Pembrolizumab and chemotherapy in high-risk, early-stage, ER + /HER2 - breast cancer: a randomized phase 3 trial","aka":[],"tldr":"Published report from the KEYNOTE-756 trial registered as NCT03725059, in Nature Medicine (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Addition of pembrolizumab to neoadjuvant chemotherapy followed by adjuvant pembrolizumab improved outcomes in patients with high-risk, early-stage, triple-negative breast cancer. However, whether the addition of neoadjuvant pembrolizumab to chemotherapy would improve outcomes in high-risk, early-stage, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER + /HER2 -) breast cancer remains unclear. We conducted a double-blind, placebo-controlled phase 3 study (KEYNOTE-756) in which patients with previously untreated ER + /HER2 - grade 3 high-risk invasive breast cancer (T1c-2 (≥2 cm), cN1-2 or T3-4, cN0-2) were randomly assigned (1:1) to neoadjuvant pembrolizumab 200 mg or placebo Q3W given with paclitaxel QW for 12 weeks, followed by four cycles of doxorubicin or epirubicin plus cyclophosphamide Q2W or Q3W. After surgery (with/without adjuvant radiation therapy), patients received adjuvant pembrolizumab or placebo for nine cycles plus adjuvant endocrine therapy. Dual primary endpoints were pathological complete response and event-free survival in the intention-to-treat population. In total, 635 patients were assigned to the pembrolizumab-chemotherapy arm and 643 to the placebo-chemotherapy arm. At the study's prespecified first interim analysis, the pathological complete response rate was 24.3% (95% confidence interval (CI), 21.0-27.8%) in the pembrolizumab-chemotherapy arm and 15.6% (95% CI, 12.8-18.6%) in the placebo-chemotherapy arm (estimated treatment difference, 8.5 percentage points; 95% CI, 4.2-12.8; P = 0.00005). Event-free survival was not mature in this analysis. During the neoadjuvant phase, treatment-related adverse events of grade ≥3 were reported in 52.5% and 46.4% of patients in the pembrolizumab-chemotherapy and placebo-chemotherapy arms, respectively. In summary, the addition of pembrolizumab to neoadjuvant chemotherapy significantly improved the pathological complete response rate in patients with high-risk, early-stage ER + /HER2 - breast cancer. Safety was consistent with the known profiles of each study treatment. Follow-up continues for event-free survival. ClinicalTrials.gov identifier: NCT03725059.\n\nIndexed on Europe PMC as PubMed record 39838117 (DOI 10.1038/s41591-024-03415-7). Its abstract cites the registry id NCT03725059, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Nat Med 2025","url":"https://doi.org/10.1038/s41591-024-03415-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39838117/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39838117"},{"label":"ClinicalTrials.gov NCT03725059","url":"https://clinicaltrials.gov/study/NCT03725059"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct03725059"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2025,"doi":"10.1038/s41591-024-03415-7","pmid":"39838117","authors":"Cardoso F, O'Shaughnessy J, Liu Z, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03725059 with the most citations, so it is the natural first reading for anyone following the KEYNOTE-756 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-pembrolizumab-urothelial-n-engl-j-med-2017","kind":"paper","name":"Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma","aka":[],"tldr":"Phase 2 or 3 results paper on Pembrolizumab in Bladder & urothelial cancer, in New England Journal of Medicine (2017), one of the most cited Europe PMC records with Pembrolizumab in its title.","summary":"Background: Patients with advanced urothelial carcinoma that progresses after platinum-based chemotherapy have a poor prognosis and limited treatment options.\n\nMethods: In this open-label, international, phase 3 trial, we randomly assigned 542 patients with advanced urothelial cancer that recurred or progressed after platinum-based chemotherapy to receive pembrolizumab (a highly selective, humanized monoclonal IgG4κ isotype antibody against programmed death 1 [PD-1]) at a dose of 200 mg every 3 weeks or the investigator's choice of chemotherapy with paclitaxel, docetaxel, or vinflunine. The coprimary end points were overall survival and progression-free survival, which were assessed among all patients and among patients who had a tumor PD-1 ligand (PD-L1) combined positive score (the percentage of PD-L1-expressing tumor and infiltrating immune cells relative to the total number of tumor cells) of 10% or more.\n\nResults: The median overall survival in the total population was 10.3 months (95% confidence interval [CI], 8.0 to 11.8) in the pembrolizumab group, as compared with 7.4 months (95% CI, 6.1 to 8.3) in the chemotherapy group (hazard ratio for death, 0.73; 95% CI, 0.59 to 0.91; P=0.002). The median overall survival among patients who had a tumor PD-L1 combined positive score of 10% or more was 8.0 months (95% CI, 5.0 to 12.3) in the pembrolizumab group, as compared with 5.2 months (95% CI, 4.0 to 7.4) in the chemotherapy group (hazard ratio, 0.57; 95% CI, 0.37 to 0.88; P=0.005). There was no significant between-group difference in the duration of progression-free survival in the total population (hazard ratio for death or disease progression, 0.98; 95% CI, 0.81 to 1.19; P=0.42) or among patients who had a tumor PD-L1 combined positive score of 10% or more (hazard ratio, 0.89; 95% CI, 0.61 to 1.28; P=0.24). Fewer treatment-related adverse events of any grade were reported in the pembrolizumab group than in the chemotherapy group (60.9% vs. 90.2%); there were also fewer events of grade 3, 4, or 5 severity reported in the pembrolizumab group than in the chemotherapy group (15.0% vs. 49.4%).\n\nConclusions: Pembrolizumab was associated with significantly longer overall survival (by approximately 3 months) and with a lower rate of treatment-related adverse events than chemotherapy as second-line therapy for platinum-refractory advanced urothelial carcinoma. (Funded by Merck; KEYNOTE-045 ClinicalTrials.gov number, NCT02256436.).\n\nIndexed on Europe PMC as PubMed record 28212060 (DOI 10.1056/nejmoa1613683). Its title names Pembrolizumab and its text names Bladder & urothelial cancer; PubMed types it as a clinical trial report (Clinical Trial, Phase III, Research Support, Non-U.S. Gov't, research-article, Multicenter Study, Randomized Controlled Trial). It was matched automatically to the idea \"Bladder preservation for MIBC after perioperative EV + pembrolizumab complete response\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2017","url":"https://doi.org/10.1056/nejmoa1613683"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28212060/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28212060"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2017,"doi":"10.1056/nejmoa1613683","pmid":"28212060","authors":"Bellmunt J, de Wit R, Vaughn DJ, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Pembrolizumab in Bladder & urothelial cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Pembrolizumab in the title and Bladder & urothelial cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-keynote-522-n-engl-j-med-2020","kind":"paper","name":"Pembrolizumab for Early Triple-Negative Breast Cancer","aka":[],"tldr":"Published report from the KEYNOTE-522 trial registered as NCT03036488, in New England Journal of Medicine (2020), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Previous trials showed promising antitumor activity and an acceptable safety profile associated with pembrolizumab in patients with early triple-negative breast cancer. Whether the addition of pembrolizumab to neoadjuvant chemotherapy would significantly increase the percentage of patients with early triple-negative breast cancer who have a pathological complete response (defined as no invasive cancer in the breast and negative nodes) at definitive surgery is unclear.\n\nMethods: In this phase 3 trial, we randomly assigned (in a 2:1 ratio) patients with previously untreated stage II or stage III triple-negative breast cancer to receive neoadjuvant therapy with four cycles of pembrolizumab (at a dose of 200 mg) every 3 weeks plus paclitaxel and carboplatin (784 patients; the pembrolizumab-chemotherapy group) or placebo every 3 weeks plus paclitaxel and carboplatin (390 patients; the placebo-chemotherapy group); the two groups then received an additional four cycles of pembrolizumab or placebo, and both groups received doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide. After definitive surgery, the patients received adjuvant pembrolizumab or placebo every 3 weeks for up to nine cycles. The primary end points were a pathological complete response at the time of definitive surgery and event-free survival in the intention-to-treat population.\n\nResults: At the first interim analysis, among the first 602 patients who underwent randomization, the percentage of patients with a pathological complete response was 64.8% (95% confidence interval [CI], 59.9 to 69.5) in the pembrolizumab-chemotherapy group and 51.2% (95% CI, 44.1 to 58.3) in the placebo-chemotherapy group (estimated treatment difference, 13.6 percentage points; 95% CI, 5.4 to 21.8; P<0.001). After a median follow-up of 15.5 months (range, 2.7 to 25.0), 58 of 784 patients (7.4%) in the pembrolizumab-chemotherapy group and 46 of 390 patients (11.8%) in the placebo-chemotherapy group had disease progression that precluded definitive surgery, had local or distant recurrence or a second primary tumor, or died from any cause (hazard ratio, 0.63; 95% CI, 0.43 to 0.93). Across all treatment phases, the incidence of treatment-related adverse events of grade 3 or higher was 78.0% in the pembrolizumab-chemotherapy group and 73.0% in the placebo-chemotherapy group, including death in 0.4% (3 patients) and 0.3% (1 patient), respectively.\n\nConclusions: Among patients with early triple-negative breast cancer, the percentage with a pathological complete response was significantly higher among those who received pembrolizumab plus neoadjuvant chemotherapy than among those who received placebo plus neoadjuvant chemotherapy. (Funded by Merck Sharp & Dohme [a subsidiary of Merck]; KEYNOTE-522 ClinicalTrials.gov number, NCT03036488.).\n\nIndexed on Europe PMC as PubMed record 32101663 (DOI 10.1056/nejmoa1910549). Its abstract cites the registry id NCT03036488, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2020","url":"https://doi.org/10.1056/nejmoa1910549"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32101663/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32101663"},{"label":"ClinicalTrials.gov NCT03036488","url":"https://clinicaltrials.gov/study/NCT03036488"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-522"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2020,"doi":"10.1056/nejmoa1910549","pmid":"32101663","authors":"Schmid P, Cortes J, Pusztai L, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03036488 with the most citations, so it is the natural first reading for anyone following the KEYNOTE-522 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-pembrolizumab-head-and-neck-j-clin-oncol-2017","kind":"paper","name":"Pembrolizumab for Platinum- and Cetuximab-Refractory Head and Neck Cancer: Results From a Single-Arm, Phase II Study","aka":[],"tldr":"Phase 2 or 3 results paper on Pembrolizumab in Head and neck squamous cell carcinoma, in Journal of Clinical Oncology (2017), one of the most cited Europe PMC records with Pembrolizumab in its title.","summary":"Purpose There are no approved treatments for recurrent/metastatic head and neck squamous cell carcinoma refractory to platinum and cetuximab. In the single-arm, phase II KEYNOTE-055 study, we evaluated pembrolizumab, an anti-programmed death 1 receptor antibody, in this platinum- and cetuximab-pretreated population with poor prognosis. Methods Eligibility stipulated disease progression within 6 months of platinum and cetuximab treatment. Patients received pembrolizumab 200 mg every 3 weeks. Imaging was performed every 6 to 9 weeks. Primary end points: overall response rate (Response Evaluation Criteria in Solid Tumors v1.1, central review) and safety. Efficacy was assessed in all dosed patients and in subgroups on the basis of programmed death ligand 1 (PD-L1) expression and human papillomavirus (HPV) status. Results Among 171 patients treated, 75% received two or more prior lines of therapy for metastatic disease, 82% were PD-L1 positive, and 22% were HPV positive. At the time of analysis, 109 patients (64%) experienced a treatment-related adverse event; 26 patients (15%) experienced a grade ≥ 3 event. Seven patients (4%) discontinued treatment, and one died of treatment-related adverse events. Overall response rate was 16% (95% CI, 11% to 23%), with a median duration of response of 8 months (range, 2+ to 12+ months); 75% of responses were ongoing at the time of analysis. Response rates were similar in all HPV and PD-L1 subgroups. Median progression-free survival was 2.1 months, and median overall survival was 8 months. Conclusion Pembrolizumab exhibited clinically meaningful antitumor activity and an acceptable safety profile in recurrent/metastatic head and neck squamous cell carcinoma previously treated with platinum and cetuximab.\n\nIndexed on Europe PMC as PubMed record 28328302 (DOI 10.1200/jco.2016.70.1524). Its title names Pembrolizumab and its text names Head and neck squamous cell carcinoma; PubMed types it as a clinical trial report (Clinical Trial, Phase II, research-article, Multicenter Study). It was matched automatically to the idea \"Test one-tenth-dose immunotherapy where the full dose is unaffordable\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2017","url":"https://doi.org/10.1200/jco.2016.70.1524"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28328302/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28328302"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2017,"doi":"10.1200/jco.2016.70.1524","pmid":"28328302","authors":"Bauml J, Seiwert TY, Pfister DG, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Pembrolizumab in Head and neck squamous cell carcinoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Pembrolizumab in the title and Head and neck squamous cell carcinoma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-keynote-158-ann-oncol-2022-update","kind":"paper","name":"Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers: updated analysis from the phase II KEYNOTE-158 study","aka":[],"tldr":"Later report from the KEYNOTE-158 trial registered as NCT02628067, in Annals of Oncology (2022); its title describes an updated or longer-term analysis.","summary":"Background: Pembrolizumab demonstrated durable antitumor activity in 233 patients with previously treated advanced microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) advanced solid tumors in the phase II multicohort KEYNOTE-158 (NCT02628067) study. Herein, we report safety and efficacy outcomes with longer follow-up for more patients with previously treated advanced MSI-H/dMMR noncolorectal cancers who were included in cohort K of the KEYNOTE-158 (NCT02628067) study.\n\nPatients and methods: Eligible patients with previously treated advanced noncolorectal MSI-H/dMMR solid tumors, measurable disease as per RECIST v1.1, and Eastern Cooperative Oncology Group performance status of 0 or 1 received pembrolizumab 200 mg Q3W for 35 cycles or until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) as per RECIST v1.1 by independent central radiologic review.\n\nResults: Three hundred and fifty-one patients with various tumor types were enrolled in KEYNOTE-158 cohort K. The most common tumor types were endometrial (22.5%), gastric (14.5%), and small intestine (7.4%). Median time from first dose to database cut-off (5 October 2020) was 37.5 months (range, 0.2-55.6 months). ORR among 321 patients in the efficacy population (patients who received ≥1 dose of pembrolizumab enrolled ≥6 months before the data cut-off date) was 30.8% [95% confidence interval (CI) 25.8% to 36.2%]. Median duration of response was 47.5 months (range, 2.1+ to 51.1+ months; '+' indicates no progressive disease by the time of last disease assessment). Median progression-free survival was 3.5 months (95% CI 2.3-4.2 months) and median overall survival was 20.1 months (95% CI 14.1-27.1 months). Treatment-related adverse events (AEs) occurred in 227 patients (64.7%). Grade 3-4 treatment-related AEs occurred in 39 patients (11.1%); 3 (0.9%) had grade 5 treatment-related AEs (myocarditis, pneumonia, and Guillain-Barre syndrome, n = 1 each).\n\nConclusions: Pembrolizumab demonstrated clinically meaningful and durable benefit, with a high ORR of 30.8%, long median duration of response of 47.5 months, and manageable safety across a range of heavily pretreated, advanced MSI-H/dMMR noncolorectal cancers, providing support for use of pembrolizumab in this setting.\n\nIndexed on Europe PMC as PubMed record 35680043 (DOI 10.1016/j.annonc.2022.05.519). Its abstract cites the registry id NCT02628067, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2022","url":"https://doi.org/10.1016/j.annonc.2022.05.519"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35680043/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35680043"},{"label":"ClinicalTrials.gov NCT02628067","url":"https://clinicaltrials.gov/study/NCT02628067"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-158"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2022,"doi":"10.1016/j.annonc.2022.05.519","pmid":"35680043","authors":"Maio M, Ascierto PA, Manzyuk L, et al.","paperType":"observational","findings":[],"whatItMeans":"A second publication from the KEYNOTE-158 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-nct02332668-lancet-oncol-2020","kind":"paper","name":"Pembrolizumab in paediatric patients with advanced melanoma or a PD-L1-positive, advanced, relapsed, or refractory solid tumour or lymphoma (KEYNOTE-051): interim analysis of an open-label, single-arm, phase 1-2 trial","aka":[],"tldr":"Published report from the KEYNOTE-051 trial registered as NCT02332668, in The Lancet Oncology (2020), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Pembrolizumab is approved for the treatment of advanced cancer in adults; however, no information is available on safety and efficacy in paediatric patients. We aimed to establish the recommended phase 2 dose of pembrolizumab and its safety and antitumour activity in advanced paediatric cancer.\n\nMethods: KEYNOTE-051 is an ongoing phase 1-2 open-label trial. In this interim analysis, children aged 6 months to 17 years were recruited at 30 hospitals located in Australia, Brazil, Canada, France, Germany, Israel, Italy, South Korea, Sweden, the UK, and the USA. Patients with melanoma or a centrally confirmed, PD-L1-positive, relapsed or refractory solid tumour or lymphoma, and a Lansky Play/Karnofsky Performance status score of 50 or higher, received intravenous pembrolizumab at an initial dose of 2 mg/kg every 3 weeks. Pharmacokinetics and dose-limiting toxicities were used to establish the recommended phase 2 dose, and the safety and antitumour activity of this dose were assessed. Primary endpoints were determination of dose-limiting toxicities at the maximum administered dose, safety and tolerability, and the proportion of patients with objective response to pembrolizumab for each tumour type according to the Response Evaluation Criteria in Solid Tumours version 1.1 or the International Neuroblastoma Response Criteria. Safety and efficacy were assessed in all treated patients who received at least one dose of pembrolizumab. Separate reporting of the cohort of patients with relapsed or refractory classical Hodgkin lymphoma was a post-hoc decision. The data cutoff for this interim analysis was Sept 3, 2018. This trial is still enrolling patients and is registered with ClinicalTrials.gov, number NCT02332668.\n\nFindings: Of 863 patients screened between March 23, 2015, and Sept 3, 2018, 796 had tumours that were evaluable for PD-L1 expression (278 [35%] were PD-L1-positive); 155 eligible patients were enrolled and 154 had at least one dose of pembrolizumab. The median age of the enrolled patients was 13 years (IQR 8-15). Median follow-up was 8·6 months (IQR 2·5-16·4). No dose-limiting toxicities were reported in phase 1, and pembrolizumab plasma concentrations were consistent with those previously reported in adults; the recommended phase 2 dose was therefore established as 2 mg/kg every 3 weeks. Of the 154 patients treated, 69 (45%) experienced grade 3-5 adverse events, most commonly anaemia in 14 (9%) patients and decreased lymphocyte count in nine (6%) patients. 13 (8%) of the 154 patients had grade 3-5 treatment-related adverse events, most commonly decreased lymphocyte count in three (2%) patients and anaemia in two (1%) patients. 14 (9%) patients had serious treatment-related adverse events, most commonly pyrexia (four [3%]), and hypertension and pleural effusion (two [1%] each). Four patients (3%) discontinued treatment because of treatment-related adverse events, and two (1%) died (one due to pulmonary oedema and one due to pleural effusion and pneumonitis). Of 15 patients with relapsed or refractory Hodgkin lymphoma, two had complete and seven had partial responses; thus, nine patients achieved an objective response (60·0%; 95% CI 32·3-83·7). Of 136 patients with solid tumours and other lymphomas, eight had partial responses (two patients each with adrenocortical carcinoma and mesothelioma, and one patient each with malignant ganglioglioma, epithelioid sarcoma, lymphoepithelial carcinoma, and malignant rhabdoid tumour); the proportion of patients with an objective response was 5·9% (95% CI 2·6-11·3).\n\nInterpretation: Pembrolizumab was well tolerated and showed encouraging antitumour activity in paediatric patients with relapsed or refractory Hodgkin lymphoma, consistent with experience in adult patients. Pembrolizumab had low antitumour activity in the majority of paediatric tumour types, and responses were observed in only a few rare PD-L1-positive tumour types, suggesting that PD-L1 expression alone is not sufficient as a biomarker for the selection of paediatric patients who are likely to respond to PD-1 checkpoint inhibitors. Final results of KEYNOTE-051, expected by September, 2022, with the possibility for extension, will report further on the activity of pembrolizumab in Hodgkin lymphoma, microsatellite instability-high tumours, and melanoma.\n\nFunding: Merck Sharp & Dohme, a subsidiary of Merck & Co.\n\nIndexed on Europe PMC as PubMed record 31812554 (DOI 10.1016/s1470-2045(19)30671-0). Its abstract cites the registry id NCT02332668, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2020","url":"https://doi.org/10.1016/s1470-2045(19)30671-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31812554/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31812554"},{"label":"ClinicalTrials.gov NCT02332668","url":"https://clinicaltrials.gov/study/NCT02332668"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct02332668"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2020,"doi":"10.1016/s1470-2045(19)30671-0","pmid":"31812554","authors":"Geoerger B, Kang HJ, Yalon-Oren M, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02332668 with the most citations, so it is the natural first reading for anyone following the KEYNOTE-051 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-antoine-italiano-j-clin-oncol-2022","kind":"paper","name":"Pembrolizumab in Patients With Microsatellite Instability-High Advanced Endometrial Cancer: Results From the KEYNOTE-158 Study","aka":[],"tldr":"Paper by Antoine Italiano indexed on Europe PMC as PubMed record 34990208, in Journal of Clinical Oncology (2022), one of the most cited records naming an author with this name at Institut Bergonié.","summary":"Purpose: Pembrolizumab demonstrated durable antitumor activity in patients with previously treated, advanced microsatellite instability-high or mismatch repair-deficient (MSI-H/dMMR) tumors, including endometrial cancer, in the nonrandomized, open-label, multicohort, phase II KEYNOTE-158 study (NCT02628067). We report efficacy and safety outcomes for patients with MSI-H/dMMR endometrial cancer enrolled in KEYNOTE-158.\n\nMethods: Eligible patients from cohorts D (endometrial cancer, regardless of MSI-H/dMMR status) and K (any MSI-H/dMMR solid tumor, except colorectal) with previously treated, advanced MSI-H/dMMR endometrial cancer received pembrolizumab 200 mg once every 3 weeks for 35 cycles. The primary end point was objective response rate per RECIST version 1.1 by independent central radiologic review. Secondary end points included duration of response, progression-free survival, overall survival, and safety.\n\nResults: at October 5, 2020, 18 of 90 treated patients (20%) had completed 35 cycles of pembrolizumab and 52 (58%) had discontinued treatment. In the efficacy population (patients who received ≥ 1 dose of pembrolizumab and had ≥ 26 weeks of follow-up; N = 79), the median time from first dose to data cutoff was 42.6 (range, 6.4-56.1) months. The objective response rate was 48% (95% CI, 37 to 60), and median duration of response was not reached (2.9-49.7+ months). Median progression-free survival was 13.1 (95% CI, 4.3 to 34.4) months, and median overall survival was not reached (95% CI, 27.2 months to not reached). Among all treated patients, 76% had ≥ 1 treatment-related adverse event (grades 3-4, 12%). There were no fatal treatment-related events. Immune-mediated adverse events or infusion reactions occurred in 28% of patients (grades 3-4, 7%; no fatal events).\n\nConclusion: Pembrolizumab demonstrated robust and durable antitumor activity and encouraging survival outcomes with manageable toxicity in patients with previously treated, advanced MSI-H/dMMR endometrial cancer.\n\nIndexed on Europe PMC as PubMed record 34990208 (DOI 10.1200/jco.21.01874). Its author list gives \"Italiano A\" with the affiliation \"Early Phase Trials and Sarcoma Units, Institut Bergonie, Bordeaux, France\", which names Institut Bergonié; that is how the record was matched to Antoine Italiano, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2022","url":"https://doi.org/10.1200/jco.21.01874"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34990208/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34990208"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["antoine-italiano"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2022,"doi":"10.1200/jco.21.01874","pmid":"34990208","authors":"O'Malley DM, Bariani GM, Cassier PA, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Antoine Italiano at Institut Bergonié, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-blay-lancet-oncol","kind":"paper","name":"Pembrolizumab in patients with rare and ultra-rare sarcomas (AcSé Pembrolizumab): analysis of a subgroup from a non-randomised, open-label, phase 2, basket trial","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 37429302 and published in The Lancet Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background: Sarcoma is a heterogeneous group of diseases with few treatment options. Immunotherapy has shown little activity in studies including unselected sarcomas, but immune checkpoint blockers have shown activity in specific histotypes. We evaluated the activity of pembrolizumab in rare and ultra-rare sarcomas.\n\nMethods: AcSé Pembrolizumab is an ongoing phase 2, basket, multitumour study investigating the activity of pembrolizumab monotherapy in rare cancers. Here, we report the results obtained in patients with selected histotypes of rare sarcomas (incidence of less than one case per 1 000 000 people per year) recruited at 24 French hospitals. Key inclusion criteria were age 15 years or older, Eastern Cooperative Oncology Group performance status of 0-1, and advanced disease that was untreated and resistant to treatment. Patients were given pembrolizumab 200 mg intravenously on day 1 of every 21-day cycle for a maximum of 24 months. The primary endpoint was objective response rate at week 12 using Response Evaluation Criteria in Solid Tumours version 1.1, assessed by local investigators. The primary endpoint and safety were analysed in the intention-to-treat population. The AcSé Pembrolizumab study is registered with ClinicalTrials.gov, NCT03012620.\n\nFindings: Between Sept 4, 2017, and Dec 29, 2020, 98 patients were enrolled, of whom 97 received treatment and were included in analyses (median age 51 years [IQR 35-65]; 53 [55%] were male; 44 [45%] were female; no data were collected on race or ethnicity). 34 (35%) patients had chordomas, 14 (14%) had alveolar soft part sarcomas, 12 (12%) had SMARCA4-deficient sarcomas or malignant rhabdoid tumours, eight (8%) had desmoplastic small round cell tumours, six (6%) had epithelioid sarcomas, four (4%) had dendritic cell sarcomas, three (3%) each had clear cell sarcomas, solitary fibrous tumours, and myxoid liposarcomas, and ten (10%) had other ultra-rare histotypes. at data cutoff (April 11, 2022), median follow-up was 13·1 months (range 0·1-52·8; IQR 4·3-19·7). At week 12, objective response rate was 6·2% (95% CI 2·3-13·0), with no complete responses and six partial responses in the 97 patients. The most common grade 3-4 adverse events were anaemia (eight [8%] of 97), alanine aminotransferase and aspartate aminotransferase increase (six [6%]), and dyspnoea (five [5%]). 86 serious adverse events were reported in 37 patients. Five deaths due to adverse events were reported, none of which were determined to be related to treatment (two due to disease progression, two due to cancer, and one due to unknown cause).\n\nInterpretation: Our data show the activity and manageable toxicity of pembrolizumab in some rare and ultra-rare sarcoma histotypes, and support the PD-1/PD-L1 pathway as a potential therapeutic target in selected histotypes. The completion of the basket study will provide further evidence regarding the activity and toxicity of pembrolizumab in identified rare types of cancer.\n\nFunding: The Ligue contre le cancer, INCa, MSD.\n\nTranslation: For the French translation of the abstract see Supplementary Materials section.\n\nIndexed on Europe PMC as PubMed record 37429302 (DOI 10.1016/s1470-2045(23)00282-6). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2023","url":"https://doi.org/10.1016/s1470-2045(23)00282-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37429302/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37429302"}],"tags":["europepmc-ingest"],"related":["epithelioid-sarcoma"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2023,"doi":"10.1016/s1470-2045(23)00282-6","pmid":"37429302","authors":"Blay JY, Chevret S, Le Cesne A, et al.","paperType":"rct","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-giaccone-pembrolizumab-thymic-carcinoma-lancet-oncol-2018","kind":"paper","name":"Pembrolizumab in patients with thymic carcinoma: a single-arm phase 2 study","aka":[],"tldr":"Immunotherapy shrank thymic carcinoma in about one patient in five after chemotherapy, but caused severe immune attacks on the heart and muscle more often than in other cancers, so it is used with care.","summary":"Single-centre phase 2 study of 40 patients with recurrent thymic carcinoma after at least one line of chemotherapy, treated with pembrolizumab every three weeks.\n\nThe objective response rate was 22.5 percent with a median progression-free survival of 4.2 months and durable responses in a subset; 15 percent of patients had severe autoimmune toxicity including myocarditis, myositis and hepatitis, higher than in most tumour types. Patients with thymoma were excluded because of this risk.","asOf":"2026-09-18","links":[{"label":"Lancet Oncol 2018","url":"https://doi.org/10.1016/S1470-2045(18)30062-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29395863/"}],"tags":[],"related":[],"cancers":["thymic-carcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2018,"doi":"10.1016/S1470-2045(18)30062-7","pmid":"29395863","authors":"Giaccone G, Kim C, Thompson J, et al.","paperType":"observational","findings":["Objective response 22.5 percent; median progression-free survival 4.2 months.","Severe immune-related adverse events, including myocarditis, in 15 percent of patients."],"whatItMeans":"PD-1 blockade is an option for thymic carcinoma after chemotherapy in expert centres, with close monitoring for myocarditis; it is not used in thymoma because of autoimmunity.","caveats":["Single-arm, single-centre study.","The rate of serious autoimmune toxicity is much higher than in other cancers."],"changedPractice":true,"participants":40},{"id":"paper-keynote-407-n-engl-j-med-2018","kind":"paper","name":"Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer","aka":[],"tldr":"Published report from the KEYNOTE-407 trial registered as NCT02775435, in New England Journal of Medicine (2018), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Standard first-line therapy for metastatic, squamous non-small-cell lung cancer (NSCLC) is platinum-based chemotherapy or pembrolizumab (for patients with programmed death ligand 1 [PD-L1] expression on ≥50% of tumor cells). More recently, pembrolizumab plus chemotherapy was shown to significantly prolong overall survival among patients with nonsquamous NSCLC.\n\nMethods: In this double-blind, phase 3 trial, we randomly assigned, in a 1:1 ratio, 559 patients with untreated metastatic, squamous NSCLC to receive 200 mg of pembrolizumab or saline placebo for up to 35 cycles; all the patients also received carboplatin and either paclitaxel or nanoparticle albumin-bound [nab]-paclitaxel for the first 4 cycles. Primary end points were overall survival and progression-free survival.\n\nResults: After a median follow-up of 7.8 months, the median overall survival was 15.9 months (95% confidence interval [CI], 13.2 to not reached) in the pembrolizumab-combination group and 11.3 months (95% CI, 9.5 to 14.8) in the placebo-combination group (hazard ratio for death, 0.64; 95% CI, 0.49 to 0.85; P<0.001). The overall survival benefit was consistent regardless of the level of PD-L1 expression. The median progression-free survival was 6.4 months (95% CI, 6.2 to 8.3) in the pembrolizumab-combination group and 4.8 months (95% CI, 4.3 to 5.7) in the placebo-combination group (hazard ratio for disease progression or death, 0.56; 95% CI, 0.45 to 0.70; P<0.001). Adverse events of grade 3 or higher occurred in 69.8% of the patients in the pembrolizumab-combination group and in 68.2% of the patients in the placebo-combination group. Discontinuation of treatment because of adverse events was more frequent in the pembrolizumab-combination group than in the placebo-combination group (13.3% vs. 6.4%).\n\nConclusions: In patients with previously untreated metastatic, squamous NSCLC, the addition of pembrolizumab to chemotherapy with carboplatin plus paclitaxel or nab-paclitaxel resulted in significantly longer overall survival and progression-free survival than chemotherapy alone. (Funded by Merck Sharp & Dohme; KEYNOTE-407 ClinicalTrials.gov number, NCT02775435.).\n\nIndexed on Europe PMC as PubMed record 30280635 (DOI 10.1056/nejmoa1810865). Its abstract cites the registry id NCT02775435, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2018","url":"https://doi.org/10.1056/nejmoa1810865"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30280635/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30280635"},{"label":"ClinicalTrials.gov NCT02775435","url":"https://clinicaltrials.gov/study/NCT02775435"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-407"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2018,"doi":"10.1056/nejmoa1810865","pmid":"30280635","authors":"Paz-Ares L, Luft A, Vicente D, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02775435 with the most citations, so it is the natural first reading for anyone following the KEYNOTE-407 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-keynote-407-j-clin-oncol-2023-update","kind":"paper","name":"Pembrolizumab Plus Chemotherapy in Squamous Non-Small-Cell Lung Cancer: 5-Year Update of the Phase III KEYNOTE-407 Study","aka":[],"tldr":"Later report from the KEYNOTE-407 trial registered as NCT02775435, in Journal of Clinical Oncology (2023); its title describes an updated or longer-term analysis.","summary":"Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. We report 5-year efficacy and safety outcomes from the phase III KEYNOTE-407 study (ClinicalTrials.gov identifier: NCT02775435). Eligible patients with previously untreated, metastatic squamous non-small-cell lung cancer (NSCLC) were randomly assigned 1:1 to pembrolizumab 200 mg or placebo plus carboplatin and paclitaxel/nab-paclitaxel once every 3 weeks for four cycles, followed by pembrolizumab or placebo for up to 35 cycles. Primary end points were overall survival (OS) and progression-free survival (PFS) per RECIST version 1.1 by blinded independent central review (BICR). Five hundred fifty-nine patients were randomly assigned in the intention-to-treat population (pembrolizumab plus chemotherapy, n = 278; placebo plus chemotherapy, n = 281). The median time from random assignment to data cutoff was 56.9 (range, 49.9-66.2) months. OS and PFS were improved with pembrolizumab plus chemotherapy versus placebo plus chemotherapy (hazard ratio [95% CI], 0.71 [0.59 to 0.85] and 0.62 [0.52 to 0.74]), with 5-year OS rates of 18.4% versus 9.7%, respectively. Toxicity was manageable. Among 55 patients who completed 35 cycles of pembrolizumab, the objective response rate was 90.9% and the 3-year OS rate after completion of 35 cycles (approximately 5 years after random assignment) was 69.5%. Pembrolizumab plus chemotherapy maintained an OS and PFS benefit versus placebo plus chemotherapy in previously untreated, metastatic squamous NSCLC and is a standard-of-care first-line treatment option for metastatic squamous NSCLC regardless of programmed death ligand 1 expression.\n\nIndexed on Europe PMC as PubMed record 36735893 (DOI 10.1200/jco.22.01990). Its abstract cites the registry id NCT02775435, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2023","url":"https://doi.org/10.1200/jco.22.01990"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36735893/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36735893"},{"label":"ClinicalTrials.gov NCT02775435","url":"https://clinicaltrials.gov/study/NCT02775435"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-407"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2023,"doi":"10.1200/jco.22.01990","pmid":"36735893","authors":"Novello S, Kowalski DM, Luft A, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the KEYNOTE-407 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-keynote-355-lancet-2020","kind":"paper","name":"Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial","aka":[],"tldr":"Published report from the KEYNOTE-355 trial registered as NCT02819518, in The Lancet (2020), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Pembrolizumab monotherapy showed durable antitumour activity and manageable safety in patients with metastatic triple-negative breast cancer. We aimed to examine whether the addition of pembrolizumab would enhance the antitumour activity of chemotherapy in patients with metastatic triple-negative breast cancer.\n\nMethods: In this randomised, placebo-controlled, double-blind, phase 3 trial, done in 209 sites in 29 countries, we randomly assigned patients 2:1 with untreated locally recurrent inoperable or metastatic triple-negative breast cancer using a block method (block size of six) and an interactive voice-response system with integrated web-response to pembrolizumab (200 mg) every 3 weeks plus chemotherapy (nab-paclitaxel; paclitaxel; or gemcitabine plus carboplatin) or placebo plus chemotherapy. Randomisation was stratified by type of on-study chemotherapy (taxane or gemcitabine-carboplatin), PD-L1 expression at baseline (combined positive score [CPS] ≥1 or <1), and previous treatment with the same class of chemotherapy in the neoadjuvant or adjuvant setting (yes or no). Eligibility criteria included age at least 18 years, centrally confirmed triple-negative breast cancer; at least one measurable lesion; provision of a newly obtained tumour sample for determination of triple-negative breast cancer status and PD-L1 status by immunohistochemistry at a central laboratory; an Eastern Cooperative Oncology Group performance status score 0 or 1; and adequate organ function. The sponsor, investigators, other study site staff (except for the unmasked pharmacist), and patients were masked to pembrolizumab versus saline placebo administration. In addition, the sponsor, the investigators, other study site staff, and patients were masked to patient-level tumour PD-L1 biomarker results. Dual primary efficacy endpoints were progression-free survival and overall survival assessed in the PD-L1 CPS of 10 or more, CPS of 1 or more, and intention-to-treat populations. The definitive assessment of progression-free survival was done at this interim analysis; follow-up to assess overall survival is continuing. For progression-free survival, a hierarchical testing strategy was used, such that testing was done first in patients with CPS of 10 or more (prespecified statistical criterion was α=0·00411 at this interim analysis), then in patients with CPS of 1 or more (α=0·00111 at this interim analysis, with partial alpha from progression-free survival in patients with CPS of 10 or more passed over), and finally in the intention-to-treat population (α=0·00111 at this interim analysis). This study is registered with ClinicalTrials.gov, NCT02819518, and is ongoing.\n\nFindings: Between Jan 9, 2017, and June 12, 2018, of 1372 patients screened, 847 were randomly assigned to treatment, with 566 patients in the pembrolizumab-chemotherapy group and 281 patients in the placebo-chemotherapy group. At the second interim analysis (data cutoff, Dec 11, 2019), median follow-up was 25·9 months (IQR 22·8-29·9) in the pembrolizumab-chemotherapy group and 26·3 months (22·7-29·7) in the placebo-chemotherapy group. Among patients with CPS of 10 or more, median progression-free survival was 9·7 months with pembrolizumab-chemotherapy and 5·6 months with placebo-chemotherapy (hazard ratio [HR] for progression or death, 0·65, 95% CI 0·49-0·86; one-sided p=0·0012 [primary objective met]). Median progression-free survival was 7·6 and 5·6 months (HR, 0·74, 0·61-0·90; one-sided p=0·0014 [not significant]) among patients with CPS of 1 or more and 7·5 and 5·6 months (HR, 0·82, 0·69-0·97 [not tested]) among the intention-to-treat population. The pembrolizumab treatment effect increased with PD-L1 enrichment. Grade 3-5 treatment-related adverse event rates were 68% in the pembrolizumab-chemotherapy group and 67% in the placebo-chemotherapy group, including death in <1% in the pembrolizumab-chemotherapy group and 0% in the placebo-chemotherapy group.\n\nInterpretation: Pembrolizumab-chemotherapy showed a significant and clinically meaningful improvement in progression-free survival versus placebo-chemotherapy among patients with metastatic triple-negative breast cancer with CPS of 10 or more. These findings suggest a role for the addition of pembrolizumab to standard chemotherapy for the first-line treatment of metastatic triple-negative breast cancer.\n\nFunding: Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc.\n\nIndexed on Europe PMC as PubMed record 33278935 (DOI 10.1016/s0140-6736(20)32531-9). Its abstract cites the registry id NCT02819518, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet 2020","url":"https://doi.org/10.1016/s0140-6736(20)32531-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33278935/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33278935"},{"label":"ClinicalTrials.gov NCT02819518","url":"https://clinicaltrials.gov/study/NCT02819518"}],"tags":["europepmc-ingest"],"related":["pd-l1-cps"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["dako-pd-l1-22c3-pharmdx"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-355"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2020,"doi":"10.1016/s0140-6736(20)32531-9","pmid":"33278935","authors":"Cortes J, Cescon DW, Rugo HS, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02819518 with the most citations, so it is the natural first reading for anyone following the KEYNOTE-355 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-nct02861573-eur-urol-2022","kind":"paper","name":"Pembrolizumab Plus Docetaxel and Prednisone in Patients with Metastatic Castration-resistant Prostate Cancer: Long-term Results from the Phase 1b/2 KEYNOTE-365 Cohort B Study","aka":[],"tldr":"Published report from the KEYNOTE-365 trial registered as NCT02861573, in European Urology (2022), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Patients with metastatic castration-resistant prostate cancer (mCRPC) frequently receive docetaxel after they develop resistance to abiraterone or enzalutamide and need more efficacious treatments.\n\nObjective: To evaluate the efficacy and safety of pembrolizumab plus docetaxel and prednisone in patients with mCRPC.\n\nDesign, setting, and participants: The trial included patients with mCRPC in the phase 1b/2 KEYNOTE-365 cohort B study who were chemotherapy naïve and who experienced failure of or were intolerant to ≥4 wk of abiraterone or enzalutamide for mCRPC with progressive disease within 6 mo of screening.\n\nIntervention: Pembrolizumab 200 mg intravenously (IV) every 3 wk (Q3W), docetaxel 75 mg/m 2 IV Q3W, and prednisone 5 mg orally twice daily.\n\nOutcome measurements and statistical analysis: The primary endpoints were safety, the prostate-specific antigen (PSA) response rate, and the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by blinded independent central review (BICR). Secondary endpoints included time to PSA progression; the disease control rate (DCR) and duration of response (DOR) according to RECIST v1.1 by BICR; ORR, DCR, DOR, and radiographic progression-free survival (rPFS) according to Prostate Cancer Working Group 3-modified RECIST v1.1 by BICR; and overall survival (OS).\n\nResults and limitations: Among 104 treated patients, 52 had measurable disease. The median time from allocation to data cutoff (July 9, 2020) was 32.4 mo, during which 101 patients discontinued treatment, 81 (78%) for disease progression. The confirmed PSA response rate was 34% and the confirmed ORR (RECIST v1.1) was 23%. Median rPFS and OS were 8.5 mo and 20.2 mo, respectively. Treatment-related adverse events (TRAEs) occurred in 100 patients (96%). Grade 3-5 TRAEs occurred in 46 patients (44%). Seven AE-related deaths (6.7%) occurred (2 due to treatment-related pneumonitis). Limitations of the study include the single-arm design and small sample size.\n\nConclusions: Pembrolizumab plus docetaxel and prednisone demonstrated antitumor activity in chemotherapy-naïve patients with mCRPC treated with abiraterone or enzalutamide for mCRPC. Safety was consistent with profiles for the individual agents. Further investigation is warranted.\n\nPatient summary: We evaluated the efficacy and safety of the anti-PD-1 antibody pembrolizumab combined with the chemotherapy drug docetaxel and the steroid prednisone for patients with metastatic prostate cancer resistant to androgen deprivation therapy, and who never received chemotherapy. The combination showed antitumor activity and manageable safety in this patient population. This trial is registered on ClinicalTrials.gov as NCT02861573.\n\nIndexed on Europe PMC as PubMed record 35397952 (DOI 10.1016/j.eururo.2022.02.023). Its abstract cites the registry id NCT02861573, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Eur Urol 2022","url":"https://doi.org/10.1016/j.eururo.2022.02.023"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35397952/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35397952"},{"label":"ClinicalTrials.gov NCT02861573","url":"https://clinicaltrials.gov/study/NCT02861573"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct02861573"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["european-urology"],"dependsOn":[],"notes":[],"journal":"European Urology","year":2022,"doi":"10.1016/j.eururo.2022.02.023","pmid":"35397952","authors":"Yu EY, Kolinsky MP, Berry WR, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02861573 with the most citations, so it is the natural first reading for anyone following the KEYNOTE-365 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-keynote-177-lancet-oncol-2022-update","kind":"paper","name":"Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): final analysis of a randomised, open-label, phase 3 study","aka":[],"tldr":"Later report from the KEYNOTE-177 trial registered as NCT02563002, in The Lancet Oncology (2022); its title describes an updated or longer-term analysis.","summary":"Background: Pembrolizumab has shown improved progression-free survival versus chemotherapy in patients with newly diagnosed microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer. However, the treatment's effect on overall survival in this cohort of patients was unknown. Here, we present the final overall survival analysis of the KEYNOTE-177 study.\n\nMethods: This randomised, open-label, phase 3 study was done in 193 academic medical centres and hospitals in 23 countries. We recruited patients aged at least 18 years, with an Eastern Cooperative Oncology Group performance status of 0 or 1, and who had previously untreated microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer. Patients were randomly assigned (1:1) in blocks of four using an interactive voice response system or integrated web response system to intravenous pembrolizumab 200 mg every 3 weeks or to the investigator's choice of intravenous mFOLFOX6 (oxaliplatin 85 mg/m 2 on day 1, leucovorin 400 mg/m 2 on day 1, and fluorouracil 400 mg/m 2 bolus on day 1 followed by a continuous infusion of 1200 mg/m 2 per day for 2 days on days 1-2) or intravenous FOLFIRI (irinotecan 180 mg/m 2 on day 1, leucovorin 400 mg/m 2 on day 1, and fluorouracil 400 mg/m 2 bolus on day 1 followed by a continuous infusion of 1200 mg/m 2 per day for 2 days on days 1-2), every 2 weeks with or without intravenous bevacizumab 5 mg/kg every 2 weeks or intravenous weekly cetuximab (first dose 400 mg/m 2, then 250 mg/m 2 for every subsequent dose). Patients receiving chemotherapy could cross over to pembrolizumab for up to 35 treatment cycles after progression. The co-primary endpoints were overall survival and progression-free survival in the intention-to-treat population. KEYNOTE-177 is registered at ClinicalTrials.gov, NCT02563002, and is no longer enrolling patients.\n\nFindings: Between Feb 11, 2016, and Feb 19, 2018, 852 patients were screened, of whom 307 (36%) were randomly assigned to pembrolizumab (n=153) or chemotherapy (n=154). 93 (60%) patients crossed over from chemotherapy to anti-PD-1 or anti-PD-L1 therapy (56 patients to on-study pembrolizumab and 37 patients to off-study therapy). At final analysis (median follow-up of 44·5 months [IQR 39·7-49·8]), median overall survival was not reached (NR; 95% CI 49·2-NR) with pembrolizumab vs 36·7 months (27·6-NR) with chemotherapy (hazard ratio [HR] 0·74; 95% CI 0·53-1·03; p=0·036). Superiority of pembrolizumab versus chemotherapy for overall survival was not demonstrated because the prespecified α of 0·025 needed for statistical significance was not achieved. At this updated analysis, median progression-free survival was 16·5 months (95% CI 5·4-38·1) with pembrolizumab versus 8·2 months (6·1-10·2) with chemotherapy (HR 0·59, 95% CI 0·45-0·79). Treatment-related adverse events of grade 3 or worse occurred in 33 (22%) of 153 patients in the pembrolizumab group versus 95 (66%) of 143 patients in the chemotherapy group. Common adverse events of grade 3 or worse that were attributed to pembrolizumab were increased alanine aminotransferase, colitis, diarrhoea, and fatigue in three (2%) patients each, and those attributed to chemotherapy were decreased neutrophil count (in 24 [17%] patients), neutropenia (22 [15%]), diarrhoea (14 [10%]), and fatigue (13 [9%]). Serious adverse events attributed to study treatment occurred in 25 (16%) patients in the pembrolizumab group and in 41 (29%) patients in the chemotherapy group. No deaths attributed to pembrolizumab occurred; one death due to intestinal perforation was attributed to chemotherapy.\n\nInterpretation: In this updated analysis, although pembrolizumab continued to show durable antitumour activity and fewer treatment-related adverse events compared with chemotherapy, there was no significant difference in overall survival between the two treatment groups. These findings support pembrolizumab as an efficacious first-line therapy in patients with microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer.\n\nFunding: MSD.\n\nIndexed on Europe PMC as PubMed record 35427471 (DOI 10.1016/s1470-2045(22)00197-8). Its abstract cites the registry id NCT02563002, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2022","url":"https://doi.org/10.1016/s1470-2045(22)00197-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35427471/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35427471"},{"label":"ClinicalTrials.gov NCT02563002","url":"https://clinicaltrials.gov/study/NCT02563002"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-177"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2022,"doi":"10.1016/s1470-2045(22)00197-8","pmid":"35427471","authors":"Diaz LA, Shiu KK, Kim TW, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the KEYNOTE-177 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-keynote-042-lancet-2019","kind":"paper","name":"Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial","aka":[],"tldr":"Published report from the KEYNOTE-042 trial registered as NCT02220894, in The Lancet (2019), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: First-line pembrolizumab monotherapy improves overall and progression-free survival in patients with untreated metastatic non-small-cell lung cancer with a programmed death ligand 1 (PD-L1) tumour proportion score (TPS) of 50% or greater. We investigated overall survival after treatment with pembrolizumab monotherapy in patients with a PD-L1 TPS of 1% or greater.\n\nMethods: This randomised, open-label, phase 3 study was done in 213 medical centres in 32 countries. Eligible patients were adults (≥18 years) with previously untreated locally advanced or metastatic non-small-cell lung cancer without a sensitising EGFR mutation or ALK translocation and with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, life expectancy 3 months or longer, and a PD-L1 TPS of 1% or greater. Randomisation was computer generated, accessed via an interactive voice-response and integrated web-response system, and stratified by region of enrolment (east Asia vs rest of world), ECOG performance status score (0 vs 1), histology (squamous vs non-squamous), and PD-L1 TPS (≥50% vs 1-49%). Enrolled patients were randomly assigned 1:1 in blocks of four per stratum to receive pembrolizumab 200 mg every 3 weeks for up to 35 cycles or the investigator's choice of platinum-based chemotherapy for four to six cycles. Primary endpoints were overall survival in patients with a TPS of 50% or greater, 20% or greater, and 1% or greater (one-sided significance thresholds, p=0·0122, p=0·0120, and p=0·0124, respectively) in the intention-to-treat population, assessed sequentially if the previous findings were significant. This study is registered at ClinicalTrials.gov, number NCT02220894.\n\nFindings: From Dec 19, 2014, to March 6, 2017, 1274 patients (902 men, 372 women, median age 63 years [IQR 57-69]) with a PD-L1 TPS of 1% or greater were allocated to pembrolizumab (n=637) or chemotherapy (n=637) and included in the intention-to-treat population. 599 (47%) had a TPS of 50% or greater and 818 patients (64%) had a TPS of 20% or greater. at Feb 26, 2018, median follow-up was 12·8 months. Overall survival was significantly longer in the pembrolizumab group than in the chemotherapy group in all three TPS populations (≥50% hazard ratio 0·69, 95% CI 0·56-0·85, p=0·0003; ≥20% 0·77, 0·64-0·92, p=0·0020, and ≥1% 0·81, 0·71-0·93, p=0·0018). The median surival values by TPS population were 20·0 months (95% CI 15·4-24·9) for pembrolizumab versus 12·2 months (10·4-14·2) for chemotherapy, 17·7 months (15·3-22·1) versus 13·0 months (11·6-15·3), and 16·7 months (13·9-19·7) versus 12·1 months (11·3-13·3), respectively. Treatment-related adverse events of grade 3 or worse occurred in 113 (18%) of 636 treated patients in the pembrolizumab group and in 252 (41%) of 615 in the chemotherapy group and led to death in 13 (2%) and 14 (2%) patients, respectively.\n\nInterpretation: The benefit-to-risk profile suggests that pembrolizumab monotherapy can be extended as first-line therapy to patients with locally advanced or metastatic non-small-cell lung cancer without sensitising EGFR or ALK alterations and with low PD-L1 TPS.\n\nFunding: Merck Sharp & Dohme.\n\nIndexed on Europe PMC as PubMed record 30955977 (DOI 10.1016/s0140-6736(18)32409-7). Its abstract cites the registry id NCT02220894, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet 2019","url":"https://doi.org/10.1016/s0140-6736(18)32409-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30955977/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30955977"},{"label":"ClinicalTrials.gov NCT02220894","url":"https://clinicaltrials.gov/study/NCT02220894"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-042"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2019,"doi":"10.1016/s0140-6736(18)32409-7","pmid":"30955977","authors":"Mok TSK, Wu YL, Kudaba I, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02220894 with the most citations, so it is the natural first reading for anyone following the KEYNOTE-042 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-jean-pascal-machiels-lancet-2019","kind":"paper","name":"Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study","aka":[],"tldr":"Paper by Jean-Pascal Machiels indexed on Europe PMC as PubMed record 30509740, in The Lancet (2019), one of the most cited records naming an author with this name at King Albert II Cancer Institute, Cliniques universitaires Saint-Luc.","summary":"Background: There are few effective treatment options for patients with recurrent or metastatic head-and-neck squamous cell carcinoma. Pembrolizumab showed antitumour activity and manageable toxicity in early-phase trials. We aimed to compare the efficacy and safety of pembrolizumab versus standard-of-care therapy for the treatment of head-and-neck squamous cell carcinoma.\n\nMethods: We did a randomised, open-label, phase 3 study at 97 medical centres in 20 countries. Patients with head-and-neck squamous cell carcinoma that progressed during or after platinum-containing treatment for recurrent or metastatic disease (or both), or whose disease recurred or progressed within 3-6 months of previous multimodal therapy containing platinum for locally advanced disease, were randomly assigned (1:1) in blocks of four per stratum with an interactive voice-response and integrated web-response system to receive pembrolizumab 200 mg every 3 weeks intravenously or investigator's choice of standard doses of methotrexate, docetaxel, or cetuximab intravenously (standard-of-care group). The primary endpoint was overall survival in the intention-to-treat population. Safety was analysed in the as-treated population. This trial is registered with ClinicalTrials.gov, number NCT02252042, and is no longer enrolling patients.\n\nFindings: Between Dec 24, 2014, and May 13, 2016, 247 patients were randomly allocated to pembrolizumab and 248 were randomly allocated to standard of care. at May 15, 2017, 181 (73%) of 247 patients in the pembrolizumab group and 207 (83%) of 248 patients in the standard-of-care group had died. Median overall survival in the intention-to-treat population was 8·4 months (95% CI 6·4-9·4) with pembrolizumab and 6·9 months (5·9-8·0) with standard of care (hazard ratio 0·80, 0·65-0·98; nominal p=0·0161). Fewer patients treated with pembrolizumab than with standard of care had grade 3 or worse treatment-related adverse events (33 [13%] of 246 vs 85 [36%] of 234). The most common treatment-related adverse event was hypothyroidism with pembrolizumab (in 33 [13%] patients) and fatigue with standard of care (in 43 [18%]). Treatment-related death occurred in four patients treated with pembrolizumab (unspecified cause, large intestine perforation, malignant neoplasm progression, and Stevens-Johnson syndrome) and two patients treated with standard of care (malignant neoplasm progression and pneumonia).\n\nInterpretation: The clinically meaningful prolongation of overall survival and favourable safety profile of pembrolizumab in patients with recurrent or metastatic head and neck squamous cell carcinoma support the further evaluation of pembrolizumab as a monotherapy and as part of combination therapy in earlier stages of disease.\n\nFunding: Merck Sharp & Dohme, a subsidiary of Merck & Co.\n\nIndexed on Europe PMC as PubMed record 30509740 (DOI 10.1016/s0140-6736(18)31999-8). Its author list gives \"Machiels JP\" with the affiliation \"Cliniques Universitaires Saint-Luc, Brussels, Belgium; Université Catholique de Louvain, Louvain-la-Neuve, Belgium\", which names King Albert II Cancer Institute, Cliniques universitaires Saint-Luc; that is how the record was matched to Jean-Pascal Machiels, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet 2019","url":"https://doi.org/10.1016/s0140-6736(18)31999-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30509740/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30509740"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["jean-pascal-machiels"],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2019,"doi":"10.1016/s0140-6736(18)31999-8","pmid":"30509740","authors":"Cohen EEW, Soulières D, Le Tourneau C, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Jean-Pascal Machiels at King Albert II Cancer Institute, Cliniques universitaires Saint-Luc, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-keynote-716-lancet-oncol-2022-update","kind":"paper","name":"Pembrolizumab versus placebo as adjuvant therapy in resected stage IIB or IIC melanoma (KEYNOTE-716): distant metastasis-free survival results of a multicentre, double-blind, randomised, phase 3 trial","aka":[],"tldr":"Later report from the KEYNOTE-716 trial registered as NCT03553836, in The Lancet Oncology (2022); its title describes an updated or longer-term analysis.","summary":"Background: Patients with stage IIB or IIC melanoma who undergo surgery alone are at a substantial risk for disease recurrence. Adjuvant pembrolizumab significantly improved recurrence-free survival versus placebo in stage IIB or IIC melanoma in the first interim analysis of the KEYNOTE-716 trial. Here, we report results from the secondary endpoint of distant metastasis-free survival (prespecified third interim analysis), and recurrence-free survival with longer follow-up.\n\nMethods: KEYNOTE-716 is a multicentre, double-blind, placebo-controlled, crossover or rechallenge, randomised, phase 3 trial done at 160 academic medical centres and hospitals across 16 countries. Eligible patients were aged 12 years and older with newly-diagnosed, completely resected, and histologically confirmed stage IIB (T3b or T4a) or IIC (T4b) cutaneous melanoma; negative sentinel lymph node biopsy; and an Eastern Cooperative Oncology Group performance status of 0-1. Patients were randomly assigned (1:1) to receive either 200 mg of pembrolizumab (2 mg/kg up to a maximum of 200 mg in paediatric patients) or placebo, both intravenously, every 3 weeks for 17 cycles (part 1) or until disease recurrence or unacceptable toxicity. Eligible patients with disease recurrence could receive further treatment with pembrolizumab in the part 2 crossover or rechallenge phase. Randomisation was done using an interactive response technology system and stratified by T category and paediatric status. The primary endpoint was investigator-assessed recurrence-free survival (assessed here with longer follow-up), and we report the prespecified third interim analysis of distant metastasis-free survival (secondary endpoint). Efficacy analyses were done in the intention-to-treat population (all patients who were randomly assigned, according to assigned group) and safety was assessed in all patients who were randomly assigned and received at least one dose of trial treatment, according to the treatment received. KEYNOTE-716 is registered at ClinicalTrials.gov, NCT03553836, and has completed recruitment.\n\nFindings: Between Sept 23, 2018, and Nov 4, 2020, 976 patients were randomly assigned to receive pembrolizumab (n=487) or placebo (n=489). At a median follow-up of 27·4 months (IQR 23·1-31·7), median distant metastasis-free survival was not reached (95% CI not reached [NR]-NR) in either group. Pembrolizumab significantly improved distant metastasis-free survival (hazard ratio [HR] 0·64, 95% CI 0·47-0·88, p=0·0029) versus placebo. Median recurrence-free survival was 37·2 months (95% CI NR-NR) in the pembrolizumab group and not reached in the placebo group (95% CI NR-NR). The risk of recurrence remained lower with pembrolizumab versus placebo (HR 0·64, 95% CI 0·50-0·84). The most common grade 3 or worse adverse events were hypertension (16 [3%] of 483 patients in the pembrolizumab group vs 17 [4%] of 486 patients in the placebo group), diarrhoea (eight [2%] vs one [<1%]), rash (seven [1%] vs two [<1%]), autoimmune hepatitis (seven [1%] vs two [<1%]), and increased lipase (six [1%] vs eight [2%]). Treatment-related serious adverse events occurred in 49 (10%) patients in the pembrolizumab group and 11 (2%) patients in the placebo group. No treatment-related deaths were reported.\n\nInterpretation: Adjuvant pembrolizumab is an efficacious treatment option for resected stage IIB and IIC melanoma, with significant improvement in distant-metastasis free survival versus placebo and continued reduction in the risk of recurrence with an adverse event profile consistent with previous studies of pembrolizumab. The overall benefit-risk of pembrolizumab continues to be positive in the adjuvant setting.\n\nFunding: Merck Sharp & Dohme, a subsidiary of Merck & Co.\n\nIndexed on Europe PMC as PubMed record 36265502 (DOI 10.1016/s1470-2045(22)00559-9). Its abstract cites the registry id NCT03553836, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2022","url":"https://doi.org/10.1016/s1470-2045(22)00559-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36265502/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36265502"},{"label":"ClinicalTrials.gov NCT03553836","url":"https://clinicaltrials.gov/study/NCT03553836"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-716"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2022,"doi":"10.1016/s1470-2045(22)00559-9","pmid":"36265502","authors":"Long GV, Luke JJ, Khattak MA, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the KEYNOTE-716 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-cooper-chem-soc-rev","kind":"paper","name":"Peptides as a platform for targeted therapeutics for cancer: peptide-drug conjugates (PDCs)","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 33346298 and published in Chemical Society reviews; the citing page links this DOI, which is how the record was matched.","summary":"Peptides can offer the versatility needed for a successful oncology drug discovery approach. Peptide-drug conjugates (PDCs) are an emerging targeted therapeutic that present increased tumour penetration and selectivity. Despite these advantages, there are still limitations for the use of peptides as therapeutics exemplified through their slow progression to get into the clinic and limited oral bioavailability. New approaches to address these problems have been studied and successfully implemented to enhance the stability of peptides and their constructs. There is great promise for the future of PDCs with two molecules already on the market and many variations currently undergoing clinical trials, such as bicycle-toxin conjugates and peptide-dendrimer conjugates. This review summarises the entire process needed for the design and successful development of an oncology PDC including chemical and nanomaterial strategies to enhance peptide stability within circulation, the function of each component of a PDC construct, and current examples in clinical trials.\n\nIndexed on Europe PMC as PubMed record 33346298 (DOI 10.1039/d0cs00556h). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Chem Soc Rev 2021","url":"https://doi.org/10.1039/d0cs00556h"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33346298/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33346298"}],"tags":["europepmc-ingest"],"related":["peptide-drug-conjugate"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Chemical Society reviews","year":2021,"doi":"10.1039/d0cs00556h","pmid":"33346298","authors":"Cooper BM, Iegre J, O' Donovan DH, et al.","paperType":"review","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-patel-jama-surg","kind":"paper","name":"Performance of a Genomic Sequencing Classifier for the Preoperative Diagnosis of Cytologically Indeterminate Thyroid Nodules","aka":[],"tldr":"Paper cited by one treatment page, indexed on Europe PMC as PubMed record 29799911 and published in JAMA surgery; the citing page links this DOI, which is how the record was matched.","summary":"Importance: Use of next-generation sequencing of RNA and machine learning algorithms can classify the risk of malignancy in cytologically indeterminate thyroid nodules to limit unnecessary diagnostic surgery.\n\nObjective: To measure the performance of a genomic sequencing classifier for cytologically indeterminate thyroid nodules.\n\nDesign, setting, and participants: A blinded validation study was conducted on a set of cytologically indeterminate thyroid nodules collected by fine-needle aspiration biopsy between June 2009 and December 2010 from 49 academic and community centers in the United States. All patients underwent surgery without genomic information and were assigned a histopathology diagnosis by an expert panel blinded to all genomic information. There were 210 potentially eligible thyroid biopsy samples with Bethesda III or IV indeterminate cytopathology that constituted a cohort previously used to validate the gene expression classifier. Of these, 191 samples (91.0%) had adequate residual RNA for validation of the genomic sequencing classifier. Algorithm development and independent validation occurred between August 2016 and May 2017.\n\nExposures: Thyroid nodule surgical histopathology diagnosis by an expert panel blinded to all genomic data.\n\nMain outcomes and measures: The primary end point was measurement of genomic sequencing classifier sensitivity, specificity, and negative and positive predictive values in biopsies from Bethesda III and IV nodules. The secondary end point was measurement of classifier performance in biopsies from Bethesda II, V, and VI nodules.\n\nResults: Of the 183 included patients, 142 (77.6%) were women, and the mean (range) age was 51.7 (22.0-85.0) years. The genomic sequencing classifier had a sensitivity of 91% (95% CI, 79-98) and a specificity of 68% (95% CI, 60-76). At 24% cancer prevalence, the negative predictive value was 96% (95% CI, 90-99) and the positive predictive value was 47% (95% CI, 36-58).\n\nConclusions and relevance: The genomic sequencing classifier demonstrates high sensitivity and accuracy for identifying benign nodules. Its 36% increase in specificity compared with the gene expression classifier potentially increases the number of patients with benign nodules who can safely avoid unnecessary diagnostic surgery.\n\nIndexed on Europe PMC as PubMed record 29799911 (DOI 10.1001/jamasurg.2018.1153). Matched by DOI alone: one treatment page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA Surg 2018","url":"https://doi.org/10.1001/jamasurg.2018.1153"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29799911/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29799911"}],"tags":["europepmc-ingest"],"related":["afirma"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"JAMA surgery","year":2018,"doi":"10.1001/jamasurg.2018.1153","pmid":"29799911","authors":"Patel KN, Angell TE, Babiarz J, et al.","paperType":"observational","findings":[],"whatItMeans":"One treatment page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nhs-galleri-performance-nat-med-2026","kind":"paper","name":"Performance of a multi-cancer early detection test in the randomized controlled NHS-Galleri trial","aka":[],"tldr":"In the NHS-Galleri trial about one person in a hundred had a positive blood test in each of three yearly rounds, roughly half of those positives were cancer, and the test missed most cancers diagnosed during the trial. The paper says the main endpoint, fewer late-stage diagnoses, was not met and is reported elsewhere.","summary":"Prespecified secondary test-performance analysis of NHS-Galleri, the randomised controlled trial of GRAIL's Galleri multi-cancer early detection (MCED) test added to usual NHS care. Participants aged 50 to 77 (N = 142,250) were randomised 1:1 to the MCED test or control; intervention-arm participants with a positive result were referred to NHS standard-of-care diagnostic pathways, with referrals informed by the predicted cancer signal origin. The analyses were descriptive, with no hypothesis testing. The abstract states that the primary endpoint, a reduction in the incidence of stage III/IV cancer diagnoses in the intervention arm versus the control arm, was not met and was reported elsewhere.\n\nPositive results were returned for 722 of 70,325 (1.03 percent), 518 of 64,498 (0.80 percent) and 561 of 62,323 (0.90 percent) participants in rounds 1 to 3. In aggregate 937 participants had MCED-detected primary cancers. By-round cancer detection rates were 0.60, 0.40 and 0.41 percent; positive predictive values 58.0 percent (419/722), 50.4 percent (261/518) and 45.8 percent (257/561); negative predictive values 98.98 percent (68,895/69,603), 98.90 percent (63,278/63,980) and 98.86 percent (61,058/61,762). Across rounds, specificity ranged from 99.50 to 99.60 percent, episode sensitivity from 26.7 to 37.2 percent for all cancers and from 47.6 to 63.4 percent for 12 prespecified cancer types, and cancer signal origin accuracy from 91.1 to 93.6 percent. The 12 prespecified types are named on the ClinicalTrials.gov record (NCT05611632): lung, head and neck, colorectal, pancreas, myeloma or plasma cell neoplasm, liver or bile duct, stomach, oesophagus, anus, lymphoma, ovary and bladder.","asOf":"2026-09-23","links":[{"label":"Nature Medicine 2026","url":"https://doi.org/10.1038/s41591-026-04652-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42773209/"},{"label":"ClinicalTrials.gov NCT05611632","url":"https://clinicaltrials.gov/study/NCT05611632"},{"label":"ISRCTN91431511","url":"https://www.isrctn.com/ISRCTN91431511"}],"tags":[],"related":["paper-nhs-galleri-design-cancers-2022","paper-pathfinder-lancet-2023","ctdna-tests"],"cancers":["lung-cancer","head-and-neck","colorectal","pancreatic","multiple-myeloma","hcc","cholangiocarcinoma","gastric","esophageal","anal","hodgkin-lymphoma","non-hodgkin-lymphoma","ovarian","urothelial"],"sections":["early-detection"],"technologies":["mced","cfdna-methylation-testing","methylation-profiling","liquid-biopsy"],"targets":[],"drugs":["galleri"],"companies":["grail"],"institutions":[],"pathways":[],"terms":["ppv","stage-shift","screening","sensitivity-specificity"],"trials":["nhs-galleri"],"people":["peter-sasieni","charles-swanton","peter-johnson"],"bottlenecks":["b-early-detection","b-overdiagnosis"],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2026,"doi":"10.1038/s41591-026-04652-8","pmid":"42773209","authors":"Neal RD, Dolly S, Johnson P, et al.","paperType":"rct","findings":["Positive test results in 722 of 70,325 (1.03 percent), 518 of 64,498 (0.80 percent) and 561 of 62,323 (0.90 percent) intervention-arm participants in rounds 1 to 3; 937 participants had MCED-detected primary cancers in aggregate.","Cancer detection rates 0.60, 0.40 and 0.41 percent by round; positive predictive values 58.0 percent (419/722), 50.4 percent (261/518) and 45.8 percent (257/561).","Negative predictive values 98.98, 98.90 and 98.86 percent; specificity 99.50 to 99.60 percent across rounds.","Episode sensitivity 26.7 to 37.2 percent for all cancers and 47.6 to 63.4 percent for the 12 prespecified cancer types; cancer signal origin accuracy 91.1 to 93.6 percent.","The primary endpoint, a reduction in stage III/IV cancer incidence in the intervention arm versus control, was not met and is reported elsewhere (the abstract's words; no figures are given in this paper)."],"whatItMeans":"For someone offered the test, these are the numbers that describe what a result means in an NHS population: about 1 in 100 tests came back positive each year, between 46 and 58 in 100 positives were cancer, and a negative result left about 1 in 100 with an undetected cancer within the year. The test found between a quarter and a third of all cancers diagnosed in a screening round, and about half to two thirds of the 12 cancer types it was designed to find. Whether finding them this way reduces late-stage diagnoses is the primary question, and this paper says only that the answer was no; the primary-endpoint paper had not appeared on Europe PMC by 23 September 2026.","caveats":["Descriptive secondary endpoints in the intervention arm only; the abstract states there was no hypothesis testing.","The primary endpoint was not met and is reported elsewhere; this paper gives no stage III/IV, stage IV or mortality figures.","Performance is for one commercial assay in one health system over three annual rounds; the denominators fall from 70,325 to 62,323 across rounds as participants left the screened population.","Episode sensitivity and specificity are quoted as ranges across rounds in the abstract; per-round values are not transcribed here."],"changedPractice":false,"participants":142250},{"id":"paper-impassion031-nat-med-2025-update","kind":"paper","name":"Peri-operative atezolizumab in early-stage triple-negative breast cancer: final results and ctDNA analyses from the randomized phase 3 IMpassion031 trial","aka":[],"tldr":"Later report from the IMpassion031 trial registered as NCT03197935, in Nature Medicine (2025); its title describes an updated or longer-term analysis.","summary":"Previously published results demonstrated that the randomized phase 3 IMpassion031 trial met its primary objective: adding atezolizumab to neoadjuvant chemotherapy significantly improved pathologic complete response (pCR) rate in patients with stage II/III triple-negative breast cancer (TNBC). Here we report the prespecified final analysis of the secondary endpoints with 3 years' follow-up, together with exploratory analyses of circulating tumor (ct)DNA. Patients with previously untreated stage II/III TNBC enrolled in 75 academic and community sites in 13 countries were randomized 1:1 to receive neoadjuvant chemotherapy with either peri-operative atezolizumab (n = 165) or preoperative placebo (n = 168). Descriptive secondary endpoints included event-free, disease-free and overall survival. Long-term outcomes favored the atezolizumab group (event-free survival hazard ratio (HR), 0.76; 95% confidence interval (CI), 0.47-1.21; disease-free survival HR, 0.76; 95% CI, 0.44-1.30; overall survival HR, 0.56; 95% CI, 0.30-1.04). Among patients without pCR, 14 of 70 (20%) atezolizumab-treated and 33 of 99 (33%) placebo-treated patients received additional adjuvant therapy, frequently capecitabine. In exploratory biomarker analyses, patients with baseline ctDNA-negative status (6%) had excellent long-term outcomes. Most patients (87%) had cleared ctDNA at surgery. ctDNA-positive status at surgery identified a subset of non-pCR patients with poorest prognosis. Long-term safety was consistent with primary results. These data show that adding atezolizumab to chemotherapy for stage II/III TNBC is associated with favorable long-term outcomes, and ctDNA dynamics provide prognostic value beyond pCR. ClinicalTrials.gov identifier: NCT03197935.\n\nIndexed on Europe PMC as PubMed record 40467898 (DOI 10.1038/s41591-025-03725-4). Its abstract cites the registry id NCT03197935, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Nat Med 2025","url":"https://doi.org/10.1038/s41591-025-03725-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40467898/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40467898"},{"label":"ClinicalTrials.gov NCT03197935","url":"https://clinicaltrials.gov/study/NCT03197935"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["impassion031"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2025,"doi":"10.1038/s41591-025-03725-4","pmid":"40467898","authors":"Mittendorf EA, Assaf ZJ, Harbeck N, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the IMpassion031 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-nct03767244-n-engl-j-med-2026","kind":"paper","name":"Perioperative Apalutamide in High-Risk Localized Prostate Cancer","aka":[],"tldr":"Published report from the PROTEUS trial registered as NCT03767244, in New England Journal of Medicine (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Radical prostatectomy is potentially curative in patients with high-risk localized or locally advanced prostate cancer; however, relapse occurs within 5 years in up to 50% of patients.\n\nMethods: We conducted a phase 3, double-blind, placebo-controlled trial in which patients with newly diagnosed high-risk localized or locally advanced prostate cancer were randomly assigned in a 1:1 ratio to receive androgen-deprivation therapy (ADT) plus apalutamide (240 mg per day) or ADT plus placebo for 6 cycles (28 days each) before and after radical prostatectomy with pelvic lymph-node dissection. The dual primary end points were a composite of pathological complete response or minimal residual disease (defined as a pathological stage of ypT2 or lower, with a tumor size of ≤5 mm in the greatest dimension) and metastasis-free survival, as assessed with conventional imaging or prostate-specific membrane antigen positron-emission tomography. Secondary end points included event-free survival, first subsequent treatment, and distant metastasis (assessed in time-to-event analyses), as well as safety.\n\nResults: A total of 2109 patients underwent randomization: 1057 were assigned to receive ADT plus apalutamide, and 1052 to receive ADT plus placebo. The median follow-up was 61.7 months. The percentage of patients with a pathological complete response or minimal residual disease was significantly higher in the apalutamide group than in the placebo group (8.9% vs. 1.0%; odds ratio, 10.17; 95% confidence interval [CI], 5.27 to 19.64; P<0.001), as was the percentage of patients with metastasis-free survival (probability of metastasis-free survival at 5 years, 78.2% vs. 73.5%; hazard ratio for distant metastasis or death, 0.80; 95% CI, 0.67 to 0.96; P = 0.02). Event-free survival, time to the first subsequent treatment, and time to distant metastasis significantly favored ADT plus apalutamide over ADT plus placebo (P<0.001 for all between-group comparisons). Grade 3 or 4 adverse events occurred in 39.6% of the patients in the apalutamide group and in 31.0% of those in the placebo group, with the difference between the groups driven primarily by a higher incidence of rash in the apalutamide group.\n\nConclusions: Perioperative treatment with ADT plus apalutamide was associated with better oncologic outcomes of radical prostatectomy in patients with high-risk localized or locally advanced prostate cancer than treatment with ADT plus placebo. Adverse events were more common in the apalutamide group than in the placebo group. (Funded by Johnson & Johnson; PROTEUS ClinicalTrials.gov number, NCT03767244.).\n\nIndexed on Europe PMC as PubMed record 42223077 (DOI 10.1056/nejmoa2603878). Its abstract cites the registry id NCT03767244, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2026","url":"https://doi.org/10.1056/nejmoa2603878"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42223077/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42223077"},{"label":"ClinicalTrials.gov NCT03767244","url":"https://clinicaltrials.gov/study/NCT03767244"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct03767244"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2026,"doi":"10.1056/nejmoa2603878","pmid":"42223077","authors":"Taplin ME, Gleave M, Shore ND, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03767244 with the most citations, so it is the natural first reading for anyone following the PROTEUS trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-heymach-aegean-perioperative-durvalumab-nejm-2023","kind":"paper","name":"Perioperative durvalumab for resectable non-small-cell lung cancer","aka":[],"tldr":"Giving immunotherapy both before and after lung cancer surgery cut the risk of recurrence by about a third, and left 17.2 percent of tumours with no viable cancer at all in the specimen.","summary":"The AEGEAN investigators, reported by Heymach, Harpole, Mitsudomi and colleagues, randomised 802 patients with resectable stage II to IIIB (N2) non-small-cell lung cancer to platinum chemotherapy with durvalumab or placebo for four cycles before surgery, followed by durvalumab or placebo every four weeks for twelve cycles afterwards. Patients with EGFR or ALK alterations were excluded from the efficacy analyses.\n\nAEGEAN, KEYNOTE-671 and CheckMate 77T all give immunotherapy on both sides of the operation, and CheckMate 816 gives it only before. None of them has been compared against the others, so which of the four schedules is best remains the largest unanswered question in early-stage lung cancer.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2023","url":"https://doi.org/10.1056/NEJMoa2304875"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37870974/"},{"label":"Updated outcomes, J Clin Oncol 2026","url":"https://doi.org/10.1200/JCO-25-02659"},{"label":"ClinicalTrials.gov NCT03800134","url":"https://clinicaltrials.gov/study/NCT03800134"},{"label":"N Engl J Med 2023","url":"https://doi.org/10.1056/nejmoa2304875"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37870974"}],"tags":["lung-evidence"],"related":["paper-checkmate-816-nejm-2022","paper-keynote-671-n-engl-j-med-2023","paper-felip-impower010-adjuvant-atezolizumab-lancet-2021"],"cancers":["lung-cancer","nsclc","resectable-nsclc"],"sections":["immunotherapy","surgery"],"technologies":["checkpoint-inhibitor"],"targets":["pd1"],"drugs":["durvalumab","cisplatin","carboplatin"],"companies":["astrazeneca"],"institutions":[],"pathways":["immune-checkpoint"],"terms":["neoadjuvant-adjuvant","pdl1"],"trials":["nct03800134"],"people":["john-heymach","martin-reck"],"bottlenecks":["b-immunotherapy-response","b-dormancy-mrd","b-trial-design"],"keyPapers":[],"journals":["nejm","jco"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/NEJMoa2304875","pmid":"37870974","authors":"Heymach JV, Harpole D, Mitsudomi T, et al.","paperType":"rct","findings":["Event-free survival was significantly longer with durvalumab: stratified hazard ratio for disease progression, recurrence or death 0.68 (95 percent confidence interval 0.53 to 0.88; P equals 0.004) at the first interim analysis.","At the 12-month landmark, event-free survival was 73.4 percent with durvalumab (67.9 to 78.1) against 64.5 percent with placebo (58.8 to 69.6).","Pathological complete response 17.2 percent against 4.3 percent at the final analysis: difference 13.0 percentage points (8.7 to 17.6).","802 patients were randomised, 400 to durvalumab and 402 to placebo.","In the 2026 updated report (median follow-up 25.9 months) the event-free survival hazard ratio remained 0.69 (0.55 to 0.88), with disease-free survival 0.66 (0.47 to 0.92) and overall survival 0.89 (0.70 to 1.14)."],"whatItMeans":"Perioperative immunotherapy is now standard for resectable lung cancer without a targetable driver. The updated overall survival hazard ratio of 0.89, with a confidence interval crossing one, is the honest state of the evidence on whether it cures more people.","caveats":["Event-free survival and pathological complete response are the endpoints; overall survival remains numerically favourable but not significant in the updated analysis.","Patients with EGFR or ALK alterations were excluded from efficacy analyses, and those patients are now treated with targeted adjuvant therapy instead.","Adjuvant durvalumab is given to everybody, including patients already cured by surgery and chemotherapy, and the contribution of the adjuvant half of the regimen has never been isolated."],"changedPractice":true,"participants":802},{"id":"paper-nct05061550-nat-med-2025","kind":"paper","name":"Perioperative durvalumab plus chemotherapy plus new agents for resectable non-small-cell lung cancer: the platform phase 2 NeoCOAST-2 trial","aka":[],"tldr":"Published report from the NeoCOAST-2 trial registered as NCT05061550, in Nature Medicine (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"In the phase II NeoCOAST-2 platform study, 202 patients with untreated, resectable stage IIA-IIIB non-small-cell lung cancer (NSCLC) were randomized to receive neoadjuvant durvalumab plus platinum-doublet chemotherapy with oleclumab, a CD73 inhibitor (Arm 1), or with monalizumab, a NKG2A inhibitor (Arm 2), or neoadjuvant durvalumab plus single-agent platinum chemotherapy with the TROP-2 antibody-drug conjugate (ADC) datopotamab deruxtecan (Arm 4), followed by surgical resection and adjuvant durvalumab with oleclumab or monalizumab (Arms 1 and 2) or durvalumab alone (Arm 4). Primary endpoints were pathological complete response (pCR) rate and safety; secondary endpoints included feasibility of surgery and major pathological response (mPR) rate. In the modified intention-to-treat population (n = 198; Arm 1, n = 74; Arm 2, n = 70; Arm 4, n = 54), pCR rates were 20.3% (15/74; 95% CI, 11.8-31.2), 25.7% (18/70; 95% CI, 16.0-37.6) and 35.2% (19/54; 95% CI, 22.7-49.4), and mPR rates were 41.9% (31/74; 95% CI, 30.5-53.9), 50.0% (35/70; 95% CI, 37.8-62.2) and 63.0% (34/54; 95% CI, 48.7-75.7) in arms 1, 2, and 4, respectively. In the safety population, 69/74 (93.2%), 66/71 (93.0%), and 51/54 (94.4%) patients underwent surgery, respectively. Overall, grade ≥3 treatment-related adverse events occurred in 27/74 (36.5%), 29/71 (40.8%) and 11/54 (20.4%) patients, respectively. In NeoCOAST-2, the first neoadjuvant trial examining an ADC plus chemo-immunotherapy in resectable NSCLC, pCR rates were highest in the datopotamab-deruxtecan-containing arm, warranting further investigation in larger trials of ADCs and checkpoint inhibition in the neoadjuvant setting. ClinicalTrials.gov identifier: NCT05061550.\n\nIndexed on Europe PMC as PubMed record 40450142 (DOI 10.1038/s41591-025-03746-z). Its abstract cites the registry id NCT05061550, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Nat Med 2025","url":"https://doi.org/10.1038/s41591-025-03746-z"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40450142/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40450142"},{"label":"ClinicalTrials.gov NCT05061550","url":"https://clinicaltrials.gov/study/NCT05061550"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05061550"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2025,"doi":"10.1038/s41591-025-03746-z","pmid":"40450142","authors":"Cascone T, Bonanno L, Guisier F, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05061550 with the most citations, so it is the natural first reading for anyone following the NeoCOAST-2 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-provencio-nadim-ii-perioperative-nivolumab-stage-iii-nejm-2023","kind":"paper","name":"Perioperative nivolumab and chemotherapy in stage III non-small-cell lung cancer","aka":[],"tldr":"A Spanish trial of 86 patients with stage III lung cancer. Adding immunotherapy before surgery left 37 percent with no viable tumour in the specimen against 7 percent, and 85 percent were alive at two years against 64.","summary":"The NADIM II investigators, reported by Provencio, Nadal, Gonzalez-Larriba and colleagues, randomised 86 patients with resectable stage IIIA or IIIB non-small-cell lung cancer to neoadjuvant nivolumab with platinum chemotherapy or chemotherapy alone, followed by surgery, with six months of adjuvant nivolumab after an R0 resection in the experimental group. The primary endpoint was pathological complete response.\n\nIt is a small investigator-initiated phase 2 trial with an effect size the large industry trials have not matched, and it is the trial that made pathological complete response credible as a surrogate. It also showed something the larger trials mostly do not report: more patients in the immunotherapy arm actually reached the operating theatre.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2023","url":"https://doi.org/10.1056/NEJMoa2215530"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37379158/"},{"label":"ClinicalTrials.gov NCT03838159","url":"https://clinicaltrials.gov/study/NCT03838159"}],"tags":["lung-evidence"],"related":["paper-checkmate-816-nejm-2022","paper-heymach-aegean-perioperative-durvalumab-nejm-2023","paper-keynote-671-n-engl-j-med-2023"],"cancers":["lung-cancer","nsclc","resectable-nsclc"],"sections":["immunotherapy","surgery"],"technologies":["checkpoint-inhibitor"],"targets":["pd1"],"drugs":["nivolumab","cisplatin","carboplatin","paclitaxel"],"companies":["bms"],"institutions":[],"pathways":["immune-checkpoint"],"terms":["neoadjuvant-adjuvant"],"trials":[],"people":[],"bottlenecks":["b-immunotherapy-response","b-trial-design","b-surgery-radiation-innovation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/NEJMoa2215530","pmid":"37379158","authors":"Provencio M, Nadal E, Gonzalez-Larriba JL, et al.","paperType":"rct","findings":["Pathological complete response in 37 percent of the nivolumab group against 7 percent of the control group (relative risk 5.34, 95 percent confidence interval 1.34 to 21.23; P equals 0.02).","Surgery was performed in 93 percent of the nivolumab group against 69 percent of controls (relative risk 1.35, 1.05 to 1.74).","Progression-free survival at 24 months 67.2 percent against 40.9 percent (hazard ratio 0.47, 0.25 to 0.88).","Overall survival at 24 months 85.0 percent against 63.6 percent (hazard ratio for death 0.43, 0.19 to 0.98).","Grade 3 or 4 adverse events in 11 of 57 patients (19 percent) in the experimental group and 3 of 29 (10 percent) in the control group.","86 patients underwent randomisation, 57 to the experimental group and 29 to the control group."],"whatItMeans":"The strongest signal that neoadjuvant immunotherapy makes stage III lung cancer operable as well as more often curable. Twenty-four percentage points more patients reaching surgery is a result that only a neoadjuvant design can produce.","caveats":["86 patients in a phase 2 trial; the confidence intervals are wide and the overall survival hazard ratio only just excludes one.","Open-label, with chemotherapy alone as the comparator, in a single country.","The adjuvant nivolumab component means the trial cannot separate the effect of treatment before surgery from treatment after it."],"changedPractice":true,"participants":86},{"id":"paper-nct04025879-n-engl-j-med-2024","kind":"paper","name":"Perioperative Nivolumab in Resectable Lung Cancer","aka":[],"tldr":"Published report from the CheckMate 77T trial registered as NCT04025879, in New England Journal of Medicine (2024), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Standard treatment with neoadjuvant nivolumab plus chemotherapy significantly improves outcomes in patients with resectable non-small-cell lung cancer (NSCLC). Perioperative treatment (i.e., neoadjuvant therapy followed by surgery and adjuvant therapy) with nivolumab may further improve clinical outcomes.\n\nMethods: In this phase 3, randomized, double-blind trial, we assigned adults with resectable stage IIA to IIIB NSCLC to receive neoadjuvant nivolumab plus chemotherapy or neoadjuvant chemotherapy plus placebo every 3 weeks for 4 cycles, followed by surgery and adjuvant nivolumab or placebo every 4 weeks for 1 year. The primary outcome was event-free survival according to blinded independent review. Secondary outcomes were pathological complete response and major pathological response according to blinded independent review, overall survival, and safety.\n\nResults: At this prespecified interim analysis (median follow-up, 25.4 months), the percentage of patients with 18-month event-free survival was 70.2% in the nivolumab group and 50.0% in the chemotherapy group (hazard ratio for disease progression or recurrence, abandoned surgery, or death, 0.58; 97.36% confidence interval [CI], 0.42 to 0.81; P<0.001). A pathological complete response occurred in 25.3% of the patients in the nivolumab group and in 4.7% of those in the chemotherapy group (odds ratio, 6.64; 95% CI, 3.40 to 12.97); a major pathological response occurred in 35.4% and 12.1%, respectively (odds ratio, 4.01; 95% CI, 2.48 to 6.49). Grade 3 or 4 treatment-related adverse events occurred in 32.5% of the patients in the nivolumab group and in 25.2% of those in the chemotherapy group.\n\nConclusions: Perioperative treatment with nivolumab resulted in significantly longer event-free survival than chemotherapy in patients with resectable NSCLC. No new safety signals were observed. (Funded by Bristol Myers Squibb; CheckMate 77T ClinicalTrials.gov number, NCT04025879.).\n\nIndexed on Europe PMC as PubMed record 38749033 (DOI 10.1056/nejmoa2311926). Its abstract cites the registry id NCT04025879, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2024","url":"https://doi.org/10.1056/nejmoa2311926"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38749033/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38749033"},{"label":"ClinicalTrials.gov NCT04025879","url":"https://clinicaltrials.gov/study/NCT04025879"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04025879"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2024,"doi":"10.1056/nejmoa2311926","pmid":"38749033","authors":"Cascone T, Awad MM, Spicer JD, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04025879 with the most citations, so it is the natural first reading for anyone following the CheckMate 77T trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-keynote-671-n-engl-j-med-2023","kind":"paper","name":"Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer","aka":[],"tldr":"Published report from the KEYNOTE-671 trial registered as NCT03425643, in New England Journal of Medicine (2023), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Among patients with resectable early-stage non-small-cell lung cancer (NSCLC), a perioperative approach that includes both neoadjuvant and adjuvant immune checkpoint inhibition may provide benefit beyond either approach alone.\n\nMethods: We conducted a randomized, double-blind, phase 3 trial to evaluate perioperative pembrolizumab in patients with early-stage NSCLC. Participants with resectable stage II, IIIA, or IIIB (N2 stage) NSCLC were assigned in a 1:1 ratio to receive neoadjuvant pembrolizumab (200 mg) or placebo once every 3 weeks, each of which was given with cisplatin-based chemotherapy for 4 cycles, followed by surgery and adjuvant pembrolizumab (200 mg) or placebo once every 3 weeks for up to 13 cycles. The dual primary end points were event-free survival (the time from randomization to the first occurrence of local progression that precluded the planned surgery, unresectable tumor, progression or recurrence, or death) and overall survival. Secondary end points included major pathological response, pathological complete response, and safety.\n\nResults: A total of 397 participants were assigned to the pembrolizumab group, and 400 to the placebo group. At the prespecified first interim analysis, the median follow-up was 25.2 months. Event-free survival at 24 months was 62.4% in the pembrolizumab group and 40.6% in the placebo group (hazard ratio for progression, recurrence, or death, 0.58; 95% confidence interval [CI], 0.46 to 0.72; P<0.001). The estimated 24-month overall survival was 80.9% in the pembrolizumab group and 77.6% in the placebo group (P = 0.02, which did not meet the significance criterion). A major pathological response occurred in 30.2% of the participants in the pembrolizumab group and in 11.0% of those in the placebo group (difference, 19.2 percentage points; 95% CI, 13.9 to 24.7; P<0.0001; threshold, P = 0.0001), and a pathological complete response occurred in 18.1% and 4.0%, respectively (difference, 14.2 percentage points; 95% CI, 10.1 to 18.7; P<0.0001; threshold, P = 0.0001). Across all treatment phases, 44.9% of the participants in the pembrolizumab group and 37.3% of those in the placebo group had treatment-related adverse events of grade 3 or higher, including 1.0% and 0.8%, respectively, who had grade 5 events.\n\nConclusions: Among patients with resectable, early-stage NSCLC, neoadjuvant pembrolizumab plus chemotherapy followed by resection and adjuvant pembrolizumab significantly improved event-free survival, major pathological response, and pathological complete response as compared with neoadjuvant chemotherapy alone followed by surgery. Overall survival did not differ significantly between the groups in this analysis. (Funded by Merck Sharp and Dohme; KEYNOTE-671 ClinicalTrials.gov number, NCT03425643.).\n\nIndexed on Europe PMC as PubMed record 37272513 (DOI 10.1056/nejmoa2302983). Its abstract cites the registry id NCT03425643, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2023","url":"https://doi.org/10.1056/nejmoa2302983"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37272513/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37272513"},{"label":"ClinicalTrials.gov NCT03425643","url":"https://clinicaltrials.gov/study/NCT03425643"}],"tags":["europepmc-ingest"],"related":["lung-cancer-evidence-roadmap","paper-heymach-aegean-perioperative-durvalumab-nejm-2023","paper-felip-impower010-adjuvant-atezolizumab-lancet-2021"],"cancers":["lung-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-671"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/nejmoa2302983","pmid":"37272513","authors":"Wakelee H, Liberman M, Kato T, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03425643 with the most citations, so it is the natural first reading for anyone following the KEYNOTE-671 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-nct04379635-lancet-respir-med-2025","kind":"paper","name":"Perioperative tislelizumab plus neoadjuvant chemotherapy for patients with resectable non-small-cell lung cancer (RATIONALE-315): an interim analysis of a randomised clinical trial","aka":[],"tldr":"Published report from the trial registered as NCT04379635, in The Lancet. Respiratory medicine (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Treatment guidelines recommend neoadjuvant or adjuvant chemotherapy, with or without immune checkpoint inhibitors, for resectable non-small-cell lung cancer (NSCLC). We report the interim results for the phase 3 RATIONALE-315 study, which aimed to investigate perioperative tislelizumab for the treatment of resectable NSCLC.\n\nMethods: RATIONALE-315 is a randomised, double-blind, placebo-controlled phase 3 trial conducted at 50 sites (hospitals or academic research centres) in China. Patients (aged ≥18 years) with untreated stage II-IIIA squamous or non-squamous NSCLC were randomly assigned (1:1) to neoadjuvant tislelizumab 200 mg or placebo intravenously every 3 weeks, plus platinum-based doublet chemotherapy followed by surgery and adjuvant tislelizumab 400 mg or placebo every 6 weeks. Dual primary endpoints were major pathological response rate and event-free survival, analysed by intention to treat. Safety was also assessed in all patients who received at least one dose of study treatment. RATIONALE-315 is registered with ClinicalTrials.gov, NCT04379635, and is active but not recruiting.\n\nFindings: Between June 8, 2020, and Aug 31, 2022, 453 patients were assigned to tislelizumab (n=226) or placebo (n=227). The median age of patients was 62·0 years (IQR 56·0-67·0). 410 (91%) of 453 patients were male and 43 (9%) were female. at Aug 21, 2023 (data cutoff for the interim analysis of event-free survival), median duration of follow-up was 22·0 months (IQR 15·5-28·0). Tislelizumab significantly improved event-free survival versus placebo (stratified hazard ratio 0·56 [95% CI 0·40-0·79]; one-sided p=0·0003). The major pathological response rate was significantly higher in the tislelizumab group (56% [95% CI 50-63]) than in the placebo group (15% [11-20]; difference 41% [33-49]; one-sided p<0·0001). Grade 3 or worse adverse events and serious treatment-related adverse events occurred in 163 (72%) of 226 patients and 35 (15%) of 226 patients, respectively, in the tislelizumab group, and in 150 (66%) and 18 (8%) patients, respectively, in the placebo group. The most common grade 3 or worse treatment-related adverse event was decreased neutrophil count (138 [61%] of 226 in the tislelizumab group vs 134 [59%] of 226 in the placebo group). 31 (14%) of 226 patients in the tislelizumab group and 45 (20%) of 227 patients in the placebo group died during the study.\n\nInterpretation: Perioperative tislelizumab plus neoadjuvant chemotherapy showed a clinically meaningful and statistically significant improvement in efficacy and a manageable safety profile compared with neoadjuvant chemotherapy in patients with resectable stage II-IIIA NSCLC.\n\nFunding: BeiGene.\n\nIndexed on Europe PMC as PubMed record 39581197 (DOI 10.1016/s2213-2600(24)00269-8). Its abstract cites the registry id NCT04379635, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Respir Med 2025","url":"https://doi.org/10.1016/s2213-2600(24)00269-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39581197/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39581197"},{"label":"ClinicalTrials.gov NCT04379635","url":"https://clinicaltrials.gov/study/NCT04379635"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04379635"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Lancet. Respiratory medicine","year":2025,"doi":"10.1016/s2213-2600(24)00269-8","pmid":"39581197","authors":"Yue D, Wang W, Liu H, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04379635 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-nct04379635-ann-oncol-2026-update","kind":"paper","name":"Perioperative tislelizumab plus neoadjuvant chemotherapy for patients with resectable non-small-cell lung cancer: final analysis of the randomized RATIONALE-315 trial","aka":[],"tldr":"Later report from the trial registered as NCT04379635, in Annals of Oncology (2026); its title describes an updated or longer-term analysis.","summary":"Background: Perioperative immunotherapy, particularly anti-programmed cell death protein 1 therapy, combined with neoadjuvant chemotherapy has emerged as one of the standard-of-care options for resectable non-small-cell lung cancer (NSCLC). We report the final analysis of RATIONALE-315, a randomized, double-blind, phase III trial evaluating the efficacy and safety of perioperative tislelizumab plus neoadjuvant chemotherapy versus neoadjuvant chemotherapy alone in patients with resectable, stage II-IIIA NSCLC.\n\nPatients and methods: Adult patients in China were randomized (1: 1) to receive either perioperative tislelizumab or placebo in combination with neoadjuvant chemotherapy. The dual primary endpoints were event-free survival (EFS) and major pathological response, assessed by blinded independent central review. The secondary endpoints included pathological complete response, overall survival (OS), disease-free survival, and safety.\n\nResults: In total, 453 patients were randomized (226 to tislelizumab and 227 to placebo). At the final analysis (median study follow-up of 38.5 months), patients in the tislelizumab group experienced statistically significantly improved OS versus those in the placebo group {hazard ratio (HR) 0.65 [95% confidence interval (CI) 0.45-0.93]; P = 0.009}. The median OS was not reached in either group. The 36-month OS rate was 79.3% in the tislelizumab group versus 69.3% in the placebo group. The median EFS was not reached in the tislelizumab group versus 30.6 months in the placebo group [HR 0.58 (95% CI 0.43-0.79)]. Survival benefits were generally consistent across subgroups. The safety profile of tislelizumab plus chemotherapy was tolerable and consistent with known profiles of the individual therapies.\n\nConclusions: Neoadjuvant tislelizumab plus chemotherapy and adjuvant tislelizumab demonstrated a statistically significant, clinically meaningful OS benefit and sustained, clinically meaningful EFS improvement compared with neoadjuvant chemotherapy, with a tolerable safety profile in patients with resectable stage II-IIIA NSCLC. These results support the use of this regimen in this patient population.\n\nClinical trial number: NCT04379635.\n\nIndexed on Europe PMC as PubMed record 41344593 (DOI 10.1016/j.annonc.2025.11.017). Its abstract cites the registry id NCT04379635, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2026","url":"https://doi.org/10.1016/j.annonc.2025.11.017"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41344593/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41344593"},{"label":"ClinicalTrials.gov NCT04379635","url":"https://clinicaltrials.gov/study/NCT04379635"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04379635"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2026,"doi":"10.1016/j.annonc.2025.11.017","pmid":"41344593","authors":"Wang C, Wang W, Liu H, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-perseus-dara-vrd-transplant-nejm-2024","kind":"paper","name":"PERSEUS: daratumumab added to bortezomib-lenalidomide-dexamethasone around autologous transplant in newly diagnosed myeloma","aka":[],"tldr":"Adding daratumumab to the standard three-drug induction, transplant and maintenance cut progression or death by 58% and pushed MRD-negativity to three-quarters of patients.","summary":"PERSEUS randomised 709 transplant-eligible patients with newly diagnosed multiple myeloma to daratumumab plus bortezomib, lenalidomide and dexamethasone (D-VRd) induction and consolidation with daratumumab-lenalidomide maintenance, or VRd with lenalidomide maintenance. The primary endpoint was PFS. At 48 months PFS was 84.3% versus 67.7% (hazard ratio 0.42); complete response or better was 87.9% versus 70.1% and MRD-negativity at 10^-5 was 75.2% versus 47.5%. Daratumumab could be stopped after two years of maintenance in patients with sustained MRD-negativity. Grade 3-4 neutropenia, thrombocytopenia and infections were more frequent with daratumumab.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa2312054"},{"label":"ClinicalTrials.gov NCT03710603","url":"https://clinicaltrials.gov/study/NCT03710603"}],"tags":[],"related":["cd38-plus-triplet"],"cancers":["multiple-myeloma"],"sections":[],"technologies":["autologous-stem-cell-transplant","mrd-testing"],"targets":["cd38"],"drugs":["daratumumab","bortezomib","lenalidomide"],"companies":["johnson-johnson"],"institutions":[],"pathways":[],"terms":["pfs","mrd-negativity-myeloma"],"trials":["perseus"],"people":[],"bottlenecks":["b-dormancy-mrd","b-trial-design"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2024,"doi":"10.1056/NEJMoa2312054","authors":"Sonneveld P, Dimopoulos MA, Boccadoro M, et al.","paperType":"rct","findings":["709 transplant-eligible patients; D-VRd + D-R maintenance vs VRd + R maintenance.","48-month PFS 84.3% vs 67.7%; hazard ratio 0.42.","Complete response or better 87.9% vs 70.1%.","MRD-negativity (10^-5) 75.2% vs 47.5%; sustained MRD-negativity over 12 months 64.8% vs 29.7%.","More grade 3-4 neutropenia (62.1% vs 51.0%) and infections with daratumumab."],"whatItMeans":"PERSEUS, with the earlier GRIFFIN and CASSIOPEIA trials, made a four-drug daratumumab quadruplet the standard for fit patients heading to transplant. It also introduced MRD-directed stopping of the antibody, a step towards treatment that is deep but not indefinite. Whether transplant itself remains necessary on top of a quadruplet is now the open question.","caveats":["PFS, not overall survival, was the primary endpoint; OS follow-up is immature.","Both arms had autologous transplant, so it does not test transplant versus no transplant.","MRD-guided discontinuation applied only to daratumumab, not lenalidomide.","Younger, fitter patients than typical clinic populations."],"changedPractice":true,"participants":709},{"id":"paper-shen-cell","kind":"paper","name":"Persistent Cancer Cells: The Deadly Survivors","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 33186528 and published in Cell; the citing page links this DOI, which is how the record was matched.","summary":"Persistent cancer cells are the discrete and usually undetected cells that survive cancer drug treatment and constitute a major cause of treatment failure. These cells are characterized by their slow proliferation, highly flexible energy consumption, adaptation to their microenvironment, and phenotypic plasticity. Mechanisms that underlie their persistence offer highly coveted and sought-after therapeutic targets, and include diverse epigenetic, transcriptional, and translational regulatory processes, as well as complex cell-cell interactions. Although the successful clinical targeting of persistent cancer cells remains to be realized, immense progress has been made in understanding their persistence, yielding promising preclinical results.\n\nIndexed on Europe PMC as PubMed record 33186528 (DOI 10.1016/j.cell.2020.10.027). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cell 2020","url":"https://doi.org/10.1016/j.cell.2020.10.027"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33186528/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33186528"}],"tags":["europepmc-ingest"],"related":["drug-tolerant-persisters"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Cell","year":2020,"doi":"10.1016/j.cell.2020.10.027","pmid":"33186528","authors":"Shen S, Vagner S, Robert C","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-javle-mypathway-her2-biliary-lancet-oncol-2021","kind":"paper","name":"Pertuzumab and trastuzumab for HER2-positive, metastatic biliary tract cancer (MyPathway): a multicentre, open-label, phase 2a, multiple basket study","aka":[],"tldr":"Two HER2 antibodies together shrank tumours in about a quarter of 39 patients with HER2-positive bile duct or gallbladder cancer that had already been treated, with manageable side effects, prompting the later randomised HER2 trials.","summary":"MyPathway is a non-randomised, multicentre, open-label, phase 2a, multiple basket study of approved therapies in non-indicated tumours with actionable alterations. Patients aged 18 or older with previously treated metastatic biliary tract cancer with HER2 amplification, overexpression or both and ECOG performance status 0 to 2 were enrolled at 23 United States sites and received pertuzumab (840 mg loading, then 420 mg every 3 weeks) plus trastuzumab (8 mg/kg loading, then 6 mg/kg every 3 weeks). The primary endpoint was investigator-assessed objective response rate by RECIST 1.1.\n\n39 patients enrolled between October 2014 and May 2019 were evaluable at the March 2020 cut-off (median follow-up 8.1 months). Nine of 39 achieved a partial response (objective response rate 23%, 95% CI 11 to 39). Grade 3 to 4 treatment-emergent adverse events occurred in 18 (46%) of 39, most commonly raised alanine and aspartate aminotransferase (13% each); treatment-related grade 3 events in 3 (8%); no treatment-related serious adverse events, grade 4 events or deaths.","asOf":"2026-09-24","links":[{"label":"Javle et al., Lancet Oncol 2021: pertuzumab and trastuzumab in HER2-positive biliary tract cancer (MyPathway)","url":"https://doi.org/10.1016/s1470-2045(21)00336-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34339623/"},{"label":"ClinicalTrials.gov NCT02091141","url":"https://clinicaltrials.gov/study/NCT02091141"}],"tags":[],"related":[],"cancers":["gallbladder","biliary-tract-cancer","cholangiocarcinoma"],"sections":[],"technologies":[],"targets":["her2"],"drugs":["pertuzumab","trastuzumab"],"companies":["roche-genentech"],"institutions":[],"pathways":[],"terms":[],"trials":["mypathway"],"people":["ghassan-abou-alfa"],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2021,"doi":"10.1016/s1470-2045(21)00336-3","pmid":"34339623","authors":"Javle M, Borad MJ, Azad NS, et al.","paperType":"observational","findings":["Objective response rate 23% (9 of 39; 95% CI 11 to 39) with pertuzumab plus trastuzumab in previously treated HER2-positive biliary tract cancer.","Grade 3 to 4 treatment-emergent adverse events in 46%; treatment-related grade 3 in 8%; no treatment-related deaths.","HER2 positivity defined as amplification, overexpression or both."],"whatItMeans":"The first prospective evidence that HER2 blockade works in biliary cancer, which led to HERIZON-BTC-01 and the HER2 antibody-drug conjugate studies; the definition of HER2-positive here (amplification or overexpression) is looser than the later IHC 3+ label.","caveats":["Single-arm basket cohort of 39; no comparator.","Investigator-assessed responses."],"changedPractice":false,"participants":39},{"id":"paper-mypathway-lancet-oncol-2019","kind":"paper","name":"Pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer (MyPathway): an updated report from a multicentre, open-label, phase 2a, multiple basket study","aka":[],"tldr":"Published report from the MyPathway trial registered as NCT02091141, in The Lancet Oncology (2019), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Therapies targeting HER2 have improved clinical outcomes in HER2-positive breast and gastric cancers, and are emerging as potential treatments for HER2-positive metastatic colorectal cancer. MyPathway evaluates the activity of targeted therapies in non-indicated tumour types with potentially predictive molecular alterations. We aimed to assess the activity of pertuzumab and trastuzumab in patients with HER2-amplified metastatic colorectal cancer.\n\nMethods: MyPathway is an ongoing, phase 2a, multiple basket study. Patients in this subset analysis were aged 18 years or older and had treatment-refractory, histologically confirmed HER2-amplified metastatic colorectal cancer with measurable or evaluable disease and an Eastern Cooperative Oncology Group performance status score of 2 or less, enrolled from 25 hospitals or clinics in 16 states of the USA. Patients received pertuzumab (840 mg loading dose, then 420 mg every 3 weeks, intravenously) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg every 3 weeks, intravenously). The primary endpoint was the proportion of patients who achieved an objective response based on investigator-reported tumour responses. Analyses were done per protocol. This ongoing trial is registered with ClinicalTrials.gov, number NCT02091141.\n\nFindings: Between Oct 20, 2014, and June 22, 2017, 57 patients with HER2-amplified metastatic colorectal cancer were enrolled in the MyPathway study and deemed eligible for inclusionin this cohort analysis. Among these 57 evaluable patients, at Aug 1, 2017, one (2%) patient had a complete response and 17 (30%) had partial responses; thus overall 18 of 57 patients achieved an objective response (32%, 95% CI 20-45). The most common treatment-emergent adverse events were diarrhoea (19 [33%] of 57 patients), fatigue (18 [32%] patients), and nausea (17 [30%] patients). Grade 3-4 treatment-emergent adverse events were recorded in 21 (37%) of 57 patients, most commonly hypokalaemia and abdominal pain (each three [5%] patients). Serious treatment-emergent adverse events were reported in ten (18%) patients and two (4%) of these adverse events (ie, chills and infusion-related reaction) were considered treatment related. There were no treatment-related deaths.\n\nInterpretation: Dual HER2-targeted therapy with pertuzumab plus trastuzumab is well tolerated and could represent a therapeutic opportunity for patients with heavily pretreated, HER2-amplified metastatic colorectal cancer.\n\nFunding: F Hoffmann-La Roche/Genentech.\n\nIndexed on Europe PMC as PubMed record 30857956 (DOI 10.1016/s1470-2045(18)30904-5). Its abstract cites the registry id NCT02091141, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2019","url":"https://doi.org/10.1016/s1470-2045(18)30904-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30857956/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30857956"},{"label":"ClinicalTrials.gov NCT02091141","url":"https://clinicaltrials.gov/study/NCT02091141"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["mypathway"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2019,"doi":"10.1016/s1470-2045(18)30904-5","pmid":"30857956","authors":"Meric-Bernstam F, Hurwitz H, Raghav KPS, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02091141 with the most citations, so it is the natural first reading for anyone following the MyPathway trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-gupta-jco-precis-oncol","kind":"paper","name":"Pertuzumab Plus Trastuzumab in Patients With Colorectal Cancer With ERBB2 Amplification or ERBB2/3 Mutations: Results From the TAPUR Study","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 36315917 and published in JCO Precision Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: The TAPUR Study is a pragmatic phase II basket trial evaluating antitumor activity of commercially available targeted agents in patients with advanced cancers harboring potentially actionable genomic alterations. Data from two cohorts of patients with colorectal cancer (CRC) with either ERBB2 amplifications or ERBB2 or ERBB3 (ERBB2/3) mutations treated with pertuzumab plus trastuzumab (P + T) are reported.\n\nMethods: Eligible patients with measurable CRC were selected for treatment with P + T according to protocol-specified genomic matching rules. Patients had no remaining standard treatment options, Eastern Cooperative Oncology Group performance status 0-2, and adequate organ function. Simon's two-stage design was used with a primary study end point of disease control (DC; objective response [OR] or stable disease of at least 16 weeks duration [SD16+]). Secondary end points include safety, response duration, progression-free survival (PFS), and overall survival (OS).\n\nResults: Thirty-eight patients with CRC with ERBB2 amplification (N = 28) or ERBB2 / 3 mutations (N = 10) were treated with P + T. For the ERBB2 amplification cohort, DC and OR were observed in 54% and 25% of patients, respectively; the median PFS and median OS (95% CIs) were 17.2 (11.1 to 27.4) weeks and 60.0 (32.1 to 102.3) weeks, respectively. For the ERBB2 / 3 mutation cohort, DC and OR were observed in 10% and 0% of patients, respectively; the median PFS and median OS were 9.6 (5.1 to 16.0) weeks and 28.8 (7.6 to 146.3) weeks, respectively. Four of 38 patients experienced grade 3 adverse events or serious adverse events including anemia, infusion reaction, diarrhea, left ventricular systolic dysfunction, and decreased lymphocyte count.\n\nConclusion: Although P + T treatment does not appear to have antitumor activity in CRC with ERBB2/3 mutations, this combination has antitumor activity in patients with CRC with ERBB2 amplification and warrants further study.\n\nIndexed on Europe PMC as PubMed record 36315917 (DOI 10.1200/po.22.00306). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JCO Precis Oncol 2022","url":"https://doi.org/10.1200/po.22.00306"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36315917/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36315917"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["tapur"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco-precision-oncology"],"dependsOn":[],"notes":[],"journal":"JCO Precision Oncology","year":2022,"doi":"10.1200/po.22.00306","pmid":"36315917","authors":"Gupta R, Meric-Bernstam F, Rothe M, et al.","paperType":"observational","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-cleopatra-n-engl-j-med-2012","kind":"paper","name":"Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer","aka":[],"tldr":"Published report from the CLEOPATRA trial registered as NCT00567190, in New England Journal of Medicine (2012), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: The anti-human epidermal growth factor receptor 2 (HER2) humanized monoclonal antibody trastuzumab improves the outcome in patients with HER2-positive metastatic breast cancer. However, most cases of advanced disease eventually progress. Pertuzumab, an anti-HER2 humanized monoclonal antibody that inhibits receptor dimerization, has a mechanism of action that is complementary to that of trastuzumab, and combination therapy with the two antibodies has shown promising activity and an acceptable safety profile in phase 2 studies involving patients with HER2-positive breast cancer.\n\nMethods: We randomly assigned 808 patients with HER2-positive metastatic breast cancer to receive placebo plus trastuzumab plus docetaxel (control group) or pertuzumab plus trastuzumab plus docetaxel (pertuzumab group) as first-line treatment until the time of disease progression or the development of toxic effects that could not be effectively managed. The primary end point was independently assessed progression-free survival. Secondary end points included overall survival, progression-free survival as assessed by the investigator, the objective response rate, and safety.\n\nResults: The median progression-free survival was 12.4 months in the control group, as compared with 18.5 months in the pertuzumab group (hazard ratio for progression or death, 0.62; 95% confidence interval, 0.51 to 0.75; P<0.001). The interim analysis of overall survival showed a strong trend in favor of pertuzumab plus trastuzumab plus docetaxel. The safety profile was generally similar in the two groups, with no increase in left ventricular systolic dysfunction; the rates of febrile neutropenia and diarrhea of grade 3 or above were higher in the pertuzumab group than in the control group.\n\nConclusions: The combination of pertuzumab plus trastuzumab plus docetaxel, as compared with placebo plus trastuzumab plus docetaxel, when used as first-line treatment for HER2-positive metastatic breast cancer, significantly prolonged progression-free survival, with no increase in cardiac toxic effects. (Funded by F. Hoffmann-La Roche/Genentech; ClinicalTrials.gov number, NCT00567190.).\n\nIndexed on Europe PMC as PubMed record 22149875 (DOI 10.1056/nejmoa1113216). Its abstract cites the registry id NCT00567190, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2012","url":"https://doi.org/10.1056/nejmoa1113216"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22149875/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/22149875"},{"label":"ClinicalTrials.gov NCT00567190","url":"https://clinicaltrials.gov/study/NCT00567190"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["cleopatra"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2012,"doi":"10.1056/nejmoa1113216","pmid":"22149875","authors":"Baselga J, Cortés J, Kim SB, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT00567190 with the most citations, so it is the natural first reading for anyone following the CLEOPATRA trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-cleopatra-lancet-oncol-2013-update","kind":"paper","name":"Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study","aka":[],"tldr":"Later report from the CLEOPATRA trial registered as NCT00567190, in The Lancet Oncology (2013); its title describes an updated or longer-term analysis.","summary":"Background: CLEOPATRA is a phase 3 study to compare the efficacy and safety of pertuzumab, trastuzumab, and docetaxel with placebo, trastuzumab, and docetaxel in patients with HER2-positive first-line metastatic breast cancer. The results of the primary analysis showed significantly longer median progression-free survival in the pertuzumab group than in the placebo group. Interim analysis of overall survival favoured the pertuzumab group but was not significant. Here, we report results for overall survival after an additional year of follow-up.\n\nMethods: The study was a double-blind randomised trial undertaken at 204 centres in 25 countries. Patients with HER2-positive metastatic breast cancer who had not received previous chemotherapy or biological treatment for their metastatic disease were randomly assigned to receive either pertuzumab, trastuzumab, and docetaxel (n=402) or the same regimen with a matching placebo replacing pertuzumab (n=406). Randomisation was in a 1:1 ratio, stratified by geographical region and previous treatment status. The primary endpoint was progression-free survival (assessed independently), which has been reported previously; no follow-up data were gathered for the primary endpoint. Secondary endpoints included overall survival, progression-free survival (assessed by investigator), objective response rate, and safety. Median follow-up was 30 months in both groups. Efficacy endpoints were analysed in the intention-to-treat population and safety was analysed by treatment received. The study is completed but safety and survival data continue to be followed up. This trial is registered with ClinicalTrials.gov, number NCT00567190.\n\nFindings: In the intention-to-treat population, 267 patients died by data cutoff (May 14, 2012), 154 (38%) of 406 in the placebo group and 113 (28%) of 402 in the pertuzumab group. Median overall survival was 37.6 months (95% CI 34.3-NE [not estimable]) in the placebo group but had not been reached (95% CI 42.4-NE) in the pertuzumab group (hazard ratio 0.66, 95% CI 0.52-0.84; p=0.0008). Investigator-assessed median progression-free survival was 12.4 months (95% CI 10.4-13.5) in the placebo group and 18.7 months (16.6-21.6) in the pertuzumab group (hazard ratio 0.69, 95% CI 0.58-0.81). Serious adverse events were reported in 115 (29%) of 396 patients who received placebo, trastuzumab, and docetaxel and 148 (36%) of 408 who received pertuzumab, trastuzumab, and docetaxel, and included febrile neutropenia, neutropenia, diarrhoea, pneumonia, and cellulitis. Overall, adverse events were similar to those reported at the primary analysis with respect to frequency, severity, and specificity.\n\nInterpretation: Our analysis shows a significant improvement in overall survival with pertuzumab, trastuzumab, and docetaxel in patients with HER2-positive metastatic breast cancer, compared with placebo, trastuzumab, and docetaxel. Since this effect was not achieved at the expense of adverse events, this regimen represents a substantial improvement on the standard of care for this population of patients.\n\nFunding: F Hoffmann-La Roche, Genentech.\n\nIndexed on Europe PMC as PubMed record 23602601 (DOI 10.1016/s1470-2045(13)70130-x). Its abstract cites the registry id NCT00567190, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2013","url":"https://doi.org/10.1016/s1470-2045(13)70130-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23602601/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/23602601"},{"label":"ClinicalTrials.gov NCT00567190","url":"https://clinicaltrials.gov/study/NCT00567190"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["cleopatra"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2013,"doi":"10.1016/s1470-2045(13)70130-x","pmid":"23602601","authors":"Swain SM, Kim SB, Cortés J, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the CLEOPATRA trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-wang-notch-pest-mutations-tnbc-ccr-2015","kind":"paper","name":"PEST domain mutations in Notch receptors comprise an oncogenic driver segment in triple-negative breast cancer sensitive to a gamma-secretase inhibitor","aka":[],"tldr":"Mutations that destroy the off-switch (PEST domain) of NOTCH1, NOTCH2 and NOTCH3, plus focal amplifications, cluster in triple-negative tumours in TCGA and made patient-derived tumours highly sensitive to a gamma-secretase inhibitor.","summary":"Novel algorithms applied to TCGA breast cancer sequencing identified mutations within and upstream of the PEST domains of NOTCH1, NOTCH2 and NOTCH3, arising by several genetic mechanisms and compromising the negative regulatory domain, plus focal NOTCH2 and NOTCH3 amplifications and rarer heterodimerisation or extracellular domain mutations. Alterations activated canonical Notch targets and functional mutations were significantly enriched in TNBC. Patient-derived xenografts with PEST mutations were highly sensitive to PF-03084014.","asOf":"2026-09-24","links":[{"label":"Wang et al., Clin Cancer Res 2015: PEST domain Notch mutations as a TNBC driver segment","url":"https://doi.org/10.1158/1078-0432.CCR-14-1348"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25564152/"}],"tags":[],"related":[],"cancers":["tnbc"],"sections":[],"technologies":[],"targets":["notch1","gamma-secretase"],"drugs":[],"companies":[],"institutions":[],"pathways":["notch"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2015,"doi":"10.1158/1078-0432.CCR-14-1348","pmid":"25564152","authors":"Wang K, Zhang Q, Li D, et al.","paperType":"translational","findings":["PEST-domain mutations across NOTCH1/2/3 and focal NOTCH2/3 amplifications enriched in TNBC.","PEST-mutant patient-derived xenografts responded to the gamma-secretase inhibitor PF-03084014."],"whatItMeans":"It widens the NOTCH driver segment beyond rearrangements to PEST mutations that ordinary DNA panels can report, the finding that fed NOTCH-mutant cohorts into basket trials.","caveats":["Computational discovery with xenograft validation; no clinical response data.","Frequencies in the abstract are qualitative."],"changedPractice":false},{"id":"paper-ahl2011-pet-adapted-treatment-advanced-hodgkin-lancet-oncol-2019","kind":"paper","name":"PET-adapted treatment for newly diagnosed advanced Hodgkin lymphoma (AHL2011): a randomised, multicentre, non-inferiority, phase 3 study","aka":["AHL2011","Casasnovas 2019"],"tldr":"Starting with the most intensive Hodgkin chemotherapy and switching to the gentler standard once the scan cleared gave the same disease control with far less anaemia, bleeding risk and infection.","summary":"A randomised non-inferiority phase 3 study at 90 centres in Belgium and France. Eligible patients were aged 16 to 60 with newly diagnosed Hodgkin lymphoma excluding the nodular lymphocyte predominant subtype, performance status under 3, and stage III, IV or IIB with a mediastinum-to-thorax ratio of 0.33 or more or extranodal localisation. All patients received two cycles of escalated BEACOPP. The standard group then completed six cycles regardless of the scan; the scan-driven group switched to four cycles of ABVD if the scan after two cycles was negative and continued escalated BEACOPP if it was positive. The non-inferiority margin was 10 percentage points.\n\nFrom 19 May 2011 to 29 April 2014, 823 patients were enrolled, 413 to standard care and 410 to the scan-driven arm; 346 (84 per cent) of the scan-driven arm switched to ABVD and 51 (12 per cent) continued escalated BEACOPP. At a median follow-up of 50.4 months (interquartile range 42.9 to 59.3), five-year progression-free survival by intention to treat was 86.2 per cent (95 per cent confidence interval 81.6 to 89.8) with standard treatment and 85.7 per cent (81.4 to 89.1) with scan-driven treatment (hazard ratio 1.084, 0.737 to 1.596, p = 0.65).","asOf":"2026-10-01","links":[{"label":"Lancet Oncology 2019","url":"https://doi.org/10.1016/S1470-2045(18)30784-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30658935/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30658935"}],"tags":["lymphoma-evidence"],"related":["lymphoma-roadmap"],"cancers":["advanced-stage-classical-hodgkin-lymphoma","hodgkin-lymphoma"],"sections":["chemotherapy","imaging"],"technologies":["pet-ct"],"targets":[],"drugs":["bleomycin","etoposide","doxorubicin","cyclophosphamide","vincristine","procarbazine","prednisone","vinblastine","dacarbazine"],"companies":["lysa"],"institutions":[],"pathways":[],"terms":["deauville-score","abvd-beacopp","non-inferiority"],"trials":["ahl2011","hd18","rathl"],"people":[],"bottlenecks":["b-toxicity-qol","b-survivorship"],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"Lancet Oncology","year":2019,"doi":"10.1016/S1470-2045(18)30784-8","pmid":"30658935","authors":"Casasnovas RO, Bouabdallah R, Brice P, et al.","paperType":"rct","findings":["Five-year progression-free survival by intention to treat was 85.7 per cent with scan-driven treatment against 86.2 per cent with standard escalated BEACOPP (hazard ratio 1.084, 95 per cent confidence interval 0.737 to 1.596, p = 0.65), meeting non-inferiority.","346 of 410 patients (84 per cent) in the scan-driven arm switched to ABVD after a negative scan.","Grade 3 to 4 anaemia occurred in 69 per cent of the standard group against 28 per cent of the scan-driven group, and thrombocytopenia in 66 against 40 per cent.","Febrile neutropenia occurred in 35 against 23 per cent, and infections in 22 against 11 per cent.","Serious treatment-related adverse events were reported in 47 per cent of the standard group against 28 per cent of the scan-driven group; six treatment-related deaths occurred in the standard group."],"whatItMeans":"Confirmation, by a different route from HD18, that the interim scan can safely direct de-escalation in advanced Hodgkin lymphoma, and that most of the toxicity of escalated BEACOPP can be avoided in the 84 per cent of patients who respond early.","caveats":["Non-inferiority margin of 10 percentage points is wide for a disease with five-year progression-free survival above 85 per cent.","Open-label and investigator-assessed.","Everyone received two cycles of escalated BEACOPP first, so the trial does not test starting with ABVD."],"changedPractice":true,"participants":823},{"id":"paper-ghsg-hd18-pet-guided-escalated-beacopp-lancet-2017","kind":"paper","name":"PET-guided treatment in patients with advanced-stage Hodgkin's lymphoma (HD18): final results of an open-label, international, randomised phase 3 trial by the German Hodgkin Study Group","aka":["HD18","Borchmann 2017"],"tldr":"People whose scan cleared after two rounds of the most intensive Hodgkin regimen could stop after four rounds instead of six or eight, halving severe infections with no loss of control.","summary":"An open-label, randomised, parallel-group phase 3 trial recruiting patients aged 18 to 60 with newly diagnosed advanced-stage Hodgkin's lymphoma at 301 hospitals and practices in Germany, Switzerland, Austria, the Netherlands and the Czech Republic. After central review of the scan following two cycles of escalated BEACOPP, scan-positive patients were randomised between six further cycles of escalated BEACOPP and the same with rituximab, and scan-negative patients between six further cycles and two further cycles. A 2011 amendment reduced the standard to six cycles in total.\n\nBetween 14 May 2008 and 18 July 2014, 2,101 patients were recruited, 137 found ineligible before randomisation and 19 after. Among 434 randomised scan-positive patients, five-year progression-free survival was 89.7 per cent (95 per cent confidence interval 85.4 to 94.0) with escalated BEACOPP and 88.1 per cent (83.5 to 92.7) with rituximab added (log-rank p = 0.46). Among scan-negative patients, five-year progression-free survival was 90.8 per cent (87.9 to 93.7) with eight or six cycles and 92.2 per cent (89.4 to 95.0) with four (difference 1.4 per cent, minus 2.7 to 5.4). Four cycles caused fewer severe infections (40 of 498, 8 per cent, against 75 of 502, 15 per cent) and fewer organ toxicities (38 of 498, 8 per cent, against 91 of 502, 18 per cent).","asOf":"2026-10-01","links":[{"label":"Lancet 2017","url":"https://doi.org/10.1016/S0140-6736(17)32134-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29061295/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29061295"}],"tags":["lymphoma-evidence"],"related":["lymphoma-roadmap"],"cancers":["advanced-stage-classical-hodgkin-lymphoma","hodgkin-lymphoma"],"sections":["chemotherapy","imaging"],"technologies":["pet-ct"],"targets":[],"drugs":["bleomycin","etoposide","doxorubicin","cyclophosphamide","vincristine","procarbazine","prednisone","rituximab"],"companies":["ghsg"],"institutions":[],"pathways":[],"terms":["deauville-score","abvd-beacopp","non-inferiority"],"trials":["hd18","hd21"],"people":["peter-borchmann","andreas-engert"],"bottlenecks":["b-toxicity-qol","b-survivorship"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"Lancet","year":2017,"doi":"10.1016/S0140-6736(17)32134-7","pmid":"29061295","authors":"Borchmann P, Goergen H, Kobe C, et al.","paperType":"rct","findings":["Among scan-negative patients, five-year progression-free survival was 92.2 per cent with four cycles of escalated BEACOPP and 90.8 per cent with six or eight (difference 1.4 percentage points, 95 per cent confidence interval minus 2.7 to 5.4).","Four cycles caused severe infections in 8 per cent against 15 per cent, and organ toxicities in 8 per cent against 18 per cent.","Adding rituximab to escalated BEACOPP in scan-positive patients did not improve five-year progression-free survival (89.7 against 88.1 per cent, log-rank p = 0.46).","Ten treatment-related deaths occurred across the trial.","2,101 patients were recruited; 156 were found ineligible before or after randomisation."],"whatItMeans":"The basis for four cycles of escalated BEACOPP as the German standard when the interim scan is negative, and the reason rituximab was abandoned as an addition to that regimen. The authors recommend the scan-guided strategy for all patients with advanced-stage disease.","caveats":["A protocol amendment mid-trial changed the standard arm from eight cycles to six, so the comparator is not uniform across the recruitment period.","Escalated BEACOPP is not the standard in North America or the United Kingdom, where ABVD-based and brentuximab or nivolumab-based regimens are used, so the de-escalation question looks different there.","Primary analyses in the scan-negative cohort were per protocol."],"changedPractice":true,"participants":1945},{"id":"paper-tap-lancet","kind":"paper","name":"Pexidartinib versus placebo for advanced tenosynovial giant cell tumour (ENLIVEN): a randomised phase 3 trial","aka":[],"tldr":"Paper cited by one cancer page, one trial page, one treatment page and one target page, indexed on Europe PMC as PubMed record 31229240 and published in The Lancet; the citing pages link this DOI, which is how the record was matched.","summary":"Background: Tenosynovial giant cell tumour (TGCT), a rare, locally aggressive neoplasm, overexpresses colony-stimulating factor 1 (CSF1). Surgery is standard with no approved systemic therapy. We aimed to evaluate pexidartinib, a CSF1 receptor inhibitor, in patients with TGCT to provide them with a viable systemic treatment option, especially in cases that are not amenable to surgical resection.\n\nMethods: This phase 3 randomised trial had two parts. Part one was a double-blind study in which patients with symptomatic, advanced TGCT for whom surgery was not recommended were randomly assigned via an integrated web response system (1:1) to the pexidartinib or placebo group. Individuals in the pexidartinib group received a loading dose of 1000 mg pexidartinib per day orally (400 mg morning; 600 mg evening) for the first 2 weeks, followed by 800 mg per day (400 mg twice a day) for 22 weeks. Part two was an open-label study of pexidartinib for all patients. The primary endpoint, assessed in all intention-to-treat patients, was overall response at week 25, and was centrally reviewed by RECIST, version 1.1. Safety was analysed in all patients who received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, number NCT02371369.\n\nFindings: Between May 11, 2015, and Sept 30, 2016, of 174 patients assessed for eligibility, 120 patients were randomly assigned to, and received, pexidartinib (n=61) or placebo (n=59). There were 11 dropouts in the placebo group and nine in the pexidartinib group. Emergence of mixed or cholestatic hepatotoxicity caused the data monitoring committee to stop enrolment six patients short of target. The proportion of patients who achieved overall response was higher for pexidartinib than placebo at week 25 by RECIST (24 [39%] of 61 vs none of 59; absolute difference 39% [95% CI 27-53]; p<0·0001). Serious adverse events occurred in eight (13%) of 61 patients in the pexidartinib group and one (2%) of 59 patients in the placebo group. Hair colour changes (67%), fatigue (54%), aspartate aminotransferase increase (39%), nausea (38%), alanine aminotransferase increase (28%), and dysgeusia (25%) were the most frequent pexidartinib-associated adverse events. Three patients given pexidartinib had aminotransferase elevations three or more times the upper limit of normal with total bilirubin and alkaline phosphatase two or more times the upper limit of normal indicative of mixed or cholestatic hepatotoxicity, one lasting 7 months and confirmed by biopsy.\n\nInterpretation: Pexidartinib is the first systemic therapy to show a robust tumour response in TGCT with improved patient symptoms and functional outcomes; mixed or cholestatic hepatotoxicity is an identified risk. Pexidartinib could be considered as a potential treatment for TGCT associated with severe morbidity or functional limitations in cases not amenable to improvement with surgery.\n\nFunding: Daiichi Sankyo.\n\nIndexed on Europe PMC as PubMed record 31229240 (DOI 10.1016/s0140-6736(19)30764-0). Matched by DOI alone: one cancer page, one trial page, one treatment page and one target page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet 2019","url":"https://doi.org/10.1016/s0140-6736(19)30764-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31229240/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31229240"}],"tags":["europepmc-ingest"],"related":["tenosynovial-giant-cell-tumour","pexidartinib","csf1r"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["enliven"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2019,"doi":"10.1016/s0140-6736(19)30764-0","pmid":"31229240","authors":"Tap WD, Gelderblom H, Palmerini E, et al.","paperType":"rct","findings":[],"whatItMeans":"One cancer page, one trial page, one treatment page and one target page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-pharos-encorafenib-binimetinib-riely-jco-2023","kind":"paper","name":"PHAROS: encorafenib plus binimetinib in BRAF V600E-mutant metastatic non-small-cell lung cancer","aka":[],"tldr":"A second BRAF and MEK inhibitor pair, encorafenib plus binimetinib, shrank tumours in three quarters of untreated and nearly half of previously treated patients with BRAF V600E lung cancer, giving a better-tolerated alternative to dabrafenib-trametinib.","summary":"Phase 2 study of 98 patients with BRAF V600E-mutant metastatic non-small-cell lung cancer, 59 treatment-naive and 39 previously treated, given encorafenib plus binimetinib.\n\nObjective response was 75 percent in treatment-naive and 46 percent in previously treated patients, with median duration of response not reached and 16.7 months respectively; pyrexia was less common than with dabrafenib-trametinib.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2023","url":"https://doi.org/10.1200/JCO.23.00774"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37270692/"}],"tags":[],"related":[],"cancers":["braf-v600e-nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":["binimetinib","encorafenib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["pharos"],"people":["gregory-riely"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2023,"doi":"10.1200/JCO.23.00774","pmid":"37270692","authors":"Riely GJ, Smit EF, Ahn MJ, et al.","paperType":"observational","findings":["Objective response 75 percent (treatment-naive) and 46 percent (previously treated).","Median duration of response 16.7 months in previously treated patients."],"whatItMeans":"Encorafenib-binimetinib is approved for BRAF V600E lung cancer and offers a second targeted option, particularly for patients troubled by fever on dabrafenib-trametinib.","caveats":["Single-arm; no head-to-head comparison with dabrafenib-trametinib."],"changedPractice":true,"participants":98},{"id":"paper-nct04585750-n-engl-j-med-2026","kind":"paper","name":"Phase 1 Study of Rezatapopt, a p53 Reactivator, in TP53 Y220C-Mutated Tumors","aka":[],"tldr":"Published report from the PYNNACLE trial registered as NCT04585750, in New England Journal of Medicine (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Rezatapopt is an investigational, first-in-class, oral, selective p53 reactivator that specifically binds to Y220C-mutated p53, which stabilizes p53 in its wild-type conformation and restores its functionality.\n\nMethods: In this phase 1, single-group, dose-escalation and dose-optimization study, we assigned heavily pretreated patients with locally advanced or metastatic solid tumors harboring a TP53 Y220C mutation to receive rezatapopt during continuous 21-day treatment cycles. The primary objectives were to determine the maximum tolerated dose and recommended phase 2 dose. Primary end points included dose-limiting toxic effects and adverse events. Secondary end points included preliminary efficacy and pharmacokinetic features.\n\nResults: A total of 77 patients received rezatapopt at one of eight escalating doses: 150 mg, 300 mg, 600 mg, 1150 mg, 1500 mg, 2000 mg, or 2500 mg once daily or 1500 mg twice daily. The maximum tolerated dose was 1500 mg twice daily. On the basis of safety, efficacy, and pharmacokinetic data, 2000 mg once daily with food was selected as the recommended phase 2 dose. During the treatment period, 76 patients (99%) had at least one adverse event and 29 (38%) had an adverse event of grade 1 or 2. The most common adverse events were nausea (in 58% of patients), vomiting (in 44%), an increased blood creatinine level (in 39%), fatigue (in 39%), and anemia (in 36%). Treatment-related adverse events occurred in 67 patients (87%) and those of grade 1 or 2 in 48 (62%); 2 patients (3%) discontinued rezatapopt because of a treatment-related adverse event. Most gastrointestinal adverse events resolved with the treatment of symptoms and were less frequent when rezatapopt was given with food. Anemia was the most common adverse event of grade 3 or higher during the treatment period, occurring in 16% of patients. The overall response (complete or partial response) was 20% among all patients and 30% among those who had a KRAS wild-type tumor and received a dose of at least 1150 mg once daily. Confirmed responses were seen across multiple tumor types, including ovarian and breast cancers. All patients with a response had a solid tumor that harbored TP53 Y220C and wild-type KRAS.\n\nConclusions: In this phase 1 study involving heavily pretreated patients, the most common adverse events associated with rezatapopt were nausea and vomiting. Antitumor activity occurred across multiple tumor types, providing proof of concept for p53 reactivation. (Funded by PMV Pharmaceuticals; PYNNACLE ClinicalTrials.gov number, NCT04585750.).\n\nIndexed on Europe PMC as PubMed record 41740031 (DOI 10.1056/nejmoa2508820). Its abstract cites the registry id NCT04585750, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2026","url":"https://doi.org/10.1056/nejmoa2508820"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41740031/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41740031"},{"label":"ClinicalTrials.gov NCT04585750","url":"https://clinicaltrials.gov/study/NCT04585750"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04585750"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2026,"doi":"10.1056/nejmoa2508820","pmid":"41740031","authors":"Dumbrava EE, Shapiro GI, Parikh AR, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04585750 with the most citations, so it is the natural first reading for anyone following the PYNNACLE trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-attard-abiraterone-phase-1-cyp17-jco-2008","kind":"paper","name":"Phase 1 trial of abiraterone acetate confirms that castration-resistant prostate cancer commonly remains hormone driven","aka":["Attard 2008 abiraterone phase 1","CYP17 inhibition abiraterone first-in-human"],"tldr":"Twenty-one men whose prostate cancer had already stopped responding to every hormone treatment available were given a drug that shuts off the last remaining source of androgen. Two thirds had their PSA fall, which proved the cancer had never stopped depending on the hormone.","summary":"Gerhardt Attard, Johann de Bono and colleagues at the Royal Marsden and the Institute of Cancer Research ran the first-in-human study of abiraterone acetate, a selective inhibitor of cytochrome P450 17A1 (CYP17), the enzyme that makes androgen in the adrenal gland and in the tumour itself. Twenty-one chemotherapy-naive men whose disease was resistant to multiple hormonal therapies were dosed through five levels from 250 mg to 2,000 mg.\n\nThe result settled a twenty-year argument about what castration-resistant prostate cancer is. If the disease were genuinely hormone-refractory, removing the residual androgen would do nothing. It did a great deal, and the secondary mineralocorticoid excess that the drug produces (hypertension, hypokalaemia, lower-limb oedema) was managed with a mineralocorticoid receptor antagonist, which is why abiraterone is still given with a steroid today.","asOf":"2026-09-25","links":[{"label":"J Clin Oncol 2008","url":"https://doi.org/10.1200/jco.2007.15.9749"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/18645193/"}],"tags":["prostate-evidence"],"related":["paper-cou-aa-301-abiraterone-de-bono-nejm-2011","paper-abiraterone-acetate-prostate-n-engl-j-med-2013","paper-chen-androgen-receptor-overexpression-antiandrogen-resistance-nat-med-2004","prostate-roadmap"],"cancers":["prostate","prostate-mcrpc"],"sections":["hormonal","targeted-therapy"],"technologies":[],"targets":["androgen-receptor"],"drugs":["abiraterone"],"companies":[],"institutions":["royal-marsden","icr-london"],"pathways":[],"terms":["castration-resistance","psa"],"trials":[],"people":["gerhardt-attard","johann-de-bono"],"bottlenecks":["b-resistance","b-translational-valley"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2008,"doi":"10.1200/jco.2007.15.9749","pmid":"18645193","authors":"Attard G, Reid AH, Yap TA, et al.","paperType":"rct","findings":["Declines in prostate-specific antigen of at least 30 percent in 14 of 21 patients (66 percent), at least 50 percent in 12 (57 percent) and at least 90 percent in 6 (29 percent).","Responses lasted between 69 and at least 578 days.","1,000 mg was selected for cohort expansion (9 further patients) because of a plateau in pharmacodynamic effect above that dose.","Administration suppressed serum testosterone, downstream androgenic steroids and estradiol in all patients, and raised adrenocorticotropic hormone and the steroids upstream of CYP17.","The anticipated toxicities of secondary mineralocorticoid excess (hypertension, hypokalaemia and lower-limb oedema) were managed with a mineralocorticoid receptor antagonist."],"whatItMeans":"The proof, in people, that castration-resistant prostate cancer is usually still androgen-driven. It renamed the disease (hormone-refractory became castration-resistant) and it opened the line of drugs that now dominate treatment at every stage from first diagnosis of metastatic disease onwards.","caveats":["21 patients in a dose-escalation study with no control arm; the survival evidence came from COU-AA-301 and COU-AA-302.","Prostate-specific antigen decline is a pharmacodynamic signal, not a survival endpoint.","The mineralocorticoid excess is intrinsic to CYP17 blockade and is the reason abiraterone must be given with prednisolone or a mineralocorticoid antagonist, which carries its own long-term cost."],"changedPractice":true,"participants":21},{"id":"paper-overman-capox-small-bowel-adenocarcinoma-jco-2009","kind":"paper","name":"Phase 2 study of capecitabine and oxaliplatin for advanced adenocarcinoma of the small bowel and ampulla of Vater","aka":[],"tldr":"The first prospective trial in small bowel adenocarcinoma found that the colorectal cancer regimen CAPOX shrank tumours in half of patients, and it became the backbone of treatment and of the adjuvant BALLAD trial.","summary":"Single-centre phase 2 study of 30 patients with untreated advanced adenocarcinoma of the small bowel or ampulla of Vater treated with capecitabine and oxaliplatin (CAPOX) every three weeks.\n\nThe objective response rate was 50 percent, median time to progression 11.3 months and median overall survival 20.4 months, with results in the small bowel subgroup at least as good. The regimen was adopted as a standard for advanced disease and the basis for adjuvant trials.","asOf":"2026-09-18","links":[{"label":"J Clin Oncol 2009","url":"https://doi.org/10.1200/JCO.2008.19.7145"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19164203/"}],"tags":[],"related":[],"cancers":["localised-small-bowel-adenocarcinoma","advanced-small-bowel-adenocarcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":["capox"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2009,"doi":"10.1200/JCO.2008.19.7145","pmid":"19164203","authors":"Overman MJ, Varadhachary GR, Kopetz S, et al.","paperType":"observational","findings":["Objective response rate 50 percent; median time to progression 11.3 months; median overall survival 20.4 months."],"whatItMeans":"Fluoropyrimidine plus oxaliplatin is the first-line chemotherapy for advanced small bowel adenocarcinoma and the regimen tested after surgery in BALLAD.","caveats":["Small single-arm study mixing small bowel and ampullary cancers.","No randomised comparison exists for first-line chemotherapy in this disease."],"changedPractice":true,"participants":30},{"id":"paper-tchekmedyian-lenvatinib-adenoid-cystic-jco-2019","kind":"paper","name":"Phase 2 study of lenvatinib in progressive, recurrent or metastatic adenoid cystic carcinoma","aka":[],"tldr":"The multikinase inhibitor lenvatinib shrank tumours in about one in six patients with progressing adenoid cystic carcinoma and stabilised most of the rest, making it one of the few active drugs for this slow-growing salivary cancer.","summary":"Single-arm phase 2 study of 32 patients with progressive recurrent or metastatic adenoid cystic carcinoma treated with lenvatinib 24 mg daily.\n\nPartial response occurred in 15.6 percent and stable disease in 75 percent, with a median progression-free survival of 17.5 months; most patients required dose reductions for hypertension, fatigue and oral pain.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2019","url":"https://doi.org/10.1200/JCO.18.01859"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30939095/"}],"tags":[],"related":[],"cancers":["adenoid-cystic-carcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":["lenvatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2019,"doi":"10.1200/JCO.18.01859","pmid":"30939095","authors":"Tchekmedyian V, Sherman EJ, Dunn L, et al.","paperType":"observational","findings":["Partial response 15.6 percent; stable disease 75 percent.","Median progression-free survival 17.5 months."],"whatItMeans":"Lenvatinib (like axitinib) is a guideline option for progressing adenoid cystic carcinoma; responses are uncommon, so it is reserved for documented progression rather than indolent disease.","caveats":["Small single-arm study in a slow-growing disease, where stable disease may reflect natural history.","Dose reductions were needed in most patients."],"changedPractice":true,"participants":32},{"id":"paper-viardot-blood","kind":"paper","name":"Phase 2 study of the bispecific T-cell engager (BiTE) antibody blinatumomab in relapsed/refractory diffuse large B-cell lymphoma","aka":[],"tldr":"Paper cited by one target page, indexed on Europe PMC as PubMed record 26755709 and published in Blood; the citing page links this DOI, which is how the record was matched.","summary":"Few patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) achieve prolonged disease-free survival. Blinatumomab, a bispecific T-cell engaging antibody construct, transiently links CD3-positive T cells to CD19-positive B cells. This phase 2 study evaluated stepwise (9-28-112 μg/d with weekly dose increases; n = 23) or flat (112 μg/d; n = 2) dosing of blinatumomab by continuous infusion, with dexamethasone prophylaxis, in patients with relapsed/refractory DLBCL. Patients received a median of 3 prior lines of therapy. Median time since last regimen was 1.5 months. Seventeen patients ended treatment in cycle 1 (induction), 7 in cycle 2 (consolidation), and 1 in retreatment. Among 21 evaluable patients, the overall response rate after 1 blinatumomab cycle was 43%, including complete responses (CRs) in 19%. Three patients had late CR in follow-up without other treatment. The most common adverse events with stepwise dosing were tremor (48%), pyrexia (44%), fatigue (26%), and edema (26%). Grade 3 neurologic events with stepwise dosing were encephalopathy and aphasia (each 9%) and tremor, speech disorder, dizziness, somnolence, and disorientation (each 4%). Of 5 (22%) patients who discontinued stepwise dosing because of adverse events, 4 (17%) had neurologic events. Most neurologic events resolved. The flat-dose cohort was stopped because of grade 3 neurologic events in both patients. Blinatumomab monotherapy appears effective in patients with relapsed/refractory DLBCL, a heavily pretreated patient population with a high unmet medical need. Further studies need to define the optimal approach to achieve the target dose without early dropout. The study was registered at www.clinicaltrials.gov as #NCT01741792.\n\nIndexed on Europe PMC as PubMed record 26755709 (DOI 10.1182/blood-2015-06-651380). Matched by DOI alone: one target page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Blood 2016","url":"https://doi.org/10.1182/blood-2015-06-651380"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26755709/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26755709"}],"tags":["europepmc-ingest"],"related":["cd79b"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["blood"],"dependsOn":[],"notes":[],"journal":"Blood","year":2016,"doi":"10.1182/blood-2015-06-651380","pmid":"26755709","authors":"Viardot A, Goebeler ME, Hess G, et al.","paperType":"observational","findings":[],"whatItMeans":"One target page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-royal-ipilimumab-pancreatic-j-immunother-2010","kind":"paper","name":"Phase 2 trial of single agent ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma","aka":[],"tldr":"The first checkpoint inhibitor trial in pancreatic cancer gave ipilimumab to 27 patients and not one tumour shrank by the standard measure, though one patient regressed later after apparent progression.","summary":"Adults with locally advanced or metastatic pancreatic adenocarcinoma, measurable disease, good performance status and minimal comorbidity received intravenous ipilimumab 3.0 mg/kg every 3 weeks, four doses per course, for up to two courses. Twenty-seven were enrolled (20 metastatic, 7 locally advanced), median age 55. Three had grade 3 or higher immune-mediated adverse events (colitis, encephalitis, hypophysitis). There were no responders by RECIST, although one subject had a delayed response after initial progression, with regression of the primary and 20 hepatic metastases and normalisation of tumour markers.","asOf":"2026-09-24","links":[{"label":"Royal et al., J Immunother 2010: ipilimumab in 27 patients, no RECIST response","url":"https://doi.org/10.1097/CJI.0b013e3181eec14c"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20842054/"}],"tags":[],"related":[],"cancers":["pancreatic","metastatic-pdac","locally-advanced-pdac"],"sections":[],"technologies":[],"targets":["ctla4"],"drugs":["ipilimumab"],"companies":[],"institutions":["nci-ccr"],"pathways":["pd1-checkpoint"],"terms":["cold-vs-hot"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of Immunotherapy","year":2010,"doi":"10.1097/CJI.0b013e3181eec14c","pmid":"20842054","authors":"Royal RE, Levy C, Turner K, et al.","paperType":"rct","findings":["No RECIST responses to single-agent ipilimumab in 27 patients.","One delayed regression after apparent progression."],"whatItMeans":"The first of the negative checkpoint trials that define pancreatic cancer as immunologically cold, with a single anecdote that kept the field going.","caveats":["Single-arm, 27 patients, no biomarker selection.","Predates the MSI-high exception."],"changedPractice":false,"participants":27},{"id":"paper-takahashi-trastuzumab-docetaxel-salivary-duct-jco-2019","kind":"paper","name":"Phase 2 trial of trastuzumab and docetaxel in HER2-positive salivary duct carcinoma","aka":[],"tldr":"In HER2-positive salivary duct carcinoma, an aggressive salivary cancer resembling breast cancer, trastuzumab plus docetaxel shrank tumours in 70 percent of patients, establishing HER2 testing and targeting in the disease.","summary":"Single-arm phase 2 study of 57 patients with HER2-positive locally advanced, recurrent or metastatic salivary duct carcinoma treated with trastuzumab and docetaxel.\n\nObjective response was 70.2 percent with a median progression-free survival of 8.9 months and median overall survival of 39.7 months, with toxicity similar to the regimen's use in breast cancer.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2019","url":"https://doi.org/10.1200/JCO.18.00545"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30452336/"}],"tags":[],"related":[],"cancers":["salivary-duct-carcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":["docetaxel","trastuzumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2019,"doi":"10.1200/JCO.18.00545","pmid":"30452336","authors":"Takahashi H, Tada Y, Saotome T, et al.","paperType":"observational","findings":["Objective response 70.2 percent.","Median progression-free survival 8.9 months; median overall survival 39.7 months."],"whatItMeans":"HER2 testing is standard in salivary duct carcinoma and trastuzumab-docetaxel a first-line option for HER2-positive advanced disease, with trastuzumab deruxtecan available at progression.","caveats":["Single-arm study in a rare disease.","About 30 to 40 percent of salivary duct carcinomas are HER2-positive."],"changedPractice":true,"participants":57},{"id":"paper-defibrotide-2005-01-blood-2016","kind":"paper","name":"Phase 3 trial of defibrotide for the treatment of severe veno-occlusive disease and multi-organ failure","aka":[],"tldr":"The primary report of Study 2005-01: 38 percent of transplant patients with severe veno-occlusive disease and organ failure were alive at day 100 on defibrotide, against 25 percent of carefully matched historical controls.","summary":"Phase 3 study of defibrotide in patients with established hepatic veno-occlusive disease (sinusoidal obstruction syndrome) and advanced multi-organ failure after haematopoietic stem cell transplantation, a condition with more than 80 percent mortality untreated. Patients (n = 102) given defibrotide 25 mg per kilogram per day were compared with 32 historical controls identified from 6867 medical charts of transplant patients by blinded independent reviewers; baseline characteristics were well balanced.\n\nThe primary endpoint was survival at day +100 post-transplant: observed rates were 38.2 percent in the defibrotide group and 25 percent in the controls (23 percent estimated difference; 95.1% CI 5.2 to 40.8; P = .0109, propensity-adjusted analysis). Observed day +100 complete response rates were 25.5 percent for defibrotide and 12.5 percent for controls (19 percent difference; 95.1% CI 3.5 to 34.6; P = .0160). Related adverse events included haemorrhage or hypotension; common haemorrhagic events (pulmonary alveolar 11.8 and 15.6 percent, gastrointestinal 7.8 and 9.4 percent) were similar between groups.","asOf":"2026-09-24","links":[{"label":"Blood 2016","url":"https://doi.org/10.1182/blood-2015-10-676924"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26825712/"},{"label":"ClinicalTrials.gov NCT00358501","url":"https://clinicaltrials.gov/study/NCT00358501"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["defibrotide"],"companies":["jazz"],"institutions":[],"pathways":[],"terms":["allogeneic-transplant"],"trials":["study-2005-01"],"people":["paul-richardson"],"bottlenecks":[],"keyPapers":[],"journals":["blood"],"dependsOn":[],"notes":[],"journal":"Blood","year":2016,"doi":"10.1182/blood-2015-10-676924","pmid":"26825712","authors":"Richardson PG, Riches ML, Kernan NA, et al.","paperType":"observational","findings":["Day +100 survival 38.2% with defibrotide vs 25% in historical controls; estimated difference 23% (95.1% CI 5.2 to 40.8), P = .0109.","Day +100 complete response 25.5% vs 12.5%; difference 19% (95.1% CI 3.5 to 34.6), P = .0160.","Haemorrhagic adverse events similar between groups: pulmonary alveolar bleeding 11.8% vs 15.6%, gastrointestinal bleeding 7.8% vs 9.4%."],"whatItMeans":"This is the trial behind defibrotide's March 2016 US approval, the only approved treatment for hepatic veno-occlusive disease with organ failure after transplant. The historical-control design was accepted because a randomised trial in a condition this lethal and rare was judged unfeasible; the gain is meaningful but most patients still died.","caveats":["Historically controlled, not randomised; the 32 controls were matched from chart review.","95.1% confidence intervals adjust for an interim analysis.","Absolute survival remained low (38% at day 100)."],"changedPractice":true,"participants":134},{"id":"paper-vogelzang-pemetrexed-mesothelioma-jco-2003","kind":"paper","name":"Phase 3 trial of pemetrexed plus cisplatin versus cisplatin alone in malignant pleural mesothelioma","aka":[],"tldr":"Adding pemetrexed to cisplatin lengthened survival by almost three months in pleural mesothelioma, making platinum-pemetrexed the first, and for many years the only, standard chemotherapy for the disease.","summary":"Phase 3 trial of 456 chemotherapy-naive patients with malignant pleural mesothelioma randomised to pemetrexed plus cisplatin or cisplatin alone, with folic acid and vitamin B12 supplementation introduced part-way through to reduce toxicity.\n\nMedian overall survival was 12.1 versus 9.3 months, response rate 41.3 versus 16.7 percent, and lung function and symptoms were better with the combination; vitamin supplementation markedly reduced severe toxicity.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2003","url":"https://doi.org/10.1200/JCO.2003.11.136"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/12860938/"}],"tags":[],"related":[],"cancers":["pleural-mesothelioma","peritoneal-mesothelioma"],"sections":[],"technologies":[],"targets":[],"drugs":["cisplatin","pemetrexed"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2003,"doi":"10.1200/JCO.2003.11.136","pmid":"12860938","authors":"Vogelzang NJ, Rusthoven JJ, Symanowski J, et al.","paperType":"rct","findings":["Median overall survival 12.1 vs 9.3 months.","Objective response 41.3 percent vs 16.7 percent."],"whatItMeans":"Platinum-pemetrexed remains the chemotherapy backbone in mesothelioma, now combined with pembrolizumab or bevacizumab, or replaced by dual immunotherapy in non-epithelioid disease.","caveats":["Single-agent cisplatin comparator.","Vitamin supplementation changed mid-trial."],"changedPractice":true,"participants":456},{"id":"paper-van-as-n-engl-j-med","kind":"paper","name":"Phase 3 Trial of Stereotactic Body Radiotherapy in Localized Prostate Cancer","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 39413377 and published in New England Journal of Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Background: Whether stereotactic body radiotherapy (SBRT) is noninferior to conventionally or moderately hypofractionated regimens with respect to biochemical or clinical failure in patients with localized prostate cancer is unclear.\n\nMethods: We conducted a phase 3, international, open-label, randomized, controlled trial. Men with stage T1 or T2 prostate cancer, a Gleason score of 3+4 or less, and a prostate-specific antigen (PSA) level of no more than 20 ng per milliliter were randomly assigned (in a 1:1 ratio) to receive SBRT (36.25 Gy in 5 fractions over a period of 1 or 2 weeks) or control radiotherapy (78 Gy in 39 fractions over a period of 7.5 weeks or 62 Gy in 20 fractions over a period of 4 weeks). Androgen-deprivation therapy was not permitted. The primary end point was freedom from biochemical or clinical failure, with a critical hazard ratio for noninferiority of 1.45. The analysis was performed in the intention-to-treat population.\n\nResults: A total of 874 patients underwent randomization at 38 centers (433 patients in the SBRT group and 441 in the control radiotherapy group) between August 2012 and January 2018. The median age of the patients was 69.8 years, and the median PSA level was 8.0 ng per milliliter; the National Comprehensive Cancer Network risk category was low for 8.4% of the patients and intermediate for 91.6%. At a median follow-up of 74.0 months, the 5-year incidence of freedom from biochemical or clinical failure was 95.8% (95% confidence interval [CI], 93.3 to 97.4) in the SBRT group and 94.6% (95% CI, 91.9 to 96.4) in the control radiotherapy group (unadjusted hazard ratio for biochemical or clinical failure, 0.73; 90% CI, 0.48 to 1.12; P = 0.004 for noninferiority), which indicated the noninferiority of SBRT. At 5 years, the cumulative incidence of late Radiation Therapy Oncology Group (RTOG) grade 2 or higher genitourinary toxic effects was 26.9% (95% CI, 22.8 to 31.5) with SBRT and 18.3% (95% CI, 14.8 to 22.5) with control radiotherapy (P<0.001), and the cumulative incidence of late RTOG grade 2 or higher gastrointestinal toxic effects was 10.7% (95% CI, 8.1 to 14.2) and 10.2% (95% CI, 7.7 to 13.5), respectively (P = 0.94).\n\nConclusions: Five-fraction SBRT was noninferior to control radiotherapy with respect to biochemical or clinical failure and may be an efficacious treatment option for patients with low-to-intermediate-risk localized prostate cancer as defined in this trial. (Funded by Accuray and others; PACE-B ClinicalTrials.gov number, NCT01584258.).\n\nIndexed on Europe PMC as PubMed record 39413377 (DOI 10.1056/nejmoa2403365). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2024","url":"https://doi.org/10.1056/nejmoa2403365"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39413377/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39413377"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["pace-b"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2024,"doi":"10.1056/nejmoa2403365","pmid":"39413377","authors":"van As N, Griffin C, Tree A, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nct05877430-j-immunother-cancer-2026","kind":"paper","name":"Phase I trial of CJRB-101 plus pembrolizumab in patients with metastatic non-small cell lung cancer, head and neck squamous cell carcinoma and melanoma","aka":[],"tldr":"Published report from the trial registered as NCT05877430, in Journal for ImmunoTherapy of Cancer (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Dysbiosis of gut microbiome leads to resistance to immunotherapy in various advanced solid tumors. CJRB-101 is a live biotherapeutic product consisting of a novel strain belonging to the species Leuconostoc mesenteroides. To modulate the tumor microenvironment, CJRB-101 was combined with pembrolizumab.\n\nMethods: Preclinical efficacy and mechanistic studies were performed using humanized non-small cell lung cancer (NSCLC) patient-derived xenograft (PDX) models. This is a multicenter, first-in-human, two-part, phase I, open-label study of CJRB-101 (1×10 11 or 4×10 11 colony forming unit (CFU)/day) plus pembrolizumab (200 mg every three weeks (Q3W)) in advanced NSCLC, melanoma, and head and neck squamous cell carcinoma in both immune checkpoint inhibitor (ICI)-naive and ICI-refractory settings. The primary endpoint was to assess the dose-limiting toxicities (DLTs), adverse events, and preliminary activity of the combination treatment. Exploratory endpoints included stool metagenomics analysis and pharmacodynamics parameters.\n\nResults: In four PDX models, CJRB-101 with pembrolizumab demonstrated enhanced antitumor efficacy, showing a tumor growth inhibition (TGI) of 77.3% in the CJRB-101 monotherapy group and 61.9% in the combination group, which was significantly improved compared with pembrolizumab alone. A distinct M2-to-M1 repolarization was observed and validated in vitro. Notably, increased activation of cytotoxic T cells was observed, suggesting an immune-mediated antitumor mechanism of CJRB-101. A total of 42 patients were enrolled in the low-dose cohort (one capsule once a day; n=6) and high-dose cohort (two capsules two times a day, n=36). Metastatic NSCLC accounted for 86% (n=36) and 67% (n=28) of the patients were refractory to ICIs. None of the patients experienced DLT. In ICI-naïve NSCLC (n=12) with programmed death-ligand 1 (PD-L1) >50%, the overall response rate (ORR) and disease control rate (DCR) were 58% and 75%, respectively. The ORR was 5% and DCR was 41% in the ICI-refractory NSCLC (n=22) with an ORR of 5% and DCR of 41%. After a median follow-up of 15.6 months and 8.9 months for ICI-naïve and ICI-refractory NSCLC, the median progression-free survival was 9 months (95% CI 5.6 to not reached) and 1.8 months (95% CI 1.6 to 4.3), respectively. CJRB-101 plus pembrolizumab was well-tolerated, and none of the patients experienced grade > 3 treatment-related adverse events.\n\nConclusions: Early clinical data show encouraging antitumor response of CJRB-101 plus pembrolizumab in ICI-naïve metastatic NSCLC with PD-L1 > 50%.\n\nTrial registration number: NCT05877430.\n\nIndexed on Europe PMC as PubMed record 42140743 (DOI 10.1136/jitc-2025-014702). Its abstract cites the registry id NCT05877430, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Immunother Cancer 2026","url":"https://doi.org/10.1136/jitc-2025-014702"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42140743/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42140743"},{"label":"ClinicalTrials.gov NCT05877430","url":"https://clinicaltrials.gov/study/NCT05877430"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05877430"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jitc"],"dependsOn":[],"notes":[],"journal":"Journal for ImmunoTherapy of Cancer","year":2026,"doi":"10.1136/jitc-2025-014702","pmid":"42140743","authors":"Lee JB, Baek S, Kim DK, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05877430 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-reidy-lagunes-clin-cancer-res","kind":"paper","name":"Phase I Trial of Well-Differentiated Neuroendocrine Tumors (NETs) with Radiolabeled Somatostatin Antagonist 177 Lu-Satoreotide Tetraxetan","aka":[],"tldr":"Paper cited by one idea page, indexed on Europe PMC as PubMed record 31439583 and published in Clinical Cancer Research; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: Radiolabeled somatostatin receptor 2 (SSTR2) antagonists have shown higher tumor uptake and tumor-to-organ ratios than somatostatin agonists in preclinical models of neuroendocrine tumors (NETs). We performed a phase I study to evaluate the safety and efficacy of SSTR2 antagonist 177 Lu-satoreotide tetraxetan.\n\nPatients and methods: Twenty patients with advanced SSTR2-positive NETs were treated with 177 Lu-satoreotide tetraxetan. Patients first underwent a dosimetry study with 177 Lu-satoreotide tetraxetan to determine the therapeutic activity that could be safely administered. This activity was split into two equal cycles to be delivered 3 months apart. The maximum activity was 7.4 GBq per cycle.\n\nResults: Of 20 patients with NETs (one lung, seven small bowel, nine pancreatic, one gastric, one rectal, one kidney; mean prior treatments: three), six received one cycle of 177 Lu- satoreotide tetraxetan and 14 received two cycles. Hematologic toxicity after cycle 1 was mild-moderate and reversed before cycle 2. However, grade 4 hematologic toxicity occurred in four of seven (57%) patients after cycle 2 of 177 Lu-satoreotide tetraxetan. The study was suspended, and the protocol modified to limit the cumulative absorbed bone marrow dose to 1 Gy and to reduce prescribed activity for cycle 2 by 50%. The best overall response rate was 45% [5% complete response (1/20), 40% partial response (8/20)]; with 40% stable disease (8/20) and 15% progression of disease (3/20). Median progression-free survival (PFS) was 21.0 months (95% CI, 13.6-NR).\n\nConclusions: In this trial of heavily treated NETs, preliminary data are promising for the use of 177 Lu-satoreotide tetraxetan. Additional studies are ongoing to determine optimal therapeutic dose/schedule.\n\nIndexed on Europe PMC as PubMed record 31439583 (DOI 10.1158/1078-0432.ccr-19-1026). Matched by DOI alone: one idea page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Clin Cancer Res 2019","url":"https://doi.org/10.1158/1078-0432.ccr-19-1026"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31439583/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31439583"}],"tags":["europepmc-ingest"],"related":["idea-net-antagonist-ligands"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2019,"doi":"10.1158/1078-0432.ccr-19-1026","pmid":"31439583","authors":"Reidy-Lagunes D, Pandit-Taskar N, O'Donoghue JA, et al.","paperType":"basic","findings":[],"whatItMeans":"One idea page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-cd47-colorectal-cancer-res-commun-2025","kind":"paper","name":"Phase II Clinical Trial and Preclinical Evaluation of a Novel CD47 Blockade Combination in Refractory Microsatellite-Stable Metastatic Colorectal Cancer","aka":[],"tldr":"Phase 2 or 3 results paper on CD47 in Colorectal cancer, in Cancer research communications (2025), one of the most cited Europe PMC records with CD47 in its title.","summary":"Purpose: In this preclinical human immune system patient-derived xenograft (HIS-PDX) model and phase II clinical trial, we assessed evorpacept (anti-CD47 engineered fusion protein with inactive Fc), cetuximab, and pembrolizumab (triple therapy) in microsatellite-stable (MSS) colorectal cancer.\n\nPatients and methods: HIS BALB/c-Rag2nullIl2rγnullSirpαNOD mice with PDXs were treated with triple therapy or its components. Patients with refractory MSS colorectal cancer were treated with triple therapy in a safety run-in (stage 1) followed by expansion (stage 2, planned N = 42). The co-primary objectives were to determine the recommended dose of evorpacept and objective response rate (vs. historic control).\n\nResults: In HIS-PDX mice, triple therapy decreased the growth of MSS colorectal cancer tumors and increased tumor-infiltrating CD8+ T cells. Sixteen patients were treated on the clinical trial across two evorpacept dose levels: N = 12 in stage 1 and N = 4 in stage 2. Trial enrollment was terminated early because of safety concerns (one treatment-related grade 5 event each of hemophagocytic lymphohistiocytosis and cytokine release syndrome). Otherwise, the adverse event profile was as expected. Among all patients, the objective response rate was 6.3%; formal hypothesis testing was not performed. The disease control rate was 12.5%, the median progression-free survival was 2.3 months, and the median overall survival was 10.9 months. Blood- and tumor-based clinical trial correlative analyses identified innate and adaptive immune system activation.\n\nConclusions: Whereas triple therapy demonstrated evidence of efficacy in refractory MSS colorectal cancer, safety concerns halted enrollment. Further investigation is necessary to determine the optimal use of CD47-targeted therapies in MSS colorectal cancer.\n\nSignificance: Evorpacept, cetuximab, and pembrolizumab demonstrated antitumor activity in a preclinical HIS-PDX model and clinical trial in refractory MSS colorectal cancer; however, immune-related adverse events prompted early termination of study enrollment. Evidence of innate and adaptive antitumor immune activation was identified. The role of SIRPα/CD47 blockade in the treatment of MSS colorectal cancer needs to be further elucidated in future trials.\n\nIndexed on Europe PMC as PubMed record 41171165 (DOI 10.1158/2767-9764.crc-25-0332). Its title names CD47 and its text names Colorectal cancer; PubMed types it as a clinical trial report (Clinical Trial, Phase II, Research Support, Non-U.S. Gov't, research-article). It was matched automatically to the idea \"Engineered bacteria that live in tumours and manufacture drugs there\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer Res Commun 2025","url":"https://doi.org/10.1158/2767-9764.crc-25-0332"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41171165/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41171165"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-research-communications"],"dependsOn":[],"notes":[],"journal":"Cancer research communications","year":2025,"doi":"10.1158/2767-9764.crc-25-0332","pmid":"41171165","authors":"Lentz RW, Lang J, Pitts TM, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for CD47 in Colorectal cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by CD47 in the title and Colorectal cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-nct03974022-j-clin-oncol-2025","kind":"paper","name":"Phase II Dose-Randomized Study of Sunvozertinib in Platinum-Pretreated Non-Small Cell Lung Cancer With Epidermal Growth Factor Receptor Exon 20 Insertion Mutations (WU-KONG1B)","aka":[],"tldr":"Published report from the WU-KONG1 trial registered as NCT03974022, in Journal of Clinical Oncology (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Purpose: WU-KONG1B (ClinicalTrials.gov identifier: NCT03974022) is a multinational phase II, dose-randomized study to assess the antitumor efficacy of sunvozertinib in pretreated patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor ( EGFR) exon 20 insertion mutations (exon20ins).\n\nMethods: Eligible patients with advanced-stage EGFR exon20ins NSCLC were randomly assigned by 1:1 ratio to receive sunvozertinib 200 mg or 300 mg once daily (200 and 300 mg-rand cohorts). After predefined interim analysis, additional patients were enrolled and treated with the 300 mg dose once daily. The primary end point was blinded independent review committee (IRC)-assessed confirmed objective response rate (cORR), and the key secondary end point was duration of response (DoR).\n\nResults: Among 85, 89, and 107 efficacy-evaluable patients in 200 mg-rand, 300 mg-rand, and 300 mg-all (including randomly assigned and nonrandomized patients) cohorts, the cORRs were 45.9% (97.5% CI, 33.6% to 58.5%), 47.2% (97.5% CI, 35.1% to 59.5%), and 45.8% (97.5% CI, 34.8% to 57.0%), respectively, per IRC assessment. The predefined null hypothesis was rejected with statistical significance ( P <.0001). Comparing 300 and 200 mg-rand cohorts, higher cORRs were observed in patients with baseline brain metastasis (52.4% v 28.6%) and previous amivantamab treatment (41.7% v 25%), as well as longer DoR (13.8 v 11.1 months). At 200 and 300 mg once daily, the most common treatment-related adverse events with grade ≥3 included diarrhea (2.2% v 18%), blood creatine phosphokinase increased (6.6% v 12.6%), and anemia (4.4% v 6.3%).\n\nConclusion: Sunvozertinib is efficacious at both 200 and 300 mg once daily in treating platinum-pretreated patients with advanced EGFR exon20ins NSCLC. The treatment-related adverse events of sunvozertinib were consistent with an EGFR tyrosine kinase inhibitor, with a more favorable safety profile at 200 mg than 300 mg once daily.\n\nIndexed on Europe PMC as PubMed record 40923280 (DOI 10.1200/jco-25-00788). Its abstract cites the registry id NCT03974022, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2025","url":"https://doi.org/10.1200/jco-25-00788"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40923280/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40923280"},{"label":"ClinicalTrials.gov NCT03974022","url":"https://clinicaltrials.gov/study/NCT03974022"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct03974022"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2025,"doi":"10.1200/jco-25-00788","pmid":"40923280","authors":"Yang JC, Wang M, Doucet L, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03974022 with the most citations, so it is the natural first reading for anyone following the WU-KONG1 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-cd30-hodgkin-lymphoma-j-clin-oncol-2015","kind":"paper","name":"Phase II Investigator-Initiated Study of Brentuximab Vedotin in Mycosis Fungoides and Sézary Syndrome With Variable CD30 Expression Level: A Multi-Institution Collaborative Project","aka":[],"tldr":"Phase 2 or 3 results paper on CD30 in Hodgkin lymphoma, in Journal of Clinical Oncology (2015), one of the most cited Europe PMC records with CD30 in its title.","summary":"Purpose: In contrast to Hodgkin lymphoma and systemic anaplastic large-cell lymphoma, CD30 expression of malignant lymphocytes in mycosis fungoides (MF) and Sézary syndrome (SS) is quite variable. Clinical activity and safety of brentuximab vedotin, a CD30 targeting antibody-drug conjugate, was evaluated in MF and SS. Tissue and blood biomarkers of clinical response were explored.\n\nPatients and methods: In this phase II study, patients with MF or SS with negligible to 100% CD30 expression levels were treated with brentuximab vedotin (1.8 mg/kg) every 3 weeks for a maximum of sixteen doses. The primary end point was overall global response rate. Secondary end points included correlation of tissue CD30 expression level with clinical response, time to response, duration of response, progression-free and event-free survivals, and safety.\n\nResults: Of the 32 patients enrolled and treated, 30 patients had available efficacy evaluations. Objective global response was observed in 21 (70%) of 30 patients (90% CI, 53% to 83%). CD30 expression assessed by immunohistochemistry was highly variable, with a median CD30max of 13% (range, 0% to 100%). Those with <5% CD30 expression had a lower likelihood of global response than did those with 5% or greater CD30 expression (P <.005). CD163 positive tumor-associated macrophages, many of which coexpress CD30, were abundant in tissue. Peripheral neuropathy was the most common adverse event.\n\nConclusion: Brentuximab vedotin demonstrated significant clinical activity in treatment-refractory or advanced MF or SS with a wide range of CD30 expression levels. Additional biomarker studies may help optimize rational design of combination therapies with brentuximab vedotin.\n\nIndexed on Europe PMC as PubMed record 26195720 (DOI 10.1200/jco.2014.60.3969). Its title names CD30 and its text names Hodgkin lymphoma; PubMed types it as a clinical trial report (Clinical Trial, Phase II, Research Support, Non-U.S. Gov't, research-article, Multicenter Study). It was matched automatically to the idea \"CD30 CAR-T for multiply relapsed Hodgkin lymphoma\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2015","url":"https://doi.org/10.1200/jco.2014.60.3969"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26195720/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26195720"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2015,"doi":"10.1200/jco.2014.60.3969","pmid":"26195720","authors":"Kim YH, Tavallaee M, Sundram U, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for CD30 in Hodgkin lymphoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by CD30 in the title and Hodgkin lymphoma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-reckamp-j-clin-oncol","kind":"paper","name":"Phase II Randomized Study of Ramucirumab and Pembrolizumab Versus Standard of Care in Advanced Non-Small-Cell Lung Cancer Previously Treated With Immunotherapy-Lung-MAP S1800A","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 35658002 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: Resistance to immune checkpoint inhibition (ICI) in advanced non-small-cell lung cancer (NSCLC) represents a major unmet need. Combining ICI with vascular endothelial growth factor (VEGF)/VEGF receptor inhibition has yielded promising results in multiple tumor types.\n\nMethods: In this randomized phase II Lung-MAP nonmatch substudy (S1800A), patients ineligible for a biomarker-matched substudy with NSCLC previously treated with ICI and platinum-based chemotherapy and progressive disease at least 84 days after initiation of ICI were randomly assigned to receive ramucirumab plus pembrolizumab (RP) or investigator's choice standard of care (SOC: docetaxel/ramucirumab, docetaxel, gemcitabine, and pemetrexed). With a goal of 130 eligible patients, the primary objective was to compare overall survival (OS) using a one-sided 10% level using the better of a standard log-rank (SLR) and weighted log-rank (WLR; G[rho = 0, gamma = 1]) test. Secondary end points included objective response, duration of response, investigator-assessed progression-free survival, and toxicity.\n\nResults: Of 166 patients enrolled, 136 were eligible (69 RP; 67 SOC). OS was significantly improved with RP (hazard ratio [80% CI]: 0.69 [0.51 to 0.92]; SLR one-sided P =.05; WLR one-sided P =.15). The median (80% CI) OS was 14.5 (13.9 to 16.1) months for RP and 11.6 (9.9 to 13.0) months for SOC. OS benefit for RP was seen in most subgroups. Investigator-assessed progression-free survival (hazard ratio [80% CI]: 0.86 [0.66 to 1.14]; one-sided SLR, P =.25 and.14 for WLR) and response rates (22% RP v 28% SOC, one-sided P =.19) were similar between arms. Grade ≥ 3 treatment-related adverse events occurred in 42% of patients in the RP group and 60% on SOC.\n\nConclusion: This randomized phase II trial demonstrated significantly improved OS with RP compared with SOC in patients with advanced NSCLC previously treated with ICI and chemotherapy. The safety was consistent with known toxicities of both drugs. These data warrant further evaluation.\n\nIndexed on Europe PMC as PubMed record 35658002 (DOI 10.1200/jco.22.00912). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2022","url":"https://doi.org/10.1200/jco.22.00912"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35658002/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35658002"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["lung-map-s1800a"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2022,"doi":"10.1200/jco.22.00912","pmid":"35658002","authors":"Reckamp KL, Redman MW, Dragnev KH, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-luca-gianni-cancer-med-2023","kind":"paper","name":"Phase II study (KAMELEON) of single-agent T-DM1 in patients with HER2-positive advanced urothelial bladder cancer or pancreatic cancer/cholangiocarcinoma","aka":[],"tldr":"Paper by Luca Gianni indexed on Europe PMC as PubMed record 37119523, in Cancer medicine (2023), one of the most cited records naming an author with this name at Fondazione Michelangelo.","summary":"The antibody-drug conjugate trastuzumab emtansine (T-DM1) is approved for human epidermal growth factor receptor 2 (HER2/ERBB2)-positive breast cancer. We aimed to study tumor HER2 expression and its effects on T-DM1 responses in patients with HER2-positive urothelial bladder cancer (UBC) or pancreatic cancer (PC)/cholangiocarcinoma (CC). In the phase II KAMELEON study (NCT02999672), HER2 status was centrally assessed by immunohistochemistry, with positivity defined as non-focal homogeneous or heterogeneous overexpression of HER2 in ≥30% of stained cells. We also performed exploratory biomarker analyses (e.g., gene-protein assay) on tissue samples collected from study participants and consenting patients who failed screening. Of the 284 patients successfully screened for HER2 status (UBC, n = 69; PC/CC, n = 215), 13 with UBC, four with PC, and three with CC fulfilled eligibility criteria. Due to recruitment difficulty, the sponsor terminated KAMELEON prematurely. Of the five responders in the UBC cohort (overall response rate, 38.5%), HER2 expression was heterogeneous in two and homogeneous in three. The one responder in the PC/CC cohort had PC, and the tumor displayed homogeneous expression. In the biomarker-evaluable population, composed of screen-failed and enrolled patients, 24.3% (9/37), 1.5% (1/66), and 8.2% (4/49) of those with UBC, PC, or CC, respectively, had HER2-positive tumors. In a gene-protein assay combining in situ hybridization with immunohistochemistry, greater HER2 homogeneity was associated with increased ERBB2 amplification ratio. In conclusion, KAMELEON showed that some patients with HER2-positive UBC or PC can respond to T-DM1 and provided insight into the prevalence of HER2 positivity and expression patterns in three non-breast tumor types.\n\nIndexed on Europe PMC as PubMed record 37119523 (DOI 10.1002/cam4.5893). Its author list gives \"Gianni L\" with the affiliation \"Michelangelo Foundation, Milan, Italy\", which names Fondazione Michelangelo; that is how the record was matched to Luca Gianni, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer Med 2023","url":"https://doi.org/10.1002/cam4.5893"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37119523/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37119523"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["luca-gianni"],"bottlenecks":[],"keyPapers":[],"journals":["cancer-medicine"],"dependsOn":[],"notes":[],"journal":"Cancer medicine","year":2023,"doi":"10.1002/cam4.5893","pmid":"37119523","authors":"de Vries EGE, Rüschoff J, Lolkema M, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Luca Gianni at Fondazione Michelangelo, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-reiss-rucaparib-maintenance-brca-palb2-pancreatic-jco-2021","kind":"paper","name":"Phase II study of maintenance rucaparib in patients with platinum-sensitive advanced pancreatic cancer and a pathogenic germline or somatic variant in BRCA1, BRCA2, or PALB2","aka":[],"tldr":"Rucaparib maintenance after platinum chemotherapy kept 60% of 42 patients progression-free at six months, with responses in germline BRCA2, germline PALB2 and somatic BRCA2 carriers, widening the group PARP inhibitors may help beyond POLO's germline BRCA rule.","summary":"Investigator-initiated single-arm phase 2: advanced pancreatic cancer with a germline or somatic pathogenic variant in BRCA1, BRCA2 or PALB2 after at least 16 weeks of platinum without resistance; chemotherapy stopped and rucaparib 600 mg twice daily given until progression. Of 46 enrolled, 42 were evaluable (27 gBRCA2, 7 gBRCA1, 6 gPALB2, 2 sBRCA2). Progression-free survival at 6 months was 59.5%, median 13.1 months; median overall survival 23.5 months; 12-month progression-free survival 54.8%. Response in 36 measurable patients was 41.7% (3 complete), disease control 66.7%, median duration 17.3 months; responses in gBRCA2 (11 of 27), gPALB2 (3 of 6) and sBRCA2 (1 of 2).","asOf":"2026-09-24","links":[{"label":"Reiss et al., J Clin Oncol 2021: maintenance rucaparib in 42 BRCA1, BRCA2 or PALB2 patients","url":"https://doi.org/10.1200/JCO.21.00003"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33970687/"}],"tags":[],"related":["brca-germline","brca-somatic"],"cancers":["pancreatic","brca-palb2-pdac","metastatic-pdac"],"sections":[],"technologies":[],"targets":["brca","palb2"],"drugs":["rucaparib"],"companies":[],"institutions":["penn-abramson"],"pathways":[],"terms":["synthetic-lethality","germline-vs-somatic"],"trials":[],"people":["robert-vonderheide"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2021,"doi":"10.1200/JCO.21.00003","pmid":"33970687","authors":"Reiss KA, Mick R, O'Hara MH, et al.","paperType":"rct","findings":["Six-month progression-free survival 59.5%, median 13.1 months; overall survival 23.5 months.","Response 41.7%; gPALB2 3 of 6 and sBRCA2 1 of 2 responded."],"whatItMeans":"It is the evidence that PALB2 and somatic BRCA2 belong in the PARP inhibitor conversation even though the olaparib label stops at germline BRCA.","caveats":["Single-arm, 42 evaluable, platinum-sensitive selection.","Rucaparib has no pancreatic approval."],"changedPractice":false,"participants":46},{"id":"paper-eckstein-j-clin-oncol","kind":"paper","name":"Phase II Study of Selumetinib in Children and Young Adults With Tumors Harboring Activating Mitogen-Activated Protein Kinase Pathway Genetic Alterations: Arm E of the NCI-COG Pediatric MATCH Trial","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 35363510 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: The NCI-COG Pediatric MATCH trial assigns patients age 1-21 years with relapsed or refractory solid tumors, lymphomas, and histiocytic disorders to phase II studies of molecularly targeted therapies on the basis of detection of predefined genetic alterations. Patients with tumors harboring mutations or fusions driving activation of the mitogen-activated protein kinase (MAPK) pathway were treated with the MEK inhibitor selumetinib.\n\nMethods: Patients received selumetinib twice daily for 28-day cycles until disease progression or intolerable toxicity. The primary end point was objective response rate; secondary end points included progression-free survival and tolerability of selumetinib.\n\nResults: Twenty patients (median age: 14 years) were treated. All were evaluable for response and toxicities. The most frequent diagnoses were high-grade glioma (HGG; n = 7) and rhabdomyosarcoma (n = 7). Twenty-one actionable mutations were detected: hotspot mutations in KRAS (n = 8), NRAS (n = 3), and HRAS (n = 1), inactivating mutations in NF1 (n = 7), and BRAF V600E (n = 2). No objective responses were observed. Three patients had a best response of stable disease including two patients with HGG ( NF1 mutation, six cycles; KRAS mutation, 12 cycles). Six-month progression-free survival was 15% (95% CI, 4 to 34). Five patients (25%) experienced a grade 3 or higher adverse event that was possibly or probably attributable to study drug.\n\nConclusion: A national histology-agnostic molecular screening strategy was effective at identifying children and young adults eligible for treatment with selumetinib in the first Pediatric MATCH treatment arm to be completed. MEK inhibitors have demonstrated promising responses in some pediatric tumors (eg, low-grade glioma and plexiform neurofibroma). However, selumetinib in this cohort with treatment-refractory tumors harboring MAPK alterations demonstrated limited efficacy, indicating that pathway mutation status alone is insufficient to predict response to selumetinib monotherapy for pediatric cancers.\n\nIndexed on Europe PMC as PubMed record 35363510 (DOI 10.1200/jco.21.02840). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2022","url":"https://doi.org/10.1200/jco.21.02840"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35363510/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35363510"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["pediatric-match"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2022,"doi":"10.1200/jco.21.02840","pmid":"35363510","authors":"Eckstein OS, Allen CE, Williams PM, et al.","paperType":"observational","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-smile-chemotherapy-nk-t-cell-lymphoma-jco-2011","kind":"paper","name":"Phase II study of SMILE chemotherapy for newly diagnosed stage IV, relapsed, or refractory extranodal natural killer (NK)/T-cell lymphoma, nasal type: the NK-Cell Tumor Study Group study","aka":["SMILE","Yamaguchi 2011"],"tldr":"An asparaginase-based regimen produced a response in four out of five people with an aggressive nasal lymphoma that resists ordinary chemotherapy, and nearly all of them developed dangerously low white cell counts.","summary":"A phase 2 study of the SMILE regimen, comprising dexamethasone, methotrexate, ifosfamide, L-asparaginase and etoposide, in patients with newly diagnosed stage IV, relapsed or refractory extranodal natural killer/T-cell lymphoma, nasal type, and performance status 0 to 2. Two cycles were given as the protocol treatment and the primary endpoint was the overall response rate afterwards.\n\n38 eligible patients were enrolled, with a median age of 47 (range 16 to 67) and a male to female ratio of 21 to 17. Twenty had newly diagnosed stage IV disease, 14 were in first relapse and four were primary refractory. The first two patients died from infections, after which eligibility was revised to require a lymphocyte count of 500 per microlitre or more; no treatment-related deaths occurred after the revision. The overall response rate was 79 per cent (90 per cent confidence interval 65 to 89) and the complete response rate 45 per cent. Of the 28 patients who completed the protocol treatment, 19 underwent haematopoietic stem-cell transplantation. One-year overall survival was 55 per cent (95 per cent confidence interval 38 to 69). Grade 4 neutropenia occurred in 92 per cent and grade 3 or 4 infection in 61 per cent.","asOf":"2026-10-01","links":[{"label":"Journal of Clinical Oncology 2011","url":"https://doi.org/10.1200/JCO.2011.35.6287"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21990393/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/21990393"},{"label":"P-glycoprotein expression in untreated extranodal NK/T-cell lymphoma, American Journal of Hematology 2008","url":"https://doi.org/10.1002/ajh.21256"},{"label":"No correlation between P-glycoprotein and chemotherapy resistance in nasal NK/T-cell lymphoma, Leukemia and Lymphoma 2004","url":"https://doi.org/10.1080/10428190410001693524"}],"tags":["lymphoma-evidence"],"related":["lymphoma-roadmap"],"cancers":["peripheral-t-cell-lymphoma","non-hodgkin-lymphoma"],"sections":["chemotherapy"],"technologies":[],"targets":[],"drugs":["dexamethasone","methotrexate","ifosfamide","asparaginase","etoposide"],"companies":[],"institutions":[],"pathways":[],"terms":["orr","complete-response","autologous-transplant"],"trials":["smile-enktl"],"people":[],"bottlenecks":["b-rare-cancers","b-global-access"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2011,"doi":"10.1200/JCO.2011.35.6287","pmid":"21990393","authors":"Yamaguchi M, Kwong YL, Kim WS, et al.","paperType":"rct","findings":["The overall response rate after two cycles of SMILE was 79 per cent (90 per cent confidence interval 65 to 89) and the complete response rate 45 per cent.","One-year overall survival was 55 per cent (95 per cent confidence interval 38 to 69).","Grade 4 neutropenia occurred in 92 per cent of patients and grade 3 or 4 infection in 61 per cent.","The first two patients died from infections, after which eligibility was revised to require a lymphocyte count of 500 per microlitre or more; no treatment-related deaths followed.","Of the 28 patients who completed protocol treatment, 19 underwent haematopoietic stem-cell transplantation."],"whatItMeans":"The regimen that made extranodal NK/T-cell lymphoma treatable. The usual explanation is that asparaginase is not a substrate of the P-glycoprotein pump this tumour expresses, which would explain why it works where anthracycline-based regimens do not; that mechanism is widely repeated but has been contradicted by at least one series.","caveats":["Single-arm phase 2 with 38 patients, in a disease with three different clinical presentations pooled together.","Two early treatment-related deaths led to a mid-study change in eligibility, so the safety profile describes a selected population.","Nineteen of 28 patients who completed treatment went on to transplantation, which contributes to the one-year survival figure.","No ClinicalTrials.gov record was found for this study when the registry was searched on 1 October 2026."],"changedPractice":true,"participants":38},{"id":"paper-gpc3-hcc-oncoimmunology-2016","kind":"paper","name":"Phase II study of the GPC3-derived peptide vaccine as an adjuvant therapy for hepatocellular carcinoma patients","aka":[],"tldr":"Phase 2 or 3 results paper on GPC3 in Hepatocellular carcinoma, in Oncoimmunology (2016), one of the most cited Europe PMC records with GPC3 in its title.","summary":"The recurrence rates of Hepatocellular carcinoma (HCC) are high, necessitating novel and effective adjuvant therapies. Therefore, we conducted a phase II study of glypican-3 (GPC3) peptide vaccine as an adjuvant therapy for HCC patients. Forty-one patients with initial HCC who had undergone surgery or radiofrequency ablation (RFA) were analyzed in this phase II, open-label, single-arm trial. Ten vaccinations were performed for 1 y after curative treatment. We also investigated case-control subjects, where selected patients treated surgically during the same period were analyzed. The expression of GPC3 in the available primary tumors was determined by immunohistochemical analysis. Six patients received RFA therapy while 35 received surgery. The recurrence rate tended to be lower in the 35 patients treated with surgery plus vaccination compared to 33 patients who underwent surgery alone (28.6% vs. 54.3% and 39.4% vs. 54.5% at 1 and 2 y, respectively; p = 0.346, 0.983). Twenty-five patients treated with surgery and vaccination had GPC3-positive tumors; the recurrence rate in this group was significantly lower compared to that in 21 GPC3-positive patients who received surgery only (24% vs. 48% and 52.4% vs. 61.9% at 1 and 2 y, respectively; p = 0.047, 0.387). The GPC3 peptide vaccine improved the 1-y recurrence rate in patients with GPC3-positive tumors. This study demonstrated that GPC3 expression by the primary tumor may be used as a biomarker in a putative larger randomized clinical trial to determine the efficacy of the GPC3-derived peptide vaccine.\n\nIndexed on Europe PMC as PubMed record 27467945 (DOI 10.1080/2162402x.2015.1129483). Its title names GPC3 and its text names Hepatocellular carcinoma; PubMed types it as a clinical trial report (Research Support, Non-U.S. Gov't, research-article). It was matched automatically to the idea \"In vivo CAR-T against solid-tumour antigens\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Oncoimmunology 2016","url":"https://doi.org/10.1080/2162402x.2015.1129483"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27467945/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27467945"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["oncoimmunology"],"dependsOn":[],"notes":[],"journal":"Oncoimmunology","year":2016,"doi":"10.1080/2162402x.2015.1129483","pmid":"27467945","authors":"Sawada Y, Yoshikawa T, Ofuji K, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for GPC3 in Hepatocellular carcinoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by GPC3 in the title and Hepatocellular carcinoma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-chen-exp-hematol-oncol","kind":"paper","name":"Phase II study of zevorcabtagene autoleucel, a fully human BCMA-targeting CAR T cell therapy, in patients with relapsed/refractory multiple myeloma","aka":[],"tldr":"Paper cited by one trial page and one treatment page, indexed on Europe PMC as PubMed record 41029877 and published in Experimental hematology & oncology; the citing pages link this DOI, which is how the record was matched.","summary":"Background: Zevorcabtagene autoleucel (zevor-cel) is a fully human autologous CAR T-cell therapy targeting B-cell maturation antigen approved in China since 2024 for patients with relapsed/refractory multiple myeloma (RRMM).\n\nMethods: LUMMICAR STUDY 1 is a phase 2, single-arm study conducted across 23 centers in China. RRMM patients aged ≥ 18 to ≤ 75 years with measurable disease who had received ≥ 3 prior lines of therapy, with adequate organ function and bone marrow reserve, with an Eastern Cooperative Oncology Group (ECOG) score of 0-1, were eligible. Patients previously treated with any CAR T-cell therapy, or any BCMA-directed therapy were ineligible. The primary endpoint was objective response rate (ORR) determined by an Independent Review Committee. The secondary endpoints included ORR determined by investigator, additional efficacy outcomes including complete response (CR)/ stringent complete response (sCR) rate, duration of response (DOR), minimal residual disease negativity, safety outcomes including incidence and severity of adverse events, and pharmacokinetics of zevor-cel.\n\nResults: Overall, 125 patients underwent apheresis, 105 patients received lymphodepletion, 102 patients (median age of 59.5 [range: 38, 75] years; 53.9% male and 46.1% female) received zevor-cel. The ORR was 92.2% (95% CI 85.13-96.55) with 70 patients (68.6%) achieving sCR and 3 (2.9%) achieving CR. At a median follow-up of 20.3 (interquartile range [IQR] 12.5, 23.8) months, 45 (44.1%) progression-free survival (PFS) events and 20 (19.6%) overall survival (OS) events were observed, the DOR, PFS and OS data were not mature. Cytokine release syndrome was reported in 92 (90.2%) patients, with grade 3 or 4 events in 7 (6.9%) patients. Immune effector cell associated neurotoxicity syndrome was reported in 2 patients at grade 1; no zevor-cel-related grade ≥ 3 neurotoxicity occurred.\n\nConclusion: Zevor-cel induces deep and durable responses in heavily pre-treated RRMM patients with a manageable safety profile.\n\nIndexed on Europe PMC as PubMed record 41029877 (DOI 10.1186/s40164-025-00710-y). Matched by DOI alone: one trial page and one treatment page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Exp Hematol Oncol 2025","url":"https://doi.org/10.1186/s40164-025-00710-y"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41029877/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41029877"}],"tags":["europepmc-ingest"],"related":["zevorcabtagene-autoleucel"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["lummicar-1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Experimental hematology & oncology","year":2025,"doi":"10.1186/s40164-025-00710-y","pmid":"41029877","authors":"Chen W, Fu C, Fang B, et al.","paperType":"observational","findings":[],"whatItMeans":"One trial page and one treatment page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-gucalp-bicalutamide-ar-positive-tbcrc011-ccr-2013","kind":"paper","name":"Phase II trial of bicalutamide in patients with androgen receptor-positive, estrogen receptor-negative metastatic breast cancer","aka":[],"tldr":"Screening 424 women with ER-negative breast cancer found androgen receptor in 12%; the prostate drug bicalutamide held the disease stable for six months in 19% of them, the first clinical proof that the LAR subtype can be treated through its receptor.","summary":"TBCRC 011 tested bicalutamide 150 mg daily in ER/PgR-negative advanced breast cancer with central AR immunohistochemistry (over 10% nuclear staining positive). Of 424 patients screened, 12% were AR-positive. The six-month clinical benefit rate was 19% (95% CI 7 to 39) and median progression-free survival 12 weeks; no grade 4 or 5 treatment-related events occurred.","asOf":"2026-09-24","links":[{"label":"Gucalp et al., Clin Cancer Res 2013: bicalutamide in AR-positive, ER-negative metastatic breast cancer (TBCRC 011)","url":"https://doi.org/10.1158/1078-0432.CCR-12-3327"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23965901/"}],"tags":[],"related":[],"cancers":["tnbc","tnbc-metastatic"],"sections":[],"technologies":[],"targets":["androgen-receptor"],"drugs":["bicalutamide"],"companies":[],"institutions":["mskcc"],"pathways":["ar-signaling"],"terms":["ihc"],"trials":[],"people":["sara-tolaney","hope-rugo"],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2013,"doi":"10.1158/1078-0432.CCR-12-3327","pmid":"23965901","authors":"Gucalp A, Tolaney S, Isakoff SJ, et al.","paperType":"rct","findings":["AR-positive (over 10% nuclear staining) in 12% of 424 ER/PgR-negative patients.","Six-month clinical benefit rate 19%; median PFS 12 weeks."],"whatItMeans":"It fixes the AR-positive share of ER-negative disease at about one in eight and shows anti-androgens give modest, non-toxic benefit, the rationale for enzalutamide and later CDK4/6 and PI3K combinations in LAR tumours.","caveats":["26 treated patients; single-arm.","AR positivity threshold of 10% differs from the enzalutamide trial's any-staining rule."],"changedPractice":false,"participants":424},{"id":"paper-crane-smad4-progression-pattern-locally-advanced-jco-2011","kind":"paper","name":"Phase II trial of cetuximab, gemcitabine, and oxaliplatin followed by chemoradiation with cetuximab for locally advanced (T4) pancreatic adenocarcinoma: correlation of Smad4(Dpc4) immunostaining with pattern of disease progression","aka":[],"tldr":"In 69 people with locally advanced pancreatic cancer, an ordinary Smad4 stain on the diagnostic needle sample predicted whether the cancer would grow locally or spread, the finding that supports using it to decide who gets radiotherapy.","summary":"Treatment-naive patients with locally advanced pancreatic cancer (n = 69) received gemcitabine and oxaliplatin every two weeks for four doses then radiation (50.4 Gy) with concurrent capecitabine, with cetuximab throughout. Diagnostic cytology specimens were immunostained for Smad4(Dpc4). Median overall survival was 19.2 months with 1-, 2- and 4-year survival of 66.0%, 25.0% and 11.3%; radiographic local progression was 22.8% at one year and 61.0% at two. Smad4(Dpc4) expression correlated with a local rather than distant dominant pattern of disease progression (P = .016); prospective validation of Smad4 in cytology as a predictive biomarker was recommended.","asOf":"2026-09-24","links":[{"label":"Crane et al., J Clin Oncol 2011: Smad4 immunostaining and progression pattern in 69 locally advanced patients","url":"https://doi.org/10.1200/JCO.2010.33.8038"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21709185/"}],"tags":[],"related":[],"cancers":["pancreatic","locally-advanced-pdac"],"sections":[],"technologies":[],"targets":["smad4"],"drugs":["gemcitabine","oxaliplatin","capecitabine","cetuximab"],"companies":[],"institutions":["md-anderson"],"pathways":[],"terms":["ihc"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2011,"doi":"10.1200/JCO.2010.33.8038","pmid":"21709185","authors":"Crane CH, Varadhachary GR, Yordy JS, et al.","paperType":"rct","findings":["Smad4 expression correlated with a local-dominant progression pattern (P = .016).","Median overall survival 19.2 months with chemotherapy then chemoradiation."],"whatItMeans":"It carried Iacobuzio-Donahue's autopsy finding into the clinic on a routine stain of the diagnostic sample, the basis for the still-unvalidated idea of choosing radiotherapy by SMAD4 status.","caveats":["Single-arm phase 2 with cetuximab, which has no role today.","Prospective validation of Smad4 as a predictive marker has not been completed."],"changedPractice":false,"participants":69},{"id":"paper-cd19-all-leukemia-j-clin-oncol-2014","kind":"paper","name":"Phase II trial of the anti-CD19 bispecific T cell-engager blinatumomab shows hematologic and molecular remissions in patients with relapsed or refractory B-precursor acute lymphoblastic leukemia","aka":[],"tldr":"Phase 2 or 3 results paper on CD19 in Acute lymphoblastic leukaemia, in Journal of Clinical Oncology (2014), one of the most cited Europe PMC records with CD19 in its title.","summary":"Purpose: Patients with relapsed or refractory acute lymphoblastic leukemia (ALL) have a dismal prognosis. CD19 is homogenously expressed in B-precursor ALL and can be targeted by the investigational bispecific T cell-engager antibody blinatumomab. A phase II trial was performed to determine clinical activity in this patient cohort.\n\nPatients and methods: Thirty-six patients with relapsed or refractory B-precursor ALL were treated with blinatumomab in cycles of 4-week continuous infusion followed by a 2-week treatment-free interval in a single-arm study with a dose-finding stage and an extension stage. The primary end point was complete remission (CR) or CR with partial hematologic recovery (CRh). Major secondary end points included minimal residual disease (MRD) response, rate of allogeneic hematopoietic stem-cell transplantation (HSCT) realization, relapse-free survival (RFS), overall survival (OS), and incidence of adverse events (AEs).\n\nResults: Median age was 32 years (range, 18 to 77 years). Twenty-five patients (69%) achieved a CR or CRh, with 88% of the responders achieving an MRD response. Median OS was 9.8 months (95% CI, 8.5 to 14.9), and median RFS was 7.6 months (95% CI, 4.5 to 9.5). Thirteen responders (52%) underwent HSCT after achieving a CR or CRh. The most frequent AE during treatment was pyrexia (grade 1 or 2, 75%; grade 3, 6%). In six patients with nervous system or psychiatric disorder AEs and in two patients with cytokine release syndrome, treatment had to be interrupted or discontinued. These medical events were resolved clinically.\n\nConclusion: The data support further investigation of blinatumomab for the treatment of adult patients with relapsed or refractory ALL in a larger confirmatory study.\n\nIndexed on Europe PMC as PubMed record 25385737 (DOI 10.1200/jco.2014.56.3247). Its title names CD19 and its text names Acute lymphoblastic leukaemia; PubMed types it as a clinical trial report (Clinical Trial, Phase II, Research Support, Non-U.S. Gov't, Multicenter Study). It was matched automatically to the idea \"Hospital-based CAR-T manufacturing at cost through a public network\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2014","url":"https://doi.org/10.1200/jco.2014.56.3247"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25385737/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25385737"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2014,"doi":"10.1200/jco.2014.56.3247","pmid":"25385737","authors":"Topp MS, Gökbuget N, Zugmaier G, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for CD19 in Acute lymphoblastic leukaemia, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by CD19 in the title and Acute lymphoblastic leukaemia in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-ciltacabtagene-autoleucel-multiple-myeloma-j-clin-oncol-2023","kind":"paper","name":"Phase II, Open-Label Study of Ciltacabtagene Autoleucel, an Anti-B-Cell Maturation Antigen Chimeric Antigen Receptor-T-Cell Therapy, in Chinese Patients With Relapsed/Refractory Multiple Myeloma (CARTIFAN-1)","aka":[],"tldr":"Phase 2 or 3 results paper on Ciltacabtagene autoleucel in Multiple myeloma, in Journal of Clinical Oncology (2023), one of the most cited Europe PMC records with Ciltacabtagene autoleucel in its title.","summary":"Purpose: CARTIFAN-1 aimed to evaluate the efficacy and safety of ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen-targeting chimeric antigen receptor T-cell therapy, in Chinese patients with relapsed/refractory multiple myeloma (RRMM).\n\nMethods: This pivotal phase II, open-label study (ClinicalTrials.gov identifier: NCT03758417), conducted across eight sites in China, enrolled adult patients with RRMM who had received ≥ 3 lines of prior therapy, including a proteasome inhibitor and immunomodulatory drug. Patients received a single infusion of cilta-cel (target dose 0.75 × 10 6 chimeric antigen receptor-positive viable T cells/kg). The primary end point was overall response rate. Secondary end points included progression-free survival (PFS), overall survival (OS), and incidence and severity of adverse events (AEs).\n\nResults: at the clinical cutoff of July 19, 2021, 48 patients received a cilta-cel infusion. At an 18-month median follow-up, the overall response rate was 89.6% (95% CI, 77.3 to 96.5), with a median time to first response of approximately 1 month; 77.1% of patients (95% CI, 62.7 to 88.0) achieved complete response or better. Medians for duration of response, PFS, and OS were not reached. The 18-month PFS and OS rates were 66.8% (95% CI, 49.4 to 79.4) and 78.7% (95% CI, 64.0 to 88.0), respectively. Hematologic AEs were common, including anemia (100%), neutropenia (97.9%), lymphopenia (95.8%), and thrombocytopenia (87.5%). Cytokine release syndrome occurred in 97.9% of patients (35.4% grade 3/4); the median time to onset was 7 days, and the median duration was 5 days. Infections occurred in 85.4% of patients (37.5% grade 3/4). Ten deaths occurred after cilta-cel infusion, eight of which were due to treatment-related AEs.\n\nConclusion: These data demonstrate a favorable risk-benefit profile for a single infusion of cilta-cel, resulting in early, deep, and durable responses in heavily pretreated patients with RRMM in China.\n\nIndexed on Europe PMC as PubMed record 36269898 (DOI 10.1200/jco.22.00690). Its title names Ciltacabtagene autoleucel and its text names Multiple myeloma; PubMed types it as a clinical trial report (Clinical Trial, Phase II, Research Support, Non-U.S. Gov't). It was matched automatically to the idea \"One CAR-T infusion instead of autologous transplant\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2023","url":"https://doi.org/10.1200/jco.22.00690"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36269898/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36269898"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2023,"doi":"10.1200/jco.22.00690","pmid":"36269898","authors":"Mi JQ, Zhao W, Jing H, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Ciltacabtagene autoleucel in Multiple myeloma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Ciltacabtagene autoleucel in the title and Multiple myeloma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-scagliotti-cisplatin-pemetrexed-histology-jco-2008","kind":"paper","name":"Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer","aka":[],"tldr":"1,725 patients, two chemotherapy combinations, identical survival overall. But split by what the tumour looked like down a microscope, one drug was better for adenocarcinoma and the other for squamous cancer. Histology started choosing the drug.","summary":"Scagliotti, Parikh, von Pawel and colleagues randomised 1,725 chemotherapy-naive patients with advanced non-small-cell lung cancer to cisplatin with gemcitabine (863) or cisplatin with pemetrexed (862) for up to six cycles, in a non-inferiority design.\n\nThe overall result was non-inferiority, which by itself would have changed little. The pre-specified histology analysis is what changed practice: pemetrexed was better in adenocarcinoma and large-cell carcinoma and worse in squamous cell carcinoma, a difference attributed to thymidylate synthase expression. This is the first phase 3 trial in lung cancer to show survival differences by histological type, and the reason a pathologist's subtype now has to be recorded before chemotherapy is chosen.","asOf":"2026-09-25","links":[{"label":"J Clin Oncol 2008","url":"https://doi.org/10.1200/JCO.2007.15.0375"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/18506025/"},{"label":"JCO 2023 reprint","url":"https://europepmc.org/article/MED/37146426"}],"tags":["lung-evidence"],"related":["chemotherapy-roadmap","paper-schiller-ecog-1594-four-chemotherapy-regimens-nejm-2002","paper-keynote-189-nejm-2018"],"cancers":["lung-cancer","nsclc","lung-adenocarcinoma","lung-squamous-cell-carcinoma"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":["cisplatin","pemetrexed","gemcitabine"],"companies":[],"institutions":[],"pathways":[],"terms":["histology"],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation","b-dose-optimisation"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2008,"doi":"10.1200/JCO.2007.15.0375","pmid":"18506025","authors":"Scagliotti GV, Parikh P, von Pawel J, et al.","paperType":"rct","findings":["Overall survival for cisplatin and pemetrexed was non-inferior to cisplatin and gemcitabine: median 10.3 against 10.3 months, hazard ratio 0.94 (95 percent confidence interval 0.84 to 1.05).","In adenocarcinoma (847 patients) survival was superior with pemetrexed: 12.6 against 10.9 months.","In large-cell carcinoma (153 patients) survival was superior with pemetrexed: 10.4 against 6.7 months.","In squamous cell histology (473 patients) survival was superior with gemcitabine: 10.8 against 9.4 months.","Cisplatin and pemetrexed caused less grade 3 or 4 neutropenia, anaemia and thrombocytopenia, less febrile neutropenia and less alopecia; nausea was more common.","The first prospective phase 3 study in non-small-cell lung cancer to show survival differences based on histological type."],"whatItMeans":"The moment lung cancer stopped being one disease for treatment purposes. Before this trial the pathology report said cancer or not cancer; after it, the subtype chose the drug, and the tissue had to be preserved well enough to answer the question.","caveats":["The histology effects were subgroup analyses within a non-inferiority trial, and the biological explanation (thymidylate synthase) was proposed rather than measured prospectively.","Predates molecular testing, so the adenocarcinoma arm mixes EGFR-mutant, ALK-positive and driver-negative disease.","Cross-trial comparison with modern regimens is not valid: these patients received neither maintenance therapy nor immunotherapy."],"changedPractice":true,"participants":1725},{"id":"paper-ishigami-j-clin-oncol","kind":"paper","name":"Phase III Trial Comparing Intraperitoneal and Intravenous Paclitaxel Plus S-1 Versus Cisplatin Plus S-1 in Patients With Gastric Cancer With Peritoneal Metastasis: PHOENIX-GC Trial","aka":[],"tldr":"Paper cited by one idea page, indexed on Europe PMC as PubMed record 29746229 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose Intraperitoneal paclitaxel plus systemic chemotherapy demonstrated promising clinical effects in patients with gastric cancer with peritoneal metastasis. We aimed to verify its superiority over standard systemic chemotherapy in overall survival. Patients and Methods This randomized phase III trial enrolled patients with gastric cancer with peritoneal metastasis who had received no or short-term (< 2 months) chemotherapy. Patients were randomly assigned at a two-to-one ratio to receive intraperitoneal and intravenous paclitaxel plus S-1 (IP; intraperitoneal paclitaxel 20 mg/m 2 and intravenous paclitaxel 50 mg/m 2 on days 1 and 8 plus S-1 80 mg/m 2 per day on days 1 to 14 for a 3-week cycle) or S-1 plus cisplatin (SP; S-1 80 mg/m 2 per day on days 1 to 21 plus cisplatin 60 mg/m 2 on day 8 for a 5-week cycle), stratified by center, previous chemotherapy, and extent of peritoneal metastasis. The primary end point was overall survival. Secondary end points were response rate, 3-year overall survival rate, and safety. Results We enrolled 183 patients and performed efficacy analyses in 164 eligible patients. Baseline characteristics were balanced between the arms, except that patients in the IP arm had significantly more ascites. The median survival times for the IP and SP arms were 17.7 and 15.2 months, respectively (hazard ratio, 0.72; 95% CI, 0.49 to 1.04; stratified log-rank P =.080). In the sensitivity analysis adjusted for baseline ascites, the hazard ratio was 0.59 (95% CI, 0.39 to 0.87; P =.008). The 3-year overall survival rate was 21.9% (95% CI, 14.9% to 29.9%) in the IP arm and 6.0% (95% CI, 1.6% to 14.9%) in the SP arm. Both regimens were well tolerated. Conclusion This trial failed to show statistical superiority of intraperitoneal paclitaxel plus systemic chemotherapy. However, the exploratory analyses suggested possible clinical benefits of intraperitoneal paclitaxel for gastric cancer.\n\nIndexed on Europe PMC as PubMed record 29746229 (DOI 10.1200/jco.2018.77.8613). Matched by DOI alone: one idea page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2018","url":"https://doi.org/10.1200/jco.2018.77.8613"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29746229/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29746229"}],"tags":["europepmc-ingest"],"related":["idea-peritoneal-directed-gastric"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2018,"doi":"10.1200/jco.2018.77.8613","pmid":"29746229","authors":"Ishigami H, Fujiwara Y, Fukushima R, et al.","paperType":"rct","findings":[],"whatItMeans":"One idea page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-lim-neuro-oncol","kind":"paper","name":"Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 35511454 and published in Neuro-Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background: Nearly all patients with newly diagnosed glioblastoma experience recurrence following standard-of-care radiotherapy (RT) + temozolomide (TMZ). The purpose of the phase III randomized CheckMate 548 study was to evaluate RT + TMZ combined with the immune checkpoint inhibitor nivolumab (NIVO) or placebo (PBO) in patients with newly diagnosed glioblastoma with methylated MGMT promoter (NCT02667587).\n\nMethods: Patients (N = 716) were randomized 1:1 to NIVO [(240 mg every 2 weeks × 8, then 480 mg every 4 weeks) + RT (60 Gy over 6 weeks) + TMZ (75 mg/m2 once daily during RT, then 150-200 mg/m2 once daily on days 1-5 of every 28-day cycle × 6)] or PBO + RT + TMZ following the same regimen. The primary endpoints were progression-free survival (PFS) and overall survival (OS) in patients without baseline corticosteroids and in all randomized patients.\n\nResults: at December 22, 2020, median (m)PFS (blinded independent central review) was 10.6 months (95% CI, 8.9-11.8) with NIVO + RT + TMZ vs 10.3 months (95% CI, 9.7-12.5) with PBO + RT + TMZ (HR, 1.1; 95% CI, 0.9-1.3) and mOS was 28.9 months (95% CI, 24.4-31.6) vs 32.1 months (95% CI, 29.4-33.8), respectively (HR, 1.1; 95% CI, 0.9-1.3). In patients without baseline corticosteroids, mOS was 31.3 months (95% CI, 28.6-34.8) with NIVO + RT + TMZ vs 33.0 months (95% CI, 31.0-35.1) with PBO + RT + TMZ (HR, 1.1; 95% CI, 0.9-1.4). Grade 3/4 treatment-related adverse event rates were 52.4% vs 33.6%, respectively.\n\nConclusions: NIVO added to RT + TMZ did not improve survival in patients with newly diagnosed glioblastoma with methylated or indeterminate MGMT promoter. No new safety signals were observed.\n\nIndexed on Europe PMC as PubMed record 35511454 (DOI 10.1093/neuonc/noac116). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Neuro Oncol 2022","url":"https://doi.org/10.1093/neuonc/noac116"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35511454/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35511454"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-548"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["neuro-oncology"],"dependsOn":[],"notes":[],"journal":"Neuro-Oncology","year":2022,"doi":"10.1093/neuonc/noac116","pmid":"35511454","authors":"Lim M, Weller M, Idbaih A, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-mirvetuximab-soravtansine-ovarian-ann-oncol-2021","kind":"paper","name":"Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I","aka":[],"tldr":"Phase 2 or 3 results paper on Mirvetuximab soravtansine in Ovarian cancer, in Annals of Oncology (2021), one of the most cited Europe PMC records with Mirvetuximab soravtansine in its title.","summary":"Background: Mirvetuximab soravtansine (MIRV) is an antibody-drug conjugate comprising a folate receptor alpha (FRα)-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent. The randomized, open-label, phase III study FORWARD I compared MIRV and investigator's choice chemotherapy in patients with platinum-resistant epithelial ovarian cancer (EOC).\n\nPatients and methods: Eligible patients with 1-3 prior lines of therapy and whose tumors were positive for FRα expression were randomly assigned, in a 2: 1 ratio, to receive MIRV (6 mg/kg, adjusted ideal body weight) or chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan). The primary endpoint was progression-free survival [PFS, Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, blinded independent central review] in the intention-to-treat (ITT) population and in the prespecified FRα high population.\n\nResults: A total of 366 patients were randomized; 243 received MIRV and 109 received chemotherapy. The primary endpoint, PFS, did not reach statistical significance in either the ITT [hazard ratio (HR), 0.98, P = 0.897] or the FRα high population (HR, 0.69, P = 0.049). Superior outcomes for MIRV over chemotherapy were observed in all secondary endpoints in the FRα high population including improved objective response rate (24% versus 10%), CA-125 responses (53% versus 25%), and patient-reported outcomes (27% versus 13%). Fewer treatment-related grade 3 or higher adverse events (25.1% versus 44.0%), and fewer events leading to dose reduction (19.8% versus 30.3%) and treatment discontinuation (4.5% versus 8.3%) were seen with MIRV compared with chemotherapy.\n\nConclusions: In patients with platinum-resistant EOC, MIRV did not result in a significant improvement in PFS compared with chemotherapy. Secondary endpoints consistently favored MIRV, particularly in patients with high FRα expression. MIRV showed a differentiated and more manageable safety profile than chemotherapy.\n\nIndexed on Europe PMC as PubMed record 33667670 (DOI 10.1016/j.annonc.2021.02.017). Its title names Mirvetuximab soravtansine and its text names Ovarian cancer; PubMed types it as a clinical trial report (Clinical Trial, Phase III, Research Support, Non-U.S. Gov't, Randomized Controlled Trial). It was matched automatically to the idea \"Sequence folate-receptor ADCs by payload class\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Ann Oncol 2021","url":"https://doi.org/10.1016/j.annonc.2021.02.017"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33667670/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33667670"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2021,"doi":"10.1016/j.annonc.2021.02.017","pmid":"33667670","authors":"Moore KN, Oza AM, Colombo N, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Mirvetuximab soravtansine in Ovarian cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Mirvetuximab soravtansine in the title and Ovarian cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-endocrine-society-pheochromocytoma-paraganglioma-guideline-jcem-2014","kind":"paper","name":"Pheochromocytoma and paraganglioma: an Endocrine Society clinical practice guideline","aka":[],"tldr":"The Endocrine Society guideline on catecholamine-producing tumours: test with plasma or urine metanephrines, image with CT or MRI and functional scans, offer genetic testing to everyone, block the blood pressure before surgery, and follow patients for life.","summary":"Clinical practice guideline recommending plasma free or urinary fractionated metanephrines for biochemical diagnosis, CT as first imaging with MRI and functional imaging (MIBG, FDG or somatostatin receptor PET) for metastatic or hereditary disease, shared decision-making on genetic testing for all patients with a clinical algorithm to prioritise genes, preoperative alpha-adrenergic blockade, minimally invasive adrenalectomy where appropriate, personalised management of metastatic disease, and lifelong follow-up, particularly for those with germline mutations.","asOf":"2026-09-18","links":[{"label":"J Clin Endocrinol Metab 2014","url":"https://doi.org/10.1210/jc.2014-1498"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24893135/"}],"tags":[],"related":[],"cancers":["hereditary-ppgl","metastatic-ppgl"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Journal of Clinical Endocrinology & Metabolism","year":2014,"doi":"10.1210/jc.2014-1498","pmid":"24893135","authors":"Lenders JW, Duh QY, Eisenhofer G, et al.","paperType":"guideline","findings":[],"whatItMeans":"The diagnostic, surgical and follow-up rows on both pheochromocytoma and paraganglioma pages follow this guideline.","caveats":["Predates the FIRSTMAPPP, belzutifan and high-specific-activity MIBG trials for metastatic disease.","Evidence for most recommendations is low quality by design of the rare disease."],"changedPractice":true},{"id":"paper-abou-alfa-phocus-pexa-vec-liver-cancer-2024","kind":"paper","name":"PHOCUS: an oncolytic vaccinia virus before sorafenib in liver cancer did worse than sorafenib alone","aka":[],"tldr":"Adding injections of an engineered pox virus before standard liver cancer treatment did not help and the results were worse than the control arm, so the trial was stopped early.","summary":"Randomised, open-label phase 3 trial at 142 sites in 16 countries of pexastimogene devacirepvec, an oncolytic and immunotherapeutic vaccinia virus, injected into the tumour and followed by sorafenib, against sorafenib alone, in advanced hepatocellular carcinoma with no prior systemic treatment. 459 patients were randomised between December 2015 and the interim analysis in August 2019.\n\nAt the interim analysis median overall survival was 12.7 months with the sequence and 14.0 months with sorafenib alone, which led to early termination. Median time to progression was 2.0 months against 4.2 months. Objective response was 19.2 per cent against 20.9 per cent and disease control 50.0 per cent against 57.3 per cent. Serious adverse events occurred in 53.7 per cent against 35.5 per cent, liver failure being the commonest in both arms.\n\nEarlier phase 2 work had reported a dose-related survival difference after intratumoural injection of the same virus, which is the reason the phase 3 was run.","asOf":"2026-09-25","links":[{"label":"Liver Cancer 2024","url":"https://doi.org/10.1159/000533650"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38756145/"}],"tags":[],"related":[],"cancers":["hcc"],"sections":["immunotherapy"],"technologies":["oncolytic-virus"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Liver Cancer","year":2024,"doi":"10.1159/000533650","pmid":"38756145","authors":"Abou-Alfa GK, Galle PR, Chao Y, et al.","paperType":"rct","findings":["Median overall survival 12.7 months (95% CI 9.89 to 14.95) with pexastimogene devacirepvec then sorafenib versus 14.0 months (95% CI 11.01 to 18.00) with sorafenib alone; the trial was terminated early.","Median time to progression 2.0 months versus 4.2 months.","Objective response 19.2 per cent versus 20.9 per cent; disease control 50.0 per cent versus 57.3 per cent.","Serious adverse events in 53.7 per cent versus 35.5 per cent, liver failure commonest in both arms."],"whatItMeans":"A phase 2 signal that looked like a survival benefit, tested in 459 patients, turned out to be nothing, and delaying effective systemic treatment to give the virus first made outcomes worse. The authors' own conclusion is that the arrival of checkpoint inhibitors should direct any further development of oncolytic virus strategies, which is a polite way of saying this design is finished.","caveats":["Open-label, and the sequential design confounds the virus with the delay in starting sorafenib.","Sorafenib alone was standard when the trial started but was superseded during it, so the control arm is no longer current practice.","Reported at interim analysis after early termination, so the final dataset is smaller than planned."],"changedPractice":false,"participants":459},{"id":"paper-agostinis-ca-cancer-j-clin","kind":"paper","name":"Photodynamic therapy of cancer: an update","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 21617154 and published in CA: A Cancer Journal for Clinicians; the citing page links this DOI, which is how the record was matched.","summary":"Photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic procedure that can exert a selective cytotoxic activity toward malignant cells. The procedure involves administration of a photosensitizing agent followed by irradiation at a wavelength corresponding to an absorbance band of the sensitizer. In the presence of oxygen, a series of events lead to direct tumor cell death, damage to the microvasculature, and induction of a local inflammatory reaction. Clinical studies revealed that PDT can be curative, particularly in early stage tumors. It can prolong survival in patients with inoperable cancers and significantly improve quality of life. Minimal normal tissue toxicity, negligible systemic effects, greatly reduced long-term morbidity, lack of intrinsic or acquired resistance mechanisms, and excellent cosmetic as well as organ function-sparing effects of this treatment make it a valuable therapeutic option for combination treatments. With a number of recent technological improvements, PDT has the potential to become integrated into the mainstream of cancer treatment.\n\nIndexed on Europe PMC as PubMed record 21617154 (DOI 10.3322/caac.20114). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"CA Cancer J Clin 2011","url":"https://doi.org/10.3322/caac.20114"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21617154/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/21617154"}],"tags":["europepmc-ingest"],"related":["photodynamic-therapy-lasers"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["ca-cancer-journal"],"dependsOn":[],"notes":[],"journal":"CA: A Cancer Journal for Clinicians","year":2011,"doi":"10.3322/caac.20114","pmid":"21617154","authors":"Agostinis P, Berg K, Cengel KA, et al.","paperType":"review","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-tan-phyllodes-consensus-histopathology-2016","kind":"paper","name":"Phyllodes tumours of the breast: a consensus review","aka":[],"tldr":"This international consensus review sets out how pathologists grade phyllodes tumours as benign, borderline or malignant and how those grades should guide surgery and follow-up.","summary":"Consensus review by an international group of breast pathologists on the diagnosis, grading criteria (stromal cellularity, atypia, mitoses, overgrowth and margins), differential diagnosis from fibroadenoma, molecular findings including MED12 mutations, and management implications for phyllodes tumours.","asOf":"2026-09-17","links":[{"label":"Histopathology 2016","url":"https://doi.org/10.1111/his.12876"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26768026/"}],"tags":[],"related":[],"cancers":["phyllodes-tumour"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Histopathology","year":2016,"doi":"10.1111/his.12876","pmid":"26768026","authors":"Tan BY, Acs G, Apple SK, et al.","paperType":"review","findings":[],"whatItMeans":"The three-tier grading on a phyllodes pathology report and the margin recommendations for each grade follow this review and the WHO classification it informed.","caveats":["Grading remains partly subjective and inter-observer variation persists."],"changedPractice":true},{"id":"paper-abbosh-phylogenetic-ctdna-lung-cancer-nature-2017","kind":"paper","name":"Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution","aka":[],"tldr":"By building a family tree of each tumour's mutations first, the TRACERx team could find the cancer's DNA in blood after surgery and tell which patients would relapse, before any scan showed anything.","summary":"Abbosh, Birkbak, Wilson and colleagues, with Swanton as senior author, profiled circulating tumour DNA in the first 100 TRACERx participants using a tumour-specific phylogenetic approach, including one patient also recruited to the PEACE post-mortem study.\n\nThe method is the contribution. Rather than looking for a generic panel of mutations, the assay is built from the tumour's own phylogeny, which makes it sensitive enough to detect residual disease and specific enough to say which subclone is responsible for the relapse. It is the lung cancer arm of the minimal residual disease field that ctDNA-guided colorectal trials later industrialised.","asOf":"2026-09-25","links":[{"label":"Nature 2017","url":"https://doi.org/10.1038/nature22364"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28445469/"},{"label":"ClinicalTrials.gov NCT01888601","url":"https://clinicaltrials.gov/study/NCT01888601"}],"tags":["lung-evidence"],"related":["paper-tracerx-100-nejm-2017","ctdna-tests","paper-lace-adjuvant-cisplatin-pooled-analysis-jco-2008"],"cancers":["lung-cancer","nsclc","resectable-nsclc"],"sections":["diagnostics","early-detection"],"technologies":["liquid-biopsy","ngs","wes-wgs"],"targets":[],"drugs":[],"companies":[],"institutions":["francis-crick"],"pathways":[],"terms":["ctdna","mrd","clonal-evolution"],"trials":[],"people":["charles-swanton"],"bottlenecks":["b-dormancy-mrd","b-early-detection","b-tumor-heterogeneity"],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2017,"doi":"10.1038/nature22364","pmid":"28445469","authors":"Abbosh C, Birkbak NJ, Wilson GA, et al.","paperType":"translational","findings":["Independent predictors of ctDNA release were identified and the tumour-volume detection limit analysed.","Blinded profiling of postoperative plasma showed evidence of adjuvant chemotherapy resistance and identified patients very likely to experience recurrence.","Phylogenetic ctDNA profiling tracked the subclonal nature of lung cancer relapse and metastasis."],"whatItMeans":"The foundation of minimal residual disease testing in lung cancer: a blood test that says a patient will relapse months before a scan does, and says which part of the tumour is doing it. Whether acting on that signal changes outcome is what the ctDNA-guided trials are for.","caveats":["100 patients, and ctDNA release depends on tumour volume and histology, so the test is least sensitive in the smallest tumours where it would be most useful.","A bespoke per-patient assay built from tissue sequencing, which is expensive and slow compared with a fixed panel.","Prognostic, not yet predictive: no randomised trial in lung cancer has shown that treating a ctDNA-positive patient earlier improves survival."],"changedPractice":false,"participants":100},{"id":"paper-nia-science","kind":"paper","name":"Physical traits of cancer","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 33122355 and published in Science; the citing page links this DOI, which is how the record was matched.","summary":"The role of the physical microenvironment in tumor development, progression, metastasis, and treatment is gaining appreciation. The emerging multidisciplinary field of the physical sciences of cancer is now embraced by engineers, physicists, cell biologists, developmental biologists, tumor biologists, and oncologists attempting to understand how physical parameters and processes affect cancer progression and treatment. Discoveries in this field are starting to be translated into new therapeutic strategies for cancer. In this Review, we propose four physical traits of tumors that contribute to tumor progression and treatment resistance: (i) elevated solid stresses (compression and tension), (ii) elevated interstitial fluid pressure, (iii) altered material properties (for example, increased tissue stiffness, which historically has been used to detect cancer by palpation), and (iv) altered physical microarchitecture. After defining these physical traits, we discuss their causes, consequences, and how they complement the biological hallmarks of cancer.\n\nIndexed on Europe PMC as PubMed record 33122355 (DOI 10.1126/science.aaz0868). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Science 2020","url":"https://doi.org/10.1126/science.aaz0868"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33122355/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33122355"}],"tags":["europepmc-ingest"],"related":["mechanical-theory-of-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2020,"doi":"10.1126/science.aaz0868","pmid":"33122355","authors":"Nia HT, Munn LL, Jain RK","paperType":"review","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-ghaffarizadeh-plos-comput-biol","kind":"paper","name":"PhysiCell: An open source physics-based cell simulator for 3-D multicellular systems","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 29474446 and published in PLoS computational biology; the citing page links this DOI, which is how the record was matched.","summary":"Many multicellular systems problems can only be understood by studying how cells move, grow, divide, interact, and die. Tissue-scale dynamics emerge from systems of many interacting cells as they respond to and influence their microenvironment. The ideal \"virtual laboratory\" for such multicellular systems simulates both the biochemical microenvironment (the \"stage\") and many mechanically and biochemically interacting cells (the \"players\" upon the stage). PhysiCell-physics-based multicellular simulator-is an open source agent-based simulator that provides both the stage and the players for studying many interacting cells in dynamic tissue microenvironments. It builds upon a multi-substrate biotransport solver to link cell phenotype to multiple diffusing substrates and signaling factors. It includes biologically-driven sub-models for cell cycling, apoptosis, necrosis, solid and fluid volume changes, mechanics, and motility \"out of the box.\" The C++ code has minimal dependencies, making it simple to maintain and deploy across platforms. PhysiCell has been parallelized with OpenMP, and its performance scales linearly with the number of cells. Simulations up to 105-106 cells are feasible on quad-core desktop workstations; larger simulations are attainable on single HPC compute nodes. We demonstrate PhysiCell by simulating the impact of necrotic core biomechanics, 3-D geometry, and stochasticity on the dynamics of hanging drop tumor spheroids and ductal carcinoma in situ (DCIS) of the breast. We demonstrate stochastic motility, chemical and contact-based interaction of multiple cell types, and the extensibility of PhysiCell with examples in synthetic multicellular systems (a \"cellular cargo delivery\" system, with application to anti-cancer treatments), cancer heterogeneity, and cancer immunology. PhysiCell is a powerful multicellular systems simulator that will be continually improved with new capabilities and performance improvements. It also represents a significant independent code base for replicating results from other simulation platforms. The PhysiCell source code, examples, documentation, and support are available under the BSD license at http://PhysiCell.MathCancer.org and http://PhysiCell.sf.net.\n\nIndexed on Europe PMC as PubMed record 29474446 (DOI 10.1371/journal.pcbi.1005991). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"PLoS Comput Biol 2018","url":"https://doi.org/10.1371/journal.pcbi.1005991"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29474446/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29474446"}],"tags":["europepmc-ingest"],"related":["agent-based-tumour-models"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"PLoS computational biology","year":2018,"doi":"10.1371/journal.pcbi.1005991","pmid":"29474446","authors":"Ghaffarizadeh A, Heiland R, Friedman SH, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-pioneer-avapritinib-indolent-systemic-mastocytosis-nejm-evid-2023","kind":"paper","name":"PIONEER: avapritinib versus placebo in indolent systemic mastocytosis","aka":[],"tldr":"A low dose of the KIT inhibitor avapritinib eased the itching, flushing, gut and bone symptoms of indolent systemic mastocytosis more than placebo, the first drug shown to do so in a randomised trial.","summary":"Randomised double-blind phase 2 trial of 212 patients with indolent systemic mastocytosis and moderate to severe symptoms despite best supportive care, assigned to avapritinib 25 mg daily or placebo for 24 weeks.\n\nThe total symptom score fell by 15.6 points with avapritinib against 9.2 with placebo, with parallel falls in serum tryptase, KIT D816V allele burden and bone marrow mast cells; adverse events were mostly mild. The FDA approved avapritinib for indolent systemic mastocytosis in 2023.","asOf":"2026-09-18","links":[{"label":"NEJM Evid 2023","url":"https://doi.org/10.1056/EVIDoa2200339"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38320129/"}],"tags":[],"related":[],"cancers":["indolent-systemic-mastocytosis"],"sections":[],"technologies":[],"targets":[],"drugs":["avapritinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm-evidence"],"dependsOn":[],"notes":[],"journal":"NEJM Evidence","year":2023,"doi":"10.1056/EVIDoa2200339","pmid":"38320129","authors":"Gotlib J, Castells M, Elberink HO, et al.","paperType":"rct","findings":["Total symptom score reduced by 15.6 points with avapritinib versus 9.2 with placebo at 24 weeks.","Serum tryptase, KIT D816V allele fraction and marrow mast cell burden fell with avapritinib."],"whatItMeans":"Patients with indolent systemic mastocytosis whose symptoms persist on antihistamines and mast cell stabilisers now have a disease-modifying option.","caveats":["Symptom score is subjective and the placebo response was substantial.","Long-term safety of continuous KIT inhibition in a non-fatal disease is still being followed."],"changedPractice":true,"participants":212},{"id":"paper-wilt-pivot-prostatectomy-observation-nejm-2017","kind":"paper","name":"PIVOT: follow-up of prostatectomy versus observation for early prostate cancer","aka":["PIVOT","Wilt 2017","Prostate Cancer Intervention Versus Observation Trial"],"tldr":"In men whose prostate cancer was mostly found by a blood test, surgery did not significantly reduce deaths after nearly twenty years. It did cause more incontinence and sexual problems, and it did reduce later treatment for the cancer growing.","summary":"Timothy Wilt and the PIVOT investigators randomised 731 men with localised prostate cancer to radical prostatectomy or observation between November 1994 and January 2002 in the United States Department of Veterans Affairs system, and extended follow-up to August 2014, a median of 12.7 years.\n\nPIVOT is the counterweight to SPCG-4 and it enrolled in the prostate-specific antigen era. Neither all-cause nor prostate-cancer mortality reached significance, both at P equals 0.06, and the subgroup analysis suggested benefit in intermediate-risk disease and none in low-risk disease. The harms are unambiguous: urinary incontinence and erectile and sexual dysfunction were greater with surgery through 10 years. Most of the progression that surgery prevented was asymptomatic, local or biochemical.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2017","url":"https://doi.org/10.1056/nejmoa1615869"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28700844/"},{"label":"ClinicalTrials.gov NCT00007644","url":"https://clinicaltrials.gov/study/NCT00007644"}],"tags":["prostate-evidence"],"related":["paper-bill-axelson-spcg-4-29-year-nejm-2018","paper-protect-15-year-nejm-2023","paper-klotz-active-surveillance-jco-2015","prostate-roadmap"],"cancers":["prostate","prostate-low-risk","prostate-intermediate-risk"],"sections":["surgery","early-detection"],"technologies":["active-surveillance"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["prostatectomy","psa","overdiagnosis","quality-of-life","other-cause-mortality","overtreatment"],"trials":[],"people":[],"bottlenecks":["b-overdiagnosis","b-toxicity-qol","b-trial-enrolment"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2017,"doi":"10.1056/nejmoa1615869","pmid":"28700844","authors":"Wilt TJ, Jones KM, Barry MJ, et al.","paperType":"rct","findings":["Over 19.5 years of follow-up (median 12.7 years), death occurred in 223 of 364 men (61.3 percent) assigned to surgery and 245 of 367 (66.8 percent) assigned to observation: hazard ratio 0.84 (95 percent confidence interval 0.70 to 1.01; P equals 0.06).","Death attributed to prostate cancer or its treatment occurred in 27 men (7.4 percent) assigned to surgery and 42 (11.4 percent) assigned to observation: hazard ratio 0.63 (0.39 to 1.02; P equals 0.06).","Surgery may have been associated with lower all-cause mortality in intermediate-risk disease (absolute difference 14.5 percentage points, 2.8 to 25.6) but not in low-risk (0.7 points, minus 10.5 to 11.8) or high-risk disease (2.3 points, minus 11.5 to 16.1); P equals 0.08 for interaction.","Treatment for disease progression was less frequent with surgery (absolute difference 26.2 percentage points, 19.0 to 32.9), primarily for asymptomatic, local or biochemical progression.","Urinary incontinence and erectile and sexual dysfunction were each greater with surgery than with observation through 10 years."],"whatItMeans":"The trial that made observation a defensible choice for low-risk prostate cancer found by a blood test, and that supplied the number a man needs when weighing surgery: the progression it prevents is mostly progression on a scan or a blood test, and the harms it causes are felt every day.","caveats":["Under-recruited against its own target, which is the main reason two clinically meaningful differences both landed at P equals 0.06 rather than below 0.05.","A Veterans Affairs population with substantial comorbidity, which raises competing mortality and dilutes any cancer-specific benefit.","Observation in PIVOT is not active surveillance: there was no protocol-driven magnetic resonance imaging or repeat biopsy triggering radical treatment."],"changedPractice":true,"participants":731},{"id":"paper-pietrasz-ctdna-prognostic-pancreatic-ccr-2017","kind":"paper","name":"Plasma circulating tumor DNA in pancreatic cancer patients is a prognostic marker","aka":[],"tldr":"Among 135 patients, those with detectable tumour DNA in blood lived 6.5 months against 19, and the more of it there was the shorter the survival; after surgery, finding it predicted early recurrence.","summary":"Blood samples were prospectively collected from consecutive pancreatic adenocarcinoma patients treated at one centre from 2011 to 2015, with circulating tumour DNA identified by targeted next-generation sequencing and picolitre droplet digital PCR. Of 135 patients (31 resectable, 36 locally advanced, 68 metastatic), 50 of 104 with advanced disease (48%) had detectable ctDNA at a median mutant allele fraction of 6.1%. Detection correlated strongly with poor overall survival (6.5 versus 19.0 months; multivariate hazard ratio 1.96), and allele-fraction tertiles gave 18.9, 7.8 and 4.9 months. Among 31 patients resected with curative intent, 6 had detectable ctDNA after surgery at a mean allele fraction of 4.4%, with shorter disease-free (4.6 versus 17.6 months) and overall survival (19.3 versus 32.2 months).","asOf":"2026-09-24","links":[{"label":"Pietrasz et al., Clin Cancer Res 2017: plasma ctDNA is prognostic in 135 patients","url":"https://doi.org/10.1158/1078-0432.CCR-16-0806"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27993964/"}],"tags":[],"related":["ctdna-mrd-positive"],"cancers":["pancreatic","metastatic-pdac","resectable-pdac"],"sections":[],"technologies":["liquid-biopsy","mrd-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ctdna","cfdna","mrd"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2017,"doi":"10.1158/1078-0432.CCR-16-0806","pmid":"27993964","authors":"Pietrasz D, Pecuchet N, Garlan F, et al.","paperType":"observational","findings":["ctDNA detectable in 48% of advanced patients; overall survival 6.5 versus 19.0 months.","Allele-fraction tertiles: 18.9, 7.8 and 4.9 months.","Post-resection ctDNA: disease-free survival 4.6 versus 17.6 months."],"whatItMeans":"ctDNA quantity, not just presence, grades prognosis, which is why trials now stratify by allele fraction rather than by a yes or no.","caveats":["Single centre; assays differed between patients.","Only 31 resected patients."],"changedPractice":false,"participants":135},{"id":"paper-chera-j-clin-oncol","kind":"paper","name":"Plasma Circulating Tumor HPV DNA for the Surveillance of Cancer Recurrence in HPV-Associated Oropharyngeal Cancer","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 32017652 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: Plasma circulating tumor human papillomavirus DNA (ctHPVDNA) is a sensitive and specific biomarker of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). We investigated whether longitudinal monitoring of ctHPVDNA during post-treatment surveillance could accurately detect clinical disease recurrence.\n\nMethods and materials: A prospective biomarker clinical trial was conducted among patients with nonmetastatic HPV-associated (p16-positive) OPSCC. All patients were treated with curative-intent chemoradiotherapy (CRT). Patients underwent a 3-month post-CRT positron emission tomography/computed tomography scan and were thereafter clinically evaluated every 2-4 months (years 1-2), then every 6 months (years 3-5). Chest imaging was performed every 6 months. Blood specimens were collected every 6-9 months for analysis of plasma ctHPVDNA using a multianalyte digital polymerase chain reaction assay. The primary endpoint was to estimate the negative predictive value (NPV) and positive predictive value (PPV) of ctHPVDNA surveillance.\n\nResults: One hundred fifteen patients were enrolled, and 1,006 blood samples were analyzed. After a median follow-up time of 23 months (range, 6.1-54.7 months), 15 patients (13%) developed disease recurrence. Eighty-seven patients had undetectable ctHPVDNA at all post-treatment time points, and none developed recurrence (NPV, 100%; 95% CI, 96% to 100%). Twenty-eight patients developed a positive ctHPVDNA during post-treatment surveillance, 15 of whom were diagnosed with biopsy-proven recurrence. Sixteen patients had 2 consecutively positive ctHPVDNA blood tests, 15 of whom developed biopsy-proven recurrence. Two consecutively positive ctHPVDNA blood tests had a PPV of 94% (95% CI, 70% to 99%). Median lead time between ctHPVDNA positivity and biopsy-proven recurrence was 3.9 months (range, 0.37-12.9 months).\n\nConclusion: Detection of ctHPVDNA in two consecutive plasma samples during post-treatment surveillance has high PPV and NPV for identifying disease recurrence in patients with HPV-associated oropharyngeal cancer and may facilitate earlier initiation of salvage therapy.\n\nIndexed on Europe PMC as PubMed record 32017652 (DOI 10.1200/jco.19.02444). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2020","url":"https://doi.org/10.1200/jco.19.02444"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32017652/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32017652"}],"tags":["europepmc-ingest"],"related":["cthpv-dna"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/jco.19.02444","pmid":"32017652","authors":"Chera BS, Kumar S, Shen C, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-aparicio-aggressive-variant-ccr-2013","kind":"paper","name":"Platinum-based chemotherapy for variant castration-resistant prostate cancer (aggressive variant criteria)","aka":[],"tldr":"This trial defined clinical criteria for aggressive variant prostate cancer, such as visceral spread, low PSA relative to tumour burden and neuroendocrine features, and showed that these men respond to carboplatin-docetaxel followed by etoposide-cisplatin.","summary":"Phase 2 study of 120 men with castration-resistant prostate cancer meeting proposed anaplastic (aggressive variant) criteria treated with first-line carboplatin and docetaxel followed at progression by etoposide and cisplatin.\n\nResponse to first-line therapy occurred in the majority, median overall survival was 16 months, and the clinical criteria identified a group behaving like small-cell carcinoma even when histology showed adenocarcinoma.","asOf":"2026-09-17","links":[{"label":"Clin Cancer Res 2013","url":"https://doi.org/10.1158/1078-0432.CCR-12-3791"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23649003/"}],"tags":[],"related":[],"cancers":["prostate-nepc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2013,"doi":"10.1158/1078-0432.CCR-12-3791","pmid":"23649003","authors":"Aparicio AM, Harzstark AL, Corn PG, et al.","paperType":"observational","findings":["Aggressive variant criteria defined: visceral metastases, lytic bone metastases, bulky nodes, low PSA relative to burden, neuroendocrine markers, short response to hormonal therapy.","Median overall survival 16 months with platinum-based sequential therapy."],"whatItMeans":"The aggressive variant criteria are used to select men for platinum-based chemotherapy without needing neuroendocrine histology, and underpin trials of platinum combinations and PARP inhibitors in this group.","caveats":["Single-arm phase 2; criteria were subsequently linked to combined RB1, TP53 and PTEN loss."],"changedPractice":true,"participants":120},{"id":"paper-andriole-plco-prostate-screening-nejm-2009","kind":"paper","name":"PLCO: mortality results from a randomised prostate cancer screening trial","aka":["PLCO prostate","Andriole 2009","Prostate, Lung, Colorectal and Ovarian screening trial prostate arm"],"tldr":"The American screening trial, published in the same issue as the European one and reaching the opposite conclusion. It found more cancers in the screened group and no difference in deaths, which is partly because half the men in the comparison group were being screened anyway.","summary":"Gerald Andriole and the PLCO Project Team randomised 76,693 men at 10 United States centres to annual prostate-specific antigen testing for six years with digital rectal examination for four, or to usual care. It appeared alongside the first ERSPC report on 26 March 2009.\n\nThe result was no significant difference in prostate cancer mortality, and the reason is in the paper's own numbers: screening in the usual-care group rose from 40 percent in the first year to 52 percent by the sixth. PLCO therefore compared organised screening with widespread opportunistic screening, not with no screening. Reading the two 2009 papers together is the single most useful exercise in the prostate screening literature, because they are usually quoted as a disagreement about whether screening works when they are largely a disagreement about what the control arm was.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2009","url":"https://doi.org/10.1056/nejmoa0810696"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19297565/"},{"label":"ClinicalTrials.gov NCT00002540","url":"https://clinicaltrials.gov/study/NCT00002540"}],"tags":["prostate-evidence"],"related":["paper-schroder-erspc-screening-mortality-nejm-2009","paper-plco-chest-radiograph-lung-cancer-mortality-jama-2011","paper-moyer-uspstf-prostate-screening-ann-intern-med-2012","early-detection-roadmap","prostate-roadmap"],"cancers":["prostate","prostate-low-risk","prostate-intermediate-risk"],"sections":["early-detection"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["psa","screening","number-needed-to-screen","lead-time-bias"],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-trial-design","b-overdiagnosis"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2009,"doi":"10.1056/nejmoa0810696","pmid":"19297565","authors":"Andriole GL, Crawford ED, Grubb RL, et al.","paperType":"rct","findings":["After 7 years of follow-up, prostate cancer incidence per 10,000 person-years was 116 (2,820 cancers) in the screening group and 95 (2,322 cancers) in the control group; rate ratio 1.22 (95 percent confidence interval 1.16 to 1.29).","Prostate cancer deaths per 10,000 person-years were 2.0 (50 deaths) in the screening group and 1.7 (44 deaths) in the control group; rate ratio 1.13 (0.75 to 1.70).","Screening in the control group rose from 40 percent in the first year to 52 percent in the sixth for prostate-specific antigen testing, and ranged from 41 to 46 percent for digital rectal examination.","Compliance in the screening group was 85 percent for prostate-specific antigen testing and 86 percent for digital rectal examination.","Data at 10 years were 67 percent complete and consistent with the overall findings."],"whatItMeans":"The trial that made prostate screening contested in the United States, and the reason the 2012 task force recommended against it. Its main lesson is methodological: a screening trial whose control group screens itself cannot measure the effect of screening.","caveats":["Heavy contamination of the control arm (52 percent screened by year six) means the comparison is organised against opportunistic screening.","Seven years of follow-up is short for prostate cancer mortality; the trial's own 10-year data were only 67 percent complete at publication.","Substantial pre-trial prostate-specific antigen testing among enrolled men means many prevalent cancers had already been removed from the population before randomisation."],"changedPractice":true,"participants":76693},{"id":"paper-pod1um-303-retifanlimab-anal-cancer-rao-lancet-2025","kind":"paper","name":"POD1UM-303/InterAACT-2: retifanlimab with carboplatin and paclitaxel for locally recurrent or metastatic anal squamous cell carcinoma","aka":[],"tldr":"Adding the PD-1 antibody retifanlimab to first-line carboplatin and paclitaxel for advanced anal cancer lengthened the time before the cancer progressed from 7.4 to 9.3 months and cut the risk of progression by 37 percent, with manageable extra toxicity.","summary":"Global double-blind randomised phase 3 trial: 308 patients with untreated inoperable locally recurrent or metastatic anal squamous cell carcinoma were randomised to carboplatin-paclitaxel with retifanlimab (154) or placebo (154).\n\nMedian progression-free survival was 9.3 months with retifanlimab against 7.4 months with placebo (hazard ratio 0.63, one-sided p 0.0006). Serious adverse events (47.4 against 38.8 percent) and grade 3 or worse adverse events (83.1 against 75.0 percent) were more frequent with retifanlimab; neutropenia and anaemia were the most common. One treatment-related fatal event (pancytopenia) occurred in the retifanlimab group.","asOf":"2026-09-22","links":[{"label":"Lancet 2025","url":"https://doi.org/10.1016/S0140-6736(25)00631-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40517007/"}],"tags":[],"related":[],"cancers":["metastatic-anal-cancer","anal"],"sections":[],"technologies":[],"targets":[],"drugs":["retifanlimab","carboplatin","paclitaxel"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["pod1um-303"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2025,"doi":"10.1016/S0140-6736(25)00631-2","pmid":"40517007","authors":"Rao S, Samalin-Scalzi E, Evesque L, et al.","paperType":"rct","findings":["Median progression-free survival 9.3 months (95% CI 7.5 to 11.3) versus 7.4 months (7.1 to 7.7); hazard ratio 0.63 (0.47 to 0.84), one-sided p 0.0006.","Serious adverse events 47.4 versus 38.8 percent; grade 3 or worse adverse events 83.1 versus 75.0 percent.","Grade 3 or worse neutropenia 35.1 versus 29.6 percent; anaemia 19.5 versus 20.4 percent."],"whatItMeans":"Retifanlimab with carboplatin-paclitaxel is the new first-line standard for advanced anal squamous cell carcinoma; approved in the United States in May 2025.","caveats":["Overall survival was immature at publication.","Funded and run by the manufacturer."],"changedPractice":true,"participants":308},{"id":"paper-polarix-polatuzumab-rchp-nejm-2022","kind":"paper","name":"POLARIX: swapping vincristine for the antibody-drug conjugate polatuzumab vedotin in first-line treatment of diffuse large B-cell lymphoma","aka":[],"tldr":"Replacing one chemotherapy drug in R-CHOP with a CD79b antibody-drug conjugate modestly reduced progression (2-year PFS 76.7% versus 70.2%) without changing survival or side effects.","summary":"POLARIX randomised 879 previously untreated patients with diffuse large B-cell lymphoma (IPI 2-5, age 18-80) to pola-R-CHP (polatuzumab vedotin replacing vincristine) or standard R-CHOP for six cycles plus two rituximab doses. The primary endpoint was investigator-assessed PFS. At two years PFS was 76.7% versus 70.2% (hazard ratio 0.73) while overall survival was identical (88.7% versus 88.6%) and the safety profiles were similar. Exploratory subgroups suggested most benefit in activated B-cell-like subtype, older patients and higher IPI, with little or no benefit in germinal-centre subtype. It was the first regimen to beat R-CHOP in two decades of trials.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa2115304"},{"label":"ClinicalTrials.gov NCT03274492","url":"https://clinicaltrials.gov/study/NCT03274492"}],"tags":[],"related":["lymphoma-roadmap","paper-polargo-polatuzumab-r-gemox-dlbcl-jco-2026","polar-bear"],"cancers":["dlbcl"],"sections":[],"technologies":["adc"],"targets":["cd79b","cd20"],"drugs":["polatuzumab-vedotin","rituximab","doxorubicin","vincristine"],"companies":["roche-genentech"],"institutions":[],"pathways":[],"terms":["pfs","os"],"trials":["polarix"],"people":[],"bottlenecks":["b-drug-pricing","b-biomarker-validation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/NEJMoa2115304","authors":"Tilly H, Morschhauser F, Sehn LH, et al.","paperType":"rct","findings":["879 untreated DLBCL patients, IPI 2-5; pola-R-CHP vs R-CHOP.","2-year PFS 76.7% vs 70.2%; hazard ratio 0.73 (about 6.5 percentage points absolute).","2-year overall survival 88.7% vs 88.6%; no difference.","Grade 3-4 adverse events 57.7% vs 57.5%; peripheral neuropathy rates similar.","Exploratory: benefit concentrated in ABC subtype, IPI 3-5 and age over 60; GCB subtype showed none."],"whatItMeans":"POLARIX gave the first new first-line standard for DLBCL since rituximab was added to CHOP, and pola-R-CHP is now approved and widely used, especially in higher-risk or ABC-type disease. The gain is modest and survival is unchanged, so many clinicians still use R-CHOP in lower-risk or GCB-type patients. Cost and subgroup uncertainty drive ongoing debate.","caveats":["No overall survival benefit; the PFS gain is modest in absolute terms.","Subgroup effects are exploratory and hypothesis-generating, yet influence practice.","Excluded very low IPI (0-1) and age over 80.","High cost relative to a generic-based regimen."],"changedPractice":true,"participants":879},{"id":"paper-polargo-polatuzumab-r-gemox-dlbcl-jco-2026","kind":"paper","name":"Polatuzumab vedotin plus rituximab, gemcitabine, and oxaliplatin in relapsed or refractory diffuse large B-cell lymphoma: results from the phase III, randomized POLARGO trial","aka":["POLARGO","Matasar 2026","Pola-R-GemOx"],"tldr":"Adding an antibody-drug conjugate to an outpatient chemotherapy pairing added seven months of median survival for people with relapsed aggressive lymphoma who could not have a transplant.","summary":"A randomised, open-label, global phase 3 trial. After a 15-patient safety run-in, 255 patients with relapsed or refractory diffuse large B-cell lymphoma, not otherwise specified or transformed from an indolent lymphoma, who were ineligible for autologous stem-cell transplantation, were randomised 1 to 1 to polatuzumab vedotin with rituximab, gemcitabine and oxaliplatin (129) or to rituximab, gemcitabine and oxaliplatin alone (126), every 21 days for up to eight cycles. Overall survival was the primary endpoint.\n\nAfter a median follow-up of 24.6 months, the hazard ratio for death was 0.6 (95 per cent confidence interval 0.43 to 0.83, p = 0.0017), with median overall survival 19.5 months (13.3 to not estimable) against 12.5 months (8.9 to 15.8). The commonest grade 3 or 4 adverse events were thrombocytopenia and neutropenia. Peripheral neuropathy occurred in 73 patients (57 per cent) on the polatuzumab arm against 36 (29 per cent), and was primarily grade 1. Fatal adverse events occurred in 15 patients (12 per cent) against five (4 per cent), largely driven by infections including COVID-19.","asOf":"2026-10-01","links":[{"label":"Journal of Clinical Oncology 2026","url":"https://doi.org/10.1200/JCO-25-02849"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42407012/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42407012"}],"tags":["lymphoma-evidence"],"related":["lymphoma-roadmap"],"cancers":["dlbcl","non-hodgkin-lymphoma"],"sections":["adcs","chemotherapy"],"technologies":["adc"],"targets":["cd79b","cd20"],"drugs":["polatuzumab-vedotin","rituximab","gemcitabine","oxaliplatin"],"companies":["roche-genentech"],"institutions":[],"pathways":[],"terms":[],"trials":["polargo","polarix"],"people":[],"bottlenecks":["b-aging-comorbidity","b-toxicity-qol"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2026,"doi":"10.1200/JCO-25-02849","pmid":"42407012","authors":"Matasar M, Li Z, Vassilakopoulos TP, et al.","paperType":"rct","findings":["Median overall survival was 19.5 months with polatuzumab vedotin added to rituximab, gemcitabine and oxaliplatin against 12.5 months without (hazard ratio 0.6, 95 per cent confidence interval 0.43 to 0.83, p = 0.0017).","Overall survival was the primary endpoint, not a secondary one.","Peripheral neuropathy occurred in 57 per cent of the polatuzumab group against 29 per cent, primarily grade 1.","Fatal adverse events occurred in 12 per cent against 4 per cent, largely driven by infections including COVID-19."],"whatItMeans":"An option with a demonstrated survival benefit for transplant-ineligible relapsed diffuse large B-cell lymphoma, a group for whom very little has ever shown one. The fatal adverse event imbalance belongs in the conversation alongside the survival figure.","caveats":["Open-label, so supportive care and subsequent therapy were not blinded.","Recruitment ran through the COVID-19 pandemic, which contributed to the fatal infection imbalance and makes it hard to read.","Patients who could receive CAR-T or a bispecific antibody may be better served by those, and the trial does not compare against them."],"changedPractice":true,"participants":255},{"id":"paper-polo-overall-survival-olaparib-gbrca-pancreatic-jco-2022","kind":"paper","name":"POLO final overall survival: maintenance olaparib versus placebo in germline BRCA-mutated metastatic pancreatic cancer","aka":[],"tldr":"The final results of POLO showed that olaparib did not lengthen overall survival on average, although about twice as many patients on olaparib were alive at three years, and the drug delayed the time until a second treatment was needed.","summary":"Prespecified final overall survival analysis of the POLO trial (154 patients with a germline BRCA mutation and platinum-sensitive metastatic pancreatic cancer). Median overall survival was 19.0 months with olaparib and 19.2 months with placebo (hazard ratio 0.83, not significant).\n\nSurvival curves separated late: about 34 percent of olaparib patients were alive at three years against about 18 percent on placebo. Time to second disease progression and time to second subsequent therapy favoured olaparib, and no new safety signals appeared with longer follow-up.","asOf":"2026-09-21","links":[{"label":"J Clin Oncol 2022","url":"https://doi.org/10.1200/JCO.21.01604"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35834777/"}],"tags":[],"related":["brca-germline"],"cancers":["brca-palb2-pdac","pancreatic"],"sections":[],"technologies":[],"targets":["brca"],"drugs":["olaparib"],"companies":[],"institutions":[],"pathways":[],"terms":["gbrca-mutation"],"trials":["polo"],"people":["hedy-kindler","talia-golan"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2022,"doi":"10.1200/JCO.21.01604","pmid":"35834777","authors":"Kindler HL, Hammel P, Reni M, et al.","paperType":"rct","findings":["Median overall survival 19.0 versus 19.2 months, hazard ratio 0.83, not statistically significant.","Three-year survival about 34 percent with olaparib versus 18 percent with placebo.","Time to second progression and to second subsequent therapy favoured olaparib."],"whatItMeans":"Olaparib maintenance remains a standard option because of its progression-free benefit, tolerability and long-term survivors, but patients should know that it has not been shown to extend average survival.","caveats":["Crossover to PARP inhibitors after progression on placebo was allowed, which may have diluted any survival effect.","The trial was not powered for overall survival."],"changedPractice":true,"participants":154},{"id":"paper-polo-olaparib-maintenance-gbrca-pancreatic-nejm-2019","kind":"paper","name":"POLO: maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer","aka":[],"tldr":"In patients with inherited BRCA mutations whose pancreatic cancer had been held in check by platinum chemotherapy, switching to the tablet olaparib roughly doubled the time before the disease grew again compared with placebo. It was the first biomarker-driven approval in pancreatic cancer.","summary":"International double-blind randomised phase 3 trial in 154 patients with a germline BRCA1 or BRCA2 mutation and metastatic pancreatic adenocarcinoma that had not progressed during at least 16 weeks of first-line platinum-based chemotherapy, randomised 3:2 to maintenance olaparib 300 mg twice daily or placebo.\n\nMedian progression-free survival was 7.4 months with olaparib and 3.8 months with placebo (hazard ratio 0.53); at the interim analysis there was no difference in overall survival. Health-related quality of life was maintained. The FDA approved olaparib for this indication in December 2019.","asOf":"2026-09-21","links":[{"label":"N Engl J Med 2019","url":"https://doi.org/10.1056/NEJMoa1903387"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31157963/"}],"tags":[],"related":["brca-germline"],"cancers":["brca-palb2-pdac","pancreatic"],"sections":[],"technologies":["germline-testing"],"targets":["brca"],"drugs":["olaparib"],"companies":[],"institutions":[],"pathways":["homologous-recombination-repair","ddr"],"terms":["gbrca-mutation","synthetic-lethality"],"trials":["polo"],"people":["talia-golan","hedy-kindler"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2019,"doi":"10.1056/NEJMoa1903387","pmid":"31157963","authors":"Golan T, Hammel P, Reni M, et al.","paperType":"rct","findings":["Median progression-free survival 7.4 versus 3.8 months, hazard ratio 0.53.","No overall survival difference at the interim analysis (hazard ratio about 0.9).","About 4 to 7 percent of pancreatic cancers carry a germline BRCA mutation, so germline testing is needed to find candidates."],"whatItMeans":"Germline testing for every pancreatic cancer patient, platinum first line for BRCA carriers, and olaparib maintenance for those who respond are all downstream of POLO.","caveats":["The final analysis found no significant overall survival benefit.","Only 154 of over 3,300 screened patients were randomised; the trial required platinum sensitivity and excluded those who had progressed."],"changedPractice":true,"participants":154},{"id":"paper-mavaddat-am-j-hum-genet","kind":"paper","name":"Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 30554720 and published in American journal of human genetics; the citing page links this DOI, which is how the record was matched.","summary":"Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.\n\nIndexed on Europe PMC as PubMed record 30554720 (DOI 10.1016/j.ajhg.2018.11.002). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Am J Hum Genet 2019","url":"https://doi.org/10.1016/j.ajhg.2018.11.002"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30554720/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30554720"}],"tags":["europepmc-ingest"],"related":["polygenic-risk-scores"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"American journal of human genetics","year":2019,"doi":"10.1016/j.ajhg.2018.11.002","pmid":"30554720","authors":"Mavaddat N, Michailidou K, Dennis J, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-wennmacker-gallbladder-polyp-size-threshold-surg-endosc-2019","kind":"paper","name":"Polyp size of 1 cm is insufficient to discriminate neoplastic and non-neoplastic gallbladder polyps","aka":[],"tldr":"In the Dutch national pathology archive fewer than one in a hundred removed gallbladders contained a polyp, more than four in ten of those polyps were harmless, and the one-centimetre rule for operating sorted them only moderately well.","summary":"PALGA nationwide pathology registry study of all histologically proven gallbladder polyps and focal wall thickenings over 5 mm between 2003 and 2013: 2,085 of 220,612 cholecystectomies (0.9 percent). Of these, 56.4 percent were neoplastic (40.1 percent premalignant, 59.9 percent malignant) and 43.6 percent non-neoplastic (41.5 percent cholesterol polyps, 37.0 percent adenomyomatosis). Neoplastic polyps were larger (18.1 versus 7.5 mm). Clinicopathological features differed but could not reliably indicate neoplasia, and the 1 cm surgical threshold had moderate diagnostic accuracy.","asOf":"2026-09-24","links":[{"label":"Surg Endosc 2019","url":"https://doi.org/10.1007/s00464-018-6444-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30203209/"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":["ultrasound"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["gallbladder-polyp","overdiagnosis"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Surgical Endoscopy","year":2019,"doi":"10.1007/s00464-018-6444-1","pmid":"30203209","authors":"Wennmacker SZ, van Dijk AH, Raessens JHJ, et al.","paperType":"observational","findings":["Polyps in 2,085 of 220,612 cholecystectomies (0.9 percent); 56.4 percent neoplastic, 43.6 percent non-neoplastic.","Mean size 18.1 mm for neoplastic vs 7.5 mm for non-neoplastic polyps.","The 1 cm threshold had moderate diagnostic accuracy for neoplasia."],"whatItMeans":"Size is a blunt tool: a 10 mm cut-off sends many people with cholesterol polyps to surgery and misses some neoplastic polyps below it. Better imaging (contrast-enhanced or endoscopic ultrasound) or a risk score is the research need the 2022 guideline itself acknowledges.","caveats":["Only polyps that reached pathology are counted; the denominator of polyps left in place is unknown.","Size was recorded in about half of the reports."],"changedPractice":false,"participants":2085},{"id":"paper-groarke-ponsegromab-cancer-cachexia-nejm-2024","kind":"paper","name":"Ponsegromab for the Treatment of Cancer Cachexia","aka":[],"tldr":"The 2024 phase 2 trial in which an antibody blocking the hormone GDF-15 helped patients with cancer-related wasting, a third of them with pancreatic cancer, gain about two to three kilograms in twelve weeks and become more active.","summary":"Groarke and colleagues randomised 187 patients with cancer cachexia and serum GDF-15 of 1,500 pg per millilitre or more (40 percent non-small-cell lung cancer, 32 percent pancreatic cancer, 29 percent colorectal cancer) 1:1:1:1 to ponsegromab 100, 200 or 400 mg or placebo subcutaneously every four weeks for three doses in a 12-week double-blind phase 2 trial. The primary endpoint, change in body weight at 12 weeks, favoured every dose: median between-group differences of 1.22 kg (100 mg), 1.92 kg (200 mg) and 2.81 kg (400 mg; 95 percent credible interval 1.55 to 4.08). Appetite, cachexia symptoms and digitally measured physical activity improved at 400 mg. Adverse events of any cause occurred in 70 percent on ponsegromab and 80 percent on placebo. Funded by Pfizer; NCT05546476.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2024","url":"https://doi.org/10.1056/NEJMoa2409515"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39282907/"},{"label":"ClinicalTrials.gov NCT05546476","url":"https://clinicaltrials.gov/study/NCT05546476"},{"label":"N Engl J Med 2024","url":"https://doi.org/10.1056/nejmoa2409515"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39282907"}],"tags":["pancreatic-evidence"],"related":["paper-fearon-lancet-oncol","survivorship-roadmap"],"cancers":["pancreatic","nsclc","colorectal"],"sections":["supportive-care"],"technologies":[],"targets":[],"drugs":["ponsegromab"],"companies":["pfizer"],"institutions":[],"pathways":[],"terms":[],"trials":["ponsegromab-phase-2"],"people":[],"bottlenecks":["b-cachexia-supportive"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2024,"doi":"10.1056/NEJMoa2409515","pmid":"39282907","authors":"Groarke JD, Crawford J, Collins SM, et al.","paperType":"rct","findings":["187 patients with cachexia and raised GDF-15; 32 percent pancreatic cancer.","Weight gain versus placebo at 12 weeks: 1.22 kg (100 mg), 1.92 kg (200 mg), 2.81 kg (400 mg).","Appetite, symptoms and physical activity improved at 400 mg; adverse events 70 versus 80 percent."],"whatItMeans":"The first drug to reverse cancer cachexia mechanistically rather than by appetite stimulation, in a disease where weight loss stops chemotherapy being delivered; the phase 3 programme and the question of survival remain.","caveats":["Twelve weeks, weight as the primary endpoint; effects on treatment delivery, function and survival are not shown.","Patients were selected by high GDF-15, so the result applies to that subset."],"participants":187},{"id":"paper-powell-esmo-open","kind":"paper","name":"Pooled analysis of drug-related interstitial lung disease and/or pneumonitis in nine trastuzumab deruxtecan monotherapy studies","aka":[],"tldr":"Paper cited by one pairing page, indexed on Europe PMC as PubMed record 35963179 and published in ESMO Open; the citing page links this DOI, which is how the record was matched.","summary":"Introduction: This pooled analysis of nine phase I and II trastuzumab deruxtecan (T-DXd) monotherapy studies described drug-related interstitial lung disease (ILD)/pneumonitis in patients treated with T-DXd.\n\nMethods: Patients who received T-DXd across nine studies were included. Investigator-assessed ILD/pneumonitis events were retrospectively reviewed by an independent adjudication committee; events adjudicated as drug-related ILD/pneumonitis are summarized.\n\nResults: The analysis included 1150 patients (breast cancer, 44.3%; gastric cancer, 25.6%; lung cancer, 17.7%; colorectal cancer, 9.3%; other cancer, 3.0%). Median treatment duration was 5.8 (range, 0.7-56.3) months, with a median of 4 (range, 1-27) prior lines of therapy. The overall incidence of adjudicated drug-related ILD/pneumonitis was 15.4% (grade 5, 2.2%). Most patients with ILD/pneumonitis experienced low-grade events (grade 1 or 2, 77.4%); 87.0% had their first event within 12 months [median, 5.4 (range, <0.1-46.8) months] of their first dose of T-DXd. Based on data review, adjudicated ILD/pneumonitis onset occurred earlier than identified by investigators for 53.2% of events [median difference in onset date, 43 (range, 1-499) days]. Stepwise Cox regression identified several baseline factors potentially associated with increased risk of adjudicated drug-related ILD/pneumonitis: age <65 years, enrollment in Japan, T-DXd dose >6.4 mg/kg, oxygen saturation <95%, moderate/severe renal impairment, presence of lung comorbidities, and time since initial diagnosis >4 years.\n\nConclusions: In this pooled analysis of heavily treated patients, the incidence of ILD/pneumonitis was 15.4%, with most being low grade and occurring in the first 12 months of treatment. The benefit-risk of T-DXd treatment is positive; however, some patients may be at increased risk of developing ILD/pneumonitis, and further investigation is needed to confirm ILD/pneumonitis risk factors. Close monitoring and proactive management of ILD/pneumonitis are warranted for all.\n\nIndexed on Europe PMC as PubMed record 35963179 (DOI 10.1016/j.esmoop.2022.100554). Matched by DOI alone: one pairing page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"ESMO Open 2022","url":"https://doi.org/10.1016/j.esmoop.2022.100554"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35963179/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35963179"}],"tags":["europepmc-ingest"],"related":["ild-overlap-caution"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["esmo-open"],"dependsOn":[],"notes":[],"journal":"ESMO Open","year":2022,"doi":"10.1016/j.esmoop.2022.100554","pmid":"35963179","authors":"Powell CA, Modi S, Iwata H, et al.","paperType":"observational","findings":[],"whatItMeans":"One pairing page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-gabai-kapara-population-brca-screening-pnas-2014","kind":"paper","name":"Population-based screening for breast and ovarian cancer risk due to BRCA1 and BRCA2","aka":[],"tldr":"The study that made population-wide BRCA testing defensible. Instead of measuring risk in families already known to cancer clinics, it found carriers among healthy men and then followed their female relatives, and the risk turned out to be just as high.","summary":"The objection to offering BRCA testing to everyone in a population was that the risk figures came from families referred to cancer genetics clinics, who are selected for having a lot of cancer. Ephrat Levy-Lahad and Mary-Claire King's answer was to start somewhere with no such selection. Between June 2004 and December 2010 they recruited healthy Ashkenazi Israeli men aged 30 and over with no personal history of cancer from health-screening centres and outpatient clinics: 8,222 enrolled, 8,195 (99.7 percent) were successfully genotyped for the three founder variants. Female relatives of the carriers were then enrolled and genotyped.\n\nCarrier frequency was 1.14 percent for BRCA1 and 1.03 percent for BRCA2, 2.17 percent combined. Among fully genotyped sibships, cumulative risk of breast or ovarian cancer was 0.60 by age 60 and 0.83 by age 80 for BRCA1 carriers, and 0.33 by 60 and 0.76 by 80 for BRCA2 carriers. Risk was higher in later birth cohorts: 3.8-fold higher age-specific risk for carriers born after 1958 than for those born in or before it.\n\nThe decisive number for policy is that 51 percent of the 167 carrier families had little or no relevant cancer history, so testing triggered by family history would have missed them; and only 35 percent of the 82 families that did have a high cancer burden had ever been referred for genetic counselling, in a country with universal health coverage. Israel began offering the three-variant test to every woman of Ashkenazi origin in January 2020.","asOf":"2026-09-25","links":[{"label":"PNAS 2014","url":"https://doi.org/10.1073/pnas.1415979111"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25192939/"}],"tags":[],"related":[],"cancers":["breast-hr-positive","ovarian"],"sections":["prevention"],"technologies":["germline-testing"],"targets":["brca"],"drugs":[],"companies":[],"institutions":["shaare-zedek","sheba"],"pathways":[],"terms":["founder-variant"],"trials":[],"people":["ephrat-levy-lahad","eitan-friedman"],"bottlenecks":["b-hereditary-risk"],"keyPapers":[],"journals":["pnas"],"dependsOn":[],"notes":[],"journal":"Proceedings of the National Academy of Sciences","year":2014,"doi":"10.1073/pnas.1415979111","pmid":"25192939","authors":"Gabai-Kapara E, Lahad A, Kaufman B, Friedman E, Segev S, Renbaum P, Beeri R, Gal M, Grinshpun-Cohen J, Djemal K, Mandell JB, Lee MK, Beller U, Catane R, King MC, Levy-Lahad E","paperType":"observational","findings":["Carrier frequency among 8,195 genotyped healthy Ashkenazi Israeli men: BRCA1 1.14 percent, BRCA2 1.03 percent, 2.17 percent combined.","Cumulative risk of breast or ovarian cancer by age 80: 0.83 (standard error 0.07) for BRCA1 carriers, 0.76 (0.13) for BRCA2 carriers.","Age-specific risk was 3.8-fold higher in carriers born after 1958 than in those born in or before 1958 (P = 0.006).","51 percent (85 of 167) of carrier families had little or no history of relevant cancer, so family-history criteria would not have identified them.","Only 35 percent (29 of 82) of the families with a high cancer burden had previously been referred for genetic counselling."],"whatItMeans":"This is the evidence base for offering an inherited-risk test to a whole population rather than to people who already look high risk. It is why Israel's health basket funds BRCA founder testing for every woman of Ashkenazi origin without a family history requirement, and it is quoted in every argument for doing the same elsewhere.","caveats":["Risk estimates are for three specific founder variants in one population; they do not transfer to other BRCA variants or other populations, and a negative three-variant test does not exclude inherited risk.","Ascertainment through healthy men removes clinic selection but the female relatives who agreed to be genotyped are still a volunteer sample.","The BRCA2 ovarian cancer estimate is unstable: 0.62 in fully genotyped sibships but 0.37 to 0.45 when all sibships are included with imputation."],"changedPractice":true,"participants":8195},{"id":"paper-zhu-population-specific-immunogenomics-gallbladder-cancer-mod-pathol-2025","kind":"paper","name":"Population-Specific Immunogenomic Alterations in Gallbladder Cancer and Prognostic Significance","aka":[],"tldr":"Gallbladder tumours from the United States and Chile carried the same set of mutated genes but very different immune cell make-up, which may bear on why immunotherapy helps only modestly and on how trials should be designed across regions.","summary":"Targeted next-generation sequencing and immunohistochemistry on two gallbladder cancer cohorts, from the United States (60) and Chile (62). Mutations in TP53, SMAD4, KRAS, PIK3CA, ARID2, ARID1A, ATM, FBXW7, ERBB2 and NF1 and amplifications of ERBB2, CCNE1, MDM2/CDK4 and CCND1 were found in both. Immune profiles differed: the Latin American cohort had higher densities of CD4-associated markers and PD-1 and lower CD68 macrophage density. Clustering suggested immune subgroups independent of mutations, and multiplexed single-cell imaging identified low CD4 with high VISTA as a candidate marker pair for poor outcome. The authors describe gallbladder cancer as an understudied disease and stress sensitivity to geography in therapeutic development.","asOf":"2026-09-24","links":[{"label":"Mod Pathol 2025","url":"https://doi.org/10.1016/j.modpat.2025.100824"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40541865/"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":["cgp","checkpoint-inhibitor"],"targets":["tp53","smad4","kras","pik3ca","arid1a","her2","pd1"],"drugs":[],"companies":[],"institutions":["md-anderson"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-rare-cancers","b-immunotherapy-response"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Modern Pathology","year":2025,"doi":"10.1016/j.modpat.2025.100824","pmid":"40541865","authors":"Zhu Y, Solis Soto LM, Pant S, et al.","paperType":"translational","findings":["Shared mutated genes in US and Chilean cohorts: TP53, SMAD4, KRAS, PIK3CA, ARID2, ARID1A, ATM, FBXW7, ERBB2, NF1; amplifications in ERBB2, CCNE1, MDM2/CDK4, CCND1.","Latin American cohort: higher CD4 and PD-1 marker densities, lower CD68 macrophage density."],"whatItMeans":"Evidence that the immune environment of gallbladder cancer differs by population even when the mutations do not; a reason to report gallbladder cancer and its regions separately in immunotherapy trials rather than as one biliary subgroup.","caveats":["Two cohorts of about 60; discovery-level findings.","Marker-pair prognostic claim awaits validation."],"changedPractice":false,"participants":122},{"id":"paper-portec-2-lancet-2010","kind":"paper","name":"PORTEC-2: vaginal brachytherapy versus pelvic external beam radiotherapy for high-intermediate-risk endometrial cancer","aka":[],"tldr":"For endometrial cancer of high-intermediate risk, brachytherapy to the top of the vagina alone controlled the disease as well as radiotherapy to the whole pelvis, with fewer bowel side effects and better quality of life.","summary":"Phase 3 trial of 427 women with stage I to IIA endometrial carcinoma with high-intermediate-risk features randomised to vaginal brachytherapy or external beam pelvic radiotherapy.\n\nFive-year vaginal recurrence was 1.8 versus 1.6 percent, locoregional relapse 5.1 versus 2.1 percent (not significant), and overall survival 84.8 versus 79.6 percent, with markedly less gastrointestinal toxicity after brachytherapy.","asOf":"2026-09-17","links":[{"label":"Lancet 2010","url":"https://doi.org/10.1016/S0140-6736(09)62163-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20206777/"}],"tags":[],"related":[],"cancers":["endometrial-nsmp"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["portec-2"],"people":["remi-nout"],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2010,"doi":"10.1016/S0140-6736(09)62163-2","pmid":"20206777","authors":"Nout RA, Smit VT, Putter H, et al.","paperType":"rct","findings":["Five-year vaginal recurrence 1.8 percent vs 1.6 percent.","Five-year overall survival 84.8 percent vs 79.6 percent (not significant)."],"whatItMeans":"Vaginal brachytherapy is the standard adjuvant treatment for high-intermediate-risk endometrial cancer, with pelvic radiotherapy reserved for higher-risk features such as substantial lymphovascular invasion or p53 abnormality.","caveats":["Pelvic recurrences were slightly more frequent after brachytherapy alone.","Molecular classification was not available; later analysis shows p53-abnormal tumours do poorly with either."],"changedPractice":true,"participants":427},{"id":"paper-portec-3-lancet-oncol-2018","kind":"paper","name":"PORTEC-3: adjuvant chemoradiotherapy versus radiotherapy alone for high-risk endometrial cancer","aka":[],"tldr":"Adding cisplatin during pelvic radiotherapy and four cycles of carboplatin-paclitaxel afterwards improved failure-free survival in high-risk endometrial cancer, most clearly in stage III and serous cancers, at the cost of more toxicity.","summary":"Phase 3 trial of 686 women with high-risk endometrial cancer (stage I grade 3 with deep invasion or lymphovascular invasion, stage II to III, or serous or clear cell histology) randomised to pelvic radiotherapy alone or radiotherapy with concurrent cisplatin followed by four cycles of carboplatin-paclitaxel.\n\nFive-year failure-free survival was 75.5 versus 68.6 percent (hazard ratio 0.71); overall survival was 81.4 versus 76.1 percent, significant only on longer follow-up, with the largest benefit in stage III and serous disease.","asOf":"2026-09-17","links":[{"label":"Lancet Oncol 2018","url":"https://doi.org/10.1016/S1470-2045(18)30079-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29449189/"}],"tags":[],"related":[],"cancers":["endometrial-p53-abnormal"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["portec-3"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2018,"doi":"10.1016/S1470-2045(18)30079-2","pmid":"29449189","authors":"de Boer SM, Powell ME, Mileshkin L, et al.","paperType":"rct","findings":["Five-year failure-free survival 75.5 percent vs 68.6 percent; hazard ratio 0.71.","Updated five-year overall survival 81.4 percent vs 76.1 percent."],"whatItMeans":"Chemoradiotherapy is the standard for stage III and for p53-abnormal or serous endometrial cancer; for other stage I to II tumours radiotherapy alone or brachytherapy suffices.","caveats":["Grade 3 or worse adverse events 60 percent vs 12 percent during treatment; persistent neuropathy.","The molecular sub-analysis shows benefit is concentrated in p53-abnormal tumours."],"changedPractice":true,"participants":686},{"id":"paper-van-den-heuvel-eibrink-nat-rev-urol","kind":"paper","name":"Position paper: Rationale for the treatment of Wilms tumour in the UMBRELLA SIOP-RTSG 2016 protocol","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 29089605 and published in Nature reviews. Urology; the citing page links this DOI, which is how the record was matched.","summary":"The Renal Tumour Study Group of the International Society of Paediatric Oncology (SIOP-RTSG) has developed a new protocol for the diagnosis and treatment of childhood renal tumours, the UMBRELLA SIOP-RTSG 2016 (the UMBRELLA protocol), to continue international collaboration in the treatment of childhood renal tumours. This protocol will support integrated biomarker and imaging research, focussing on assessing the independent prognostic value of genomic changes within the tumour and the volume of the blastemal component that survives preoperative chemotherapy. Treatment guidelines for Wilms tumours in the UMBRELLA protocol include recommendations for localized, metastatic, and bilateral disease, for all age groups, and for relapsed disease. These recommendations have been established by a multidisciplinary panel of leading experts on renal tumours within the SIOP-RTSG. The UMBRELLA protocol should promote international collaboration and research and serve as the SIOP-RTSG best available treatment standard.\n\nIndexed on Europe PMC as PubMed record 29089605 (DOI 10.1038/nrurol.2017.163). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Urol 2017","url":"https://doi.org/10.1038/nrurol.2017.163"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29089605/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29089605"}],"tags":["europepmc-ingest"],"related":["wilms-tumor"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature reviews. Urology","year":2017,"doi":"10.1038/nrurol.2017.163","pmid":"29089605","authors":"van den Heuvel-Eibrink MM, Hol JA, Pritchard-Jones K, et al.","paperType":"review","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-ghsg-hd16-pet-guided-early-favourable-hodgkin-jco-2019","kind":"paper","name":"Positron emission tomography-guided treatment in early-stage favorable Hodgkin lymphoma: final results of the international, randomized phase III HD16 trial by the German Hodgkin Study Group","aka":["HD16","Fuchs 2019"],"tldr":"Trying to spare radiotherapy on the strength of a clear scan after two rounds of chemotherapy cost about seven people in a hundred their remission.","summary":"An international randomised phase 3 trial recruiting patients aged 18 to 75 with newly diagnosed early-stage favourable Hodgkin lymphoma between November 2009 and December 2015. Patients were assigned to standard combined-modality treatment of two cycles of ABVD with 20 Gy of involved-field radiotherapy, or to positron emission tomography-guided treatment omitting the radiotherapy after a negative scan following two cycles. 1,150 patients were enrolled and median follow-up was 45 months.\n\nAmong 628 scan-negative patients treated per protocol, five-year progression-free survival was 93.4 per cent (95 per cent confidence interval 90.4 to 96.5) with combined-modality treatment and 86.1 per cent (81.4 to 90.9) with ABVD alone, a difference of 7.3 percentage points (1.6 to 13.0) and a hazard ratio of 1.78 (1.02 to 3.12). Five-year overall survival was 98.1 per cent (96.5 to 99.8) and 98.4 per cent (96.5 to 100.0). Among 693 patients assigned to combined-modality treatment, five-year progression-free survival was 93.2 per cent in scan-negative patients against 88.4 per cent in scan-positive patients (p = 0.047), and 93.1 against 80.9 per cent (p = 0.0011) when a Deauville score of 4 was used as the threshold for positivity.","asOf":"2026-10-01","links":[{"label":"Journal of Clinical Oncology 2019","url":"https://doi.org/10.1200/JCO.19.00964"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31498753/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31498753"}],"tags":["lymphoma-evidence"],"related":["paper-schaapveld-second-cancer-risk-40-years-hodgkin-nejm-2015","lymphoma-roadmap"],"cancers":["early-stage-classical-hodgkin-lymphoma","hodgkin-lymphoma"],"sections":["radiation","imaging"],"technologies":["radiotherapy","pet-ct"],"targets":[],"drugs":["doxorubicin","bleomycin","vinblastine","dacarbazine"],"companies":["ghsg"],"institutions":[],"pathways":[],"terms":["deauville-score","abvd-beacopp"],"trials":["hd16","radar-hodgkin"],"people":["peter-borchmann","andreas-engert"],"bottlenecks":["b-negative-results","b-survivorship"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2019,"doi":"10.1200/JCO.19.00964","pmid":"31498753","authors":"Fuchs M, Goergen H, Kobe C, et al.","paperType":"rct","findings":["Among 628 scan-negative patients, five-year progression-free survival was 93.4 per cent with combined-modality treatment and 86.1 per cent with ABVD alone (difference 7.3 percentage points, hazard ratio 1.78, 95 per cent confidence interval 1.02 to 3.12).","Five-year overall survival was 98.1 per cent with combined-modality treatment and 98.4 per cent with ABVD alone.","A positive scan after two cycles predicted worse five-year progression-free survival within the combined-modality arm, 88.4 against 93.2 per cent (p = 0.047).","Using a Deauville score of 4 as the threshold for positivity widened the difference to 80.9 against 93.1 per cent (p = 0.0011)."],"whatItMeans":"Radiotherapy cannot be omitted in early-stage favourable Hodgkin lymphoma on the basis of a negative interim scan without a clinically relevant loss of tumour control. The scan is better at identifying who needs more than at identifying who needs less.","caveats":["Median follow-up of 45 months is short relative to the late effects that make omitting radiotherapy desirable; the survival curves are identical so far.","The per-protocol analysis of scan-negative patients is not the intention-to-treat population.","20 Gy involved-field radiotherapy is a far smaller exposure than the mantle fields that produced the late-effect figures in the Dutch cohorts, so the trade-off being weighed is not the historical one."],"changedPractice":true,"participants":1150},{"id":"paper-sheikh-ann-intern-med","kind":"paper","name":"Postdiagnosis Smoking Cessation and Reduced Risk for Lung Cancer Progression and Mortality: A Prospective Cohort Study","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 34310171 and published in Annals of Internal Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Background: Lung cancer is the leading cause of cancer death worldwide, and about one half of patients with lung cancer are active smokers at diagnosis.\n\nObjective: To determine whether quitting smoking after diagnosis of lung cancer affects the risk for disease progression and mortality.\n\nDesign: Prospective study of patients with non-small cell lung cancer (NSCLC) who were recruited between 2007 and 2016 and followed annually through 2020.\n\nSetting: N.N. Blokhin National Medical Research Center of Oncology and City Clinical Oncological Hospital No. 1, Moscow, Russia.\n\nPatients: 517 current smokers who were diagnosed with early-stage (IA-IIIA) NSCLC.\n\nMeasurements: Probabilities of overall survival, progression-free survival, and lung cancer - specific mortality and hazard ratios (HRs) for all-cause and cancer-specific mortality.\n\nResults: During an average of 7 years of follow-up, 327 (63.2%) deaths, 273 (52.8%) cancer-specific deaths, and 172 (33.7%) cases of tumor progression (local recurrence or metastasis) were recorded. The adjusted median overall survival time was 21.6 months higher among patients who had quit smoking than those who continued smoking (6.6 vs. 4.8 years, respectively; P = 0.001). Higher 5-year overall survival (60.6% vs. 48.6%; P = 0.001) and progression-free survival (54.4% vs. 43.8%; P = 0.004) were observed among patients who quit than those who continued smoking. After adjustments, smoking cessation remained associated with decreased risk for all-cause mortality (HR, 0.67 [95% CI, 0.53 to 0.85]), cancer-specific mortality (HR, 0.75 [CI, 0.58 to 0.98]), and disease progression (HR, 0.70 [CI, 0.56 to 0.89]). Similar effects were observed among mild to moderate and heavy smokers and patients with earlier and later cancer stages.\n\nLimitation: Exposure measurements were based on self-reported questionnaires.\n\nConclusion: Smoking cessation after diagnosis materially improved overall and progression-free survival among current smokers with early-stage lung cancer.\n\nPrimary funding source: International Agency for Research on Cancer.\n\nIndexed on Europe PMC as PubMed record 34310171 (DOI 10.7326/m21-0252). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Ann Intern Med 2021","url":"https://doi.org/10.7326/m21-0252"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34310171/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34310171"}],"tags":["europepmc-ingest"],"related":["smoking-cessation-after-diagnosis"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-internal-medicine"],"dependsOn":[],"notes":[],"journal":"Annals of Internal Medicine","year":2021,"doi":"10.7326/m21-0252","pmid":"34310171","authors":"Sheikh M, Mukeriya A, Shangina O, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-overgaard-n-engl-j-med","kind":"paper","name":"Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 9395428 and published in New England Journal of Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Background: Irradiation after mastectomy can reduce locoregional recurrences in women with breast cancer, but whether it prolongs survival remains controversial. We conducted a randomized trial of radiotherapy after mastectomy in high-risk premenopausal women, all of whom also received adjuvant systemic chemotherapy with cyclophosphamide, methotrexate, and fluorouracil (CMF).\n\nMethods: A total of 1708 women who had undergone mastectomy for pathological stage II or III breast cancer were randomly assigned to receive eight cycles of CMF plus irradiation of the chest wall and regional lymph nodes (852 women) or nine cycles of CMF alone (856 women). The median length of follow-up was 114 months. The end points were locoregional recurrence, distant metastases, disease-free survival, and overall survival.\n\nResults: The frequency of locoregional recurrence alone or with distant metastases was 9 percent among the women who received radiotherapy plus CMF and 32 percent among those who received CMF alone (P<0.001). The probability of survival free of disease after 10 years was 48 percent among the women assigned to radiotherapy plus CMF and 34 percent among those treated only with CMF (P<0.001). Overall survival at 10 years was 54 percent among those given radiotherapy and CMF and 45 percent among those who received CMF alone (P<0.001). Multivariate analysis demonstrated that irradiation after mastectomy significantly improved disease-free survival and overall survival, irrespective of tumor size, the number of positive nodes, or the histopathological grade.\n\nConclusions: The addition of postoperative irradiation to mastectomy and adjuvant chemotherapy reduces locoregional recurrences and prolongs survival in high-risk premenopausal women with breast cancer.\n\nIndexed on Europe PMC as PubMed record 9395428 (DOI 10.1056/nejm199710023371401). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 1997","url":"https://doi.org/10.1056/nejm199710023371401"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/9395428/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/9395428"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["dbcg-82bc"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":1997,"doi":"10.1056/nejm199710023371401","pmid":"9395428","authors":"Overgaard M, Hansen PS, Overgaard J, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-asco-potentially-curable-pancreatic-guideline-update-jco-2019","kind":"paper","name":"Potentially Curable Pancreatic Adenocarcinoma: ASCO Clinical Practice Guideline Update","aka":[],"tldr":"The 2019 American guideline update that made six months of modified FOLFIRINOX the preferred chemotherapy after pancreatic cancer surgery for patients fit enough to take it, on the strength of a single trial.","summary":"ASCO convened an Expert Panel to evaluate PRODIGE 24/CCTG PA.6, the phase 3 trial of postoperative modified FOLFIRINOX versus gemcitabine presented at the 2018 ASCO Annual Meeting, and searched PubMed for other papers bearing on the existing recommendations. Only Recommendation 4.1 was updated: all patients with resected pancreatic adenocarcinoma who did not receive preoperative therapy should be offered six months of adjuvant chemotherapy in the absence of medical or surgical contraindications; modified FOLFIRINOX (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, irinotecan 150 mg/m2 day 1, fluorouracil 2.4 g/m2 over 46 hours every 14 days for 12 cycles) is preferred in the absence of concerns for toxicity or tolerance; gemcitabine plus capecitabine, gemcitabine alone or fluorouracil plus folinic acid alone can be offered instead.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2019","url":"https://doi.org/10.1200/JCO.19.00946"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31180816/"}],"tags":["pancreatic-evidence"],"related":["paper-prodige-24-adjuvant-mfolfirinox-pancreatic-nejm-2018"],"cancers":["pancreatic","resectable-pdac"],"sections":[],"technologies":[],"targets":[],"drugs":["folfirinox","gemcitabine","capecitabine"],"companies":[],"institutions":["asco"],"pathways":[],"terms":["neoadjuvant-adjuvant"],"trials":["prodige-24"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2019,"doi":"10.1200/JCO.19.00946","pmid":"31180816","authors":"Khorana AA, McKernin SE, Berlin J, et al.","paperType":"guideline","findings":["Six months of adjuvant chemotherapy for every resected patient who had no preoperative therapy, absent contraindications.","Modified FOLFIRINOX for 12 cycles is preferred; gemcitabine plus capecitabine, gemcitabine or fluorouracil plus folinic acid are alternatives."],"whatItMeans":"The formal adoption of PRODIGE 24 into practice; every later debate about giving chemotherapy before rather than after surgery starts from this recommendation.","caveats":["Based on one trial in fit patients aged 18 to 79; the guideline leaves the choice for less fit patients to the alternatives.","Written before PREOPANC-2, NORPACT-1 and Alliance A021806 addressed preoperative treatment of resectable disease."],"changedPractice":true},{"id":"paper-mohile-j-clin-oncol","kind":"paper","name":"Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Chemotherapy: ASCO Guideline for Geriatric Oncology","aka":[],"tldr":"Paper cited by one bottleneck page, indexed on Europe PMC as PubMed record 29782209 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose To provide guidance regarding the practical assessment and management of vulnerabilities in older patients undergoing chemotherapy. Methods An Expert Panel was convened to develop clinical practice guideline recommendations based on a systematic review of the medical literature. Results A total of 68 studies met eligibility criteria and form the evidentiary basis for the recommendations. Recommendations In patients ≥ 65 years receiving chemotherapy, geriatric assessment (GA) should be used to identify vulnerabilities that are not routinely captured in oncology assessments. Evidence supports, at a minimum, assessment of function, comorbidity, falls, depression, cognition, and nutrition. The Panel recommends instrumental activities of daily living to assess for function, a thorough history or validated tool to assess comorbidity, a single question for falls, the Geriatric Depression Scale to screen for depression, the Mini-Cog or the Blessed Orientation-Memory-Concentration test to screen for cognitive impairment, and an assessment of unintentional weight loss to evaluate nutrition. Either the CARG (Cancer and Aging Research Group) or CRASH (Chemotherapy Risk Assessment Scale for High-Age Patients) tools are recommended to obtain estimates of chemotherapy toxicity risk; the Geriatric-8 or Vulnerable Elders Survey-13 can help to predict mortality. Clinicians should use a validated tool listed at ePrognosis to estimate noncancer-based life expectancy ≥ 4 years. GA results should be applied to develop an integrated and individualized plan that informs cancer management and to identify nononcologic problems amenable to intervention. Collaborating with caregivers is essential to implementing GA-guided interventions. The Panel suggests that clinicians take into account GA results when recommending chemotherapy and that the information be provided to patients and caregivers to guide treatment decision making. Clinicians should implement targeted, GA-guided interventions to manage nononcologic problems. Additional information is available at www.asco.org/supportive-care-guidelines.\n\nIndexed on Europe PMC as PubMed record 29782209 (DOI 10.1200/jco.2018.78.8687). Matched by DOI alone: one bottleneck page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2018","url":"https://doi.org/10.1200/jco.2018.78.8687"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29782209/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29782209"}],"tags":["europepmc-ingest"],"related":["b-aging-comorbidity"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2018,"doi":"10.1200/jco.2018.78.8687","pmid":"29782209","authors":"Mohile SG, Dale W, Somerfield MR, et al.","paperType":"guideline","findings":[],"whatItMeans":"One bottleneck page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-hesseling-pediatr-blood-cancer","kind":"paper","name":"Practical recommendations for the management of children with endemic Burkitt lymphoma (BL) in a resource limited setting","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 23192950 and published in Pediatric Blood & Cancer; the citing page links this DOI, which is how the record was matched.","summary":"Treatment recommendations for endemic Burkitt lymphoma (BL) in settings with only minimum requirements for curative treatment (PODC setting 1) are described. The reported cure rate for endemic BL is usually <50%. Facilities within setting 1 differ. Three treatment schedules are proposed based on: (1) when accurate staging is not possible, (2) when staging is possible and for (3) relapses and poor responders to primary therapy. A literature review and personal experience were used to formulate the recommendations. Recorded 1-year event free survival was 48% for treatment 1, 61% for treatment 2, and 35% for the rescue treatment.\n\nIndexed on Europe PMC as PubMed record 23192950 (DOI 10.1002/pbc.24407). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Pediatr Blood Cancer 2013","url":"https://doi.org/10.1002/pbc.24407"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23192950/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/23192950"}],"tags":["europepmc-ingest"],"related":["burkitt-lymphoma"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["pediatric-blood-and-cancer"],"dependsOn":[],"notes":[],"journal":"Pediatric Blood & Cancer","year":2013,"doi":"10.1002/pbc.24407","pmid":"23192950","authors":"Hesseling P, Israels T, Harif M, et al.","paperType":"guideline","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-prasad-surrogate-endpoints-jama-im-2015","kind":"paper","name":"Prasad: most surrogate endpoints in cancer trials correlate poorly with survival","aka":[],"tldr":"A systematic review of 36 trial-level meta-analyses found that in over half the surrogate endpoint (response rate, progression-free survival) had a low correlation with overall survival, and only about a quarter showed a strong correlation.","summary":"Prasad and colleagues searched for trial-level meta-analyses that quantified the correlation between a surrogate endpoint and overall survival across randomised oncology trials. They identified 36 articles covering 65 surrogate-survival associations in many tumour types and settings.\n\nUsing a conventional threshold, 52% of reported correlations were low (r below 0.7), 25% medium (0.7 to 0.85) and 23% high (0.85 or more). Correlations were weakest in the metastatic setting and for response rate. A companion analysis by the same group (Kim and Prasad, JAMA Internal Medicine 2015) showed that of 54 FDA cancer drug approvals in 2008-2012, 36 were based on surrogates, and after a median 4.4 years only 5 had demonstrated an overall survival benefit.\n\nThe work catalysed the debate over accelerated approval, the FDA's 2023-2025 reforms requiring confirmatory trials to be under way at approval, and the growing use of quality-of-life and patient-reported endpoints.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1001/jamainternmed.2015.2829"},{"label":"Kim and Prasad: FDA approvals on surrogates (2015)","url":"https://doi.org/10.1001/jamainternmed.2015.5868"}],"tags":[],"related":["idea-tr1-surrogate-validation-programme","idea-tr1-power-for-meaningful-benefit","idea-prev-mced-stage-endpoint-surrogate","idea-tr1-win-ratio-net-benefit-endpoint"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["pfs","os","orr","accelerated-approval","hazard-ratio","recist"],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-regulatory-fragmentation","b-drug-pricing","b-patient-voice"],"keyPapers":[],"journals":["jama-internal-medicine"],"dependsOn":[],"notes":[],"journal":"JAMA Internal Medicine","year":2015,"doi":"10.1001/jamainternmed.2015.2829","pmid":"26098871","authors":"Prasad V, Kim C, Burotto M, Vandross A","paperType":"meta-analysis","findings":["36 trial-level meta-analyses covering 65 surrogate-OS associations reviewed","52% of surrogate-survival correlations were low (r below 0.7), 25% medium, 23% high","Response rate and PFS in the metastatic setting were the weakest surrogates","Companion analysis: of 36 approvals on surrogates (2008-2012), 5 later showed an OS benefit, 18 failed to or were not tested, and 13 remained unknown"],"whatItMeans":"A drug that shrinks tumours or delays progression on scans has not necessarily been shown to help patients live longer or better. Patients and clinicians should ask what the endpoint was; regulators should insist on timely confirmatory trials; and trialists should validate surrogates before relying on them.","caveats":["Trial-level correlation is only one way to validate a surrogate; some settings (adjuvant DFS in colon cancer) have well-validated surrogates","Low correlation may reflect crossover and post-progression therapy diluting the OS signal rather than a useless surrogate","The review depended on published meta-analyses and their heterogeneous methods","PFS can be a meaningful endpoint in itself when progression is symptomatic and treatment is tolerable"],"changedPractice":false},{"id":"paper-lee-prc2-mpnst-nat-genet-2014","kind":"paper","name":"PRC2 is recurrently inactivated through EED or SUZ12 loss in malignant peripheral nerve sheath tumours","aka":[],"tldr":"Sequencing showed that most malignant peripheral nerve sheath tumours lose the polycomb repressive complex 2 through EED or SUZ12 mutations, on top of NF1 and CDKN2A loss, explaining their biology and giving pathologists the H3K27me3 stain that diagnoses them.","summary":"Genomic analysis of malignant peripheral nerve sheath tumours identifying loss-of-function alterations in EED or SUZ12, components of PRC2, in 70 percent of sporadic and 90 percent of radiotherapy-associated tumours, co-occurring with NF1 and CDKN2A inactivation, leading to loss of H3K27 trimethylation and amplified Ras signalling.","asOf":"2026-09-17","links":[{"label":"Nat Genet 2014","url":"https://doi.org/10.1038/ng.3095"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25240281/"}],"tags":[],"related":[],"cancers":["malignant-peripheral-nerve-sheath-tumour"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":2014,"doi":"10.1038/ng.3095","pmid":"25240281","authors":"Lee W, Teckie S, Wiesner T, et al.","paperType":"translational","findings":["PRC2 component loss (EED or SUZ12) in 70 to 90 percent of MPNST.","Complete loss of H3K27me3 in PRC2-deficient tumours."],"whatItMeans":"Loss of H3K27me3 immunostaining is now a diagnostic marker for MPNST, and PRC2 loss is a target for epigenetic and combination therapies under investigation.","caveats":["Therapeutic exploitation of PRC2 loss remains experimental."],"changedPractice":true},{"id":"paper-peinado-nat-rev-cancer","kind":"paper","name":"Pre-metastatic niches: organ-specific homes for metastases","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 28303905 and published in Nature Reviews Cancer; the citing page links this DOI, which is how the record was matched.","summary":"It is well established that organs of future metastasis are not passive receivers of circulating tumour cells, but are instead selectively and actively modified by the primary tumour before metastatic spread has even occurred. Sowing the 'seeds' of metastasis requires the action of tumour-secreted factors and tumour-shed extracellular vesicles that enable the 'soil' at distant metastatic sites to encourage the outgrowth of incoming cancer cells. In this Review, we summarize the main processes and new mechanisms involved in the formation of the pre-metastatic niche.\n\nIndexed on Europe PMC as PubMed record 28303905 (DOI 10.1038/nrc.2017.6). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Cancer 2017","url":"https://doi.org/10.1038/nrc.2017.6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28303905/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28303905"}],"tags":["europepmc-ingest"],"related":["pre-metastatic-niche"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Cancer","year":2017,"doi":"10.1038/nrc.2017.6","pmid":"28303905","authors":"Peinado H, Zhang H, Matei IR, et al.","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-burden-cochrane-database-syst-rev","kind":"paper","name":"Pre-operative nutrition support in patients undergoing gastrointestinal surgery","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 23152265 and published in The Cochrane database of systematic reviews; the citing page links this DOI, which is how the record was matched.","summary":"Background: Post-operative management in gastrointestinal (GI) surgery is becoming well established with 'Enhanced Recovery After Surgery' protocols starting 24 hours prior to surgery with carbohydrate loading and early oral or enteral feeding given to patients the first day following surgery. However, whether or not nutritional intervention should be initiated earlier in the preoperative period remains unclear. Poor pre-operative nutritional status has been linked consistently to an increase in post-operative complications and poorer surgical outcome.\n\nObjectives: To review the literature on preoperative nutritional support in patients undergoing gastrointestinal surgery (GI).\n\nSearch methods: The searches were initially run in March 2011 and subsequently updated in February 2012. Databases including all EBM Reviews (Cochrane DSR, ACP Journal Club, DARE, CCTR, CMR, HTA and NHSEED) MEDLINE, EMBASE, AMED, British Nursing Index Archive using OvidSP were included and a search was run on each database separately after which duplicates were excluded.\n\nSelection criteria: The inclusion criteria were randomised controlled trials that evaluated pre-operative nutritional support in GI surgical participants using a nutritional formula delivered by a parenteral, enteral or oral route. The primary outcomes included post-operative complications and length of hospital stay.\n\nData collection and analysis: Two observers screened the abstracts for inclusion in the review and performed data extraction. Bias was assessed for each of the included studies using the bias assessment tables in the Cochrane Software Review Manager (version 5.1, Cochrane Collaboration). The trials were analysed using risk ratios with Mantel-Haenszel in fixed effects methods displayed with heterogeneity. Meta-analyses were undertaken on trials evaluating immune enhancing (IE) nutrition, standard oral supplements, enteral and parenteral nutrition (PN) which were administered pre-operatively.Study characteristics were summarised in tables. Dichotomous and ratio data were entered into meta-analyses for the primary outcomes. These were then summarised in tables with assumed and corresponding risk with relative effect giving 95% confidence intervals.\n\nMain results: The searches identified 9900 titles and, after excluding duplicates, 6433 titles were initially screened. After the initial title screen, 6266 were excluded. Abstracts were screened for 167 studies and 33 articles were identified as meeting the inclusion criteria, of which 13 were included in the review after an assessment of the complete manuscripts.Seven trials evaluating IE nutrition were included in the review, of which 6 were combined in a meta-analysis. These studies showed a low to moderate level of heterogeneity and significantly reduced total post-operative complications (risk ratio (RR) 0.67 CI 0.53 to 0.84). Three trials evaluating PN were included in a meta-analysis and a significant reduction in post-operative complications was demonstrated (RR 0.64 95% CI 0.46 to 0.87) with low heterogeneity, in predominantly malnourished participants. Two trials evaluating enteral nutrition (RR 0.79, 95% CI 0.56 to 1.10) and 3 trials evaluating standard oral supplements (RR 1.01 95% CI 0.56 to 1.10) were included, neither of which showed any difference in the primary outcomes.\n\nAuthors' conclusions: There have been significant benefits demonstrated with pre-operative administration of IE nutrition in some high quality trials. However, bias was identified which may limit the generalizability of these results to all GI surgical candidates and the data needs to be placed in context with other recent innovations in surgical management (eg-ERAS). Some unwanted effects have also been reported with components of IE nutrition in critical care patients and it is unknown whether there would be detrimental effects by administering IE nutrition to patients who could require critical care support after their surgery. The studies evaluating PN demonstrated that the provision of PN to predominantly malnourished surgical candidates reduced post-operative complications; however, these data may not be applicable to current clinical practice, not least because they have involved a high degree of 'hyperalimentation'. Trials evaluating enteral or oral nutrition were inconclusive and further studies are required to select GI surgical patients for these nutritional interventions.\n\nIndexed on Europe PMC as PubMed record 23152265 (DOI 10.1002/14651858.cd008879.pub2). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cochrane Database Syst Rev 2012","url":"https://doi.org/10.1002/14651858.cd008879.pub2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23152265/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/23152265"}],"tags":["europepmc-ingest"],"related":["immunonutrition-perioperative"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Cochrane database of systematic reviews","year":2012,"doi":"10.1002/14651858.cd008879.pub2","pmid":"23152265","authors":"Burden S, Todd C, Hill J, et al.","paperType":"meta-analysis","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-makohon-moore-precursor-cells-ductal-system-nature-2018","kind":"paper","name":"Precancerous neoplastic cells can move through the pancreatic ductal system","aka":[],"tldr":"Sequencing several precursor lesions and the cancer from the same pancreas showed that what look like separate high-grade lesions are often one neoplasm that has crawled along the duct system over years.","summary":"Somatic variants of pancreatic cancers and precursor lesions sampled from distinct regions of the same pancreas were analysed. Evolutionary inference showed an ancestral cell initiating and clonally expanding to form one or more lesions, with subsequent driver mutations eventually leading to invasive cancer, a multi-step progression generally spanning many years. Independent high-grade precursor lesions observed in a single pancreas often represent a single neoplasm that has colonised the ductal system, accumulating spatial and genetic divergence.","asOf":"2026-09-24","links":[{"label":"Makohon-Moore et al., Nature 2018: precancerous cells move through the ductal system","url":"https://doi.org/10.1038/s41586-018-0481-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30177826/"}],"tags":[],"related":[],"cancers":["pancreatic","ipmn-cystic-precursors"],"sections":[],"technologies":["wes-wgs","pancreatic-surveillance"],"targets":[],"drugs":[],"companies":[],"institutions":["mskcc","johns-hopkins"],"pathways":["clonal-evolution"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2018,"doi":"10.1038/s41586-018-0481-8","pmid":"30177826","authors":"Makohon-Moore AP, Matsukuma K, Zhang M, et al.","paperType":"translational","findings":["Apparently independent high-grade precursor lesions are often one neoplasm colonising the ducts.","Progression from ancestral cell to invasive cancer spans many years."],"whatItMeans":"It reframes multifocal high-grade dysplasia found at surveillance: the pancreas may hold one spreading lesion rather than several, which bears on how much gland to remove.","caveats":["Small number of pancreata analysed regionally.","Timing estimates rest on molecular clock assumptions."],"changedPractice":false},{"id":"paper-burd-nat-med","kind":"paper","name":"Precision medicine treatment in acute myeloid leukemia using prospective genomic profiling: feasibility and preliminary efficacy of the Beat AML Master Trial","aka":[],"tldr":"Paper cited by one trial page and one collection page, indexed on Europe PMC as PubMed record 33106665 and published in Nature Medicine; the citing pages link this DOI, which is how the record was matched.","summary":"Acute myeloid leukemia (AML) is the most common diagnosed leukemia. In older adults, AML confers an adverse outcome 1,2. AML originates from a dominant mutation, then acquires collaborative transformative mutations leading to myeloid transformation and clinical/biological heterogeneity. Currently, AML treatment is initiated rapidly, precluding the ability to consider the mutational profile of a patient's leukemia for treatment decisions. Untreated patients with AML ≥ 60 years were prospectively enrolled on the ongoing Beat AML trial (ClinicalTrials.gov NCT03013998), which aims to provide cytogenetic and mutational data within 7 days (d) from sample receipt and before treatment selection, followed by treatment assignment to a sub-study based on the dominant clone. A total of 487 patients with suspected AML were enrolled; 395 were eligible. Median age was 72 years (range 60-92 years; 38% ≥75 years); 374 patients (94.7%) had genetic and cytogenetic analysis completed within 7 d and were centrally assigned to a Beat AML sub-study; 224 (56.7%) were enrolled on a Beat AML sub-study. The remaining 171 patients elected standard of care (SOC) (103), investigational therapy (28) or palliative care (40); 9 died before treatment assignment. Demographic, laboratory and molecular characteristics were not significantly different between patients on the Beat AML sub-studies and those receiving SOC (induction with cytarabine + daunorubicin (7 + 3 or equivalent) or hypomethylation agent). Thirty-day mortality was less frequent and overall survival was significantly longer for patients enrolled on the Beat AML sub-studies versus those who elected SOC. A precision medicine therapy strategy in AML is feasible within 7 d, allowing patients and physicians to rapidly incorporate genomic data into treatment decisions without increasing early death or adversely impacting overall survival.\n\nIndexed on Europe PMC as PubMed record 33106665 (DOI 10.1038/s41591-020-1089-8). Matched by DOI alone: one trial page and one collection page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Med 2020","url":"https://doi.org/10.1038/s41591-020-1089-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33106665/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33106665"}],"tags":["europepmc-ingest"],"related":["leukemia-lymphoma-society"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["beat-aml-master-trial"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2020,"doi":"10.1038/s41591-020-1089-8","pmid":"33106665","authors":"Burd A, Levine RL, Ruppert AS, et al.","paperType":"observational","findings":[],"whatItMeans":"One trial page and one collection page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-precision-mri-targeted-biopsy-nejm-2018","kind":"paper","name":"PRECISION: MRI-targeted or standard biopsy for prostate cancer diagnosis","aka":[],"tldr":"Doing an MRI first and biopsying only suspicious areas found more clinically significant prostate cancers and fewer harmless ones than standard biopsy, while sparing a quarter of men any biopsy at all.","summary":"Multicentre randomised non-inferiority trial of 500 biopsy-naive men with suspected prostate cancer randomised to MRI with targeted biopsy of suspicious lesions only (no biopsy if MRI was negative) or standard transrectal ultrasound-guided 10 to 12 core biopsy.\n\nClinically significant cancer was detected in 38 percent of the MRI group against 26 percent with standard biopsy, clinically insignificant cancer in 9 versus 22 percent, and 28 percent of MRI-group men avoided biopsy.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2018","url":"https://doi.org/10.1056/NEJMoa1801993"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29552975/"}],"tags":[],"related":["prostate-roadmap","paper-ahmed-promis-multiparametric-mri-lancet-2017","paper-johnson-mpmri-individual-foci-eur-urol-2019","idea-prostate-per-lesion-mri-audit-before-focal-treatment"],"cancers":["prostate-low-risk","prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["pi-rads","template-mapping-biopsy"],"trials":["precision-mri"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2018,"doi":"10.1056/NEJMoa1801993","pmid":"29552975","authors":"Kasivisvanathan V, Rannikko AS, Borghi M, et al.","paperType":"rct","findings":["Clinically significant cancer detected in 38 percent vs 26 percent.","Clinically insignificant cancer in 9 percent vs 22 percent; 28 percent of MRI arm avoided biopsy."],"whatItMeans":"Pre-biopsy MRI with targeted sampling is now the standard diagnostic pathway for suspected prostate cancer, reducing overdiagnosis of low-risk disease.","caveats":["Targeted biopsy alone may miss some significant cancers; many centres combine targeted and systematic cores.","Depends on MRI quality and reader expertise."],"changedPractice":true,"participants":500},{"id":"paper-linder-nat-genet","kind":"paper","name":"Predicting RNA-seq coverage from DNA sequence as a unifying model of gene regulation","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 39779956 and published in Nature Genetics; the citing page links this DOI, which is how the record was matched.","summary":"Sequence-based machine-learning models trained on genomics data improve genetic variant interpretation by providing functional predictions describing their impact on the cis-regulatory code. However, current tools do not predict RNA-seq expression profiles because of modeling challenges. Here, we introduce Borzoi, a model that learns to predict cell-type-specific and tissue-specific RNA-seq coverage from DNA sequence. Using statistics derived from Borzoi's predicted coverage, we isolate and accurately score DNA variant effects across multiple layers of regulation, including transcription, splicing and polyadenylation. Evaluated on quantitative trait loci, Borzoi is competitive with and often outperforms state-of-the-art models trained on individual regulatory functions. By applying attribution methods to the derived statistics, we extract cis-regulatory motifs driving RNA expression and post-transcriptional regulation in normal tissues. The wide availability of RNA-seq data across species, conditions and assays profiling specific aspects of regulation emphasizes the potential of this approach to decipher the mapping from DNA sequence to regulatory function.\n\nIndexed on Europe PMC as PubMed record 39779956 (DOI 10.1038/s41588-024-02053-6). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Genet 2025","url":"https://doi.org/10.1038/s41588-024-02053-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39779956/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39779956"}],"tags":["europepmc-ingest"],"related":["enformer-borzoi"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":2025,"doi":"10.1038/s41588-024-02053-6","pmid":"39779956","authors":"Linder J, Srivastava D, Yuan H, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-roohani-nat-biotechnol","kind":"paper","name":"Predicting transcriptional outcomes of novel multigene perturbations with GEARS","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 37592036 and published in Nature Biotechnology; the citing page links this DOI, which is how the record was matched.","summary":"Understanding cellular responses to genetic perturbation is central to numerous biomedical applications, from identifying genetic interactions involved in cancer to developing methods for regenerative medicine. However, the combinatorial explosion in the number of possible multigene perturbations severely limits experimental interrogation. Here, we present graph-enhanced gene activation and repression simulator (GEARS), a method that integrates deep learning with a knowledge graph of gene-gene relationships to predict transcriptional responses to both single and multigene perturbations using single-cell RNA-sequencing data from perturbational screens. GEARS is able to predict outcomes of perturbing combinations consisting of genes that were never experimentally perturbed. GEARS exhibited 40% higher precision than existing approaches in predicting four distinct genetic interaction subtypes in a combinatorial perturbation screen and identified the strongest interactions twice as well as prior approaches. Overall, GEARS can predict phenotypically distinct effects of multigene perturbations and thus guide the design of perturbational experiments.\n\nIndexed on Europe PMC as PubMed record 37592036 (DOI 10.1038/s41587-023-01905-6). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Biotechnol 2024","url":"https://doi.org/10.1038/s41587-023-01905-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37592036/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37592036"}],"tags":["europepmc-ingest"],"related":["gears"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-biotechnology"],"dependsOn":[],"notes":[],"journal":"Nature Biotechnology","year":2024,"doi":"10.1038/s41587-023-01905-6","pmid":"37592036","authors":"Roohani Y, Huang K, Leskovec J","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-luca-gianni-j-natl-cancer-inst-2022","kind":"paper","name":"Predictive Role of CD36 Expression in HER2-Positive Breast Cancer Patients Receiving Neoadjuvant Trastuzumab","aka":[],"tldr":"Paper by Luca Gianni indexed on Europe PMC as PubMed record 35789270, in JNCI: Journal of the National Cancer Institute (2022), one of the most cited records naming an author with this name at Fondazione Michelangelo.","summary":"Background: Despite huge efforts to identify biomarkers associated with long-term clinical outcomes in patients with early-stage HER2-positive breast cancer (HER2+ BC) treated with (neo)adjuvant anti-HER2 therapy, no reliable predictors have been identified so far. Fatty acid uptake, a process mediated by the transmembrane transporter CD36, has recently emerged as a potential determinant of resistance to anti-HER2 treatments in preclinical HER2+ BC models.\n\nMethods: Here, we investigated the association between baseline intratumor CD36 gene expression and event-free survival in 180 patients enrolled in the phase III trial Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimization (NeoALTTO), which randomly assigned stage II-III HER2+ BC patients to receive neoadjuvant lapatinib, trastuzumab, or lapatinib-trastuzumab in combination with chemotherapy. To this aim, we selected NeoALTTO trial patients for whom pretreatment whole transcriptomic data were available. The main study results were validated in an independent cohort of patients enrolled in the neoadjuvant phase II trial NeoSphere.\n\nResults: In 180 NeoALTTO patients, high intratumor CD36 expression was independently associated with worse event-free survival in patients treated with trastuzumab-based therapy (hazard ratio [HR] = 1.72, 95% confidence interval [CI] = 1.20 to 2.46), but not with lapatinib-based (HR = 1.02, 95% CI = 0.68 to 1.53) or trastuzumab-lapatinib-based (HR = 1.08, 95% CI = 0.60 to 1.94) therapy. Among 331 NeoSphere patients evaluated, high CD36 expression was independently associated with worse patient disease-free survival in both the whole study cohort (HR = 1.197, 95% CI = 1.002 to 1.428) and patients receiving trastuzumab-based neoadjuvant therapy (HR = 1.282, 95% CI = 1.049 to 1.568).\n\nConclusions: High CD36 expression predicts worse clinical outcomes in early-stage HER2+ BC treated with trastuzumab-based neoadjuvant therapy.\n\nIndexed on Europe PMC as PubMed record 35789270 (DOI 10.1093/jnci/djac126). Its author list gives \"Gianni L\" with the affiliation \"Fondazione Michelangelo, Milan, Italy\", which names Fondazione Michelangelo; that is how the record was matched to Luca Gianni, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Natl Cancer Inst 2022","url":"https://doi.org/10.1093/jnci/djac126"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35789270/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35789270"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["luca-gianni"],"bottlenecks":[],"keyPapers":[],"journals":["jnci"],"dependsOn":[],"notes":[],"journal":"JNCI: Journal of the National Cancer Institute","year":2022,"doi":"10.1093/jnci/djac126","pmid":"35789270","authors":"Ligorio F, Di Cosimo S, Verderio P, et al.","paperType":"basic","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Luca Gianni at Fondazione Michelangelo, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-predimed-breast-jama-im-2015","kind":"paper","name":"PREDIMED: a Mediterranean diet with extra-virgin olive oil and fewer breast cancers","aka":[],"tldr":"In a Spanish cardiovascular prevention trial, women assigned to a Mediterranean diet supplemented with extra-virgin olive oil had about two-thirds fewer invasive breast cancers than a low-fat control group, although the number of cases was small.","summary":"PREDIMED randomised older Spanish adults at high cardiovascular risk to a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with nuts, or advice to follow a low-fat diet. This secondary analysis examined invasive breast cancer in the 4,282 women over a median 4.8 years.\n\nThirty-five incident breast cancers occurred. The olive-oil group had a hazard ratio of 0.32 versus control; the nut group's reduction was not statistically significant. The original 2018 retraction and republication of PREDIMED (for randomisation irregularities at some sites) led to a re-analysis with similar estimates.\n\nIt is the only randomised trial evidence that a whole-diet intervention reduces cancer incidence, but it rests on very few events.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1001/jamainternmed.2015.4838"},{"label":"ClinicalTrials.gov ISRCTN35739639","url":"https://clinicaltrials.gov/study/ISRCTN35739639"}],"tags":[],"related":["paper-body-fatness-iarc-nejm-2016","idea-prev-chemoprevention-master-protocol"],"cancers":["breast-hr-positive"],"sections":["nutrition-lifestyle","prevention"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-trial-design"],"keyPapers":[],"journals":["jama-internal-medicine"],"dependsOn":[],"notes":[],"journal":"JAMA Internal Medicine","year":2015,"doi":"10.1001/jamainternmed.2015.4838","authors":"Toledo E, Salas-Salvadó J, Donat-Vargas C, et al.","paperType":"rct","findings":["Invasive breast cancer HR 0.32 (95% CI 0.13-0.79) for Mediterranean diet plus extra-virgin olive oil vs control","Mediterranean diet plus nuts: HR 0.59 (95% CI 0.26-1.35), not significant","Only 35 breast cancers occurred among 4,282 women over about 5 years","Effect estimates were similar after the 2018 re-analysis excluding sites with randomisation problems"],"whatItMeans":"A Mediterranean dietary pattern rich in olive oil may lower breast cancer risk, and it is safe and good for the heart anyway. The evidence is suggestive, not definitive, because of the small number of cancers; it should not be presented as proven cancer prevention.","caveats":["Breast cancer was not a pre-specified primary endpoint and cases were few","Randomisation irregularities at some sites forced a retraction and republication of the parent trial","Older Spanish women at high cardiovascular risk; not generalisable to younger or other populations","No mammographic screening protocol, so ascertainment could differ between arms"],"changedPractice":false,"participants":4282},{"id":"paper-nct05101096-int-j-clin-oncol-2024","kind":"paper","name":"Preliminary results from ASCENT-J02: a phase 1/2 study of sacituzumab govitecan in Japanese patients with advanced solid tumors","aka":[],"tldr":"Published report from the ASCENT-J02 trial registered as NCT05101096, in International journal of clinical oncology (2024), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Sacituzumab govitecan (SG) is a Trop-2-directed antibody-drug conjugate approved outside Japan for second-line and later metastatic triple-negative breast cancer (mTNBC), based on the ASCENT study (NCT02574455). We report SG safety and efficacy in an open-label, phase 1/2 bridging study in Japanese patients with advanced solid tumors (ASCENT-J02; NCT05101096; jRCT2031210346).\n\nMethods: Phase 1 was a standard 3 + 3 design. Patients received intravenous SG 6 mg/kg, escalating to 10 mg/kg, on Days 1 and 8 per 21-day cycle; primary endpoints were safety, incidence of dose-limiting toxicity/toxicities (DLTs), and determination of the recommended phase 2 dose (RP2D). In the multicohort phase 2 study, patients in the mTNBC cohort with previously treated disease received SG at the RP2D; primary endpoint was independent review committee (IRC)-assessed objective response rate (ORR; RECIST v1.1). Safety was a secondary endpoint.\n\nResults: In phase 1 (N = 15), one DLT (grade 3 elevated transaminases) occurred with SG 10 mg/kg; RP2D was SG 10 mg/kg regardless of UGT1A1 status. In phase 2, 36 patients with mTNBC received SG 10 mg/kg. At median follow-up of 6.1 months, IRC-assessed ORR was 25.0% (95% CI 12.1-42.2; P = 0.0077). Median progression-free survival was 5.6 months (95% CI 3.9-not reached [NR]); median overall survival was NR. No treatment-emergent adverse events led to discontinuation or death.\n\nConclusions: SG RP2D was established as 10 mg/kg in Japanese patients. SG showed efficacy in Japanese patients with previously treated mTNBC, a manageable safety profile, and no new safety signals, consistent with the previous ASCENT study.\n\nIndexed on Europe PMC as PubMed record 39302614 (DOI 10.1007/s10147-024-02589-x). Its abstract cites the registry id NCT05101096, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Int J Clin Oncol 2024","url":"https://doi.org/10.1007/s10147-024-02589-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39302614/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39302614"},{"label":"ClinicalTrials.gov NCT05101096","url":"https://clinicaltrials.gov/study/NCT05101096"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05101096"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["international-journal-of-clinical-oncology"],"dependsOn":[],"notes":[],"journal":"International journal of clinical oncology","year":2024,"doi":"10.1007/s10147-024-02589-x","pmid":"39302614","authors":"Naito Y, Nakamura S, Kawaguchi-Sakita N, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05101096 with the most citations, so it is the natural first reading for anyone following the ASCENT-J02 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","The abstract cites more than one registry id (NCT02574455, NCT05101096); it was kept because the trial's acronym appears in the title."]},{"id":"paper-roa-dysplasia-to-carcinoma-interval-gastroenterology-1996","kind":"paper","name":"Preneoplastic lesions and gallbladder cancer: an estimate of the period required for progression","aka":[],"tldr":"Comparing the ages of Chilean patients with dysplasia, early cancer, advanced cancer and spread cancer of the gallbladder, the authors estimated that it takes around 15 years to go from dysplasia to advanced disease.","summary":"84 cases of dysplasia, 60 early carcinomas, 181 advanced carcinomas and 121 metastatic gallbladder cancers were analysed using age as the main parameter, with analysis of variance and multiple regression. Women were younger than men across all lesions, and mean age differed by lesion type: 46.3 years (SD 16) for dysplasia, 57.5 (16.7) for early carcinoma, 59 (13.7) for advanced carcinoma and 61.1 (12.1) for metastatic disease.\n\nMultiple regression showed a significant difference in mean age between dysplastic and carcinoma groups (r = 0.386; P < 0.001). The period required to progress from dysplasia to advanced carcinoma was estimated at around 15 years, with a continuum in the progression of the lesions.","asOf":"2026-09-24","links":[{"label":"Roa et al., Gastroenterology 1996: time from dysplasia to gallbladder carcinoma","url":"https://doi.org/10.1053/gast.1996.v111.pm8698204"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/8698204/"}],"tags":[],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["dysplasia","metaplasia-dysplasia-carcinoma-sequence"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Gastroenterology","year":1996,"doi":"10.1053/gast.1996.v111.pm8698204","pmid":"8698204","authors":"Roa I, Araya JC, Villaseca M, et al.","paperType":"observational","findings":["Mean ages: dysplasia 46.3, early carcinoma 57.5, advanced carcinoma 59, metastatic 61.1 years.","Estimated 15 years from dysplasia to advanced carcinoma.","Women younger than men at every stage."],"whatItMeans":"The origin of the 10 to 15 year window quoted for gallbladder carcinogenesis, which is the argument that cholecystectomy for stones or dysplasia in high-incidence regions prevents cancer years later.","caveats":["Cross-sectional age comparison, not longitudinal follow-up.","Chilean population with high incidence and early onset."],"changedPractice":false,"participants":446},{"id":"paper-roa-gallbladder-preneoplastic-lesions-jso-2006","kind":"paper","name":"Preneoplastic lesions in gallbladder cancer","aka":[],"tldr":"Gallbladder cancer mostly grows from flat dysplasia rather than from polyps: dysplasia and carcinoma in situ sit next to four in five cancers, adenomas are rare, and the age gap between dysplasia and invasive cancer suggests about ten years of progression.","summary":"A review of the epithelial lesions involved in gallbladder carcinogenesis, dysplasia and adenomas, which represent two biologically distinct models. Dysplasia progresses to carcinoma in situ and then invasion; over 80% of invasive gallbladder cancers have areas adjacent to carcinoma in situ and epithelial dysplasia. Adenomas are uncommon (0.14% of cholecystectomies) and adenomatous remnants are found next to fewer than 3% of early carcinomas, suggesting the limited importance of that pathway.\n\nEpithelial dysplasia unassociated with cancer is seen in about 1% of cholecystectomies for symptomatic stones. Metaplasia, dysplasia and carcinoma in situ are present in the mucosa adjacent to cancer in 66%, 81.3% and 69% of cases. The average ages of patients with isolated dysplasia (51.9 years), early carcinoma (56.8) and advanced carcinoma (62.9) form a gradient that suggests progression over roughly 10 years.","asOf":"2026-09-24","links":[{"label":"Roa et al., J Surg Oncol 2006: preneoplastic lesions in gallbladder cancer","url":"https://doi.org/10.1002/jso.20527"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/16724345/"}],"tags":[],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["dysplasia","metaplasia-dysplasia-carcinoma-sequence","intracholecystic-papillary-tubular-neoplasm"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-surgical-oncology"],"dependsOn":[],"notes":[],"journal":"Journal of Surgical Oncology","year":2006,"doi":"10.1002/jso.20527","pmid":"16724345","authors":"Roa I, de Aretxabala X, Araya JC, Roa J.","paperType":"review","findings":["Metaplasia, dysplasia and carcinoma in situ adjacent to cancer in 66%, 81.3% and 69% of cases.","Adenomas in 0.14% of cholecystectomies; adenomatous remnants next to fewer than 3% of early carcinomas.","Mean ages 51.9 (dysplasia), 56.8 (early carcinoma), 62.9 (advanced carcinoma): about a 10-year sequence."],"whatItMeans":"The morphological argument that gallbladder cancer is a flat-dysplasia disease, which is why it is invisible on imaging until late and why prevention rests on removing the diseased gallbladder rather than on polyp surveillance alone.","caveats":["Chilean cholecystectomy series; the adenoma fraction may differ elsewhere.","Age gradients estimate, rather than observe, progression time."],"changedPractice":false},{"id":"paper-preopanc-neoadjuvant-chemoradiotherapy-long-term-jco-2022","kind":"paper","name":"PREOPANC long-term results: neoadjuvant gemcitabine-based chemoradiotherapy versus upfront surgery for resectable and borderline resectable pancreatic cancer","aka":[],"tldr":"Giving chemotherapy and radiotherapy before the operation, rather than operating first, tripled the share of patients alive at five years in this Dutch trial, with the gain clearest in borderline resectable tumours. It is the strongest randomised case for treating borderline resectable pancreatic cancer before surgery.","summary":"Long-term analysis of the Dutch Pancreatic Cancer Group's randomised phase 3 PREOPANC trial, in which 246 patients with resectable or borderline resectable pancreatic cancer were assigned to neoadjuvant gemcitabine-based chemoradiotherapy followed by surgery and adjuvant gemcitabine, or to immediate surgery followed by adjuvant gemcitabine.\n\nWith a median follow-up of 59 months, overall survival favoured the neoadjuvant arm (hazard ratio 0.73), with five-year survival of 20.5 percent against 6.5 percent even though median survival differed by little (15.7 against 14.3 months). The benefit was significant in the borderline resectable subgroup and consistent across the others. The 2020 primary report had shown better R0 resection rates and disease-free survival without a significant overall survival difference.","asOf":"2026-09-21","links":[{"label":"J Clin Oncol 2022","url":"https://doi.org/10.1200/JCO.21.02233"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35084987/"}],"tags":[],"related":["paper-preopanc-preoperative-chemoradiotherapy-jco-2020","paper-preopanc-2-neoadjuvant-folfirinox-vs-chemoradiotherapy-lancet-oncol-2025"],"cancers":["borderline-resectable-pdac","resectable-pdac","pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":["gemcitabine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["preopanc"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2022,"doi":"10.1200/JCO.21.02233","pmid":"35084987","authors":"Versteijne E, van Dam JL, Suker M, et al.","paperType":"rct","findings":["Overall survival hazard ratio 0.73 favouring neoadjuvant chemoradiotherapy; five-year survival 20.5 versus 6.5 percent.","Median overall survival 15.7 versus 14.3 months, so the benefit sits in the tail of the curve.","Significant benefit in the borderline resectable subgroup."],"whatItMeans":"Neoadjuvant treatment is now the standard for borderline resectable pancreatic cancer, and PREOPANC is the trial guidelines cite; the follow-on PREOPANC-2 tested FOLFIRINOX in the same setting.","caveats":["Gemcitabine-based chemoradiotherapy is no longer the preferred neoadjuvant regimen; most centres use FOLFIRINOX-based chemotherapy.","Median survival in both arms was short by today's standards, and the trial was small."],"changedPractice":true,"participants":246},{"id":"paper-preopanc-preoperative-chemoradiotherapy-jco-2020","kind":"paper","name":"Preoperative Chemoradiotherapy Versus Immediate Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Results of the Dutch Randomized Phase III PREOPANC Trial","aka":[],"tldr":"The 2020 primary report of the Dutch PREOPANC trial: giving chemotherapy and radiotherapy before surgery did not significantly lengthen survival overall, but it raised clear-margin resections from 40 to 71 percent and helped the patients whose tumours were borderline operable.","summary":"PREOPANC randomised 246 patients with resectable or borderline resectable pancreatic cancer at 16 Dutch centres between April 2013 and July 2017 to preoperative chemoradiotherapy (three courses of gemcitabine, the second with 15 fractions of 2.4 Gy, then surgery and four courses of adjuvant gemcitabine; 119 patients) or immediate surgery followed by six courses of adjuvant gemcitabine (127). Median overall survival by intention to treat was 16.0 versus 14.3 months (hazard ratio 0.78, 95 percent confidence interval 0.58 to 1.05, P = 0.096). The resection rate was 61 versus 72 percent; the R0 rate 71 percent (51 of 72) versus 40 percent (37 of 92), P less than 0.001. Preoperative treatment was associated with better disease-free survival and locoregional failure-free interval and fewer positive nodes, perineural and venous invasion; serious adverse events occurred in 52 versus 41 percent. The long-term analysis (2022, recorded separately) showed a survival benefit at five years.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2020","url":"https://doi.org/10.1200/JCO.19.02274"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32105518/"},{"label":"Netherlands Trial Register NTR3709","url":"https://www.onderzoekmetmensen.nl/en/trial/24580"},{"label":"J Clin Oncol 2020","url":"https://doi.org/10.1200/jco.19.02274"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32105518"}],"tags":["pancreatic-evidence"],"related":["paper-preopanc-neoadjuvant-chemoradiotherapy-long-term-jco-2022","paper-preopanc-2-neoadjuvant-folfirinox-vs-chemoradiotherapy-lancet-oncol-2025"],"cancers":["pancreatic","resectable-pdac","borderline-resectable-pdac"],"sections":["radiation","surgery"],"technologies":["cytotoxic-chemotherapy","imrt-igrt"],"targets":[],"drugs":["gemcitabine"],"companies":[],"institutions":["erasmus-mc","amsterdam-umc"],"pathways":[],"terms":["resectability","resection-margins","neoadjuvant-adjuvant"],"trials":["preopanc"],"people":["marc-besselink"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/JCO.19.02274","pmid":"32105518","authors":"Versteijne E, Suker M, Groothuis K, et al.","paperType":"rct","findings":["246 patients; preoperative gemcitabine-based chemoradiotherapy versus immediate surgery.","Median overall survival 16.0 versus 14.3 months (hazard ratio 0.78, P = 0.096), not significant at the primary analysis.","R0 resection 71 versus 40 percent; resection rate 61 versus 72 percent.","Serious adverse events 52 versus 41 percent."],"whatItMeans":"The trial that made neoadjuvant treatment standard for borderline resectable disease and opened the still unresolved question for resectable disease, which PREOPANC-2, NORPACT-1, PREOPANC-3 and Alliance A021806 inherited.","caveats":["Gemcitabine alone is no longer the chemotherapy standard; the trial's regimens were superseded before it reported.","The primary endpoint was not met; the practice change rests on secondary endpoints and the long-term update."],"changedPractice":true,"participants":246},{"id":"paper-foxtrot-preoperative-chemotherapy-colon-jco-2023","kind":"paper","name":"Preoperative chemotherapy for operable colon cancer: mature results of an international randomized controlled trial (FOxTROT)","aka":[],"tldr":"Six weeks of chemotherapy before the colon cancer operation, rather than all of it afterwards, shrank tumours, left fewer incomplete resections and cut two-year recurrence from 21.5 to 16.9 percent.","summary":"FOxTROT randomly allocated patients with radiologically staged T3-4, N0-2, M0 colon cancer 2:1 to six weeks of oxaliplatin-fluoropyrimidine chemotherapy before surgery plus eighteen afterwards, or to 24 weeks afterwards; patients with RAS wild-type tumours could also be randomised 1:1 to panitumumab or not during the preoperative phase. The primary end point was residual or recurrent disease within two years, with surgical morbidity, histopathological stage, regression grade, completeness of resection and cause-specific mortality as secondary outcomes.\n\nOf 699 patients allocated to neoadjuvant chemotherapy, 674 (96 percent) started and 606 (87 percent) completed it; 30 (4.3 percent) developed obstructive symptoms requiring expedited surgery, but serious postoperative complications were fewer than in the control group.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2023","url":"https://doi.org/10.1200/JCO.22.00046"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36657089/"},{"label":"Europe PMC full text (PMC10022855)","url":"https://europepmc.org/article/MED/36657089"}],"tags":["colorectal-evidence"],"related":["paper-mosaic-oxaliplatin-adjuvant-colon-nejm-2004","paper-niche-2-nejm-2024"],"cancers":["colorectal","colon-cancer"],"sections":["chemotherapy","surgery"],"technologies":["cytotoxic-chemotherapy"],"targets":[],"drugs":["folfox","capox","oxaliplatin","panitumumab"],"companies":[],"institutions":[],"pathways":[],"terms":["neoadjuvant-adjuvant","msi"],"trials":[],"people":[],"bottlenecks":["b-surgery-radiation-innovation"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2023,"doi":"10.1200/JCO.22.00046","pmid":"36657089","authors":"Morton D, Seymour M, Magill L, et al.","paperType":"rct","findings":["Residual or recurrent disease within two years: 16.9 percent (118 of 699) with neoadjuvant chemotherapy against 21.5 percent (76 of 354); rate ratio 0.72 (95 percent CI 0.54 to 0.98, p=0.037).","Histopathologically complete resection in 94 percent (648 of 686) against 89 percent (311 of 351), p<0.001.","Marked T and N downstaging and histological tumour regression, all p<0.001.","Panitumumab did not enhance the benefit from neoadjuvant chemotherapy.","Little benefit was seen in mismatch repair-deficient tumours."],"whatItMeans":"A UK-led trial that moved part of colon cancer chemotherapy in front of the operation, and showed that tumour regression grade after six weeks predicts recurrence, which is the basis for using the response itself to choose what follows.","caveats":["A 2:1 randomisation with a composite two-year endpoint rather than overall survival.","4.3 percent of patients needed expedited surgery for obstruction during the preoperative window.","Mismatch repair-deficient tumours gained little, and immunotherapy is now the neoadjuvant option for that group."],"changedPractice":true,"participants":1053},{"id":"paper-kapiteijn-dutch-tme-preoperative-radiotherapy-nejm-2001","kind":"paper","name":"Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer (Dutch TME trial)","aka":[],"tldr":"The trial that asked whether radiotherapy still helps once the surgery is done properly. It does for local control, cutting two-year pelvic recurrence from 8.2 to 2.4 percent, but it did not lengthen life.","summary":"Kapiteijn, Marijnen, Nagtegaal and colleagues randomly assigned 1,861 patients with resectable rectal cancer to preoperative radiotherapy (5 Gy on each of five days) followed by total mesorectal excision, or to total mesorectal excision alone, with standardisation and quality control of the radiotherapy, the surgery and the pathological assessment. Of these, 1,805 were eligible and 1,748 underwent a macroscopically complete local resection.\n\nThe overall two-year survival was identical in the two groups, and the trial therefore separated local control from survival in rectal cancer for the first time.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2001","url":"https://doi.org/10.1056/NEJMoa010580"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/11547717/"}],"tags":["colorectal-evidence"],"related":["paper-heald-mesorectum-rectal-cancer-surgery-br-j-surg-1982","paper-swedish-rectal-cancer-trial-preoperative-radiotherapy-nejm-1997"],"cancers":["colorectal","rectal-cancer"],"sections":["radiation","surgery"],"technologies":["radiotherapy","mri","imrt-igrt"],"targets":[],"drugs":[],"companies":[],"institutions":["erasmus-mc"],"pathways":[],"terms":["total-mesorectal-excision","neoadjuvant-adjuvant"],"trials":[],"people":["cornelis-van-de-velde"],"bottlenecks":["b-surgery-radiation-innovation","b-toxicity-qol"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2001,"doi":"10.1056/NEJMoa010580","pmid":"11547717","authors":"Kapiteijn E, Marijnen CA, Nagtegaal ID, et al.","paperType":"rct","findings":["Two-year survival 82.0 percent with radiotherapy plus surgery against 81.8 percent with surgery alone (p=0.84).","Overall two-year local recurrence after macroscopically complete resection 5.3 percent.","Local recurrence at two years 2.4 percent with radiotherapy against 8.2 percent with surgery alone (p<0.001).","Radiotherapy, surgery and pathology were standardised and quality-controlled across the trial."],"whatItMeans":"The modern basis for offering short-course radiotherapy selectively: it buys local control, not survival, so the decision turns on the predicted recurrence risk from MRI against the long-term bowel and sexual morbidity of pelvic irradiation.","caveats":["Two-year outcomes in the primary report; the long-term follow-up showed the local control benefit persists without a survival difference.","The trial cannot say whether radiotherapy is needed in the MRI-defined low-risk tumours that would now be operated on directly.","Late toxicity, particularly faecal incontinence and sexual dysfunction, is the cost the primary report does not quantify."],"changedPractice":true,"participants":1861},{"id":"paper-sebag-montefiore-cr07-preoperative-radiotherapy-lancet-2009","kind":"paper","name":"Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016)","aka":[],"tldr":"The British trial that settled the timing question: giving everyone a short course of radiotherapy before surgery beats operating first and irradiating only those whose margins turn out to be involved.","summary":"Sebag-Montefiore, Stephens, Steele and colleagues randomised 1,350 patients with operable rectal adenocarcinoma in 80 centres in four countries to short-course preoperative radiotherapy (25 Gy in five fractions, 674 patients) or to initial surgery with selective postoperative chemoradiotherapy (45 Gy in 25 fractions with concurrent fluorouracil) restricted to patients with an involved circumferential resection margin (676 patients). The primary outcome measure was local recurrence, analysed by intention to treat.\n\nAt analysis, 330 patients had died and median follow-up of survivors was four years; 99 patients had developed local recurrence.","asOf":"2026-09-24","links":[{"label":"Lancet 2009","url":"https://doi.org/10.1016/S0140-6736(09)60484-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19269519/"},{"label":"Europe PMC full text (PMC2668947)","url":"https://europepmc.org/article/MED/19269519"}],"tags":["colorectal-evidence"],"related":["paper-kapiteijn-dutch-tme-preoperative-radiotherapy-nejm-2001","paper-sauer-preoperative-chemoradiotherapy-rectal-nejm-2004"],"cancers":["colorectal","rectal-cancer"],"sections":["radiation","surgery"],"technologies":["radiotherapy","imrt-igrt"],"targets":[],"drugs":["fluorouracil"],"companies":[],"institutions":[],"pathways":[],"terms":["total-mesorectal-excision","chemoradiation"],"trials":[],"people":[],"bottlenecks":["b-surgery-radiation-innovation"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2009,"doi":"10.1016/S0140-6736(09)60484-0","pmid":"19269519","authors":"Sebag-Montefiore D, Stephens RJ, Steele R, et al.","paperType":"rct","findings":["27 local recurrences with preoperative radiotherapy against 72 with selective postoperative chemoradiotherapy: hazard ratio 0.39 (95 percent CI 0.27 to 0.58, p<0.0001), a 61 percent relative reduction.","Absolute difference in local recurrence at three years 6.2 percent (4.4 against 10.6 percent).","Disease-free survival improved 24 percent (hazard ratio 0.76, 95 percent CI 0.62 to 0.94, p=0.013); absolute difference at three years 6.0 percent (77.5 against 71.5 percent).","Overall survival did not differ (hazard ratio 0.91, 95 percent CI 0.73 to 1.13, p=0.40)."],"whatItMeans":"The trial that made preoperative rather than postoperative radiotherapy the UK standard, and the one whose circumferential resection margin pathology protocol, led by Quirke, became the quality measure for rectal surgery worldwide.","caveats":["Selective postoperative chemoradiotherapy was given only for an involved margin, so the comparison is against a deliberately restrictive policy rather than against no radiotherapy.","No overall survival difference, as in the Dutch TME trial.","Late toxicity of universal short-course radiotherapy is the cost of the local control gain and is not captured in the primary endpoints."],"changedPractice":true,"participants":1350},{"id":"paper-kanda-panin-1-somatic-mutations-gastroenterology-2012","kind":"paper","name":"Presence of somatic mutations in most early-stage pancreatic intraepithelial neoplasia","aka":[],"tldr":"More than 99% of the smallest, lowest-grade precursor lesions in the pancreas already carry a mutation in KRAS, CDKN2A, GNAS or BRAF, showing the genetic change comes first.","summary":"More than 99% of the earliest-stage, lowest-grade pancreatic intraepithelial neoplasm-1 lesions were shown to contain mutations in KRAS, p16/CDKN2A, GNAS or BRAF.","asOf":"2026-09-24","links":[{"label":"Kanda et al., Gastroenterology 2012: somatic mutations in more than 99% of PanIN-1 lesions","url":"https://doi.org/10.1053/j.gastro.2011.12.042"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22226782/"}],"tags":[],"related":[],"cancers":["pancreatic","ipmn-cystic-precursors"],"sections":[],"technologies":[],"targets":["kras","cdkn2a","gnas","braf"],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":[],"terms":[],"trials":[],"people":["bert-vogelstein","anirban-maitra"],"bottlenecks":[],"keyPapers":[],"journals":["gastroenterology"],"dependsOn":[],"notes":[],"journal":"Gastroenterology","year":2012,"doi":"10.1053/j.gastro.2011.12.042","pmid":"22226782","authors":"Kanda M, Matthaei H, Wu J, et al.","paperType":"translational","findings":["More than 99% of PanIN-1 lesions carry a KRAS, CDKN2A, GNAS or BRAF mutation."],"whatItMeans":"It fixes the order of events, with the initiating mutation present in the smallest visible lesion, and it warns that finding mutant KRAS in a duct does not mean cancer.","caveats":["Microdissected lesions; small numbers per grade.","Mutation presence does not predict which lesions progress."],"changedPractice":false},{"id":"paper-traverso-longmire-pylorus-preservation-pancreaticoduodenectomy-sgo-1978","kind":"paper","name":"Preservation of the pylorus in pancreaticoduodenectomy","aka":[],"tldr":"The 1978 report of two patients in whom the surgeons kept the stomach outlet intact during the Whipple operation, the modification most surgeons now use.","summary":"Traverso and Longmire, Surgery, Gynecology and Obstetrics, June 1978, pages 959 to 962. The indexed abstract is the authors' own caution: further clinical observation and laboratory evaluation would be needed before recommending the modification, which preserves the pylorus and distal stomach in patients resected for benign disease or carcinoma of the distal duodenum, but the early results in the two patients described were encouraging. Their 1980 follow-up in Annals of Surgery extended the series to 18 patients, eight evaluated in detail an average of six months after surgery: every patient had marked pancreatic insufficiency on laboratory testing, 88 percent described normal bowel movements and 25 percent reported weight loss, and all required intensive pancreatic enzyme replacement.","asOf":"2026-09-24","links":[{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/653575/"},{"label":"Follow-up evaluation, 18 patients (Ann Surg 1980)","url":"https://doi.org/10.1097/00000658-198009000-00005"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/7416828/"}],"tags":["pancreatic-evidence"],"related":["paper-whipple-carcinoma-ampulla-of-vater-ann-surg-1935","paper-roberts-pert-survival-pancreatic-cancer-pancreatology-2019"],"cancers":["pancreatic","resectable-pdac"],"sections":["surgery","supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["whipple"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Surgery, Gynecology and Obstetrics","year":1978,"pmid":"653575","authors":"Traverso LW, Longmire WP.","paperType":"observational","findings":["Two patients; pylorus and distal stomach preserved during pancreaticoduodenectomy.","The authors called for further observation before recommending the modification.","In the 1980 follow-up of 18 patients, all showed pancreatic insufficiency on testing and all required intensive enzyme replacement."],"whatItMeans":"The pylorus-preserving Whipple became the standard variant, and the 1980 follow-up is an early record of the exocrine insufficiency that still goes untreated in most patients today.","caveats":["Two patients with benign or duodenal disease, not pancreatic cancer.","No DOI is indexed for the 1978 paper; the PubMed record is the anchor."],"changedPractice":true,"participants":2},{"id":"paper-alyami-lancet-oncol","kind":"paper","name":"Pressurised intraperitoneal aerosol chemotherapy: rationale, evidence, and potential indications","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 31267971 and published in The Lancet Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Pressurised intraperitoneal aerosol chemotherapy (PIPAC) was introduced as a new treatment for patients with peritoneal metastases in November, 2011. Reports of its feasibility, tolerance, and efficacy have encouraged centres worldwide to adopt PIPAC as a novel drug delivery technique. In this Review, we detail the technique and rationale of PIPAC and critically assess its evidence and potential indications. A systematic search was done to identify all relevant literature on PIPAC published between Jan 1, 2011, and Jan 31, 2019. A total of 106 articles or reports on PIPAC were identified, and 45 clinical studies on 1810 PIPAC procedures in 838 patients were included for analysis. Repeated PIPAC delivery was feasible in 64% of patients with few intraoperative and postoperative surgical complications (3% for each in prospective studies). Adverse events (Common Terminology Criteria for Adverse Events greater than grade 2) occurred after 12-15% of procedures, and commonly included bowel obstruction, bleeding, and abdominal pain. Repeated PIPAC did not have a negative effect on quality of life. Using PIPAC, an objective clinical response of 62-88% was reported for patients with ovarian cancer (median survival of 11-14 months), 50-91% for gastric cancer (median survival of 8-15 months), 71-86% for colorectal cancer (median survival of 16 months), and 67-75% (median survival of 27 months) for peritoneal mesothelioma. From our findings, PIPAC has been shown to be feasible and safe. Data on objective response and quality of life were encouraging. Therefore, PIPAC can be considered as a treatment option for refractory, isolated peritoneal metastasis of various origins. However, its use in further indications needs to be validated by prospective studies.\n\nIndexed on Europe PMC as PubMed record 31267971 (DOI 10.1016/s1470-2045(19)30318-3). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2019","url":"https://doi.org/10.1016/s1470-2045(19)30318-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31267971/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31267971"}],"tags":["europepmc-ingest"],"related":["hipec-pipac-devices"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2019,"doi":"10.1016/s1470-2045(19)30318-3","pmid":"31267971","authors":"Alyami M, Hübner M, Grass F, et al.","paperType":"review","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-checkmate-915-j-immunother-cancer-2025","kind":"paper","name":"Pretreatment and on-treatment ctDNA and tissue biomarkers predict recurrence in patients with stage IIIB-D/IV melanoma treated with adjuvant immunotherapy: CheckMate 915","aka":[],"tldr":"Published report from the CheckMate 915 trial registered as NCT03068455, in Journal for ImmunoTherapy of Cancer (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Purpose: CheckMate 915 (NCT03068455) compared adjuvant nivolumab monotherapy versus combination nivolumab+ipilimumab in patients with resected stage III/IV melanoma. This exploratory analysis was performed to identify biomarkers that correlate with benefit from adjuvant immunotherapy.\n\nPatients and methods: 1,844 patients received nivolumab 480 mg every 4 weeks or nivolumab 240 mg every 2 weeks with ipilimumab 1 mg/kg every 6 weeks. Tumor and peripheral biomarkers were evaluated, including tumor-informed circulating tumor DNA (ctDNA) at postresection baseline and on-treatment, for their association with recurrence-free survival and distant metastases-free survival.\n\nResults: Biomarker analyses were conducted in 60-96% of the intention-to-treat population. ctDNA positivity at baseline (seen in 16.2% of patients) and on-treatment was associated with higher risk of recurrence than ctDNA negativity (HR, 1.97; 95% CI, 1.57 to 2.46), with a high specificity (87%) and modest sensitivity (39%). ctDNA status, tumor mutational burden (TMB) status (TMB < or ≥350 mutations/tumor) and interferon gamma-RNA signature score (< or ≥median) evaluated together, as well as ctDNA status with tumor CD8 or cell programmed death ligand 1 expression, were more predictive of survival than ctDNA alone. Tumor bulk RNA-seq expression patterns identified gene expression at baseline associated with recurrence.\n\nConclusions: This study represents the largest assessment of ctDNA and other baseline tumor and peripheral biomarkers for predicting recurrence-free survival in patients with resected melanoma receiving adjuvant immunotherapy. ctDNA alone and in combination with more established biomarkers predicted recurrence-free and distant metastasis-free survival and has potential utility for assessing and monitoring the risk of recurrence in patients with resected melanoma treated with immunotherapy in the adjuvant setting.\n\nTrial registration number: NCT03068455.\n\nIndexed on Europe PMC as PubMed record 40645660 (DOI 10.1136/jitc-2025-012034). Its abstract cites the registry id NCT03068455, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Immunother Cancer 2025","url":"https://doi.org/10.1136/jitc-2025-012034"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40645660/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40645660"},{"label":"ClinicalTrials.gov NCT03068455","url":"https://clinicaltrials.gov/study/NCT03068455"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-915"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jitc"],"dependsOn":[],"notes":[],"journal":"Journal for ImmunoTherapy of Cancer","year":2025,"doi":"10.1136/jitc-2025-012034","pmid":"40645660","authors":"Long GV, Tang H, Desai K, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03068455 with the most citations, so it is the natural first reading for anyone following the CheckMate 915 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-beer-prevail-enzalutamide-nejm-2014","kind":"paper","name":"PREVAIL: enzalutamide in metastatic prostate cancer before chemotherapy","aka":["PREVAIL","Beer 2014 enzalutamide chemotherapy-naive"],"tldr":"The same drug given before chemotherapy rather than after it. At one year, 65 percent of men on enzalutamide had no sign of the cancer growing on scans, against 14 percent on placebo, and the need for chemotherapy was pushed a long way back.","summary":"Tomasz Beer and the PREVAIL investigators randomised 1,717 chemotherapy-naive men with metastatic castration-resistant prostate cancer to 160 mg of enzalutamide daily or placebo, with radiographic progression-free survival and overall survival as co-primary endpoints. The study was stopped at a planned interim analysis after 540 deaths.\n\nPREVAIL did for enzalutamide what COU-AA-302 did for abiraterone: it moved the drug in front of chemotherapy. The two results together are the reason a man diagnosed with castration-resistant disease today is far more likely to be offered a tablet than an infusion, and the reason the sequencing question (which tablet, then what) became the central practical problem of the disease.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2014","url":"https://doi.org/10.1056/nejmoa1405095"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24881730/"},{"label":"ClinicalTrials.gov NCT01212991","url":"https://clinicaltrials.gov/study/NCT01212991"}],"tags":["prostate-evidence"],"related":["paper-scher-affirm-enzalutamide-nejm-2012","paper-abiraterone-acetate-prostate-n-engl-j-med-2013","prostate-roadmap"],"cancers":["prostate","prostate-mcrpc"],"sections":["hormonal","targeted-therapy"],"technologies":[],"targets":["androgen-receptor"],"drugs":["enzalutamide"],"companies":["astellas","pfizer"],"institutions":[],"pathways":[],"terms":["castration-resistance","psa","radiographic-progression-free-survival","metastasis-free-survival"],"trials":[],"people":["johann-de-bono","karim-fizazi"],"bottlenecks":["b-resistance","b-combination-space"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2014,"doi":"10.1056/nejmoa1405095","pmid":"24881730","authors":"Beer TM, Armstrong AJ, Rathkopf DE, et al.","paperType":"rct","findings":["Radiographic progression-free survival at 12 months 65 percent with enzalutamide against 14 percent with placebo (hazard ratio 0.19, 95 percent confidence interval 0.15 to 0.23; P less than 0.001).","626 of the enzalutamide patients (72 percent) against 532 (63 percent) on placebo were alive at the data-cutoff; hazard ratio for death 0.71 (0.60 to 0.84; P less than 0.001).","Time until initiation of cytotoxic chemotherapy hazard ratio 0.35; time until first skeletal-related event hazard ratio 0.72.","Complete or partial soft-tissue response in 59 percent against 5 percent; decline of at least 50 percent in prostate-specific antigen in 78 percent against 3 percent (P less than 0.001 for all comparisons).","Fatigue and hypertension were the most common clinically relevant adverse events."],"whatItMeans":"The trial that made an androgen receptor inhibitor the usual first treatment for castration-resistant prostate cancer, and that delayed chemotherapy by a long margin for most men. Its effect sizes are why later trials in this setting are judged against a hazard ratio near 0.7 for survival.","caveats":["Placebo-controlled, so it does not compare enzalutamide with abiraterone or with chemotherapy given at the same point.","Most of the men in PREVAIL had not previously received an androgen receptor pathway inhibitor in hormone-sensitive disease; today most have, which makes the trial's population historical.","Radiographic progression-free survival at 12 months is a landmark analysis and is sensitive to the imaging schedule the protocol specified."],"changedPractice":true,"participants":1717},{"id":"paper-prado-lancet-oncol","kind":"paper","name":"Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 18539529 and published in The Lancet Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background: Emerging evidence on body composition suggests that sarcopenic obesity (obesity with depleted muscle mass) might be predictive of morbidity and mortality in non-malignant disease and also of toxicity to chemotherapy. We aimed to assess the prevalence and clinical implications of sarcopenic obesity in patients with cancer.\n\nMethods: Between Jan 13, 2004, and Jan 19, 2007, 2115 patients with solid tumours of the respiratory or gastrointestinal tract from a cancer treatment centre serving northern Alberta, Canada, were identified. Available lumbar CT images of the obese patients were analysed for total skeletal muscle cross-sectional area; these values were also used to estimate total body fat-free mass (FFM).\n\nFindings: Of the 2115 patients initially identified, 325 (15%) were classified as obese (body-mass index [BMI] > or =30). Of these obese patients, 250 had CT images that met the criteria for analysis. The remaining 75 patients were recorded as without assessable scans. Obese patients had a wide range of muscle mass. Sex-specific cut-offs that defined a significant association between low muscle mass with mortality were ascertained by optimum stratification analysis: 38 (15%) of 250 patients who had assessable CT images that met the criteria for analysis were below these cut-offs and were classified as having sarcopenia. Sarcopenic obesity was associated with poorer functional status compared with obese patients who did not have sarcopenia (p=0.009), and was an independent predictor of survival (hazard ratio [HR] 4.2 [95% CI 2.4-7.2], p<0.0001). Estimated FFM showed a poor association with body-surface area (r(2)=0.37). Assuming that FFM represents the volume of distribution of many cytotoxic chemotherapy drugs, we estimated that individual variation in FFM could account for up to three-times variation in effective volume of distribution for chemotherapy administered per unit body-surface area, in this population.\n\nInterpretation: This study provides evidence of the great variability of body composition in patients with cancer and links body composition, especially sarcopenic obesity, to clinical implications such as functional status, survival, and potentially, chemotherapy toxicity.\n\nIndexed on Europe PMC as PubMed record 18539529 (DOI 10.1016/s1470-2045(08)70153-0). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2008","url":"https://doi.org/10.1016/s1470-2045(08)70153-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/18539529/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/18539529"}],"tags":["europepmc-ingest"],"related":["ct-body-composition-sarcopenia"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2008,"doi":"10.1016/s1470-2045(08)70153-0","pmid":"18539529","authors":"Prado CM, Lieffers JR, McCargar LJ, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-barroso-sousa-breast-tmb-prevalence-ann-oncol-2020","kind":"paper","name":"Prevalence and mutational determinants of high tumor mutation burden in breast cancer","aka":[],"tldr":"Across nearly 4,000 breast cancers, one in twenty carried ten or more mutations per megabase, more often in triple-negative and metastatic tumours, and mostly because of APOBEC enzyme activity or mismatch repair failure.","summary":"3,969 primary or metastatic breast cancer samples from six public genomic studies with exome or panel sequencing were classified as high TMB at 10 or more mutations per megabase; eight Dana-Farber patients were added. Median TMB was 2.63 mut/Mb and varied by subtype (HR-negative/HER2-negative above HER2-positive above HR-positive/HER2-negative) and sample type (metastatic above primary). Hypermutated tumours were found in 198 patients (5%), enriched in metastatic versus primary disease (8.4% versus 2.9%). APOBEC activity (59.2%) and mismatch repair deficiency (36.4%) were the commonest mutational processes; three hypermutated patients treated with pembrolizumab-based therapy had objective durable responses.","asOf":"2026-09-24","links":[{"label":"Barroso-Sousa et al., Ann Oncol 2020: prevalence of high tumour mutation burden in 3,969 breast cancers","url":"https://doi.org/10.1016/j.annonc.2019.11.010"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32067680/"}],"tags":[],"related":["tmb-high"],"cancers":["tnbc","breast-cancer"],"sections":[],"technologies":["tmb-testing"],"targets":[],"drugs":[],"companies":[],"institutions":["dana-farber"],"pathways":[],"terms":["tmb","mutational-signature"],"trials":[],"people":["nancy-lin","sara-tolaney","eric-winer"],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2020,"doi":"10.1016/j.annonc.2019.11.010","pmid":"32067680","authors":"Barroso-Sousa R, Jain E, Cohen O, et al.","paperType":"observational","findings":["Hypermutation (10 or more mut/Mb) in 5% of breast cancers; 8.4% metastatic versus 2.9% primary.","Median TMB 2.63 mut/Mb, highest in HR-negative/HER2-negative tumours.","APOBEC 59.2% and mismatch repair deficiency 36.4% of hypermutated tumours."],"whatItMeans":"TMB-high is uncommon but not negligible in TNBC, rises at relapse, and the tumour-agnostic pembrolizumab indication makes it worth measuring on a metastatic biopsy.","caveats":["Mixed exome and panel data; panel TMB estimates are not interchangeable with exome.","Subtype-specific prevalence is described qualitatively in the abstract."],"changedPractice":false,"participants":3969},{"id":"paper-win-cancer-epidemiol-biomarkers-prev","kind":"paper","name":"Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer","aka":[],"tldr":"Paper cited by one bottleneck page, indexed on Europe PMC as PubMed record 27799157 and published in Cancer Epidemiology, Biomarkers & Prevention; the citing page links this DOI, which is how the record was matched.","summary":"Background: Although high-risk mutations in identified major susceptibility genes (DNA mismatch repair genes and MUTYH) account for some familial aggregation of colorectal cancer, their population prevalence and the causes of the remaining familial aggregation are not known. Methods: We studied the families of 5,744 colorectal cancer cases (probands) recruited from population cancer registries in the United States, Canada, and Australia and screened probands for mutations in mismatch repair genes and MUTYH We conducted modified segregation analyses using the cancer history of first-degree relatives, conditional on the proband's age at diagnosis. We estimated the prevalence of mutations in the identified genes, the prevalence of HR for unidentified major gene mutations, and the variance of the residual polygenic component. Results: We estimated that 1 in 279 of the population carry mutations in mismatch repair genes ( MLH1 = 1 in 1,946, MSH2 = 1 in 2,841, MSH6 = 1 in 758, PMS2 = 1 in 714), 1 in 45 carry mutations in MUTYH, and 1 in 504 carry mutations associated with an average 31-fold increased risk of colorectal cancer in unidentified major genes. The estimated polygenic variance was reduced by 30% to 50% after allowing for unidentified major genes and decreased from 3.3 for age <40 years to 0.5 for age ≥70 years (equivalent to sibling relative risks of 5.1 to 1.3, respectively). Conclusions: Unidentified major genes might explain one third to one half of the missing heritability of colorectal cancer. Impact: Our findings could aid gene discovery and development of better colorectal cancer risk prediction models. Cancer Epidemiol Biomarkers Prev; 26(3); 404-12. ©2016 AACR.\n\nIndexed on Europe PMC as PubMed record 27799157 (DOI 10.1158/1055-9965.epi-16-0693). Matched by DOI alone: one bottleneck page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer Epidemiol Biomarkers Prev 2017","url":"https://doi.org/10.1158/1055-9965.epi-16-0693"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27799157/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27799157"}],"tags":["europepmc-ingest"],"related":["b-hereditary-risk"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-epidemiology-biomarkers-prevention"],"dependsOn":[],"notes":[],"journal":"Cancer Epidemiology, Biomarkers & Prevention","year":2017,"doi":"10.1158/1055-9965.epi-16-0693","pmid":"27799157","authors":"Win AK, Jenkins MA, Dowty JG, et al.","paperType":"observational","findings":[],"whatItMeans":"One bottleneck page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nicolosi-germline-variants-prostate-testing-guidelines-jama-oncol-2019","kind":"paper","name":"Prevalence of germline variants in prostate cancer and implications for current genetic testing guidelines","aka":[],"tldr":"Testing 3,607 men with prostate cancer on a broad gene panel found something inheritable in one in six, and more than a third of them would not have been offered the test under the guidelines then in force.","summary":"A cross-sectional study of 3,607 men with a personal history of prostate cancer who underwent germline genetic testing between 2013 and 2018, unselected for family history, stage of disease or age at diagnosis, at an accredited diagnostic laboratory. Six hundred and twenty men, 17.2%, had a positive result, defined as a pathogenic, likely pathogenic or increased-risk variant, and only 30.7% of those were in BRCA1 or BRCA2. Positive variants in HOXB13, a gene associated only with prostate cancer risk, were identified in 30 patients, 4.5% of those with a positive result. DNA mismatch repair variants with substantial known therapeutic implications were detected in 1.74% of the total population tested. Examination of self-reported family histories indicated that 229 men with positive variants, 37%, would not have been approved for genetic testing under the National Comprehensive Cancer Network genetic and familial breast and ovarian guidelines then applying to prostate cancer.","asOf":"2026-09-25","links":[{"label":"Nicolosi et al., JAMA Oncol 2019: germline variants in 3,607 men with prostate cancer referred for testing, against the testing guidelines","url":"https://doi.org/10.1001/jamaoncol.2018.6760"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30730552/"}],"tags":[],"related":[],"cancers":["prostate"],"sections":[],"technologies":["germline-testing"],"targets":["brca","atm","chek2","msh2","mlh1"],"drugs":[],"companies":[],"institutions":[],"pathways":["homologous-recombination-repair","mismatch-repair-msi","ddr"],"terms":["germline-vs-somatic","gbrca-mutation","lynch-syndrome","msi"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2019,"doi":"10.1001/jamaoncol.2018.6760","pmid":"30730552","authors":"Nicolosi P, Ledet E, Yang S, et al.","paperType":"observational","findings":["Positive germline variants in 620 of 3,607 men, 17.2%, on a broad panel.","Only 30.7% of positives were in BRCA1 or BRCA2.","Mismatch repair variants with therapeutic implications in 1.74% of all men tested.","Thirty-seven per cent of men with a positive result would not have qualified for testing under the guideline in force."],"whatItMeans":"It is the second half of the argument for unselected germline testing, and it widens the target beyond BRCA: two thirds of the actionable inherited findings in prostate cancer are in other genes, including the mismatch repair genes that open a checkpoint inhibitor route.","caveats":["A referral cohort tested at a commercial laboratory, so ascertainment is not random and the 17.2% is higher than a population figure would be.","Increased-risk variants were counted alongside pathogenic ones.","Family histories were self-reported."],"changedPractice":true,"participants":3607},{"id":"paper-abida-msi-prostate-checkpoint-blockade-jama-oncol-2019","kind":"paper","name":"Prevalence of microsatellite instability in prostate cancer and response to immune checkpoint blockade","aka":[],"tldr":"Three in a hundred prostate cancers have a broken proofreading system, and in the men who did, immunotherapy worked and kept working.","summary":"In a case series, 1,551 tumours from 1,346 men with prostate cancer were prospectively analysed with a targeted sequencing assay between January 2015 and January 2018, with tumour mutation burden and MSIsensor score calculated and mutational signature analysis and mismatch repair immunohistochemistry performed in selected cases. Among the 1,033 men whose tumours were of adequate quality for MSIsensor analysis, 32, 3.1%, had microsatellite instability-high or mismatch repair-deficient prostate cancer: 23 with high MSIsensor scores and a further 9 with indeterminate scores but other evidence of deficient repair. Seven of the 32, 21.9%, had a pathogenic germline mutation in a Lynch syndrome-associated gene. Of the 6 men with more than one tumour analysed, 2 displayed an acquired microsatellite instability-high phenotype later in the disease course. Eleven men with microsatellite instability-high or mismatch repair-deficient castration-resistant disease received anti-PD-1 or anti-PD-L1 therapy: 6, 54.5%, had a PSA decline of more than half, 4 of them with radiographic responses, and 5 of the 6 responders were still on therapy at up to 89 weeks.","asOf":"2026-09-25","links":[{"label":"Abida et al., JAMA Oncol 2019: microsatellite instability in 1,033 assessable prostate tumours and response to checkpoint blockade","url":"https://doi.org/10.1001/jamaoncol.2018.5801"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30589920/"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["cgp","checkpoint-inhibitor"],"targets":["msh2","msh6","mlh1","pms2","mmr","pd1"],"drugs":["pembrolizumab"],"companies":[],"institutions":[],"pathways":["mismatch-repair-msi","pd1-checkpoint","cancer-immunity-cycle"],"terms":["msi","lynch-syndrome","tumour-agnostic","germline-vs-somatic","psa50"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2019,"doi":"10.1001/jamaoncol.2018.5801","pmid":"30589920","authors":"Abida W, Cheng ML, Armenia J, et al.","paperType":"observational","findings":["Microsatellite instability-high or mismatch repair-deficient disease in 32 of 1,033 men, 3.1%.","A pathogenic germline Lynch syndrome variant in 7 of the 32, 21.9%.","The phenotype was acquired during the disease course in 2 of 6 men with serial tumours.","PSA decline over 50% in 6 of 11 treated men, with 5 still on therapy at up to 89 weeks."],"whatItMeans":"It is the argument for sequencing every man with advanced prostate cancer rather than only the ones who look high risk: the phenotype is uncommon, it is invisible clinically, it opens the only durable immunotherapy route in this disease, and in one man in five it also identifies Lynch syndrome in the family.","caveats":["A single-centre case series with 11 treated men, so the response rate has wide uncertainty.","Not all microsatellite instability-high men responded, and the mechanisms of resistance were not defined.","Because the phenotype can be acquired, a negative result on an old sample does not settle the question."],"changedPractice":true,"participants":1033},{"id":"paper-nct05663866-j-thorac-oncol-2025","kind":"paper","name":"Preventing Infusion-Related Reactions With Intravenous Amivantamab-Results From SKIPPirr, a Phase 2 Study: A Brief Report","aka":[],"tldr":"Published report from the trial registered as NCT05663866, in Journal of Thoracic Oncology (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Introduction: Amivantamab, an EGFR-MET bispecific antibody, is approved for multiple indications in EGFR-mutated advanced NSCLC as monotherapy or combined with other agents. Intravenous amivantamab is associated with a 67% infusion-related reaction (IRR) rate.\n\nMethods: The phase 2 SKIPPirr study (NCT05663866) enrolled participants with EGFR-mutated (exon 19 deletion or exon 21 L858R) advanced NSCLC after progression on osimertinib and platinum-based chemotherapy who received intravenous amivantamab plus oral lazertinib (amivantamab-lazertinib), a third-generation tyrosine kinase inhibitor. Aiming to mitigate IRRs, four independent prophylactic approaches were evaluated using Simon's two-stage design with an expansion stage if a cohort passed both stages: oral dexamethasone 4 mg twice daily given on cycle (C) 1 day (D) -1 (two doses); oral dexamethasone 8 mg twice daily given on C1D-2, C1D-1, and the morning of C1D1 (five doses); oral montelukast 10 mg once daily given on C1D-4, C1D-3, C1D-2, C1D-1, and C1D1 (five doses); subcutaneous methotrexate 25 mg (one dose) given anytime between C1D-7 and C1D-3. The primary end point was C1D1 IRR incidence.\n\nResults: at June 24, 2024, 68 participants were treated across all cohorts. The dexamethasone 8 mg cohort passed stages 1 and 2 proceeding to the expansion stage, with 24 additional participants treated. At C1D1, nine of 40 participants (22.5%) experienced IRRs, resulting in an approximately threefold decrease versus historical data (67.4%). By the end of C3, 10 of 41 participants (24.4%) in the dexamethasone 8 mg cohort experienced IRRs (grades 1-2, except one grade 3 on C2D1). Amivantamab-lazertinib's safety and efficacy were consistent with previous reports.\n\nConclusions: Prophylaxis with 8 mg oral dexamethasone meaningfully reduced IRRs and can be readily implemented in clinical practice.\n\nIndexed on Europe PMC as PubMed record 39864547 (DOI 10.1016/j.jtho.2025.01.018). Its abstract cites the registry id NCT05663866, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Thorac Oncol 2025","url":"https://doi.org/10.1016/j.jtho.2025.01.018"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39864547/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39864547"},{"label":"ClinicalTrials.gov NCT05663866","url":"https://clinicaltrials.gov/study/NCT05663866"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05663866"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-thoracic-oncology"],"dependsOn":[],"notes":[],"journal":"Journal of Thoracic Oncology","year":2025,"doi":"10.1016/j.jtho.2025.01.018","pmid":"39864547","authors":"Spira AI, Paz-Ares L, Han JY, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05663866 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-vokinger-lancet-oncol","kind":"paper","name":"Prices and clinical benefit of cancer drugs in the USA and Europe: a cost-benefit analysis","aka":[],"tldr":"Paper cited by one term page and two bottleneck pages, indexed on Europe PMC as PubMed record 32359489 and published in The Lancet Oncology; the citing pages link this DOI, which is how the record was matched.","summary":"Background: Increasing cancer drug prices are a challenge for patients and health systems in the USA and Europe. By contrast with the USA, national authorities in European countries often directly negotiate drug prices with manufacturers. The American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) developed frameworks to evaluate the clinical value of cancer therapies: the ASCO-Value Framework (ASCO-VF) and the ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS). We aimed to assess the association between the clinical benefit of approved cancer drugs based on these frameworks and their drug prices in the USA and four European countries (England, Switzerland, Germany, and France).\n\nMethods: For this cost-benefit analysis, we identified all new drugs with initial indications for adult cancers that were approved by the US Food and Drug Administration between Jan 1, 2009, and Dec 31, 2017, and by the European Medicines Agency up until Sept 1, 2019. For drugs indicated for solid tumours, we assessed clinical benefit using ASCO-VF and ESMO-MCBS. We compared monthly drug treatment costs between benefit levels using hierarchical linear regression models, and calculated Spearman's correlation coefficients between costs and benefit levels for individual countries.\n\nFindings: Our cohort included 65 drugs: 47 (72%) drugs were approved for solid tumours and 18 (28%) were approved for haematological malignancies. The monthly drug treatment costs in the USA were a median of 2·31 times (IQR 1·79-3·17) as high as in the assessed European countries. There were no significant associations between monthly treatment costs for solid tumours and clinical benefit in all assessed countries, using the ESMO-MCBS (p=0·16 for the USA, p=0·98 for England, p=0·54 for Switzerland, p=0·52 for Germany, and p=0·40 for France), and for all assessed countries except France using ASCO-VF (p=0·56 for the USA, p=0·47 for England, p=0·26 for Switzerland, p=0·23 for Germany, and p=0·037 for France).\n\nInterpretation: Cancer drugs with low or uncertain clinical benefit might be prioritised for price negotiations. Value frameworks could help identify therapies providing high clinical benefit that should be made rapidly available across countries.\n\nFunding: Swiss Cancer Research Foundation (Krebsforschung Schweiz).\n\nIndexed on Europe PMC as PubMed record 32359489 (DOI 10.1016/s1470-2045(20)30139-x). Matched by DOI alone: one term page and two bottleneck pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2020","url":"https://doi.org/10.1016/s1470-2045(20)30139-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32359489/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32359489"}],"tags":["europepmc-ingest"],"related":["drug-price-transparency","b-incentive-misalignment","b-drug-pricing"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2020,"doi":"10.1016/s1470-2045(20)30139-x","pmid":"32359489","authors":"Vokinger KN, Hwang TJ, Grischott T, et al.","paperType":"observational","findings":[],"whatItMeans":"One term page and two bottleneck pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-prima-niraparib-nejm-2019","kind":"paper","name":"PRIMA: niraparib maintenance in newly diagnosed advanced ovarian cancer","aka":[],"tldr":"Niraparib maintenance after first-line chemotherapy delayed progression in newly diagnosed advanced ovarian cancer whether or not the tumour had a homologous recombination deficiency, though the gain was much larger when it did.","summary":"Phase 3 placebo-controlled trial of 733 patients with newly diagnosed advanced high-grade ovarian cancer at high risk of relapse who had responded to platinum chemotherapy, randomised to niraparib or placebo maintenance.\n\nIn homologous recombination-deficient tumours median progression-free survival was 21.9 versus 10.4 months (hazard ratio 0.43); in the overall population it was 13.8 versus 8.2 months (hazard ratio 0.62), with a smaller benefit in homologous recombination-proficient disease (hazard ratio 0.68).","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2019","url":"https://doi.org/10.1056/NEJMoa1910962"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31562799/"}],"tags":[],"related":[],"cancers":["platinum-sensitive-ovarian-cancer","high-grade-serous-ovarian-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["niraparib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["prima"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2019,"doi":"10.1056/NEJMoa1910962","pmid":"31562799","authors":"González-Martín A, Pothuri B, Vergote I, et al.","paperType":"rct","findings":["Homologous recombination-deficient: median progression-free survival 21.9 vs 10.4 months; hazard ratio 0.43.","Overall population: 13.8 vs 8.2 months; hazard ratio 0.62."],"whatItMeans":"Niraparib is approved as first-line maintenance for all comers, making PARP inhibitor maintenance available beyond BRCA-mutated disease, though the benefit in proficient tumours is modest and long-term survival data are neutral.","caveats":["No overall survival benefit at final analysis.","Haematological toxicity requires individualised starting doses."],"changedPractice":true,"participants":733},{"id":"paper-impassion131-ann-oncol-2021","kind":"paper","name":"Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer","aka":[],"tldr":"Published report from the IMpassion131 trial registered as NCT03125902, in Annals of Oncology (2021), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: In the phase III IMpassion130 trial, combining atezolizumab with first-line nanoparticle albumin-bound-paclitaxel for advanced triple-negative breast cancer (aTNBC) showed a statistically significant progression-free survival (PFS) benefit in the intention-to-treat (ITT) and programmed death-ligand 1 (PD-L1)-positive populations, and a clinically meaningful overall survival (OS) effect in PD-L1-positive aTNBC. The phase III KEYNOTE-355 trial adding pembrolizumab to chemotherapy for aTNBC showed similar PFS effects. IMpassion131 evaluated first-line atezolizumab-paclitaxel in aTNBC.\n\nPatients and methods: Eligible patients [no prior systemic therapy or ≥12 months since (neo)adjuvant chemotherapy] were randomised 2:1 to atezolizumab 840 mg or placebo (days 1, 15), both with paclitaxel 90 mg/m 2 (days 1, 8, 15), every 28 days until disease progression or unacceptable toxicity. Stratification factors were tumour PD-L1 status, prior taxane, liver metastases and geographical region. The primary endpoint was investigator-assessed PFS, tested hierarchically first in the PD-L1-positive [immune cell expression ≥1%, VENTANA PD-L1 (SP142) assay] population, and then in the ITT population. OS was a secondary endpoint.\n\nResults: Of 651 randomised patients, 45% had PD-L1-positive aTNBC. At the primary PFS analysis, adding atezolizumab to paclitaxel did not improve investigator-assessed PFS in the PD-L1-positive population [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.60-1.12; P = 0.20; median PFS 6.0 months with atezolizumab-paclitaxel versus 5.7 months with placebo-paclitaxel]. In the PD-L1-positive population, atezolizumab-paclitaxel was associated with more favourable unconfirmed best overall response rate (63% versus 55% with placebo-paclitaxel) and median duration of response (7.2 versus 5.5 months, respectively). Final OS results showed no difference between arms (HR 1.11, 95% CI 0.76-1.64; median 22.1 months with atezolizumab-paclitaxel versus 28.3 months with placebo-paclitaxel in the PD-L1-positive population). Results in the ITT population were consistent with the PD-L1-positive population. The safety profile was consistent with known effects of each study drug.\n\nConclusion: Combining atezolizumab with paclitaxel did not improve PFS or OS versus paclitaxel alone. CLINICALTRIALS.GOV: NCT03125902.\n\nIndexed on Europe PMC as PubMed record 34219000 (DOI 10.1016/j.annonc.2021.05.801). Its abstract cites the registry id NCT03125902, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2021","url":"https://doi.org/10.1016/j.annonc.2021.05.801"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34219000/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34219000"},{"label":"ClinicalTrials.gov NCT03125902","url":"https://clinicaltrials.gov/study/NCT03125902"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["impassion131"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2021,"doi":"10.1016/j.annonc.2021.05.801","pmid":"34219000","authors":"Miles D, Gligorov J, André F, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03125902 with the most citations, so it is the natural first reading for anyone following the IMpassion131 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-bonvalot-retroperitoneal-sarcoma-compartmental-jco-2009","kind":"paper","name":"Primary retroperitoneal sarcomas: a multivariate analysis of surgical factors associated with local control","aka":[],"tldr":"This French multicentre study showed that resecting a retroperitoneal sarcoma together with the adjacent organs, even when not obviously involved, reduced local recurrence more than threefold, establishing the compartmental surgical approach.","summary":"Retrospective analysis of 382 patients with primary retroperitoneal sarcoma from French Sarcoma Group centres examining surgical technique, margins and outcomes.\n\nSystematic en bloc resection of adjacent organs (compartmental resection) was associated with a 3.29-fold lower risk of abdominal recurrence compared with simple complete resection, without higher mortality, while incomplete resection and high grade predicted recurrence.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2009","url":"https://doi.org/10.1200/JCO.2008.18.0802"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19047280/"}],"tags":[],"related":[],"cancers":["retroperitoneal-sarcoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["sylvie-bonvalot"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2009,"doi":"10.1200/JCO.2008.18.0802","pmid":"19047280","authors":"Bonvalot S, Rivoire M, Castaing M, et al.","paperType":"observational","findings":["Abdominal recurrence risk reduced 3.29-fold with compartmental resection.","Postoperative mortality 3 percent."],"whatItMeans":"Extended en bloc resection in a sarcoma reference centre is the standard operation for retroperitoneal sarcoma.","caveats":["Retrospective; extended resection carries morbidity and remains debated for low-grade liposarcoma."],"changedPractice":true,"participants":382},{"id":"paper-chari-pancreatic-cancer-following-diabetes-gastroenterology-2005","kind":"paper","name":"Probability of pancreatic cancer following diabetes: a population-based study","aka":[],"tldr":"The 2005 Minnesota study that found about 1 in 100 people who develop diabetes after 50 is diagnosed with pancreatic cancer within three years, eight times the expected rate, which made new diabetes a possible early warning.","summary":"Chari and colleagues assembled a population-based cohort of 2,122 Rochester, Minnesota residents aged 50 or over who first met standardised criteria for diabetes between 1950 and 1994 and identified those diagnosed with pancreatic cancer within three years. Eighteen (0.85 percent) were, 10 of them within six months of meeting diabetes criteria, and three were resected; the observed-to-expected ratio against the Iowa SEER registry was 7.94 (95 percent confidence interval 4.70 to 12.55). Diabetic subjects with pancreatic cancer were more likely to have met diabetes criteria after age 69 (odds ratio 4.52) and did not differ in body mass index from those without. The authors concluded that about 1 percent of diabetes subjects aged 50 or over will be diagnosed with pancreatic cancer within three years and that the marker needed further evaluation.","asOf":"2026-09-24","links":[{"label":"Gastroenterology 2005","url":"https://doi.org/10.1016/j.gastro.2005.05.007"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/16083707/"}],"tags":["pancreatic-evidence"],"related":["paper-sharma-endpac-model-new-onset-diabetes-gastroenterology-2018","idea-mced-new-onset-diabetes"],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["mayo-clinic"],"pathways":[],"terms":["ppv"],"trials":[],"people":[],"bottlenecks":["b-early-detection"],"keyPapers":[],"journals":["gastroenterology"],"dependsOn":[],"notes":[],"journal":"Gastroenterology","year":2005,"doi":"10.1016/j.gastro.2005.05.007","pmid":"16083707","authors":"Chari ST, Leibson CL, Rabe KG, et al.","paperType":"observational","findings":["2,122 new diabetics aged 50 or over; 18 (0.85 percent) diagnosed with pancreatic cancer within three years.","Observed-to-expected ratio 7.94; 10 of 18 diagnosed within six months of diabetes onset.","Onset after 69 raised the odds (odds ratio 4.52); body mass index did not differ."],"whatItMeans":"The observation behind every new-onset diabetes strategy: a 1 percent prevalence is a hundred times the general population's and high enough for a blood test or scan to have a useful positive predictive value.","caveats":["Single US county, diabetes criteria from 1950 to 1994, small case count.","Three-year prevalence, not a screening result; whether finding these cancers earlier saves lives is untested."],"participants":2122},{"id":"paper-wei-cochrane-database-syst-rev","kind":"paper","name":"Probiotics for the prevention or treatment of chemotherapy- or radiotherapy-related diarrhoea in people with cancer","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 30168576 and published in The Cochrane database of systematic reviews; the citing page links this DOI, which is how the record was matched.","summary":"Background: Treament-related diarrhoea is one of the most common and troublesome adverse effects related to chemotherapy or radiotherapy in people with cancer. Its reported incidence has been as high as 50% to 80%. Severe treatment-related diarrhoea can lead to fluid and electrolyte losses and nutritional deficiencies and could adversely affect quality of life (QoL). It is also associated with increased risk of infection in people with neutropenia due to anticancer therapy and often leads to treatment delays, dose reductions, or treatment discontinuation. Probiotics may be effective in preventing or treating chemotherapy- or radiotherapy-induced diarrhoea.\n\nObjectives: To evaluate the clinical effectiveness and side effects of probiotics used alone or combined with other agents for prevention or treatment of chemotherapy- or radiotherapy-related diarrhoea in people with cancer.\n\nSearch methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 7), MEDLINE (1946 to July week 2, 2017), and Embase (1980 to 2017, week 30). We also searched prospective clinical trial registers and the reference lists of included studies.\n\nSelection criteria: We included randomised controlled trials (RCTs) investigating the effects of probiotics for prevention or treatment of chemotherapy- or radiotherapy-related diarrhoea in people with cancer.\n\nData collection and analysis: Two review authors independently selected studies, extracted data, and assessed risk of bias. We used random-effects models for all meta-analyses. If meta-analysis was not possible, we summarised the results narratively.\n\nMain results: We included 12 studies involving 1554 participants. Eleven studies were prevention studies, of which seven compared probiotics with placebo (887 participants), one compared two doses of probiotics with each other and with placebo (246 participants), and three compared probiotics with another active agent (216 participants).The remaining study assessed the effectiveness of probiotics compared with placebo for treatment of radiotherapy-related diarrhoea (205 participants).For prevention of radiotherapy (with or without chemotherapy)-induced diarrhoea, review authors identified five heterogeneous placebo-controlled studies (with 926 participants analysed). Owing to heterogeneity, we could not carry out a meta-analysis, except for two outcomes. For occurrence of any diarrhoea, risk ratios (RRs) ranged from 0.35 (95% confidence interval (CI) 0.26 to 0.47) to 1.0 (95% CI 0.94 to 1.06) (three studies; low-certainty evidence). A beneficial effect of probiotics on quality of life could neither be demonstrated nor refuted (two studies; low-certainty evidence). For occurrence of grade 2 or higher diarrhoea, the pooled RR was 0.75 (95% CI 0.55 to 1.03; four studies; 420 participants; low-certainty evidence), and for grade 3 or higher diarrhoea, RRs ranged from 0.11 (95% CI 0.06 to 0.23) to 1.24 (95% CI 0.74 to 2.08) (three studies; low-certainty evidence). For probiotic users, time to rescue medication was 36 hours longer in one study (95% CI 34.7 to 37.3), but another study reported no difference (moderate-certainty evidence). For the need for rescue medication, the pooled RR was 0.50 (95% CI 0.15 to 1.66; three studies; 194 participants; very low-certainty evidence). No study reported major differences between groups with respect to adverse effects. Although not mentioned explicitly, no studies reported deaths, except one in which one participant in the probiotics group died of myocardial infarction after three sessions of radiotherapy.Three placebo-controlled studies, with 128 analysed participants, addressed prevention of chemotherapy-induced diarrhoea. For occurrence of any diarrhoea, the pooled RR was 0.59 (95% CI 0.36 to 0.96; two studies; 106 participants; low-certainty evidence). For all other outcomes, a beneficial effect of probiotics could be neither demonstrated nor refuted (one to two studies; 46 to 106 participants; all low-certainty evidence). Studies did not address quality of life nor time to rescue medication.Three studies compared probiotics with another intervention in 213 participants treated with radiotherapy (with or without chemotherapy). One very small study (21 participants) reported less diarrhoea six weeks after treatment when dietary counselling was provided (RR 0.30, 95% CI 0.11 to 0.81; very low-certainty evidence). In another study (148 participants), grade 3 or 4 diarrhoea occurred less often in the probiotics group than in the control group (guar gum containing nutritional supplement) (odds ratio (OR) 0.38, 95% CI 0.16 to 0.89; low-certainty evidence), and two studies (63 participants) found less need for rescue medication of probiotics versus another active treatment (RR 0.44, 95% CI 0.22 to 0.86; very low-certainty evidence). Studies did not address quality of life nor time to rescue medication.One placebo-controlled study with 205 participants addressed treatment for radiotherapy-induced diarrhoea and could not demonstrate or refute a beneficial effect of probiotics on average diarrhoea grade, time to rescue medication for diarrhoea (13 hours longer in the probiotics group; 95% CI -0.9 to 26.9 hours), or need for rescue medication (RR 0.74, 95% CI 0.53 to 1.03; moderate-certainty evidence). This study did not address quality of life.No studies reported serious adverse events or diarrhoea-related deaths.\n\nAuthors' conclusions: This review presents limited low- or very low-certainty evidence supporting the effects of probiotics for prevention and treatment of diarrhoea related to radiotherapy (with or without chemotherapy) or chemotherapy alone, need for rescue medication, or occurrence of adverse events. All studies were underpowered and heterogeneous. Severe side effects were absent from all studies.Robust evidence on this topic must be provided by future methodologically well-designed trials.\n\nIndexed on Europe PMC as PubMed record 30168576 (DOI 10.1002/14651858.cd008831.pub3). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cochrane Database Syst Rev 2018","url":"https://doi.org/10.1002/14651858.cd008831.pub3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30168576/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30168576"}],"tags":["europepmc-ingest"],"related":["probiotics-treatment-diarrhoea"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Cochrane database of systematic reviews","year":2018,"doi":"10.1002/14651858.cd008831.pub3","pmid":"30168576","authors":"Wei D, Heus P, van de Wetering FT, et al.","paperType":"meta-analysis","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-autio-clin-cancer-res","kind":"paper","name":"Probody Therapeutics: An Emerging Class of Therapies Designed to Enhance On-Target Effects with Reduced Off-Tumor Toxicity for Use in Immuno-Oncology","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 31601568 and published in Clinical Cancer Research; the citing page links this DOI, which is how the record was matched.","summary":"The deep and durable antitumor effects of antibody-based immunotherapies such as immune checkpoint inhibitors (ICIs) have revolutionized oncology and transformed the therapeutic landscape for many cancers. Several anti-programmed death receptor 1 and anti-programmed death receptor ligand 1 antibodies have been approved for use in advanced solid tumors, including melanoma, non-small cell lung cancer, bladder cancer, and other cancers. ICIs are under development across many tumor types and preliminary results are compelling. However, ICIs have been associated with severe immune-related adverse events (irAEs), including rash, diarrhea, colitis, hypophysitis, hepatotoxicity, and hypothyroidism, which in some cases lead to high morbidity, are potentially life-threatening, and limit the duration of treatment. The incidence of severe irAEs increases further when programmed cell death-1 and programmed cell death ligand-1 inhibitors are combined with anti-CTLA-4 and/or other multidrug regimens. Probody therapeutics, a new class of recombinant, proteolytically activated antibody prodrugs are in early development and are designed to exploit the hallmark of dysregulation of tumor protease activity to deliver their therapeutic effects within the tumor microenvironment (TME) rather than peripheral tissue. TME targeting, rather than systemic targeting, may reduce irAEs in tissues distant from the tumor. Probody therapeutic technology has been applied to multiple antibody formats, including immunotherapies, Probody drug conjugates, and T-cell-redirecting bispecific Probody therapeutics. In preclinical models, Probody therapeutics have consistently maintained anticancer activity with improved safety in animals compared with the non-Probody parent antibody. In the clinical setting, Probody therapeutics may expand or create therapeutic windows for anticancer therapies.\n\nIndexed on Europe PMC as PubMed record 31601568 (DOI 10.1158/1078-0432.ccr-19-1457). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Clin Cancer Res 2020","url":"https://doi.org/10.1158/1078-0432.ccr-19-1457"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31601568/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31601568"}],"tags":["europepmc-ingest"],"related":["masked-adc"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2020,"doi":"10.1158/1078-0432.ccr-19-1457","pmid":"31601568","authors":"Autio KA, Boni V, Humphrey RW, et al.","paperType":"review","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-prodige-24-adjuvant-mfolfirinox-pancreatic-nejm-2018","kind":"paper","name":"PRODIGE 24/CCTG PA6: adjuvant modified FOLFIRINOX versus gemcitabine after resection of pancreatic cancer","aka":[],"tldr":"Six months of the four-drug combination modified FOLFIRINOX after surgery for pancreatic cancer kept the disease away for almost twice as long as gemcitabine alone and added about a year and a half to median survival. It is the reason fit patients are now offered FOLFIRINOX after a pancreatic operation.","summary":"Randomised phase 3 trial in 493 patients in France and Canada who had undergone a complete (R0 or R1) resection of pancreatic ductal adenocarcinoma, had a CA19-9 below 180 U/mL and were fit enough for combination chemotherapy. Patients received six months of modified FOLFIRINOX (oxaliplatin, irinotecan, leucovorin and infusional fluorouracil without the bolus) or gemcitabine.\n\nAt a median follow-up of 33.6 months, median disease-free survival was 21.6 months with modified FOLFIRINOX against 12.8 months with gemcitabine (hazard ratio 0.58), and median overall survival 54.4 against 35.0 months (hazard ratio 0.64). Grade 3 or 4 adverse events were more frequent with modified FOLFIRINOX (about 76 against 53 percent). Five-year results published in 2022 confirmed the survival benefit.","asOf":"2026-09-21","links":[{"label":"N Engl J Med 2018","url":"https://doi.org/10.1056/NEJMoa1809775"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30575490/"}],"tags":[],"related":[],"cancers":["resectable-pdac","pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":["folfirinox","gemcitabine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["prodige-24"],"people":["thierry-conroy"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2018,"doi":"10.1056/NEJMoa1809775","pmid":"30575490","authors":"Conroy T, Hammel P, Hebbar M, et al.","paperType":"rct","findings":["Median disease-free survival 21.6 versus 12.8 months, hazard ratio 0.58.","Median overall survival 54.4 versus 35.0 months, hazard ratio 0.64.","Grade 3 or 4 adverse events in about 76 percent with modified FOLFIRINOX and 53 percent with gemcitabine."],"whatItMeans":"Modified FOLFIRINOX is the adjuvant standard for patients who recover well from a pancreatic resection and can tolerate combination chemotherapy; gemcitabine-based regimens remain for those who cannot.","caveats":["Patients were selected for fitness and a low postoperative CA19-9, so the result does not transfer directly to frailer patients.","Adjuvant chemotherapy must start within 12 weeks of surgery, and many patients never recover enough to receive it, which is one argument for neoadjuvant treatment."],"changedPractice":true,"participants":493},{"id":"paper-profound-nejm-2020","kind":"paper","name":"PROfound: olaparib for metastatic castration-resistant prostate cancer with homologous recombination repair gene alterations","aka":[],"tldr":"In men with metastatic castration-resistant prostate cancer carrying BRCA1, BRCA2 or ATM alterations who had progressed on hormonal therapy, the PARP inhibitor olaparib delayed progression and lengthened survival compared with another hormonal agent.","summary":"Phase 3 trial of 387 men with metastatic castration-resistant prostate cancer progressing on enzalutamide or abiraterone, with alterations in BRCA1, BRCA2 or ATM (cohort A) or 12 other homologous recombination genes (cohort B), randomised 2:1 to olaparib or physician's choice of enzalutamide or abiraterone.\n\nIn cohort A median progression-free survival was 7.4 versus 3.6 months (hazard ratio 0.34) and median overall survival 19.1 versus 14.7 months (hazard ratio 0.69 despite crossover); benefit was driven mainly by BRCA2.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2020","url":"https://doi.org/10.1056/NEJMoa1911440"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32343890/"}],"tags":[],"related":["prostate-roadmap","paper-mateo-toparp-a-olaparib-dna-repair-nejm-2015","paper-fizazi-triton3-rucaparib-nejm-2023","idea-prostate-hrr-testing-at-metastatic-diagnosis"],"cancers":["prostate-mcrpc","prostate"],"sections":[],"technologies":[],"targets":["brca","atm","cdk12","parp"],"drugs":["olaparib"],"companies":[],"institutions":[],"pathways":["homologous-recombination-repair","base-excision-repair-parp","synthetic-lethality-map"],"terms":["germline-vs-somatic","gbrca-mutation","hrd"],"trials":["profound"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2020,"doi":"10.1056/NEJMoa1911440","pmid":"32343890","authors":"de Bono J, Mateo J, Fizazi K, et al.","paperType":"rct","findings":["Cohort A: median progression-free survival 7.4 vs 3.6 months; hazard ratio 0.34.","Cohort A: median overall survival 19.1 vs 14.7 months; hazard ratio 0.69."],"whatItMeans":"Germline and tumour testing for homologous recombination repair genes is now standard in metastatic prostate cancer, and olaparib is approved for BRCA-mutated disease after a hormonal agent.","caveats":["Benefit in ATM and the cohort B genes was weak or absent.","The comparator, a second hormonal agent, has limited activity after progression on the first."],"changedPractice":true,"participants":387},{"id":"paper-tejpar-tumour-location-crystal-fire3-jama-oncol-2017","kind":"paper","name":"Prognostic and predictive relevance of primary tumor location in patients with RAS wild-type metastatic colorectal cancer: retrospective analyses of the CRYSTAL and FIRE-3 trials","aka":[],"tldr":"Two European randomised trials, analysed separately, each showed the same thing: cetuximab helps left-sided bowel cancers with no RAS mutation and adds little on the right.","summary":"Patients with RAS wild-type metastatic colorectal cancer from the CRYSTAL and FIRE-3 trials were classified as left-sided (splenic flexure, descending colon, sigmoid colon or rectum) or right-sided (appendix, caecum, ascending colon, hepatic flexure or transverse colon). In both trials, patients with left-sided tumours (142 and 157) had markedly superior progression-free survival, overall survival and objective response rates compared with right-sided tumours (33 and 38). Among patients with left-sided tumours, FOLFIRI plus cetuximab significantly improved overall survival against the respective comparators, FOLFIRI in CRYSTAL and FOLFIRI plus bevacizumab in FIRE-3; in right-sided tumours the benefit of adding cetuximab was limited in CRYSTAL and outcomes were comparable between arms in FIRE-3. A significant interaction between primary tumour location and treatment was observed for overall survival in both studies (CRYSTAL hazard ratio 1.95; FIRE-3 hazard ratio 0.40) in multivariable models that included sex, prior adjuvant therapy and BRAF status.","asOf":"2026-09-24","links":[{"label":"Tejpar et al., JAMA Oncol 2017: primary tumour location in the RAS wild-type populations of CRYSTAL and FIRE-3","url":"https://doi.org/10.1001/jamaoncol.2016.3797"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27722750/"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":[],"targets":["egfr","kras","braf"],"drugs":["cetuximab","bevacizumab"],"companies":[],"institutions":[],"pathways":[],"terms":["sidedness","wild-type"],"trials":["crystal-fire3"],"people":["eric-van-cutsem","volker-heinemann","heinz-josef-lenz"],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2017,"doi":"10.1001/jamaoncol.2016.3797","pmid":"27722750","authors":"Tejpar S, Stintzing S, Ciardiello F, et al.","paperType":"rct","findings":["Left-sided RAS wild-type tumours had markedly better progression-free survival, overall survival and response than right-sided in both trials.","Significant location-by-treatment interaction for overall survival in CRYSTAL (1.95) and FIRE-3 (0.40) after adjusting for BRAF status."],"whatItMeans":"It showed the sidedness effect is not an artefact of pooling and survives adjustment for BRAF, which is what made guideline committees act on it.","caveats":["Retrospective subgroup analyses with small right-sided groups (33 and 38 patients).","The two trials had different comparators.","BRAF was adjusted for but the right-sided groups remain confounded by microsatellite status and other biology."],"changedPractice":true},{"id":"paper-cavallone-tnbc-ctdna-neoadjuvant-sci-rep-2020","kind":"paper","name":"Prognostic and predictive value of circulating tumor DNA during neoadjuvant chemotherapy for triple negative breast cancer","aka":[],"tldr":"In 26 women having chemotherapy before surgery for triple-negative cancer, tumour DNA in the blood fell after the first cycle in those heading for a complete response and rose again before surgery in those with cancer left behind.","summary":"Tumour and serial blood samples from 26 TNBC patients were collected before, during and after neoadjuvant chemotherapy. Individual droplet digital PCR assays were developed for 121 tumour variants (average five per patient), detecting ctDNA in 96% at baseline; baseline mutant allele frequency tracked clinical features. Levels fell sharply after one cycle, especially in eventual pCR patients, then rose significantly before surgery in patients with substantial residual tumour (P 0.0001). Detection early in treatment and at the end before surgery predicted residual tumour, though absence was less predictive of pCR when only TP53 variants were used; end-of-chemotherapy detection indicated worse relapse-free and overall survival.","asOf":"2026-09-24","links":[{"label":"Cavallone et al., Sci Rep 2020: ctDNA during neoadjuvant chemotherapy in 26 TNBC patients","url":"https://doi.org/10.1038/s41598-020-71236-y"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32895401/"}],"tags":[],"related":["ctdna-mrd-positive"],"cancers":["tnbc","tnbc-early"],"sections":[],"technologies":["liquid-biopsy"],"targets":["tp53"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ctdna","pcr"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Scientific Reports","year":2020,"doi":"10.1038/s41598-020-71236-y","pmid":"32895401","authors":"Cavallone L, Aguilar-Mahecha A, Lafleur J, et al.","paperType":"translational","findings":["ctDNA detectable in 96% at baseline with multi-variant droplet PCR.","Rise before surgery predicted residual tumour (P 0.0001); end-of-chemotherapy detection predicted worse survival."],"whatItMeans":"Multi-variant tracking beats a TP53-only assay in TNBC and supports response-adapted designs that read ctDNA mid-chemotherapy.","caveats":["26 patients; single centre.","Absence of ctDNA did not reliably predict pCR."],"changedPractice":false,"participants":26},{"id":"paper-arnold-primary-tumour-side-ras-wild-type-ann-oncol-2017","kind":"paper","name":"Prognostic and predictive value of primary tumour side in patients with RAS wild-type metastatic colorectal cancer treated with chemotherapy and EGFR directed antibodies in six randomized trials","aka":[],"tldr":"Pooling 2,159 patients from six trials showed that which side of the colon a tumour started on decides whether an EGFR antibody helps at all: a clear survival gain on the left, none on the right.","summary":"Arnold, Lueza, Douillard and colleagues retrospectively investigated the influence of primary tumour location in patients with unresectable RAS wild-type metastatic colorectal cancer in six randomised trials (CRYSTAL, FIRE-3, CALGB 80405, PRIME, PEAK and 20050181), comparing chemotherapy plus an EGFR antibody with chemotherapy or chemotherapy plus bevacizumab. Hazard ratios for overall and progression-free survival and odds ratios for response were pooled across studies, and the predictive value was evaluated by pooling the study-level interaction between treatment effect and tumour side.\n\nPrimary tumour location and RAS status were available for 2,159 of the 5,760 randomised patients (37.5 percent): 515 right-sided and 1,644 left-sided.","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2017","url":"https://doi.org/10.1093/annonc/mdx175"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28407110/"},{"label":"Europe PMC full text (PMC6246616)","url":"https://europepmc.org/article/MED/28407110"}],"tags":["colorectal-evidence"],"related":["paper-heinemann-fire-3-cetuximab-vs-bevacizumab-lancet-oncol-2014","paper-venook-calgb-80405-cetuximab-vs-bevacizumab-jama-2017","paper-douillard-prime-panitumumab-ras-nejm-2013","paper-esmo-metastatic-colorectal-cancer-guideline-ann-oncol-2023","ras-wild-type"],"cancers":["colorectal"],"sections":["targeted-therapy"],"technologies":["monoclonal-antibody"],"targets":["egfr","kras","vegf","nras"],"drugs":["cetuximab","panitumumab","bevacizumab"],"companies":[],"institutions":[],"pathways":["ras-mapk"],"terms":["sidedness","cms-subtypes","wild-type"],"trials":["paradigm","crystal-fire3"],"people":["eric-van-cutsem","josep-tabernero","andres-cervantes","heinz-josef-lenz","volker-heinemann","alan-venook"],"bottlenecks":["b-biomarker-validation"],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2017,"doi":"10.1093/annonc/mdx175","pmid":"28407110","authors":"Arnold D, Lueza B, Douillard JY, et al.","paperType":"meta-analysis","findings":["Right-sided tumours had a worse prognosis in both control and experimental arms: overall survival hazard ratios 2.03 (95 percent CI 1.69 to 2.42) and 1.38 (1.17 to 1.63).","EGFR antibody benefit in left-sided tumours: overall survival hazard ratio 0.75 (0.67 to 0.84) and progression-free survival 0.78 (0.70 to 0.87).","No benefit in right-sided tumours: 1.12 (0.87 to 1.45) and 1.12 (0.87 to 1.44); p for interaction <0.001 and 0.002.","Response odds ratios 2.12 (1.77 to 2.55) on the left against 1.47 (0.94 to 2.29) on the right (p for interaction 0.07)."],"whatItMeans":"The analysis that put 'left-sided, RAS and BRAF wild-type' into every guideline as the anti-EGFR population, and made an anatomical fact into a treatment-selection biomarker.","caveats":["Retrospective pooling on 37.5 percent of the randomised patients, which the authors themselves say demands caution.","Side is a proxy for biology (BRAF, mismatch repair deficiency, consensus molecular subtype) that is now measurable directly.","None of the six trials tested a whole treatment sequence, so the analysis speaks only to the first-line choice."],"changedPractice":true,"participants":2159},{"id":"paper-heng-j-clin-oncol","kind":"paper","name":"Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 19826129 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: There are no robust data on prognostic factors for overall survival (OS) in patients with metastatic renal cell carcinoma (RCC) treated with vascular endothelial growth factor (VEGF) -targeted therapy.\n\nMethods: Baseline characteristics and outcomes on 645 patients with anti-VEGF therapy-naïve metastatic RCC were collected from three US and four Canadian cancer centers. Cox proportional hazards regression, followed by bootstrap validation, was used to identify independent prognostic factors for OS.\n\nResults: The median OS for the whole cohort was 22 months (95% CI, 20.2 to 26.5 months), and the median follow-up was 24.5 months. Overall, 396, 200, and 49 patients were treated with sunitinib, sorafenib, and bevacizumab, respectively. Four of the five adverse prognostic factors according to the Memorial Sloan-Kettering Cancer Center (MSKCC) were independent predictors of short survival: hemoglobin less than the lower limit of normal (P <.0001), corrected calcium greater than the upper limit of normal (ULN; P =.0006), Karnofsky performance status less than 80% (P <.0001), and time from diagnosis to treatment of less than 1 year (P =.01). In addition, neutrophils greater than the ULN (P <.0001) and platelets greater than the ULN (P =.01) were independent adverse prognostic factors. Patients were segregated into three risk categories: the favorable-risk group (no prognostic factors; n = 133), in which median OS (mOS) was not reached and 2-year OS (2y OS) was 75%; the intermediate-risk group (one or two prognostic factors; n = 301), in which mOS was 27 months and 2y OS was 53%; and the poor-risk group (three to six prognostic factors; n = 152), in which mOS was 8.8 months and 2y OS was 7% (log-rank P <.0001). The C-index was 0.73.\n\nConclusion: This model validates components of the MSKCC model with the addition of platelet and neutrophil counts and can be incorporated into patient care and into clinical trials that use VEGF-targeted agents.\n\nIndexed on Europe PMC as PubMed record 19826129 (DOI 10.1200/jco.2008.21.4809). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2009","url":"https://doi.org/10.1200/jco.2008.21.4809"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19826129/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/19826129"}],"tags":["europepmc-ingest"],"related":["imdc-risk"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2009,"doi":"10.1200/jco.2008.21.4809","pmid":"19826129","authors":"Heng DY, Xie W, Regan MM, et al.","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-schmid-placental-site-trophoblastic-tumour-outcomes-lancet-2009","kind":"paper","name":"Prognostic markers and long-term outcome of placental-site trophoblastic tumours: a retrospective observational study","aka":[],"tldr":"The largest series of this rare trophoblastic tumour showed that women whose tumour appeared four or more years after the causative pregnancy did badly whatever the treatment, and that early-stage disease is cured by hysterectomy alone.","summary":"Retrospective study of 62 women with placental-site trophoblastic tumour treated in the UK trophoblastic disease centres from 1976 to 2006.\n\nTen-year overall survival was about 70 percent; stage I disease was cured by hysterectomy without chemotherapy, stage II to IV disease required platinum-based chemotherapy (EP/EMA), and an interval of 48 months or more since the antecedent pregnancy was the strongest adverse prognostic factor, with almost no long-term survivors in that group.","asOf":"2026-09-18","links":[{"label":"Lancet 2009","url":"https://doi.org/10.1016/S0140-6736(09)60618-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19552948/"}],"tags":[],"related":[],"cancers":["placental-site-trophoblastic-tumour"],"sections":[],"technologies":[],"targets":[],"drugs":["etoposide","cisplatin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2009,"doi":"10.1016/S0140-6736(09)60618-8","pmid":"19552948","authors":"Schmid P, Nagai Y, Agarwal R, et al.","paperType":"observational","findings":["Ten-year overall survival about 70 percent; hysterectomy alone cured stage I disease.","Interval of 48 months or more from the antecedent pregnancy predicted death from disease regardless of treatment."],"whatItMeans":"Placental-site trophoblastic tumour is managed by hysterectomy for early disease and platinum chemotherapy for advanced disease, and the interval since pregnancy identifies women who need intensified or experimental treatment.","caveats":["Retrospective series over thirty years with changing treatments.","Numbers in the poor-prognosis group were small."],"changedPractice":true,"participants":62},{"id":"paper-kras-colorectal-j-clin-oncol-2010","kind":"paper","name":"Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60-00 trial","aka":[],"tldr":"Phase 2 or 3 results paper on KRAS in Colorectal cancer, in Journal of Clinical Oncology (2010), one of the most cited Europe PMC records with KRAS in its title.","summary":"Purpose: Mutations within the KRAS proto-oncogene have predictive value but are of uncertain prognostic value in the treatment of advanced colorectal cancer. We took advantage of PETACC-3, an adjuvant trial with 3,278 patients with stage II to III colon cancer, to evaluate the prognostic value of KRAS and BRAF tumor mutation status in this setting.\n\nPatients and methods: Formalin-fixed paraffin-embedded tissue blocks (n = 1,564) were prospectively collected and DNA was extracted from tissue sections from 1,404 cases. Planned analysis of KRAS exon 2 and BRAF exon 15 mutations was performed by allele-specific real-time polymerase chain reaction. Survival analyses were based on univariate and multivariate proportional hazard regression models.\n\nResults: KRAS and BRAF tumor mutation rates were 37.0% and 7.9%, respectively, and were not significantly different according to tumor stage. In a multivariate analysis containing stage, tumor site, nodal status, sex, age, grade, and microsatellite instability (MSI) status, KRAS mutation was associated with grade (P =.0016), while BRAF mutation was significantly associated with female sex (P =.017), and highly significantly associated with right-sided tumors, older age, high grade, and MSI-high tumors (all P < 10(-4)). In univariate and multivariate analysis, KRAS mutations did not have a major prognostic value regarding relapse-free survival (RFS) or overall survival (OS). BRAF mutation was not prognostic for RFS, but was for OS, particularly in patients with MSI-low (MSI-L) and stable (MSI-S) tumors (hazard ratio, 2.2; 95% CI, 1.4 to 3.4; P =.0003).\n\nConclusion: In stage II-III colon cancer, the KRAS mutation status does not have major prognostic value. BRAF is prognostic for OS in MS-L/S tumors.\n\nIndexed on Europe PMC as PubMed record 20008640 (DOI 10.1200/jco.2009.23.3452). Its title names KRAS and its text names Colorectal cancer; PubMed types it as a clinical trial report (Clinical Trial, Research Support, Non-U.S. Gov't, Randomized Controlled Trial). It was matched automatically to the idea \"Covalent chemistry for the RAS mutations that still have no drug\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2010","url":"https://doi.org/10.1200/jco.2009.23.3452"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20008640/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/20008640"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2010,"doi":"10.1200/jco.2009.23.3452","pmid":"20008640","authors":"Roth AD, Tejpar S, Delorenzi M, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for KRAS in Colorectal cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by KRAS in the title and Colorectal cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-church-pole-endometrial-jnci-2015","kind":"paper","name":"Prognostic significance of POLE proofreading mutations in endometrial cancer","aka":[],"tldr":"Endometrial cancers with mutations in the proofreading domain of POLE, though hypermutated and often high grade, almost never recur, identifying a group of women who can be spared adjuvant treatment.","summary":"Analysis of 788 endometrial cancers from the PORTEC-1 and PORTEC-2 trials for POLE exonuclease domain mutations, found in 6.1 percent, with survival analysis and a meta-analysis of published series.\n\nPOLE-mutant tumours were more often high grade yet had excellent recurrence-free survival (hazard ratio 0.14) and cancer-specific survival, independent of other prognostic factors.","asOf":"2026-09-17","links":[{"label":"J Natl Cancer Inst 2015","url":"https://doi.org/10.1093/jnci/dju402"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25505230/"}],"tags":[],"related":[],"cancers":["endometrial-pole-ultramutated"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jnci"],"dependsOn":[],"notes":[],"journal":"JNCI: Journal of the National Cancer Institute","year":2015,"doi":"10.1093/jnci/dju402","pmid":"25505230","authors":"Church DN, Stelloo E, Nout RA, et al.","paperType":"translational","findings":["POLE exonuclease domain mutations in 6.1 percent of tumours.","Recurrence-free survival hazard ratio 0.14 for POLE-mutant tumours."],"whatItMeans":"POLE sequencing is now part of endometrial cancer classification, and guidelines allow omission of adjuvant therapy for stage I to II POLE-mutated tumours.","caveats":["Retrospective analysis of trial cohorts; only pathogenic hotspot mutations carry the favourable prognosis."],"changedPractice":true,"participants":788},{"id":"paper-kang-t2-gallbladder-cancer-location-meta-analysis-jcm-2021","kind":"paper","name":"Prognostic Significance of Tumor Location in T2 Gallbladder Cancer: A Systematic Review and Meta-Analysis","aka":[],"tldr":"Pooling seven studies, muscle-invading gallbladder cancers on the liver side were about twice as likely to be fatal as those on the free side, yet the bigger operation did not clearly improve survival in either group.","summary":"Systematic review and random-effects meta-analysis of studies to September 2020: seven studies, 1,789 resected T2 gallbladder cancers. Overall survival was worse for T2b (hepatic side) than T2a: hazard ratio 2.141 (95 percent CI 1.140 to 4.023; I2 71.4 percent). Lymph node metastasis was 26.6 percent in T2a and 36.6 percent in T2b (odds ratio 2.164, 1.309 to 3.575). Extended and simple cholecystectomy showed no survival difference in T2a (odds ratio 0.802, 0.618 to 1.042) or T2b (0.820, 0.620 to 1.083). The authors call for large prospective studies to set evidence-based treatment for T2 disease.","asOf":"2026-09-24","links":[{"label":"J Clin Med 2021","url":"https://doi.org/10.3390/jcm10153317"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34362101/"}],"tags":["gallbladder-evidence"],"related":["paper-khan-t2-gallbladder-cancer-liver-resection-meta-analysis-updates-surg-2021"],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["t2a-versus-t2b","radical-cholecystectomy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Medicine","year":2021,"doi":"10.3390/jcm10153317","pmid":"34362101","authors":"Kang H, Choi YS, Suh SW, et al.","paperType":"meta-analysis","findings":["T2b vs T2a overall survival hazard ratio 2.141 (95 percent CI 1.140 to 4.023).","Nodal metastasis 26.6 percent in T2a vs 36.6 percent in T2b (odds ratio 2.164).","Extended vs simple cholecystectomy: no survival difference in T2a (odds ratio 0.802) or T2b (0.820)."],"whatItMeans":"The prognostic split is solid; the surgical consequence is not. Whether T2a tumours can safely skip liver resection, and whether T2b tumours gain from it, is a randomised or prospective-registry question that nobody has yet run.","caveats":["Retrospective studies with high heterogeneity (I2 71 percent) for the survival comparison.","Selection into extended versus simple cholecystectomy was not random."],"changedPractice":false,"participants":1789},{"id":"paper-karschnia-neuro-oncol","kind":"paper","name":"Prognostic validation of a new classification system for extent of resection in glioblastoma: A report of the RANO resect group","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 35961053 and published in Neuro-Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background: Terminology to describe extent of resection in glioblastoma is inconsistent across clinical trials. A surgical classification system was previously proposed based upon residual contrast-enhancing (CE) tumor. We aimed to (1) explore the prognostic utility of the classification system and (2) define how much removed non-CE tumor translates into a survival benefit.\n\nMethods: The international RANO resect group retrospectively searched previously compiled databases from 7 neuro-oncological centers in the USA and Europe for patients with newly diagnosed glioblastoma per WHO 2021 classification. Clinical and volumetric information from pre- and postoperative MRI were collected.\n\nResults: We collected 1,008 patients with newly diagnosed IDHwt glioblastoma. 744 IDHwt glioblastomas were treated with radiochemotherapy per EORTC-26981/22981 (TMZ/RT→TMZ) following surgery. Among these homogenously treated patients, lower absolute residual tumor volumes (in cm3) were favorably associated with outcome: patients with \"maximal CE resection\" (class 2) had superior outcome compared to patients with \"submaximal CE resection\" (class 3) or \"biopsy\" (class 4). Extensive resection of non-CE tumor (≤5 cm3 residual non-CE tumor) was associated with better survival among patients with complete CE resection, thus defining class 1 (\"supramaximal CE resection\"). The prognostic value of the resection classes was retained on multivariate analysis when adjusting for molecular and clinical markers.\n\nConclusions: The proposed \"RANO categories for extent of resection in glioblastoma\" are highly prognostic and may serve for stratification within clinical trials. Removal of non-CE tumor beyond the CE tumor borders may translate into additional survival benefit, providing a rationale to explicitly denominate such \"supramaximal CE resection.\"\n\nIndexed on Europe PMC as PubMed record 35961053 (DOI 10.1093/neuonc/noac193). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Neuro Oncol 2023","url":"https://doi.org/10.1093/neuonc/noac193"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35961053/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35961053"}],"tags":["europepmc-ingest"],"related":["extent-of-resection"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["neuro-oncology"],"dependsOn":[],"notes":[],"journal":"Neuro-Oncology","year":2023,"doi":"10.1093/neuonc/noac193","pmid":"35961053","authors":"Karschnia P, Young JS, Dono A, et al.","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-park-tils-untreated-early-tnbc-ann-oncol-2019","kind":"paper","name":"Prognostic value of tumor-infiltrating lymphocytes in patients with early-stage triple-negative breast cancers (TNBC) who did not receive adjuvant chemotherapy","aka":[],"tldr":"In 476 women with early triple-negative cancer who had no chemotherapy, more lymphocytes in the tumour still meant fewer relapses, and stage I patients with 30% or more had a 97% chance of no distant relapse at five years.","summary":"Individual data from 476 TNBC patients not treated with chemotherapy at four centres (1989 to 2015; median age 64, median tumour 1.6 cm, 83% node-negative) were pooled. Median sTILs were 10% (interquartile range 4 to 30%). In multivariable analysis each 10% increment gave hazard ratios of 0.90 (iDFS), 0.86 (D-DFS) and 0.88 (OS). Stage I patients with sTILs 30% or more (74) had five-year iDFS 91%, D-DFS 97% and OS 98%.","asOf":"2026-09-24","links":[{"label":"Park et al., Ann Oncol 2019: TILs in 476 early TNBC patients who received no chemotherapy","url":"https://doi.org/10.1093/annonc/mdz395"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31566659/"}],"tags":[],"related":[],"cancers":["tnbc","tnbc-early"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tils"],"trials":[],"people":["loi-sherene","giuseppe-curigliano","fabrice-andre","kim-sung-bae"],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2019,"doi":"10.1093/annonc/mdz395","pmid":"31566659","authors":"Park JH, Jonas SF, Bataillon G, et al.","paperType":"observational","findings":["Median sTILs 10% in untreated early TNBC.","Each 10% increment: iDFS HR 0.90, D-DFS 0.86, OS 0.88.","Stage I with sTILs 30% or more: five-year D-DFS 97%, OS 98%."],"whatItMeans":"TILs are prognostic without chemotherapy, which is what a de-escalation biomarker has to show before trials omit treatment on its basis.","caveats":["Retrospective, older and node-negative patients who were selected not to receive chemotherapy.","Only 74 patients in the stage I high-TIL group."],"changedPractice":false,"participants":476},{"id":"paper-albrecht-pdl1-western-gallbladder-cancers-2021","kind":"paper","name":"Programmed death ligand-1 (PD-L1) is an independent negative prognosticator in Western-world gallbladder cancer","aka":[],"tldr":"In 131 German gallbladder cancers about one in seven had PD-L1 on tumour cells and fewer than one in twenty had a lot; high PD-L1 marked poorly differentiated tumours and shorter survival, and a second checkpoint, TIGIT, was present in some.","summary":"PD-L1 was assessed immunohistochemically in 131 gallbladder cancer patients as tumour proportion score (TPS), immune cell score and combined positive score. Tumour cells expressed PD-L1 in 14.7% of patients at a TPS cut-off of 1%; TPS above 10% and 25% was reached in 4.7% and 3.1%. At the 10% cut-off, TPS was associated with distinct histomorphological subtypes and poor differentiation.\n\nSurvival analysis showed a TPS above 10% to be a highly significant and independent negative prognosticator. PD-L1 expression was associated with increased CD4-positive, CD8-positive and PD-1-positive immune cell densities. In 14.8% of cases scattered immune cells expressed TIGIT, correlated with tumour expression of its ligand CD155.","asOf":"2026-09-24","links":[{"label":"Albrecht et al., Cancers 2021: PD-L1 in 131 Western gallbladder cancers","url":"https://doi.org/10.3390/cancers13071682"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33918309/"}],"tags":[],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":["pdl1","pd1"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ihc","tils"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancers-mdpi"],"dependsOn":[],"notes":[],"journal":"Cancers","year":2021,"doi":"10.3390/cancers13071682","pmid":"33918309","authors":"Albrecht T, Brinkmann F, Albrecht M, et al.","paperType":"observational","findings":["PD-L1 TPS 1% or more in 14.7%, above 10% in 4.7%, above 25% in 3.1% of 131 Western gallbladder cancers.","TPS above 10% an independent negative prognostic factor, linked to poor differentiation and denser CD4, CD8 and PD-1 infiltrates.","TIGIT on scattered immune cells in 14.8%, correlated with tumoral CD155."],"whatItMeans":"The Western counterpart to the Indian series, with lower rates and a prognostic signal in the opposite direction from what immunotherapy enthusiasts might hope. The TIGIT and CD155 finding names a second checkpoint for future trials.","caveats":["Single German centre; 131 patients.","Scoring systems and clone differ from the Indian study, so the rates are not directly comparable."],"changedPractice":false,"participants":131},{"id":"paper-yang-j-oncol-pract","kind":"paper","name":"Projected supply of and demand for oncologists and radiation oncologists through 2025: an aging, better-insured population will result in shortage","aka":[],"tldr":"Paper cited by one bottleneck page and 15 idea pages, indexed on Europe PMC as PubMed record 24443733 and published in JCO Oncology Practice; the citing pages link this DOI, which is how the record was matched.","summary":"Purpose: The American Society of Clinical Oncology (ASCO) published a study in 2007 that anticipated a shortage of oncologists by 2020. This study aims to update and better assess the market for chemotherapy and radiation therapy and the impact of health reform on capacity of and demand for oncologists and radiation oncologists.\n\nMethods: The supply of oncologists and radiation oncologists, by age, sex, and specialty, was projected through 2025 with an input-output model. The Medical Expenditure Panel Survey, commercial claims, and Medicare claims were analyzed to determine patterns of use by patient characteristics such as age, sex, health insurance coverage, cancer site, physician specialty, and service type. Patterns of use were then applied to the projected prevalence of cancer, using data from the SEER Program of the National Cancer Institute.\n\nResults: Beginning in 2012, 16,347 oncologists and radiation oncologists were active and supplying 15,190 full-time equivalents (FTEs) of patient care. Without consideration of the Affordable Care Act (ACA), overall demand for oncologist services is projected to grow 40% (21,255 FTEs), whereas supply may grow only 25% (18,997 FTEs), generating a shortage of 2,258 FTEs in 2025. When fully implemented, the ACA could increase the demand for oncologists and radiation oncologists by 500,000 visits per year, increasing the shortage to 2,393 FTEs in 2025.\n\nConclusion: Anticipated shortages are largely consistent with the projections of the ASCO 2007 workforce study but somewhat more delayed. The ACA may modestly exacerbate the shortage. Unless oncologist productivity can be enhanced, the anticipated shortage will strain the ability to provide quality cancer care.\n\nIndexed on Europe PMC as PubMed record 24443733 (DOI 10.1200/jop.2013.001319). Matched by DOI alone: one bottleneck page and 15 idea pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Oncol Pract 2014","url":"https://doi.org/10.1200/jop.2013.001319"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24443733/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/24443733"}],"tags":["europepmc-ingest"],"related":["b-workforce","idea-acc-advanced-practice-radiation-therapists","idea-acc-ambient-ai-documentation-oncology","idea-acc-clinical-officer-oncology-track","idea-acc-open-oncology-workforce-model","idea-acc-community-health-workers-oncology","idea-moon-task-shifting-ai-oncology-capacity","idea-acc-fast-track-relicensing-oncologists","idea-acc-nurse-led-follow-up-clinics","idea-acc-oncology-pharmacist-prescribing","idea-acc-mainstream-tele-genetic-counselling","idea-acc-remote-medical-physics-qa","idea-acc-pathologist-assistants-and-ai-triage","idea-acc-regional-oncology-training-hubs","idea-acc-retention-packages-oncology","idea-acc-district-surgeon-oncology-mentorship"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco-oncology-practice"],"dependsOn":[],"notes":[],"journal":"JCO Oncology Practice","year":2014,"doi":"10.1200/jop.2013.001319","pmid":"24443733","authors":"Yang W, Williams JH, Hogan PF, et al.","paperType":"observational","findings":[],"whatItMeans":"One bottleneck page and 15 idea pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-marinac-jama-oncol","kind":"paper","name":"Prolonged Nightly Fasting and Breast Cancer Prognosis","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 27032109 and published in JAMA Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Importance: Rodent studies demonstrate that prolonged fasting during the sleep phase positively influences carcinogenesis and metabolic processes that are putatively associated with risk and prognosis of breast cancer. To our knowledge, no studies in humans have examined nightly fasting duration and cancer outcomes.\n\nObjective: To investigate whether duration of nightly fasting predicted recurrence and mortality among women with early-stage breast cancer and, if so, whether it was associated with risk factors for poor outcomes, including glucoregulation (hemoglobin A1c), chronic inflammation (C-reactive protein), obesity, and sleep.\n\nDesign, setting, and participants: Data were collected from 2413 women with breast cancer but without diabetes mellitus who were aged 27 to 70 years at diagnosis and participated in the prospective Women's Healthy Eating and Living study between March 1, 1995, and May 3, 2007. Data analysis was conducted from May 18 to October 5, 2015.\n\nExposures: Nightly fasting duration was estimated from 24-hour dietary recalls collected at baseline, year 1, and year 4.\n\nMain outcomes and measures: Clinical outcomes were invasive breast cancer recurrence and new primary breast tumors during a mean of 7.3 years of study follow-up as well as death from breast cancer or any cause during a mean of 11.4 years of surveillance. Baseline sleep duration was self-reported, and archived blood samples were used to assess concentrations of hemoglobin A1c and C-reactive protein.\n\nResults: The cohort of 2413 women (mean [SD] age, 52.4 [8.9] years) reported a mean (SD) fasting duration of 12.5 (1.7) hours per night. In repeated-measures Cox proportional hazards regression models, fasting less than 13 hours per night (lower 2 tertiles of nightly fasting distribution) was associated with an increase in the risk of breast cancer recurrence compared with fasting 13 or more hours per night (hazard ratio, 1.36; 95% CI, 1.05-1.76). Nightly fasting less than 13 hours was not associated with a statistically significant higher risk of breast cancer mortality (hazard ratio, 1.21; 95% CI, 0.91-1.60) or a statistically significant higher risk of all-cause mortality (hazard ratio, 1.22; 95% CI, 0.95-1.56). In multivariable linear regression models, each 2-hour increase in the nightly fasting duration was associated with significantly lower hemoglobin A1c levels (β = -0.37; 95% CI, -0.72 to -0.01) and a longer duration of nighttime sleep (β = 0.20; 95% CI, 0.14-0.26).\n\nConclusions and relevance: Prolonging the length of the nightly fasting interval may be a simple, nonpharmacologic strategy for reducing the risk of breast cancer recurrence. Improvements in glucoregulation and sleep may be mechanisms linking nightly fasting with breast cancer prognosis.\n\nIndexed on Europe PMC as PubMed record 27032109 (DOI 10.1001/jamaoncol.2016.0164). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA Oncol 2016","url":"https://doi.org/10.1001/jamaoncol.2016.0164"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27032109/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27032109"}],"tags":["europepmc-ingest"],"related":["time-restricted-eating"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2016,"doi":"10.1001/jamaoncol.2016.0164","pmid":"27032109","authors":"Marinac CR, Nelson SH, Breen CI, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-promid-rinke-jco-2009","kind":"paper","name":"PROMID: octreotide LAR in the control of tumour growth in metastatic midgut neuroendocrine tumours","aka":[],"tldr":"The PROMID trial was the first to show that a somatostatin analogue, octreotide, slows tumour growth in midgut neuroendocrine tumours, more than doubling the time to progression compared with placebo.","summary":"Phase 3 placebo-controlled trial of 85 treatment-naive patients with well-differentiated metastatic midgut neuroendocrine tumours randomised to octreotide LAR 30 mg monthly or placebo.\n\nMedian time to tumour progression was 14.3 versus 6.0 months (hazard ratio 0.34), with the greatest benefit in patients with low hepatic tumour load and resected primary tumours.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2009","url":"https://doi.org/10.1200/JCO.2009.22.8510"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19704057/"}],"tags":[],"related":[],"cancers":["small-intestinal-net"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["promid"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2009,"doi":"10.1200/JCO.2009.22.8510","pmid":"19704057","authors":"Rinke A, Müller HH, Schade-Brittinger C, et al.","paperType":"rct","findings":["Median time to progression 14.3 vs 6.0 months; hazard ratio 0.34.","Benefit largest with hepatic tumour load of 10 percent or less."],"whatItMeans":"Octreotide LAR became a standard first-line antiproliferative therapy for small intestinal neuroendocrine tumours, later joined by lanreotide after CLARINET.","caveats":["Small trial that closed early for slow accrual.","No overall survival benefit because of crossover."],"changedPractice":true,"participants":85},{"id":"paper-ahmed-promis-multiparametric-mri-lancet-2017","kind":"paper","name":"PROMIS: diagnostic accuracy of multiparametric MRI and TRUS biopsy in prostate cancer","aka":["PROMIS","Ahmed 2017","PROMIS multiparametric MRI triage"],"tldr":"Every man with a raised PSA used to get a needle biopsy through the rectum, which misses half the serious cancers and can cause sepsis. This trial gave 576 men a scan, a standard biopsy and an exhaustive mapping biopsy, and showed the scan could safely spare a quarter of them the needle.","summary":"Hashim Ahmed, Mark Emberton and the PROMIS study group ran a paired-cohort confirmatory study in which men with prostate-specific antigen up to 15 nanograms per millilitre and no previous biopsy had 1.5 Tesla multiparametric magnetic resonance imaging, then both transrectal ultrasound-guided biopsy and template prostate mapping biopsy as the reference standard, each read blind to the others.\n\nThe design is the point. Comparing a scan against the biopsy it is meant to replace tells you nothing, because the biopsy is itself inaccurate; PROMIS compared both against an exhaustive mapping biopsy. The result, that the scan is far more sensitive and far less specific than the standard biopsy, is what made magnetic resonance imaging a triage test rather than a confirmatory one, and PRECISION the following year showed the pathway works in practice.","asOf":"2026-09-25","links":[{"label":"Lancet 2017","url":"https://doi.org/10.1016/s0140-6736(16)32401-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28110982/"},{"label":"ClinicalTrials.gov NCT01292291","url":"https://clinicaltrials.gov/study/NCT01292291"}],"tags":["prostate-evidence"],"related":["paper-precision-mri-targeted-biopsy-nejm-2018","paper-johnson-mpmri-individual-foci-eur-urol-2019","paper-goteborg-2-n-engl-j-med-2022","prostate-roadmap"],"cancers":["prostate","prostate-low-risk","prostate-intermediate-risk","prostate-high-risk"],"sections":["diagnostics","imaging","early-detection"],"technologies":["mri","prostate-screening-psa-mri"],"targets":[],"drugs":[],"companies":[],"institutions":["uclh"],"pathways":[],"terms":["psa","screening","gleason-grade-group","template-mapping-biopsy","pi-rads","whole-mount-pathology"],"trials":[],"people":["mark-emberton"],"bottlenecks":["b-overdiagnosis","b-early-detection","b-biomarker-validation"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2017,"doi":"10.1016/s0140-6736(16)32401-1","pmid":"28110982","authors":"Ahmed HU, El-Shater Bosaily A, Brown LC, et al.","paperType":"observational","findings":["Of 576 men completing all three tests, 408 (71 percent) had cancer on template mapping biopsy and 230 (40 percent) had clinically significant cancer.","For clinically significant cancer, multiparametric magnetic resonance imaging was more sensitive than transrectal ultrasound-guided biopsy (93 percent, 95 percent confidence interval 88 to 96, against 48 percent, 42 to 55; p less than 0.0001).","Magnetic resonance imaging was less specific than the biopsy (41 percent, 36 to 46, against 96 percent, 94 to 98; p less than 0.0001).","Using the scan to triage might allow 27 percent of men to avoid a primary biopsy and diagnose 5 percent fewer clinically insignificant cancers, and could detect up to 18 percent more cases of clinically significant cancer if subsequent biopsies were directed by the scan.","44 of 740 enrolled patients (5.9 percent) reported serious adverse events, including 8 cases of sepsis."],"whatItMeans":"The evidence that put a scan in front of the biopsy. It reduces the number of men who are biopsied at all, reduces the number of harmless cancers found, and increases the number of dangerous ones, which is the only combination that improves a screening pathway on both sides at once.","caveats":["Clinically significant cancer was defined as Gleason 4+3 or above, or a maximum cancer core length of 6 mm or more; a different definition changes the accuracy figures.","1.5 Tesla imaging read by expert radiologists in a trial setting; accuracy in routine services depends on scanner, protocol and reader, which is the argument for per-centre audit.","Template mapping biopsy is the best available reference standard but is not perfect, and 8 cases of sepsis in the study are a reminder that the reference standard has harms of its own."],"changedPractice":true,"participants":576},{"id":"paper-prophecy-arv7-validation-jco-2019","kind":"paper","name":"PROPHECY: prospective multicentre validation of androgen receptor splice variant 7 and hormone therapy resistance in high-risk castration-resistant prostate cancer","aka":[],"tldr":"A blinded study across several hospitals confirmed that men whose circulating tumour cells carry the shortened androgen receptor live less long on hormone tablets, on two different tests that agree with each other four times in five.","summary":"PROPHECY was a multicentre, prospective, blinded study of men with high-risk metastatic castration-resistant prostate cancer starting abiraterone acetate or enzalutamide. The primary objective was to validate the prognostic significance of baseline circulating tumour cell AR-V7 using the Johns Hopkins University modified AdnaTest messenger RNA assay and the Epic Sciences nuclear-specific AR-V7 protein assay. One hundred and eighteen men were enrolled. AR-V7 detection by both assays was independently associated with shorter progression-free survival, hazard ratios 1.9 and 2.4, and with shorter overall survival, hazard ratios 4.2 and 3.5, after adjusting for circulating tumour cell number and clinical prognostic factors. AR-V7-positive men had confirmed PSA responses in 0 to 11% and soft-tissue responses in 0 to 6%. The observed percentage agreement between the two assays was 82%.","asOf":"2026-09-25","links":[{"label":"Armstrong et al., J Clin Oncol 2019: PROPHECY, prospective multicentre validation of circulating tumour cell AR-V7 in 118 men with high-risk mCRPC","url":"https://doi.org/10.1200/JCO.18.01731"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30865549/"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["liquid-biopsy"],"targets":["androgen-receptor"],"drugs":[],"companies":[],"institutions":[],"pathways":["ar-signaling","rna-splicing","intravasation-ctc-survival","resistance-routes-map"],"terms":["ar-v7","liquid-biopsy","castration-resistance","resistance","psa50"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2019,"doi":"10.1200/JCO.18.01731","pmid":"30865549","authors":"Armstrong AJ, Halabi S, Luo J, et al.","paperType":"observational","findings":["Independent association with shorter progression-free survival on both assays (hazard ratios 1.9 and 2.4).","Independent association with shorter overall survival (hazard ratios 4.2 and 3.5).","Confirmed PSA responses in 0 to 11% of AR-V7-positive men.","Agreement between the two assays 82%."],"whatItMeans":"It turned a single-centre observation into a prospectively validated one and concluded that AR-V7-positive men should be offered alternatives to abiraterone and enzalutamide. It also quantified the honest limit: two assays for the same analyte disagree on nearly one sample in five.","caveats":["A high-risk enriched population, so the prevalence does not generalise to all castration-resistant disease.","Prognostic and not, on its own, a randomised demonstration that changing treatment helps.","Still not in any label, and available only at specialist centres."],"changedPractice":false,"participants":118},{"id":"paper-auperin-prophylactic-cranial-irradiation-sclc-nejm-1999","kind":"paper","name":"Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission","aka":[],"tldr":"Pooling 987 patients from seven trials showed that irradiating the brain of people whose small-cell lung cancer had gone into remission, before any brain secondaries appeared, made them live longer.","summary":"Aupérin, Arriagada, Pignon, Le Péchoux and the Prophylactic Cranial Irradiation Overview Collaborative Group analysed individual data on 987 patients with small-cell lung cancer in complete remission from seven trials comparing prophylactic cranial irradiation with none. Survival was the main endpoint.\n\nIt is one of the few interventions in oncology that treats an organ with no detectable disease in it and extends life, and the principle it established, that micrometastatic sanctuary sites can be treated pre-emptively, is the direct ancestor of the brain metastasis prevention question that next-generation ALK and EGFR inhibitors now raise.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 1999","url":"https://doi.org/10.1056/NEJM199908123410703"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/10441603/"}],"tags":["lung-evidence"],"related":["paper-slotman-n-engl-j-med","paper-turrisi-twice-daily-thoracic-radiotherapy-limited-sclc-nejm-1999","idea-bio2-brain-met-prevention-trials"],"cancers":["lung-cancer","sclc","limited-stage-sclc","extensive-stage-sclc"],"sections":["radiation"],"technologies":["radiotherapy","stereotactic-radiosurgery"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["brain-metastases","prophylactic-cranial-irradiation","mrd"],"trials":[],"people":[],"bottlenecks":["b-brain-delivery","b-dormancy-mrd","b-toxicity-qol"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":1999,"doi":"10.1056/NEJM199908123410703","pmid":"10441603","authors":"Aupérin A, Arriagada R, Pignon JP, et al.","paperType":"meta-analysis","findings":["Relative risk of death 0.84 (95 percent confidence interval 0.73 to 0.97; P equals 0.01), corresponding to a 5.4 percentage point increase in three-year survival, from 15.3 percent to 20.7 percent.","Relative risk of recurrence or death 0.75 (0.65 to 0.86).","Individual data on 987 patients in complete remission from seven randomised trials."],"whatItMeans":"Treating the brain before the cancer gets there works in small-cell lung cancer, and it is the proof of principle behind every later attempt to prevent rather than treat brain metastases.","caveats":["Trials from before routine brain MRI, so some patients classified as having no brain disease would today be found to have it.","Neurocognitive effects were not measured with modern instruments, and hippocampal-avoidance techniques did not exist; the risk-benefit calculation has shifted.","Extensive-stage disease was addressed separately and remains contested, with the Japanese trial finding no survival benefit when MRI surveillance is used instead."],"changedPractice":true,"participants":987},{"id":"paper-slotman-n-engl-j-med","kind":"paper","name":"Prophylactic cranial irradiation in extensive small-cell lung cancer","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 17699816 and published in New England Journal of Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Background: We conducted a randomized trial of prophylactic cranial irradiation in patients with extensive small-cell lung cancer who had had a response to chemotherapy.\n\nMethods: Patients between the ages of 18 and 75 years with extensive small-cell lung cancer were randomly assigned to undergo prophylactic cranial irradiation (irradiation group) or receive no further therapy (control group). The primary end point was the time to symptomatic brain metastases. Computed tomography or magnetic resonance imaging of the brain was performed when any predefined key symptom suggestive of brain metastases was present.\n\nResults: The two groups (each with 143 patients) were well balanced regarding baseline characteristics. Patients in the irradiation group had a lower risk of symptomatic brain metastases (hazard ratio, 0.27; 95% confidence interval [CI], 0.16 to 0.44; P<0.001). The cumulative risk of brain metastases within 1 year was 14.6% in the irradiation group (95% CI, 8.3 to 20.9) and 40.4% in the control group (95% CI, 32.1 to 48.6). Irradiation was associated with an increase in median disease-free survival from 12.0 weeks to 14.7 weeks and in median overall survival from 5.4 months to 6.7 months after randomization. The 1-year survival rate was 27.1% (95% CI, 19.4 to 35.5) in the irradiation group and 13.3% (95% CI, 8.1 to 19.9) in the control group. Irradiation had side effects but did not have a clinically significant effect on global health status.\n\nConclusions: Prophylactic cranial irradiation reduces the incidence of symptomatic brain metastases and prolongs disease-free and overall survival. (ClinicalTrials.gov number, NCT00016211 [ClinicalTrials.gov].).\n\nIndexed on Europe PMC as PubMed record 17699816 (DOI 10.1056/nejmoa071780). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2007","url":"https://doi.org/10.1056/nejmoa071780"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/17699816/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/17699816"}],"tags":["europepmc-ingest"],"related":["lung-cancer-evidence-roadmap","paper-auperin-prophylactic-cranial-irradiation-sclc-nejm-1999"],"cancers":["lung-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["slotman-pci-es-sclc"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2007,"doi":"10.1056/nejmoa071780","pmid":"17699816","authors":"Slotman B, Faivre-Finn C, Kramer G, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-takahashi-lancet-oncol","kind":"paper","name":"Prophylactic cranial irradiation versus observation in patients with extensive-disease small-cell lung cancer: a multicentre, randomised, open-label, phase 3 trial","aka":[],"tldr":"Paper cited by one trial page and one idea page, indexed on Europe PMC as PubMed record 28343976 and published in The Lancet Oncology; the citing pages link this DOI, which is how the record was matched.","summary":"Background: Results from a previous phase 3 study suggested that prophylactic cranial irradiation reduces the incidence of symptomatic brain metastases and prolongs overall survival compared with no prophylactic cranial irradiation in patients with extensive-disease small-cell lung cancer. However, because of the absence of brain imaging before enrolment and variations in chemotherapeutic regimens and irradiation doses, concerns have been raised about these findings. We did a phase 3 trial to reassess the efficacy of prophylactic cranial irradiation in the treatment of extensive-disease small-cell lung cancer.\n\nMethods: We did this randomised, open-label, phase 3 study at 47 institutions in Japan. Patients with extensive-disease small-cell lung cancer who had any response to platinum-based doublet chemotherapy and no brain metastases on MRI were randomly assigned (1:1) to receive prophylactic cranial irradiation (25 Gy in ten daily fractions of 2·5 Gy) or observation. All patients were required to have brain MRI at 3-month intervals up to 12 months and at 18 and 24 months after enrolment. Randomisation was done by computer-generated allocation sequence, with age as a stratification factor and minimisation by institution, Eastern Cooperative Oncology Group performance status, and response to initial chemotherapy. The primary endpoint was overall survival, analysed in the intention-to-treat population. This trial is registered with the UMIN Clinical Trials Registry, number UMIN000001755, and is closed to new participants.\n\nFindings: Between April 3, 2009, and July 17, 2013, 224 patients were enrolled and randomly assigned (113 to prophylactic cranial irradiation and 111 to observation). In the planned interim analysis on June 18, 2013, of the first 163 enrolled patients, Bayesian predictive probability of prophylactic cranial irradiation being superior to observation was 0·011%, resulting in early termination of the study because of futility. In the final analysis, median overall survival was 11·6 months (95% CI 9·5-13·3) in the prophylactic cranial irradiation group and 13·7 months (10·2-16·4) in the observation group (hazard ratio 1·27, 95% CI 0·96-1·68; p=0·094). The most frequent grade 3 or worse adverse events at 3 months were anorexia (six [6%] of 106 in the prophylactic cranial irradiation group vs two [2%] of 111 in the observation group), malaise (three [3%] vs one [<1%]), and muscle weakness in a lower limb (one [<1%] vs six [5%]). No treatment-related deaths occurred in either group.\n\nInterpretation: In this Japanese trial, prophylactic cranial irradiation did not result in longer overall survival compared with observation in patients with extensive-disease small-cell lung cancer. Prophylactic cranial irradiation is therefore not essential for patients with extensive-disease small-cell lung cancer with any response to initial chemotherapy and a confirmed absence of brain metastases when patients receive periodic MRI examination during follow-up.\n\nFunding: The Ministry of Health, Labour and Welfare of Japan.\n\nIndexed on Europe PMC as PubMed record 28343976 (DOI 10.1016/s1470-2045(17)30230-9). Matched by DOI alone: one trial page and one idea page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2017","url":"https://doi.org/10.1016/s1470-2045(17)30230-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28343976/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28343976"}],"tags":["europepmc-ingest"],"related":["idea-mri-surveillance-replaces-pci"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["takahashi-pci"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2017,"doi":"10.1016/s1470-2045(17)30230-9","pmid":"28343976","authors":"Takahashi T, Yamanaka T, Seto T, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page and one idea page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-islami-ca-cancer-j-clin","kind":"paper","name":"Proportion and number of cancer cases and deaths attributable to potentially modifiable risk factors in the United States","aka":[],"tldr":"Paper cited by one bottleneck page and 27 idea pages, indexed on Europe PMC as PubMed record 29160902 and published in CA: A Cancer Journal for Clinicians; the citing pages link this DOI, which is how the record was matched.","summary":"Contemporary information on the fraction of cancers that potentially could be prevented is useful for priority setting in cancer prevention and control. Herein, the authors estimate the proportion and number of invasive cancer cases and deaths, overall (excluding nonmelanoma skin cancers) and for 26 cancer types, in adults aged 30 years and older in the United States in 2014, that were attributable to major, potentially modifiable exposures (cigarette smoking; secondhand smoke; excess body weight; alcohol intake; consumption of red and processed meat; low consumption of fruits/vegetables, dietary fiber, and dietary calcium; physical inactivity; ultraviolet radiation; and 6 cancer-associated infections). The numbers of cancer cases were obtained from the Centers for Disease Control and Prevention (CDC) and the National Cancer Institute; the numbers of deaths were obtained from the CDC; risk factor prevalence estimates were obtained from nationally representative surveys; and associated relative risks of cancer were obtained from published, large-scale pooled analyses or meta-analyses. In the United States in 2014, an estimated 42.0% of all incident cancers (659,640 of 1570,975 cancers, excluding nonmelanoma skin cancers) and 45.1% of cancer deaths (265,150 of 587,521 deaths) were attributable to evaluated risk factors. Cigarette smoking accounted for the highest proportion of cancer cases (19.0%; 298,970 cases) and deaths (28.8%; 169,180 deaths), followed by excess body weight (7.8% and 6.5%, respectively) and alcohol intake (5.6% and 4.0%, respectively). Lung cancer had the highest number of cancers (184,970 cases) and deaths (132,960 deaths) attributable to evaluated risk factors, followed by colorectal cancer (76,910 cases and 28,290 deaths). These results, however, may underestimate the overall proportion of cancers attributable to modifiable factors, because the impact of all established risk factors could not be quantified, and many likely modifiable risk factors are not yet firmly established as causal. Nevertheless, these findings underscore the vast potential for reducing cancer morbidity and mortality through broad and equitable implementation of known preventive measures. CA Cancer J Clin 2018;68:31-54. © 2017 American Cancer Society.\n\nIndexed on Europe PMC as PubMed record 29160902 (DOI 10.3322/caac.21440). Matched by DOI alone: one bottleneck page and 27 idea pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"CA Cancer J Clin 2018","url":"https://doi.org/10.3322/caac.21440"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29160902/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29160902"}],"tags":["europepmc-ingest"],"related":["b-prevention-adoption","idea-prev-therapeutic-hpv-vaccine-cin","idea-prev-glp1-cancer-prevention-rct","idea-prev-hpylori-childhood-vaccine","idea-prev-ebv-vaccine","idea-prev-hpylori-stool-resistance-guided","idea-prev-commercial-sunbed-ban","idea-prev-alcohol-cancer-warning-labels","idea-prev-hpv-male-catchup-oropharynx","idea-prev-pharmacy-prevention-hub","idea-nl-upf-controlled-feeding-trial","idea-prev-hcv-test-treat-surveillance-linkage","idea-nl-alcohol-minimum-pricing-cancer-endpoints","idea-prev-clean-air-never-smoker-endpoints","idea-prev-opt-out-cessation-in-lung-screening","idea-prev-hpylori-family-test-and-treat","idea-prev-glp1-endometrial-hyperplasia","idea-prev-low-dose-tamoxifen-uptake","idea-prev-radon-testing-at-property-sale","idea-prev-minimum-unit-pricing-cancer-endpoints","idea-prev-hpv-vaccinate-at-screening","idea-prev-chemoprevention-master-protocol","idea-prev-pay-for-prevention-outcomes","idea-prev-hpv-self-sampling-mailed-default","idea-prev-cytisine-essential-medicine","idea-prev-precursor-endpoints-for-approval","idea-prev-opportunistic-salpingectomy-default","idea-prev-screening-default-appointments"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["ca-cancer-journal"],"dependsOn":[],"notes":[],"journal":"CA: A Cancer Journal for Clinicians","year":2018,"doi":"10.3322/caac.21440","pmid":"29160902","authors":"Islami F, Goding Sauer A, Miller KD, et al.","paperType":"observational","findings":[],"whatItMeans":"One bottleneck page and 27 idea pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-epstein-neuroendocrine-prostate-morphologic-classification-ajsp-2014","kind":"paper","name":"Proposed morphologic classification of prostate cancer with neuroendocrine differentiation","aka":[],"tldr":"A working committee sorted the confusing family of neuroendocrine prostate cancers into named categories, so that a few scattered stained cells would stop being reported in the same words as a small cell carcinoma.","summary":"A Prostate Cancer Foundation working committee on the molecular biology and pathologic classification of neuroendocrine differentiation in prostate cancer convened in July 2013, prompted by clinical and molecular data emerging from prostate cancers treated with contemporary androgen deprivation therapies as well as from primary lesions. The resulting classification comprises usual prostate adenocarcinoma with neuroendocrine differentiation; adenocarcinoma with Paneth cell neuroendocrine differentiation; carcinoid tumour; small cell carcinoma; large cell neuroendocrine carcinoma; and mixed neuroendocrine carcinoma with acinar adenocarcinoma. The article also highlights prostate carcinoma with overlapping features of small cell carcinoma and acinar adenocarcinoma, and castration-resistant prostate cancer with a small cell cancer-like clinical presentation.","asOf":"2026-09-25","links":[{"label":"Epstein et al., Am J Surg Pathol 2014: proposed morphologic classification of prostate cancer with neuroendocrine differentiation (Prostate Cancer Foundation working committee)","url":"https://doi.org/10.1097/PAS.0000000000000208"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24705311/"}],"tags":[],"related":[],"cancers":["prostate","prostate-nepc"],"sections":[],"technologies":["histopathology-ihc"],"targets":["androgen-receptor"],"drugs":[],"companies":[],"institutions":[],"pathways":["lineage-plasticity-neuroendocrine"],"terms":["histologic-transformation","ihc","castration-resistance"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"American Journal of Surgical Pathology","year":2014,"doi":"10.1097/PAS.0000000000000208","pmid":"24705311","authors":"Epstein JI, Amin MB, Beltran H, et al.","paperType":"guideline","findings":["Six named categories of prostate cancer with neuroendocrine differentiation.","Two further descriptive situations for tumours with overlapping features and for clinically small cell-like castration-resistant disease.","A separation between incidental neuroendocrine staining in ordinary adenocarcinoma and a true neuroendocrine carcinoma."],"whatItMeans":"It made the reporting of these tumours mean something. The distinction it draws is the one that changes treatment: a few chromogranin-positive cells in an ordinary adenocarcinoma is not the same event as a small cell carcinoma emerging under hormonal treatment, and only the second leads to platinum and etoposide.","caveats":["A consensus proposal rather than an outcome study.","The categories were defined before the molecular phenotyping that has since split the androgen receptor-null tumours further.","Interobserver reproducibility of the categories has not been extensively tested."],"changedPractice":true},{"id":"paper-propsma-hofman-lancet-2020","kind":"paper","name":"proPSMA: PSMA PET-CT versus conventional imaging for staging high-risk prostate cancer","aka":[],"tldr":"PSMA PET-CT was 27 percentage points more accurate than CT and bone scan for finding spread in men with high-risk prostate cancer before treatment, with less radiation and more influence on management, and it has replaced conventional imaging where available.","summary":"Randomised multicentre trial of 302 men with high-risk localised prostate cancer randomised to conventional imaging (CT and bone scan) or gallium-68 PSMA PET-CT for staging, with crossover imaging to define a reference standard.\n\nAccuracy was 92 percent for PSMA PET-CT against 65 percent for conventional imaging, with higher sensitivity (85 versus 38 percent) and specificity, fewer equivocal results, lower radiation dose and more frequent management change.","asOf":"2026-09-17","links":[{"label":"Lancet 2020","url":"https://doi.org/10.1016/S0140-6736(20)30314-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32209449/"}],"tags":[],"related":["prostate-roadmap"],"cancers":["prostate-bcr","prostate-high-risk","prostate"],"sections":[],"technologies":["psma-pet","pet-ct"],"targets":["psma"],"drugs":[],"companies":[],"institutions":[],"pathways":["prostate-cancer-signalling"],"terms":["theranostics"],"trials":["propsma"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2020,"doi":"10.1016/S0140-6736(20)30314-7","pmid":"32209449","authors":"Hofman MS, Lawrentschuk N, Francis RJ, et al.","paperType":"rct","findings":["Accuracy 92 percent vs 65 percent (27 percent absolute difference).","Sensitivity 85 percent vs 38 percent; specificity 98 percent vs 91 percent."],"whatItMeans":"PSMA PET-CT is the preferred staging investigation for high-risk prostate cancer and for biochemical recurrence, though most treatment trials were designed with conventional imaging.","caveats":["Reference standard relied partly on imaging follow-up rather than histology.","Detecting more disease does not by itself prove better outcomes."],"changedPractice":true,"participants":302},{"id":"paper-brca-risk-reducing-surgery-jama-2010","kind":"paper","name":"PROSE consortium: preventive surgery lowers cancer and death in BRCA1 and BRCA2 carriers","aka":[],"tldr":"Among 2,482 women with BRCA1 or BRCA2 mutations, removing the ovaries and fallopian tubes was associated with 60% lower all-cause mortality, and no breast cancers occurred in the women who had preventive mastectomy.","summary":"The PROSE consortium followed 2,482 women with a BRCA1 or BRCA2 mutation at 22 centres in Europe and North America from 1974 to 2008, comparing outcomes in those who did and did not undergo risk-reducing mastectomy (RRM) or risk-reducing salpingo-oophorectomy (RRSO).\n\nNo breast cancers were diagnosed in the 247 women who had RRM over 3 years of follow-up, compared with 98 in the 1,372 who did not. RRSO was associated with lower risk of ovarian cancer, of first breast cancer in BRCA1 carriers, and with reduced all-cause mortality (10% vs 3%), breast cancer-specific mortality and ovarian cancer-specific mortality.\n\nIt was the first study to link risk-reducing surgery to a survival advantage and cemented RRSO as the standard recommendation for carriers by age 35-40 (BRCA1) or 40-45 (BRCA2).","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1001/jama.2010.1237"}],"tags":[],"related":["idea-moon-population-germline-screening","idea-prev-population-germline-screening-at-30","idea-prev-brca1-denosumab-prevention"],"cancers":["ovarian","breast-hr-positive","tnbc"],"sections":["prevention","surgery"],"technologies":["germline-testing"],"targets":["brca"],"drugs":[],"companies":[],"institutions":["penn-abramson"],"pathways":[],"terms":["germline-vs-somatic"],"trials":[],"people":["susan-domchek"],"bottlenecks":["b-hereditary-risk","b-prevention-adoption"],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2010,"doi":"10.1001/jama.2010.1237","pmid":"20810374","authors":"Domchek SM, Friebel TM, Singer CF, et al.","paperType":"observational","findings":["Risk-reducing mastectomy: 0 breast cancers in 247 women vs 98 in 1,372 without surgery","RRSO associated with lower all-cause mortality: 3% vs 10% (HR 0.40, 95% CI 0.26-0.61)","RRSO associated with lower breast cancer-specific mortality (HR 0.44) and ovarian cancer-specific mortality (HR 0.21)","RRSO reduced ovarian cancer risk in women with no prior breast cancer (HR 0.28 in BRCA1 carriers)"],"whatItMeans":"For women who carry a BRCA mutation, preventive removal of the ovaries and tubes saves lives, and preventive mastectomy almost eliminates breast cancer. These are the strongest prevention effects in oncology, which is why finding carriers before they develop cancer matters so much.","caveats":["Observational; women choosing surgery may differ from those who do not (healthy-adopter bias)","Follow-up after RRM was short (about 3 years)","Surgical menopause has cardiovascular, bone and quality-of-life costs not captured here","Later analyses questioned whether RRSO reduces breast cancer risk once ascertainment bias is addressed"],"changedPractice":true,"participants":2482},{"id":"paper-prospect-nejm-2023","kind":"paper","name":"PROSPECT: neoadjuvant FOLFOX with selective use of chemoradiotherapy for locally advanced rectal cancer","aka":[],"tldr":"For rectal cancers of intermediate risk suitable for sphincter-sparing surgery, six cycles of FOLFOX chemotherapy, with radiotherapy only if the tumour did not shrink, was as effective as routine chemoradiation and spared nine in ten patients pelvic radiotherapy.","summary":"Phase 3 non-inferiority trial of 1,194 patients with cT2 node-positive, cT3 node-negative or cT3 node-positive rectal cancer candidates for sphincter-sparing surgery, randomised to neoadjuvant FOLFOX with chemoradiotherapy only for poor response, or standard pelvic chemoradiotherapy.\n\nFive-year disease-free survival was 80.8 versus 78.6 percent (non-inferior), local recurrence 1.8 versus 1.6 percent, and only 9 percent of FOLFOX patients needed chemoradiotherapy; quality of life differed in bowel, sexual and neuropathy domains by arm.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2023","url":"https://doi.org/10.1056/NEJMoa2303269"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37272534/"}],"tags":[],"related":[],"cancers":["rectal-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["prospect"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/NEJMoa2303269","pmid":"37272534","authors":"Schrag D, Shi Q, Weiser MR, et al.","paperType":"rct","findings":["Five-year disease-free survival 80.8 percent vs 78.6 percent (non-inferior).","Chemoradiotherapy avoided in 91 percent of the FOLFOX arm."],"whatItMeans":"Selected patients with intermediate-risk rectal cancer can avoid radiotherapy altogether, with chemotherapy alone before surgery, trading neuropathy for better long-term bowel and sexual function.","caveats":["Excluded T4 tumours, threatened mesorectal fascia and low tumours needing abdominoperineal resection.","Non-inferiority margin allowed a modest loss of efficacy."],"changedPractice":true,"participants":1194},{"id":"paper-chung-comprehensive-genomic-profiling-prostate-jco-po-2019","kind":"paper","name":"Prospective comprehensive genomic profiling of 3,476 primary and metastatic prostate tumours","aka":["Chung 2019","FoundationOne prostate 3476","real-world prostate genomic profiling"],"tldr":"The largest routine-practice picture of what is broken in prostate tumours. Across 3,476 samples sent for commercial sequencing, TP53 was altered in 44 percent and PTEN in 32 percent, and just over half carried something a drug is being developed against.","summary":"Jon Chung, Jeffrey Ross and colleagues at Foundation Medicine analysed 3,476 clinically advanced prostate tumours sent for comprehensive genomic profiling, 1,660 from primary sites and 1,816 from metastases in unmatched patients, and reported both gene-level alterations and genome-wide signatures: loss of heterozygosity, microsatellite instability and tumour mutational burden.\n\nThis is the real-world counterpart to TCGA and the SU2C cohort, and it is the right citation for what a clinician actually sees on a report. It also makes two points the research cohorts do not. Median tumour mutational burden is low at 2.6 mutations per megabase and only 3 percent of tumours are high, of which 71 percent are also microsatellite-unstable, which is why immunotherapy fails in this disease. And CDK12-altered tumours, unlike BRCA and ATR-altered ones, are infrequently high for genome-wide loss of heterozygosity, so they are not homologous recombination deficient in the sense PARP inhibitors need.","asOf":"2026-09-25","links":[{"label":"JCO Precis Oncol 2019","url":"https://doi.org/10.1200/po.18.00283"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31218271/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31218271"}],"tags":["prostate-evidence"],"related":["paper-robinson-integrative-clinical-genomics-advanced-prostate-cell-2015","paper-antonarakis-keynote-199-pembrolizumab-jco-2020","paper-fizazi-triton3-rucaparib-nejm-2023","prostate-roadmap"],"cancers":["prostate","prostate-mcrpc","prostate-mhspc"],"sections":["diagnostics","targeted-therapy"],"technologies":[],"targets":["tp53","pten","erg","tmprss2","androgen-receptor","brca","cdk12","rb1","pik3ca"],"drugs":[],"companies":["foundation-medicine"],"institutions":[],"pathways":[],"terms":["hrd","tmb","msi","ngs","genome-wide-loss-of-heterozygosity","chromoplexy"],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation","b-immunotherapy-response","b-real-world-evidence"],"keyPapers":[],"journals":["jco-precision-oncology"],"dependsOn":[],"notes":[],"journal":"JCO Precision Oncology","year":2019,"doi":"10.1200/po.18.00283","pmid":"31218271","authors":"Chung JH, Dewal N, Sokol E, et al.","paperType":"real-world","findings":["Frequently altered genes across 3,476 tumours were TP53 (44 percent), PTEN (32 percent), TMPRSS2-ERG (31 percent) and the androgen receptor (23 percent).","DNA repair pathway alterations included homologous recombination repair (23 percent), Fanconi anaemia (5 percent), CDK12 (6 percent) and mismatch repair (4 percent).","BRCA1 and BRCA2, ATR and FANCA alterations were associated with high genome-wide loss of heterozygosity, whereas CDK12-altered tumours were infrequently loss-of-heterozygosity high.","Median tumour mutational burden was low at 2.6 mutations per megabase; 3 percent of cases were tumour mutational burden high, of which 71 percent also had high microsatellite instability.","Metastatic site tumours were enriched for the 11q13 amplicon (CCND1, FGF19, FGF4, FGF3) and for alterations in the androgen receptor, LYN, MYC, NCOR1, PIK3CB and RB1 compared with primary tumours; alterations that are investigational biomarkers for targeted therapies were identified in 57 percent of cases."],"whatItMeans":"What a prostate cancer sequencing report looks like in practice, and the numerical basis for two clinical rules: do not expect checkpoint immunotherapy to work unless the tumour is mismatch repair deficient, and do not treat a CDK12 alteration as if it were a BRCA alteration.","caveats":["Commercial sequencing referrals, so the cohort is selected by who was tested and cannot give population prevalences.","No clinical outcome data are linked, which the authors name as the study's main limitation.","Primary and metastatic samples come from different, unmatched patients, so the enrichment seen in metastases is a between-group comparison rather than a within-patient evolution."],"changedPractice":false,"participants":3476},{"id":"paper-jordan-prospective-lung-adenocarcinoma-msk-cancer-discov-2017","kind":"paper","name":"Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies","aka":[],"tldr":"Sequencing 860 patients with advanced lung adenocarcinoma as they arrived in clinic answered a question nobody had measured: how many of them actually get a treatment because of the test. Just over a third did.","summary":"Eight hundred and sixty patients with metastatic lung adenocarcinoma were analysed prospectively for mutations in more than 300 cancer-associated genes. Potentially actionable genetic events were stratified into four levels by the published evidence that the alteration confers sensitivity to a standard or investigational therapy. Overall, 319 of 860 patients, 37.1%, received a matched therapy guided by the molecular profile. Excluding alterations already associated with standard-of-care therapy, 69 of 478 patients, 14.4%, received matched therapy, with clinical benefit in 52% of them. Use of matched therapy was strongly influenced by the level of pre-existing evidence that the alteration predicts drug response. Analysis of genes mutated significantly more often in tumours without a known actionable alteration nominated STK11 and KEAP1 as possible targetable mitogenic drivers.","asOf":"2026-09-25","links":[{"label":"Jordan et al., Cancer Discov 2017: prospective molecular characterisation of 860 metastatic lung adenocarcinomas (MSK-IMPACT)","url":"https://doi.org/10.1158/2159-8290.CD-16-1337"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28336552/"},{"label":"cBioPortal study lung_msk_2017 (MSK, Cancer Discov 2017; 915 MSK-IMPACT samples from the 860 prospectively sequenced metastatic lung adenocarcinomas)","url":"https://www.cbioportal.org/study/summary?id=lung_msk_2017"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":["cgp"],"targets":["egfr","kras","alk","met","her2","braf","stk11","keap1","ret","ros1"],"drugs":[],"companies":[],"institutions":["mskcc"],"pathways":["nsclc-signalling","rtk-activation","ras-mapk"],"terms":["driver-mutation","ngs","stk11-keap1"],"trials":[],"people":["gregory-riely"],"bottlenecks":[],"keyPapers":[],"journals":["cancer-discovery"],"dependsOn":[],"notes":[],"journal":"Cancer Discovery","year":2017,"doi":"10.1158/2159-8290.CD-16-1337","pmid":"28336552","authors":"Jordan EJ, Kim HR, Arcila ME, et al.","paperType":"observational","findings":["37.1% of prospectively sequenced patients received a therapy matched to the result.","Outside standard-of-care alterations, 14.4% received a matched therapy, with benefit in 52%.","The level of published evidence, not the presence of the alteration, determined whether treatment followed.","STK11 and KEAP1 emerged as the recurrent alterations in tumours with no other actionable driver."],"whatItMeans":"It is the honest accounting of precision oncology in the disease where it works best: broad sequencing changes treatment for about one patient in three, and the bottleneck is evidence rather than detection.","caveats":["A single referral centre with early access to trials, so the matched-therapy rate is a ceiling rather than an average.","Benefit was assessed without a control group.","Panel sequencing, so fusion and copy-number detection depend on the panel's design."],"changedPractice":false,"participants":860},{"id":"paper-lowery-prospective-germline-exocrine-pancreatic-jnci-2018","kind":"paper","name":"Prospective evaluation of germline alterations in patients with exocrine pancreatic neoplasms","aka":[],"tldr":"Offering a 76-gene inherited-risk test to 615 consecutive pancreatic tumour patients at Memorial Sloan Kettering found a pathogenic variant in one in five, more than 40% of whom would not have qualified for testing under the guidelines of the time.","summary":"615 unselected patients with exocrine pancreatic neoplasms consented to somatic tumour and matched normal profiling of 410 to 468 genes; germline testing of 76 susceptibility genes was performed in an identified manner in 356 and anonymised in 259. Pathogenic germline alterations were present in 122 (19.8%) across 24 genes including BRCA1/2, ATM, PALB2 and other DNA damage response genes; 41.8% did not meet then-current testing guidelines. Median overall survival did not differ by germline status (50.8 months carriers). Loss of heterozygosity was found in 60.0% of BRCA1/2 tumours. The alterations were judged therapeutically actionable in about 5 to 10% of patients.","asOf":"2026-09-24","links":[{"label":"Lowery et al., JNCI 2018: prospective germline testing of 615 exocrine pancreatic neoplasms (MSK)","url":"https://doi.org/10.1093/jnci/djy024"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29506128/"}],"tags":[],"related":["brca-germline"],"cancers":["pancreatic","brca-palb2-pdac"],"sections":[],"technologies":["germline-testing"],"targets":["brca","atm","palb2"],"drugs":[],"companies":[],"institutions":["mskcc"],"pathways":[],"terms":["gbrca-mutation","vus"],"trials":[],"people":["maeve-lowery","eileen-oreilly"],"bottlenecks":[],"keyPapers":[],"journals":["jnci"],"dependsOn":[],"notes":[],"journal":"JNCI: Journal of the National Cancer Institute","year":2018,"doi":"10.1093/jnci/djy024","pmid":"29506128","authors":"Lowery MA, Wong W, Jordan EJ, et al.","paperType":"observational","findings":["Pathogenic germline alteration in 19.8% of 615 on a 76-gene panel.","41.8% of carriers outside testing guidelines; 60% of BRCA1/2 tumours showed loss of heterozygosity."],"whatItMeans":"The broad-panel figure: one patient in five carries something inheritable, and about one in fifteen carries something treatable.","caveats":["Includes non-ductal exocrine neoplasms; 76 genes include moderate-penetrance genes.","Single tertiary centre."],"changedPractice":true,"participants":615},{"id":"paper-szmulewitz-j-clin-oncol","kind":"paper","name":"Prospective International Randomized Phase II Study of Low-Dose Abiraterone With Food Versus Standard Dose Abiraterone In Castration-Resistant Prostate Cancer","aka":[],"tldr":"Paper cited by one idea page, indexed on Europe PMC as PubMed record 29590007 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose Abiraterone acetate (AA) is a standard of care for metastatic castration-resistant prostate cancer (CRPC). Despite a large food effect, AA was administered under fasting conditions in its pivotal trials. We sought to test the hypothesis that low-dose AA (LOW; 250 mg with a low-fat meal) would have comparable activity to standard AA (STD; 1,000 mg fasting) in patients with CRPC. Patients and Methods Patients (n = 72) with progressive CRPC from seven institutions in the United States and Singapore were randomly assigned to STD or LOW. Both arms received prednisone 5 mg twice daily. Prostate-specific antigen (PSA) was assessed monthly, and testosterone/dehydroepiandrosterone sulfate were assessed every 12 weeks with disease burden radiographic assessments. Plasma was collected for drug concentrations. Log change in PSA, as a pharmacodynamic biomarker for efficacy, was the primary end point, using a noninferiority design. Progression-free survival (PFS), PSA response (≥ 50% reduction), change in androgen levels, and pharmacokinetics were secondary end points. Results Thirty-six patients were accrued to both arms. At 12 weeks, there was a greater effect on PSA in the LOW arm (mean log change, -1.59) compared with STD (-1.19), and noninferiority of LOW was established according to predefined criteria. The PSA response rate was 58% in LOW and 50% in STD, and the median PFS was approximately 9 months in both groups. Androgen levels decreased similarly in both arms. Although there was no difference in PSA response or PFS, abiraterone concentrations were higher in STD. Conclusion Low-dose AA (with low-fat breakfast) is noninferior to standard dosing with respect to PSA metrics. Given the pharmacoeconomic implications, these data warrant consideration by prescribers, payers, and patients. Additional studies are indicated to assess the long-term efficacy of this approach.\n\nIndexed on Europe PMC as PubMed record 29590007 (DOI 10.1200/jco.2017.76.4381). Matched by DOI alone: one idea page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2018","url":"https://doi.org/10.1200/jco.2017.76.4381"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29590007/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29590007"}],"tags":["europepmc-ingest"],"related":["idea-cost-low-dose-abiraterone-food"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2018,"doi":"10.1200/jco.2017.76.4381","pmid":"29590007","authors":"Szmulewitz RZ, Peer CJ, Ibraheem A, et al.","paperType":"rct","findings":[],"whatItMeans":"One idea page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-barth-phyllodes-adjuvant-radiotherapy-ann-surg-oncol-2009","kind":"paper","name":"Prospective multi-institutional study of adjuvant radiotherapy after resection of borderline and malignant phyllodes tumours","aka":[],"tldr":"In a prospective study, no woman whose borderline or malignant phyllodes tumour was excised with clear margins and then given radiotherapy had a local recurrence, supporting radiotherapy after breast-conserving surgery for these tumours.","summary":"Prospective study of 46 women with borderline or malignant phyllodes tumours treated with margin-negative breast-conserving resection followed by adjuvant radiotherapy.\n\nWith a median follow-up of 56 months there were no local recurrences, compared with historical local recurrence rates of 15 to 30 percent after surgery alone, though distant metastases occurred in a small number of malignant cases.","asOf":"2026-09-17","links":[{"label":"Ann Surg Oncol 2009","url":"https://doi.org/10.1245/s10434-009-0489-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19424757/"}],"tags":[],"related":[],"cancers":["phyllodes-tumour"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-surgical-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of surgical oncology","year":2009,"doi":"10.1245/s10434-009-0489-2","pmid":"19424757","authors":"Barth RJ, Wells WA, Mitchell SE, et al.","paperType":"observational","findings":["Local recurrence 0 percent at a median of 56 months after resection plus radiotherapy."],"whatItMeans":"Adjuvant radiotherapy is considered after breast conservation for borderline and malignant phyllodes tumours; it does not address the risk of distant spread.","caveats":["Small, non-randomised study with a historical comparison."],"changedPractice":true,"participants":46},{"id":"paper-nagata-int-j-radiat-oncol-biol-phys","kind":"paper","name":"Prospective Trial of Stereotactic Body Radiation Therapy for Both Operable and Inoperable T1N0M0 Non-Small Cell Lung Cancer: Japan Clinical Oncology Group Study JCOG0403","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 26581137 and published in International Journal of Radiation Oncology, Biology, Physics; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: To evaluate, in Japan Clinical Oncology Group study 0403, the safety and efficacy of stereotactic body radiation therapy (SBRT) in patients with T1N0M0 non-small cell lung cancer (NSCLC).\n\nMethods and materials: Eligibility criteria included histologically or cytologically proven NSCLC, clinical T1N0M0. Prescribed dose was 48 Gy at the isocenter in 4 fractions. The primary endpoint was the percent (%) 3-year overall survival. The threshold % 3-year survival to be rejected was set at 35% for inoperable patients, whereas the expected % 3-year survival was 80% for operable patients.\n\nResults: Between July 2004 and November 2008, 169 patients from 15 institutions were registered. One hundred inoperable and 64 operable patients (total 164) were eligible. Patients' characteristics were 122 male, 47 female; median age 78 years (range, 50-91 years); adenocarcinomas, 90; squamous cell carcinomas, 61; others, 18. Of the 100 inoperable patients, the % 3-year OS was 59.9% (95% confidence interval 49.6%-68.8%). Grade 3 and 4 toxicities were observed in 10 and 2 patients, respectively. No grade 5 toxicity was observed. Of the 64 operable patients, the % 3-year OS was 76.5% (95% confidence interval 64.0%-85.1%). Grade 3 toxicities were observed in 5 patients. No grade 4 and 5 toxicities were observed.\n\nConclusions: Stereotactic body radiation therapy for stage I NSCLC is effective, with low incidences of severe toxicity. This treatment can be considered a standard treatment for inoperable stage I NSCLC. This treatment is promising as an alternative to surgery for operable stage I NSCLC.\n\nIndexed on Europe PMC as PubMed record 26581137 (DOI 10.1016/j.ijrobp.2015.07.2278). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Int J Radiat Oncol Biol Phys 2015","url":"https://doi.org/10.1016/j.ijrobp.2015.07.2278"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26581137/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26581137"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["jcog0403"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["ijrobp"],"dependsOn":[],"notes":[],"journal":"International Journal of Radiation Oncology, Biology, Physics","year":2015,"doi":"10.1016/j.ijrobp.2015.07.2278","pmid":"26581137","authors":"Nagata Y, Hiraoka M, Shibata T, et al.","paperType":"observational","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-prosper-nejm-2018","kind":"paper","name":"PROSPER: enzalutamide in men with non-metastatic castration-resistant prostate cancer","aka":[],"tldr":"Enzalutamide delayed metastases by almost two years in men with rapidly rising PSA on hormone therapy and no visible spread, and longer follow-up showed it also lengthened survival.","summary":"Phase 3 placebo-controlled trial of 1,401 men with non-metastatic castration-resistant prostate cancer and PSA doubling time of ten months or less randomised 2:1 to enzalutamide or placebo with continued androgen deprivation.\n\nMedian metastasis-free survival was 36.6 versus 14.7 months (hazard ratio 0.29), and the final analysis showed median overall survival of 67.0 versus 56.3 months (hazard ratio 0.73); fatigue, hypertension and falls were more common.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2018","url":"https://doi.org/10.1056/NEJMoa1800536"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29949494/"}],"tags":[],"related":[],"cancers":["prostate-nmcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":["enzalutamide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["prosper"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2018,"doi":"10.1056/NEJMoa1800536","pmid":"29949494","authors":"Hussain M, Fizazi K, Saad F, et al.","paperType":"rct","findings":["Median metastasis-free survival 36.6 vs 14.7 months; hazard ratio 0.29.","Median overall survival 67.0 vs 56.3 months; hazard ratio 0.73."],"whatItMeans":"Enzalutamide is one of three androgen receptor inhibitors standard for high-risk non-metastatic castration-resistant prostate cancer.","caveats":["Fatigue and cognitive effects are more prominent than with darolutamide.","Conventional imaging defined non-metastatic status."],"changedPractice":true,"participants":1401},{"id":"paper-welch-albertsen-psa-era-diagnosis-treatment-jnci-2009","kind":"paper","name":"Prostate cancer diagnosis and treatment after the introduction of prostate-specific antigen screening, 1986 to 2005","aka":["Welch and Albertsen 2009","1.3 million extra prostate cancer diagnoses"],"tldr":"Counting what the blood test did to a country. In the twenty years after PSA testing began in the United States, an extra 1.3 million men were diagnosed with prostate cancer and about a million were definitively treated, for a benefit that on the most generous assumption reached one man in twenty of them.","summary":"H. Gilbert Welch and Peter Albertsen took age-specific incidence and initial treatment from the Surveillance, Epidemiology, and End Results programme and United States Census population estimates, and computed the excess number of men diagnosed and treated in each year after 1986, the year before prostate-specific antigen screening was introduced.\n\nThe age pattern is the part usually left out of the summary. Relative incidence in 2005 against 1986 was 0.56 in men aged 80 and over, and 7.23 in men under 50: the test moved diagnosis down the age distribution, into men with decades of life ahead of them and the most to lose from incontinence and erectile dysfunction. The authors then made the most favourable possible assumption, that the entire fall in prostate cancer mortality over the period was caused by screening, and still found that more than 20 men had to be diagnosed for each one who benefited.","asOf":"2026-09-25","links":[{"label":"J Natl Cancer Inst 2009","url":"https://doi.org/10.1093/jnci/djp278"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19720969/"}],"tags":["prostate-evidence"],"related":["paper-draisma-lead-time-overdiagnosis-psa-jnci-2009","paper-loeb-overdiagnosis-overtreatment-prostate-eur-urol-2014","paper-klotz-active-surveillance-jco-2015","idea-prev-indolent-lesion-nomenclature-body","prostate-roadmap"],"cancers":["prostate","prostate-low-risk"],"sections":["early-detection","prevention"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["psa","screening","overdiagnosis","lead-time-bias","overtreatment"],"trials":[],"people":[],"bottlenecks":["b-overdiagnosis","b-early-detection","b-toxicity-qol"],"keyPapers":[],"journals":["jnci"],"dependsOn":[],"notes":[],"journal":"JNCI: Journal of the National Cancer Institute","year":2009,"doi":"10.1093/jnci/djp278","pmid":"19720969","authors":"Welch HG, Albertsen PC.","paperType":"observational","findings":["An estimated additional 1,305,600 men were diagnosed with prostate cancer in the United States after 1986, of whom 1,004,800 were definitively treated.","Relative incidence in 2005 against 1986 was 0.56 in men aged 80 and over, 1.09 at 70 to 79, 1.91 at 60 to 69, 3.64 at 50 to 59, and 7.23 in men under 50.","Under the most optimistic assumption, that the entire decline in prostate cancer mortality over the period is attributable to the additional diagnosis, more than 20 men had to be diagnosed for each man who experienced the presumed benefit.","Overall incidence rose rapidly after 1986, peaked in 1992 and then declined to levels still considerably above 1986.","The authors concluded that most of the excess incidence must represent overdiagnosis, given the time elapsed since screening began."],"whatItMeans":"The number that anchors the overdiagnosis argument in prostate cancer: over a million American men treated for a cancer that, for most of them, was never going to surface. It is the reason active surveillance exists as a formal pathway and the reason magnetic resonance imaging was brought in front of the biopsy.","caveats":["An ecological analysis of registry data, not a randomised comparison; the excess is inferred from trends rather than observed per man.","The estimate of benefit assumes the entire mortality decline came from screening, which is generous and is stated as such by the authors; some of the decline is treatment.","United States figures in a period of unusually intense opportunistic testing; the size of the excess in systems with less testing is smaller."],"changedPractice":false},{"id":"paper-goteborg-2-n-engl-j-med-2022","kind":"paper","name":"Prostate Cancer Screening with PSA and MRI Followed by Targeted Biopsy Only","aka":[],"tldr":"Published report from the trial registered as ISRCTN94604465, in New England Journal of Medicine (2022), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Screening for prostate cancer is burdened by a high rate of overdiagnosis. The most appropriate algorithm for population-based screening is unknown.\n\nMethods: We invited 37,887 men who were 50 to 60 years of age to undergo regular prostate-specific antigen (PSA) screening. Participants with a PSA level of 3 ng per milliliter or higher underwent magnetic resonance imaging (MRI) of the prostate; one third of the participants were randomly assigned to a reference group that underwent systematic biopsy as well as targeted biopsy of suspicious lesions shown on MRI. The remaining participants were assigned to the experimental group and underwent MRI-targeted biopsy only. The primary outcome was clinically insignificant prostate cancer, defined as a Gleason score of 3+3. The secondary outcome was clinically significant prostate cancer, defined as a Gleason score of at least 3+4. Safety was also assessed.\n\nResults: Of the men who were invited to undergo screening, 17,980 (47%) participated in the trial. A total of 66 of the 11,986 participants in the experimental group (0.6%) received a diagnosis of clinically insignificant prostate cancer, as compared with 72 of 5994 participants (1.2%) in the reference group, a difference of -0.7 percentage points (95% confidence interval [CI], -1.0 to -0.4; relative risk, 0.46; 95% CI, 0.33 to 0.64; P<0.001). The relative risk of clinically significant prostate cancer in the experimental group as compared with the reference group was 0.81 (95% CI, 0.60 to 1.1). Clinically significant cancer that was detected only by systematic biopsy was diagnosed in 10 participants in the reference group; all cases were of intermediate risk and involved mainly low-volume disease that was managed with active surveillance. Serious adverse events were rare (<0.1%) in the two groups.\n\nConclusions: The avoidance of systematic biopsy in favor of MRI-directed targeted biopsy for screening and early detection in persons with elevated PSA levels reduced the risk of overdiagnosis by half at the cost of delaying detection of intermediate-risk tumors in a small proportion of patients. (Funded by Karin and Christer Johansson's Foundation and others; GÖTEBORG-2 ISRCTN Registry number, ISRCTN94604465.).\n\nIndexed on Europe PMC as PubMed record 36477032 (DOI 10.1056/nejmoa2209454). Its abstract cites the registry id ISRCTN94604465, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2022","url":"https://doi.org/10.1056/nejmoa2209454"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36477032/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36477032"},{"label":"ClinicalTrials.gov ISRCTN94604465","url":"https://clinicaltrials.gov/study/ISRCTN94604465"}],"tags":["europepmc-ingest"],"related":["prostate-roadmap","paper-ahmed-promis-multiparametric-mri-lancet-2017","idea-prostate-metastatic-presentation-as-the-screening-endpoint"],"cancers":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["polygenic-risk-score","pi-rads","number-needed-to-screen"],"trials":["goteborg-2"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/nejmoa2209454","pmid":"36477032","authors":"Hugosson J, Månsson M, Wallström J, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id ISRCTN94604465 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-esteva-npj-digit-med","kind":"paper","name":"Prostate cancer therapy personalization via multi-modal deep learning on randomized phase III clinical trials","aka":[],"tldr":"Paper cited by one pairing page, indexed on Europe PMC as PubMed record 35676445 and published in NPJ digital medicine; the citing page links this DOI, which is how the record was matched.","summary":"Prostate cancer is the most frequent cancer in men and a leading cause of cancer death. Determining a patient's optimal therapy is a challenge, where oncologists must select a therapy with the highest likelihood of success and the lowest likelihood of toxicity. International standards for prognostication rely on non-specific and semi-quantitative tools, commonly leading to over- and under-treatment. Tissue-based molecular biomarkers have attempted to address this, but most have limited validation in prospective randomized trials and expensive processing costs, posing substantial barriers to widespread adoption. There remains a significant need for accurate and scalable tools to support therapy personalization. Here we demonstrate prostate cancer therapy personalization by predicting long-term, clinically relevant outcomes using a multimodal deep learning architecture and train models using clinical data and digital histopathology from prostate biopsies. We train and validate models using five phase III randomized trials conducted across hundreds of clinical centers. Histopathological data was available for 5654 of 7764 randomized patients (71%) with a median follow-up of 11.4 years. Compared to the most common risk-stratification tool-risk groups developed by the National Cancer Center Network (NCCN)-our models have superior discriminatory performance across all endpoints, ranging from 9.2% to 14.6% relative improvement in a held-out validation set. This artificial intelligence-based tool improves prognostication over standard tools and allows oncologists to computationally predict the likeliest outcomes of specific patients to determine optimal treatment. Outfitted with digital scanners and internet access, any clinic could offer such capabilities, enabling global access to therapy personalization.\n\nIndexed on Europe PMC as PubMed record 35676445 (DOI 10.1038/s41746-022-00613-w). Matched by DOI alone: one pairing page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"NPJ Digit Med 2022","url":"https://doi.org/10.1038/s41746-022-00613-w"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35676445/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35676445"}],"tags":["europepmc-ingest"],"related":["ai-pathology-to-adt","prostate-roadmap","paper-taylor-integrative-genomic-profiling-cancer-cell-2010"],"cancers":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"NPJ digital medicine","year":2022,"doi":"10.1038/s41746-022-00613-w","pmid":"35676445","authors":"Esteva A, Feng J, van der Wal D, et al.","paperType":"rct","findings":[],"whatItMeans":"One pairing page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-murthy-j-clin-oncol","kind":"paper","name":"Prostate-Only Versus Whole-Pelvic Radiation Therapy in High-Risk and Very High-Risk Prostate Cancer (POP-RT): Outcomes From Phase III Randomized Controlled Trial","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 33497252 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: We report the clinical outcomes of a randomized trial comparing prophylactic whole-pelvic nodal radiotherapy to prostate-only radiotherapy (PORT) in high-risk prostate cancer.\n\nMethods: This phase III, single center, randomized controlled trial enrolled eligible patients undergoing radical radiotherapy for node-negative prostate adenocarcinoma, with estimated nodal risk ≥ 20%. Randomization was 1:1 to PORT (68 Gy/25# to prostate) or whole-pelvic radiotherapy (WPRT, 68 Gy/25# to prostate, 50 Gy/25# to pelvic nodes, including common iliac) using computerized stratified block randomization, stratified by Gleason score, type of androgen deprivation, prostate-specific antigen at diagnosis, and prior transurethral resection of the prostate. All patients received image-guided, intensity-modulated radiotherapy and minimum 2 years of androgen deprivation therapy. The primary end point was 5-year biochemical failure-free survival (BFFS), and secondary end points were disease-free survival (DFS) and overall survival (OS).\n\nResults: From November 2011 to August 2017, a total of 224 patients were randomly assigned (PORT = 114, WPRT = 110). At a median follow-up of 68 months, 36 biochemical failures (PORT = 25, WPRT = 7) and 24 deaths (PORT = 13, WPRT = 11) were recorded. Five-year BFFS was 95.0% (95% CI, 88.4 to 97.9) with WPRT versus 81.2% (95% CI, 71.6 to 87.8) with PORT, with an unadjusted hazard ratio (HR) of 0.23 (95% CI, 0.10 to 0.52; P <.0001). WPRT also showed higher 5-year DFS (89.5% v 77.2%; HR, 0.40; 95% CI, 0.22 to 0.73; P =.002), but 5-year OS did not appear to differ (92.5% v 90.8%; HR, 0.92; 95% CI, 0.41 to 2.05; P =.83). Distant metastasis-free survival was also higher with WPRT (95.9% v 89.2%; HR, 0.35; 95% CI, 0.15 to 0.82; P =.01). Benefit in BFFS and DFS was maintained across prognostic subgroups.\n\nConclusion: Prophylactic pelvic irradiation for high-risk, locally advanced prostate cancer improved BFFS and DFS as compared with PORT, but OS did not appear to differ.\n\nIndexed on Europe PMC as PubMed record 33497252 (DOI 10.1200/jco.20.03282). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2021","url":"https://doi.org/10.1200/jco.20.03282"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33497252/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33497252"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["pop-rt"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2021,"doi":"10.1200/jco.20.03282","pmid":"33497252","authors":"Murthy V, Maitre P, Kannan S, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-stamey-psa-serum-marker-nejm-1987","kind":"paper","name":"Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate","aka":["Stamey 1987","PSA serum marker 1987"],"tldr":"The paper that turned a protein made by the prostate into the blood test now used on millions of men a year. It showed the level tracked how much cancer there was, fell to nothing after surgery, and rose again when the cancer came back.","summary":"Thomas Stamey and colleagues at Stanford measured prostate-specific antigen and prostatic acid phosphatase by radioimmunoassay in 2,200 serum samples from 699 patients, 378 of whom had prostate cancer, and compared the two markers directly.\n\nProstate-specific antigen won on every axis that mattered for monitoring: it was more sensitive, it tracked tumour volume, it fell to undetectable after radical prostatectomy with a half-life of 2.2 days, and it detected recurrence. The paper's own conclusion is careful in a way the following twenty years were not: because both markers are also raised in benign prostatic hyperplasia, neither is specific. Stamey later became one of the loudest critics of the screening programme his paper enabled.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 1987","url":"https://doi.org/10.1056/nejm198710083171501"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/2442609/"}],"tags":["prostate-evidence"],"related":["paper-catalona-psa-screening-test-nejm-1991","paper-welch-albertsen-psa-era-diagnosis-treatment-jnci-2009","prostate-roadmap"],"cancers":["prostate","prostate-low-risk","prostate-intermediate-risk","prostate-high-risk"],"sections":["diagnostics","early-detection"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["psa","biochemical-recurrence","prostatectomy"],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-overdiagnosis","b-biomarker-validation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":1987,"doi":"10.1056/nejm198710083171501","pmid":"2442609","authors":"Stamey TA, Yang N, Hay AR, et al.","paperType":"observational","findings":["Prostate-specific antigen was elevated in 122 of 127 patients with newly diagnosed, untreated prostatic cancer, including 7 of 12 with unsuspected early disease and all 115 with more advanced disease.","The level increased with advancing clinical stage and was proportional to the estimated volume of the tumour; prostatic acid phosphatase was elevated in only 57 of the cancer patients and correlated less closely with volume.","Prostate-specific antigen was increased in 86 percent and prostatic acid phosphatase in 14 percent of patients with benign prostatic hyperplasia.","After radical prostatectomy the antigen routinely fell to undetectable levels, with a half-life of 2.2 days.","The authors concluded that because both markers may be elevated in benign prostatic hyperplasia, neither is specific."],"whatItMeans":"The origin of the blood test that defines how prostate cancer is found, monitored and declared to have recurred. Its strength was always monitoring a known cancer; the problems began when the same test was used to look for cancer in men who had no symptoms.","caveats":["A marker validation study in a hospital population, not a screening study; the screening question was not asked here.","The paper states plainly that the marker is not specific, a caveat that the subsequent adoption of population testing largely ignored.","Radioimmunoassay values from 1987 are not directly comparable with modern assays, and there is no single international standard threshold."],"changedPractice":true,"participants":699},{"id":"paper-martin-jama","kind":"paper","name":"Prostate-Specific Antigen Screening and 15-Year Prostate Cancer Mortality: A Secondary Analysis of the CAP Randomized Clinical Trial","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 38581198 and published in JAMA; the citing page links this DOI, which is how the record was matched.","summary":"Importance: The Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP) reported no effect of prostate-specific antigen (PSA) screening on prostate cancer mortality at a median 10-year follow-up (primary outcome), but the long-term effects of PSA screening on prostate cancer mortality remain unclear.\n\nObjective: To evaluate the effect of a single invitation for PSA screening on prostate cancer-specific mortality at a median 15-year follow-up compared with no invitation for screening.\n\nDesign, setting, and participants: This secondary analysis of the CAP randomized clinical trial included men aged 50 to 69 years identified at 573 primary care practices in England and Wales. Primary care practices were randomized between September 25, 2001, and August 24, 2007, and men were enrolled between January 8, 2002, and January 20, 2009. Follow-up was completed on March 31, 2021.\n\nIntervention: Men received a single invitation for a PSA screening test with subsequent diagnostic tests if the PSA level was 3.0 ng/mL or higher. The control group received standard practice (no invitation).\n\nMain outcomes and measures: The primary outcome was reported previously. Of 8 prespecified secondary outcomes, results of 4 were reported previously. The 4 remaining prespecified secondary outcomes at 15-year follow-up were prostate cancer-specific mortality, all-cause mortality, and prostate cancer stage and Gleason grade at diagnosis.\n\nResults: Of 415 357 eligible men (mean [SD] age, 59.0 [5.6] years), 98% were included in these analyses. Overall, 12 013 and 12 958 men with a prostate cancer diagnosis were in the intervention and control groups, respectively (15-year cumulative risk, 7.08% [95% CI, 6.95%-7.21%] and 6.94% [95% CI, 6.82%-7.06%], respectively). At a median 15-year follow-up, 1199 men in the intervention group (0.69% [95% CI, 0.65%-0.73%]) and 1451 men in the control group (0.78% [95% CI, 0.73%-0.82%]) died of prostate cancer (rate ratio [RR], 0.92 [95% CI, 0.85-0.99]; P =.03). Compared with the control, the PSA screening intervention increased detection of low-grade (Gleason score [GS] ≤6: 2.2% vs 1.6%; P <.001) and localized (T1/T2: 3.6% vs 3.1%; P <.001) disease but not intermediate (GS of 7), high-grade (GS ≥8), locally advanced (T3), or distally advanced (T4/N1/M1) tumors. There were 45 084 all-cause deaths in the intervention group (23.2% [95% CI, 23.0%-23.4%]) and 50 336 deaths in the control group (23.3% [95% CI, 23.1%-23.5%]) (RR, 0.97 [95% CI, 0.94-1.01]; P =.11). Eight of the prostate cancer deaths in the intervention group (0.7%) and 7 deaths in the control group (0.5%) were related to a diagnostic biopsy or prostate cancer treatment.\n\nConclusions and relevance: In this secondary analysis of a randomized clinical trial, a single invitation for PSA screening compared with standard practice without routine screening reduced prostate cancer deaths at a median follow-up of 15 years. However, the absolute reduction in deaths was small.\n\nTrial registration: isrctn.org Identifier: ISRCTN92187251.\n\nIndexed on Europe PMC as PubMed record 38581198 (DOI 10.1001/jama.2024.4011). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA 2024","url":"https://doi.org/10.1001/jama.2024.4011"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38581198/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38581198"}],"tags":["europepmc-ingest"],"related":["prostate-screening-psa-mri","prostate-roadmap","paper-schroder-erspc-screening-mortality-nejm-2009","paper-andriole-plco-prostate-screening-nejm-2009","idea-prostate-metastatic-presentation-as-the-screening-endpoint"],"cancers":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2024,"doi":"10.1001/jama.2024.4011","pmid":"38581198","authors":"Martin RM, Turner EL, Young GJ, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-silver-psma-expression-normal-malignant-tissues-ccr-1997","kind":"paper","name":"Prostate-specific membrane antigen expression in normal and malignant human tissues","aka":[],"tldr":"The survey that mapped where PSMA is found in the body, and showed it is almost nowhere except the prostate, which is what makes it safe to aim a radioactive drug at it.","summary":"An extensive immunohistochemical analysis was performed on a panel of well-characterised normal and malignant human tissues to define the pattern of prostate-specific membrane antigen expression. Detectable levels were identified in prostatic epithelium, duodenal mucosa and a subset of proximal renal tubules, and a subpopulation of neuroendocrine cells in the colonic crypts also showed immunoreactivity; all other normal tissues, including cerebral cortex and cerebellum, had undetectable levels. Thirty-three of 35 primary prostate adenocarcinomas and 7 of 8 lymph node metastases showed tumour cell staining, while 8 of 18 prostate tumours metastatic to bone expressed it. All other non-prostatic primary tumours studied had undetectable levels, but intense staining was seen in capillary endothelial cells in peritumoral and endotumoral areas of certain malignancies, including 8 of 17 renal cell carcinomas, 7 of 13 transitional cell carcinomas and 3 of 19 colon carcinomas. The decrease in immunoreactivity in advanced prostate cancer suggested that expression is linked to the degree of tumour differentiation.","asOf":"2026-09-25","links":[{"label":"Silver et al., Clin Cancer Res 1997: prostate-specific membrane antigen expression across normal and malignant human tissues by immunohistochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/9815541/"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["histopathology-ihc","psma-pet","radioligand-therapy"],"targets":["psma"],"drugs":[],"companies":[],"institutions":[],"pathways":["prostate-cancer-signalling"],"terms":["ihc","theranostics"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":1997,"pmid":"9815541","authors":"Silver DA, Pellicer I, Fair WR, Heston WD, Cordon-Cardo C.","paperType":"basic","findings":["Detectable PSMA in normal prostatic epithelium, duodenal mucosa, some proximal renal tubules and colonic neuroendocrine cells only.","Staining in 33 of 35 primary prostate adenocarcinomas and 7 of 8 lymph node metastases.","Staining in only 8 of 18 bone metastases, with expression linked to differentiation.","Neovascular endothelial staining in renal, transitional and colon carcinomas."],"whatItMeans":"It is the anatomical basis for PSMA imaging and PSMA radioligand therapy, and it predicted two of the practical problems three decades early: salivary, lacrimal and renal uptake as sources of toxicity, and falling expression in dedifferentiated disease as the reason some men are ineligible for treatment.","caveats":["A small immunohistochemical survey from 1997 with the antibodies of the time.","Eighteen bone metastases is a thin basis for the differentiation claim, although later work supports it.","It predates PET imaging entirely, so the link to scan positivity is inferred."],"changedPractice":false},{"id":"paper-bekes-nat-rev-drug-discov","kind":"paper","name":"PROTAC targeted protein degraders: the past is prologue","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 35042991 and published in Nature Reviews Drug Discovery; the citing page links this DOI, which is how the record was matched.","summary":"Targeted protein degradation (TPD) is an emerging therapeutic modality with the potential to tackle disease-causing proteins that have historically been highly challenging to target with conventional small molecules. In the 20 years since the concept of a proteolysis-targeting chimera (PROTAC) molecule harnessing the ubiquitin-proteasome system to degrade a target protein was reported, TPD has moved from academia to industry, where numerous companies have disclosed programmes in preclinical and early clinical development. With clinical proof-of-concept for PROTAC molecules against two well-established cancer targets provided in 2020, the field is poised to pursue targets that were previously considered 'undruggable'. In this Review, we summarize the first two decades of PROTAC discovery and assess the current landscape, with a focus on industry activity. We then discuss key areas for the future of TPD, including establishing the target classes for which TPD is most suitable, expanding the use of ubiquitin ligases to enable precision medicine and extending the modality beyond oncology.\n\nIndexed on Europe PMC as PubMed record 35042991 (DOI 10.1038/s41573-021-00371-6). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Drug Discov 2022","url":"https://doi.org/10.1038/s41573-021-00371-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35042991/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35042991"}],"tags":["europepmc-ingest"],"related":["ubiquitin-proteasome-system"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-drug-discovery"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Drug Discovery","year":2022,"doi":"10.1038/s41573-021-00371-6","pmid":"35042991","authors":"Békés M, Langley DR, Crews CM","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-protect-nejm-2016","kind":"paper","name":"ProtecT: 10-year outcomes after monitoring, surgery or radiotherapy for localised prostate cancer","aka":[],"tldr":"In the only randomised trial to compare active monitoring, surgery and radiotherapy for PSA-detected localised prostate cancer, deaths from prostate cancer were rare and equal at ten years in all three groups, though monitoring led to more metastases and progression.","summary":"Phase 3 trial of 1,643 men with PSA-detected localised prostate cancer randomised to active monitoring, radical prostatectomy or radiotherapy with six months of androgen deprivation.\n\nProstate cancer-specific mortality at ten years was about 1 percent in every group (17 deaths in total), while metastases (6.3 versus 2.4 and 3.0 per 1,000 person-years) and clinical progression were more frequent with monitoring; patient-reported outcomes showed distinct side-effect patterns for each treatment.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2016","url":"https://doi.org/10.1056/NEJMoa1606220"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27626136/"}],"tags":[],"related":["prostate-roadmap","paper-bill-axelson-spcg-4-29-year-nejm-2018","paper-wilt-pivot-prostatectomy-observation-nejm-2017"],"cancers":["prostate-intermediate-risk","prostate-low-risk","prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["protect"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2016,"doi":"10.1056/NEJMoa1606220","pmid":"27626136","authors":"Hamdy FC, Donovan JL, Lane JA, et al.","paperType":"rct","findings":["Prostate cancer-specific mortality about 1 percent at ten years in all groups.","Metastases 6.3 per 1,000 person-years with monitoring vs 2.4 (surgery) and 3.0 (radiotherapy)."],"whatItMeans":"Most men with low- and favourable intermediate-risk prostate cancer can safely choose monitoring, and treatment choice should weigh urinary, sexual and bowel side effects against a small difference in progression.","caveats":["Most men had low-risk disease; about 20 percent were intermediate or high risk.","Active monitoring was less intensive than modern active surveillance with MRI."],"changedPractice":true,"participants":1643},{"id":"paper-protect-15-year-nejm-2023","kind":"paper","name":"ProtecT: fifteen-year outcomes after monitoring, surgery or radiotherapy for prostate cancer","aka":[],"tldr":"Fifteen years on, ProtecT still found no difference in prostate cancer deaths between monitoring, surgery and radiotherapy, with about 97 percent of men alive from their cancer in every group, confirming that many men can defer or avoid treatment.","summary":"Fifteen-year follow-up of the 1,643 men randomised in ProtecT to active monitoring, prostatectomy or radiotherapy.\n\nProstate cancer-specific mortality was 3.1 percent with monitoring, 2.2 percent with surgery and 2.9 percent with radiotherapy (no significant difference); metastases occurred in 9.4, 4.7 and 5.0 percent respectively; about a quarter of men in the monitoring group remained untreated at 15 years.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2023","url":"https://doi.org/10.1056/NEJMoa2214122"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36912538/"}],"tags":[],"related":["prostate-roadmap","paper-bill-axelson-spcg-4-29-year-nejm-2018","paper-uspstf-prostate-screening-jama-2018"],"cancers":["prostate-low-risk","prostate-intermediate-risk","prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["protect"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/NEJMoa2214122","pmid":"36912538","authors":"Hamdy FC, Donovan JL, Lane JA, et al.","paperType":"rct","findings":["Fifteen-year prostate cancer mortality 3.1 percent (monitoring), 2.2 percent (surgery), 2.9 percent (radiotherapy).","Metastatic disease 9.4 percent vs 4.7 percent vs 5.0 percent."],"whatItMeans":"Long-term data support active surveillance as a safe choice for low and much intermediate-risk disease, while the lower metastasis rate with treatment informs the discussion for men with longer life expectancy.","caveats":["Trial design predates MRI-based diagnosis and modern surveillance protocols."],"changedPractice":true,"participants":1643},{"id":"paper-iozzo-j-cell-mol-med","kind":"paper","name":"Proteoglycans in cancer biology, tumour microenvironment and angiogenesis","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 21155971 and published in Journal of cellular and molecular medicine; the citing page links this DOI, which is how the record was matched.","summary":"Proteoglycans, key molecular effectors of cell surface and pericellular microenvironments, perform multiple functions in cancer and angiogenesis by virtue of their polyhedric nature and their ability to interact with both ligands and receptors that regulate neoplastic growth and neovascularization. Some proteoglycans such as perlecan, have pro- and anti-angiogenic activities, whereas other proteoglycans, such as syndecans and glypicans, can also directly affect cancer growth by modulating key signalling pathways. The bioactivity of these proteoglycans is further modulated by several classes of enzymes within the tumour microenvironment: (i) sheddases that cleave transmembrane or cell-associated syndecans and glypicans, (ii) various proteinases that cleave the protein core of pericellular proteoglycans and (iii) heparanases and endosulfatases which modify the structure and bioactivity of various heparan sulphate proteoglycans and their bound growth factors. In contrast, some of the small leucine-rich proteoglycans, such as decorin and lumican, act as tumour repressors by physically antagonizing receptor tyrosine kinases including the epidermal growth factor and the Met receptors or integrin receptors thereby evoking anti-survival and pro-apoptotic pathways. In this review we will critically assess the expanding repertoire of molecular interactions attributed to various proteoglycans and will discuss novel proteoglycan functions modulating cancer progression, invasion and metastasis and how these factors regulate the tumour microenvironment.\n\nIndexed on Europe PMC as PubMed record 21155971 (DOI 10.1111/j.1582-4934.2010.01236.x). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Cell Mol Med 2011","url":"https://doi.org/10.1111/j.1582-4934.2010.01236.x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21155971/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/21155971"}],"tags":["europepmc-ingest"],"related":["proteoglycans-in-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of cellular and molecular medicine","year":2011,"doi":"10.1111/j.1582-4934.2010.01236.x","pmid":"21155971","authors":"Iozzo RV, Sanderson RD","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-mascia-jama-oncol","kind":"paper","name":"Proton FLASH Radiotherapy for the Treatment of Symptomatic Bone Metastases: The FAST-01 Nonrandomized Trial","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 36273324 and published in JAMA Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Importance: To our knowledge, there have been no clinical trials of ultra-high-dose-rate radiotherapy delivered at more than 40 Gy/sec, known as FLASH therapy, nor first-in-human use of proton FLASH.\n\nObjectives: To assess the clinical workflow feasibility and treatment-related toxic effects of FLASH and pain relief at the treatment sites.\n\nDesign, setting, and participants: In the FAST-01 nonrandomized trial, participants treated at Cincinnati Children's/UC Health Proton Therapy Center underwent palliative FLASH radiotherapy to extremity bone metastases. Patients 18 years and older with 1 to 3 painful extremity bone metastases and life expectancies of 2 months or more were eligible. Patients were excluded if they had foot, hand, and wrist metastases; metastases locally treated in the 2 weeks prior; metal implants in the treatment field; known enhanced tissue radiosensitivity; and implanted devices at risk of malfunction with radiotherapy. One of 11 patients who consented was excluded based on eligibility. The end points were evaluated at 3 months posttreatment, and patients were followed up through death or loss to follow-up for toxic effects and pain assessments. Of the 10 included patients, 2 died after the 2-month follow-up but before the 3-month follow-up; 8 participants completed the 3-month evaluation. Data were collected from November 3, 2020, to January 28, 2022, and analyzed from January 28, 2022, to September 1, 2022.\n\nInterventions: Bone metastases were treated on a FLASH-enabled (≥40 Gy/sec) proton radiotherapy system using a single-transmission proton beam. This is consistent with standard of care using the same prescription (8 Gy in a single fraction) but on a conventional-dose-rate (approximately 0.03 Gy/sec) photon radiotherapy system.\n\nMain outcome and measures: Main outcomes included patient time on the treatment couch, device-related treatment delays, adverse events related to FLASH, patient-reported pain scores, and analgesic use.\n\nResults: A total of 10 patients (age range, 27-81 years [median age, 63 years]; 5 [50%] male) underwent FLASH radiotherapy at 12 metastatic sites. There were no FLASH-related technical issues or delays. The average (range) time on the treatment couch was 18.9 (11-33) minutes per patient and 15.8 (11-22) minutes per treatment site. Median (range) follow-up was 4.8 (2.3-13.0) months. Adverse events were mild and consistent with conventional radiotherapy. Transient pain flares occurred in 4 of the 12 treated sites (33%). In 8 of the 12 sites (67%) patients reported pain relief, and in 6 of the 12 sites (50%) patients reported a complete response (no pain).\n\nConclusions and relevance: In this nonrandomized trial, clinical workflow metrics, treatment efficacy, and safety data demonstrated that ultra-high-dose-rate proton FLASH radiotherapy was clinically feasible. The treatment efficacy and the profile of adverse events were comparable with those of standard-of-care radiotherapy. These findings support the further exploration of FLASH radiotherapy in patients with cancer.\n\nTrial registration: ClinicalTrials.gov Identifier: NCT04592887.\n\nIndexed on Europe PMC as PubMed record 36273324 (DOI 10.1001/jamaoncol.2022.5843). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA Oncol 2023","url":"https://doi.org/10.1001/jamaoncol.2022.5843"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36273324/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36273324"}],"tags":["europepmc-ingest"],"related":["flash-research-accelerators"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2023,"doi":"10.1001/jamaoncol.2022.5843","pmid":"36273324","authors":"Mascia AE, Daugherty EC, Zhang Y, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-psogi-pseudomyxoma-appendiceal-classification-am-j-surg-pathol-2016","kind":"paper","name":"PSOGI consensus for classification and pathological reporting of pseudomyxoma peritonei and associated appendiceal neoplasia","aka":[],"tldr":"Pathologists from around the world agreed on what to call the mucinous tumours of the appendix and the jelly-like peritoneal disease they cause, replacing a tangle of older names with low-grade appendiceal mucinous neoplasm, high-grade neoplasm and adenocarcinoma.","summary":"Modified Delphi consensus of the Peritoneal Surface Oncology Group International defining terminology for appendiceal mucinous neoplasms (low-grade appendiceal mucinous neoplasm or LAMN, high-grade appendiceal mucinous neoplasm, and mucinous adenocarcinoma with well, moderately or poorly differentiated grades, the last including signet ring cells) and for pseudomyxoma peritonei (acellular mucin, low-grade, high-grade, and high-grade with signet ring cells).\n\nThe scheme was adopted by the WHO 2019 digestive classification and underpins prognosis and the decision to offer cytoreductive surgery with HIPEC.","asOf":"2026-09-18","links":[{"label":"Am J Surg Pathol 2016","url":"https://doi.org/10.1097/PAS.0000000000000535"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26492181/"}],"tags":[],"related":[],"cancers":["low-grade-appendiceal-mucinous-neoplasm","appendiceal-adenocarcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"American Journal of Surgical Pathology","year":2016,"doi":"10.1097/PAS.0000000000000535","pmid":"26492181","authors":"Carr NJ, Cecil TD, Mohamed F, et al.","paperType":"review","findings":[],"whatItMeans":"Whether an appendiceal tumour is called LAMN or adenocarcinoma, and whether peritoneal disease is graded low or high, decides prognosis and treatment; this paper set those names.","caveats":["Consensus of experts rather than outcome data.","Terms such as 'mucinous carcinoma peritonei' in older papers do not map cleanly onto the new grades."],"changedPractice":true},{"id":"paper-ferraldeschi-pten-protein-loss-abiraterone-eur-urol-2015","kind":"paper","name":"PTEN protein loss and clinical outcome from castration-resistant prostate cancer treated with abiraterone acetate","aka":[],"tldr":"Staining tumour samples from 144 men showed that the 40% who had lost a particular protein lived about seven months less on abiraterone.","summary":"Men who had received abiraterone and had hormone-sensitive or castration-resistant prostate cancer tissue available for PTEN immunohistochemistry were identified retrospectively, with overall survival from the start of abiraterone as the primary endpoint. One hundred and forty-four men who had received abiraterone after docetaxel had available tumour tissue. Loss of PTEN expression was observed in 40%. Matched hormone-sensitive and castration-resistant tumour biopsies were available for 41 men, and PTEN status in castration-resistant tissue matched the hormone-sensitive tissue in 86% of those cases. Loss of PTEN expression was associated with shorter median overall survival, 14 against 21 months, hazard ratio 1.75, and shorter median duration of abiraterone treatment, 24 against 28 weeks, hazard ratio 1.6. PTEN protein loss, high lactate dehydrogenase and visceral metastases were independent prognostic factors on multivariable analysis.","asOf":"2026-09-25","links":[{"label":"Ferraldeschi et al., Eur Urol 2015: PTEN protein loss by immunohistochemistry and outcome on abiraterone in 144 men","url":"https://doi.org/10.1016/j.eururo.2014.10.027"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25454616/"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["histopathology-ihc"],"targets":["pten","akt"],"drugs":["abiraterone"],"companies":[],"institutions":[],"pathways":["pi3k-akt-mtor","ar-signaling"],"terms":["ihc","castration-resistance","resistance"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["european-urology"],"dependsOn":[],"notes":[],"journal":"European Urology","year":2015,"doi":"10.1016/j.eururo.2014.10.027","pmid":"25454616","authors":"Ferraldeschi R, Nava Rodrigues D, Riisnaes R, et al.","paperType":"observational","findings":["PTEN protein loss in 40% of 144 men treated with abiraterone after docetaxel.","Median overall survival 14 against 21 months with PTEN loss, hazard ratio 1.75.","PTEN status concordant between hormone-sensitive and castration-resistant biopsies in 86% of 41 paired cases.","PTEN loss an independent prognostic factor alongside lactate dehydrogenase and visceral disease."],"whatItMeans":"It made PTEN a protein test rather than a genomic one in this disease, and the concordance between early and late biopsies is the practical point: the diagnostic block usually answers the question, so a fresh biopsy is not needed to make this call.","caveats":["Retrospective and single-institution, in men treated after docetaxel.","Immunohistochemistry for PTEN is notoriously assay-dependent, which is why the phase 3 trial specified a single validated assay.","Prognostic, and it does not by itself say abiraterone should be withheld."],"changedPractice":false,"participants":144},{"id":"paper-ptld-1-risk-stratified-sequential-treatment-trappe-jco-2017","kind":"paper","name":"PTLD-1: response to rituximab induction as a predictive marker allowing stratification into rituximab or R-CHOP consolidation in B-cell post-transplant lymphoproliferative disorder","aka":[],"tldr":"In lymphoma arising after an organ transplant, starting with rituximab alone and then choosing between more rituximab and chemotherapy by response gave complete remission in seven of ten patients and a median survival of more than six years.","summary":"International prospective phase 2 trial of risk-stratified sequential treatment in CD20-positive post-transplant lymphoproliferative disorder after solid organ transplantation: four weekly rituximab infusions, then four further rituximab doses for patients in complete remission or four cycles of R-CHOP for all others.\n\n111 of 126 patients responded (88 percent), 88 with a complete response (70 percent); the three-year response duration estimate was 82 percent and median overall survival 6.6 years. Grade 3 or 4 infections occurred in 34 percent and treatment-related mortality was 8 percent. Response to rituximab induction remained prognostic for survival.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2017","url":"https://doi.org/10.1200/JCO.2016.69.3564"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27992268/"}],"tags":[],"related":[],"cancers":["post-transplant-lymphoproliferative-disorder"],"sections":[],"technologies":[],"targets":[],"drugs":["rituximab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["ptld-1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2017,"doi":"10.1200/JCO.2016.69.3564","pmid":"27992268","authors":"Trappe RU, Dierickx D, Zimmermann H, et al.","paperType":"observational","findings":["Overall response 88 percent (95% CI 81 to 93); complete response 70 percent (61 to 77).","Three-year response duration 82 percent; median overall survival 6.6 years (95% CI 5.5 to 7.6).","Grade 3 or 4 infections 34 percent; treatment-related mortality 8 percent."],"whatItMeans":"Risk-stratified sequential treatment is the standard first-line approach to post-transplant lymphoproliferative disorder, sparing complete responders to rituximab from chemotherapy.","caveats":["Single-arm phase 2; Burkitt, T-cell and CNS disease were excluded."],"changedPractice":true,"participants":126},{"id":"paper-ross-bmj","kind":"paper","name":"Publication of NIH funded trials registered in ClinicalTrials.gov: cross sectional analysis","aka":[],"tldr":"Paper cited by one bottleneck page, indexed on Europe PMC as PubMed record 22214755 and published in BMJ; the citing page links this DOI, which is how the record was matched.","summary":"Objective: To review patterns of publication of clinical trials funded by US National Institutes of Health (NIH) in peer reviewed biomedical journals indexed by Medline.\n\nDesign: Cross sectional analysis.\n\nSetting: Clinical trials funded by NIH and registered within ClinicalTrials.gov (clinicaltrials.gov), a trial registry and results database maintained by the US National Library of Medicine, after 30 September 2005 and updated as having been completed by 31 December 2008, allowing at least 30 months for publication after completion of the trial.\n\nMain outcome measures: Publication and time to publication in the biomedical literature, as determined through Medline searches, the last of which was performed in June 2011.\n\nResults: Among 635 clinical trials completed by 31 December 2008, 294 (46%) were published in a peer reviewed biomedical journal, indexed by Medline, within 30 months of trial completion. The median period of follow-up after trial completion was 51 months (25th-75th centiles 40-68 months), and 432 (68%) were published overall. Among published trials, the median time to publication was 23 months (14-36 months). Trials completed in either 2007 or 2008 were more likely to be published within 30 months of study completion compared with trials completed before 2007 (54% (196/366) v 36% (98/269); P<0.001).\n\nConclusions: Despite recent improvement in timely publication, fewer than half of trials funded by NIH are published in a peer reviewed biomedical journal indexed by Medline within 30 months of trial completion. Moreover, after a median of 51 months after trial completion, a third of trials remained unpublished.\n\nIndexed on Europe PMC as PubMed record 22214755 (DOI 10.1136/bmj.d7292). Matched by DOI alone: one bottleneck page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"BMJ 2012","url":"https://doi.org/10.1136/bmj.d7292"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22214755/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/22214755"}],"tags":["europepmc-ingest"],"related":["b-negative-results"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["bmj"],"dependsOn":[],"notes":[],"journal":"BMJ","year":2012,"doi":"10.1136/bmj.d7292","pmid":"22214755","authors":"Ross JS, Tse T, Zarin DA, et al.","paperType":"observational","findings":[],"whatItMeans":"One bottleneck page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-pugh-self-experimentation-publication-jme-2026","kind":"paper","name":"Pugh 2026: should a journal publish a scientist's experiment on herself?","aka":[],"tldr":"Three ethicists work through whether it was right to publish the virologist's case, separating the question of whether she should have done it from whether the result should have been printed.","summary":"Pugh, Wilkinson and Savulescu take the 2024 self-experimentation case report as their worked example and separate two questions that are usually run together: the performance question, whether it is ethical to experiment on oneself, and the publication question, whether it is ethical to publish the findings as research. They note that the case report's authors reported difficulty publishing because of concerns raised about the ethics of self-experimentation.\n\nThey argue that self-experimentation is not inherently unethical, and equally that there is no reason in principle to exempt it from ethical evaluation. Applying respect for autonomy, reasonable risk and prevention of harm to others, they conclude that publication of this particular report can be morally justified: the self-experimenter understood the choice, the viruses had a good safety profile, and the authors were explicit about the limited generalisability and that self-medication should not be a first approach. They note that live viruses do carry shedding and transmission risk to others, and that publication carries the separate risk of tempting other patients towards unconventional therapies before standard ones.\n\nThey recommend case-by-case assessment by ethics committees and journal editors rather than a blanket rule, encourage self-experimenters to seek review where publication is foreseeable, and give a decision algorithm. They set the case in a long history that includes Werner Forssmann and Barry Marshall, who both later received Nobel prizes, and scientists who died of their own experiments.","asOf":"2026-09-25","links":[{"label":"J Med Ethics 2026 (open access)","url":"https://doi.org/10.1136/jme-2025-110730"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40930709/"},{"label":"Europe PMC full text","url":"https://europepmc.org/articles/PMC7618749"}],"tags":[],"related":["paper-halassy-self-experiment-ovt-vaccines-2024"],"cancers":[],"sections":["immunotherapy"],"technologies":["oncolytic-virus"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["beata-halassy"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of Medical Ethics","year":2026,"doi":"10.1136/jme-2025-110730","pmid":"40930709","authors":"Pugh J, Wilkinson D, Savulescu J","paperType":"review","findings":["The performance question and the publication question are distinct: liberal norms of non-interference may govern whether a person may experiment on themselves, but not whether the result should be published as research.","Self-experimentation is not inherently unethical, and is not in principle exempt from ethical evaluation either.","Live oncolytic viruses expose others to shedding and unintentional transmission risk, which is a genuine harm-to-others consideration, mitigable by storage, handling and administration protocols.","Publication can tempt other patients towards unconventional therapy ahead of standard treatment, which is a reason for authors to state limits explicitly, as these authors did.","The authors conclude that publishing this report was morally justifiable, and propose a decision algorithm for editors facing similar submissions."],"whatItMeans":"The reason this case matters beyond one tumour is that it forced journals to decide a question they had avoided. The answer these authors give is not permission: it is that each case needs assessing against the values ethics committees exist to protect, and that a self-experimenter who expects to publish should seek review beforehand. For a reader the practical point is the one both papers make, that a published case is a record of what happened to one person and not an instruction.","caveats":["A normative ethics paper, not empirical research; the decision algorithm is a proposal and has no formal standing.","It analyses a case in which the self-experimenter was a professional virologist with laboratory access, and the authors are explicit that the reasoning does not extend to amateur self-experimentation.","One declared interest: a bioethics consultancy and advisory roles are disclosed by one author."]},{"id":"paper-baca-punctuated-evolution-chromoplexy-cell-2013","kind":"paper","name":"Punctuated evolution of prostate cancer genomes","aka":["Baca 2013","chromoplexy","chromoplexy prostate cancer"],"tldr":"Cancer is usually described as accumulating damage one change at a time. Sequencing 57 whole prostate cancer genomes showed something else: chains of translocations and deletions that happen together in one burst, disrupting several cancer genes at once.","summary":"Sylvan Baca, Levi Garraway, Mark Rubin and colleagues sequenced the genomes of 57 prostate tumours and matched normal tissue, then modelled how the rearrangements they found could have arisen. Translocations and deletions were abundant and highly interdependent, arriving in coordinated chains the authors named chromoplexy.\n\nThe consequence is a model of punctuated rather than gradual evolution: a small number of events can derange a large amount of genome at once, and the classical picture of stepwise mutation accumulation does not describe how this cancer is built. By ordering the clonal hierarchy of lesions the authors also charted a path of oncogenic events, which is the beginning of the timing work that Gundem extended to metastasis.","asOf":"2026-09-25","links":[{"label":"Cell 2013","url":"https://doi.org/10.1016/j.cell.2013.03.021"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23622249/"}],"tags":["prostate-evidence"],"related":["paper-grasso-mutational-landscape-lethal-crpc-nature-2012","paper-gundem-evolutionary-history-lethal-metastatic-prostate-nature-2015","prostate-roadmap"],"cancers":["prostate","prostate-high-risk"],"sections":["diagnostics"],"technologies":[],"targets":["erg","tmprss2"],"drugs":[],"companies":[],"institutions":["broad-institute","weill-cornell-meyer-cancer-center"],"pathways":[],"terms":["ngs","chromoplexy"],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity","b-undruggable-targets"],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Cell","year":2013,"doi":"10.1016/j.cell.2013.03.021","pmid":"23622249","authors":"Baca SC, Prandi D, Lawrence MS, et al.","paperType":"basic","findings":["Whole-genome sequencing of 57 prostate tumours and matched normal tissue characterised somatic alterations and how they accumulate during oncogenesis and progression.","Modelling the genesis of genomic rearrangements identified abundant DNA translocations and deletions arising in a highly interdependent manner, a phenomenon the authors named chromoplexy.","Chromoplexy frequently accounts for the dysregulation of prostate cancer genes and appears to disrupt multiple cancer genes coordinately.","The modelling suggests chromoplexy may induce considerable genomic derangement over relatively few events, supporting a model of punctuated cancer evolution.","Characterising the clonal hierarchy of genomic lesions charted a path of oncogenic events along which chromoplexy may drive prostate carcinogenesis."],"whatItMeans":"A different picture of how a cancer genome is built, and one that explains why prostate cancer has few point mutations and a great deal of structural damage. It is also why whole-genome rather than exome sequencing is the right assay for this disease.","caveats":["57 genomes, mostly primary tumours; the frequency of chromoplexy across the disease is not established here.","Chromoplexy is inferred from the pattern of rearrangements by modelling rather than observed as it happens.","No treatment follows from the finding; it changes the model of the disease rather than what is done about it."],"changedPractice":false,"participants":57},{"id":"paper-rashid-purist-pancreatic-subtype-classifier-ccr-2020","kind":"paper","name":"Purity Independent Subtyping of Tumors (PurIST), a clinically robust, single-sample classifier for tumor subtyping in pancreatic cancer","aka":[],"tldr":"Comparing the competing subtype schemes across trials and public data, this study found the two-type tumour-intrinsic scheme the most reproducible and built PurIST, a classifier that works on one biopsy at a time and relates to FOLFIRINOX response.","summary":"Three major subtype classification schemas were assessed against results from two clinical trials and by meta-analysis of public expression data for robustness and clinical relevance. A tumour-intrinsic two-subtype schema was most robust, replicable and clinically relevant. A single-sample classifier, PurIST, was developed by penalised logistic regression, with replicable performance across platforms and sample types including low-input biopsies; PurIST subtypes associated with prognosis and with treatment response to FOLFIRINOX.","asOf":"2026-09-24","links":[{"label":"Rashid et al., Clin Cancer Res 2020: PurIST single-sample classifier","url":"https://doi.org/10.1158/1078-0432.CCR-19-1467"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31754050/"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":["rna-seq"],"targets":[],"drugs":["folfirinox"],"companies":[],"institutions":["unc-lineberger"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2020,"doi":"10.1158/1078-0432.CCR-19-1467","pmid":"31754050","authors":"Rashid NU, Peng XL, Jin C, et al.","paperType":"methods","findings":["Two-subtype tumour-intrinsic schema most robust across datasets.","PurIST works on single low-input samples and associates with prognosis and FOLFIRINOX response."],"whatItMeans":"PurIST is the assay form of the Moffitt subtypes and the tool prospective subtype-stratified trials use.","caveats":["Retrospective association with FOLFIRINOX response.","Subtype-discordant tumours (about 12%) remain hard to call."],"changedPractice":false},{"id":"paper-kastenhuber-cell","kind":"paper","name":"Putting p53 in Context","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 28886379 and published in Cell; the citing page links this DOI, which is how the record was matched.","summary":"TP53 is the most frequently mutated gene in human cancer. Functionally, p53 is activated by a host of stress stimuli and, in turn, governs an exquisitely complex anti-proliferative transcriptional program that touches upon a bewildering array of biological responses. Despite the many unveiled facets of the p53 network, a clear appreciation of how and in what contexts p53 exerts its diverse effects remains unclear. How can we interpret p53's disparate activities and the consequences of its dysfunction to understand how cell type, mutation profile, and epigenetic cell state dictate outcomes, and how might we restore its tumor-suppressive activities in cancer?\n\nIndexed on Europe PMC as PubMed record 28886379 (DOI 10.1016/j.cell.2017.08.028). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cell 2017","url":"https://doi.org/10.1016/j.cell.2017.08.028"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28886379/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28886379"}],"tags":["europepmc-ingest"],"related":["p53-mdm2-axis"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Cell","year":2017,"doi":"10.1016/j.cell.2017.08.028","pmid":"28886379","authors":"Kastenhuber ER, Lowe SW","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-quail-joyce-microenvironment-metastasis-natmed-2013","kind":"paper","name":"Quail and Joyce 2013: microenvironmental regulation of tumour progression and metastasis","aka":[],"tldr":"A review of how the normal cells around a tumour, including fibroblasts, immune cells and blood vessels, are recruited to help it grow and spread, and how distant organs are prepared to receive metastases before the cancer cells arrive.","summary":"Quail and Joyce surveyed the tumour microenvironment at each step of progression and metastasis: how cancer-associated fibroblasts, tumour-associated macrophages, other myeloid and lymphoid cells and the vasculature support primary tumour growth, invasion and intravasation; how bone marrow-derived cells and tumour-secreted factors establish a pre-metastatic niche in distant organs; and how the microenvironment at secondary sites governs dormancy and outgrowth. They discussed therapies aimed at these host cells, including macrophage-targeting and anti-angiogenic drugs, as complements to treatments aimed at the cancer cell.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1038/nm.3394"}],"tags":[],"related":["paper-coussens-werb-inflammation-cancer-nature-2002"],"cancers":[],"sections":[],"technologies":["antiangiogenic"],"targets":["csf1r"],"drugs":[],"companies":[],"institutions":["mskcc"],"pathways":["metastatic-cascade","pre-metastatic-niche"],"terms":["metastasis","cancer-associated-fibroblasts","tumor-associated-macrophages","angiogenesis"],"trials":[],"people":["johanna-joyce"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2013,"doi":"10.1038/nm.3394","authors":"Quail DF, Joyce JA.","paperType":"review","findings":["Stromal, immune and vascular cells are co-opted at every stage from primary growth to metastatic colonisation.","Tumour-derived factors and bone marrow-derived cells prepare pre-metastatic niches in distant organs before cancer cells arrive.","The microenvironment at secondary sites controls whether disseminated cells stay dormant or grow out."],"whatItMeans":"This review is the standard map of the tumour microenvironment and the reason microenvironment-directed drugs, from anti-angiogenics to macrophage and fibroblast targeting agents, are developed alongside tumour-cell-directed ones.","caveats":["A review; many mechanisms rest on mouse models.","Microenvironment-targeted therapies have had mixed clinical success so far."],"changedPractice":false},{"id":"paper-kaminski-adenoma-detection-rate-interval-cancer-nejm-2010","kind":"paper","name":"Quality indicators for colonoscopy and the risk of interval cancer","aka":[],"tldr":"Patients examined by endoscopists who find adenomas in fewer than one in five people are around ten times more likely to develop a cancer before their next scheduled test. Who does the colonoscopy matters as much as whether it is done.","summary":"Kaminski, Regula, Kraszewska and colleagues used a multivariate Cox model to test whether colonoscopy quality indicators predict interval cancer, using data from 186 endoscopists in a colonoscopy-based screening programme covering 45,026 people. Interval cancer was defined as a colorectal adenocarcinoma diagnosed between the screening colonoscopy and the scheduled surveillance colonoscopy; quality indicators came from the programme database and interval cancers from cancer registries.\n\nForty-two interval colorectal cancers were identified over 188,788 person-years. The adenoma detection rate predicted them; the caecal intubation rate did not.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2010","url":"https://doi.org/10.1056/NEJMoa0907667"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20463339/"}],"tags":["colorectal-evidence"],"related":["paper-nordicc-nejm-2022","paper-zauber-national-polyp-study-colonoscopic-polypectomy-nejm-2012"],"cancers":["colorectal"],"sections":["early-detection"],"technologies":["colonoscopy","endoscopy","colorectal-screening","ai-endoscopy-detection"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-workforce","b-care-fragmentation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2010,"doi":"10.1056/NEJMoa0907667","pmid":"20463339","authors":"Kaminski MF, Regula J, Kraszewska E, et al.","paperType":"observational","findings":["42 interval colorectal cancers over 188,788 person-years across 186 endoscopists.","Adenoma detection rate was significantly associated with interval cancer risk (p=0.008); caecal intubation rate was not (p=0.50).","Against a detection rate of 20 percent or higher, hazard ratios were 10.94 (95 percent CI 1.37 to 87.01) for rates under 11 percent, 10.75 (1.36 to 85.06) for 11 to 14.9 percent and 12.50 (1.51 to 103.43) for 15 to 19.9 percent."],"whatItMeans":"The paper that made the adenoma detection rate the central quality measure of every screening endoscopy service, and the reason endoscopist-level auditing is a condition of accreditation.","caveats":["42 events give very wide confidence intervals; the size of the effect is uncertain even though its direction is not.","Observational: endoscopists with low detection rates may differ in other ways.","Detection rates have risen since 2010, so the modern gradient is shallower."],"changedPractice":true,"participants":45026},{"id":"paper-bentzen-int-j-radiat-oncol-biol-phys","kind":"paper","name":"Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC): an introduction to the scientific issues","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 20171515 and published in International Journal of Radiation Oncology, Biology, Physics; the citing page links this DOI, which is how the record was matched.","summary":"Advances in dose-volume/outcome (or normal tissue complication probability, NTCP) modeling since the seminal Emami paper from 1991 are reviewed. There has been some progress with an increasing number of studies on large patient samples with three-dimensional dosimetry. Nevertheless, NTCP models are not ideal. Issues related to the grading of side effects, selection of appropriate statistical methods, testing of internal and external model validity, and quantification of predictive power and statistical uncertainty, all limit the usefulness of much of the published literature. Synthesis (meta-analysis) of data from multiple studies is often impossible because of suboptimal primary analysis, insufficient reporting and variations in the models and predictors analyzed. Clinical limitations to the current knowledge base include the need for more data on the effect of patient-related cofactors, interactions between dose distribution and cytotoxic or molecular targeted agents, and the effect of dose fractions and overall treatment time in relation to nonuniform dose distributions. Research priorities for the next 5-10 years are proposed.\n\nIndexed on Europe PMC as PubMed record 20171515 (DOI 10.1016/j.ijrobp.2009.09.040). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Int J Radiat Oncol Biol Phys 2010","url":"https://doi.org/10.1016/j.ijrobp.2009.09.040"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20171515/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/20171515"}],"tags":["europepmc-ingest"],"related":["tumour-control-probability-models"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["ijrobp"],"dependsOn":[],"notes":[],"journal":"International Journal of Radiation Oncology, Biology, Physics","year":2010,"doi":"10.1016/j.ijrobp.2009.09.040","pmid":"20171515","authors":"Bentzen SM, Constine LS, Deasy JO, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-quantum-first-quizartinib-lancet-2023","kind":"paper","name":"QuANTUM-First: quizartinib added to intensive chemotherapy and continued as maintenance in newly diagnosed FLT3-ITD AML","aka":[],"tldr":"Adding the FLT3 inhibitor quizartinib to standard chemotherapy, and continuing it for up to three years, roughly doubled median survival in FLT3-ITD acute myeloid leukaemia.","summary":"QuANTUM-First randomised 539 adults aged 18-75 with newly diagnosed FLT3-ITD-positive AML to quizartinib or placebo added to standard 7+3 induction and consolidation, continued after allogeneic transplant where performed, and then as maintenance for up to 36 cycles. The primary endpoint was overall survival. Median OS was 31.9 versus 15.1 months (hazard ratio 0.78), with similar remission rates but lower relapse in the quizartinib arm. QT prolongation and cytopenias were more frequent with quizartinib. It followed RATIFY (midostaurin) as the second phase 3 trial to show a survival benefit from a FLT3 inhibitor in front-line therapy, and the first with a selective type II inhibitor.","asOf":"2026-09-08","links":[{"label":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=QuANTUM-First%20quizartinib%20FLT3-ITD%20Erba%20Lancet%202023"},{"label":"ClinicalTrials.gov NCT02668653","url":"https://clinicaltrials.gov/study/NCT02668653"}],"tags":[],"related":["flt3i-plus-7-3","paper-admiral-gilteritinib-flt3-nejm-2019"],"cancers":["aml"],"sections":[],"technologies":["allogeneic-hsct"],"targets":["flt3"],"drugs":["quizartinib","midostaurin","gilteritinib","cytarabine-7-3"],"companies":["daiichi-sankyo"],"institutions":[],"pathways":[],"terms":["os"],"trials":["quantum-first"],"people":[],"bottlenecks":["b-resistance","b-dose-optimisation"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2023,"doi":"10.1016/S0140-6736(23)00464-6","pmid":"37116523","authors":"Erba HP, Montesinos P, Kim HJ, et al.","paperType":"rct","findings":["539 patients aged 18-75 with FLT3-ITD AML; quizartinib vs placebo with 7+3, consolidation and up to 3 years of maintenance.","Median OS 31.9 vs 15.1 months; hazard ratio 0.78.","Complete remission rates were similar (around 55%), so benefit came from deeper remissions and fewer relapses.","Benefit maintained in patients who proceeded to allogeneic transplant with post-transplant quizartinib.","More grade 3 QT prolongation, neutropenia and infections with quizartinib."],"whatItMeans":"QuANTUM-First gave FLT3-ITD AML patients a second front-line targeted option and showed that continuing a FLT3 inhibitor as long-term maintenance, including after transplant, pays off. Quizartinib was approved for this indication in 2023. Head-to-head data against midostaurin are lacking, and the design leaves open how much of the benefit came from maintenance.","caveats":["Applies only to FLT3-ITD, not FLT3-TKD mutations.","Contribution of maintenance versus induction-phase quizartinib cannot be separated.","Placebo, rather than midostaurin, was the comparator.","Cardiac monitoring for QT prolongation is required; older patients gained less."],"changedPractice":true,"participants":539},{"id":"paper-quartz-lancet-2016","kind":"paper","name":"QUARTZ: whole-brain radiotherapy versus supportive care alone for brain metastases from non-small-cell lung cancer","aka":[],"tldr":"For patients with lung cancer brain metastases unsuitable for surgery or radiosurgery, whole-brain radiotherapy added no meaningful survival or quality of life compared with steroids and supportive care alone.","summary":"Non-inferiority phase 3 trial of 538 patients with brain metastases from non-small-cell lung cancer unsuitable for resection or stereotactic radiotherapy, randomised to optimal supportive care with dexamethasone with or without whole-brain radiotherapy (20 Gy in five fractions).\n\nQuality-adjusted life years were 46.4 days with radiotherapy and 41.7 days without, a difference within the non-inferiority margin, and overall survival was about nine weeks in both arms.","asOf":"2026-09-17","links":[{"label":"Lancet 2016","url":"https://doi.org/10.1016/S0140-6736(16)30825-X"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27604504/"}],"tags":[],"related":[],"cancers":["secondary-brain-tumours"],"sections":[],"technologies":[],"targets":[],"drugs":["dexamethasone"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["quartz"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2016,"doi":"10.1016/S0140-6736(16)30825-X","pmid":"27604504","authors":"Mulvenna P, Nankivell M, Barton R, et al.","paperType":"rct","findings":["Quality-adjusted life years 46.4 vs 41.7 days (non-inferior).","Median overall survival about 9 weeks in both arms."],"whatItMeans":"Whole-brain radiotherapy is not a default for poor-prognosis brain metastases; supportive care alone is an acceptable choice, with radiotherapy reserved for selected younger, fitter patients.","caveats":["Population had very short survival; subgroups such as those under 60 may benefit.","Predates targeted therapy for driver-mutated lung cancer with brain penetration."],"changedPractice":true,"participants":538},{"id":"paper-quazar-aml-001-wei-nejm-2020","kind":"paper","name":"QUAZAR AML-001: oral azacitidine maintenance for acute myeloid leukaemia in first remission","aka":[],"tldr":"Older adults with acute myeloid leukaemia who took an azacitidine tablet for two weeks of every four after chemotherapy lived a median of ten months longer than those on placebo, with mostly gut side effects and no loss of quality of life.","summary":"Phase 3, randomised, double-blind, placebo-controlled trial of oral azacitidine (CC-486) 300 mg daily for 14 of 28 days as maintenance in 472 patients aged 55 or older with acute myeloid leukaemia in first remission after intensive chemotherapy who were not transplant candidates.\n\nMedian overall survival was 24.7 months with CC-486 against 14.8 months with placebo, and relapse-free survival was also significantly longer. Side effects were mainly gastrointestinal symptoms and neutropenia; quality-of-life measures were maintained.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2020","url":"https://doi.org/10.1056/NEJMoa2004444"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33369355/"}],"tags":[],"related":[],"cancers":["aml","aml-older-unfit"],"sections":[],"technologies":[],"targets":[],"drugs":["azacitidine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["quazar-aml-001"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2020,"doi":"10.1056/NEJMoa2004444","pmid":"33369355","authors":"Wei AH, Döhner H, Pocock C, et al.","paperType":"rct","findings":["Median overall survival 24.7 months with oral azacitidine versus 14.8 months with placebo (hazard ratio 0.69, 95% CI 0.55 to 0.86; p 0.0009).","Relapse-free survival significantly longer with oral azacitidine.","Side effects mainly gastrointestinal and neutropenia; quality of life maintained."],"whatItMeans":"The first maintenance therapy shown to lengthen survival in acute myeloid leukaemia; oral azacitidine (Onureg) was approved in the United States in 2020 for patients in first remission who cannot complete intensive curative therapy.","caveats":["Oral azacitidine is not bioequivalent to injectable azacitidine and the two are not interchangeable.","Patients going to transplant were excluded."],"changedPractice":true,"participants":472},{"id":"paper-carey-race-breast-cancer-subtypes-cbcs-jama-2006","kind":"paper","name":"Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study","aka":[],"tldr":"The 2006 North Carolina study that found the basal-like subtype in 39 percent of breast cancers in premenopausal African American women against 16 percent in other women, offering a biological reason for the worse survival of young Black women with breast cancer.","summary":"Carey, Perou, Livasy, Dressler and colleagues applied immunohistochemical surrogates for the gene-expression subtypes to 496 incident invasive breast cancers from the population-based Carolina Breast Cancer Study (1993 to 1996), which oversampled premenopausal and African American women. Basal-like was defined as oestrogen receptor-, progesterone receptor- and HER2-negative with cytokeratin 5/6 and/or HER1 positivity. The basal-like subtype was more prevalent among premenopausal African American women (39 percent) than postmenopausal African American women (14 percent) or non-African American women of any age (16 percent; p<0.001), and luminal A less prevalent (36 versus 59 and 54 percent). Compared with luminal A, basal-like tumours had more TP53 mutations (44 versus 15 percent), higher mitotic index (odds ratio 11.0), more nuclear pleomorphism (9.7) and higher grade (8.3). Breast cancer-specific survival differed by subtype, shortest for HER2-positive/oestrogen receptor-negative and basal-like tumours.","asOf":"2026-09-24","links":[{"label":"JAMA 2006","url":"https://doi.org/10.1001/jama.295.21.2492"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/16757721/"}],"tags":["tnbc-evidence"],"related":["paper-foulkes-brca1-basal-phenotype-jnci-2003","paper-copson-posh-ethnicity-young-breast-cancer-uk-bjc-2014"],"cancers":["tnbc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["unc-lineberger"],"pathways":[],"terms":["ihc"],"trials":[],"people":["charles-perou"],"bottlenecks":["b-trial-diversity"],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2006,"doi":"10.1001/jama.295.21.2492","pmid":"16757721","authors":"Carey LA, Perou CM, Livasy CA, et al.","paperType":"observational","findings":["Basal-like prevalence 39 percent in premenopausal African American women vs 14 percent postmenopausal African American and 16 percent non-African American women (p<0.001).","Basal-like vs luminal A: TP53 mutation 44 vs 15 percent; mitotic index odds ratio 11.0; grade odds ratio 8.3.","Shortest breast cancer-specific survival in HER2-positive/oestrogen receptor-negative and basal-like subtypes."],"whatItMeans":"The paper that made race a biological as well as a social variable in triple-negative breast cancer, and the reason the US disparity is described as roughly twice the incidence in Black women; the UK POSH study later found a smaller but real excess.","caveats":["Immunohistochemical surrogate for basal-like, not gene expression.","Ancestry, socioeconomic and reproductive factors are entangled; the study cannot separate them."],"changedPractice":true,"participants":496},{"id":"paper-radiant-3-everolimus-pnet-yao-nejm-2011","kind":"paper","name":"RADIANT-3: everolimus for advanced pancreatic neuroendocrine tumours","aka":[],"tldr":"The mTOR inhibitor everolimus more than doubled the time to progression in advanced pancreatic neuroendocrine tumours, becoming one of the first two targeted drugs approved for the disease in 2011.","summary":"Phase 3 placebo-controlled trial of 410 patients with advanced, low- or intermediate-grade, progressive pancreatic neuroendocrine tumours randomised to everolimus 10 mg daily or placebo.\n\nMedian progression-free survival was 11.0 versus 4.6 months (hazard ratio 0.35), with stomatitis, rash, diarrhoea and hyperglycaemia as the characteristic toxicities; overall survival was similar because of crossover.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2011","url":"https://doi.org/10.1056/NEJMoa1009290"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21306238/"}],"tags":[],"related":[],"cancers":["pancreatic-net"],"sections":[],"technologies":[],"targets":[],"drugs":["everolimus"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2011,"doi":"10.1056/NEJMoa1009290","pmid":"21306238","authors":"Yao JC, Shah MH, Ito T, et al.","paperType":"rct","findings":["Median progression-free survival 11.0 vs 4.6 months; hazard ratio 0.35.","Objective response 5 percent; benefit was disease stabilisation."],"whatItMeans":"Everolimus is a standard option for progressive pancreatic neuroendocrine tumours, alongside sunitinib, chemotherapy and radioligand therapy.","caveats":["Crossover obscured any survival benefit.","Hyperglycaemia is a particular concern in this population."],"changedPractice":true,"participants":410},{"id":"paper-radiant-4-everolimus-lancet-2016","kind":"paper","name":"RADIANT-4: everolimus for advanced non-functional neuroendocrine tumours of the lung or gastrointestinal tract","aka":[],"tldr":"Everolimus more than doubled the time to progression in advanced non-functioning neuroendocrine tumours of the lung and gut, the first drug with randomised evidence in lung carcinoids.","summary":"Phase 3 placebo-controlled trial of 302 patients with advanced progressive, well-differentiated, non-functional neuroendocrine tumours of lung or gastrointestinal origin randomised 2:1 to everolimus 10 mg daily or placebo.\n\nMedian progression-free survival was 11.0 versus 3.9 months (hazard ratio 0.48), with consistent benefit in lung and gastrointestinal subgroups; stomatitis, diarrhoea and infections were the main toxicities.","asOf":"2026-09-17","links":[{"label":"Lancet 2016","url":"https://doi.org/10.1016/S0140-6736(15)00817-X"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26703889/"}],"tags":[],"related":[],"cancers":["lung-net","small-intestinal-net"],"sections":[],"technologies":[],"targets":[],"drugs":["everolimus"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2016,"doi":"10.1016/S0140-6736(15)00817-X","pmid":"26703889","authors":"Yao JC, Fazio N, Singh S, et al.","paperType":"rct","findings":["Median progression-free survival 11.0 vs 3.9 months; hazard ratio 0.48.","Lung subgroup: 9.2 vs 3.6 months."],"whatItMeans":"Everolimus is approved for progressive lung and gastrointestinal neuroendocrine tumours and is a standard option after somatostatin analogues, particularly in lung carcinoids where radioligand therapy is off label.","caveats":["No overall survival benefit shown.","Response rates were low; benefit is disease stabilisation."],"changedPractice":true,"participants":302},{"id":"paper-rtog-9601-n-engl-j-med-2017","kind":"paper","name":"Radiation with or without Antiandrogen Therapy in Recurrent Prostate Cancer","aka":[],"tldr":"Published report from the RTOG 9601 trial registered as NCT00002874, in New England Journal of Medicine (2017), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Salvage radiation therapy is often necessary in men who have undergone radical prostatectomy and have evidence of prostate-cancer recurrence signaled by a persistently or recurrently elevated prostate-specific antigen (PSA) level. Whether antiandrogen therapy with radiation therapy will further improve cancer control and prolong overall survival is unknown.\n\nMethods: In a double-blind, placebo-controlled trial conducted from 1998 through 2003, we assigned 760 eligible patients who had undergone prostatectomy with a lymphadenectomy and had disease, as assessed on pathological testing, with a tumor stage of T2 (confined to the prostate but with a positive surgical margin) or T3 (with histologic extension beyond the prostatic capsule), no nodal involvement, and a detectable PSA level of 0.2 to 4.0 ng per milliliter to undergo radiation therapy and receive either antiandrogen therapy (24 months of bicalutamide at a dose of 150 mg daily) or daily placebo tablets during and after radiation therapy. The primary end point was the rate of overall survival.\n\nResults: The median follow-up among the surviving patients was 13 years. The actuarial rate of overall survival at 12 years was 76.3% in the bicalutamide group, as compared with 71.3% in the placebo group (hazard ratio for death, 0.77; 95% confidence interval, 0.59 to 0.99; P=0.04). The 12-year incidence of death from prostate cancer, as assessed by means of central review, was 5.8% in the bicalutamide group, as compared with 13.4% in the placebo group (P<0.001). The cumulative incidence of metastatic prostate cancer at 12 years was 14.5% in the bicalutamide group, as compared with 23.0% in the placebo group (P=0.005). The incidence of late adverse events associated with radiation therapy was similar in the two groups. Gynecomastia was recorded in 69.7% of the patients in the bicalutamide group, as compared with 10.9% of those in the placebo group (P<0.001).\n\nConclusions: The addition of 24 months of antiandrogen therapy with daily bicalutamide to salvage radiation therapy resulted in significantly higher rates of long-term overall survival and lower incidences of metastatic prostate cancer and death from prostate cancer than radiation therapy plus placebo. (Funded by the National Cancer Institute and AstraZeneca; RTOG 9601 ClinicalTrials.gov number, NCT00002874.).\n\nIndexed on Europe PMC as PubMed record 28146658 (DOI 10.1056/nejmoa1607529). Its abstract cites the registry id NCT00002874, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2017","url":"https://doi.org/10.1056/nejmoa1607529"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28146658/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28146658"},{"label":"ClinicalTrials.gov NCT00002874","url":"https://clinicaltrials.gov/study/NCT00002874"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["rtog-9601"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2017,"doi":"10.1056/nejmoa1607529","pmid":"28146658","authors":"Shipley WU, Seiferheld W, Lukka HR, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT00002874 with the most citations, so it is the natural first reading for anyone following the RTOG 9601 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-radicals-rt-lancet-2020","kind":"paper","name":"RADICALS-RT: timing of radiotherapy after radical prostatectomy","aka":[],"tldr":"Giving radiotherapy to every man with risk factors immediately after prostatectomy was no better than waiting and treating only those whose PSA rose, so early salvage radiotherapy became the standard and spared many men unnecessary treatment.","summary":"Phase 3 trial of 1,396 men after radical prostatectomy with at least one risk factor (pT3/4, Gleason 7 to 10, positive margins or preoperative PSA of 10 or more) randomised to adjuvant radiotherapy within six months or an observation policy with early salvage radiotherapy at biochemical failure.\n\nFive-year biochemical progression-free survival was 85 percent with adjuvant and 88 percent with salvage policy (hazard ratio 1.10, no difference), with only a third of the salvage group receiving radiotherapy by five years and more urinary and bowel toxicity in the adjuvant group; a meta-analysis with two similar trials (ARTISTIC) confirmed the result.","asOf":"2026-09-17","links":[{"label":"Lancet 2020","url":"https://doi.org/10.1016/S0140-6736(20)31553-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33002429/"}],"tags":[],"related":[],"cancers":["prostate-bcr"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["chris-parker"],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2020,"doi":"10.1016/S0140-6736(20)31553-1","pmid":"33002429","authors":"Parker CC, Clarke NW, Cook AD, et al.","paperType":"rct","findings":["Five-year biochemical progression-free survival 85 percent (adjuvant) vs 88 percent (salvage policy).","Only 33 percent of the salvage-policy group had received radiotherapy at five years."],"whatItMeans":"Observation with early salvage radiotherapy at PSA recurrence is standard after prostatectomy, avoiding radiotherapy in most men who would never have needed it.","caveats":["Men with the highest-risk features (multiple adverse factors) were under-represented.","Longer follow-up for metastasis-free survival is pending."],"changedPractice":true,"participants":1396},{"id":"paper-omuro-neuro-oncol","kind":"paper","name":"Radiotherapy combined with nivolumab or temozolomide for newly diagnosed glioblastoma with unmethylated MGMT promoter: An international randomized phase III trial","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 35419607 and published in Neuro-Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background: Addition of temozolomide (TMZ) to radiotherapy (RT) improves overall survival (OS) in patients with glioblastoma (GBM), but previous studies suggest that patients with tumors harboring an unmethylated MGMT promoter derive minimal benefit. The aim of this open-label, phase III CheckMate 498 study was to evaluate the efficacy of nivolumab (NIVO) + RT compared with TMZ + RT in newly diagnosed GBM with unmethylated MGMT promoter.\n\nMethods: Patients were randomized 1:1 to standard RT (60 Gy) + NIVO (240 mg every 2 weeks for eight cycles, then 480 mg every 4 weeks) or RT + TMZ (75 mg/m2 daily during RT and 150-200 mg/m2/day 5/28 days during maintenance). The primary endpoint was OS.\n\nResults: A total of 560 patients were randomized, 280 to each arm. Median OS (mOS) was 13.4 months (95% CI, 12.6 to 14.3) with NIVO + RT and 14.9 months (95% CI, 13.3 to 16.1) with TMZ + RT (hazard ratio [HR], 1.31; 95% CI, 1.09 to 1.58; P =.0037). Median progression-free survival was 6.0 months (95% CI, 5.7 to 6.2) with NIVO + RT and 6.2 months (95% CI, 5.9 to 6.7) with TMZ + RT (HR, 1.38; 95% CI, 1.15 to 1.65). Response rates were 7.8% (9/116) with NIVO + RT and 7.2% (8/111) with TMZ + RT; grade 3/4 treatment-related adverse event (TRAE) rates were 21.9% and 25.1%, and any-grade serious TRAE rates were 17.3% and 7.6%, respectively.\n\nConclusions: The study did not meet the primary endpoint of improved OS; TMZ + RT demonstrated a longer mOS than NIVO + RT. No new safety signals were detected with NIVO in this study. The difference between the study treatment arms is consistent with the use of TMZ + RT as the standard of care for GBM.ClinicalTrials.gov NCT02617589.\n\nIndexed on Europe PMC as PubMed record 35419607 (DOI 10.1093/neuonc/noac099). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Neuro Oncol 2023","url":"https://doi.org/10.1093/neuonc/noac099"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35419607/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35419607"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-498"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["neuro-oncology"],"dependsOn":[],"notes":[],"journal":"Neuro-Oncology","year":2023,"doi":"10.1093/neuonc/noac099","pmid":"35419607","authors":"Omuro A, Brandes AA, Carpentier AF, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-bonner-cetuximab-radiotherapy-nejm-2006","kind":"paper","name":"Radiotherapy plus cetuximab for locoregionally advanced squamous cell carcinoma of the head and neck","aka":[],"tldr":"Adding the EGFR antibody cetuximab to radiotherapy lengthened survival in locally advanced head and neck cancer by about 20 months without increasing the mucosal toxicity of radiotherapy, giving patients unfit for cisplatin an alternative.","summary":"Phase 3 trial of 424 patients with stage III to IV squamous cell carcinoma of the oropharynx, hypopharynx or larynx randomised to high-dose radiotherapy alone or with weekly cetuximab.\n\nMedian overall survival was 49.0 versus 29.3 months (hazard ratio 0.74) and locoregional control 24.4 versus 14.9 months; apart from acneiform rash and infusion reactions, toxicity was not increased. Later analyses suggested the benefit was concentrated in oropharyngeal cancer.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2006","url":"https://doi.org/10.1056/NEJMoa053422"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/16467544/"}],"tags":[],"related":[],"cancers":["hpv-negative-head-and-neck-cancer","hypopharyngeal-cancer","lip-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["cetuximab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2006,"doi":"10.1056/NEJMoa053422","pmid":"16467544","authors":"Bonner JA, Harari PM, Giralt J, et al.","paperType":"rct","findings":["Median overall survival 49.0 vs 29.3 months; hazard ratio 0.74.","Median locoregional control 24.4 vs 14.9 months."],"whatItMeans":"Cetuximab-radiotherapy is the standard for patients who cannot receive cisplatin; head-to-head trials in HPV-positive disease (RTOG 1016, De-ESCALaTE) later showed it inferior to cisplatin where cisplatin is possible.","caveats":["Never compared directly with cisplatin chemoradiation in this trial.","HPV status was not known."],"changedPractice":true,"participants":424},{"id":"paper-parker-lancet","kind":"paper","name":"Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 30355464 and published in The Lancet; the citing page links this DOI, which is how the record was matched.","summary":"Background: Based on previous findings, we hypothesised that radiotherapy to the prostate would improve overall survival in men with metastatic prostate cancer, and that the benefit would be greatest in patients with a low metastatic burden. We aimed to compare standard of care for metastatic prostate cancer, with and without radiotherapy.\n\nMethods: We did a randomised controlled phase 3 trial at 117 hospitals in Switzerland and the UK. Eligible patients had newly diagnosed metastatic prostate cancer. We randomly allocated patients open-label in a 1:1 ratio to standard of care (control group) or standard of care and radiotherapy (radiotherapy group). Randomisation was stratified by hospital, age at randomisation, nodal involvement, WHO performance status, planned androgen deprivation therapy, planned docetaxel use (from December, 2015), and regular aspirin or non-steroidal anti-inflammatory drug use. Standard of care was lifelong androgen deprivation therapy, with up-front docetaxel permitted from December, 2015. Men allocated radiotherapy received either a daily (55 Gy in 20 fractions over 4 weeks) or weekly (36 Gy in six fractions over 6 weeks) schedule that was nominated before randomisation. The primary outcome was overall survival, measured as the number of deaths; this analysis had 90% power with a one-sided α of 2·5% for a hazard ratio (HR) of 0·75. Secondary outcomes were failure-free survival, progression-free survival, metastatic progression-free survival, prostate cancer-specific survival, and symptomatic local event-free survival. Analyses used Cox proportional hazards and flexible parametric models, adjusted for stratification factors. The primary outcome analysis was by intention to treat. Two prespecified subgroup analyses tested the effects of prostate radiotherapy by baseline metastatic burden and radiotherapy schedule. This trial is registered with ClinicalTrials.gov, number NCT00268476.\n\nFindings: Between Jan 22, 2013, and Sept 2, 2016, 2061 men underwent randomisation, 1029 were allocated the control and 1032 radiotherapy. Allocated groups were balanced, with a median age of 68 years (IQR 63-73) and median amount of prostate-specific antigen of 97 ng/mL (33-315). 367 (18%) patients received early docetaxel. 1082 (52%) participants nominated the daily radiotherapy schedule before randomisation and 979 (48%) the weekly schedule. 819 (40%) men had a low metastatic burden, 1120 (54%) had a high metastatic burden, and the metastatic burden was unknown for 122 (6%). Radiotherapy improved failure-free survival (HR 0·76, 95% CI 0·68-0·84; p<0·0001) but not overall survival (0·92, 0·80-1·06; p=0·266). Radiotherapy was well tolerated, with 48 (5%) adverse events (Radiation Therapy Oncology Group grade 3-4) reported during radiotherapy and 37 (4%) after radiotherapy. The proportion reporting at least one severe adverse event (Common Terminology Criteria for Adverse Events grade 3 or worse) was similar by treatment group in the safety population (398 [38%] with control and 380 [39%] with radiotherapy).\n\nInterpretation: Radiotherapy to the prostate did not improve overall survival for unselected patients with newly diagnosed metastatic prostate cancer.\n\nFunding: Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Astellas, Clovis Oncology, Janssen, Novartis, Pfizer, and Sanofi-Aventis.\n\nIndexed on Europe PMC as PubMed record 30355464 (DOI 10.1016/s0140-6736(18)32486-3). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet 2018","url":"https://doi.org/10.1016/s0140-6736(18)32486-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30355464/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30355464"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["stampede"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2018,"doi":"10.1016/s0140-6736(18)32486-3","pmid":"30355464","authors":"Parker CC, James ND, Brawley CD, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-stampede-plos-med-2022-update","kind":"paper","name":"Radiotherapy to the prostate for men with metastatic prostate cancer in the UK and Switzerland: Long-term results from the STAMPEDE randomised controlled trial","aka":[],"tldr":"Later report from the STAMPEDE trial registered as NCT00268476, in PLOS Medicine (2022); its title describes an updated or longer-term analysis.","summary":"Background: STAMPEDE has previously reported that radiotherapy (RT) to the prostate improved overall survival (OS) for patients with newly diagnosed prostate cancer with low metastatic burden, but not those with high-burden disease. In this final analysis, we report long-term findings on the primary outcome measure of OS and on the secondary outcome measures of symptomatic local events, RT toxicity events, and quality of life (QoL).\n\nMethods and findings: Patients were randomised at secondary care sites in the United Kingdom and Switzerland between January 2013 and September 2016, with 1:1 stratified allocation: 1,029 to standard of care (SOC) and 1,032 to SOC+RT. No masking of the treatment allocation was employed. A total of 1,939 had metastatic burden classifiable, with 42% low burden and 58% high burden, balanced by treatment allocation. Intention-to-treat (ITT) analyses used Cox regression and flexible parametric models (FPMs), adjusted for stratification factors age, nodal involvement, the World Health Organization (WHO) performance status, regular aspirin or nonsteroidal anti-inflammatory drug (NSAID) use, and planned docetaxel use. QoL in the first 2 years on trial was assessed using prospectively collected patient responses to QLQ-30 questionnaire. Patients were followed for a median of 61.3 months. Prostate RT improved OS in patients with low, but not high, metastatic burden (respectively: 202 deaths in SOC versus 156 in SOC+RT, hazard ratio (HR) = 0·64, 95% CI 0.52, 0.79, p < 0.001; 375 SOC versus 386 SOC+RT, HR = 1.11, 95% CI 0.96, 1.28, p = 0·164; interaction p < 0.001). No evidence of difference in time to symptomatic local events was found. There was no evidence of difference in Global QoL or QLQ-30 Summary Score. Long-term urinary toxicity of grade 3 or worse was reported for 10 SOC and 10 SOC+RT; long-term bowel toxicity of grade 3 or worse was reported for 15 and 11, respectively.\n\nConclusions: Prostate RT improves OS, without detriment in QoL, in men with low-burden, newly diagnosed, metastatic prostate cancer, indicating that it should be recommended as a SOC.\n\nTrial registration: ClinicalTrials.gov NCT00268476, ISRCTN.com ISRCTN78818544.\n\nIndexed on Europe PMC as PubMed record 35671327 (DOI 10.1371/journal.pmed.1003998). Its abstract cites the registry id NCT00268476, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"PLoS Med 2022","url":"https://doi.org/10.1371/journal.pmed.1003998"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35671327/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35671327"},{"label":"ClinicalTrials.gov NCT00268476","url":"https://clinicaltrials.gov/study/NCT00268476"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["stampede"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["plos-medicine"],"dependsOn":[],"notes":[],"journal":"PLOS Medicine","year":2022,"doi":"10.1371/journal.pmed.1003998","pmid":"35671327","authors":"Parker CC, James ND, Brawley CD, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the STAMPEDE trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-anthony-nichols-lancet-oncol-2019","kind":"paper","name":"Radiotherapy versus transoral robotic surgery and neck dissection for oropharyngeal squamous cell carcinoma (ORATOR): an open-label, phase 2, randomised trial","aka":[],"tldr":"Paper by Anthony C. Nichols indexed on Europe PMC as PubMed record 31416685, in The Lancet Oncology (2019), one of the most cited records naming an author with this name at Verspeeten Family Cancer Centre, London Health Sciences Centre.","summary":"Background: Transoral robotic surgery (TORS) with concurrent neck dissection has supplanted radiotherapy in the USA as the most common treatment for oropharyngeal squamous cell carcinoma (OPSCC), yet no randomised trials have compared these modalities. We aimed to evaluate differences in quality of life (QOL) 1 year after treatment.\n\nMethods: The ORATOR trial was an investigator-initiated, multicentre, international, open-label, parallel-group, phase 2, randomised study. Patients were enrolled at six hospitals in Canada and Australia. We randomly assigned (1:1) patients aged 18 years or older, with Eastern Cooperative Oncology Group scores of 0-2, and with T1-T2, N0-2 (≤4 cm) OPSCC tumour types to radiotherapy (70 Gy, with chemotherapy if N1-2) or TORS plus neck dissection (with or without adjuvant chemoradiotherapy, based on pathology). Following stratification by p16 status, patients were randomly assigned using a computer-generated randomisation list with permuted blocks of four. The primary endpoint was swallowing-related QOL at 1 year as established using the MD Anderson Dysphagia Inventory (MDADI) score, powered to detect a 10-point improvement (a clinically meaningful change) in the TORS plus neck dissection group. All analyses were done by intention to treat. This study is registered with ClinicalTrials.gov (NCT01590355) and is active, but not currently recruiting.\n\nFindings: 68 patients were randomly assigned (34 per group) between Aug 10, 2012, and June 9, 2017. Median follow-up was 25 months (IQR 20-33) for the radiotherapy group and 29 months (23-43) for the TORS plus neck dissection group. MDADI total scores at 1 year were mean 86·9 (SD 11·4) in the radiotherapy group versus 80·1 (13·0) in the TORS plus neck dissection group (p=0·042). There were more cases of neutropenia (six [18%] of 34 patients vs none of 34), hearing loss (13 [38%] vs five [15%]), and tinnitus (12 [35%] vs two [6%]) reported in the radiotherapy group than in the TORS plus neck dissection group, and more cases of trismus in the TORS plus neck dissection group (nine [26%] vs one [3%]). The most common adverse events in the radiotherapy group were dysphagia (n=6), hearing loss (n=6), and mucositis (n=4), all grade 3, and in the TORS plus neck dissection group, dysphagia (n=9, all grade 3) and there was one death caused by bleeding after TORS.\n\nInterpretation: Patients treated with radiotherapy showed superior swallowing-related QOL scores 1 year after treatment, although the difference did not represent a clinically meaningful change. Toxicity patterns differed between the groups. Patients with OPSCC should be informed about both treatment options.\n\nFunding: Canadian Cancer Society Research Institute Grant (#701842), Ontario Institute for Cancer Research Clinician-Scientist research grant, and the Wolfe Surgical Research Professorship in the Biology of Head and Neck Cancers grant.\n\nIndexed on Europe PMC as PubMed record 31416685 (DOI 10.1016/s1470-2045(19)30410-3). Its author list gives \"Nichols AC\" with the affiliation \"Department of Otolaryngology-Head and Neck Surgery, Western University, London, ON, Canada. Electronic address: anthony.nichols@lhsc.on.ca\", which names Verspeeten Family Cancer Centre, London Health Sciences Centre; that is how the record was matched to Anthony C. Nichols, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2019","url":"https://doi.org/10.1016/s1470-2045(19)30410-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31416685/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31416685"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["anthony-nichols"],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2019,"doi":"10.1016/s1470-2045(19)30410-3","pmid":"31416685","authors":"Nichols AC, Theurer J, Prisman E, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Anthony C. Nichols at Verspeeten Family Cancer Centre, London Health Sciences Centre, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-rahib-projecting-cancer-deaths-2030-cancerres-2014","kind":"paper","name":"Rahib 2014: projecting US cancer incidence and deaths to 2030","aka":[],"tldr":"A projection that by 2030 pancreatic and liver cancers would overtake breast, prostate and colorectal cancers to become the second and third leading causes of cancer death in the United States, because progress against the common cancers was not being matched in these two.","summary":"Rahib and colleagues at the Pancreatic Cancer Action Network combined US population projections with registry trends in incidence and mortality to project cancer cases and deaths to 2030. They forecast that lung cancer would remain the leading cause of cancer death, that pancreatic and liver cancers would rise to second and third place, and that thyroid, melanoma and uterine cancers would be among the fastest-growing in incidence, while colorectal cancer would fall in rank. The paper was widely used to argue for research funding directed at cancers with stagnant outcomes.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1158/0008-5472.CAN-14-0155"}],"tags":[],"related":["paper-siegel-cancer-statistics-2024-cacancer-2024","paper-rahib-projection-us-cancer-2040-jama-netw-open-2021"],"cancers":["pancreatic","hcc","colorectal"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["incidence-vs-prevalence","mortality"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Cancer Research","year":2014,"doi":"10.1158/0008-5472.CAN-14-0155","authors":"Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM.","paperType":"observational","findings":["Projected that pancreatic and liver cancers would become the second and third leading causes of US cancer death by 2030, after lung cancer.","Breast, prostate and lung cancers projected to remain the most commonly diagnosed; thyroid, melanoma and uterine cancers among the fastest rising in incidence.","Projections driven by an ageing population combined with flat or rising death rates for pancreatic and liver cancer."],"whatItMeans":"This paper reframed pancreatic and liver cancer as the coming burden and is cited in most arguments for investing in them. Its pancreatic cancer projection has been tracking close to reality in the years since.","caveats":["Projections assume that recent trends continue and cannot anticipate new treatments or screening.","US-specific."],"changedPractice":false},{"id":"paper-rainbow-ramucirumab-paclitaxel-lancet-oncol-2014","kind":"paper","name":"RAINBOW: ramucirumab plus paclitaxel versus placebo plus paclitaxel in previously treated advanced gastric cancer","aka":[],"tldr":"Adding the anti-VEGFR2 antibody ramucirumab to weekly paclitaxel lengthened survival by over two months in gastric cancer that had progressed after first-line chemotherapy, establishing the standard second-line regimen.","summary":"Phase 3 placebo-controlled trial of 665 patients with advanced gastric or junctional adenocarcinoma progressing after first-line platinum-fluoropyrimidine chemotherapy randomised to ramucirumab or placebo with weekly paclitaxel.\n\nMedian overall survival was 9.6 versus 7.4 months (hazard ratio 0.81), progression-free survival 4.4 versus 2.9 months and response 28 versus 16 percent; neutropenia, hypertension and fatigue were more frequent with ramucirumab.","asOf":"2026-09-17","links":[{"label":"Lancet Oncol 2014","url":"https://doi.org/10.1016/S1470-2045(14)70420-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25240821/"}],"tags":[],"related":[],"cancers":["gastric-pdl1-high","gastric-cldn18-2-positive"],"sections":[],"technologies":[],"targets":[],"drugs":["ramucirumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["rainbow"],"people":["hansjochen-wilke"],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2014,"doi":"10.1016/S1470-2045(14)70420-6","pmid":"25240821","authors":"Wilke H, Muro K, Van Cutsem E, et al.","paperType":"rct","findings":["Median overall survival 9.6 vs 7.4 months; hazard ratio 0.81.","Median progression-free survival 4.4 vs 2.9 months."],"whatItMeans":"Ramucirumab-paclitaxel is the second-line standard for HER2-negative gastric cancer after chemo-immunotherapy, and the comparator for newer agents.","caveats":["Regional differences: benefit was smaller in Asian patients, partly because of more third-line therapy."],"changedPractice":true,"participants":665},{"id":"paper-ramp-201-avutometinib-defactinib-lgsoc-jco-2025","kind":"paper","name":"RAMP 201: avutometinib with or without defactinib in recurrent low-grade serous ovarian cancer","aka":[],"tldr":"The combination of the RAF/MEK clamp avutometinib and the FAK inhibitor defactinib shrank tumours in about a third of women with recurrent low-grade serous ovarian cancer and in 44 percent of those with KRAS mutations, leading to the first approval specific to this disease.","summary":"Phase 2 study of 115 patients with recurrent low-grade serous ovarian cancer treated with avutometinib alone or with defactinib; the combination was selected for expansion.\n\nIn the combination arm, objective response was 31 percent overall and 44 percent in KRAS-mutant tumours (17 percent in KRAS wild-type), with median duration of response of 31 months and median progression-free survival of 12.9 months overall; toxicity included creatine kinase elevation, nausea and rash.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2025","url":"https://doi.org/10.1200/JCO-25-00112"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40644648/"}],"tags":[],"related":[],"cancers":["low-grade-serous-ovarian-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["ramp-201"],"people":["susana-banerjee"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2025,"doi":"10.1200/JCO-25-00112","pmid":"40644648","authors":"Banerjee SN, Van Nieuwenhuysen E, Aghajanian C, et al.","paperType":"observational","findings":["Objective response 31 percent overall; 44 percent in KRAS-mutant and 17 percent in KRAS wild-type tumours.","Median duration of response 31.1 months."],"whatItMeans":"Avutometinib plus defactinib is approved for KRAS-mutant recurrent low-grade serous ovarian cancer, making KRAS testing a routine part of managing the disease; RAMP 301 is comparing it with standard therapy.","caveats":["Single-arm; approval was accelerated pending the randomised RAMP 301 trial."],"changedPractice":true,"participants":115},{"id":"paper-nct02411448-lancet-oncol-2019","kind":"paper","name":"Ramucirumab plus erlotinib in patients with untreated, EGFR-mutated, advanced non-small-cell lung cancer (RELAY): a randomised, double-blind, placebo-controlled, phase 3 trial","aka":[],"tldr":"Published report from the RELAY trial registered as NCT02411448, in The Lancet Oncology (2019), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Dual blockade of the EGFR and VEGF pathways in EGFR-mutated metastatic non-small-cell lung cancer (NSCLC) is supported by preclinical and clinical data, yet the approach is not widely implemented. RELAY assessed erlotinib, an EGFR tyrosine kinase inhibitor (TKI) standard of care, plus ramucirumab, a human IgG1 VEGFR2 antagonist, or placebo in patients with untreated EGFR-mutated metastatic NSCLC.\n\nMethods: This is a worldwide, double-blind, phase 3 trial done in 100 hospitals, clinics, and medical centres in 13 countries. Eligible patients were aged 18 years or older (20 years or older in Japan and Taiwan) at the time of study entry, had stage IV NSCLC, with an EGFR exon 19 deletion (ex19del) or exon 21 substitution (Leu858Arg) mutation, an Eastern Cooperative Oncology Group performance status of 0 or 1, and no CNS metastases. We randomly assigned eligible patients in a 1:1 ratio to receive oral erlotinib (150 mg/day) plus either intravenous ramucirumab (10 mg/kg) or matching placebo once every 2 weeks. Randomisation was done by an interactive web response system with a computer-generated sequence and stratified by sex, geographical region, EGFR mutation type, and EGFR testing method. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This trial is registered at ClinicalTrials.gov, NCT02411448, and is ongoing for long-term survival follow-up.\n\nFindings: Between Jan 28, 2016, and Feb 1, 2018, 449 eligible patients were enrolled and randomly assigned to treatment with ramucirumab plus erlotinib (n=224) or placebo plus erlotinib (n=225). Median duration of follow-up was 20·7 months (IQR 15·8-27·2). At the time of primary analysis, progression-free survival was significantly longer in the ramucirumab plus erlotinib group (19·4 months [95% CI 15·4-21·6]) than in the placebo plus erlotinib group (12·4 months [11·0-13·5]), with a stratified hazard ratio of 0·59 (95% CI 0·46-0·76; p<0·0001). Grade 3-4 treatment-emergent adverse events were reported in 159 (72%) of 221 patients in the ramucirumab plus erlotinib group versus 121 (54%) of 225 in the placebo plus erlotinib group. The most common grade 3-4 treatment-emergent adverse events in the ramucirumab plus erlotinib group were hypertension (52 [24%]; grade 3 only) and dermatitis acneiform (33 [15%]), and in the placebo plus erlotinib group were dermatitis acneiform (20 [9%]) and increased alanine aminotransferase (17 [8%]). Treatment-emergent serious adverse events were reported in 65 (29%) of 221 patients in the ramucirumab plus erlotinib group and 47 (21%) of 225 in the placebo plus erlotinib group. The most common serious adverse events of any grade in the ramucirumab plus erlotinib group were pneumonia (seven [3%]) and cellulitis and pneumothorax (four [2%], each); the most common in the placebo plus erlotinib group were pyrexia (four [2%]) and pneumothorax (three [1%]). One on-study treatment-related death due to an adverse event occurred (haemothorax after a thoracic drainage procedure for a pleural empyema) in the ramucirumab plus erlotinib group.\n\nInterpretation: Ramucirumab plus erlotinib demonstrated superior progression-free survival compared with placebo plus erlotinib in patients with untreated EGFR-mutated metastatic NSCLC. Safety was consistent with the safety profiles of the individual compounds in advanced lung cancer. The RELAY regimen is a viable new treatment option for the initial treatment of EGFR-mutated metastatic NSCLC.\n\nFunding: Eli Lilly.\n\nIndexed on Europe PMC as PubMed record 31591063 (DOI 10.1016/s1470-2045(19)30634-5). Its abstract cites the registry id NCT02411448, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2019","url":"https://doi.org/10.1016/s1470-2045(19)30634-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31591063/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31591063"},{"label":"ClinicalTrials.gov NCT02411448","url":"https://clinicaltrials.gov/study/NCT02411448"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct02411448"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2019,"doi":"10.1016/s1470-2045(19)30634-5","pmid":"31591063","authors":"Nakagawa K, Garon EB, Seto T, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02411448 with the most citations, so it is the natural first reading for anyone following the RELAY trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-hardcastle-nottingham-faecal-occult-blood-lancet-1996","kind":"paper","name":"Randomised controlled trial of faecal-occult-blood screening for colorectal cancer (Nottingham)","aka":[],"tldr":"The British trial, in 152,850 people around Nottingham, that showed offering a home stool test for hidden blood every two years cut deaths from bowel cancer by 15 percent. It is the trial the NHS Bowel Cancer Screening Programme was built on.","summary":"Between February 1981 and January 1991, Hardcastle and colleagues recruited 152,850 people aged 45 to 74 living in the Nottingham area and randomly allocated them to faecal occult blood screening or to no screening; controls were not told about the study. Screening-group participants were sent a Haemoccult test kit with instructions from their family doctor, the tests were not rehydrated, and those with negative results were re-invited every two years. Screening stopped in February 1995, by which time participants had been offered between three and six tests, and everyone was followed to June 1995.\n\nOf 893 cancers diagnosed in the screening group, 236 were detected by screening, 249 presented after a negative test or investigation and 400 presented in people who had never responded.","asOf":"2026-09-24","links":[{"label":"Lancet 1996","url":"https://doi.org/10.1016/S0140-6736(96)03386-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/8942775/"},{"label":"NHS bowel cancer screening","url":"https://www.nhs.uk/tests-and-treatments/bowel-cancer-screening/"}],"tags":["colorectal-evidence"],"related":["paper-minnesota-fobt-nejm-1993","paper-kronborg-funen-faecal-occult-blood-lancet-1996"],"cancers":["colorectal"],"sections":["early-detection","prevention"],"technologies":["colorectal-screening","endoscopy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["fit-test"],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-prevention-adoption"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":1996,"doi":"10.1016/S0140-6736(96)03386-7","pmid":"8942775","authors":"Hardcastle JD, Chamberlain JO, Robinson MH, et al.","paperType":"rct","findings":["75,253 in the screening group and 74,998 controls after exclusions; median follow-up 7.8 years.","44,838 (59.6 percent) completed at least one screen; 30,415 (40.4 percent) never completed any test.","360 deaths from colorectal cancer in the screening group against 420 in controls: a 15 percent reduction, odds ratio 0.85 (95 percent CI 0.74 to 0.98, p=0.026).","20 percent of screen-group cancers were stage A against 11 percent in controls."],"whatItMeans":"The evidence that a cheap home test posted to a whole population saves lives, and the reason England, Scotland, Wales and Northern Ireland all run bowel screening programmes; the 40 percent who never did the test are the reason uptake is still the biggest lever.","caveats":["Guaiac testing, superseded by the more sensitive and more acceptable faecal immunochemical test.","The 15 percent mortality reduction is an intention-to-screen figure diluted by the 40 percent who never took part.","No effect on all-cause mortality was demonstrated, as in every screening trial of this size."],"changedPractice":true,"participants":152850},{"id":"paper-hayashi-site-specific-vs-empirical-chemotherapy-cup-jco-2019","kind":"paper","name":"Randomised phase 2 trial of site-specific treatment based on gene expression profiling versus carboplatin and paclitaxel in cancer of unknown primary","aka":[],"tldr":"Using a gene expression test to guess where a cancer of unknown primary came from, and treating it as that cancer, did not help patients live longer than standard carboplatin and paclitaxel.","summary":"Japanese multicentre randomised phase 2 trial of 130 patients with cancer of unknown primary, assigned to site-specific chemotherapy chosen from a 2,000-gene expression tissue-of-origin assay or to empirical carboplatin plus paclitaxel.\n\nOne-year survival was 44.2 percent with site-specific treatment against 54.9 percent with empirical chemotherapy, and progression-free survival did not differ. The trial, like the earlier GEFCAPI 04 study, argued against routine tissue-of-origin testing to direct chemotherapy.","asOf":"2026-09-18","links":[{"label":"J Clin Oncol 2019","url":"https://doi.org/10.1200/JCO.18.00771"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30653423/"}],"tags":[],"related":[],"cancers":["cup-favourable-subsets","cup-unfavourable"],"sections":[],"technologies":[],"targets":[],"drugs":["carboplatin","paclitaxel"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2019,"doi":"10.1200/JCO.18.00771","pmid":"30653423","authors":"Hayashi H, Kurata T, Takiguchi Y, et al.","paperType":"rct","findings":["One-year survival 44.2 percent with site-specific therapy versus 54.9 percent with carboplatin and paclitaxel; no improvement."],"whatItMeans":"Predicting the primary site by gene expression and treating accordingly is not better than empirical chemotherapy, so guidelines do not recommend it; the field moved to genomic profiling for actionable targets instead.","caveats":["Randomised phase 2 with survival as the primary endpoint; underpowered for small differences.","Some predicted primaries received chemotherapy of limited efficacy, which may have blunted any benefit."],"changedPractice":true,"participants":130},{"id":"paper-kronborg-funen-faecal-occult-blood-lancet-1996","kind":"paper","name":"Randomised study of screening for colorectal cancer with faecal-occult-blood test (Funen)","aka":[],"tldr":"The Danish twin of the Nottingham trial: 61,933 people on the island of Funen, stool tests every two years for ten years, and an 18 percent fall in deaths from bowel cancer.","summary":"Kronborg, Fenger, Olsen, Jørgensen and Søndergaard randomised 137,485 people aged 45 to 75 living in Funen, Denmark in blocks of 14, allocating three per 14 to screening (30,967), three per 14 to a control group (30,966) and eight per 14 to no enrolment. Controls were not told about the study. Hemoccult-II tests, with dietary restrictions and without rehydration, were sent to the screening group; only those who completed the first round were invited to the remaining four rounds over ten years.\n\nThe same number of cancers arose in each group (481 against 483), but fewer people died of them, which is what a screening test that finds cancers earlier is expected to do when it is not also removing the precursor lesions at scale.","asOf":"2026-09-24","links":[{"label":"Lancet 1996","url":"https://doi.org/10.1016/S0140-6736(96)03430-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/8942774/"}],"tags":["colorectal-evidence"],"related":["paper-hardcastle-nottingham-faecal-occult-blood-lancet-1996","paper-minnesota-fobt-nejm-1993"],"cancers":["colorectal"],"sections":["early-detection","prevention"],"technologies":["colorectal-screening"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["fit-test"],"trials":[],"people":[],"bottlenecks":["b-early-detection"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":1996,"doi":"10.1016/S0140-6736(96)03430-7","pmid":"8942774","authors":"Kronborg O, Fenger C, Olsen J, Jørgensen OD, Søndergaard O.","paperType":"rct","findings":["20,672 of 30,967 (67 percent) completed the first screening round; more than 90 percent of those accepted repeat screening.","481 colorectal cancers in the screening group and 483 in controls over ten years.","205 deaths attributable to colorectal cancer in the screening group against 249 in controls: mortality ratio 0.82 (95 percent CI 0.68 to 0.99, p=0.03)."],"whatItMeans":"The second randomised trial to show the same effect in a different health system; together with Nottingham and Minnesota it made biennial stool testing an accepted public health intervention across Europe.","caveats":["Guaiac testing without rehydration, which has low single-test sensitivity; the benefit comes from repeating it.","Identical cancer incidence in the two groups shows that guaiac screening shifts stage rather than preventing cancer, unlike endoscopic screening."],"changedPractice":true,"participants":61933},{"id":"paper-grever-j-clin-oncol","kind":"paper","name":"Randomized comparison of pentostatin versus interferon alfa-2a in previously untreated patients with hairy cell leukemia: an intergroup study","aka":[],"tldr":"Paper cited by one treatment page, indexed on Europe PMC as PubMed record 7707126 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: Therapy of hairy cell leukemia has markedly improved. Interferon alfa-2a and pentostatin are active agents. The National Cancer Institute organized an intergroup trial to compare these agents prospectively in untreated patients.\n\nMethods: Patients were randomized to receive either interferon alfa-2a (3 x 10(6) U subcutaneously three times per week) or pentostatin (4 mg/m2 intravenously every 2 weeks). Patients who did not respond to initial treatment were crossed over.\n\nResults: Of 356 patients on study, 313 were eligible. Among interferon patients, 17 of 159 (11%) achieved a confirmed complete remission and 60 of 159 (38%) had a confirmed complete or partial remission. Among pentostatin patients, 117 of 154 (76%) achieved a confirmed complete remission and 121 of 154 (79%) had a confirmed complete or partial remission. Additional patients achieved criteria for complete remission, but lacked confirmatory follow-up evaluation. Response rates were significantly higher (P <.0001) and relapse-free survival was significantly longer with pentostatin than interferon (P <.0001). The median follow-up duration is 57 months (range, 19 to 82). Myelosuppression was more frequent with pentostatin (P =.013). A multivariate logistic regression analysis of the confirmed complete remissions on pentostatin showed the following factors to be important for achieving a complete remission: high hemoglobin level (two-tailed P =.024), young age (P =.0085), and no or little splenomegaly (P =.0029).\n\nConclusion: Both agents were well tolerated. Pentostatin produced higher response rates, and the responses were durable. Patient age and clinical status had an impact on outcome with pentostatin. Pentostatin is effective therapy for hairy cell leukemia.\n\nIndexed on Europe PMC as PubMed record 7707126 (DOI 10.1200/jco.1995.13.4.974). Matched by DOI alone: one treatment page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 1995","url":"https://doi.org/10.1200/jco.1995.13.4.974"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/7707126/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/7707126"}],"tags":["europepmc-ingest"],"related":["pentostatin"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":1995,"doi":"10.1200/jco.1995.13.4.974","pmid":"7707126","authors":"Grever M, Kopecky K, Foucar MK, et al.","paperType":"rct","findings":[],"whatItMeans":"One treatment page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-sandhya-j-clin-oncol","kind":"paper","name":"Randomized Double-Blind Placebo-Controlled Study of Olanzapine for Chemotherapy-Related Anorexia in Patients With Locally Advanced or Metastatic Gastric, Hepatopancreaticobiliary, and Lung Cancer","aka":[],"tldr":"Paper cited by one trial page and one technology page, indexed on Europe PMC as PubMed record 36977285 and published in Journal of Clinical Oncology; the citing pages link this DOI, which is how the record was matched.","summary":"Purpose: Anorexia occurs in 30%-80% of patients with advanced malignancies, which may be worsened with chemotherapy. This trial assessed the efficacy of olanzapine in stimulating appetite and improving weight gain in patients receiving chemotherapy.\n\nMethods: Adults (≥18 years) with untreated, locally advanced, or metastatic gastric, hepatopancreaticobiliary (HPB), and lung cancers were randomly assigned (double-blind) to receive olanzapine (2.5 mg once a day for 12 weeks) or placebo along with chemotherapy. Both groups received standard nutritional assessment and dietary advice. The primary outcomes were the proportion of patients with weight gain > 5% and the improvement in appetite (assessed by the visual analog scale [VAS] and the Functional Assessment of Chronic Illness Therapy system of Quality-of-Life questionnaires Anorexia Cachexia subscale [FAACT ACS]). Secondary end points were change in nutritional status, quality of life (QOL), and chemotherapy toxicity.\n\nResults: We enrolled 124 patients (olanzapine, 63 and placebo, 61) with a median age of 55 years (18-78 years), of whom 112 (olanzapine, 58 and placebo, 54) were analyzable. The majority (n = 99, 80%) had metastatic cancer (gastric [n = 68, 55%] > lung [n = 43, 35%] > HPB [n = 13, 10%]). The olanzapine arm had a greater proportion of patients with a weight gain of > 5% (35 of 58 [60%] v 5 of 54 [9%], P <.001) and improvement in appetite by VAS (25 of 58 [43%] v 7 of 54 [13%], P <.001) and by FAACT ACS (scores ≥37:13 of 58 [22%] v 2 of 54 [4%], P =.004). Patients on olanzapine had better QOL, nutritional status, and lesser chemotoxicity. Side effects attributable to olanzapine were minimal.\n\nConclusion: Low-dose, daily olanzapine is a simple, inexpensive, well-tolerated intervention that significantly improves appetite and weight gain in newly diagnosed patients on chemotherapy.\n\nIndexed on Europe PMC as PubMed record 36977285 (DOI 10.1200/jco.22.01997). Matched by DOI alone: one trial page and one technology page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2023","url":"https://doi.org/10.1200/jco.22.01997"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36977285/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36977285"}],"tags":["europepmc-ingest"],"related":["cachexia-appetite-pharmacotherapy"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["olanzapine-appetite-tmh"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2023,"doi":"10.1200/jco.22.01997","pmid":"36977285","authors":"Sandhya L, Devi Sreenivasan N, Goenka L, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page and one technology page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-carboplatin-glioblastoma-neuro-oncol-2015","kind":"paper","name":"Randomized phase 2 study of carboplatin and bevacizumab in recurrent glioblastoma","aka":[],"tldr":"Phase 2 or 3 results paper on Carboplatin in Glioma & glioblastoma, in Neuro-Oncology (2015), one of the most cited Europe PMC records with Carboplatin in its title.","summary":"Background: The optimal use of bevacizumab in recurrent glioblastoma (GBM), including the choice of monotherapy or combination therapy, remains uncertain. The purpose of this study was to compare combination therapy with bevacizumab monotherapy.\n\nMethods: This was a 2-part randomized phase 2 study. Eligibility criteria included recurrent GBM after radiotherapy and temozolomide, no other chemotherapy for GBM, and Eastern Cooperative Oncology Group performance status 0-2. The primary objective (Part 1) was to determine the effect of bevacizumab plus carboplatin versus bevacizumab monotherapy on progression-free survival (PFS) using modified Response Assessment in Neuro-Oncology criteria. Bevacizumab was given every 2 weeks, 10 mg/kg; and carboplatin every 4 weeks, (AUC 5). On progression, patients able to continue were randomized to continue or cease bevacizumab (Part 2). Secondary endpoints included objective radiological response rate (ORR), quality of life, toxicity, and overall survival (OS).\n\nResults: One hundred twenty-two patients (median age, 55y) were enrolled to Part 1 from 18 Australian sites. Median follow-up was 32 months, and median on-treatment time was 3.3 months. Median PFS was 3.5 months for each arm (hazard ratio [HR]: 0.92, 95% CI: 0.64-1.33, P =.66). ORR was 14% (combination) versus 6% (monotherapy) (P =.18). Median OS was 6.9 (combination) versus 7.5 months (monotherapy) (HR: 1.18, 95% CI: 0.82-1.69, P =.38). The incidence of bevacizumab-related adverse events was similar to prior literature, with no new toxicity signals. Toxicities were higher in the combination arm. Part 2 data (n = 48) will be reported separately.\n\nConclusions: Adding carboplatin resulted in more toxicity without additional clinical benefit. Clinical outcomes in patients with recurrent GBM treated with bevacizumab were inferior to those in previously reported studies.\n\nClinical trials registration nr: ACTRN12610000915055.\n\nIndexed on Europe PMC as PubMed record 26130744 (DOI 10.1093/neuonc/nov104). Its title names Carboplatin and its text names Glioma & glioblastoma; PubMed types it as a clinical trial report (Clinical Trial, Phase II, Research Support, Non-U.S. Gov't, research-article, Multicenter Study, Randomized Controlled Trial). It was matched automatically to the idea \"A skull ultrasound implant that opens the barrier at every cycle\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Neuro Oncol 2015","url":"https://doi.org/10.1093/neuonc/nov104"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26130744/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26130744"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["neuro-oncology"],"dependsOn":[],"notes":[],"journal":"Neuro-Oncology","year":2015,"doi":"10.1093/neuonc/nov104","pmid":"26130744","authors":"Field KM, Simes J, Nowak AK, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Carboplatin in Glioma & glioblastoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Carboplatin in the title and Glioma & glioblastoma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-pembrolizumab-glioblastoma-clin-cancer-res-2021","kind":"paper","name":"Randomized Phase II and Biomarker Study of Pembrolizumab plus Bevacizumab versus Pembrolizumab Alone for Patients with Recurrent Glioblastoma","aka":[],"tldr":"Phase 2 or 3 results paper on Pembrolizumab in Glioma & glioblastoma, in Clinical Cancer Research (2021), one of the most cited Europe PMC records with Pembrolizumab in its title.","summary":"Purpose: VEGF is upregulated in glioblastoma and may contribute to immunosuppression. We performed a phase II study of pembrolizumab alone or with bevacizumab in recurrent glioblastoma.\n\nPatients and methods: Eighty bevacizumab-naïve patients with recurrent glioblastoma were randomized to pembrolizumab with bevacizumab (cohort A, n = 50) or pembrolizumab monotherapy (cohort B, n = 30). The primary endpoint was 6-month progression-free survival (PFS-6). Assessed biomarkers included evaluation of tumor programmed death-ligand 1 expression, tumor-infiltrating lymphocyte density, immune activation gene expression signature, and plasma cytokines. The neurologic assessment in neuro-oncology (NANO) scale was used to prospectively assess neurologic function.\n\nResults: Pembrolizumab alone or with bevacizumab was well tolerated but of limited benefit. For cohort A, PFS-6 was 26.0% [95% confidence interval (CI), 16.3-41.5], median overall survival (OS) was 8.8 months (95% CI, 7.7-14.2), objective response rate (ORR) was 20%, and median duration of response was 48 weeks. For cohort B, PFS-6 was 6.7% (95% CI, 1.7-25.4), median OS was 10.3 months (95% CI, 8.5-12.5), and ORR was 0%. Tumor immune markers were not associated with OS, but worsened OS correlated with baseline dexamethasone use and increased posttherapy plasma VEGF (cohort A) and mutant IDH1, unmethylated MGMT, and increased baseline PlGF and sVEGFR1 levels (cohort B). The NANO scale contributed to overall outcome assessment.\n\nConclusions: Pembrolizumab was ineffective as monotherapy and with bevacizumab for recurrent glioblastoma. The infrequent radiographic responses to combinatorial therapy were durable. Tumor immune biomarkers did not predict outcome. Baseline dexamethasone use and tumor MGMT warrant further study as potential biomarkers in glioblastoma immunotherapy trials.\n\nIndexed on Europe PMC as PubMed record 33199490 (DOI 10.1158/1078-0432.ccr-20-2500). Its title names Pembrolizumab and its text names Glioma & glioblastoma; PubMed types it as a clinical trial report (Clinical Trial, Phase II, Comparative Study, Research Support, Non-U.S. Gov't, research-article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural). It was matched automatically to the idea \"Neoadjuvant immunotherapy with surgical window for glioblastoma\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Clin Cancer Res 2021","url":"https://doi.org/10.1158/1078-0432.ccr-20-2500"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33199490/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33199490"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2021,"doi":"10.1158/1078-0432.ccr-20-2500","pmid":"33199490","authors":"Nayak L, Molinaro AM, Peters K, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Pembrolizumab in Glioma & glioblastoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Pembrolizumab in the title and Glioma & glioblastoma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-ligibel-npj-breast-cancer","kind":"paper","name":"Randomized phase III trial evaluating the role of weight loss in adjuvant treatment of overweight and obese women with early breast cancer (Alliance A011401): study design","aka":[],"tldr":"Paper cited by one trial page and one technology page, indexed on Europe PMC as PubMed record 28948213 and published in NPJ breast cancer; the citing pages link this DOI, which is how the record was matched.","summary":"Excess body weight is a poor prognostic factor in women with early breast cancer, but the effect of weight loss on the risk of breast cancer recurrence and mortality in women who are overweight or obese at the time of breast cancer diagnosis has not been evaluated. The Alliance for Clinical Trials in Oncology Breast Cancer Weight Loss trial, also known as A011401, is testing the impact of a telephone-based weight loss program on invasive disease-free survival in 3136 women with a body mass index ≥27 kg/m 2 who have recently been diagnosed with stage II-III, HER-2 negative breast cancer. Secondary outcomes of the trial include the impact of the weight loss intervention on overall survival, body weight, physical activity, dietary intakes, incidence of comorbidities, serum biomarkers and patient reported outcomes. Participants are randomized 1:1 to a 2-year, telephone-based weight loss intervention or to an education control group. The intervention is delivered through 42 telephone calls, delivered by health coaches based at the Dana-Farber Cancer Institute. Calls are supplemented by an intervention workbook, as well as a number of tools to help facilitate weight loss. Intervention goals include loss of 10% of baseline body weight, achieved through caloric restriction and increased physical activity. This large-scale study testing the impact of purposeful weight loss after cancer diagnosis on the risk of breast cancer recurrence and mortality has the potential to make weight loss programs a standard part of breast cancer treatment.\n\nIndexed on Europe PMC as PubMed record 28948213 (DOI 10.1038/s41523-017-0040-8). Matched by DOI alone: one trial page and one technology page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"NPJ Breast Cancer 2017","url":"https://doi.org/10.1038/s41523-017-0040-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28948213/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28948213"}],"tags":["europepmc-ingest"],"related":["dietitian-led-weight-loss-breast"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["bwel"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"NPJ breast cancer","year":2017,"doi":"10.1038/s41523-017-0040-8","pmid":"28948213","authors":"Ligibel JA, Barry WT, Alfano C, et al.","paperType":"review","findings":[],"whatItMeans":"One trial page and one technology page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-phoenix-ibrutinib-r-chop-non-gcb-dlbcl-jco-2019","kind":"paper","name":"Randomized phase III trial of ibrutinib and R-CHOP in non-germinal centre B-cell diffuse large B-cell lymphoma (PHOENIX)","aka":["PHOENIX trial","Younes 2019","Ibrutinib with R-CHOP in non-germinal centre diffuse large B-cell lymphoma"],"tldr":"Adding a targeted tablet to standard first-line chemotherapy failed overall, helped people under 60 substantially, and harmed people over 60 by making them unable to finish the chemotherapy.","summary":"PHOENIX is the most instructive negative trial in diffuse large B-cell lymphoma, because the reason it failed is legible. 838 patients with non-germinal-centre disease, 75.9 per cent of them of the activated B-cell subtype, were randomised to ibrutinib 560 mg daily or placebo with R-CHOP. Median age was 62.\n\nThe trial missed its primary endpoint in both the intention-to-treat population (event-free survival hazard ratio 0.934) and the activated B-cell subgroup (0.949). A preplanned analysis found a significant interaction between treatment and age. In patients under 60, ibrutinib improved event-free survival (hazard ratio 0.579), progression-free survival (0.556) and overall survival (0.330), with serious adverse events rising from 28.6 to 35.7 per cent and the proportion receiving at least six cycles of R-CHOP unchanged at 92.9 against 93.0 per cent. In patients aged 60 or over, ibrutinib worsened all three endpoints, raised serious adverse events from 38.2 to 63.4 per cent, and cut the proportion completing six cycles of R-CHOP from 88.8 to 73.7 per cent.\n\nThe mechanism of the failure is therefore not biological but practical: the added drug stopped older patients from receiving the chemotherapy that cures the disease. That is the finding behind every subsequent attempt to use a better-tolerated Bruton tyrosine kinase inhibitor in this setting, including the ARCHED trial.","asOf":"2026-10-01","links":[{"label":"Journal of Clinical Oncology 2019","url":"https://doi.org/10.1200/JCO.18.02403"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30901302/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30901302"}],"tags":["lymphoma-evidence"],"related":["paper-schmitz-genetics-pathogenesis-dlbcl-nejm-2018","paper-hans-immunohistochemistry-cell-of-origin-dlbcl-blood-2004","lymphoma-roadmap"],"cancers":["dlbcl","non-hodgkin-lymphoma"],"sections":["targeted-therapy","chemotherapy"],"technologies":[],"targets":["btk","cd20"],"drugs":["ibrutinib","rituximab","cyclophosphamide","doxorubicin","vincristine","prednisone"],"companies":[],"institutions":[],"pathways":["bcr-signalling"],"terms":["r-chop","cell-of-origin"],"trials":["phoenix","arched"],"people":["laurie-sehn","peter-johnson"],"bottlenecks":["b-negative-results","b-aging-comorbidity","b-biomarker-validation"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2019,"doi":"10.1200/JCO.18.02403","pmid":"30901302","authors":"Younes A, Sehn LH, Johnson P, et al.","paperType":"rct","findings":["Ibrutinib with R-CHOP did not improve event-free survival in the intention-to-treat population (hazard ratio 0.934) or in the activated B-cell population (0.949).","A preplanned analysis showed a significant interaction between treatment and age.","In patients under 60, ibrutinib improved event-free survival (hazard ratio 0.579), progression-free survival (0.556) and overall survival (0.330).","In patients aged 60 or over, ibrutinib worsened all three endpoints and raised serious adverse events from 38.2 to 63.4 per cent.","The proportion of patients receiving at least six cycles of R-CHOP fell from 88.8 to 73.7 per cent with ibrutinib in those aged 60 or over, but was unchanged in those under 60."],"whatItMeans":"A failure worth reading: the drug worked where patients could tolerate the regimen it was added to, and harmed where they could not. It is the strongest argument in lymphoma for designing first-line combinations around what an older patient can finish.","caveats":["The age subgroup result is a subgroup analysis, even though the interaction test was preplanned, and has never been confirmed by a trial restricted to younger patients.","Patients were selected by the Hans immunohistochemistry algorithm rather than by genetic subtype; LymphGen and the Schmitz classification suggest the responsive group is narrower than non-germinal-centre.","Ibrutinib is the least selective of the Bruton tyrosine kinase inhibitors, so the toxicity finding may not transfer to acalabrutinib or zanubrutinib."],"changedPractice":false,"participants":838},{"id":"paper-halo-301-pegvorhyaluronidase-jco-2020","kind":"paper","name":"Randomized Phase III Trial of Pegvorhyaluronidase Alfa With Nab-Paclitaxel Plus Gemcitabine for Patients With Hyaluronan-High Metastatic Pancreatic Adenocarcinoma","aka":[],"tldr":"The 2020 trial of an enzyme meant to dissolve the dense matrix around pancreatic tumours so chemotherapy could reach them: more tumours shrank, but patients lived no longer, and the drug was abandoned.","summary":"HALO 109-301 was a phase 3, randomised, double-blind, placebo-controlled trial in untreated, metastatic, hyaluronan-high pancreatic ductal adenocarcinoma. Patients were randomised 2:1 to pegvorhyaluronidase alfa (PEGPH20, 3.0 micrograms per kilogram twice weekly in cycle 1 then weekly) plus nab-paclitaxel and gemcitabine, or placebo plus the same chemotherapy; 494 were randomised and 492 analysed (327 versus 165). With 330 deaths, median overall survival was 11.2 versus 11.5 months (hazard ratio 1.00, 95 percent confidence interval 0.80 to 1.27, P = 0.97); median progression-free survival 7.1 versus 7.1 months; objective response 47 versus 36 percent. Grade 3 or higher fatigue (16.0 versus 9.6 percent), muscle spasms (6.5 versus 0.6) and hyponatraemia (8.0 versus 3.8) were commoner with PEGPH20. The authors concluded the results do not support further development.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2020","url":"https://doi.org/10.1200/JCO.20.00590"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32706635/"},{"label":"ClinicalTrials.gov NCT02715804","url":"https://clinicaltrials.gov/study/NCT02715804"},{"label":"Trial design rationale (Future Oncol 2018)","url":"https://doi.org/10.2217/fon-2017-0338"},{"label":"J Clin Oncol 2020","url":"https://doi.org/10.1200/jco.20.00590"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32706635"}],"tags":["pancreatic-evidence"],"related":["paper-ozdemir-caf-depletion-accelerates-pancreatic-cancer-cancer-cell-2014","paper-mpact-nab-paclitaxel-gemcitabine-nejm-2013","mechanical-theory-of-cancer","microenvironment-inflammation-theory"],"cancers":["pancreatic","metastatic-pdac"],"sections":[],"technologies":[],"targets":[],"drugs":["gemcitabine-nab-paclitaxel"],"companies":[],"institutions":[],"pathways":["caf-activation-desmoplasia","tumor-microenvironment"],"terms":["desmoplasia","desmoplastic-stroma-rich"],"trials":[],"people":["eric-van-cutsem"],"bottlenecks":["b-negative-results","b-tme-immunosuppression"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/JCO.20.00590","pmid":"32706635","authors":"Van Cutsem E, Tempero MA, Sigal D, et al.","paperType":"rct","findings":["492 patients analysed, hyaluronan-high, 2:1 randomisation, double-blind.","Median overall survival 11.2 versus 11.5 months (hazard ratio 1.00); progression-free survival 7.1 versus 7.1 months.","Objective response 47 versus 36 percent.","More grade 3 or higher fatigue, muscle spasms and hyponatraemia with PEGPH20."],"whatItMeans":"The definitive negative result for first-generation stromal targeting: a biomarker-selected population, a drug that did what it was designed to do to the matrix, and no survival benefit; the stroma ideas on this page start from here.","caveats":["Hyaluronan-high selection by a companion assay; the result does not exclude other stromal targets.","Response rate rose without survival, a pattern seen again with other pancreatic agents."],"changedPractice":true,"participants":494},{"id":"paper-elkins-j-clin-oncol","kind":"paper","name":"Randomized trial of a hypnosis intervention for treatment of hot flashes among breast cancer survivors","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 18809612 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: Hot flashes are a significant problem for many breast cancer survivors. Hot flashes can cause discomfort, disrupted sleep, anxiety, and decreased quality of life. A well-tolerated and effective mind-body treatment for hot flashes would be of great value. On the basis of previous case studies, this study was developed to evaluate the effect of a hypnosis intervention for hot flashes.\n\nPatients and methods: Sixty female breast cancer survivors with hot flashes were randomly assigned to receive hypnosis intervention (five weekly sessions) or no treatment. Eligible patients had to have a history of primary breast cancer without evidence of detectable disease and 14 or more weekly hot flashes for at least 1 month. The major outcome measure was a bivariate construct that represented hot flash frequency and hot flash score, which was analyzed by a classic sums and differences comparison. Secondary outcome measures were self-reports of interference of hot flashes on daily activities.\n\nResults: Fifty-one randomly assigned women completed the study. By the end of the treatment period, hot flash scores (frequency x average severity) decreased 68% from baseline to end point in the hypnosis arm (P <.001). Significant improvements in self-reported anxiety, depression, interference of hot flashes on daily activities, and sleep were observed for patients who received the hypnosis intervention (P <.005) in comparison to the no treatment control group.\n\nConclusion: Hypnosis appears to reduce perceived hot flashes in breast cancer survivors and may have additional benefits such as reduced anxiety and depression, and improved sleep.\n\nIndexed on Europe PMC as PubMed record 18809612 (DOI 10.1200/jco.2008.16.6389). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2008","url":"https://doi.org/10.1200/jco.2008.16.6389"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/18809612/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/18809612"}],"tags":["europepmc-ingest"],"related":["hypnosis-cancer-care"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2008,"doi":"10.1200/jco.2008.16.6389","pmid":"18809612","authors":"Elkins G, Marcus J, Stearns V, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-verwaal-cytoreduction-hipec-peritoneal-colorectal-jco-2003","kind":"paper","name":"Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer","aka":[],"tldr":"The Dutch trial that put heated chemotherapy into the abdomen after stripping out all visible tumour, and nearly doubled median survival from 12.6 to 22.3 months. Eight percent of patients died of the treatment.","summary":"Verwaal, van Ruth, de Bree and colleagues randomly assigned 105 patients between February 1998 and August 2001 to standard treatment (systemic fluorouracil-leucovorin with or without palliative surgery) or to aggressive cytoreduction with hyperthermic intraperitoneal chemotherapy followed by the same systemic regimen. The primary end point was survival.\n\nSubgroup analysis showed that patients with fewer regions of the abdominal cavity involved, and those in whom cytoreduction was macroscopically complete, did far better, which is the selection principle every peritoneal service has used since.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2003","url":"https://doi.org/10.1200/JCO.2003.04.187"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/14551293/"}],"tags":["colorectal-evidence"],"related":["paper-quenet-prodige-7-hipec-peritoneal-colorectal-lancet-oncol-2021"],"cancers":["colorectal"],"sections":["surgery"],"technologies":["hipec"],"targets":[],"drugs":["fluorouracil","leucovorin"],"companies":[],"institutions":["nki"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-surgery-radiation-innovation","b-care-fragmentation"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2003,"doi":"10.1200/JCO.2003.04.187","pmid":"14551293","authors":"Verwaal VJ, van Ruth S, de Bree E, et al.","paperType":"rct","findings":["After a median 21.6 months, median survival 12.6 months with standard treatment against 22.3 months with cytoreduction plus hyperthermic intraperitoneal chemotherapy (log-rank p=0.032).","Treatment-related mortality in the aggressive therapy group 8 percent, with most complications related to bowel leakage.","Patients with 0 to 5 of seven abdominal regions involved survived significantly longer than those with 6 or 7 (p<0.0001).","Macroscopically complete cytoreduction was associated with significantly better survival than limited or extensive residual disease (p<0.0001)."],"whatItMeans":"The trial that created peritoneal surface malignancy as a speciality, and the reason patients with limited peritoneal disease are referred to designated centres; PRODIGE 7 later showed the benefit belongs to the surgery, not to the heated chemotherapy.","caveats":["105 patients, and the control arm received fluorouracil-leucovorin alone, a standard superseded within two years by oxaliplatin and irinotecan combinations.","8 percent treatment-related mortality.","The trial could not separate the contribution of the cytoreduction from that of the intraperitoneal chemotherapy, which is the question PRODIGE 7 was designed to answer."],"changedPractice":true,"participants":105},{"id":"paper-citron-j-clin-oncol","kind":"paper","name":"Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 12668651 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: Using a 2 x 2 factorial design, we studied the adjuvant chemotherapy of women with axillary node-positive breast cancer to compare sequential doxorubicin (A), paclitaxel (T), and cyclophosphamide (C) with concurrent doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T) for disease-free (DFS) and overall survival (OS); to determine whether the dose density of the agents improves DFS and OS; and to compare toxicities.\n\nPatients and methods: A total of 2,005 female patients were randomly assigned to receive one of the following regimens: (I) sequential A x 4 (doses) --> T x 4 --> C x 4 with doses every 3 weeks, (II) sequential A x 4 --> T x 4 --> C x 4 every 2 weeks with filgrastim, (III) concurrent AC x 4 --> T x 4 every 3 weeks, or (IV) concurrent AC x 4 --> T x 4 every 2 weeks with filgrastim.\n\nResults: A protocol-specified analysis was performed at a median follow-up of 36 months: 315 patients had experienced relapse or died, compared with 515 expected treatment failures. Dose-dense treatment improved the primary end point, DFS (risk ratio [RR] = 0.74; P =.010), and OS (RR = 0.69; P =.013). Four-year DFS was 82% for the dose-dense regimens and 75% for the others. There was no difference in either DFS or OS between the concurrent and sequential schedules. There was no interaction between density and sequence. Severe neutropenia was less frequent in patients who received the dose-dense regimens.\n\nConclusion: Dose density improves clinical outcomes significantly, despite the lower than expected number of events at this time. Sequential chemotherapy is as effective as concurrent chemotherapy.\n\nIndexed on Europe PMC as PubMed record 12668651 (DOI 10.1200/jco.2003.09.081). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2003","url":"https://doi.org/10.1200/jco.2003.09.081"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/12668651/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/12668651"}],"tags":["europepmc-ingest"],"related":["norton-simon-hypothesis"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2003,"doi":"10.1200/jco.2003.09.081","pmid":"12668651","authors":"Citron ML, Berry DA, Cirrincione C, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-trog-99-03-radiotherapy-systemic-therapy-early-follicular-jco-2018","kind":"paper","name":"Randomized trial of systemic therapy after involved-field radiotherapy in patients with early-stage follicular lymphoma: TROG 99.03","aka":["TROG 99.03","MacManus 2018","ALLG NHLLOW5"],"tldr":"Adding six cycles of drug treatment after radiotherapy for early follicular lymphoma cut relapses outside the treated area and improved ten-year freedom from progression from 41 to 59 per cent.","summary":"A multicentre randomised controlled trial enrolling patients with stage I to II low-grade follicular lymphoma after computed tomography staging and bone marrow biopsy; positron emission tomography was not mandatory. Patients were randomised to 30 Gy of involved-field radiotherapy alone, or the same radiotherapy followed by six cycles of cyclophosphamide, vincristine and prednisolone. From 2006 rituximab was added to the systemic arm.\n\nBetween 2000 and 2012, 150 patients were enrolled, 75 per arm; of the 75 in the systemic arm, 44 received CVP and 31 R-CVP. At randomisation 75 per cent had stage I disease, median age was 57, 52 per cent were male and 48 per cent had positron emission tomography staging. At a median follow-up of 9.6 years (range 3.1 to 15.8), progression-free survival favoured the systemic arm (hazard ratio 0.57, 95 per cent confidence interval 0.34 to 0.95, p = 0.033), with ten-year rates of 59 per cent (46 to 74) against 41 per cent (30 to 57).","asOf":"2026-10-01","links":[{"label":"Journal of Clinical Oncology 2018","url":"https://doi.org/10.1200/JCO.2018.77.9892"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29975623/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29975623"}],"tags":["lymphoma-evidence"],"related":["lymphoma-roadmap"],"cancers":["follicular-lymphoma","non-hodgkin-lymphoma"],"sections":["radiation","chemotherapy"],"technologies":["radiotherapy","pet-ct"],"targets":[],"drugs":["cyclophosphamide","vincristine","prednisone","rituximab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["trog-99-03","fortplus"],"people":[],"bottlenecks":["b-rare-cancers","b-trial-enrolment"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2018,"doi":"10.1200/JCO.2018.77.9892","pmid":"29975623","authors":"MacManus M, Fisher R, Roos D, et al.","paperType":"rct","findings":["Ten-year progression-free survival was 59 per cent (95 per cent confidence interval 46 to 74) with radiotherapy followed by systemic therapy against 41 per cent (30 to 57) with radiotherapy alone (hazard ratio 0.57, 0.34 to 0.95, p = 0.033).","Patients who received R-CVP did markedly better than contemporaneous radiotherapy-only patients (hazard ratio 0.26, 0.07 to 0.97, p = 0.045).","Overall survival was not significantly different, at 95 per cent against 87 per cent at ten years (p = 0.40).","Histological transformation occurred in four patients in the combined arm and ten in the radiotherapy arm (p = 0.1).","Fewer involved regions (p = 0.047) and positron emission tomography staging (p = 0.056) were associated with better progression-free survival."],"whatItMeans":"The evidence that early follicular lymphoma is less often confined to the radiation field than staging suggests, and that a short course of systemic treatment after radiotherapy reduces relapse. It is also the reason modern practice stages this disease with positron emission tomography.","caveats":["150 patients recruited over twelve years, which is small and slow, and gives wide confidence intervals.","Only 48 per cent had positron emission tomography staging, so some apparent stage I disease was probably advanced.","The systemic arm changed mid-trial when rituximab was added, so the two chemotherapy regimens are not separately randomised.","No overall survival difference, in a disease where ten-year survival exceeds 87 per cent in both arms."],"changedPractice":true,"participants":150},{"id":"paper-mayer-recourse-tas-102-nejm-2015","kind":"paper","name":"Randomized trial of TAS-102 for refractory metastatic colorectal cancer (RECOURSE)","aka":[],"tldr":"An oral chemotherapy that works where fluorouracil no longer does, adding 1.8 months after everything else has failed, and delaying the slide in performance status by nearly two months.","summary":"Mayer, Van Cutsem, Falcone and colleagues randomly assigned 800 patients with refractory colorectal cancer 2:1 to TAS-102, an oral agent combining trifluridine and tipiracil hydrochloride, or placebo in a double-blind trial, with overall survival as the primary end point. Early trials conducted primarily in Japan had suggested activity in this setting.\n\nOne death related to TAS-102 was reported. The time to worsening of ECOG performance status from 0 or 1 to 2 or more was a pre-specified secondary endpoint and favoured treatment.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2015","url":"https://doi.org/10.1056/NEJMoa1414325"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25970050/"}],"tags":["colorectal-evidence"],"related":["paper-prager-sunlight-trifluridine-tipiracil-bevacizumab-nejm-2023","paper-grothey-correct-regorafenib-lancet-2013"],"cancers":["colorectal"],"sections":["chemotherapy"],"technologies":["cytotoxic-chemotherapy"],"targets":[],"drugs":["trifluridine-tipiracil"],"companies":["taiho"],"institutions":[],"pathways":[],"terms":["performance-status"],"trials":[],"people":["eric-van-cutsem","josep-tabernero","yoshino-takayuki","heinz-josef-lenz"],"bottlenecks":["b-toxicity-qol"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2015,"doi":"10.1056/NEJMoa1414325","pmid":"25970050","authors":"Mayer RJ, Van Cutsem E, Falcone A, et al.","paperType":"rct","findings":["Median overall survival 7.1 months with TAS-102 against 5.3 months with placebo: hazard ratio 0.68 (95 percent CI 0.58 to 0.81, p<0.001).","Neutropenia in 38 percent and leukopenia in 21 percent of those treated; febrile neutropenia in 4 percent.","Median time to worsening performance status 5.7 against 4.0 months (hazard ratio 0.66, 0.56 to 0.78, p<0.001)."],"whatItMeans":"Trifluridine-tipiracil became the other refractory-line standard alongside regorafenib, and the backbone that SUNLIGHT later improved on by adding bevacizumab.","caveats":["Myelosuppression rather than the hand-foot toxicity of regorafenib; the two drugs differ in how they are tolerated rather than in how much they add.","No predictive biomarker.","Funded by the manufacturer."],"changedPractice":true,"participants":800},{"id":"paper-chesney-j-clin-oncol","kind":"paper","name":"Randomized, Double-Blind, Placebo-Controlled, Global Phase III Trial of Talimogene Laherparepvec Combined With Pembrolizumab for Advanced Melanoma","aka":[],"tldr":"Paper cited by one pairing page, indexed on Europe PMC as PubMed record 35998300 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: The combination of talimogene laherparepvec (T-VEC) and pembrolizumab previously demonstrated an acceptable safety profile and an encouraging complete response rate (CRR) in patients with advanced melanoma in a phase Ib study. We report the efficacy and safety from a phase III, randomized, double-blind, multicenter, international study of T-VEC plus pembrolizumab (T-VEC-pembrolizumab) versus placebo plus pembrolizumab (placebo-pembrolizumab) in patients with advanced melanoma.\n\nMethods: Patients with stage IIIB-IVM1c unresectable melanoma, naïve to antiprogrammed cell death protein-1, were randomly assigned 1:1 to T-VEC-pembrolizumab or placebo-pembrolizumab. T-VEC was administered at ≤ 4 × 10 6 plaque-forming unit (PFU) followed by ≤ 4 × 10 8 PFU 3 weeks later and once every 2 weeks until dose 5 and once every 3 weeks thereafter. Pembrolizumab was administered intravenously 200 mg once every 3 weeks. The dual primary end points were progression-free survival (PFS) per modified RECIST 1.1 by blinded independent central review and overall survival (OS). Secondary end points included objective response rate per mRECIST, CRR, and safety. Here, we report the primary analysis for PFS, the second preplanned interim analysis for OS, and the final analysis.\n\nResults: Overall, 692 patients were randomly assigned (346 T-VEC-pembrolizumab and 346 placebo-pembrolizumab). T-VEC-pembrolizumab did not significantly improve PFS (hazard ratio, 0.86; 95% CI, 0.71 to 1.04; P =.13) or OS (hazard ratio, 0.96; 95% CI, 0.76 to 1.22; P =.74) compared with placebo-pembrolizumab. The objective response rate was 48.6% for T-VEC-pembrolizumab (CRR 17.9%) and 41.3% for placebo-pembrolizumab (CRR 11.6%); the durable response rate was 42.2% and 34.1% for the arms, respectively. Grade ≥ 3 treatment-related adverse events occurred in 20.7% of patients in the T-VEC-pembrolizumab arm and in 19.5% of patients in the placebo-pembrolizumab arm.\n\nConclusion: T-VEC-pembrolizumab did not significantly improve PFS or OS compared with placebo-pembrolizumab. Safety results of the T-VEC-pembrolizumab combination were consistent with the safety profiles of each agent alone.\n\nIndexed on Europe PMC as PubMed record 35998300 (DOI 10.1200/jco.22.00343). Matched by DOI alone: one pairing page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2023","url":"https://doi.org/10.1200/jco.22.00343"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35998300/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35998300"}],"tags":["europepmc-ingest"],"related":["oncolytic-plus-pd1"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2023,"doi":"10.1200/jco.22.00343","pmid":"35998300","authors":"Chesney JA, Ribas A, Long GV, et al.","paperType":"rct","findings":[],"whatItMeans":"One pairing page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-andrew-lassman-j-clin-oncol-2023","kind":"paper","name":"RANO 2.0: Update to the Response Assessment in Neuro-Oncology Criteria for High- and Low-Grade Gliomas in Adults","aka":[],"tldr":"Paper by Andrew B. Lassman indexed on Europe PMC as PubMed record 37774317, in Journal of Clinical Oncology (2023), one of the most cited records naming an author with this name at Herbert Irving Comprehensive Cancer Center, Columbia University.","summary":"Purpose: The Response Assessment in Neuro-Oncology (RANO) criteria for high-grade gliomas (RANO-HGG) and low-grade gliomas (RANO-LGG) were developed to improve reliability of response assessment in glioma trials. Over time, some limitations of these criteria were identified, and challenges emerged regarding integrating features of the modified RANO (mRANO) or the immunotherapy RANO (iRANO) criteria.\n\nMethods: Informed by data from studies evaluating the different criteria, updates to the RANO criteria are proposed (RANO 2.0).\n\nResults: We recommend a standard set of criteria for both high- and low-grade gliomas, to be used for all trials regardless of the treatment modalities being evaluated. In the newly diagnosed setting, the postradiotherapy magnetic resonance imaging (MRI), rather than the postsurgical MRI, will be used as the baseline for comparison with subsequent scans. Since the incidence of pseudoprogression is high in the 12 weeks after radiotherapy, continuation of treatment and confirmation of progression during this period with a repeat MRI, or histopathologic evidence of unequivocal recurrent tumor, are required to define tumor progression. However, confirmation scans are not mandatory after this period nor for the evaluation of treatment for recurrent tumors. For treatments with a high likelihood of pseudoprogression, mandatory confirmation of progression with a repeat MRI is highly recommended. The primary measurement remains the maximum cross-sectional area of tumor (two-dimensional) but volumetric measurements are an option. For IDH wild-type glioblastoma, the nonenhancing disease will no longer be evaluated except when assessing response to antiangiogenic agents. In IDH-mutated tumors with a significant nonenhancing component, clinical trials may require evaluating both the enhancing and nonenhancing tumor components for response assessment.\n\nConclusion: The revised RANO 2.0 criteria refine response assessment in gliomas.\n\nIndexed on Europe PMC as PubMed record 37774317 (DOI 10.1200/jco.23.01059). Its author list gives \"Lassman AB\" with the affiliation \"Division of Neuro-Oncology, Department of Neurology, Herbert Irving Comprehensive Cancer Center and Irving Institute for Clinical and Translational Research, Columbia University Vagelos College of Physicians and Surgeons and New York-Presbyterian Hospital, New York, NY\", which names Herbert Irving Comprehensive Cancer Center, Columbia University; that is how the record was matched to Andrew B. Lassman, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2023","url":"https://doi.org/10.1200/jco.23.01059"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37774317/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37774317"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["andrew-lassman"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2023,"doi":"10.1200/jco.23.01059","pmid":"37774317","authors":"Wen PY, van den Bent M, Youssef G, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Andrew B. Lassman at Herbert Irving Comprehensive Cancer Center, Columbia University, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-rapid-pet-directed-therapy-early-hodgkin-nejm-2015","kind":"paper","name":"RAPID: PET-directed therapy for early-stage Hodgkin lymphoma","aka":[],"tldr":"Patients with early Hodgkin lymphoma whose PET scan was clear after three cycles of ABVD did almost as well without radiotherapy as with it, with a small extra risk of relapse but no difference in survival, giving them a choice.","summary":"UK randomised non-inferiority trial of 602 patients with stage IA or IIA non-bulky Hodgkin lymphoma; those with a negative PET after three cycles of ABVD (420 patients) were randomised to involved-field radiotherapy of 30 Gy or no further treatment.\n\nThree-year progression-free survival was 94.6 percent with radiotherapy against 90.8 percent without, which did not meet the pre-specified non-inferiority margin in the intention-to-treat analysis, while overall survival was the same. Omitting radiotherapy trades a few percentage points of relapse for avoiding late radiation effects.","asOf":"2026-09-18","links":[{"label":"N Engl J Med 2015","url":"https://doi.org/10.1056/NEJMoa1408648"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25901426/"}],"tags":[],"related":[],"cancers":["early-stage-classical-hodgkin-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["doxorubicin","vinblastine","dacarbazine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2015,"doi":"10.1056/NEJMoa1408648","pmid":"25901426","authors":"Radford J, Illidge T, Counsell N, et al.","paperType":"rct","findings":["Three-year progression-free survival 94.6 percent with radiotherapy versus 90.8 percent without in PET-negative patients.","No difference in overall survival; non-inferiority was not formally shown."],"whatItMeans":"PET-negative early Hodgkin lymphoma can be treated with chemotherapy alone at a small cost in relapse, an option many younger patients take to avoid radiation to the chest and neck.","caveats":["Relapses after chemotherapy alone are usually salvaged, but require more intensive treatment.","The trial used ABVD alone; the balance may differ with newer regimens."],"changedPractice":true,"participants":602},{"id":"paper-gatta-eur-j-cancer","kind":"paper","name":"Rare cancers are not so rare: the rare cancer burden in Europe","aka":[],"tldr":"Paper cited by one bottleneck page and twelve idea pages, indexed on Europe PMC as PubMed record 22033323 and published in European Journal of Cancer; the citing pages link this DOI, which is how the record was matched.","summary":"Purpose: Epidemiologic information on rare cancers is scarce. The project Surveillance of Rare Cancers in Europe (RARECARE) provides estimates of the incidence, prevalence and survival of rare cancers in Europe based on a new and comprehensive list of these diseases.\n\nMaterials and methods: RARECARE analysed population-based cancer registry (CR) data on European patients diagnosed from 1988 to 2002, with vital status information available up to 31st December 2003 (latest date for which most CRs had verified data). The mean population covered was about 162,000,000. Cancer incidence and survival rates for 1995-2002 and prevalence at 1st January 2003 were estimated.\n\nResults: Based on the RARECARE definition (incidence <6/100,000/year), the estimated annual incidence rate of all rare cancers in Europe was about 108 per 100,000, corresponding to 541,000 new diagnoses annually or 22% of all cancer diagnoses. Five-year relative survival was on average worse for rare cancers (47%) than common cancers (65%). About 4,300,000 patients are living today in the European Union with a diagnosis of a rare cancer, 24% of the total cancer prevalence.\n\nConclusion: Our estimates of the rare cancer burden in Europe provide the first indication of the size of the public health problem due to these diseases and constitute a useful base for further research. Centres of excellence for rare cancers or groups of rare cancers could provide the necessary organisational structure and critical mass for carrying out clinical trials and developing alternative approaches to clinical experimentation for these cancers.\n\nIndexed on Europe PMC as PubMed record 22033323 (DOI 10.1016/j.ejca.2011.08.008). Matched by DOI alone: one bottleneck page and twelve idea pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Eur J Cancer 2011","url":"https://doi.org/10.1016/j.ejca.2011.08.008"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22033323/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/22033323"}],"tags":["europepmc-ingest"],"related":["b-rare-cancers","idea-bio2-rare-cancer-telepathology-network","idea-bio2-shared-compound-access-pool","idea-bio2-bayesian-borrowing-acceptance","idea-bio2-rare-tumour-model-bank","idea-bio2-paediatric-first-development","idea-bio2-mechanism-defined-baskets","idea-bio2-patient-partnered-rare-commons","idea-moon-rare-cancer-global-network","idea-bio2-rare-cancer-umbrella-platform","idea-moon-open-source-oncology-drug-discovery","idea-bio2-registry-embedded-randomisation","idea-bio2-functional-precision-rare"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["european-journal-of-cancer"],"dependsOn":[],"notes":[],"journal":"European Journal of Cancer","year":2011,"doi":"10.1016/j.ejca.2011.08.008","pmid":"22033323","authors":"Gatta G, van der Zwan JM, Casali PG, et al.","paperType":"observational","findings":[],"whatItMeans":"One bottleneck page and twelve idea pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-alchemist-jama-oncol-2022","kind":"paper","name":"Rates of Guideline-Concordant Surgery and Adjuvant Chemotherapy Among Patients With Early-Stage Lung Cancer in the US ALCHEMIST Study (Alliance A151216)","aka":[],"tldr":"Published report from the ALCHEMIST trial registered as NCT02194738, in JAMA Oncology (2022), chosen as the most cited paper whose own text cites the registry id.","summary":"Importance: Standard treatment for resectable non-small cell lung cancer (NSCLC) includes anatomic resection with adequate lymph node dissection and adjuvant chemotherapy for appropriate patients. Historically, many patients with early-stage NSCLC have not received such treatment, which may affect the interpretation of the results of adjuvant therapy trials.\n\nObjective: To ascertain patterns of guideline-concordant treatment among patients enrolled in a US-wide screening protocol for adjuvant treatment trials for resected NSCLC.\n\nDesign, setting, and participants: This retrospective cohort study included 2833 patients with stage IB to IIIA NSCLC (per American Joint Committee on Cancer 7th edition criteria) who enrolled in the Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST) screening study (Alliance for Clinical Trials in Oncology A151216) from August 18, 2014, to April 1, 2019, and who did not enroll in a therapeutic adjuvant clinical trial; patients had tumors of at least 4 cm and/or with positive lymph nodes. Statistical analysis was conducted from June 1, 2020, through October 1, 2021.\n\nExposures: Care patterns were ascertained overall and by sociodemographic and clinical factors, including age, sex, race and ethnicity, educational level, marital status, geography, histologic characteristics, stage, genomic variant status, smoking history, and comorbidities.\n\nMain outcomes and measures: Five outcomes are reported: whether patients (1) had anatomic surgical resection, (2) had adequate lymph node dissection (≥1 N1 nodal station plus ≥3 N2 nodal stations), (3) received any adjuvant chemotherapy, (4) received any cisplatin-based adjuvant chemotherapy, and (5) received at least 4 cycles of adjuvant chemotherapy.\n\nResults: Of the 2833 patients (1505 women [53%]; mean [SD] age, 66.5 [9.2] years) included in this analysis, 2697 (95%) had anatomic surgical resection, 1513 (53%) had adequate lymph node dissection, 1617 (57%) received any adjuvant chemotherapy, 1237 (44%) received at least 4 cycles of adjuvant platinum-based chemotherapy, and 965 (34%) received any cisplatin-based adjuvant chemotherapy. Rates were similar across race and ethnicity.\n\nConclusions and relevance: This cohort study found that among participants in a screening protocol for adjuvant clinical trials for resected early-stage NSCLC, just 53% underwent adequate lymph node dissection, and 57% received adjuvant chemotherapy, despite indications for such treatment. These results may affect the interpretation of adjuvant trials. Efforts are needed to optimize the use of proven therapies for early-stage NSCLC.\n\nTrial registration: ClinicalTrials.gov Identifier: NCT02194738.\n\nIndexed on Europe PMC as PubMed record 35297944 (DOI 10.1001/jamaoncol.2022.0039). Its abstract cites the registry id NCT02194738, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"JAMA Oncol 2022","url":"https://doi.org/10.1001/jamaoncol.2022.0039"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35297944/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35297944"},{"label":"ClinicalTrials.gov NCT02194738","url":"https://clinicaltrials.gov/study/NCT02194738"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["alchemist"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2022,"doi":"10.1001/jamaoncol.2022.0039","pmid":"35297944","authors":"Kehl KL, Zahrieh D, Yang P, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02194738 with the most citations, so it is the natural first reading for anyone following the ALCHEMIST trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-rathl-interim-pet-adapted-abvd-advanced-hodgkin-nejm-2016","kind":"paper","name":"RATHL: adapted treatment guided by interim PET-CT in advanced Hodgkin lymphoma","aka":[],"tldr":"Using a PET scan after two cycles to decide the rest of treatment let patients with a clear scan drop bleomycin, sparing their lungs without losing cure, while those with a positive scan were escalated to stronger chemotherapy.","summary":"International randomised trial of 1,214 patients with advanced Hodgkin lymphoma who had an interim PET-CT after two cycles of ABVD; PET-negative patients were randomised to continue ABVD or switch to AVD (omitting bleomycin), and PET-positive patients were escalated to BEACOPP.\n\nThree-year progression-free survival was 85.7 percent with ABVD and 84.4 percent with AVD, with fewer pulmonary adverse events after bleomycin was dropped; PET-positive patients escalated to BEACOPP had a three-year progression-free survival of 67.5 percent, better than expected. PET-adapted therapy became standard.","asOf":"2026-09-18","links":[{"label":"N Engl J Med 2016","url":"https://doi.org/10.1056/NEJMoa1510093"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27332902/"}],"tags":[],"related":["lymphoma-roadmap","paper-ghsg-hd18-pet-guided-escalated-beacopp-lancet-2017","paper-ahl2011-pet-adapted-treatment-advanced-hodgkin-lancet-oncol-2019"],"cancers":["advanced-stage-classical-hodgkin-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["doxorubicin","vinblastine","dacarbazine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["rathl"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2016,"doi":"10.1056/NEJMoa1510093","pmid":"27332902","authors":"Johnson P, Federico M, Kirkwood A, et al.","paperType":"rct","findings":["Three-year progression-free survival 85.7 percent with continued ABVD versus 84.4 percent with AVD after a negative interim PET.","Fewer pulmonary and other toxic effects without bleomycin; PET-positive patients escalated to BEACOPP had 67.5 percent three-year progression-free survival."],"whatItMeans":"An interim PET scan after two cycles guides treatment of advanced Hodgkin lymphoma: drop bleomycin if negative, intensify if positive.","caveats":["The non-inferiority margin for AVD was not formally met in the intention-to-treat analysis, though the difference was small.","Predates brentuximab vedotin and nivolumab combinations, which now often replace ABVD."],"changedPractice":true,"participants":1214},{"id":"paper-ratify-midostaurin-nejm-2017","kind":"paper","name":"RATIFY: midostaurin added to chemotherapy for acute myeloid leukaemia with a FLT3 mutation","aka":[],"tldr":"Adding the FLT3 inhibitor midostaurin to standard induction and consolidation chemotherapy, then as maintenance, lengthened survival in adults under 60 with FLT3-mutated acute myeloid leukaemia, the first targeted drug to do so.","summary":"Phase 3 placebo-controlled trial of 717 patients aged 18 to 59 with newly diagnosed FLT3-mutated AML (ITD or TKD) randomised to midostaurin or placebo with daunorubicin-cytarabine induction, high-dose cytarabine consolidation and a year of maintenance.\n\nMedian overall survival was 74.7 months with midostaurin against 25.6 months with placebo (hazard ratio 0.78), with benefit across FLT3 subtypes and in patients who went on to transplant.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2017","url":"https://doi.org/10.1056/NEJMoa1614359"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28644114/"}],"tags":[],"related":[],"cancers":["aml-flt3"],"sections":[],"technologies":[],"targets":[],"drugs":["midostaurin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["ratify"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2017,"doi":"10.1056/NEJMoa1614359","pmid":"28644114","authors":"Stone RM, Mandrekar SJ, Sanford BL, et al.","paperType":"rct","findings":["Median overall survival 74.7 vs 25.6 months; hazard ratio for death 0.78.","Four-year overall survival 51.4 percent vs 44.3 percent."],"whatItMeans":"FLT3 testing at diagnosis and a FLT3 inhibitor during chemotherapy became standard. Quizartinib (QuANTUM-First) is an alternative for FLT3-ITD, and the approach extended FLT3 inhibitors into maintenance and relapse.","caveats":["Patients over 60 were excluded.","The contribution of maintenance midostaurin could not be isolated."],"changedPractice":true,"participants":717},{"id":"paper-ku-rb1-trp53-lineage-plasticity-science-2017","kind":"paper","name":"Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis and antiandrogen resistance","aka":[],"tldr":"Deleting two tumour suppressor genes in mouse prostate cancer let the tumour change cell type, spread, and shrug off hormone treatment, and a drug that resets the chromatin reversed it.","summary":"Studying mouse models, the authors showed that Rb1 loss facilitates lineage plasticity and metastasis of prostate adenocarcinoma initiated by Pten mutation, and that additional loss of Trp53 causes resistance to antiandrogen therapy. Gene expression profiling indicated that the mouse tumours resemble human prostate cancer neuroendocrine variants, and both mouse and human tumours showed increased expression of epigenetic reprogramming factors such as Ezh2 and Sox2. Clinically relevant EZH2 inhibitors restored androgen receptor expression and sensitivity to antiandrogen therapy.","asOf":"2026-09-25","links":[{"label":"Ku et al., Science 2017: Rb1 and Trp53 loss cooperating to allow lineage plasticity, metastasis and antiandrogen resistance in mouse prostate cancer","url":"https://doi.org/10.1126/science.aah4199"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28059767/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28059767"}],"tags":[],"related":["prostate-roadmap","paper-mu-sox2-lineage-plasticity-science-2017","idea-prostate-plasticity-surveillance-before-it-is-neuroendocrine","lineage-plasticity-neuroendocrine"],"cancers":["prostate","prostate-mcrpc","prostate-nepc"],"sections":[],"technologies":[],"targets":["rb1","tp53","pten","ezh2","sox2","androgen-receptor"],"drugs":[],"companies":[],"institutions":[],"pathways":["lineage-plasticity-neuroendocrine","epigenetic-reprogramming","p53-cell-cycle","ar-signaling"],"terms":["histologic-transformation","resistance","castration-resistance"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2017,"doi":"10.1126/science.aah4199","pmid":"28059767","authors":"Ku SY, Rosario S, Wang Y, et al.","paperType":"basic","findings":["Rb1 loss enables lineage plasticity and metastasis in Pten-mutant prostate adenocarcinoma.","Additional Trp53 loss causes antiandrogen resistance.","Increased Ezh2 and Sox2 expression in both mouse and human neuroendocrine-like tumours.","EZH2 inhibition restored androgen receptor expression and antiandrogen sensitivity."],"whatItMeans":"It turned neuroendocrine transformation from a pathological curiosity into a mechanism with a genotype and a candidate intervention, and it is the reason EZH2 inhibitors are in prostate cancer trials at all.","caveats":["Genetically engineered mouse models, and the human confirmation is correlative.","EZH2 inhibition has not yet been shown to prevent or reverse transformation in men.","Loss of RB1 and TP53 is necessary but clearly not sufficient, since most such tumours do not transform."],"changedPractice":false},{"id":"paper-pembrolizumab-glioblastoma-clin-cancer-res-2025","kind":"paper","name":"Re-Irradiation Plus Pembrolizumab: A Phase II Study for Patients with Recurrent Glioblastoma","aka":[],"tldr":"Phase 2 or 3 results paper on Pembrolizumab in Glioma & glioblastoma, in Clinical Cancer Research (2025), one of the most cited Europe PMC records with Pembrolizumab in its title.","summary":"Purpose: Radiotherapy may enhance antitumor immune responses by several mechanisms, including induction of immunogenic cell death. We performed a phase 2 study of pembrolizumab with re-irradiation in patients with recurrent glioblastoma.\n\nPatients and methods: Sixty patients with recurrent glioblastoma received pembrolizumab with re-irradiation alone (cohort A, bevacizumab-naïve; n = 30) or with bevacizumab continuation (cohort B, n = 30). Dual primary endpoints, including the overall response rate and overall survival (OS) at either 12 (OS-12; cohort A) or 6 months (OS-6; cohort B), were assessed per cohort relative to historic benchmarks. Paired paraffin-embedded formalin-fixed tumor samples were assessed for immunologic biomarkers by IHC using digital quantification and co-detection-by-indexing (CODEX).\n\nResults: Study therapy was well tolerated, with most toxicities being grade ≤3. For cohort B, the primary endpoint of OS-6 was achieved (57%); however, survival was not improved for cohort A patients. The overall response rate was 3.3% and 6.7% for cohorts A and B, respectively. CODEX analysis of paired tumor samples from five patients revealed an increase of activated T cells in the tumor microenvironment after study therapy.\n\nConclusions: Compared with historic controls, re-irradiation plus pembrolizumab seemed to improve survival among bevacizumab-refractory patients but not among bevacizumab-naïve patients. CODEX revealed evidence of intratumoral infiltration of activated immune effector cells. A randomized, properly controlled trial of PD-1 blockade plus re-irradiation is warranted to further evaluate this regimen for bevacizumab-refractory patients, but alternative approaches are needed for bevacizumab-naïve patients.\n\nIndexed on Europe PMC as PubMed record 39513953 (DOI 10.1158/1078-0432.ccr-24-1629). Its title names Pembrolizumab and its text names Glioma & glioblastoma; PubMed types it as a clinical trial report (Clinical Trial, Phase II). It was matched automatically to the idea \"Neoadjuvant immunotherapy with surgical window for glioblastoma\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Clin Cancer Res 2025","url":"https://doi.org/10.1158/1078-0432.ccr-24-1629"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39513953/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39513953"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2025,"doi":"10.1158/1078-0432.ccr-24-1629","pmid":"39513953","authors":"Iwamoto FM, Tanguturi SK, Nayak L, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Pembrolizumab in Glioma & glioblastoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Pembrolizumab in the title and Glioma & glioblastoma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-de-savornin-lohman-re-resection-incidental-gallbladder-cancer-aso-2020","kind":"paper","name":"Re-resection in Incidental Gallbladder Cancer: Survival and the Incidence of Residual Disease","aka":[],"tldr":"In the Dutch national registry only one in four people with a chance-found gallbladder cancer had the recommended second operation; those who did lived about four times longer, and a third of them had cancer left behind that the operation removed.","summary":"Netherlands Cancer Registry study of 463 patients with incidental gallbladder cancer; 110 (24 percent) underwent re-resection after a median of 66 days, and their pathology reports were reviewed. Residual disease was present in 35 percent, most often in lymph nodes (23 percent); R0 resection was achieved in 92 percent. Median overall survival was 13.7 months (95 percent CI 11.6 to 15.6) without re-resection and 52.6 months (36.3 to 68.8) with it. Residual disease was the only significant prognostic factor after re-resection and was predicted by pT and pN stage. The authors note re-resection remains infrequent and is often performed after the optimal interval.","asOf":"2026-09-24","links":[{"label":"Ann Surg Oncol 2020","url":"https://doi.org/10.1245/s10434-019-08074-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31741109/"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["incidental-gallbladder-cancer","radical-cholecystectomy"],"trials":[],"people":[],"bottlenecks":["b-care-fragmentation"],"keyPapers":[],"journals":["annals-of-surgical-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Surgical Oncology","year":2020,"doi":"10.1245/s10434-019-08074-4","pmid":"31741109","authors":"de Savornin Lohman EAJ, van der Geest LG, de Bitter TJJ, et al.","paperType":"real-world","findings":["24 percent (110 of 463) of incidental gallbladder cancers were re-resected, after a median of 66 days.","Residual disease in 35 percent, most often lymph nodes (23 percent); R0 in 92 percent.","Median overall survival 52.6 months with re-resection vs 13.7 months without."],"whatItMeans":"A whole-country picture of the gap between guideline and practice: three quarters of eligible patients never reached the second operation. The survival difference is confounded by selection but the residual disease rate is not.","caveats":["Unmatched comparison; patients selected for re-resection were fitter and had less advanced disease.","Registry data; reasons for not re-resecting were not captured."],"changedPractice":false,"participants":463},{"id":"paper-aguirre-real-time-genomic-characterisation-pancreatic-cancer-discov-2018","kind":"paper","name":"Real-time genomic characterization of advanced pancreatic cancer to enable precision medicine","aka":[],"tldr":"A Boston programme biopsied and sequenced 71 patients with advanced pancreatic cancer fast enough to change treatment in 30%, finding a treatable alteration in half and an inherited one in almost one in five.","summary":"A biopsy protocol delivered time-sensitive whole-exome and RNA sequencing for patients with advanced pancreatic ductal adenocarcinoma. Therapeutically relevant genomic alterations were identified in 48% (34 of 71) and pathogenic or likely pathogenic germline alterations in 18% (13 of 71); 30% (21 of 71) had a change in management as a result. Twenty-six patients had germline and/or somatic DNA-damage repair alterations and five more had homologous recombination deficiency signatures without an identified cause. Two patients had oncogenic in-frame BRAF deletions, with the first clinical evidence that this alteration confers sensitivity to MAPK pathway inhibition. Tumour and stroma expression signatures with clinical relevance were identified.","asOf":"2026-09-24","links":[{"label":"Aguirre et al., Cancer Discov 2018: real-time exome and RNA sequencing of 71 advanced patients","url":"https://doi.org/10.1158/2159-8290.CD-18-0275"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29903880/"}],"tags":[],"related":[],"cancers":["pancreatic","metastatic-pdac"],"sections":[],"technologies":["wes-wgs","rna-seq","germline-testing"],"targets":["braf","brca"],"drugs":[],"companies":[],"institutions":["dana-farber","broad-institute"],"pathways":["ras-mapk","homologous-recombination-repair"],"terms":["germline-vs-somatic","hrd"],"trials":[],"people":["andrew-aguirre","david-tuveson"],"bottlenecks":[],"keyPapers":[],"journals":["cancer-discovery"],"dependsOn":[],"notes":[],"journal":"Cancer Discovery","year":2018,"doi":"10.1158/2159-8290.CD-18-0275","pmid":"29903880","authors":"Aguirre AJ, Nowak JA, Camarda ND, et al.","paperType":"translational","findings":["Actionable alterations 48%, germline 18%, management changed in 30%.","26 with DNA-damage repair alterations plus 5 with an HRD signature and no cause.","In-frame BRAF deletions respond to MAPK inhibition."],"whatItMeans":"Together with COMPASS it made sequencing at diagnosis of advanced disease a standard expectation, and it found the BRAF-deletion class that a hotspot test misses.","caveats":["Single academic centre with a dedicated biopsy team.","Management change does not equal survival benefit."],"changedPractice":false,"participants":71},{"id":"paper-singhi-targeted-genome-profiling-3594-pdac-gastroenterology-2019","kind":"paper","name":"Real-time targeted genome profile analysis of pancreatic ductal adenocarcinomas identifies genetic alterations that might be targeted with existing drugs or used as biomarkers","aka":[],"tldr":"Targeted sequencing of 3,594 pancreatic cancers, the largest such series, found KRAS in 88%, a drug-matchable alteration in 17%, BRCA or FANC repair gene changes in 14%, and microsatellite instability or very high mutation burden in only 0.5%.","summary":"Targeted genomic profiling of 3,594 pancreatic ductal adenocarcinoma samples from an international cohort covered up to 315 cancer genes and the introns of 28 rearranged genes, with tumour mutation burden over 1.14 megabases (high at 20 or more per megabase) and MSI over 114 loci. KRAS, TP53, CDKN2A and SMAD4 were the most frequently altered genes; KRAS was mutated in 88%. Among KRAS wild-type tumours, actionable MAPK pathway alterations (n = 132; 4%) included gene fusions (51), amplifications (35), missense mutations (30) and deletions (16), mostly in receptor tyrosine kinase, RAS or MAPK genes. Beyond TP53, DNA damage repair alterations (BRCA and FANC) were found in 14%. MSI-high and/or TMB-high phenotypes were detected in 0.5% of 2,563 and 1,021 evaluated. FGF23, CCND2, PIK3CA and FGF6 alterations were commoner in IPMN-associated cancers. Overall 17% carried alterations that might make tumours susceptible to existing agents.","asOf":"2026-09-24","links":[{"label":"Singhi et al., Gastroenterology 2019: targeted profiling of 3,594 pancreatic ductal adenocarcinomas","url":"https://doi.org/10.1053/j.gastro.2019.02.037"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30836094/"}],"tags":[],"related":[],"cancers":["pancreatic","kras-wild-type-pdac","msi-high-pdac"],"sections":[],"technologies":["tmb-testing","msi-mmr-testing"],"targets":["kras","tp53","cdkn2a","smad4","brca"],"drugs":["foundationone-cdx"],"companies":[],"institutions":["upmc-hillman"],"pathways":[],"terms":["tmb","msi","ngs"],"trials":[],"people":["anirban-maitra","talia-golan"],"bottlenecks":[],"keyPapers":[],"journals":["gastroenterology"],"dependsOn":[],"notes":[],"journal":"Gastroenterology","year":2019,"doi":"10.1053/j.gastro.2019.02.037","pmid":"30836094","authors":"Singhi AD, George B, Greenbowe JR, et al.","paperType":"real-world","findings":["KRAS 88%; KRAS wild-type tumours carry MAPK pathway fusions, amplifications and mutations (4% of all).","BRCA and FANC alterations 14%; MSI-high and/or TMB-high 0.5%.","17% with alterations matched to existing drugs."],"whatItMeans":"It fixed the working numbers for a comprehensive panel in pancreatic cancer: a hit worth acting on in about one patient in six, most of it in repair genes and the KRAS wild-type minority.","caveats":["Commercial referral cohort (FoundationOne); germline status not separated from somatic.","TMB-high defined at 20, not the 10 used for the tumour-agnostic label."],"changedPractice":false,"participants":3594},{"id":"paper-malla-ctdna-resected-biliary-tract-cancer-esmo-gi-onc-2026","kind":"paper","name":"Real-world analysis of ctDNA and other biomarkers in patients with curatively resected stage I-III biliary tract cancer","aka":[],"tldr":"In 167 people whose bile duct or gallbladder cancer had been removed, a blood test for tumour DNA in the weeks after surgery picked out those whose cancer would return far better than the standard blood markers.","summary":"Retrospective real-world analysis of 167 patients with stage I to III resectable biliary tract cancer tested with a personalised, tumour-informed 16-plex PCR next-generation sequencing assay (Signatera) between July 2020 and February 2024; 751 plasma samples were drawn before surgery, in a 2 to 12 week post-surgical window and during surveillance, and compared with CA 19-9 and CEA. Median follow-up was 21 months. ctDNA detection rates were 23 percent (19 of 82) in the residual disease window and 38 percent (31 of 82) in surveillance. Positivity in either window was associated with worse relapse-free and overall survival; in the residual disease window it was the strongest prognostic factor for relapse-free survival (hazard ratio 15.86, 95 percent CI 4.69 to 53.6), and ctDNA outperformed the conventional markers.","asOf":"2026-09-24","links":[{"label":"ESMO Gastrointest Oncol 2026","url":"https://doi.org/10.1016/j.esmogo.2026.100344"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42583118/"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder","cholangiocarcinoma","biliary-tract-cancer"],"sections":[],"technologies":["liquid-biopsy","mrd-testing"],"targets":[],"drugs":["signatera"],"companies":["natera"],"institutions":[],"pathways":[],"terms":["ctdna","mrd","ca19-9"],"trials":[],"people":[],"bottlenecks":["b-dormancy-mrd"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"ESMO Gastrointestinal Oncology","year":2026,"doi":"10.1016/j.esmogo.2026.100344","pmid":"42583118","authors":"Malla M, Esmail A, Tin A, et al.","paperType":"real-world","findings":["ctDNA detected in 23 percent (19 of 82) in the 2 to 12 week residual disease window and 38 percent (31 of 82) during surveillance.","Residual disease window positivity: relapse-free survival hazard ratio 15.86 (95 percent CI 4.69 to 53.6).","ctDNA outperformed CA 19-9 and CEA for prognosis."],"whatItMeans":"Together with the JCO Precision Oncology cohort this makes residual disease testing in biliary cancer prognostic to the same degree as in colon cancer. Nobody has yet shown that acting on it helps; that is the trial gap the ideas on this page name.","caveats":["Retrospective commercial testing cohort; testing was ordered selectively.","Mixed biliary sites; gallbladder numbers are not given in the abstract."],"changedPractice":false,"participants":167},{"id":"paper-hulscher-ivermectin-mebendazole-cohort-anticancer-res-2026","kind":"paper","name":"Real-world clinical outcomes of ivermectin and mebendazole in cancer patients: results from a prospective observational cohort (with 2026 expression of concern)","aka":[],"tldr":"A telemedicine company's survey of patients it prescribed ivermectin and mebendazole reported that most felt better; the journal has attached an expression of concern while it checks whether the diagnoses, the regressions and the ethical approval can be verified.","summary":"The cohort comprised 197 patients with cancer prescribed compounded ivermectin 25 mg with mebendazole 250 mg off-label through a US telemedicine platform, of whom 122 completed a six-month digital survey; the authors report a self-assessed 'clinical benefit ratio' of 84.4 percent, with 48.4 percent reporting regression or no evidence of disease, 36.1 percent stable and 15.6 percent progression, side effects in 25.4 percent, and 27.9 percent also on chemotherapy (Hulscher cohort 2026). On 9 June 2026 the journal's editorial board issued an expression of concern citing serious concerns about the verifiability, statistical reliability and ethical oversight of the dataset, and opened an audit of the institutional review board documentation, the source records confirming the 197 baseline diagnoses and the medical documentation behind the reported regressions (Anticancer Research expression of concern 2026). The board also stated that it does not endorse or condone unvalidated off-label use of medications for unapproved oncological indications (Anticancer Research expression of concern 2026).","asOf":"2026-09-24","links":[{"label":"Hulscher cohort 2026","url":"https://doi.org/10.21873/anticanres.18194"},{"label":"Anticancer Research expression of concern 2026","url":"https://doi.org/10.21873/anticanres.18276"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42203321/"},{"label":"Expression of concern on PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42300708/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["fenbendazole-ivermectin-repurposing-claims"],"targets":[],"drugs":["ivermectin","mebendazole"],"companies":[],"institutions":[],"pathways":[],"terms":["off-label"],"trials":[],"people":[],"bottlenecks":["b-misinformation"],"keyPapers":[],"journals":["anticancer-research"],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo agent (Claude Fable 5.1)","editedOn":"2026-09-24","note":"Written from cached ClinicalTrials.gov v2, Europe PMC, DailyMed, Drugs@FDA and WHO eEML responses; no figure appears without its source link."},"journal":"Anticancer Research","year":2026,"doi":"10.21873/anticanres.18194","pmid":"42203321","authors":"Hulscher N, Victory K, Thorp JA, et al.","paperType":"observational","findings":["197 prescribed, 122 surveyed at six months; outcomes were self-reported by the patients, not measured by scans read for the study.","Expression of concern, 9 June 2026: audit of ethical approval, baseline diagnoses and the documentation behind reported regressions."],"whatItMeans":"This is the paper most often quoted online as proof. Patients reporting how they feel to the company that sold them the treatment, with 38 percent not answering, cannot show whether a cancer shrank, and the journal is now checking whether the underlying records exist.","caveats":["Self-reported outcomes through digital surveys; no independent imaging review; 38 percent lost to follow-up.","Expression of concern issued 9 June 2026; a further update notice is indexed on Europe PMC (PMID 42703869, September 2026) whose content OnCo has not read.","Many participants were also receiving chemotherapy, radiotherapy or surgery."],"changedPractice":false,"participants":197},{"id":"paper-carver-pi3k-ar-reciprocal-feedback-prostate-cancer-cell-2011","kind":"paper","name":"Reciprocal feedback regulation of PI3K and androgen receptor signalling in PTEN-deficient prostate cancer","aka":[],"tldr":"Two growth pathways in prostate cancer prop each other up: block one and the other switches on, which is why single drugs fail and the pair has to be blocked together.","summary":"Androgen receptor transcriptional output is decreased in human and murine prostate tumours with PTEN deletion, and PI3K pathway inhibition activates androgen receptor signalling by relieving feedback inhibition of the HER kinases. Conversely, androgen receptor inhibition activates AKT signalling by reducing levels of the AKT phosphatase PHLPP. The two oncogenic pathways therefore cross-regulate each other by reciprocal feedback, and inhibiting one activates the other, maintaining tumour cell survival. Combined pharmacological inhibition of PI3K and androgen receptor signalling caused near-complete prostate cancer regressions in a Pten-deficient murine prostate cancer model and in human prostate cancer xenografts.","asOf":"2026-09-25","links":[{"label":"Carver et al., Cancer Cell 2011: reciprocal feedback between PI3K and androgen receptor signalling in PTEN-deficient prostate cancer","url":"https://doi.org/10.1016/j.ccr.2011.04.008"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21575859/"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":[],"targets":["pten","akt","androgen-receptor","pik3ca"],"drugs":[],"companies":[],"institutions":[],"pathways":["pi3k-akt-mtor","ar-signaling","rtk-activation","resistance-routes-map"],"terms":["resistance","castration-resistance"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-cell"],"dependsOn":[],"notes":[],"journal":"Cancer Cell","year":2011,"doi":"10.1016/j.ccr.2011.04.008","pmid":"21575859","authors":"Carver BS, Chapinski C, Wongvipat J, et al.","paperType":"basic","findings":["Androgen receptor output is reduced in PTEN-deleted prostate tumours.","PI3K inhibition reactivates androgen receptor signalling by relieving feedback on the HER kinases.","Androgen receptor inhibition activates AKT by reducing the phosphatase PHLPP.","Combined inhibition produced near-complete regressions in Pten-deficient models and xenografts."],"whatItMeans":"It is the reason every prostate PI3K or AKT trial gives the drug with abiraterone rather than alone, and the reason PTEN loss is used to select for those combinations rather than as a general prognostic marker.","caveats":["Mouse models and xenografts; the human confirmation is the randomised trial, which met only one of its two co-primary endpoints.","The feedback is described for PTEN-deficient disease and may not generalise.","Toxicity of dual blockade in men has proved a limiting factor the models did not predict."],"changedPractice":false},{"id":"paper-gonda-precede-consortium-recommendations-gastroenterology-2021","kind":"paper","name":"Recommendations for a more organized and effective approach to the early detection of pancreatic cancer from the PRECEDE (Pancreatic Cancer Early Detection) consortium","aka":[],"tldr":"The PRECEDE consortium set out how the field should organise itself to detect pancreatic cancer early: shared enrolment criteria, a common data and biospecimen registry, and international collaboration rather than isolated single-centre cohorts.","summary":"The Pancreatic Cancer Early Detection consortium published recommendations for a more organised and effective approach to early detection of pancreatic cancer, covering the coordination of high-risk cohorts, standardised data collection and biospecimen banking across centres.","asOf":"2026-09-24","links":[{"label":"Gonda et al., Gastroenterology 2021: PRECEDE consortium recommendations for early detection","url":"https://doi.org/10.1053/j.gastro.2021.08.036"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34454916/"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":["pancreatic-surveillance","liquid-biopsy"],"targets":[],"drugs":[],"companies":[],"institutions":["nyu-perlmutter"],"pathways":[],"terms":[],"trials":["precede"],"people":["diane-simeone"],"bottlenecks":[],"keyPapers":[],"journals":["gastroenterology"],"dependsOn":[],"notes":[],"journal":"Gastroenterology","year":2021,"doi":"10.1053/j.gastro.2021.08.036","pmid":"34454916","authors":"Gonda TA, Everett JN, Wallace M, Simeone DM, PRECEDE Consortium.","paperType":"guideline","findings":["A coordinated multi-centre structure for high-risk cohorts, data and biospecimens is proposed."],"whatItMeans":"PRECEDE is the infrastructure answer to CAPS's problem: no single centre can enrol enough high-risk people to validate an early detection test.","caveats":["Recommendations, not results; no abstract text is indexed for this record.","Outcomes from the consortium cohort are not yet published."],"changedPractice":false},{"id":"paper-cheson-j-clin-oncol","kind":"paper","name":"Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification","aka":[],"tldr":"Paper cited by two term pages, indexed on Europe PMC as PubMed record 25113753 and published in Journal of Clinical Oncology; the citing pages link this DOI, which is how the record was matched.","summary":"The purpose of this work was to modernize recommendations for evaluation, staging, and response assessment of patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). A workshop was held at the 11th International Conference on Malignant Lymphoma in Lugano, Switzerland, in June 2011, that included leading hematologists, oncologists, radiation oncologists, pathologists, radiologists, and nuclear medicine physicians, representing major international lymphoma clinical trials groups and cancer centers. Clinical and imaging subcommittees presented their conclusions at a subsequent workshop at the 12th International Conference on Malignant Lymphoma, leading to revised criteria for staging and of the International Working Group Guidelines of 2007 for response. As a result, fluorodeoxyglucose (FDG) positron emission tomography (PET), computed tomography (CT) was formally incorporated into standard staging for FDG-avid lymphomas. A modification of the Ann Arbor descriptive terminology will be used for anatomic distribution of disease extent, but the suffixes A or B for symptoms will only be included for HL. A bone marrow biopsy is no longer indicated for the routine staging of HL and most diffuse large B-cell lymphomas. However, regardless of stage, general practice is to treat patients based on limited (stages I and II, nonbulky) or advanced (stage III or IV) disease, with stage II bulky disease considered as limited or advanced disease based on histology and a number of prognostic factors. PET-CT will be used to assess response in FDG-avid histologies using the 5-point scale. The product of the perpendicular diameters of a single node can be used to identify progressive disease. Routine surveillance scans are discouraged. These recommendations should improve evaluation of patients with lymphoma and enhance the ability to compare outcomes of clinical trials.\n\nIndexed on Europe PMC as PubMed record 25113753 (DOI 10.1200/jco.2013.54.8800). Matched by DOI alone: two term pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2014","url":"https://doi.org/10.1200/jco.2013.54.8800"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25113753/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25113753"}],"tags":["europepmc-ingest"],"related":["deauville-score","deauville","lymphoma-roadmap","paper-scherer-ctdna-lymphoma-subtypes-genome-evolution-sci-transl-med-2016"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2014,"doi":"10.1200/jco.2013.54.8800","pmid":"25113753","authors":"Cheson BD, Fisher RI, Barrington SF, et al.","paperType":"guideline","findings":[],"whatItMeans":"Two term pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-smith-j-clin-oncol","kind":"paper","name":"Recommendations for the Use of WBC Growth Factors: American Society of Clinical Oncology Clinical Practice Guideline Update","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 26169616 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: To update the 2006 American Society of Clinical Oncology guideline on the use of hematopoietic colony-stimulating factors (CSFs).\n\nMethods: The American Society of Clinical Oncology convened an Update Committee and conducted a systematic review of randomized clinical trials, meta-analyses, and systematic reviews from October 2005 through September 2014. Guideline recommendations were based on the review of the evidence by the Update Committee.\n\nResults: Changes to previous recommendations include the addition of tbo-filgrastim and filgrastim-sndz, moderation of the recommendation regarding routine use of CSFs in older patients with diffuse aggressive lymphoma, and addition of recommendations against routine dose-dense chemotherapy in lymphoma and in favor of high-dose-intensity chemotherapy in urothelial cancer. The Update Committee did not address recommendations regarding use of CSFs in acute myeloid leukemia or myelodysplastic syndromes in adults.\n\nRecommendations: Prophylactic use of CSFs to reduce the risk of febrile neutropenia is warranted when the risk of febrile neutropenia is approximately 20% or higher and no other equally effective and safe regimen that does not require CSFs is available. Primary prophylaxis is recommended for the prevention of febrile neutropenia in patients who are at high risk on the basis of age, medical history, disease characteristics, and myelotoxicity of the chemotherapy regimen. Dose-dense regimens that require CSFs should only be used within an appropriately designed clinical trial or if supported by convincing efficacy data. Current recommendations for the management of patients exposed to lethal doses of total-body radiotherapy, but not doses high enough to lead to certain death as a result of injury to other organs, include the prompt administration of CSFs.\n\nIndexed on Europe PMC as PubMed record 26169616 (DOI 10.1200/jco.2015.62.3488). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2015","url":"https://doi.org/10.1200/jco.2015.62.3488"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26169616/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26169616"}],"tags":["europepmc-ingest"],"related":["g-csf-growth-factors"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2015,"doi":"10.1200/jco.2015.62.3488","pmid":"26169616","authors":"Smith TJ, Bohlke K, Lyman GH, et al.","paperType":"review","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-esmo-rectal-cancer-guideline-ann-oncol-2017","kind":"paper","name":"Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","aka":[],"tldr":"The European guideline for rectal cancer: how MRI decides the treatment, when radiotherapy is given before the operation, and how the mesorectum is removed.","summary":"ESMO Clinical Practice Guidelines for rectal cancer, published in Annals of Oncology in 2017 by Glynne-Jones, Wyrwicz, Tiret, Brown, Rödel, Cervantes and Arnold for the ESMO Guidelines Committee. Europe PMC indexes no abstract for this article, so OnCo carries no figures from it.\n\nIts organising idea is risk stratification by MRI: the distance from the tumour or an involved node to the mesorectal fascia, extramural venous invasion and nodal status decide whether a patient has surgery alone, short-course radiotherapy, or long-course chemoradiotherapy before total mesorectal excision.","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2017","url":"https://doi.org/10.1093/annonc/mdx224"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28881920/"}],"tags":["colorectal-evidence"],"related":["esmo-guidelines"],"cancers":["colorectal","rectal-cancer"],"sections":[],"technologies":["mri","radiotherapy","imrt-igrt"],"targets":[],"drugs":[],"companies":[],"institutions":["esmo"],"pathways":[],"terms":["total-mesorectal-excision","neoadjuvant-adjuvant","chemoradiation"],"trials":[],"people":["andres-cervantes"],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2017,"doi":"10.1093/annonc/mdx224","pmid":"28881920","authors":"Glynne-Jones R, Wyrwicz L, Tiret E, et al.","paperType":"guideline","findings":["No abstract is indexed on Europe PMC; recommendations are read from the guideline itself."],"whatItMeans":"The document behind the MRI-first rectal cancer pathway used across Europe and the UK; the total neoadjuvant therapy trials (RAPIDO, PRODIGE 23, OPRA) that came after it are the main reason an update was needed.","caveats":["Predates RAPIDO (2021), PRODIGE 23 (2021), OPRA (2022) and the dostarlimab organ-preservation series, all of which changed what is offered before surgery.","Guideline text, not a trial."],"changedPractice":true},{"id":"paper-badalian-very-braf-mutations-lch-blood-2010","kind":"paper","name":"Recurrent BRAF mutations in Langerhans cell histiocytosis","aka":[],"tldr":"More than half of Langerhans cell histiocytosis samples carried the same BRAF V600E mutation seen in melanoma, settling a long argument by showing the disease is a clonal neoplasm and opening it to targeted therapy.","summary":"Genotyping of 61 archived LCH samples with a mass-spectrometric cancer mutation panel found BRAF V600E in 35 (57 percent), across ages and sites, with no other recurrent oncogene mutations detected; the mutation was confirmed by immunohistochemistry and was present in the pathological CD1a-positive cells.","asOf":"2026-09-18","links":[{"label":"Blood 2010","url":"https://doi.org/10.1182/blood-2010-04-279083"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20519626/"}],"tags":[],"related":[],"cancers":["lch-single-system","lch-multisystem"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["blood"],"dependsOn":[],"notes":[],"journal":"Blood","year":2010,"doi":"10.1182/blood-2010-04-279083","pmid":"20519626","authors":"Badalian-Very G, Vergilio JA, Degar BA, et al.","paperType":"translational","findings":["BRAF V600E in 35 of 61 LCH samples (57 percent)."],"whatItMeans":"LCH is a MAPK-pathway-driven neoplasm; BRAF testing is now routine and BRAF and MEK inhibitors are used for refractory disease.","caveats":["Archived samples; later work found MAP2K1 and other MAPK alterations in most BRAF wild-type cases.","Mutation status did not clearly predict outcome in this series."],"changedPractice":true,"participants":61},{"id":"paper-persson-myb-nfib-pnas-2009","kind":"paper","name":"Recurrent fusion of MYB and NFIB transcription factor genes in adenoid cystic carcinoma","aka":[],"tldr":"This study discovered that adenoid cystic carcinomas of the salivary gland and breast are driven by a fusion of the MYB and NFIB genes, providing the defining molecular feature of the tumour and a diagnostic marker.","summary":"Molecular study identifying a recurrent t(6;9) translocation in adenoid cystic carcinoma that fuses the MYB oncogene to NFIB, leading to MYB overexpression by loss of microRNA-mediated repression, present in the majority of tumours of both head and neck and breast origin.","asOf":"2026-09-17","links":[{"label":"Proc Natl Acad Sci U S A 2009","url":"https://doi.org/10.1073/pnas.0909114106"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19841262/"}],"tags":[],"related":[],"cancers":["adenoid-cystic-carcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["pnas"],"dependsOn":[],"notes":[],"journal":"Proceedings of the National Academy of Sciences","year":2009,"doi":"10.1073/pnas.0909114106","pmid":"19841262","authors":"Persson M, Andrén Y, Mark J, et al.","paperType":"basic","findings":["MYB-NFIB fusion detected in the majority of adenoid cystic carcinomas.","Fusion leads to MYB overexpression through loss of 3' untranslated region regulation."],"whatItMeans":"MYB immunostaining and MYB-NFIB fusion testing are now diagnostic tools for adenoid cystic carcinoma, and MYB is the principal target of therapeutic research in the disease.","caveats":["No approved MYB-directed therapy has yet followed."],"changedPractice":true},{"id":"paper-tomlins-tmprss2-ets-fusion-science-2005","kind":"paper","name":"Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer","aka":["Tomlins 2005","TMPRSS2-ERG fusion","TMPRSS2-ETV1"],"tldr":"Gene fusions were thought to be a feature of leukaemias, not common solid cancers. This study found one in prostate cancer that joins a switch controlled by testosterone to a growth gene, and found it in most of the tumours it looked at.","summary":"Scott Tomlins, Arul Chinnaiyan and colleagues at Michigan used a bioinformatics method that looks for genes expressed at extreme levels in a minority of samples, identified ERG and ETV1 as outliers in prostate cancer, and then found recurrent fusions joining the 5 prime untranslated region of TMPRSS2 to one or the other.\n\nThe mechanism is elegant and specifically prostatic: TMPRSS2 is androgen-responsive, so the fusion puts an ETS transcription factor under the control of the hormone that the prostate is bathed in. It was the first recurrent chromosomal rearrangement found in a common carcinoma, and it broke the assumption that fusions belong to haematological cancers. Twenty years later it defines the largest molecular subtype of prostate cancer and has still produced no drug, which is the honest state of the finding.","asOf":"2026-09-25","links":[{"label":"Science 2005","url":"https://doi.org/10.1126/science.1117679"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/16254181/"}],"tags":["prostate-evidence"],"related":["paper-taylor-integrative-genomic-profiling-cancer-cell-2010","paper-tcga-molecular-taxonomy-primary-prostate-cell-2015","prostate-roadmap"],"cancers":["prostate","prostate-high-risk","prostate-mcrpc"],"sections":["diagnostics","targeted-therapy"],"technologies":["cytogenetics-fish","rna-seq"],"targets":["erg","tmprss2","androgen-receptor","etv1"],"drugs":[],"companies":[],"institutions":["michigan-rogel"],"pathways":["prostate-cancer-signalling","ar-signaling","transcription-addiction"],"terms":["ngs","gene-fusion","fish","driver-mutation"],"trials":[],"people":["arul-chinnaiyan"],"bottlenecks":["b-undruggable-targets","b-biomarker-validation"],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2005,"doi":"10.1126/science.1117679","pmid":"16254181","authors":"Tomlins SA, Rhodes DR, Perner S, et al.","paperType":"basic","findings":["Recurrent gene fusions of the 5 prime untranslated region of TMPRSS2 to ERG or ETV1 were identified in prostate cancer tissues with outlier expression.","Fluorescence in situ hybridisation demonstrated rearrangements in ERG or ETV1 in 23 of 29 prostate cancer samples.","Cell line experiments suggest the androgen-responsive promoter elements of TMPRSS2 mediate the overexpression of ETS family members.","The finding established that recurrent chromosomal rearrangements, previously characterised mainly in haematological malignancies, occur in a common carcinoma."],"whatItMeans":"The most common single molecular event in prostate cancer, present in roughly half of tumours in most series, and the reason prostate cancer is classified by fusion status. It is also a standing reminder that finding the driver and drugging it are different problems: no ETS-directed therapy has reached the clinic.","caveats":["23 of 29 samples is a discovery cohort, not a prevalence estimate; large series put ERG rearrangement at roughly half of prostate cancers and lower in men of African ancestry.","Fusion status has repeatedly failed to predict prognosis consistently across cohorts.","Transcription factors remain difficult to drug; two decades on, ETS fusion status changes classification and not treatment."],"changedPractice":false,"participants":29},{"id":"paper-wu-gnas-ipmn-sci-transl-med-2011","kind":"paper","name":"Recurrent GNAS mutations define an unexpected pathway for pancreatic cyst development","aka":[],"tldr":"Sequencing the fluid from pancreatic cysts found that two-thirds of the mucinous kind carry a mutation at one spot in the GNAS gene, and the same mutation turns up in the cancers that grow out of them, giving a marker for which cyst is which.","summary":"DNA from IPMN cyst fluids of 19 patients was searched for mutations in 169 cancer genes. Besides the expected KRAS mutations, recurrent mutations at codon 201 of GNAS were identified; 113 further IPMNs were analysed, giving GNAS mutations in 66% and KRAS or GNAS in 96%. In seven of eight invasive adenocarcinomas arising with GNAS-mutant IPMNs, the same GNAS mutation was present in the invasive lesion. GNAS mutations were not found in other cystic neoplasms of the pancreas or in invasive adenocarcinomas unassociated with IPMN.","asOf":"2026-09-24","links":[{"label":"Wu et al., Sci Transl Med 2011: recurrent GNAS mutations in IPMN","url":"https://doi.org/10.1126/scitranslmed.3002543"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21775669/"}],"tags":[],"related":[],"cancers":["pancreatic","ipmn-cystic-precursors"],"sections":[],"technologies":[],"targets":["gnas","kras"],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":[],"terms":["biopsy"],"trials":[],"people":["bert-vogelstein","anirban-maitra","luis-diaz"],"bottlenecks":[],"keyPapers":[],"journals":["science-translational-medicine"],"dependsOn":[],"notes":[],"journal":"Science Translational Medicine","year":2011,"doi":"10.1126/scitranslmed.3002543","pmid":"21775669","authors":"Wu J, Matthaei H, Maitra A, et al.","paperType":"translational","findings":["GNAS codon 201 mutations in 66% of IPMNs; KRAS or GNAS in 96%.","The same GNAS mutation was in the invasive cancer in 7 of 8 IPMN-associated carcinomas.","GNAS mutations absent from other cyst types and from non-IPMN cancers."],"whatItMeans":"A GNAS mutation in cyst fluid says the cyst is an IPMN, and in a cancer it says the cancer came from one, which is the molecular basis of cyst triage.","caveats":["Resected cysts; selection towards larger lesions.","GNAS presence does not grade dysplasia."],"changedPractice":false,"participants":132},{"id":"paper-jo-idh2-r172-mutations-snuc-mod-pathol-2017","kind":"paper","name":"Recurrent IDH2 R172X mutations in sinonasal undifferentiated carcinoma","aka":[],"tldr":"Sequencing showed that most sinonasal undifferentiated carcinomas, a cancer long defined only by what it is not, carry a mutation in the IDH2 gene found in no other head and neck cancer, giving the disease a molecular identity, a diagnostic antibody test and a possible drug target.","summary":"Targeted next-generation sequencing of 300 cancer-related genes in 11 sinonasal undifferentiated carcinomas from Brigham and Women's Hospital and Dana-Farber Cancer Institute. IDH2 R172 mutations (R172S, R172T and R172M) were found in 55 percent of cases, and a multispecific mutant IDH1/2 antibody stained all mutant tumours with available tissue (3 of 3) and none of the wild-type (0 of 4). Review of 412 sequenced head and neck tumours at the same institutions found IDH-activating mutations in no other tumour type.\n\nIDH2 wild-type cases carried SMARCA4 loss with loss of protein expression, NOTCH1 gain-of-function or TET2 loss-of-function alterations, foreshadowing the later separation of SWI/SNF-deficient sinonasal carcinoma. Published alongside a Memorial Sloan Kettering series with the same finding, the paper established IDH2 R172 as the defining alteration of the disease.","asOf":"2026-09-18","links":[{"label":"Mod Pathol 2017","url":"https://doi.org/10.1038/modpathol.2016.239"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28084339/"}],"tags":[],"related":[],"cancers":["sinonasal-undifferentiated-carcinoma"],"sections":[],"technologies":["histopathology-ihc","cgp"],"targets":["idh"],"drugs":["enasidenib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Modern Pathology","year":2017,"doi":"10.1038/modpathol.2016.239","pmid":"28084339","authors":"Jo VY, Chau NG, Hornick JL, Krane JF, Sholl LM.","paperType":"translational","findings":["IDH2 R172 mutations in 55 percent of 11 sinonasal undifferentiated carcinomas (R172S, R172T, R172M).","Mutant IDH1/2 immunohistochemistry was positive in 3 of 3 mutant and negative in 4 of 4 wild-type tumours.","No IDH-activating mutation in 412 other head and neck tumours; IDH2 wild-type cases showed SMARCA4, NOTCH1 or TET2 alterations."],"whatItMeans":"Sinonasal undifferentiated carcinoma can be confirmed by IDH2 testing or mutant-IDH immunohistochemistry rather than diagnosed by exclusion, and IDH2 inhibitors such as enasidenib became rational candidates for trials.","caveats":["Eleven cases from two institutions; later series put the IDH2 mutation rate at roughly 50 to 80 percent.","Diagnostic value rests on the mutation being absent from mimics, which larger cohorts have since confirmed for carcinomas but not for a subset of high-grade esthesioneuroblastomas."],"changedPractice":true,"participants":11},{"id":"paper-seshagiri-rspo-fusions-colon-nature-2012","kind":"paper","name":"Recurrent R-spondin fusions in colon cancer","aka":[],"tldr":"Sequencing the DNA and the RNA of more than 70 colon tumours turned up a new way of switching on the growth signal that drives the disease: two genes fused so that an amplifier of the WNT pathway is overproduced, in tumours whose usual brake gene is intact.","summary":"More than 70 pairs of primary human colon tumours and matched normal tissue were analysed by exome, transcriptome and copy-number sequencing, identifying 36,303 protein-altering somatic changes. New recurrent mutations were found in the WNT pathway gene TCF7L2, in chromatin-remodelling genes including TET2 and TET3, and in receptor tyrosine kinases including ERBB3; 23 significantly mutated genes were identified, including ATM. Copy-number and RNA sequencing found amplification and corresponding overexpression of IGF2. Recurrent gene fusions involving RSPO2 and RSPO3 together occurred in 10% of the tumours, were mutually exclusive with APC mutation, and potentiated WNT signalling in functional assays.\n\nDeposited as coadread_genentech on cBioPortal (72 sequenced tumours).","asOf":"2026-09-24","links":[{"label":"Seshagiri et al., Nature 2012: recurrent R-spondin fusions in colon cancer (more than 70 tumour pairs)","url":"https://doi.org/10.1038/nature11282"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22895193/"},{"label":"cBioPortal study coadread_genentech (Genentech, Nature 2012; 72 sequenced colon tumours, the R-spondin fusion discovery set)","url":"https://www.cbioportal.org/study/summary?id=coadread_genentech"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["wes-wgs","rna-seq"],"targets":["rspo3","rspo2","tcf7l2","apc","atm"],"drugs":[],"companies":[],"institutions":[],"pathways":["wnt","rtk-activation"],"terms":["gene-fusion"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2012,"doi":"10.1038/nature11282","pmid":"22895193","authors":"Seshagiri S, Stawiski EW, Durinck S, et al.","paperType":"translational","findings":["RSPO2 and RSPO3 fusions in 10% of colon tumours, mutually exclusive with APC mutation.","IGF2 amplification with matching overexpression.","New recurrent mutations in TCF7L2, TET2, TET3 and ERBB3."],"whatItMeans":"It gave the WNT pathway a second, druggable entry point: RSPO fusion tumours still need the upstream receptor complex, so they are the population porcupine and RSPO3 inhibitors are being tested in.","caveats":["Small discovery cohort; DNA panels find RSPO fusions far less often (0.4% in 7,237 MSK-IMPACT samples) because intron coverage is partial.","No approved therapy follows from an RSPO fusion."],"changedPractice":false,"participants":74},{"id":"paper-carson-jama","kind":"paper","name":"Red Blood Cell Transfusion: 2023 AABB International Guidelines","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 37824153 and published in JAMA; the citing page links this DOI, which is how the record was matched.","summary":"Importance: Red blood cell transfusion is a common medical intervention with benefits and harms.\n\nObjective: To provide recommendations for use of red blood cell transfusion in adults and children.\n\nEvidence review: Standards for trustworthy guidelines were followed, including using Grading of Recommendations Assessment, Development and Evaluation methods, managing conflicts of interest, and making values and preferences explicit. Evidence from systematic reviews of randomized controlled trials was reviewed.\n\nFindings: For adults, 45 randomized controlled trials with 20 599 participants compared restrictive hemoglobin-based transfusion thresholds, typically 7 to 8 g/dL, with liberal transfusion thresholds of 9 to 10 g/dL. For pediatric patients, 7 randomized controlled trials with 2730 participants compared a variety of restrictive and liberal transfusion thresholds. For most patient populations, results provided moderate quality evidence that restrictive transfusion thresholds did not adversely affect patient-important outcomes. Recommendation 1: for hospitalized adult patients who are hemodynamically stable, the international panel recommends a restrictive transfusion strategy considering transfusion when the hemoglobin concentration is less than 7 g/dL (strong recommendation, moderate certainty evidence). In accordance with the restrictive strategy threshold used in most trials, clinicians may choose a threshold of 7.5 g/dL for patients undergoing cardiac surgery and 8 g/dL for those undergoing orthopedic surgery or those with preexisting cardiovascular disease. Recommendation 2: for hospitalized adult patients with hematologic and oncologic disorders, the panel suggests a restrictive transfusion strategy considering transfusion when the hemoglobin concentration is less than 7 g/dL (conditional recommendations, low certainty evidence). Recommendation 3: for critically ill children and those at risk of critical illness who are hemodynamically stable and without a hemoglobinopathy, cyanotic cardiac condition, or severe hypoxemia, the international panel recommends a restrictive transfusion strategy considering transfusion when the hemoglobin concentration is less than 7 g/dL (strong recommendation, moderate certainty evidence). Recommendation 4: for hemodynamically stable children with congenital heart disease, the international panel suggests a transfusion threshold that is based on the cardiac abnormality and stage of surgical repair: 7 g/dL (biventricular repair), 9 g/dL (single-ventricle palliation), or 7 to 9 g/dL (uncorrected congenital heart disease) (conditional recommendation, low certainty evidence).\n\nConclusions and relevance: It is good practice to consider overall clinical context and alternative therapies to transfusion when making transfusion decisions about an individual patient.\n\nIndexed on Europe PMC as PubMed record 37824153 (DOI 10.1001/jama.2023.12914). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA 2023","url":"https://doi.org/10.1001/jama.2023.12914"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37824153/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37824153"}],"tags":["europepmc-ingest"],"related":["transfusion-support"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2023,"doi":"10.1001/jama.2023.12914","pmid":"37824153","authors":"Carson JL, Stanworth SJ, Guyatt G, et al.","paperType":"guideline","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-armstrong-n-engl-j-med","kind":"paper","name":"Reduction in Late Mortality among 5-Year Survivors of Childhood Cancer","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 26761625 and published in New England Journal of Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Background: Among patients in whom childhood cancer was diagnosed in the 1970s and 1980s, 18% of those who survived for 5 years died within the subsequent 25 years. In recent decades, cancer treatments have been modified with the goal of reducing life-threatening late effects.\n\nMethods: We evaluated late mortality among 34,033 patients in the Childhood Cancer Survivor Study cohort who survived at least 5 years after childhood cancer (i.e., cancer diagnosed before the age of 21 years) for which treatment was initiated during the period from 1970 through 1999. The median follow-up was 21 years (range, 5 to 38). We evaluated demographic and disease factors that were associated with death from health-related causes (i.e., conditions that exclude recurrence or progression of the original cancer and external causes but include the late effects of cancer therapy) using cumulative incidence and piecewise exponential models to estimate relative rates and 95% confidence intervals.\n\nResults: Of the 3958 deaths that occurred during the study period, 1618 (41%) were attributable to health-related causes, including 746 deaths from subsequent neoplasms, 241 from cardiac causes, 137 from pulmonary causes, and 494 from other causes. A reduction in 15-year mortality was observed for death from any cause (from 12.4% in the early 1970s to 6.0% in the 1990s, P<0.001 for trend) and from health-related causes (from 3.5% to 2.1%, P<0.001 for trend). These reductions were attributable to decreases in the rates of death from subsequent neoplasm (P<0.001), cardiac causes (P<0.001), and pulmonary causes (P=0.04). Changes in therapy according to decade included reduced rates of cranial radiotherapy for acute lymphoblastic leukemia (85% in the 1970s, 51% in the 1980s, and 19% in the 1990s), of abdominal radiotherapy for Wilms' tumor (78%, 53%, and 43%, respectively), of chest radiotherapy for Hodgkin's lymphoma (87%, 79%, and 61%, respectively), and of anthracycline exposure. Reduction in treatment exposure was associated with reduced late mortality among survivors of acute lymphoblastic leukemia and Wilms' tumor.\n\nConclusions: The strategy of lowering therapeutic exposure has contributed to an observed decline in late mortality among 5-year survivors of childhood cancer. (Funded by the National Cancer Institute and the American Lebanese-Syrian Associated Charities.).\n\nIndexed on Europe PMC as PubMed record 26761625 (DOI 10.1056/nejmoa1510795). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2016","url":"https://doi.org/10.1056/nejmoa1510795"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26761625/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26761625"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["ccss"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2016,"doi":"10.1056/nejmoa1510795","pmid":"26761625","authors":"Armstrong GT, Chen Y, Yasui Y, et al.","paperType":"observational","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-lehmann-tnbctype-4-refinement-plos-one-2016","kind":"paper","name":"Refinement of Triple-Negative Breast Cancer Molecular Subtypes: Implications for Neoadjuvant Chemotherapy Selection","aka":[],"tldr":"The 2016 revision that cut the six triple-negative subtypes to four after showing the immune and stem-like signals came from surrounding cells, and found that response to standard chemotherapy before surgery ranged from 41 percent in basal-like 1 to 18 percent in basal-like 2.","summary":"Lehmann, Jovanović, Chen, Estrada and colleagues used histopathological quantification and laser-capture microdissection to show that transcripts of the immunomodulatory and mesenchymal stem-like subtypes came from infiltrating lymphocytes and tumour-associated stromal cells, and refined the classification to four tumour-specific subtypes (TNBCtype-4: BL1, BL2, M and LAR) that differ in age at diagnosis, grade, local and distant progression and histopathology. Retrospective evaluation of more than 300 triple-negative patients across five public neoadjuvant chemotherapy data sets showed pathological complete response in 41 percent of BL1 (95 percent confidence interval 33 to 51), 18 percent of BL2 (9 to 28) and 29 percent of LAR (17 to 41) tumours.","asOf":"2026-09-24","links":[{"label":"PLoS One 2016","url":"https://doi.org/10.1371/journal.pone.0157368"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27310713/"}],"tags":["tnbc-evidence"],"related":["paper-lehmann-tnbc-subtypes-jci-2011"],"cancers":["tnbc","tnbc-early"],"sections":[],"technologies":["rna-seq"],"targets":["androgen-receptor"],"drugs":[],"companies":[],"institutions":["vanderbilt-ingram"],"pathways":[],"terms":["pcr","tils"],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"PLoS One","year":2016,"doi":"10.1371/journal.pone.0157368","pmid":"27310713","authors":"Lehmann BD, Jovanović B, Chen X, et al.","paperType":"translational","findings":["Immunomodulatory and mesenchymal stem-like signals traced to infiltrating lymphocytes and stroma; subtypes reduced to BL1, BL2, M and LAR.","Pathological complete response to neoadjuvant chemotherapy: BL1 41 percent (95 percent CI 33 to 51), BL2 18 percent (9 to 28), LAR 29 percent (17 to 41)."],"whatItMeans":"The first evidence that molecular subtype predicts chemotherapy response in triple-negative disease, and the origin of the observation that the immune signal in these tumours is real and measurable, which tumour-infiltrating lymphocyte scoring later turned into a prognostic tool.","caveats":["Retrospective, pooled public data with heterogeneous regimens.","No prospective trial has yet assigned treatment by TNBCtype."],"changedPractice":false,"participants":300},{"id":"paper-reflect-lenvatinib-lancet-2018","kind":"paper","name":"REFLECT: lenvatinib versus sorafenib in first-line treatment of unresectable hepatocellular carcinoma","aka":[],"tldr":"Lenvatinib matched sorafenib for survival in advanced liver cancer while shrinking tumours far more often and delaying progression longer, making it the first new first-line option in ten years.","summary":"Phase 3 non-inferiority trial of 954 patients with unresectable hepatocellular carcinoma randomised to lenvatinib (weight-based 8 or 12 mg) or sorafenib.\n\nMedian overall survival was 13.6 versus 12.3 months (hazard ratio 0.92, non-inferior), progression-free survival 7.4 versus 3.7 months, and response 24.1 versus 9.2 percent; hypertension, proteinuria and decreased appetite were more frequent with lenvatinib.","asOf":"2026-09-17","links":[{"label":"Lancet 2018","url":"https://doi.org/10.1016/S0140-6736(18)30207-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29433850/"}],"tags":[],"related":[],"cancers":["hcc-advanced"],"sections":[],"technologies":[],"targets":[],"drugs":["lenvatinib","sorafenib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["reflect"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2018,"doi":"10.1016/S0140-6736(18)30207-1","pmid":"29433850","authors":"Kudo M, Finn RS, Qin S, et al.","paperType":"rct","findings":["Median overall survival 13.6 vs 12.3 months; hazard ratio 0.92 (non-inferior).","Objective response 24.1 percent vs 9.2 percent."],"whatItMeans":"Lenvatinib is a first-line alternative to sorafenib and the preferred kinase inhibitor when immunotherapy is contraindicated, such as after liver transplantation.","caveats":["Excluded main portal vein invasion and over 50 percent liver involvement.","Non-inferiority rather than superiority."],"changedPractice":true,"participants":954},{"id":"paper-narayan-gallbladder-regional-mutations-cancer-2019","kind":"paper","name":"Regional differences in gallbladder cancer pathogenesis: insights from a multi-institutional comparison of tumor mutations","aka":[],"tldr":"Comparing gallbladder tumours from Chile, Japan and the United States, Japanese patients were older with fewer stone-related cancers and different mutations, while SMAD4 loss was common everywhere and went with shorter survival.","summary":"Primary tumours from 81 patients with gallbladder cancer treated in Chile (21), Japan (11) and the United States (49) between 1999 and 2016 underwent targeted sequencing of known cancer-associated genes. Japanese patients were older (median 72 years versus 59 in Chile and 66 in the United States), had more well-differentiated tumours (46% versus 0%) and fewer gallstone-associated cancers (36% versus 67% and 69%), and had a higher median mutation burden (6 versus 7 in Chile and 4 in the United States; P = 0.006).\n\nTumours from Japanese patients lacked ARID1A and PIK3CA mutations, whereas Chilean tumours lacked ERBB3 and ARID2 mutations. SMAD4 was mutated similarly across centres (38% in Chile, 36% in Japan, 27% in the United States) and was univariately associated with worse overall survival (median 10 versus 25 months; P = 0.039). At least one potentially actionable gene was altered in 80% of tumours.","asOf":"2026-09-24","links":[{"label":"Narayan et al., Cancer 2019: regional differences in gallbladder cancer mutations (Chile, Japan, United States)","url":"https://doi.org/10.1002/cncr.31850"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30427539/"},{"label":"cBioPortal study gbc_msk_2018 (Gallbladder Cancer, MSK, Cancer 2018; 103 samples)","url":"https://www.cbioportal.org/study/summary?id=gbc_msk_2018"}],"tags":[],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":["smad4","arid1a","pik3ca","her3","arid2"],"drugs":[],"companies":[],"institutions":["mskcc"],"pathways":[],"terms":[],"trials":[],"people":["ghassan-abou-alfa"],"bottlenecks":[],"keyPapers":[],"journals":["cancer-wiley"],"dependsOn":[],"notes":[],"journal":"Cancer","year":2019,"doi":"10.1002/cncr.31850","pmid":"30427539","authors":"Narayan RR, Creasy JM, Goldman DA, et al.","paperType":"observational","findings":["SMAD4 mutated in 38% (Chile), 36% (Japan) and 27% (United States); median survival 10 versus 25 months with and without it.","Japanese tumours lacked ARID1A and PIK3CA mutations; Chilean tumours lacked ERBB3 and ARID2.","At least one potentially actionable alteration in 80% of tumours."],"whatItMeans":"Regional biology is real but partial: exposures and age differ, some genes differ, and SMAD4 loss emerges as the shared bad-prognosis marker. It is the paper behind the MSK 2018 gallbladder study on cBioPortal (gbc_msk_2018).","caveats":["Only 11 Japanese and 21 Chilean tumours; absence of a mutation in such small groups is weak evidence.","Targeted panel, so tumour mutation burden is a panel count, not a per-megabase figure."],"changedPractice":false,"participants":81},{"id":"paper-ma-20-n-engl-j-med-2015","kind":"paper","name":"Regional Nodal Irradiation in Early-Stage Breast Cancer","aka":[],"tldr":"Published report from the trial registered as NCT00005957, in New England Journal of Medicine (2015), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Most women with breast cancer who undergo breast-conserving surgery receive whole-breast irradiation. We examined whether the addition of regional nodal irradiation to whole-breast irradiation improved outcomes.\n\nMethods: We randomly assigned women with node-positive or high-risk node-negative breast cancer who were treated with breast-conserving surgery and adjuvant systemic therapy to undergo either whole-breast irradiation plus regional nodal irradiation (including internal mammary, supraclavicular, and axillary lymph nodes) (nodal-irradiation group) or whole-breast irradiation alone (control group). The primary outcome was overall survival. Secondary outcomes were disease-free survival, isolated locoregional disease-free survival, and distant disease-free survival.\n\nResults: Between March 2000 and February 2007, a total of 1832 women were assigned to the nodal-irradiation group or the control group (916 women in each group). The median follow-up was 9.5 years. At the 10-year follow-up, there was no significant between-group difference in survival, with a rate of 82.8% in the nodal-irradiation group and 81.8% in the control group (hazard ratio, 0.91; 95% confidence interval [CI], 0.72 to 1.13; P=0.38). The rates of disease-free survival were 82.0% in the nodal-irradiation group and 77.0% in the control group (hazard ratio, 0.76; 95% CI, 0.61 to 0.94; P=0.01). Patients in the nodal-irradiation group had higher rates of grade 2 or greater acute pneumonitis (1.2% vs. 0.2%, P=0.01) and lymphedema (8.4% vs. 4.5%, P=0.001).\n\nConclusions: Among women with node-positive or high-risk node-negative breast cancer, the addition of regional nodal irradiation to whole-breast irradiation did not improve overall survival but reduced the rate of breast-cancer recurrence. (Funded by the Canadian Cancer Society Research Institute and others; MA.20 ClinicalTrials.gov number, NCT00005957.).\n\nIndexed on Europe PMC as PubMed record 26200977 (DOI 10.1056/nejmoa1415340). Its abstract cites the registry id NCT00005957, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2015","url":"https://doi.org/10.1056/nejmoa1415340"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26200977/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26200977"},{"label":"ClinicalTrials.gov NCT00005957","url":"https://clinicaltrials.gov/study/NCT00005957"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["ma-20"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2015,"doi":"10.1056/nejmoa1415340","pmid":"26200977","authors":"Whelan TJ, Olivotto IA, Parulekar WR, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT00005957 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-grothey-correct-regorafenib-lancet-2013","kind":"paper","name":"Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT)","aka":[],"tldr":"The first pill to extend life after every standard treatment had failed, by 1.4 months, at the price of hand-foot skin reaction in one patient in six.","summary":"Grothey, Van Cutsem, Sobrero and colleagues ran CORRECT at 114 centres in 16 countries in patients with metastatic colorectal cancer progressing during or within three months after the last standard therapy, randomising them 2:1 to best supportive care plus oral regorafenib 160 mg or placebo once daily for the first three weeks of each four-week cycle. The primary endpoint was overall survival, and efficacy analyses were by intention to treat.\n\nBetween April 2010 and March 2011, 760 patients were randomised (505 regorafenib, 255 placebo) and 753 started treatment. The primary endpoint was met at a preplanned interim analysis.","asOf":"2026-09-24","links":[{"label":"Lancet 2013","url":"https://doi.org/10.1016/S0140-6736(12)61900-X"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23177514/"}],"tags":["colorectal-evidence"],"related":["paper-mayer-recourse-tas-102-nejm-2015","paper-dasari-fresco-2-fruquintinib-lancet-2023"],"cancers":["colorectal"],"sections":["targeted-therapy"],"technologies":["kinase-inhibitors","antiangiogenic"],"targets":["vegf"],"drugs":["regorafenib"],"companies":["bayer"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["eric-van-cutsem","yoshino-takayuki","heinz-josef-lenz"],"bottlenecks":["b-toxicity-qol","b-resistance"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2013,"doi":"10.1016/S0140-6736(12)61900-X","pmid":"23177514","authors":"Grothey A, Van Cutsem E, Sobrero A, et al.","paperType":"rct","findings":["Median overall survival 6.4 months with regorafenib against 5.0 months with placebo: hazard ratio 0.77 (95 percent CI 0.64 to 0.94, one-sided p=0.0052).","Treatment-related adverse events in 465 of 500 (93 percent) on regorafenib against 154 of 253 (61 percent) on placebo.","Commonest grade 3 or higher regorafenib-related events: hand-foot skin reaction 83 patients (17 percent), fatigue 48 (10 percent), diarrhoea 36 (7 percent), hypertension 36 (7 percent), rash or desquamation 29 (6 percent)."],"whatItMeans":"The start of the refractory-line era in colorectal cancer: a survival benefit measured in weeks, with real toxicity, which is why dose-escalation strategies and patient selection have occupied the field since.","caveats":["1.4 months of median survival at a high rate of grade 3 toxicity; quality of life is the contested part of the result.","No biomarker selects responders, and none has been found since.","Funded by the manufacturer."],"changedPractice":true,"participants":760},{"id":"paper-brown-n-engl-j-med","kind":"paper","name":"Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 28029927 and published in New England Journal of Medicine; the citing page links this DOI, which is how the record was matched.","summary":"A patient with recurrent multifocal glioblastoma received chimeric antigen receptor (CAR)-engineered T cells targeting the tumor-associated antigen interleukin-13 receptor alpha 2 (IL13Rα2). Multiple infusions of CAR T cells were administered over 220 days through two intracranial delivery routes - infusions into the resected tumor cavity followed by infusions into the ventricular system. Intracranial infusions of IL13Rα2-targeted CAR T cells were not associated with any toxic effects of grade 3 or higher. After CAR T-cell treatment, regression of all intracranial and spinal tumors was observed, along with corresponding increases in levels of cytokines and immune cells in the cerebrospinal fluid. This clinical response continued for 7.5 months after the initiation of CAR T-cell therapy. (Funded by Gateway for Cancer Research and others; ClinicalTrials.gov number, NCT02208362.).\n\nIndexed on Europe PMC as PubMed record 28029927 (DOI 10.1056/nejmoa1610497). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2016","url":"https://doi.org/10.1056/nejmoa1610497"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28029927/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28029927"}],"tags":["europepmc-ingest"],"related":["glioma-car-t"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2016,"doi":"10.1056/nejmoa1610497","pmid":"28029927","authors":"Brown CE, Alizadeh D, Starr R, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-wotherspoon-h-pylori-malt-lancet-1993","kind":"paper","name":"Regression of primary low-grade gastric MALT lymphoma after eradication of Helicobacter pylori","aka":[],"tldr":"In six patients, eradicating the stomach bacterium Helicobacter pylori with antibiotics made low-grade gastric lymphoma regress, proving that a cancer could be caused by, and treated through, a chronic infection.","summary":"Case series of six patients with primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type and Helicobacter pylori infection treated with antibiotics to eradicate the organism.\n\nIn five patients the lymphoma regressed histologically and endoscopically after eradication, supporting the hypothesis that the lymphoma is driven by antigenic stimulation from the infection.","asOf":"2026-09-17","links":[{"label":"Lancet 1993","url":"https://doi.org/10.1016/0140-6736(93)91409-F"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/8102719/"}],"tags":[],"related":["lymphoma-roadmap","paper-ielsg-19-chlorambucil-rituximab-malt-jco-2017"],"cancers":["marginal-zone-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":1993,"doi":"10.1016/0140-6736(93)91409-F","pmid":"8102719","authors":"Wotherspoon AC, Doglioni C, Diss TC, et al.","paperType":"observational","findings":["Lymphoma regression in five of six patients after Helicobacter pylori eradication."],"whatItMeans":"Antibiotic eradication is the first-line treatment for Helicobacter pylori-positive gastric MALT lymphoma, curing most patients without chemotherapy or radiotherapy.","caveats":["Six patients; lymphomas with t(11;18) or deep invasion often do not respond and need radiotherapy."],"changedPractice":true,"participants":6},{"id":"paper-downing-n-engl-j-med","kind":"paper","name":"Regulatory review of novel therapeutics--comparison of three regulatory agencies","aka":[],"tldr":"Paper cited by one bottleneck page, indexed on Europe PMC as PubMed record 22591257 and published in New England Journal of Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Background: The upcoming reauthorization of the Prescription Drug User Fee Act focuses on improving the review process for new drug applications at the Food and Drug Administration (FDA).\n\nMethods: Using publicly available information from the FDA, the European Medicines Agency (EMA), and Health Canada, we compared the time for completion of the first review and the total review time for all applications involving novel therapeutic agents approved by the three regulatory agencies from 2001 through 2010 and determined the geographic area in which each novel therapeutic agent was first approved for use.\n\nResults: There were 510 applications for novel therapeutic agents approved from 2001 through 2010--225 by the FDA, 186 by the EMA, and 99 by Health Canada; among the applications, there were 289 unique agents. The median length of time for completion of the first review was 303 days (interquartile range, 185 to 372) for applications approved by the FDA, 366 days (interquartile range, 310 to 445) for those approved by the EMA, and 352 days (interquartile range, 255 to 420) for those approved by Health Canada (P<0.001 for the comparison across the three agencies). The median total review time was also shorter at the FDA than at the EMA or Health Canada (P=0.002). Among the 289 unique novel therapeutic agents, 190 were approved in both the United States and Europe (either by the EMA or through the mutual recognition process), of which 121 (63.7%) were first approved in the United States; similarly, 154 were approved in both the United States and Canada, of which 132 (85.7%) were first approved in the United States.\n\nConclusions: For novel therapeutic agents approved between 2001 and 2010, the FDA reviewed applications involving novel therapeutics more quickly, on average, than did the EMA or Health Canada, and the vast majority of these new therapeutic agents were first approved for use in the United States. (Funded by the Pew Charitable Trusts.).\n\nIndexed on Europe PMC as PubMed record 22591257 (DOI 10.1056/nejmsa1200223). Matched by DOI alone: one bottleneck page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2012","url":"https://doi.org/10.1056/nejmsa1200223"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22591257/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/22591257"}],"tags":["europepmc-ingest"],"related":["b-regulatory-fragmentation"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2012,"doi":"10.1056/nejmsa1200223","pmid":"22591257","authors":"Downing NS, Aminawung JA, Shah ND, et al.","paperType":"observational","findings":[],"whatItMeans":"One bottleneck page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-tempero-ca19-9-lewis-antigens-cancer-res-1987","kind":"paper","name":"Relationship of carbohydrate antigen 19-9 and Lewis antigens in pancreatic cancer","aka":[],"tldr":"The 1987 study showing that people who lack the Lewis blood group antigens cannot make the CA 19-9 tumour marker, so in about one patient in ten a normal blood test says nothing about the cancer.","summary":"Tempero and colleagues studied 20 pancreatic cancer patients: Lewis a and b phenotype in saliva or on red cells, serum CA 19-9 by radioimmunoassay, and CA 19-9 and Lewis antigen expression in tumour tissue by immunoperoxidase. Patients who were Lewis a-negative b-negative failed to express CA 19-9 in tumour tissue and had normal or low serum levels (below 37 units per millilitre; P = 0.0011 versus Lewis-positive patients), whereas 88 percent of Lewis a-positive or b-positive patients had raised serum CA 19-9. The authors concluded that Lewis-negative patients cannot manufacture CA 19-9, and noted that Lewis a-positive patients unexpectedly expressed Lewis b antigen in tumour tissue.","asOf":"2026-09-24","links":[{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/3308077/"},{"label":"Europe PMC record","url":"https://europepmc.org/article/MED/3308077"}],"tags":["pancreatic-evidence"],"related":["paper-fahrmann-ca19-9-lead-time-gastroenterology-2021"],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ca19-9","tumour-markers","lewis-negative"],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation"],"keyPapers":[],"journals":["cancer-research"],"dependsOn":[],"notes":[],"journal":"Cancer Research","year":1987,"pmid":"3308077","authors":"Tempero MA, Uchida E, Takasaki H, et al.","paperType":"translational","findings":["Lewis a-negative b-negative patients did not express CA 19-9 in tumour or serum (P = 0.0011).","88 percent of Lewis-positive patients had serum CA 19-9 above 37 units per millilitre."],"whatItMeans":"The reason a normal CA 19-9 never rules pancreatic cancer out, why Lewis-negative patients need a different marker (CA 125, CEA or CA 19-9-independent panels), and a constraint on every blood-based detection idea on this page.","caveats":["Twenty patients, 1987 assays.","No DOI is indexed; the PubMed record is the anchor."],"participants":20},{"id":"paper-paganetti-phys-med-biol","kind":"paper","name":"Relative biological effectiveness (RBE) values for proton beam therapy. Variations as a function of biological endpoint, dose, and linear energy transfer","aka":[],"tldr":"Paper cited by two term pages, indexed on Europe PMC as PubMed record 25361443 and published in Physics in medicine and biology; the citing pages link this DOI, which is how the record was matched.","summary":"Proton therapy treatments are based on a proton RBE (relative biological effectiveness) relative to high-energy photons of 1.1. The use of this generic, spatially invariant RBE within tumors and normal tissues disregards the evidence that proton RBE varies with linear energy transfer (LET), physiological and biological factors, and clinical endpoint. Based on the available experimental data from published literature, this review analyzes relationships of RBE with dose, biological endpoint and physical properties of proton beams. The review distinguishes between endpoints relevant for tumor control probability and those potentially relevant for normal tissue complication. Numerous endpoints and experiments on sub-cellular damage and repair effects are discussed. Despite the large amount of data, considerable uncertainties in proton RBE values remain. As an average RBE for cell survival in the center of a typical spread-out Bragg peak (SOBP), the data support a value of ~1.15 at 2 Gy/fraction. The proton RBE increases with increasing LETd and thus with depth in an SOBP from ~1.1 in the entrance region, to ~1.15 in the center, ~1.35 at the distal edge and ~1.7 in the distal fall-off (when averaged over all cell lines, which may not be clinically representative). For small modulation widths the values could be increased. Furthermore, there is a trend of an increase in RBE as (α/β)x decreases. In most cases the RBE also increases with decreasing dose, specifically for systems with low (α/β)x. Data on RBE for endpoints other than clonogenic cell survival are too diverse to allow general statements other than that the RBE is, on average, in line with a value of ~1.1. This review can serve as a source for defining input parameters for applying or refining biophysical models and to identify endpoints where additional radiobiological data are needed in order to reduce the uncertainties to clinically acceptable levels.\n\nIndexed on Europe PMC as PubMed record 25361443 (DOI 10.1088/0031-9155/59/22/r419). Matched by DOI alone: two term pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Phys Med Biol 2014","url":"https://doi.org/10.1088/0031-9155/59/22/r419"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25361443/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25361443"}],"tags":["europepmc-ingest"],"related":["linear-energy-transfer","relative-biological-effectiveness"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Physics in medicine and biology","year":2014,"doi":"10.1088/0031-9155/59/22/r419","pmid":"25361443","authors":"Paganetti H","paperType":"review","findings":[],"whatItMeans":"Two term pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-relativity-047-nejm-2022","kind":"paper","name":"RELATIVITY-047: relatlimab plus nivolumab, the first LAG-3 checkpoint combination, in untreated advanced melanoma","aka":[],"tldr":"Adding an antibody against a second immune brake, LAG-3, to nivolumab delayed progression in advanced melanoma compared with nivolumab alone, with far fewer serious side effects than the ipilimumab combination.","summary":"Double-blind phase 3 trial of 714 patients with untreated advanced melanoma randomised to a fixed-dose combination of relatlimab (anti-LAG-3) and nivolumab or nivolumab alone. Primary endpoint was PFS by blinded review.\n\nMedian PFS was 10.1 vs 4.6 months (HR 0.75). Grade 3-4 treatment-related adverse events were 18.9% vs 9.7%, much lower than the roughly 55-59% seen with nivolumab plus ipilimumab. It validated LAG-3 as the third checkpoint target after CTLA-4 and PD-1, led to FDA approval of the combination (Opdualag) in 2022, and provided a gentler dual-checkpoint option.","asOf":"2026-09-08","links":[{"label":"NEJM 2022","url":"https://doi.org/10.1056/NEJMoa2109970"},{"label":"ClinicalTrials.gov NCT03470922","url":"https://clinicaltrials.gov/study/NCT03470922"}],"tags":[],"related":[],"cancers":["melanoma"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["lag3","pd1"],"drugs":["relatlimab-nivolumab","nivolumab"],"companies":["bms"],"institutions":["md-anderson"],"pathways":[],"terms":["pfs","os","irae","first-line"],"trials":["checkmate-067"],"people":[],"bottlenecks":["b-immunotherapy-response","b-toxicity-qol","b-combination-space"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/NEJMoa2109970","authors":"Tawbi HA, Schadendorf D, Lipson EJ, et al.","paperType":"rct","findings":["Median PFS 10.1 vs 4.6 months; HR 0.75 (95% CI 0.62-0.92); 12-month PFS 47.7% vs 36.0%.","Benefit consistent across LAG-3 and PD-L1 expression subgroups, so neither is used for selection.","Grade 3-4 treatment-related adverse events 18.9% vs 9.7%; discontinuation for toxicity 14.6% vs 6.7%.","Overall survival (updated analysis): median 51.0 vs 34.1 months, HR 0.80, not meeting the prespecified significance threshold.","Objective response 43.1% vs 32.6% in later analyses."],"whatItMeans":"Patients with newly diagnosed advanced melanoma have a dual-checkpoint option that improves on nivolumab alone with only a modest increase in serious side effects, making it attractive for those unable to tolerate or unwilling to risk the toxicity of ipilimumab. It did not prove superior survival, and it has not been compared with nivolumab plus ipilimumab, which remains preferred for patients with brain metastases or other high-risk features. LAG-3 is now an established target under study in many other cancers.","caveats":["Overall survival improvement did not reach statistical significance.","No head-to-head comparison with nivolumab plus ipilimumab; indirect comparisons suggest the ipilimumab combination may be more active in poor-prognosis subgroups.","Patients with active brain metastases were excluded.","Whether relatlimab adds benefit in other tumours is not yet demonstrated in phase 3."],"changedPractice":true,"participants":714},{"id":"paper-nct02411448-j-thorac-oncol-2025-update","kind":"paper","name":"RELAY: Final Overall Survival for Erlotinib Plus Ramucirumab or Placebo in Untreated, EGFR-Mutated Metastatic NSCLC","aka":[],"tldr":"Later report from the RELAY trial registered as NCT02411448, in Journal of Thoracic Oncology (2025); its title describes an updated or longer-term analysis.","summary":"Introduction: RELAY, a global double-blind, placebo-controlled phase 3 study (NCT02411448) found statistically significant improvement in progression-free survival (primary end point) for ramucirumab (RAM) plus erlotinib (ERL) (RAM + ERL) in patients with untreated EGFR-mutated metastatic NSCLC (hazard ratio [HR] = 0.59, 95% confidence interval [CI]: 0.46-0.76, p < 0.0001; median progression-free survival: 19.4 versus 12.4 mo). Here, we report the final overall survival (OS; secondary end point) outcomes for the intention-to-treat population.\n\nMethods: Between January 2016 and February 2018, 449 eligible patients with an EGFR exon 19del or L858R mutation and no central nervous system metastases were randomized (1:1) to ERL (150 mg/day) with RAM (10 mg/kg every two weeks, N = 224) or placebo (N = 225).\n\nResults: At data cutoff, 297 deaths were reported (overall event rate = 66%), with a median follow-up of 45.1 months (interquartile range: 26.7-71.2), an OS HR of 0.98 (95% CI: 0.78-1.24, p = 0.864), and median OS of 51.1 months (RAM + ERL) and 46.0 months (placebo + ERL). Outcomes in subsets of patients with poor prognosis (L858R or TP53 co-mutation) suggest a directional improvement in OS (L858R: HR = 0.87, 95% CI: 0.62-1.22; exon 19del: HR = 1.13, 95% CI: 0.83-1.55; TP53 co-mutation: HR = 0.83, 95% CI: 0.58-1.19; TP53-wild-type: HR = 1.22, 95% CI: 0.87-1.72). Treatment-emergent T790M rates were similar between arms. Over 80% of patients received post-study discontinuation therapy (>50% received osimertinib in comparable numbers between arms). The safety profile for RAM + ERL was consistent with previous reports with no increased toxicity over time or new safety signals observed.\n\nConclusion: In RELAY, OS was not significantly improved with similar long OS durations in both treatment arms.\n\nClinical trial information: ClinicalTrials.gov Identifier: NCT02411448.\n\nIndexed on Europe PMC as PubMed record 39622410 (DOI 10.1016/j.jtho.2024.11.032). Its abstract cites the registry id NCT02411448, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Thorac Oncol 2025","url":"https://doi.org/10.1016/j.jtho.2024.11.032"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39622410/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39622410"},{"label":"ClinicalTrials.gov NCT02411448","url":"https://clinicaltrials.gov/study/NCT02411448"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct02411448"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-thoracic-oncology"],"dependsOn":[],"notes":[],"journal":"Journal of Thoracic Oncology","year":2025,"doi":"10.1016/j.jtho.2024.11.032","pmid":"39622410","authors":"Nakagawa K, Garon EB, Seto T, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the RELAY trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-relevance-rituximab-lenalidomide-follicular-lymphoma-morschhauser-nejm-2018","kind":"paper","name":"RELEVANCE: rituximab plus lenalidomide in advanced untreated follicular lymphoma","aka":[],"tldr":"A chemotherapy-free combination of rituximab and lenalidomide worked as well as rituximab with chemotherapy for untreated follicular lymphoma, though not better, with different side effects.","summary":"Open-label phase 3 superiority trial: 1,030 patients with previously untreated follicular lymphoma were randomised to rituximab plus lenalidomide (513) or rituximab plus chemotherapy (517), each followed by rituximab maintenance.\n\nConfirmed or unconfirmed complete response at 120 weeks was 48 percent against 53 percent (p 0.13) and interim three-year progression-free survival 77 against 78 percent. Grade 3 or 4 neutropenia (32 against 50 percent) and febrile neutropenia (2 against 7 percent) were more common with chemotherapy; grade 3 or 4 cutaneous reactions (7 against 1 percent) were more common with lenalidomide.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2018","url":"https://doi.org/10.1056/NEJMoa1805104"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30184451/"}],"tags":[],"related":[],"cancers":["follicular-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["lenalidomide","rituximab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["relevance"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2018,"doi":"10.1056/NEJMoa1805104","pmid":"30184451","authors":"Morschhauser F, Fowler NH, Feugier P, et al.","paperType":"rct","findings":["Complete or unconfirmed complete response at 120 weeks 48 percent (95% CI 44 to 53) versus 53 percent (49 to 57), p 0.13.","Interim three-year progression-free survival 77 versus 78 percent.","Grade 3 or 4 neutropenia 32 versus 50 percent; grade 3 or 4 cutaneous reactions 7 versus 1 percent."],"whatItMeans":"Rituximab-lenalidomide is an accepted chemotherapy-free first-line alternative for follicular lymphoma, chosen on toxicity profile and patient preference rather than efficacy.","caveats":["Designed to show superiority, which it did not; equivalence was not formally tested.","Rituximab maintenance was given in both arms."],"changedPractice":true,"participants":1030},{"id":"paper-ying-cancer-med","kind":"paper","name":"Relmacabtagene autoleucel (relma-cel) CD19 CAR-T therapy for adults with heavily pretreated relapsed/refractory large B-cell lymphoma in China","aka":[],"tldr":"Paper cited by one trial page and one treatment page, indexed on Europe PMC as PubMed record 33382529 and published in Cancer medicine; the citing pages link this DOI, which is how the record was matched.","summary":"Background: Despite numerous chimeric antigen receptor T-cell (CAR-T) trials conducted in China, no CAR-T has been registered in the country. Furthermore, China law and regulations restrict the export of patient material for CAR-T manufacture abroad. Relma-cel (JWCAR029), an anti-CD19 product produced with a commercial-ready process in China, was evaluated in the first prospective, single-arm, multicenter, pivotal study of CAR-T therapy conducted under Chinese IND to support an NMPA-accepted BLA submission in relapsed/refractory (r/r) LBCL (NCT04089215).\n\nMethods: Patients were randomized to receive either 100 × 10 6 (low dose, n = 27) or 150 × 10 6 (high dose, n = 32) CAR+ T-cells as a single infusion following lymphodepleting chemotherapy (fludarabine 25 mg/m 2 and cyclophosphamide 250 mg/m 2 daily × 3), and then, monitored for efficacy and safety outcomes and pharmacokinetics. The primary endpoint was ORR at 3 months, as assessed by the investigators. Secondary endpoints included DOR, PFS, OS, and adverse event frequency/severity and cell expansion kinetics.\n\nResults: at the data cutoff on 17 June 2020, 68 patients were enrolled, and 59 were treated. Among the 58 efficacy-evaluable patients, the primary endpoint of 3 month ORR was 60.3% (95% CI, 46.6-73.0), excluding the null hypothesis rate of 20%. Any grade and severe grade CRS occurred in 47.5% and 5.1%, respectively, and any grade and severe grade neurotoxicity events occurred in 20.3% and 5.1%.\n\nConclusions: Relma-cel met the primary endpoint analysis and demonstrated a high rate of durable responses and low rate of CAR-T-associated toxicities in patients with r/r LBCL in a multicenter trial supporting regulatory submission in China.\n\nIndexed on Europe PMC as PubMed record 33382529 (DOI 10.1002/cam4.3686). Matched by DOI alone: one trial page and one treatment page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer Med 2021","url":"https://doi.org/10.1002/cam4.3686"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33382529/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33382529"}],"tags":["europepmc-ingest"],"related":["relmacabtagene-autoleucel"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["reliance"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-medicine"],"dependsOn":[],"notes":[],"journal":"Cancer medicine","year":2021,"doi":"10.1002/cam4.3686","pmid":"33382529","authors":"Ying Z, Yang H, Guo Y, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page and one treatment page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-remora-lenvatinib-thymic-carcinoma-lancet-oncol-2020","kind":"paper","name":"REMORA: lenvatinib in advanced or metastatic thymic carcinoma","aka":[],"tldr":"In a Japanese trial the multi-kinase inhibitor lenvatinib shrank thymic carcinoma in about four in ten patients whose disease had progressed after platinum chemotherapy, leading to its approval in Japan.","summary":"Multicentre single-arm phase 2 trial of 42 patients with unresectable advanced or metastatic thymic carcinoma previously treated with platinum-based chemotherapy, given lenvatinib 24 mg daily.\n\nThe objective response rate was 38 percent and median progression-free survival 9.3 months. Hypertension and hand-foot syndrome were common and most patients needed dose reductions.","asOf":"2026-09-18","links":[{"label":"Lancet Oncol 2020","url":"https://doi.org/10.1016/S1470-2045(20)30162-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32502444/"}],"tags":[],"related":[],"cancers":["thymic-carcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":["lenvatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2020,"doi":"10.1016/S1470-2045(20)30162-5","pmid":"32502444","authors":"Sato J, Satouchi M, Itoh S, et al.","paperType":"observational","findings":["Objective response rate 38 percent; median progression-free survival 9.3 months.","Grade 3 hypertension and palmar-plantar erythrodysaesthesia were frequent and dose reductions were the rule."],"whatItMeans":"Lenvatinib is one of the few drugs with prospective evidence in thymic carcinoma after chemotherapy, alongside sunitinib and pembrolizumab.","caveats":["Single-arm, single-country trial; no comparator.","Toxicity at the 24 mg dose limits use in frail patients."],"changedPractice":true,"participants":42},{"id":"paper-hsieh-nat-rev-dis-primers","kind":"paper","name":"Renal cell carcinoma","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 28276433 and published in Nature reviews. Disease primers; the citing page links this DOI, which is how the record was matched.","summary":"Renal cell carcinoma (RCC) denotes cancer originated from the renal epithelium and accounts for >90% of cancers in the kidney. The disease encompasses >10 histological and molecular subtypes, of which clear cell RCC (ccRCC) is most common and accounts for most cancer-related deaths. Although somatic VHL mutations have been described for some time, more-recent cancer genomic studies have identified mutations in epigenetic regulatory genes and demonstrated marked intra-tumour heterogeneity, which could have prognostic, predictive and therapeutic relevance. Localized RCC can be successfully managed with surgery, whereas metastatic RCC is refractory to conventional chemotherapy. However, over the past decade, marked advances in the treatment of metastatic RCC have been made, with targeted agents including sorafenib, sunitinib, bevacizumab, pazopanib and axitinib, which inhibit vascular endothelial growth factor (VEGF) and its receptor (VEGFR), and everolimus and temsirolimus, which inhibit mechanistic target of rapamycin complex 1 (mTORC1), being approved. Since 2015, agents with additional targets aside from VEGFR have been approved, such as cabozantinib and lenvatinib; immunotherapies, such as nivolumab, have also been added to the armamentarium for metastatic RCC. Here, we provide an overview of the biology of RCC, with a focus on ccRCC, as well as updates to complement the current clinical guidelines and an outline of potential future directions for RCC research and therapy.\n\nIndexed on Europe PMC as PubMed record 28276433 (DOI 10.1038/nrdp.2017.9). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Dis Primers 2017","url":"https://doi.org/10.1038/nrdp.2017.9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28276433/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28276433"}],"tags":["europepmc-ingest"],"related":["renal-cell-carcinoma-signalling"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature reviews. Disease primers","year":2017,"doi":"10.1038/nrdp.2017.9","pmid":"28276433","authors":"Hsieh JJ, Purdue MP, Signoretti S, et al.","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-sonabend-lancet-oncol","kind":"paper","name":"Repeated blood-brain barrier opening with an implantable ultrasound device for delivery of albumin-bound paclitaxel in patients with recurrent glioblastoma: a phase 1 trial","aka":[],"tldr":"Paper cited by one idea page, indexed on Europe PMC as PubMed record 37142373 and published in The Lancet Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background: Low-intensity pulsed ultrasound with concomitant administration of intravenous microbubbles (LIPU-MB) can be used to open the blood-brain barrier. We aimed to assess the safety and pharmacokinetics of LIPU-MB to enhance the delivery of albumin-bound paclitaxel to the peritumoural brain of patients with recurrent glioblastoma.\n\nMethods: We conducted a dose-escalation phase 1 clinical trial in adults (aged ≥18 years) with recurrent glioblastoma, a tumour diameter of 70 mm or smaller, and a Karnofsky performance status of at least 70. A nine-emitter ultrasound device was implanted into a skull window after tumour resection. LIPU-MB with intravenous albumin-bound paclitaxel infusion was done every 3 weeks for up to six cycles. Six dose levels of albumin-bound paclitaxel (40 mg/m 2, 80 mg/m 2, 135 mg/m 2, 175 mg/m 2, 215 mg/m 2, and 260 mg/m 2) were evaluated. The primary endpoint was dose-limiting toxicity occurring during the first cycle of sonication and albumin-bound paclitaxel chemotherapy. Safety was assessed in all treated patients. Analyses were done in the per-protocol population. Blood-brain barrier opening was investigated by MRI before and after sonication. We also did pharmacokinetic analyses of LIPU-MB in a subgroup of patients from the current study and a subgroup of patients who received carboplatin as part of a similar trial (NCT03744026). This study is registered with ClinicalTrials.gov, NCT04528680, and a phase 2 trial is currently open for accrual.\n\nFindings: 17 patients (nine men and eight women) were enrolled between Oct 29, 2020, and Feb 21, 2022. at data cutoff on Sept 6, 2022, median follow-up was 11·89 months (IQR 11·12-12·78). One patient was treated per dose level of albumin-bound paclitaxel for levels 1 to 5 (40-215 mg/m 2), and 12 patients were treated at dose level 6 (260 mg/m 2). A total of 68 cycles of LIPU-MB-based blood-brain barrier opening were done (median 3 cycles per patient [range 2-6]). At a dose of 260 mg/m 2, encephalopathy (grade 3) occurred in one (8%) of 12 patients during the first cycle (considered a dose-limiting toxicity), and in one other patient during the second cycle (grade 2). In both cases, the toxicity resolved and treatment continued at a lower dose of albumin-bound paclitaxel, with a dose of 175 mg/m 2 in the case of the grade 3 encephalopathy, and to 215 mg/m 2 in the case of the grade 2 encephalopathy. Grade 2 peripheral neuropathy was observed in one patient during the third cycle of 260 mg/m 2 albumin-bound paclitaxel. No progressive neurological deficits attributed to LIPU-MB were observed. LIPU-MB-based blood-brain barrier opening was most commonly associated with immediate yet transient grade 1-2 headache (12 [71%] of 17 patients). The most common grade 3-4 treatment-emergent adverse events were neutropenia (eight [47%]), leukopenia (five [29%]), and hypertension (five [29%]). No treatment-related deaths occurred during the study. Imaging analysis showed blood-brain barrier opening in the brain regions targeted by LIPU-MB, which diminished over the first 1 h after sonication. Pharmacokinetic analyses showed that LIPU-MB led to increases in the mean brain parenchymal concentrations of albumin-bound paclitaxel (from 0·037 μM [95% CI 0·022-0·063] in non-sonicated brain to 0·139 μM [0·083-0·232] in sonicated brain [3·7-times increase], p<0·0001) and carboplatin (from 0·991 μM [0·562-1·747] in non-sonicated brain to 5·878 μM [3·462-9·980] μM in sonicated brain [5·9-times increase], p=0·0001).\n\nInterpretation: LIPU-MB using a skull-implantable ultrasound device transiently opens the blood-brain barrier allowing for safe, repeated penetration of cytotoxic drugs into the brain. This study has prompted a subsequent phase 2 study combining LIPU-MB with albumin-bound paclitaxel plus carboplatin (NCT04528680), which is ongoing.\n\nFunding: National Institutes of Health and National Cancer Institute, Moceri Family Foundation, and the Panattoni family.\n\nIndexed on Europe PMC as PubMed record 37142373 (DOI 10.1016/s1470-2045(23)00112-2). Matched by DOI alone: one idea page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2023","url":"https://doi.org/10.1016/s1470-2045(23)00112-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37142373/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37142373"}],"tags":["europepmc-ingest"],"related":["idea-fus-plus-adc-glioma"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2023,"doi":"10.1016/s1470-2045(23)00112-2","pmid":"37142373","authors":"Sonabend AM, Gould A, Amidei C, et al.","paperType":"observational","findings":[],"whatItMeans":"One idea page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-sorlie-repeated-observation-subtypes-brca1-basal-pnas-2003","kind":"paper","name":"Repeated observation of breast tumor subtypes in independent gene expression data sets","aka":[],"tldr":"The 2003 paper that found the same breast cancer subtypes in other laboratories' data and showed that tumours from women with an inherited BRCA1 fault fall into the basal-like group, linking hereditary and triple-negative disease.","summary":"Sørlie, Tibshirani, Parker, Hastie and colleagues analysed 115 malignant breast tumours by hierarchical clustering on 534 intrinsic genes, selected for similar expression between paired samples from the same tumour taken 15 weeks apart during neoadjuvant treatment. The tumours subdivided into one basal-like, one ERBB2-overexpressing, two luminal-like and one normal breast tissue-like subgroup. Cluster analysis of two published independent data sets from different laboratories uncovered some of the same subtypes, and in the set with time to distant metastasis the subtypes differed significantly. Including tumours from BRCA1 carriers showed that this genotype predisposes to the basal tumour subtype.","asOf":"2026-09-24","links":[{"label":"Proc Natl Acad Sci 2003","url":"https://doi.org/10.1073/pnas.0932692100"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/12829800/"}],"tags":["tnbc-evidence"],"related":["paper-foulkes-brca1-basal-phenotype-jnci-2003"],"cancers":["tnbc"],"sections":[],"technologies":[],"targets":["brca"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["pam50","germline-testing"],"trials":[],"people":["charles-perou"],"bottlenecks":[],"keyPapers":[],"journals":["pnas"],"dependsOn":[],"notes":[],"journal":"Proceedings of the National Academy of Sciences","year":2003,"doi":"10.1073/pnas.0932692100","pmid":"12829800","authors":"Sørlie T, Tibshirani R, Parker J, et al.","paperType":"translational","findings":["115 tumours on 534 intrinsic genes: basal-like, ERBB2-overexpressing, two luminal-like and normal-like subgroups reproduced in two independent data sets.","BRCA1 carrier tumours fell into the basal subtype."],"whatItMeans":"The molecular bridge between germline BRCA1 and triple-negative breast cancer; it is why every triple-negative patient under 60 is now offered germline testing and why PARP inhibitors were tried in this disease first.","caveats":["Small BRCA1 group.","Independent data sets reproduced some, not all, subtypes."],"changedPractice":true,"participants":115},{"id":"paper-reproducibility-project-cancer-biology-elife-2021","kind":"paper","name":"Reproducibility Project: Cancer Biology found that landmark preclinical results mostly shrank or vanished on replication","aka":[],"tldr":"An eight-year effort to repeat 50 experiments from 23 high-impact cancer biology papers found that replication effect sizes were on average 85% smaller than the originals, and fewer than half of the effects replicated by most criteria.","summary":"The Center for Open Science and Science Exchange set out in 2013 to replicate selected experiments from 53 high-impact cancer biology papers published 2010-2012, with registered reports and original-author consultation. Only 50 experiments from 23 papers could be completed; the companion paper (Errington et al., eLife 2021, 'Challenges for assessing replicability') documents that no original paper contained enough methodological detail to design a replication without contacting the authors, and that about a third of authors were unhelpful or unresponsive.\n\nAcross 158 measured effects, the median replication effect size was 85% smaller than the original; 92% of replication effects were smaller than the originals. Using five criteria, 46% of effects replicated on more criteria than they failed; for original positive results, about 40% replicated, while null results replicated at 80%.\n\nThe project quantified the preclinical reproducibility problem that pharmaceutical groups (Begley and Ellis 2012; Prinz 2011) had reported anecdotally, and shaped funder requirements for rigour and data sharing.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.7554/eLife.71601"},{"label":"Companion paper: challenges for assessing replicability","url":"https://doi.org/10.7554/eLife.67995"}],"tags":[],"related":["idea-tr1-surrogate-validation-programme","idea-fund-public-nonprofit-cro"],"cancers":[],"sections":["drug-discovery"],"technologies":["pdx-models","organoids"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-reproducibility","b-translational-valley","b-preclinical-models","b-negative-results"],"keyPapers":[],"journals":["elife"],"dependsOn":[],"notes":[],"journal":"eLife","year":2021,"doi":"10.7554/eLife.71601","pmid":"34874005","authors":"Errington TM, Mathur M, Soderberg CK, et al.","paperType":"meta-analysis","findings":["50 experiments from 23 papers completed out of 193 planned from 53 papers","Median replication effect size 85% smaller than original; 92% of replication effects smaller than originals","46% of 158 effects replicated on more criteria than they failed; original positive results replicated about 40% of the time, null results 80%","No original paper described methods in enough detail to replicate without author contact; 32% of authors were minimally helpful or unresponsive"],"whatItMeans":"Many exciting laboratory findings that motivate drug programmes are weaker or less reliable than published, which helps explain the high failure rate of drugs entering clinical trials. It argues for pre-registration, detailed methods, data sharing and independent replication before major translational investment.","caveats":["Replications used the original protocols where possible, but reagents, animals and laboratories differ; some failures may reflect context sensitivity rather than error","Selection of high-impact papers may not represent the field","Under-powered replications could miss true effects; effect-size shrinkage is the more robust finding","Only about a quarter of planned experiments were completed, which limits generalisation"],"changedPractice":false},{"id":"paper-andrea-decensi-diabetologia-2017","kind":"paper","name":"Repurposing metformin for the prevention of cancer and cancer recurrence","aka":[],"tldr":"Paper by Andrea DeCensi indexed on Europe PMC as PubMed record 28776080, in Diabetologia (2017), one of the most cited records naming an author with this name at E.O. Ospedali Galliera.","summary":"Multiple epidemiological studies have documented an association between metformin, used for treatment of type 2 diabetes, and reduced cancer incidence and mortality. Cell line models may not accurately reflect the effects of metformin in the clinical setting. Moreover, findings from animal model studies have been inconsistent, whilst those from more recent epidemiological studies have tempered the overall effect size. The purpose of this review is to examine metformin's chemopreventive potential by outlining relevant mechanisms of action, the most recent epidemiologic evidence, and recently completed and ongoing clinical trials. Although repurposing drugs with excellent safety profiles is an appealing strategy for cancer prevention and treatment in the adjuvant setting, there is no substitute for well-executed, large randomised clinical trials to define efficacy and determine the populations that are most likely to benefit from an intervention. Thus, enthusiasm remains for understanding the role of metformin in cancer through ongoing clinical research.\n\nIndexed on Europe PMC as PubMed record 28776080 (DOI 10.1007/s00125-017-4372-6). Its author list gives \"DeCensi A\" with the affiliation \"Division of Medical Oncology, Ente Ospedaliero Ospedali Galliera, Genoa, Italy\", which names E.O. Ospedali Galliera; that is how the record was matched to Andrea DeCensi, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Diabetologia 2017","url":"https://doi.org/10.1007/s00125-017-4372-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28776080/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28776080"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["andrea-decensi"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Diabetologia","year":2017,"doi":"10.1007/s00125-017-4372-6","pmid":"28776080","authors":"Heckman-Stoddard BM, DeCensi A, Sahasrabuddhe VV, et al.","paperType":"review","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Andrea DeCensi at E.O. Ospedali Galliera, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-gpc3-gastric-pathol-res-pract-2026","kind":"paper","name":"Research progress of GPC3 and gastric cancer: Clinicopathologic characteristics and application prospects","aka":[],"tldr":"Review on GPC3 in Gastric & gastro-oesophageal junction cancer, in Pathology, research and practice (2026), one of the most cited Europe PMC records with GPC3 in its title.","summary":"The identification of new biomarkers and druggable targets is critical for improving the management of gastric cancer. Glypican-3 (GPC3), a glycosylphosphatidylinositol-anchored heparan sulfate proteoglycan, has emerged as a molecule of substantial translational interest due to its well-documented roles in tumorigenesis and its growing validation as a therapeutic target. Current research has found that GPC3 is expressed in some gastric adenocarcinomas and serves as a highly sensitive biomarker for alpha-fetoprotein-producing gastric cancer (AFPGC). GPC3 positivity is significantly correlated with adverse clinicopathologic features and poorer patient prognosis. As a key membrane-anchored biomarker, current research has identified GPC3 as a direct target for antibodies or cell therapies (such as CAR-T), with indications mainly focused on hepatocellular carcinoma, and it is also expected to provide a therapeutic approach for AFPGC and other solid cancers with abnormal expression of GPC3. Therefore, there is strong potential in identifying patients with GPC3-positive gastric cancer (GPC3-GC) for risk-stratified surveillance or enrollment in biomarker-guided therapeutic trials. However, current evidence on its clinicopathologic impact and clinical applicability in gastric cancer is fragmented and sometimes contradictory. This review systematically consolidates recent research progress to clarify the expression and prognostic significance of GPC3 in gastric cancer, explore its underlying molecular mechanisms, and evaluate its emerging promise as a target for novel therapies. Ultimately, we aim to bridge the gap between basic research and clinical practice, highlighting why GPC3 warrants focused investigation in the current gastric cancer research landscape.\n\nIndexed on Europe PMC as PubMed record 42035578 (DOI 10.1016/j.prp.2026.156477). Its title names GPC3 and its text names Gastric & gastro-oesophageal junction cancer; PubMed types it as a review (Review). It was matched automatically to the idea \"In vivo CAR-T against solid-tumour antigens\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Pathol Res Pract 2026","url":"https://doi.org/10.1016/j.prp.2026.156477"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42035578/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42035578"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Pathology, research and practice","year":2026,"doi":"10.1016/j.prp.2026.156477","pmid":"42035578","authors":"Ma H, Li Z, Shu P, et al.","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for GPC3 in Gastric & gastro-oesophageal junction cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by GPC3 in the title and Gastric & gastro-oesophageal junction cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-shaw-alk-l1198f-resensitisation-nejm-2016","kind":"paper","name":"Resensitization to crizotinib by the lorlatinib ALK resistance mutation L1198F","aka":[],"tldr":"A patient's cancer became resistant to one drug, then to a second, then to a third, and the mutation that defeated the third drug made the first one work again. She was rechallenged with it and recovered.","summary":"In a patient with metastatic ALK-rearranged lung cancer, resistance to crizotinib developed through a C1156Y mutation in the ALK kinase domain. Her tumour did not respond to a second-generation ALK inhibitor but did respond to lorlatinib. When her tumour relapsed, sequencing revealed an ALK L1198F mutation in addition to C1156Y. The L1198F substitution confers resistance to lorlatinib through steric interference with drug binding, but paradoxically enhances binding to crizotinib, negating the effect of C1156Y and resensitising the cancer to crizotinib. The patient received crizotinib again and her cancer-related symptoms and liver failure resolved.","asOf":"2026-09-25","links":[{"label":"Shaw et al., N Engl J Med 2016: resensitisation to crizotinib by the lorlatinib resistance mutation ALK L1198F","url":"https://doi.org/10.1056/NEJMoa1508887"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26698910/"}],"tags":[],"related":["alk-fusion"],"cancers":["nsclc"],"sections":[],"technologies":["kinase-inhibitors","cgp"],"targets":["alk"],"drugs":["crizotinib","lorlatinib"],"companies":[],"institutions":["mgh"],"pathways":["resistance-routes-map","rtk-activation","clonal-evolution"],"terms":["resistance","cross-resistance"],"trials":[],"people":["alice-shaw"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2016,"doi":"10.1056/NEJMoa1508887","pmid":"26698910","authors":"Shaw AT, Friboulet L, Leshchiner I, et al.","paperType":"translational","findings":["A compound ALK mutation, C1156Y with L1198F, conferred resistance to lorlatinib.","The same compound mutation restored crizotinib binding.","Rechallenge with crizotinib produced clinical recovery."],"whatItMeans":"It is the cleanest demonstration in oncology that resistance is a property of a particular drug bound to a particular protein rather than a property of the tumour, and that genotyping at every progression can reopen an option that looked closed.","caveats":["A single patient.","Compound mutations of this kind are rare.","The strategy has not been tested prospectively."],"changedPractice":false,"participants":1},{"id":"paper-yau-rcb-pooled-analysis-5161-lancet-oncol-2022","kind":"paper","name":"Residual cancer burden after neoadjuvant chemotherapy and long-term survival outcomes in breast cancer: a multicentre pooled analysis of 5161 patients","aka":[],"tldr":"A pooled analysis of 5,161 patients from 12 European and US institutions and trials confirming that the residual cancer burden score predicts relapse in every breast cancer subtype, and proposing it become part of standard pathology reporting after pre-surgery chemotherapy.","summary":"Yau, Osdoit, van der Noordaa, Shad and colleagues obtained participant-level residual cancer burden results and clinical data from 12 institutes and trials in Europe and the USA for patients with stage I to III breast cancer treated with neoadjuvant chemotherapy and surgery between September 1994 and February 2019 (5,161 patients, median age 49, median follow-up 56 months, 1,164 events). Higher residual cancer burden was associated with worse event-free survival within each subtype: the univariable hazard ratio per unit ranged from 1.55 (95 percent confidence interval 1.41 to 1.71) in hormone receptor-positive/HER2-negative disease to 2.16 (1.79 to 2.61) in hormone receptor-negative/HER2-positive disease (p<0.0001 for all), and remained prognostic after adjustment for age, grade, T category and nodes (adjusted hazard ratios 1.52 to 2.09). The authors conclude the score and class are independently prognostic in all subtypes and generalisable across practice settings.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2022","url":"https://doi.org/10.1016/S1470-2045(21)00589-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34902335/"}],"tags":["tnbc-evidence"],"related":["paper-symmans-rcb-long-term-prognosis-subtype-jco-2017"],"cancers":["tnbc","breast-hr-positive","breast-her2-positive"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nci"],"pathways":[],"terms":["rcb","efs","hazard-ratio"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2022,"doi":"10.1016/S1470-2045(21)00589-1","pmid":"34902335","authors":"Yau C, Osdoit M, van der Noordaa M, et al.","paperType":"meta-analysis","findings":["Hazard ratio per unit residual cancer burden 1.55 to 2.16 across subtypes (p<0.0001 for all); adjusted 1.52 to 2.09.","Prognostic in every subtype across 12 cohorts from 1994 to 2019."],"whatItMeans":"The external validation the 2017 paper asked for; it is why residual cancer burden is reported in UK and European pathology and used as a trial entry criterion rather than an MD Anderson curiosity.","caveats":["Retrospective pooling with variable subtype definitions and treatments.","Follow-up shorter than the single-institution cohorts."],"changedPractice":true,"participants":5161},{"id":"paper-liedtke-neoadjuvant-response-survival-tnbc-jco-2008","kind":"paper","name":"Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer","aka":[],"tldr":"The 2008 MD Anderson series of 1,118 women that defined the triple-negative paradox: these tumours disappear completely with pre-surgery chemotherapy twice as often as other breast cancers, yet survival is worse, because the women left with residual disease relapse early and often.","summary":"Liedtke, Mazouni, Hess, André and colleagues analysed 1,118 patients treated with neoadjuvant chemotherapy at MD Anderson for stage I to III breast cancer between 1985 and 2004 with complete receptor data; 255 (23 percent) were triple-negative. Triple-negative patients had higher pathological complete response rates (22 versus 11 percent, p=0.034) but lower three-year progression-free and overall survival (both p<0.0001), more visceral metastases (p=0.0005), fewer bone recurrences (p=0.027) and shorter post-recurrence survival (p<0.0001), with excess recurrence and death confined to the first three years. Patients achieving pathological complete response had similar survival whether triple-negative or not (p=0.24); those with residual disease had worse survival if triple-negative (p<0.0001).","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2008","url":"https://doi.org/10.1200/JCO.2007.14.4147"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/18250347/"}],"tags":["tnbc-evidence"],"related":["paper-symmans-j-clin-oncol","paper-cortazar-ctneobc-pcr-pooled-analysis-lancet-2014"],"cancers":["tnbc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["md-anderson"],"pathways":[],"terms":["pcr","rcb","neoadjuvant-adjuvant"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2008,"doi":"10.1200/JCO.2007.14.4147","pmid":"18250347","authors":"Liedtke C, Mazouni C, Hess KR, et al.","paperType":"observational","findings":["Pathological complete response 22 vs 11 percent for triple-negative vs other breast cancer (p=0.034).","Three-year progression-free and overall survival worse in triple-negative disease (p<0.0001); excess risk confined to the first three years.","With pathological complete response survival was equal (p=0.24); with residual disease triple-negative survival was worse (p<0.0001)."],"whatItMeans":"Made pathological complete response the organising endpoint of triple-negative drug development and residual disease its central unsolved problem; every post-neoadjuvant trial from CREATE-X to ASCENT-05 follows from this observation.","caveats":["Single-institution, retrospective, pre-taxane and taxane eras mixed.","Receptor testing methods changed over 1985 to 2004."],"changedPractice":true,"participants":1118},{"id":"paper-teply-restore-bipolar-androgen-therapy-lancet-oncol-2018","kind":"paper","name":"RESTORE: bipolar androgen therapy after progression on enzalutamide in metastatic castration-resistant prostate cancer","aka":["RESTORE","Teply 2018 bipolar androgen therapy","BAT after enzalutamide"],"tldr":"Prostate cancer adapts to having almost no testosterone. This trial did the opposite of what the textbook says and gave men large doses of testosterone. Three in ten responded, and more than half responded again to the hormone-blocking drug that had stopped working.","summary":"Benjamin Teply, Samuel Denmeade and colleagues at Johns Hopkins gave monthly intramuscular testosterone cipionate 400 mg, on top of continued luteinising hormone-releasing hormone agonist therapy, to 30 asymptomatic men whose metastatic castration-resistant prostate cancer had progressed on enzalutamide. Rapid cycling between high and low serum testosterone is called bipolar androgen therapy.\n\nThe rationale is the same adaptation described by Visakorpi and Chen. A cell that has upregulated the androgen receptor to survive castration is, on that account, vulnerable to a flood of ligand. The co-primary endpoints were the proportion with a 50 percent fall in prostate-specific antigen on bipolar androgen therapy and on enzalutamide rechallenge afterwards, and both were met. It is the resensitisation result, not the direct response rate, that makes the approach interesting.","asOf":"2026-09-25","links":[{"label":"Lancet Oncol 2018","url":"https://doi.org/10.1016/s1470-2045(17)30906-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29248236/"},{"label":"ClinicalTrials.gov NCT02090114","url":"https://clinicaltrials.gov/study/NCT02090114"}],"tags":["prostate-evidence"],"related":["paper-denmeade-transformer-bipolar-androgen-therapy-jco-2021","paper-chen-androgen-receptor-overexpression-antiandrogen-resistance-nat-med-2004","idea-bio1-alternating-schedules","prostate-roadmap"],"cancers":["prostate","prostate-mcrpc"],"sections":["hormonal"],"technologies":[],"targets":["androgen-receptor"],"drugs":["enzalutamide"],"companies":[],"institutions":["johns-hopkins"],"pathways":[],"terms":["castration-resistance","psa","bipolar-androgen-therapy"],"trials":[],"people":[],"bottlenecks":["b-resistance","b-generic-repurposing","b-combination-space"],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2018,"doi":"10.1016/s1470-2045(17)30906-3","pmid":"29248236","authors":"Teply BA, Wang H, Luber B, et al.","paperType":"rct","findings":["A 50 percent decline in prostate-specific antigen on bipolar androgen therapy in 9 of 30 patients (30 percent; 95 percent confidence interval 15 to 49; p less than 0.0001).","Of 21 men who proceeded to enzalutamide rechallenge after bipolar androgen therapy, 15 (52 percent; 33 to 71; p less than 0.0001) had a 50 percent decline in prostate-specific antigen.","The only grade 3 to 4 adverse event occurring in more than one patient during bipolar androgen therapy was hypertension, in three (10 percent).","Single grade 3 or worse events during bipolar androgen therapy included pulmonary embolism, myocardial infarction, urinary obstruction, gallstone and sepsis, one each.","No treatment-related deaths were reported during either bipolar androgen therapy or enzalutamide retreatment."],"whatItMeans":"A demonstration that a drug that has stopped working can be made to work again by changing the environment the tumour has adapted to, rather than by changing the drug. It is the strongest clinical evidence in prostate cancer for treating resistance as something reversible.","caveats":["30 patients at one centre, single-arm and open-label, with prostate-specific antigen response as the endpoint rather than survival.","Men with more than five sites of visceral disease or bone lesions at risk of fracture were excluded because of the risk of tumour flare; the approach is not safe in symptomatic or high-burden disease.","Cardiovascular and thromboembolic events occurred; supraphysiological testosterone is not a low-risk intervention and needs monitoring."],"changedPractice":false,"participants":30},{"id":"paper-lichtman-j-pain-symptom-manage","kind":"paper","name":"Results of a Double-Blind, Randomized, Placebo-Controlled Study of Nabiximols Oromucosal Spray as an Adjunctive Therapy in Advanced Cancer Patients with Chronic Uncontrolled Pain","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 28923526 and published in Journal of pain and symptom management; the citing page links this DOI, which is how the record was matched.","summary":"Context: Prior Phase 2/3 studies found that cannabinoids might provide adjunctive analgesia in advanced cancer patients with uncontrolled pain.\n\nObjectives: To assess adjunctive nabiximols (Sativex ®), an extract of Cannabis sativa containing two potentially therapeutic cannabinoids (Δ9-tetrahydrocannabinol [27 mg/mL] and cannabidiol [25 mg/mL]), in advanced cancer patients with chronic pain unalleviated by optimized opioid therapy.\n\nMethods: Phase 3, double-blind, randomized, placebo-controlled trial in patients with advanced cancer and average pain Numerical Rating Scale scores ≥4 and ≤8 despite optimized opioid therapy. Patients randomized to nabiximols (n = 199) or placebo (n = 198) self-titrated study medications over a two-week period, followed by a three-week treatment period at the titrated dose.\n\nResults: Median percent improvements in average pain Numerical Rating Scale score from baseline to end of treatment in the nabiximols and placebo groups were 10.7% vs. 4.5% (P = 0.0854) in the intention-to-treat population (primary variable) and 15.5% vs. 6.3% (P = 0.0378) in the per-protocol population. Nabiximols was statistically superior to placebo on two of three quality-of-life instruments at Week 3 and on all three at Week 5. In exploratory post hoc analyses, U.S. patients, but not patients from the rest of the world, experienced significant benefits from nabiximols on multiple secondary endpoints. Possible contributing factors to differences in nabiximols efficacy include: 1) the U.S. participants received lower doses of opioids at baseline than the rest of the world and 2) the subgroups had different distribution of cancer pain types, which may have been related to differences in pathophysiology of pain. The safety profile of nabiximols was consistent with earlier studies.\n\nConclusions: Although not superior to placebo on the primary efficacy endpoint, nabiximols had benefits on multiple secondary endpoints, particularly in the U.S.\n\nPatients: Nabiximols might have utility in patients with advanced cancer who receive a lower opioid dose, such as individuals with early intolerance to opioid therapy.\n\nIndexed on Europe PMC as PubMed record 28923526 (DOI 10.1016/j.jpainsymman.2017.09.001). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Pain Symptom Manage 2018","url":"https://doi.org/10.1016/j.jpainsymman.2017.09.001"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28923526/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28923526"}],"tags":["europepmc-ingest"],"related":["cannabinoids-pain-appetite"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of pain and symptom management","year":2018,"doi":"10.1016/j.jpainsymman.2017.09.001","pmid":"28923526","authors":"Lichtman AH, Lux EA, McQuade R, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nct04152499-j-hematol-oncol-2025","kind":"paper","name":"Results of a phase 1/2 study of sacituzumab tirumotecan in patients with unresectable locally advanced or metastatic solid tumors refractory to standard therapies","aka":[],"tldr":"Published report from the TROP2 ADC trial registered as NCT04152499, in Journal of hematology & oncology (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Sacituzumab tirumotecan (sac-TMT) is an antibody-drug conjugate composed of an anti-TROP2 monoclonal antibody coupled to a cytotoxic belotecan-derived topoisomerase I inhibitor (KL610023) via a novel linker. We report results from the phase 1 dose-escalation cohorts in advanced solid tumors and phase 2 expansion cohorts for metastatic triple-negative breast cancer (TNBC) from the first-in-human MK-2870-001 (KL264-01) study (NCT04152499).\n\nMethods: Patients had unresectable locally advanced/metastatic solid tumors refractory to standard therapies. In the phase 1 dose-escalation cohorts, patients had unresectable locally advanced/metastatic solid tumors refractory to standard therapies. Sac-TMT was administered by intravenous administration every 2 weeks at 2 to 12 mg/kg. In phase 2, patients with TNBC and HR+/HER2- breast cancer received sac-TMT per recommended doses for expansion (RDEs) identified in phase 1. Primary objectives were determining maximum tolerated dose (MTD) of sac-TMT and establishing RDEs (phase 1) and determining ORR per RECIST v1.1 by investigator assessment (phase 2). Adverse events were assessed per NCI-CTCAE version 5.0.\n\nResults: Thirty patients were enrolled in phase 1 and received sac-TMT 2 mg/kg (n = 4), 4 mg/kg (n = 7), 5 mg/kg (n = 7), 5.5 mg/kg (n = 5), and 6 mg/kg (n = 7). Five patients had dose-limiting toxicities: grade 3 stomatitis at 4, 5.5, and 6 mg/kg; grade 3 rash at 5 mg/kg; and grade 3 urticaria at 6 mg/kg. MTD was 5.5 mg/kg and RDEs were 4 and 5 mg/kg. In the phase 2 dose expansion, ORR (95% CI) was 34.8% (16.4%, 57.3%) in the 4-mg/kg group (n = 23) and 38.9% (23.1%, 56.5%) in the 5-mg/kg group (n = 36) for TNBC. ORR (95% CI) was 31.7% (18.1%, 48.1%) for HR+/HER2- breast cancer (n = 41).\n\nConclusions: Sac-TMT demonstrated manageable safety profile in patients with unresectable locally advanced/metastatic solid tumors and promising antitumor activity in metastatic TNBC and HR+/HER2 - breast cancer. Sac-TMT is being investigated in phase 3 studies.\n\nTrial registration: ClinicalTrials.gov, NCT04152499.\n\nIndexed on Europe PMC as PubMed record 40481574 (DOI 10.1186/s13045-025-01705-2). Its abstract cites the registry id NCT04152499, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Hematol Oncol 2025","url":"https://doi.org/10.1186/s13045-025-01705-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40481574/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40481574"},{"label":"ClinicalTrials.gov NCT04152499","url":"https://clinicaltrials.gov/study/NCT04152499"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04152499"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-hematology-and-oncology"],"dependsOn":[],"notes":[],"journal":"Journal of hematology & oncology","year":2025,"doi":"10.1186/s13045-025-01705-2","pmid":"40481574","authors":"Ouyang Q, Rodon J, Liang Y, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04152499 with the most citations, so it is the natural first reading for anyone following the TROP2 ADC trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-turner-c-trak-tn-ctdna-pembrolizumab-ann-oncol-2023","kind":"paper","name":"Results of the c-TRAK TN trial: a clinical trial utilising ctDNA mutation tracking to detect molecular residual disease and trigger intervention in patients with moderate- and high-risk early-stage triple-negative breast cancer","aka":[],"tldr":"The UK trial that watched 161 women with early triple-negative breast cancer by three-monthly blood tests for tumour DNA: 27 percent tested positive within a year, but by then nearly three quarters already had visible metastases, and none of the five who started pembrolizumab cleared the DNA. The lesson was to test earlier and more sensitively.","summary":"c-TRAK TN (Turner, Swift, Jenkins, Kilburn and colleagues), a multicentre phase 2 trial with prospective ctDNA surveillance by digital PCR, enrolled patients with early-stage triple-negative breast cancer and residual disease after neoadjuvant chemotherapy, or stage II to III disease after adjuvant chemotherapy, for three-monthly sampling to 12 months (18 if samples were missed during the pandemic). ctDNA-positive patients were randomised 2:1 to intervention (staging scans, then pembrolizumab if free of recurrence) or observation until a September 2020 amendment allocated all to intervention. Of 208 registered, 185 had tumour sequenced, 171 (92.4 percent) had trackable mutations and 161 entered surveillance. ctDNA was detected by 12 months in 27.3 percent (44 of 161, 95 percent confidence interval 20.6 to 34.9); seven patients relapsed without prior detection. Of 32 allocated to intervention, 72 percent (23) had metastases on staging at ctDNA detection and four declined pembrolizumab; none of the five who started it achieved sustained ctDNA clearance.","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2023","url":"https://doi.org/10.1016/j.annonc.2022.11.005"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36423745/"},{"label":"ClinicalTrials.gov NCT03145961","url":"https://clinicaltrials.gov/study/NCT03145961"}],"tags":["tnbc-evidence"],"related":["ctdna-tests","paper-radovich-ctdna-ctc-bre12-158-jama-oncol-2020","ctdna-mrd-positive"],"cancers":["tnbc","tnbc-early"],"sections":[],"technologies":["liquid-biopsy","mrd-testing","checkpoint-inhibitor"],"targets":[],"drugs":["pembrolizumab"],"companies":[],"institutions":["royal-marsden","cruk","icr-london"],"pathways":[],"terms":["ctdna","mrd","rcb"],"trials":[],"people":["nicholas-turner"],"bottlenecks":["b-dormancy-mrd","b-trial-design"],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2023,"doi":"10.1016/j.annonc.2022.11.005","pmid":"36423745","authors":"Turner NC, Swift C, Jenkins B, et al.","paperType":"rct","findings":["ctDNA detected by 12 months in 27.3 percent (44 of 161; 95 percent CI 20.6 to 34.9); 7 relapses without prior detection.","72 percent (23 of 32) of ctDNA-positive patients allocated to intervention already had metastases on staging.","None of 5 patients who started pembrolizumab achieved sustained ctDNA clearance."],"whatItMeans":"The first prospective test of acting on ctDNA in triple-negative disease, and a negative one: with a quarterly, single-mutation assay the window between detectable DNA and visible metastasis was too short to intervene. Later designs use tumour-informed assays, earlier sampling and drugs with more single-agent activity.","caveats":["Digital PCR tracking one or two mutations is less sensitive than current tumour-informed panels.","Pembrolizumab alone was the intervention; only five patients received it."],"changedPractice":false,"participants":208},{"id":"paper-makis-fenbendazole-case-series-retracted-2025","kind":"paper","name":"RETRACTED: Fenbendazole as an anticancer agent? A case series of self-administration in three patients","aka":[],"tldr":"A 2025 report of three patients said to have gone into remission on a dog dewormer was retracted by the journal in January 2026. It should not be cited as evidence.","summary":"The paper reported three patients with advanced breast cancer, prostate cancer and melanoma, two said to have achieved complete remission and one near-complete remission after adding fenbendazole to other therapies excluding chemotherapy, with no adverse effects (Makis case series 2025, retracted). The journal published a retraction statement on 21 January 2026 (Retraction notice 2026).","asOf":"2026-09-24","links":[{"label":"Makis case series 2025, retracted","url":"https://doi.org/10.1159/000546362"},{"label":"Retraction notice 2026","url":"https://doi.org/10.1159/000549387"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40605964/"},{"label":"Retraction notice on PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41574240/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["fenbendazole-ivermectin-repurposing-claims"],"targets":[],"drugs":["fenbendazole"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-misinformation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo agent (Claude Fable 5.1)","editedOn":"2026-09-24","note":"Written from cached ClinicalTrials.gov v2, Europe PMC, DailyMed, Drugs@FDA and WHO eEML responses; no figure appears without its source link."},"journal":"Case Reports in Oncology","year":2025,"doi":"10.1159/000546362","pmid":"40605964","authors":"Makis W, Baghli I, Martinez P.","paperType":"observational","findings":["Retracted 21 January 2026; the claims of remission no longer stand in the scholarly record."],"whatItMeans":"This paper circulates widely online. Anyone quoting it should know that the journal has withdrawn it.","caveats":["Retracted publication; the retraction notice (PMID 41574240) is indexed on PubMed."],"changedPractice":false,"participants":3},{"id":"paper-patil-mebendazole-glioma-phase-1-cancer-med-2020","kind":"paper","name":"Reverse swing-M, phase 1 study of repurposing mebendazole in recurrent high-grade glioma","aka":[],"tldr":"An Indian phase 1 trial gave a worm medicine to 11 people with recurrent glioblastoma alongside chemotherapy or re-irradiation, found the dose they could tolerate, and saw anaemia and nausea as the most common side effects.","summary":"Eleven patients with recurrent glioblastoma were enrolled in an accelerated titration design: arm A1 added mebendazole to re-irradiation with concurrent temozolomide, arm B1 to lomustine and arm C1 to temozolomide alone (Reverse swing-M phase 1 2020). The maximum tolerated dose was not reached in arms A1 and C1, giving a recommended phase 2 dose of 1600 mg three times a day, while with lomustine it was 1600 mg three times a day and the recommended dose 800 mg three times a day; the most common adverse events were anaemia in 9 patients, nausea in 7 and fatigue in 6 (Reverse swing-M phase 1 2020).","asOf":"2026-09-24","links":[{"label":"Reverse swing-M phase 1 2020","url":"https://doi.org/10.1002/cam4.3094"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32400117/"}],"tags":[],"related":[],"cancers":["glioblastoma"],"sections":[],"technologies":["drug-repurposing"],"targets":[],"drugs":["mebendazole","temozolomide","lomustine"],"companies":[],"institutions":[],"pathways":[],"terms":["rp2d","dose-escalation-design"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-medicine"],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo agent (Claude Fable 5.1)","editedOn":"2026-09-24","note":"Written from cached ClinicalTrials.gov v2, Europe PMC, DailyMed, Drugs@FDA and WHO eEML responses; no figure appears without its source link."},"journal":"Cancer Medicine","year":2020,"doi":"10.1002/cam4.3094","pmid":"32400117","authors":"Patil VM, Bhelekar A, Menon N, et al.","paperType":"translational","findings":["Recommended phase 2 dose 1600 mg three times a day with temozolomide or chemoradiation; 800 mg three times a day with lomustine.","Anaemia 82 percent, nausea 64 percent, fatigue 55 percent."],"whatItMeans":"This is what legitimate repurposing looks like: a registered dose-finding trial that reports its toxicities. It says nothing yet about whether mebendazole helps glioblastoma.","caveats":["Phase 1 with 11 patients; no efficacy endpoint."],"changedPractice":false,"participants":11},{"id":"paper-weaver-j-cell-biol","kind":"paper","name":"Reversion of the malignant phenotype of human breast cells in three-dimensional culture and in vivo by integrin blocking antibodies","aka":[],"tldr":"Paper cited by two term pages, indexed on Europe PMC as PubMed record 9105051 and published in The Journal of cell biology; the citing pages link this DOI, which is how the record was matched.","summary":"In a recently developed human breast cancer model, treatment of tumor cells in a 3-dimensional culture with inhibitory beta1-integrin antibody or its Fab fragments led to a striking morphological and functional reversion to a normal phenotype. A stimulatory beta1-integrin antibody proved to be ineffective. The newly formed reverted acini re-assembled a basement membrane and re-established E-cadherin-catenin complexes, and re-organized their cytoskeletons. At the same time they downregulated cyclin D1, upregulated p21(cip,wat-1), and stopped growing. Tumor cells treated with the same antibody and injected into nude mice had significantly reduced number and size of tumors in nude mice. The tissue distribution of other integrins was also normalized, suggesting the existence of intimate interactions between the different integrin pathways as well as adherens junctions. On the other hand, nonmalignant cells when treated with either alpha6 or beta4 function altering antibodies continued to grow, and had disorganized colony morphologies resembling the untreated tumor colonies. This shows a significant role of the alpha6/beta4 heterodimer in directing polarity and tissue structure. The observed phenotypes were reversible when the cells were disassociated and the antibodies removed. Our results illustrate that the extracellular matrix and its receptors dictate the phenotype of mammary epithelial cells, and thus in this model system the tissue phenotype is dominant over the cellular genotype.\n\nIndexed on Europe PMC as PubMed record 9105051 (DOI 10.1083/jcb.137.1.231). Matched by DOI alone: two term pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Cell Biol 1997","url":"https://doi.org/10.1083/jcb.137.1.231"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/9105051/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/9105051"}],"tags":["europepmc-ingest"],"related":["mechanical-theory-of-cancer","tissue-organisation-field-theory"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Journal of cell biology","year":1997,"doi":"10.1083/jcb.137.1.231","pmid":"9105051","authors":"Weaver VM, Petersen OW, Wang F, et al.","paperType":"basic","findings":[],"whatItMeans":"Two term pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-ata-medullary-thyroid-guideline-wells-thyroid-2015","kind":"paper","name":"Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma","aka":[],"tldr":"The American Thyroid Association guideline for medullary thyroid cancer sets out RET germline testing for every patient, the timing of prophylactic thyroidectomy in hereditary carriers by mutation risk, surgical extent, and systemic therapy for advanced disease.","summary":"Comprehensive guideline covering diagnosis and genetic testing, risk categories for RET mutations (highest, high, moderate) with recommended ages for prophylactic surgery, initial surgical management, postoperative calcitonin surveillance, management of persistent or recurrent disease, external radiotherapy and kinase inhibitors.","asOf":"2026-09-17","links":[{"label":"Thyroid 2015","url":"https://doi.org/10.1089/thy.2014.0335"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25810047/"}],"tags":[],"related":[],"cancers":["medullary-thyroid-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["samuel-wells"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Thyroid","year":2015,"doi":"10.1089/thy.2014.0335","pmid":"25810047","authors":"Wells SA, Asa SL, Dralle H, et al.","paperType":"guideline","findings":[],"whatItMeans":"The medullary thyroid cancer page's approach to hereditary carriers and to surgery without radioactive iodine follows this guideline.","caveats":["Predates selpercatinib and pralsetinib; systemic therapy recommendations are outdated."],"changedPractice":true},{"id":"paper-emile-revised-classification-of-histiocytoses-blood-2016","kind":"paper","name":"Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages","aka":[],"tldr":"The Histiocyte Society reorganised more than a hundred histiocytic disorders into five groups, putting Langerhans cell histiocytosis and Erdheim-Chester disease together as clonal MAPK-driven neoplasms and Rosai-Dorfman disease in its own group.","summary":"Classification from the Histiocyte Society dividing histiocytic disorders into five groups: L (Langerhans cell histiocytosis, indeterminate cell histiocytosis, Erdheim-Chester disease and mixed forms), C (cutaneous and mucocutaneous non-Langerhans histiocytoses), R (Rosai-Dorfman disease and related), M (malignant histiocytoses) and H (haemophagocytic lymphohistiocytosis and macrophage activation syndrome).\n\nIt reflects the discovery that LCH and ECD are clonal neoplasms driven by MAPK pathway mutations, and its groupings were carried into the WHO 2022 classification.","asOf":"2026-09-18","links":[{"label":"Blood 2016","url":"https://doi.org/10.1182/blood-2016-01-690636"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26966089/"}],"tags":[],"related":[],"cancers":["erdheim-chester-disease","rosai-dorfman-disease","lch-single-system"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["blood"],"dependsOn":[],"notes":[],"journal":"Blood","year":2016,"doi":"10.1182/blood-2016-01-690636","pmid":"26966089","authors":"Emile JF, Abla O, Fraitag S, et al.","paperType":"review","findings":[],"whatItMeans":"The way OnCo groups the histiocytoses, and the recognition that LCH and ECD are cancers rather than inflammatory conditions, come from this classification.","caveats":["Some entities remain hard to place, and mixed LCH-ECD presentations blur the groups.","Molecular findings have continued to reshape the categories."],"changedPractice":true},{"id":"paper-fukuoka-2017-consensus-guidelines-ipmn-pancreatology-2017","kind":"paper","name":"Revised international consensus Fukuoka guidelines for the management of IPMN of the pancreas (2017)","aka":[],"tldr":"The international rulebook for pancreatic cysts: which features mean a cyst should be removed straight away (high-risk stigmata), which mean it needs a closer look with endoscopic ultrasound (worrisome features), and how often smaller cysts should be scanned.","summary":"Revision of the 2012 Fukuoka consensus from the International Association of Pancreatology for intraductal papillary mucinous neoplasms and mucinous cystic neoplasms. High-risk stigmata that indicate resection are obstructive jaundice from a cyst in the head, an enhancing mural nodule of 5 mm or more and a main pancreatic duct of 10 mm or more. Worrisome features that indicate endoscopic ultrasound include cyst size of 3 cm or more, enhancing mural nodule under 5 mm, thickened enhancing cyst walls, main duct 5 to 9 mm, abrupt change in duct calibre with distal atrophy, lymphadenopathy, raised CA19-9 and cyst growth of 5 mm or more in two years.\n\nSurveillance intervals for cysts without these features are set by cyst size, and the revision addresses surgery for main-duct IPMN, extent of resection and follow-up after resection.","asOf":"2026-09-21","links":[{"label":"Pancreatology 2017","url":"https://doi.org/10.1016/j.pan.2017.07.007"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28735806/"}],"tags":[],"related":[],"cancers":["ipmn-cystic-precursors","pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Pancreatology","year":2017,"doi":"10.1016/j.pan.2017.07.007","pmid":"28735806","authors":"Tanaka M, Fernández-Del Castillo C, Kamisawa T, et al.","paperType":"guideline","findings":["High-risk stigmata for resection: obstructive jaundice, enhancing mural nodule 5 mm or more, main duct 10 mm or more.","Worrisome features for endoscopic ultrasound: cyst 3 cm or more, small nodule, thickened wall, main duct 5 to 9 mm, raised CA19-9, growth 5 mm in two years, among others.","Size-based surveillance intervals for cysts without worrisome features."],"whatItMeans":"Most radiology reports and surgical decisions on pancreatic cysts still follow the Fukuoka criteria or their 2024 Kyoto revision.","caveats":["Expert consensus resting on retrospective series; no randomised trial of surveillance strategies exists.","The criteria are sensitive but not specific, so many resected cysts turn out to be low grade."],"changedPractice":true},{"id":"paper-r-iss-palumbo-jco-2015","kind":"paper","name":"Revised International Staging System (R-ISS) for multiple myeloma","aka":[],"tldr":"The revised staging system for myeloma combines the older albumin and beta-2 microglobulin stage with high-risk chromosome changes and a raised lactate dehydrogenase, giving three groups with very different survival.","summary":"Analysis of 3,060 patients from eleven international trials to build a staging system combining ISS stage, chromosomal abnormalities detected by fluorescence in situ hybridisation (del(17p), t(4;14), t(14;16)) and serum lactate dehydrogenase.\n\nFive-year overall survival was 82 percent in R-ISS stage I, 62 percent in stage II and 40 percent in stage III. The R-ISS became the standard prognostic framework and the basis for trial stratification.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2015","url":"https://doi.org/10.1200/JCO.2015.61.2267"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26240224/"}],"tags":[],"related":[],"cancers":["myeloma-transplant-eligible","plasma-cell-leukaemia","myeloma-relapsed-refractory"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2015,"doi":"10.1200/JCO.2015.61.2267","pmid":"26240224","authors":"Palumbo A, Avet-Loiseau H, Oliva S, et al.","paperType":"methods","findings":["Five-year overall survival 82, 62 and 40 percent in stages I, II and III.","Five-year progression-free survival 55, 36 and 24 percent."],"whatItMeans":"The stage on a myeloma report, and the label of high-risk disease that drives intensified treatment and trial choice, comes from the R-ISS; the 2022 R2-ISS adds 1q gain.","caveats":["Stage II is a large heterogeneous group.","Derived from trial patients treated with older regimens."],"changedPractice":true,"participants":3060},{"id":"paper-frazier-j-clin-oncol","kind":"paper","name":"Revised risk classification for pediatric extracranial germ cell tumors based on 25 years of clinical trial data from the United Kingdom and United States","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 25452439 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: To risk stratify malignant extracranial pediatric germ cell tumors (GCTs).\n\nPatients and methods: Data from seven GCT trials conducted by the Children's Oncology Group (United States) or the Children's Cancer and Leukemia Group (United Kingdom) between 1985 and 2009 were merged to create a data set of patients with stage II to IV disease treated with platinum-based therapy. A parametric cure model was used to evaluate the prognostic importance of age, tumor site, stage, histology, tumor markers, and treatment regimen and estimate the percentage of patients who achieved long-term disease-free (LTDF) survival in each subgroup of the final model. Validation of the model was conducted using the bootstrap method.\n\nResults: In multivariable analysis of 519 patients with GCTs, stage IV disease (P =.001), age ≥ 11 years (P <.001), and tumor site (P <.001) were significant predictors of worse LTDF survival. Elevated alpha-fetoprotein (AFP) ≥ 10,000 ng/mL was associated with worse outcome, whereas pure yolk sac tumor (YST) was associated with better outcome, although neither met criteria for statistical significance. The analysis identified a group of patients age > 11 years with either stage III to IV extragonadal tumors or stage IV ovarian tumors with predicted LTDF survival < 70%. A bootstrap procedure showed retention of age, tumor site, and stage in > 94%, AFP in 12%, and YST in 27% of the replications.\n\nConclusion: Clinical trial data from two large national pediatric clinical trial organizations have produced a new evidence-based risk stratification of malignant pediatric GCTs that identifies a poor-risk group warranting intensified therapy.\n\nIndexed on Europe PMC as PubMed record 25452439 (DOI 10.1200/jco.2014.58.3369). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2015","url":"https://doi.org/10.1200/jco.2014.58.3369"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25452439/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25452439"}],"tags":["europepmc-ingest"],"related":["paediatric-germ-cell-tumours"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2015,"doi":"10.1200/jco.2014.58.3369","pmid":"25452439","authors":"Frazier AL, Hale JP, Rodriguez-Galindo C, et al.","paperType":"observational","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-olsen-mycosis-fungoides-staging-blood-2007","kind":"paper","name":"Revisions to the staging and classification of mycosis fungoides and Sezary syndrome (ISCL/EORTC)","aka":[],"tldr":"The 2007 international revision of the TNMB staging system for mycosis fungoides and Sezary syndrome defined skin, node, visceral and blood classes that remain the basis for staging, treatment choice and trial eligibility.","summary":"Consensus proposal from the International Society for Cutaneous Lymphomas and the EORTC cutaneous lymphoma task force revising the tumour, node, metastasis and blood (TNMB) classification, defining blood involvement classes B0 to B2, patch/plaque/tumour skin classes and clinical stages IA to IVB.","asOf":"2026-09-17","links":[{"label":"Blood 2007","url":"https://doi.org/10.1182/blood-2007-03-055749"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/17540844/"}],"tags":[],"related":[],"cancers":["cutaneous-t-cell-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["blood"],"dependsOn":[],"notes":[],"journal":"Blood","year":2007,"doi":"10.1182/blood-2007-03-055749","pmid":"17540844","authors":"Olsen E, Vonderheid E, Pimpinelli N, et al.","paperType":"guideline","findings":[],"whatItMeans":"The stages quoted on the cutaneous T-cell lymphoma page and the skin-directed versus systemic treatment split by stage follow this classification.","caveats":["Updated in 2022 to refine blood staging using flow cytometry."],"changedPractice":true},{"id":"paper-robey-nat-rev-cancer","kind":"paper","name":"Revisiting the role of ABC transporters in multidrug-resistant cancer","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 29643473 and published in Nature Reviews Cancer; the citing page links this DOI, which is how the record was matched.","summary":"Most patients who die of cancer have disseminated disease that has become resistant to multiple therapeutic modalities. Ample evidence suggests that the expression of ATP-binding cassette (ABC) transporters, especially the multidrug resistance protein 1 (MDR1, also known as P-glycoprotein or P-gp), which is encoded by ABC subfamily B member 1 (ABCB1), can confer resistance to cytotoxic and targeted chemotherapy. However, the development of MDR1 as a therapeutic target has been unsuccessful. At the time of its discovery, appropriate tools for the characterization and clinical development of MDR1 as a therapeutic target were lacking. Thirty years after the initial cloning and characterization of MDR1 and the implication of two additional ABC transporters, the multidrug resistance-associated protein 1 (MRP1; encoded by ABCC1)), and ABCG2, in multidrug resistance, interest in investigating these transporters as therapeutic targets has waned. However, with the emergence of new data and advanced techniques, we propose to re-evaluate whether these transporters play a clinical role in multidrug resistance. With this Opinion article, we present recent evidence indicating that it is time to revisit the investigation into the role of ABC transporters in efficient drug delivery in various cancer types and at the blood-brain barrier.\n\nIndexed on Europe PMC as PubMed record 29643473 (DOI 10.1038/s41568-018-0005-8). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Cancer 2018","url":"https://doi.org/10.1038/s41568-018-0005-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29643473/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29643473"}],"tags":["europepmc-ingest"],"related":["drug-efflux-pumps"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Cancer","year":2018,"doi":"10.1038/s41568-018-0005-8","pmid":"29643473","authors":"Robey RW, Pluchino KM, Hall MD, et al.","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-reya-cancer-stem-cells-nature-2001","kind":"paper","name":"Reya 2001: stem cells, cancer and cancer stem cells","aka":[],"tldr":"The review that framed the cancer stem cell idea: only a small subset of cells in a tumour may be able to renew it, so treatments that shrink a tumour without removing those cells let it grow back.","summary":"Reya, Morrison, Clarke and Weissman set out the parallels between normal stem cells and cancer. Normal stem cells self-renew and give rise to differentiated progeny, and the same signalling pathways that control self-renewal, including Wnt, Notch and Sonic hedgehog, are recurrently altered in cancers. Drawing on experiments in which only rare, marker-defined cells from human leukaemia could re-establish the disease in mice, they proposed that many cancers are maintained by a minority of cancer stem cells and that these cells, rather than the tumour bulk, should be the target of therapy.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1038/35102167"}],"tags":[],"related":[],"cancers":["aml"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["stanford"],"pathways":[],"terms":["stem-cell","relapse-recurrence"],"trials":[],"people":["irving-weissman"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature","year":2001,"doi":"10.1038/35102167","authors":"Reya T, Morrison SJ, Clarke MF, Weissman IL.","paperType":"review","findings":["Self-renewal pathways of normal stem cells (Wnt, Notch, Sonic hedgehog) are frequently deregulated in cancer.","In acute myeloid leukaemia only a rare, marker-defined subset of cells could transplant the disease into immunodeficient mice, the first experimental cancer stem cells.","Proposed that tumour growth and relapse are driven by cancer stem cells and that therapies should be judged by their effect on that population."],"whatItMeans":"The paper launched two decades of work on tumour-initiating cells in solid cancers, on why relapse follows apparently complete responses, and on measuring residual disease at the level of the cells that can regrow it. It also connected developmental biology pathways to cancer drug discovery.","caveats":["Whether cancer stem cells are a fixed population or a reversible cell state remains debated.","Transplantation assays in mice may select for cells that survive the assay rather than cells that drive the disease in patients."],"changedPractice":false},{"id":"paper-ribas-wolchok-checkpoint-blockade-science-2018","kind":"paper","name":"Ribas and Wolchok 2018: cancer immunotherapy using checkpoint blockade","aka":[],"tldr":"A review by two of the field's leading trialists, written as checkpoint inhibitors reached a dozen cancers, explaining how CTLA-4 and PD-1 blockade work, why only some patients respond, and how resistance arises.","summary":"Ribas and Wolchok summarised the science and clinical results of checkpoint blockade at the point where PD-1 pathway antibodies had been approved across many cancers. They described CTLA-4 blockade as broadening the T cell repertoire and PD-1 blockade as reinvigorating exhausted T cells already in the tumour; reviewed the features of responding tumours, including mutational burden, pre-existing T cell infiltration and interferon-gamma signalling; and catalogued primary and acquired resistance mechanisms such as loss of antigen presentation and interferon signalling defects. They argued for rational combinations based on these mechanisms.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1126/science.aar4060"}],"tags":[],"related":["paper-pardoll-immune-checkpoint-blockade-nrc-2012","paper-tumeh-pd1-adaptive-immune-resistance-nature-2014"],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["ctla4","pd1","pdl1"],"drugs":[],"companies":[],"institutions":["ucla-jonsson","mskcc"],"pathways":[],"terms":["immune-checkpoint","tmb","irae"],"trials":[],"people":["antoni-ribas","jedd-wolchok"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Science","year":2018,"doi":"10.1126/science.aar4060","authors":"Ribas A, Wolchok JD.","paperType":"review","findings":["CTLA-4 blockade acts mainly at T cell priming and broadens the repertoire; PD-1 blockade reinvigorates antigen-experienced T cells in the tumour.","Response is associated with mutational burden, pre-existing T cell infiltration and intact interferon-gamma signalling.","Resistance arises through loss of antigen presentation (for example beta-2-microglobulin), JAK-STAT defects and immunosuppressive microenvironments."],"whatItMeans":"This is the standard overview of checkpoint immunotherapy for clinicians and scientists, tying together the trial results and the biology of response and resistance that guide today's combination trials.","caveats":["A review; the field has moved on with LAG-3 blockade, neoadjuvant use and new biomarkers.","Both authors led many of the trials discussed."],"changedPractice":false},{"id":"paper-monaleesa-2-n-engl-j-med-2016","kind":"paper","name":"Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer","aka":[],"tldr":"Published report from the MONALEESA-2 trial registered as NCT01958021, in New England Journal of Medicine (2016), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: The inhibition of cyclin-dependent kinases 4 and 6 (CDK4/6) could potentially overcome or delay resistance to endocrine therapy in advanced breast cancer that is positive for hormone receptor (HR) and negative for human epidermal growth factor receptor 2 (HER2).\n\nMethods: In this randomized, placebo-controlled, phase 3 trial, we evaluated the efficacy and safety of the selective CDK4/6 inhibitor ribociclib combined with letrozole for first-line treatment in 668 postmenopausal women with HR-positive, HER2-negative recurrent or metastatic breast cancer who had not received previous systemic therapy for advanced disease. We randomly assigned the patients to receive either ribociclib (600 mg per day on a 3-weeks-on, 1-week-off schedule) plus letrozole (2.5 mg per day) or placebo plus letrozole. The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival, overall response rate, and safety. A preplanned interim analysis was performed on January 29, 2016, after 243 patients had disease progression or died. Prespecified criteria for superiority required a hazard ratio of 0.56 or less with P<1.29×10 -5.\n\nResults: The duration of progression-free survival was significantly longer in the ribociclib group than in the placebo group (hazard ratio, 0.56; 95% CI, 0.43 to 0.72; P=3.29×10 -6 for superiority). The median duration of follow-up was 15.3 months. After 18 months, the progression-free survival rate was 63.0% (95% confidence interval [CI], 54.6 to 70.3) in the ribociclib group and 42.2% (95% CI, 34.8 to 49.5) in the placebo group. In patients with measurable disease at baseline, the overall response rate was 52.7% and 37.1%, respectively (P<0.001). Common grade 3 or 4 adverse events that were reported in more than 10% of the patients in either group were neutropenia (59.3% in the ribociclib group vs. 0.9% in the placebo group) and leukopenia (21.0% vs. 0.6%); the rates of discontinuation because of adverse events were 7.5% and 2.1%, respectively.\n\nConclusions: Among patients receiving initial systemic treatment for HR-positive, HER2-negative advanced breast cancer, the duration of progression-free survival was significantly longer among those receiving ribociclib plus letrozole than among those receiving placebo plus letrozole, with a higher rate of myelosuppression in the ribociclib group. (Funded by Novartis Pharmaceuticals; ClinicalTrials.gov number, NCT01958021.).\n\nIndexed on Europe PMC as PubMed record 27717303 (DOI 10.1056/nejmoa1609709). Its abstract cites the registry id NCT01958021, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2016","url":"https://doi.org/10.1056/nejmoa1609709"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27717303/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27717303"},{"label":"ClinicalTrials.gov NCT01958021","url":"https://clinicaltrials.gov/study/NCT01958021"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["monaleesa-2"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2016,"doi":"10.1056/nejmoa1609709","pmid":"27717303","authors":"Hortobagyi GN, Stemmer SM, Burris HA, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT01958021 with the most citations, so it is the natural first reading for anyone following the MONALEESA-2 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-natalee-jama-oncol-2025-update","kind":"paper","name":"Ribociclib Plus Endocrine Therapy in Hormone Receptor-Positive/ERBB2-Negative Early Breast Cancer: 4-Year Outcomes From the NATALEE Randomized Clinical Trial","aka":[],"tldr":"Later report from the NATALEE trial registered as NCT03701334, in JAMA Oncology (2025); its title describes an updated or longer-term analysis.","summary":"Importance: Ribociclib plus a nonsteroidal aromatase inhibitor (NSAI) has demonstrated a statistically significant invasive disease-free survival (iDFS) benefit over NSAI alone in patients with hormone receptor-positive/ERBB2 (formerly HER2)-negative early breast cancer. Evaluating the efficacy and safety of adjuvant ribociclib beyond the planned 3-year treatment period is critical for understanding the long-term impact on recurrences.\n\nObjective: To evaluate efficacy and safety of adjuvant ribociclib in an exploratory 4-year analysis of the NATALEE (New Adjuvant Trial With Ribociclib [LEE011]) randomized clinical trial, with all patients no longer receiving ribociclib treatment.\n\nDesign, setting, and participants: This exploratory analysis of an international, open-label, randomized phase 3 trial analyzed adjuvant treatment for premenopausal and postmenopausal women and men with hormone receptor-positive/ERBB2-negative early breast cancer. Eligible patients had anatomic stage IIA (either N0 with additional risk factors or N1 [1-3 axillary lymph nodes]), IIB, or III disease per the American Joint Committee on Cancer Staging Manual, eighth edition. The data cutoff date was April 29, 2024.\n\nInterventions: Patients were randomized 1:1 to receive ribociclib (400 mg once daily, days 1-21 of a 28-day cycle, over 36 months) plus NSAI (letrozole, 2.5 mg, or anastrozole, 1 mg, once daily continuously for 60 months) or NSAI alone. Men and premenopausal women also received goserelin (3.6 mg once every 28 days administered subcutaneously).\n\nMain outcomes and measures: The primary end point was iDFS, and secondary efficacy end points included distant disease-free survival, recurrence-free survival, and overall survival. Survival was evaluated by the Kaplan-Meier method.\n\nResults: Among 5101 patients included in the analysis (median [range] age, 52 [24-90] years; 5081 [99.6%] female), the median follow-up for iDFS was 44.2 months (range, 0-63 months). Ribociclib plus NSAI continued to show iDFS benefit over NSAI alone (hazard ratio, 0.72; 95% CI, 0.61-0.84), with 3-year iDFS rates of 90.8% vs 88.1% (difference, 2.7 percentage points) and 4-year rates of 88.5% vs 83.6% (difference, 4.9 percentage points). The efficacy benefit was consistent across subgroups and secondary end points. Overall survival data remain immature, although a trend in favor of ribociclib plus NSAI over NSAI alone was observed (hazard ratio, 0.83; 95% CI, 0.64-1.07). The incidence of adverse events has remained stable.\n\nConclusions and relevance: This exploratory analysis of the NATALEE randomized clinical trial, with a median follow-up beyond the 3-year treatment duration, demonstrated consistent iDFS benefit with ribociclib plus NSAI over NSAI alone.\n\nTrial registration: ClinicalTrials.gov Identifier: NCT03701334.\n\nIndexed on Europe PMC as PubMed record 40996773 (DOI 10.1001/jamaoncol.2025.3700). Its abstract cites the registry id NCT03701334, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"JAMA Oncol 2025","url":"https://doi.org/10.1001/jamaoncol.2025.3700"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40996773/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40996773"},{"label":"ClinicalTrials.gov NCT03701334","url":"https://clinicaltrials.gov/study/NCT03701334"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["natalee"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2025,"doi":"10.1001/jamaoncol.2025.3700","pmid":"40996773","authors":"Fasching PA, Stroyakovskiy D, Yardley DA, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the NATALEE trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-canto-caps-long-term-surveillance-gastroenterology-2018","kind":"paper","name":"Risk of Neoplastic Progression in Individuals at High Risk for Pancreatic Cancer Undergoing Long-term Surveillance","aka":[],"tldr":"The 2018 Johns Hopkins report of 354 people with inherited or family risk scanned for up to 16 years: 7 percent progressed to cancer or a high-grade precursor, 9 of the 10 cancers found by the scans were operable, and 85 percent of those patients were alive at three years.","summary":"Canto and colleagues analysed 354 high-risk individuals enrolled in the Cancer of the Pancreas Screening cohorts at tertiary academic centres from 1998 to 2014 (median follow-up 5.6 years), evaluated at baseline by endoscopic ultrasound and followed with endoscopic ultrasound, MRI and/or CT. Lesions with worrisome features (solid mass, multiple cysts, cyst over 3 cm, thickened walls, mural nodule, main duct over 5 mm, abrupt duct change) or rapid cyst growth were found in 68 patients (19 percent). Twenty-four (7 percent) had neoplastic progression (14 cancers, 10 high-grade dysplasia) over 16 years, 1.6 percent per year; 93 percent had detectable worrisome features beforehand. Nine of 10 cancers found during routine surveillance were resectable, and 85 percent of those patients survived three years against 25 percent of the four with symptomatic unresectable cancers that arose outside surveillance (P less than 0.0001). Median age at progression was 67 and median time from baseline to cancer 4.8 years.","asOf":"2026-09-24","links":[{"label":"Gastroenterology 2018","url":"https://doi.org/10.1053/j.gastro.2018.05.035"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29803839/"}],"tags":["pancreatic-evidence"],"related":["paper-caps-consortium-surveillance-recommendations-gut-2020","paper-dbouk-caps5-stage-survival-jco-2022"],"cancers":["pancreatic","ipmn-cystic-precursors","resectable-pdac"],"sections":[],"technologies":["pancreatic-surveillance","mri","ct"],"targets":[],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":[],"terms":[],"trials":["precede"],"people":[],"bottlenecks":["b-hereditary-risk","b-early-detection"],"keyPapers":[],"journals":["gastroenterology"],"dependsOn":[],"notes":[],"journal":"Gastroenterology","year":2018,"doi":"10.1053/j.gastro.2018.05.035","pmid":"29803839","authors":"Canto MI, Almario JA, Schulick RD, et al.","paperType":"observational","findings":["354 high-risk individuals, 16 years; 7 percent progressed (14 cancers, 10 high-grade dysplasia), 1.6 percent per year.","9 of 10 surveillance-detected cancers resectable; three-year survival 85 versus 25 percent for cancers arising outside surveillance.","Median time from baseline to cancer 4.8 years."],"whatItMeans":"The first long-term evidence that surveillance in high-risk people finds operable cancers, and the source of the imaging features that trigger surgery in the CAPS recommendations.","caveats":["Single-programme, expert-centre cohort; lead-time and length-time bias inflate survival comparisons.","Four unresectable cancers is a small comparison group."],"participants":354},{"id":"paper-wisdom-trial-jama-2026","kind":"paper","name":"Risk-Based vs Annual Breast Cancer Screening: The WISDOM Randomized Clinical Trial","aka":[],"tldr":"Published report from the WISDOM trial registered as NCT02620852, in JAMA (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Importance: Individual breast cancer risk can guide screening initiation, frequency, use of supplemental imaging, and preventive measures to improve breast cancer screening by shifting resources from low-risk women to high-risk women.\n\nObjective: To determine whether risk-based breast cancer screening is a feasible alternative to annual mammography.\n\nDesign, setting, and participants: Parallel-group, pragmatic, multicenter randomized clinical trial comparing risk-based (n = 14 212) with annual (n = 14 160) breast cancer screening. Women aged 40 to 74 years without prior diagnoses of breast cancer or ductal carcinoma in situ, or prophylactic bilateral mastectomy, were recruited from all 50 US states from September 2016 to February 2023, with follow-up through September 5, 2025 (median follow-up, 5.1 years). Statistical analysis was conducted between July and November 2025. All study procedures were conducted via an online platform. Women who declined randomization were enrolled in an observational cohort.\n\nInterventions: Risk assessment included sequencing of 9 susceptibility genes, polygenic risk score, and the Breast Cancer Surveillance Consortium version 2 model. The risk-based group received 1 of 4 recommendations: (1) highest risk (≥6% 5-year risk, high-penetrance pathogenic variant): alternating mammography and magnetic resonance imaging (MRI) every 6 months and counseling; (2) elevated risk (top 2.5 risk percentile by age): annual mammography and risk-reduction counseling; (3) average risk: biennial mammography; and (4) low risk (aged 40-49 years and <1.3% 5-year risk): no screening until risk is 1.3% or greater or age 50 years.\n\nMain outcomes and measures: The coprimary outcomes included noninferiority for stage ≥IIB cancers and superiority in reducing biopsy rates. Secondary outcomes included identification of stage ≥IIA cancers, mammogram rates, uptake of prevention strategies in higher risk cohorts, preference for screening group in the observational cohort, ductal carcinoma in situ, MRI, and stage-specific cancer rates.\n\nResults: A total of 28 372 women were randomized. The mean (SD) age was 54 (9.6) years and the majority were non-Hispanic White (77%). The rate of stage ≥IIB cancers was noninferior in the risk-based compared with the annual group (risk-based: 30.0 [95% CI, 16.3-43.8] vs annual: 48.0 [95% CI, 30.1-65.5] per 100 000 person-years; rate difference, -18.0 per 100 000 person-years [95% CI, -40.2 to 4.1]). The rate of breast biopsies was not lower in the risk-based group (rate difference, 98.7 per 100 000 person-years [95% CI, -17.9 to 215.3]) despite fewer mammograms (rate difference, -3835.9 [95% CI, -4516.8 to -3154.9]). The cumulative incidence of cancer, biopsy, mammogram, and MRI increased as risk category increased. In the observational cohort, 89% of participants (15 980/18 031) chose risk based.\n\nConclusions: Risk-based breast cancer screening that includes population-based genetic testing safely stratified risk and screening intensity, but did not reduce biopsy rates.\n\nTrial registration: ClinicalTrials.gov Identifier: NCT02620852.\n\nIndexed on Europe PMC as PubMed record 41385349 (DOI 10.1001/jama.2025.24784). Its abstract cites the registry id NCT02620852, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"JAMA 2026","url":"https://doi.org/10.1001/jama.2025.24784"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41385349/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41385349"},{"label":"ClinicalTrials.gov NCT02620852","url":"https://clinicaltrials.gov/study/NCT02620852"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["wisdom-trial"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2026,"doi":"10.1001/jama.2025.24784","pmid":"41385349","authors":"Esserman LJ, Fiscalini AS, Naeim A, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02620852 with the most citations, so it is the natural first reading for anyone following the WISDOM trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-lyma-rituximab-maintenance-after-transplant-mantle-cell-nejm-2017","kind":"paper","name":"Rituximab after autologous stem-cell transplantation in mantle-cell lymphoma","aka":["LyMa","Le Gouill 2017"],"tldr":"Three years of an antibody every two months after a stem cell transplant kept younger people with mantle cell lymphoma in remission longer and helped them live longer.","summary":"A phase 3 trial in 299 patients younger than 66 at diagnosis with mantle-cell lymphoma. After four courses of R-DHAP induction (rituximab, dexamethasone, high-dose cytarabine and a platinum derivative), the overall response rate was 89 per cent and the complete response rate 77 per cent. Transplantation was performed in 257 patients, and 240 were randomised 1 to 1 to rituximab 375 mg per square metre every two months for three years or to observation after transplantation; 59 patients did not undergo randomisation. The primary endpoint was event-free survival after transplantation among randomised patients, with an event defined as progression, relapse, death, allergy to rituximab or severe infection.\n\nAt a median follow-up of 50.2 months from randomisation (range 46.4 to 54.2), four-year event-free survival was 79 per cent (95 per cent confidence interval 70 to 86) with rituximab against 61 per cent (51 to 70) with observation (p = 0.001), and four-year progression-free survival 83 per cent (73 to 88) against 64 per cent (55 to 73). Overall survival was also prolonged.","asOf":"2026-10-01","links":[{"label":"New England Journal of Medicine 2017","url":"https://doi.org/10.1056/NEJMoa1701769"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28953447/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28953447"}],"tags":["lymphoma-evidence"],"related":["lymphoma-roadmap"],"cancers":["mantle-cell-lymphoma","non-hodgkin-lymphoma"],"sections":["immunotherapy","cell-therapy"],"technologies":[],"targets":["cd20","ccnd1"],"drugs":["rituximab","dexamethasone","cytarabine","cisplatin"],"companies":["lysa"],"institutions":[],"pathways":[],"terms":["maintenance-therapy","autologous-transplant","lymphoma-tx-transplant-role"],"trials":["lyma","triangle"],"people":["catherine-thieblemont"],"bottlenecks":["b-toxicity-qol"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2017,"doi":"10.1056/NEJMoa1701769","pmid":"28953447","authors":"Le Gouill S, Thieblemont C, Oberic L, et al.","paperType":"rct","findings":["Four-year event-free survival was 79 per cent (95 per cent confidence interval 70 to 86) with rituximab maintenance against 61 per cent (51 to 70) with observation (p = 0.001).","Four-year progression-free survival was 83 per cent (73 to 88) against 64 per cent (55 to 73).","Rituximab maintenance prolonged overall survival as well as event-free and progression-free survival.","After four courses of R-DHAP induction the overall response rate was 89 per cent and the complete response rate 77 per cent.","Of 299 patients enrolled, 257 were transplanted and 240 were randomised."],"whatItMeans":"One of the few maintenance strategies in lymphoma that improved overall survival rather than only progression-free survival, and the reason three years of rituximab became standard after autologous transplantation in mantle cell lymphoma.","caveats":["The event-free survival definition included allergy to rituximab and severe infection as events, which cuts both ways in a trial of rituximab.","Restricted to patients under 66 fit enough for R-DHAP and autologous transplantation.","59 of 299 enrolled patients were never randomised, mostly because they did not reach transplantation.","TRIANGLE has since questioned whether the transplant itself is needed when ibrutinib is added, which changes the setting in which this result applies."],"changedPractice":true,"participants":240},{"id":"paper-minard-colin-n-engl-j-med","kind":"paper","name":"Rituximab for High-Risk, Mature B-Cell Non-Hodgkin's Lymphoma in Children","aka":[],"tldr":"Paper cited by one cancer page and one trial page, indexed on Europe PMC as PubMed record 32492302 and published in New England Journal of Medicine; the citing pages link this DOI, which is how the record was matched.","summary":"Background: Rituximab added to chemotherapy prolongs survival among adults with B-cell cancer. Data on its efficacy and safety in children with high-grade, mature B-cell non-Hodgkin's lymphoma are limited.\n\nMethods: We conducted an open-label, international, randomized, phase 3 trial involving patients younger than 18 years of age with high-risk, mature B-cell non-Hodgkin's lymphoma (stage III with an elevated lactate dehydrogenase level or stage IV) or acute leukemia to compare the addition of six doses of rituximab to standard lymphomes malins B (LMB) chemotherapy with standard LMB chemotherapy alone. The primary end point was event-free survival. Overall survival and toxic effects were also assessed.\n\nResults: Analyses were based on 328 patients who underwent randomization (164 patients per group); 85.7% of the patients had Burkitt's lymphoma. The median follow-up was 39.9 months. Events were observed in 10 patients in the rituximab-chemotherapy group and in 28 in the chemotherapy group. Event-free survival at 3 years was 93.9% (95% confidence interval [CI], 89.1 to 96.7) in the rituximab-chemotherapy group and 82.3% (95% CI, 75.7 to 87.5) in the chemotherapy group (hazard ratio for primary refractory disease or first occurrence of progression, relapse after response, death from any cause, or second cancer, 0.32; 95% CI, 0.15 to 0.66; one-sided P = 0.00096, which reached the significance level required for this analysis). Eight patients in the rituximab-chemotherapy group died (4 deaths were disease-related, 3 were treatment-related, and 1 was from a second cancer), as did 20 in the chemotherapy group (17 deaths were disease-related, and 3 were treatment-related) (hazard ratio, 0.36; 95% CI, 0.16 to 0.82). The incidence of acute adverse events of grade 4 or higher after prephase treatment was 33.3% in the rituximab-chemotherapy group and 24.2% in the chemotherapy group (P = 0.07); events were related mainly to febrile neutropenia and infection. Approximately twice as many patients in the rituximab-chemotherapy group as in the chemotherapy group had a low IgG level 1 year after trial inclusion.\n\nConclusions: Rituximab added to standard LMB chemotherapy markedly prolonged event-free survival and overall survival among children and adolescents with high-grade, high-risk, mature B-cell non-Hodgkin's lymphoma and was associated with a higher incidence of hypogammaglobulinemia and, potentially, more episodes of infection. (Funded by the Clinical Research Hospital Program of the French Ministry of Health and others; ClinicalTrials.gov number, NCT01516580.).\n\nIndexed on Europe PMC as PubMed record 32492302 (DOI 10.1056/nejmoa1915315). Matched by DOI alone: one cancer page and one trial page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2020","url":"https://doi.org/10.1056/nejmoa1915315"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32492302/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32492302"}],"tags":["europepmc-ingest"],"related":["burkitt-lymphoma"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["inter-b-nhl-ritux-2010"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2020,"doi":"10.1056/nejmoa1915315","pmid":"32492302","authors":"Minard-Colin V, Aupérin A, Pillon M, et al.","paperType":"rct","findings":[],"whatItMeans":"One cancer page and one trial page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-prima-rituximab-maintenance-follicular-lancet-2011","kind":"paper","name":"Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial","aka":["PRIMA 2011","Salles 2011"],"tldr":"Two years of an antibody given every two months after first-line chemotherapy raised the proportion still free of progression at three years from 58 to 75 per cent.","summary":"An open-label randomised trial at 223 centres in 25 countries. 1,217 patients with previously untreated follicular lymphoma needing systemic therapy received one of three non-randomised immunochemotherapy induction regimens used in routine practice, and the 1,019 who achieved a complete or partial response were randomised to rituximab 375 mg per square metre every eight weeks for two years or to observation.\n\n505 patients were assigned to maintenance and 513 to observation (one died during randomisation). With a median follow-up of 36 months, progression-free survival was 74.9 per cent (95 per cent confidence interval 70.9 to 78.9) with maintenance, with 130 progressions, against 57.6 per cent (53.2 to 62.0) with observation, with 218 progressions: hazard ratio 0.55 (0.44 to 0.68).","asOf":"2026-10-01","links":[{"label":"Lancet 2011","url":"https://doi.org/10.1016/S0140-6736(10)62175-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21176949/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/21176949"}],"tags":["lymphoma-evidence"],"related":["paper-prima-final-rituximab-maintenance-follicular-jco-2019","lymphoma-roadmap"],"cancers":["follicular-lymphoma","non-hodgkin-lymphoma"],"sections":["immunotherapy"],"technologies":[],"targets":["cd20"],"drugs":["rituximab"],"companies":["lysa"],"institutions":[],"pathways":[],"terms":["maintenance-therapy","lymphoma-tx-maintenance","flipi"],"trials":["prima-follicular"],"people":["gilles-salles"],"bottlenecks":["b-toxicity-qol"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"Lancet","year":2011,"doi":"10.1016/S0140-6736(10)62175-7","pmid":"21176949","authors":"Salles G, Seymour JF, Offner F, et al.","paperType":"rct","findings":["Three-year progression-free survival was 74.9 per cent (95 per cent confidence interval 70.9 to 78.9) with two years of rituximab maintenance against 57.6 per cent (53.2 to 62.0) with observation.","130 patients progressed in the maintenance group against 218 in the observation group (hazard ratio 0.55, 0.44 to 0.68).","1,217 patients received induction and 1,019 responders were randomised.","Induction regimen was chosen by the centre rather than randomised, reflecting routine practice across 25 countries."],"whatItMeans":"The trial that made two years of rituximab maintenance a routine offer after first-line immunochemotherapy for follicular lymphoma with a high tumour burden.","caveats":["Open-label with observation rather than placebo as the comparator, so progression assessment was not blinded.","Induction was not randomised, so the arms differ in induction mix only by chance.","At 36 months the trial could not address overall survival; the 2019 report did, and found no difference."],"changedPractice":true,"participants":1018},{"id":"paper-sparano-blood","kind":"paper","name":"Rituximab plus concurrent infusional EPOCH chemotherapy is highly effective in HIV-associated B-cell non-Hodgkin lymphoma","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 20023215 and published in Blood; the citing page links this DOI, which is how the record was matched.","summary":"Rituximab plus intravenous bolus chemotherapy is a standard treatment for immunocompetent patients with B-cell non-Hodgkin lymphoma (NHL). Some studies have suggested that rituximab is associated with excessive toxicity in HIV-associated NHL, and that infusional chemotherapy may be more effective. We performed a randomized phase 2 trial of rituximab (375 mg/m(2)) given either concurrently before each infusional etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone (EPOCH) chemotherapy cycle or sequentially (weekly for 6 weeks) after completion of all chemotherapy in HIV-associated NHL. EPOCH consisted of a 96-hour intravenous infusion of etoposide, doxorubicin, and vincristine plus oral prednisone followed by intravenous bolus cyclophosphamide given every 21 days for 4 to 6 cycles. In the concurrent arm, 35 of 48 evaluable patients (73%; 95% confidence interval, 58%-85%) had a complete response. In the sequential arm, 29 of 53 evaluable patients (55%; 95% confidence interval, 41%-68%) had a complete response. The primary efficacy endpoint was met for the concurrent arm only. Toxicity was comparable in the 2 arms, although patients with a baseline CD4 count less than 50/microL had a high infectious death rate in the concurrent arm. We conclude that concurrent rituximab plus infusional EPOCH is an effective regimen for HIV-associated lymphoma.\n\nIndexed on Europe PMC as PubMed record 20023215 (DOI 10.1182/blood-2009-08-231613). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Blood 2010","url":"https://doi.org/10.1182/blood-2009-08-231613"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20023215/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/20023215"}],"tags":["europepmc-ingest"],"related":["hiv-associated-lymphoma"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["blood"],"dependsOn":[],"notes":[],"journal":"Blood","year":2010,"doi":"10.1182/blood-2009-08-231613","pmid":"20023215","authors":"Sparano JA, Lee JY, Kaplan LD, et al.","paperType":"rct","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-rizvi-mutational-landscape-pd1-science-2015","kind":"paper","name":"Rizvi 2015: the mutational landscape determines who responds to PD-1 blockade in lung cancer","aka":[],"tldr":"Lung cancers with more mutations, typically those caused by smoking, were more likely to respond to pembrolizumab, the study that established tumour mutational burden as a biomarker for immunotherapy.","summary":"Rizvi, Hellmann, Snyder and colleagues at Memorial Sloan Kettering sequenced the exomes of non-small-cell lung cancers from patients treated with pembrolizumab in a discovery cohort of 16 and a validation cohort of 18. A higher number of nonsynonymous mutations was associated with a higher response rate, more durable clinical benefit and longer progression-free survival. A molecular smoking signature, a higher predicted neoantigen burden and mutations in DNA repair genes also tracked with benefit, and in one responder the team detected T cells recognising a specific neoantigen.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1126/science.aaa1348"}],"tags":[],"related":["paper-pardoll-immune-checkpoint-blockade-nrc-2012","tmb-high"],"cancers":["nsclc"],"sections":[],"technologies":["checkpoint-inhibitor","wes-wgs","tmb-testing"],"targets":["pd1","pdl1","kras"],"drugs":["pembrolizumab"],"companies":[],"institutions":["mskcc"],"pathways":["cancer-immunity-cycle","mutagenesis-signatures","pd1-checkpoint"],"terms":["tmb","neoantigen","mutational-signature"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Science","year":2015,"doi":"10.1126/science.aaa1348","authors":"Rizvi NA, Hellmann MD, Snyder A, et al.","paperType":"translational","findings":["Whole-exome sequencing of NSCLC from 16 patients (discovery) and 18 (validation) treated with pembrolizumab.","Higher nonsynonymous mutation burden was associated with durable clinical benefit (73% vs 13% in the discovery cohort) and longer progression-free survival.","A transversion-high smoking signature, predicted neoantigen burden and DNA repair pathway mutations were also associated with benefit.","Neoantigen-specific T cells were detected in a responding patient."],"whatItMeans":"This paper turned a hypothesis into a biomarker: tumour mutational burden is now measured by commercial panels and underpins the tissue-agnostic approval of pembrolizumab for TMB-high tumours. It also explains why smokers' lung cancers, long the hardest to treat, respond better to immunotherapy than never-smokers' cancers.","caveats":["Small cohorts; the mutation burden cut-off was set within the study.","TMB has proved a weaker and less consistent predictor in later, larger trials, and panel-based estimates differ between assays."],"changedPractice":true,"participants":34},{"id":"paper-sethna-rna-neoantigen-vaccine-long-lived-t-cells-nature-2025","kind":"paper","name":"RNA neoantigen vaccines prime long-lived CD8+ T cells in pancreatic cancer","aka":[],"tldr":"The 2025 follow-up of the personalised mRNA vaccine trial in pancreatic cancer: at three years, patients whose immune systems responded to the vaccine had still mostly not relapsed, and the T cells the vaccine made were predicted to live for years.","summary":"Sethna, Balachandran and colleagues report the extended 3.2-year median follow-up of the phase 1 trial of surgery, atezolizumab, autogene cevumeran (individualised uridine mRNA-lipoplex neoantigen vaccine) and modified FOLFIRINOX in resected pancreatic ductal adenocarcinoma. Responders with vaccine-induced T cells (8) had prolonged recurrence-free survival (median not reached) compared with non-responders (8; median 13.4 months; P = 0.007). Vaccine-induced CD8-positive T cell clones had an average estimated lifespan of 7.7 years (range 1.5 to roughly 100), about 20 percent with latent multi-decade lifespans; 86 percent of clones per patient persisted at substantial frequency about three years after vaccination. Using PhenoTrack, the clones were shown to be absent from pre-vaccination tissue and to assume a cytotoxic, tissue-resident memory-like state with preserved neoantigen-specific function. Two responders recurred with fewer vaccine-induced T cells, and recurrent tumours were pruned of vaccine-targeted clones.","asOf":"2026-09-24","links":[{"label":"Nature 2025","url":"https://doi.org/10.1038/s41586-024-08508-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39972124/"},{"label":"ClinicalTrials.gov NCT04161755","url":"https://clinicaltrials.gov/study/NCT04161755"},{"label":"ClinicalTrials.gov NCT05968326","url":"https://clinicaltrials.gov/study/NCT05968326"}],"tags":["pancreatic-evidence"],"related":["paper-rojas-mrna-neoantigen-vaccine-pancreatic-nature-2023","immunotherapy-roadmap"],"cancers":["pancreatic","resectable-pdac"],"sections":[],"technologies":["neoantigen-mrna-vaccine","checkpoint-inhibitor"],"targets":[],"drugs":["autogene-cevumeran","atezolizumab","folfirinox"],"companies":["biontech","roche-genentech"],"institutions":["mskcc"],"pathways":[],"terms":["neoantigen","cold-vs-hot"],"trials":["nct05968326"],"people":["vinod-balachandran","ugur-sahin","eileen-oreilly"],"bottlenecks":["b-tme-immunosuppression","b-immunotherapy-response"],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2025,"doi":"10.1038/s41586-024-08508-4","pmid":"39972124","authors":"Sethna Z, Guasp P, Reiche C, et al.","paperType":"translational","findings":["3.2-year median follow-up; responders (8) median recurrence-free survival not reached versus 13.4 months in non-responders (8), P = 0.007.","Vaccine-induced CD8 clones with an estimated average lifespan of 7.7 years; 86 percent of clones persisted at about three years.","Recurrent tumours in two responders had lost the vaccine-targeted clones."],"whatItMeans":"The strongest human evidence that a cancer vaccine can make durable T cells in a tumour with few mutations; the randomised phase 2 IMCODE003 (260 patients, primary completion listed for January 2031) is the test of whether that translates into fewer relapses.","caveats":["Sixteen patients, half responders; responder status could mark a favourable immune system rather than a vaccine effect.","Manufacturing an individual vaccine within weeks of surgery is a logistical and cost constraint at scale."],"participants":16},{"id":"paper-bradley-nat-rev-cancer","kind":"paper","name":"RNA splicing dysregulation and the hallmarks of cancer","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 36627445 and published in Nature Reviews Cancer; the citing page links this DOI, which is how the record was matched.","summary":"Dysregulated RNA splicing is a molecular feature that characterizes almost all tumour types. Cancer-associated splicing alterations arise from both recurrent mutations and altered expression of trans-acting factors governing splicing catalysis and regulation. Cancer-associated splicing dysregulation can promote tumorigenesis via diverse mechanisms, contributing to increased cell proliferation, decreased apoptosis, enhanced migration and metastatic potential, resistance to chemotherapy and evasion of immune surveillance. Recent studies have identified specific cancer-associated isoforms that play critical roles in cancer cell transformation and growth and demonstrated the therapeutic benefits of correcting or otherwise antagonizing such cancer-associated mRNA isoforms. Clinical-grade small molecules that modulate or inhibit RNA splicing have similarly been developed as promising anticancer therapeutics. Here, we review splicing alterations characteristic of cancer cell transcriptomes, dysregulated splicing's contributions to tumour initiation and progression, and existing and emerging approaches for targeting splicing for cancer therapy. Finally, we discuss the outstanding questions and challenges that must be addressed to translate these findings into the clinic.\n\nIndexed on Europe PMC as PubMed record 36627445 (DOI 10.1038/s41568-022-00541-7). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Cancer 2023","url":"https://doi.org/10.1038/s41568-022-00541-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36627445/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36627445"}],"tags":["europepmc-ingest"],"related":["rna-splicing"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Cancer","year":2023,"doi":"10.1038/s41568-022-00541-7","pmid":"36627445","authors":"Bradley RK, Anczuków O","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-monje-cell","kind":"paper","name":"Roadmap for the Emerging Field of Cancer Neuroscience","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 32302564 and published in Cell; the citing page links this DOI, which is how the record was matched.","summary":"Mounting evidence indicates that the nervous system plays a central role in cancer pathogenesis. In turn, cancers and cancer therapies can alter nervous system form and function. This Commentary seeks to describe the burgeoning field of \"cancer neuroscience\" and encourage multidisciplinary collaboration for the study of cancer-nervous system interactions.\n\nIndexed on Europe PMC as PubMed record 32302564 (DOI 10.1016/j.cell.2020.03.034). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cell 2020","url":"https://doi.org/10.1016/j.cell.2020.03.034"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32302564/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32302564"}],"tags":["europepmc-ingest"],"related":["cancer-neuroscience"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Cell","year":2020,"doi":"10.1016/j.cell.2020.03.034","pmid":"32302564","authors":"Monje M, Borniger JC, D'Silva NJ, et al.","paperType":"observational","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-rohaas-til-vs-ipilimumab-nejm-2022","kind":"paper","name":"Rohaas 2022: the first randomised trial of TIL therapy, against ipilimumab, in advanced melanoma","aka":[],"tldr":"In a head-to-head trial, tumour-infiltrating lymphocyte therapy halved the risk of progression compared with ipilimumab in melanoma that had mostly already failed PD-1 blockade.","summary":"This academic phase 3 trial from the Netherlands Cancer Institute and Copenhagen randomised 168 patients with unresectable stage IIIC-IV melanoma, 86% of whom had progressed on anti-PD-1 therapy, to TIL therapy (tumour resection, ex vivo expansion, cyclophosphamide-fludarabine lymphodepletion, infusion and high-dose interleukin-2) or ipilimumab 3 mg/kg. The primary endpoint was progression-free survival. Median PFS was 7.2 versus 3.1 months (hazard ratio 0.50); objective response was 49% versus 21% and complete response 20% versus 7%. Grade 3 or higher adverse events occurred in all TIL patients, driven by chemotherapy and IL-2, and were transient. Median overall survival was 25.8 versus 18.9 months, not statistically significant. It is the first randomised evidence that a cell therapy improves outcomes in a solid tumour.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa2210233"},{"label":"ClinicalTrials.gov NCT02278887","url":"https://clinicaltrials.gov/study/NCT02278887"}],"tags":[],"related":["paper-c-144-01-lifileucel-melanoma-jco-2021"],"cancers":["melanoma"],"sections":[],"technologies":["til-therapy"],"targets":["ctla4"],"drugs":["ipilimumab","aldesleukin","cyclophosphamide","lifileucel"],"companies":[],"institutions":["nki"],"pathways":[],"terms":["tils","pfs"],"trials":[],"people":["john-haanen","ton-schumacher"],"bottlenecks":["b-manufacturing-cell-therapy","b-funding-allocation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/NEJMoa2210233","authors":"Rohaas MW, Borch TH, van den Berg JH, et al.","paperType":"rct","findings":["168 patients with advanced melanoma (86% anti-PD-1 refractory); TIL therapy vs ipilimumab.","Median PFS 7.2 vs 3.1 months; hazard ratio 0.50.","Objective response 49% vs 21%; complete response 20% vs 7%.","Median OS 25.8 vs 18.9 months (hazard ratio 0.83, not significant).","Grade 3 or higher adverse events 100% vs 57%, mostly lymphodepletion- and IL-2-related and resolving before discharge."],"whatItMeans":"This trial supplied the randomised proof that was missing for TIL therapy and showed academic centres can run cell-therapy phase 3 trials without industry. It supports TIL as a standard option after checkpoint inhibitor failure in melanoma and underpinned reimbursement in the Netherlands. The comparator, ipilimumab, is itself only modestly effective in this setting, and overall survival did not differ significantly.","caveats":["Ipilimumab monotherapy is a weak comparator in PD-1-refractory melanoma.","Overall survival benefit was not statistically significant; crossover was allowed.","Severe but transient toxicity requiring inpatient care.","Academic manufacturing at two centres; scalability and reproducibility outside them are unproven."],"changedPractice":true,"participants":168},{"id":"paper-rojas-mrna-neoantigen-vaccine-pancreatic-nature-2023","kind":"paper","name":"Rojas 2023: a personalised mRNA vaccine trained T cells against each patient's pancreatic cancer, and those who responded stayed cancer-free longer","aka":[],"tldr":"Individualised mRNA vaccines encoding up to 20 of each patient's tumour mutations generated strong T-cell responses in half of pancreatic cancer patients after surgery, and those responders had far fewer relapses.","summary":"In this phase 1 study at Memorial Sloan Kettering, 16 patients with resected pancreatic ductal adenocarcinoma received atezolizumab followed by autogene cevumeran, an individualised uridine mRNA-lipoplex vaccine encoding up to 20 predicted neoantigens manufactured within about nine weeks of surgery, and then modified FOLFIRINOX chemotherapy. The vaccine expanded high-magnitude neoantigen-specific T cells in 8 of 16 patients. At a median follow-up of 18 months, responders had not reached median recurrence-free survival whereas non-responders had a median of 13.4 months (hazard ratio 0.08). Vaccine-induced T-cell clones were shown to be newly generated and, in a 2025 follow-up, persisted for years with continued separation of recurrence curves. A randomised phase 2 trial (IMCODE003) in the same setting is under way.","asOf":"2026-09-08","links":[{"label":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Personalized%20RNA%20neoantigen%20vaccines%20stimulate%20T%20cells%20in%20pancreatic%20cancer%20Rojas%20Nature%202023"},{"label":"ClinicalTrials.gov NCT04161755","url":"https://clinicaltrials.gov/study/NCT04161755"}],"tags":[],"related":["vaccine-plus-pd1","paper-sethna-rna-neoantigen-vaccine-long-lived-t-cells-nature-2025"],"cancers":["pancreatic","melanoma"],"sections":[],"technologies":["neoantigen-mrna-vaccine"],"targets":["pd1"],"drugs":["autogene-cevumeran","atezolizumab","intismeran-autogene"],"companies":["biontech","roche-genentech"],"institutions":["mskcc"],"pathways":[],"terms":["neoantigen","tmb"],"trials":["interpath-001"],"people":[],"bottlenecks":["b-immunotherapy-response","b-manufacturing-cell-therapy","b-tme-immunosuppression"],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2023,"doi":"10.1038/s41586-023-06063-y","pmid":"37165196","authors":"Rojas LA, Sethna Z, Soares KC, et al.","paperType":"translational","findings":["16 patients with resected pancreatic cancer; atezolizumab, then individualised mRNA neoantigen vaccine (up to 20 neoantigens), then mFOLFIRINOX.","Vaccine manufactured and delivered within about 9 weeks of surgery in most patients.","High-magnitude neoantigen-specific T-cell responses in 8 of 16 (50%).","Median recurrence-free survival not reached in responders vs 13.4 months in non-responders; hazard ratio 0.08.","Responding T-cell clones were de novo and persisted for up to several years in the 2025 follow-up."],"whatItMeans":"Pancreatic cancer was thought to be immunologically inert because of its low mutation burden; this study showed that with the right vaccine platform its few neoantigens can still be targeted. It is the strongest human evidence so far that personalised cancer vaccines can generate durable, tumour-specific immunity, and it justifies the randomised trials now running in pancreatic cancer and melanoma. Benefit is not yet proven, because responders may simply have had more immunogenic tumours.","caveats":["Tiny, non-randomised study; the association between immune response and recurrence could reflect confounding.","Half the patients did not mount a response, for reasons that are only partly understood (for example, splenectomy).","Manufacturing an individual vaccine within weeks of surgery is expensive and logistically complex.","Clinical benefit awaits the randomised IMCODE003 result."],"changedPractice":false,"participants":16},{"id":"paper-rolapitant-study-3-schwartzberg-lancet-oncol-2015","kind":"paper","name":"Rolapitant for prevention of chemotherapy-induced nausea and vomiting after moderately emetogenic chemotherapy or anthracycline and cyclophosphamide regimens: a randomised, active-controlled, double-blind, phase 3 trial","aka":[],"tldr":"Adding a single rolapitant tablet to the standard two anti-sickness drugs kept 71 percent of patients free of vomiting and rescue medicine in the days after moderately strong chemotherapy, against 62 percent without it.","summary":"Primary publication of rolapitant Study 3 (NCT01500226). A global, randomised, double-blind, active-controlled phase 3 study at 170 cancer centres in 23 countries enrolled patients aged 18 or older who had not previously received moderately or highly emetogenic chemotherapy. Patients were allocated to oral rolapitant 180 mg or matching placebo one to two hours before moderately emetogenic chemotherapy; all received granisetron 2 mg and dexamethasone 20 mg on day 1 and granisetron on days 2 to 3. The primary endpoint was complete response (no emesis or rescue medication) in the delayed phase (more than 24 to 120 hours) in cycle 1, in the modified intention-to-treat population.\n\nBetween 5 March 2012 and 6 September 2013, 1,369 patients were randomised (684 rolapitant, 685 active control); 666 per group were analysed. Complete response in the delayed phase was 475 (71 percent) versus 410 (62 percent); odds ratio 1.6 (95 percent CI 1.2 to 2.0; p = 0.0002). Adverse events were similar between groups, with fatigue, constipation and headache the most frequent treatment-related events; grade 3 to 4 neutropenia in cycle 1 was 5 percent versus 3 percent. No serious adverse event was treatment related.","asOf":"2026-09-24","links":[{"label":"Lancet Oncology 2015","url":"https://doi.org/10.1016/S1470-2045(15)00034-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26272768/"},{"label":"ClinicalTrials.gov NCT01500226","url":"https://clinicaltrials.gov/study/NCT01500226"}],"tags":[],"related":[],"cancers":[],"sections":["supportive-care"],"technologies":[],"targets":[],"drugs":["rolapitant"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["ts-p04834"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2015,"doi":"10.1016/S1470-2045(15)00034-0","pmid":"26272768","authors":"Schwartzberg LS, Modiano MR, Rapoport BL, et al.","paperType":"rct","findings":["Delayed-phase complete response 71 percent with rolapitant vs 62 percent with active control (odds ratio 1.6, 95 percent CI 1.2 to 2.0; p = 0.0002).","1,369 patients randomised; 666 per arm in the modified intention-to-treat efficacy population.","Adverse events similar between arms; grade 3 to 4 neutropenia in cycle 1 5 percent vs 3 percent; no treatment-related serious adverse event."],"whatItMeans":"Together with the two cisplatin studies, this trial supported the September 2015 US approval of rolapitant for delayed nausea and vomiting. Its long half-life means one tablet covers the delayed phase, and unlike aprepitant it does not need a dexamethasone dose adjustment.","caveats":["The active control was granisetron plus dexamethasone with placebo, so the trial tests adding rolapitant, not rolapitant against another NK1 antagonist.","The efficacy population excludes patients treated at sites later found non-compliant with Good Clinical Practice.","Funded by Tesaro; the product is now marketed by TerSera."],"changedPractice":true,"participants":1369},{"id":"paper-van-poznak-j-clin-oncol","kind":"paper","name":"Role of Bone-Modifying Agents in Metastatic Breast Cancer: An American Society of Clinical Oncology-Cancer Care Ontario Focused Guideline Update","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 29035643 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose To update, in collaboration with Cancer Care Ontario (CCO), key recommendations of the American Society of Clinical Oncology (ASCO) guideline on the role of bone-modifying agents (BMAs) in metastatic breast cancer. This focused update addressed the new data on intervals between dosing and the role of BMAs in control of bone pain. Methods A joint ASCO-CCO Update Committee conducted targeted systematic literature reviews to identify relevant studies. Results The Update Committee reviewed three phase III noninferiority trials of dosing intervals, one systematic review and meta-analysis of studies of de-escalation of BMAs, and two randomized trials of BMAs in control of pain secondary to bone metastases. Recommendations Patients with breast cancer who have evidence of bone metastases should be treated with BMAs. Options include denosumab, 120 mg subcutaneously, every 4 weeks; pamidronate, 90 mg intravenously, every 3 to 4 weeks; or zoledronic acid, 4 mg intravenously every 12 weeks or every 3 to 4 weeks. The analgesic effects of BMAs are modest, and they should not be used alone for bone pain. The Update Committee recommends that the current standard of care for supportive care and pain management-analgesia, adjunct therapies, radiotherapy, surgery, systemic anticancer therapy, and referral to supportive care and pain management-be applied. Evidence is insufficient to support the use of one BMA over another. Additional information is available at www.asco.org/breast-cancer-guidelines and www.asco.org/guidelineswiki.\n\nIndexed on Europe PMC as PubMed record 29035643 (DOI 10.1200/jco.2017.75.4614). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2017","url":"https://doi.org/10.1200/jco.2017.75.4614"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29035643/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29035643"}],"tags":["europepmc-ingest"],"related":["bone-modifying-agents"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2017,"doi":"10.1200/jco.2017.75.4614","pmid":"29035643","authors":"Van Poznak C, Somerfield MR, Barlow WE, et al.","paperType":"guideline","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-jak2-polycythaemia-vera-nat-rev-cancer-2007","kind":"paper","name":"Role of JAK2 in the pathogenesis and therapy of myeloproliferative disorders","aka":[],"tldr":"Review on JAK2 in Polycythaemia vera, in Nature Reviews Cancer (2007), one of the most cited Europe PMC records with JAK2 in its title.","summary":"The myeloproliferative disorders polycythaemia vera (PV), essential thombocythaemia (ET), and primary myelofibrosis (PMF) are clonal disorders of multipotent haematopoietic progenitors. The genetic cause of these diseases was not known until 2005, when several independent groups demonstrated that most patients with PV, ET and PMF acquire a single point mutation in the cytoplasmic tyrosine kinase JAK2 (JAK2V617F). These discoveries have changed the landscape for diagnosis and classification of PV, ET and PMF, and show the ability of genomic technologies to identify new molecular targets in human malignancies with pathogenetic, diagnostic and therapeutic significance.\n\nIndexed on Europe PMC as PubMed record 17721432 (DOI 10.1038/nrc2210). Its title names JAK2 and its text names Polycythaemia vera; PubMed types it as a review (Research Support, Non-U.S. Gov't, Review, Research Support, N.I.H., Extramural). It was matched automatically to the idea \"Clearing the JAK2 clone in polycythaemia vera: interferon plus mutant-selective inhibitors as a route to treatment-free remission\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Cancer 2007","url":"https://doi.org/10.1038/nrc2210"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/17721432/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/17721432"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Cancer","year":2007,"doi":"10.1038/nrc2210","pmid":"17721432","authors":"Levine RL, Pardanani A, Tefferi A, et al.","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for JAK2 in Polycythaemia vera, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by JAK2 in the title and Polycythaemia vera in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-gisslinger-lancet-haematol","kind":"paper","name":"Ropeginterferon alfa-2b versus standard therapy for polycythaemia vera (PROUD-PV and CONTINUATION-PV): a randomised, non-inferiority, phase 3 trial and its extension study","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 32014125 and published in The Lancet Haematology; the citing page links this DOI, which is how the record was matched.","summary":"Background: The PROUD-PV and CONTINUATION-PV trials aimed to compare the novel monopegylated interferon ropeginterferon alfa-2b with hydroxyurea, the standard therapy for patients with polycythaemia vera, over 3 years of treatment.\n\nMethods: PROUD-PV and its extension study, CONTINUATION-PV, were phase 3, randomised, controlled, open-label, trials done in 48 clinics in Europe. Patients were eligible if 18 years or older with early stage polycythaemia vera (no history of cytoreductive treatment or less than 3 years of previous hydroxyurea treatment) diagnosed by WHO's 2008 criteria. Patients were randomly assigned 1:1 to ropeginterferon alfa-2b (subcutaneously every 2 weeks, starting at 100 μg) or hydroxyurea (orally starting at 500 mg/day). After 1 year, patients could opt to enter the extension part of the trial, CONTINUATION-PV. The primary endpoint in PROUD-PV was non-inferiority of ropeginterferon alfa-2b versus hydroxyurea regarding complete haematological response with normal spleen size (longitudinal diameter of ≤12 cm for women and ≤13 cm for men) at 12 months; in CONTINUATION-PV, the coprimary endpoints were complete haematological response with normalisation of spleen size and with improved disease burden (ie, splenomegaly, microvascular disturbances, pruritus, and headache). We present the final results of PROUD-PV and an interim analysis at 36 months of the CONTINUATION-PV study (per statistical analysis plan). Analyses for safety and efficacy were per-protocol. The trials were registered on EudraCT, 2012-005259-18 (PROUD-PV) and 2014-001357-17 (CONTINUATION-PV, which is ongoing).\n\nFindings: Patients were recruited from Sept 17, 2013 to March 13, 2015 with 306 enrolled. 257 patients were randomly assigned, 127 were treated in each group (three patients withdrew consent in the hydroxyurea group), and 171 rolled over to the CONTINUATION-PV trial. Median follow-up was 182·1 weeks (IQR 166·3-201·7) in the ropeginterferon alfa-2b and 164·5 weeks (144·4-169·3) in the standard therapy group. In PROUD-PV, 26 (21%) of 122 patients in the ropeginterferon alfa-2b group and 34 (28%) of 123 patients in the standard therapy group met the composite primary endpoint of complete haematological response with normal spleen size. In CONTINUATION-PV, complete haematological response with improved disease burden was met in 50 (53%) of 95 patients in the ropeginterferon alfa-2b group versus 28 (38%) of 74 patients in the hydroxyurea group, p=0·044 at 36 months. Complete haematological response without the spleen criterion in the ropeginterferon alfa-2b group versus standard therapy group were: 53 (43%) of 123 patients versus 57 (46%) of 125 patients, p=0·63 at 12 months (PROUD-PV), and 67 (71%) of 95 patients versus 38 (51%) of 74 patients, p=0·012 at 36 months (CONTINUATION-PV). The most frequently reported grade 3 and grade 4 treatment-related adverse events were increased γ-glutamyltransferase (seven [6%] of 127 patients) and increased alanine aminotransferase (four [3%] of 127 patients) in the ropeginterferon alfa-2b group, and leucopenia (six [5%] of 127 patients) and thrombocytopenia (five [4%] of 127 patients) in the standard therapy group. Treatment-related serious adverse events occurred in three (2%) of 127 patients in the ropeginterferon alfa-2b group and five (4%) of 127 patients in the hydroxyurea group. One treatment-related death was reported in the standard therapy group (acute leukaemia).\n\nInterpretation: In patients with early polycythaemia vera, who predominantly presented without splenomegaly, ropeginterferon alfa-2b was effective in inducing haematological responses; non-inferiority to hydroxyurea regarding haematological response and normal spleen size was not shown at 12 months. However, response to ropeginterferon alfa-2b continued to increase over time with improved responses compared with hydroxyurea at 36 months. Considering the high and durable haematological and molecular responses and its good tolerability, ropeginterferon alfa-2b offers a valuable and safe long-term treatment option with features distinct from hydroxyurea.\n\nFunding: AOP Orphan Pharmaceuticals AG.\n\nIndexed on Europe PMC as PubMed record 32014125 (DOI 10.1016/s2352-3026(19)30236-4). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Haematol 2020","url":"https://doi.org/10.1016/s2352-3026(19)30236-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32014125/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32014125"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["proud-pv"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-haematology"],"dependsOn":[],"notes":[],"journal":"The Lancet Haematology","year":2020,"doi":"10.1016/s2352-3026(19)30236-4","pmid":"32014125","authors":"Gisslinger H, Klade C, Georgiev P, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-bergethon-ros1-rearrangements-lung-jco-2012","kind":"paper","name":"ROS1 rearrangements define a unique molecular class of lung cancers","aka":[],"tldr":"Screening more than a thousand lung cancers found a rearranged ROS1 gene in about one in sixty, in younger patients who had mostly never smoked, and the first patient treated with a matched pill nearly cleared her cancer.","summary":"A fluorescence in situ hybridisation assay was used to screen 1,073 patients with non-small-cell lung cancer, and rearrangement status was correlated with clinical characteristics, overall survival and ALK status. Eighteen tumours, 1.7%, were ROS1-rearranged and 31, 2.9%, were ALK-rearranged. Compared with the ROS1-negative group, ROS1-rearranged patients were significantly younger and more likely to be never smokers, all tumours were adenocarcinomas with a tendency towards higher grade, and overall survival did not differ. A ROS1-rearranged cell line and cells transfected with CD74-ROS1 were sensitive to crizotinib, and one patient treated in an expanded phase 1 cohort showed tumour shrinkage approaching a complete response.","asOf":"2026-09-25","links":[{"label":"Bergethon et al., J Clin Oncol 2012: ROS1 rearrangements define a unique molecular class of lung cancers (1,073 screened)","url":"https://doi.org/10.1200/JCO.2011.35.6345"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22215748/"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":["cytogenetics-fish","kinase-inhibitors"],"targets":["ros1","alk"],"drugs":["crizotinib"],"companies":[],"institutions":["mgh"],"pathways":["rtk-activation"],"terms":["gene-fusion","driver-mutation","fish"],"trials":[],"people":["alice-shaw"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2012,"doi":"10.1200/JCO.2011.35.6345","pmid":"22215748","authors":"Bergethon K, Shaw AT, Ou SH, et al.","paperType":"translational","findings":["ROS1 rearrangement in 18 of 1,073 lung cancers, 1.7%, against ALK in 31, 2.9%.","Patients were younger and more often never smokers; all tumours were adenocarcinomas.","Overall survival did not differ by ROS1 status.","Laboratory and first-patient evidence of crizotinib sensitivity."],"whatItMeans":"It defined a class of lung cancer by a rearrangement and a clinical phenotype at the same time, and it is the reason ROS1 testing is recommended for every patient with adenocarcinoma rather than only for those with an obvious risk profile.","caveats":["Eighteen positive cases, so the clinical description rests on few patients.","Fluorescence in situ hybridisation does not identify the fusion partner, which matters for inhibitor choice.","The treatment evidence at the time was a single patient."],"changedPractice":true,"participants":1073},{"id":"paper-rosella-relacorilant-lancet-2025","kind":"paper","name":"ROSELLA: relacorilant plus nab-paclitaxel in platinum-resistant ovarian cancer","aka":[],"tldr":"Adding relacorilant, a drug that blocks the cortisol receptor and thereby restores chemotherapy sensitivity, to nab-paclitaxel lengthened progression-free and overall survival in platinum-resistant ovarian cancer regardless of any biomarker.","summary":"Phase 3 trial of 381 patients with platinum-resistant ovarian cancer and one to three prior lines randomised to intermittent relacorilant plus nab-paclitaxel or nab-paclitaxel alone.\n\nMedian progression-free survival was 6.54 versus 5.52 months (hazard ratio 0.70) and interim median overall survival 15.97 versus 11.50 months (hazard ratio 0.69), with a similar safety profile between arms.","asOf":"2026-09-17","links":[{"label":"Lancet 2025","url":"https://doi.org/10.1016/S0140-6736(25)01040-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40473448/"}],"tags":[],"related":[],"cancers":["platinum-resistant-ovarian-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["relacorilant"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["rosella"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2025,"doi":"10.1016/S0140-6736(25)01040-2","pmid":"40473448","authors":"Olawaiye AB, Gladieff L, O'Malley DM, et al.","paperType":"rct","findings":["Median progression-free survival 6.54 vs 5.52 months; hazard ratio 0.70.","Interim median overall survival 15.97 vs 11.50 months; hazard ratio 0.69."],"whatItMeans":"Relacorilant with nab-paclitaxel is a new option for platinum-resistant disease that does not depend on folate receptor status, with regulatory review following the trial.","caveats":["Open-label design.","Overall survival analysis was interim."],"changedPractice":true,"participants":381},{"id":"paper-rosewood-zanubrutinib-obinutuzumab-follicular-jco-2023","kind":"paper","name":"ROSEWOOD: a phase II randomized study of zanubrutinib plus obinutuzumab versus obinutuzumab monotherapy in patients with relapsed or refractory follicular lymphoma","aka":["ROSEWOOD","Zinzani 2023"],"tldr":"Adding a targeted tablet to an antibody roughly halved the risk of progression in follicular lymphoma that had already returned twice.","summary":"A randomised phase 2 study in patients with relapsed or refractory follicular lymphoma who had received two or more lines of therapy including an anti-CD20 antibody and an alkylating agent. 217 patients were randomised 2 to 1 to zanubrutinib with obinutuzumab (145) or obinutuzumab alone (72). The primary endpoint was overall response rate by independent central review.\n\nAt a median study follow-up of 20.2 months the primary endpoint was met: overall response rate was 69 per cent with the combination against 46 per cent with obinutuzumab alone (p = 0.001). The complete response rate was 39 against 19 per cent, the 18-month duration of response rate 69 against 42 per cent, and median progression-free survival 28.0 against 10.4 months (hazard ratio 0.50, 95 per cent confidence interval 0.33 to 0.75).","asOf":"2026-10-01","links":[{"label":"Journal of Clinical Oncology 2023","url":"https://doi.org/10.1200/JCO.23.00775"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37506346/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37506346"}],"tags":["lymphoma-evidence"],"related":["lymphoma-roadmap"],"cancers":["follicular-lymphoma","non-hodgkin-lymphoma"],"sections":["targeted-therapy","immunotherapy"],"technologies":[],"targets":["btk","cd20"],"drugs":["zanubrutinib","obinutuzumab"],"companies":[],"institutions":[],"pathways":["bcr-signalling"],"terms":["orr","complete-response"],"trials":["rosewood"],"people":[],"bottlenecks":["b-combination-space"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2023,"doi":"10.1200/JCO.23.00775","pmid":"37506346","authors":"Zinzani PL, Mayer J, Flowers CR, et al.","paperType":"rct","findings":["Overall response rate by independent central review was 69 per cent with zanubrutinib and obinutuzumab against 46 per cent with obinutuzumab alone (p = 0.001).","Complete response rate was 39 per cent against 19 per cent.","The 18-month duration of response rate was 69 per cent against 42 per cent.","Median progression-free survival was 28.0 months against 10.4 months (hazard ratio 0.50, 95 per cent confidence interval 0.33 to 0.75)."],"whatItMeans":"Evidence that the B-cell receptor pathway is worth attacking in follicular lymphoma when a Bruton tyrosine kinase inhibitor is paired with a type II CD20 antibody, after single-agent inhibitors had disappointed in this disease.","caveats":["A randomised phase 2, not a phase 3: the result establishes activity rather than a position in a treatment sequence.","Obinutuzumab monotherapy is not a standard comparator in this setting, which inflates the apparent difference.","Median follow-up of 20.2 months, with no overall survival result."],"changedPractice":true,"participants":217},{"id":"paper-rtog-91-11-forastiere-nejm-2003","kind":"paper","name":"RTOG 91-11: concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer","aka":[],"tldr":"Giving cisplatin at the same time as radiotherapy preserved the larynx in more patients with advanced laryngeal cancer than either induction chemotherapy followed by radiotherapy or radiotherapy alone, defining the standard larynx-preserving treatment.","summary":"Phase 3 trial of 547 patients with stage III to IV laryngeal cancer randomised to induction cisplatin-fluorouracil followed by radiotherapy, concurrent cisplatin with radiotherapy, or radiotherapy alone.\n\nLaryngectomy-free survival was similar between the chemotherapy arms, but laryngeal preservation at two years was 88 percent with concurrent chemoradiation against 75 percent with induction and 70 percent with radiotherapy alone, and locoregional control was best with concurrent treatment; overall survival was similar in all arms.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2003","url":"https://doi.org/10.1056/NEJMoa031317"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/14645636/"}],"tags":[],"related":[],"cancers":["laryngeal-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["rtog-91-11"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2003,"doi":"10.1056/NEJMoa031317","pmid":"14645636","authors":"Forastiere AA, Goepfert H, Maor M, et al.","paperType":"rct","findings":["Two-year laryngeal preservation 88 percent (concurrent) vs 75 percent (induction) vs 70 percent (radiotherapy alone).","Overall survival similar across arms."],"whatItMeans":"Concurrent cisplatin chemoradiation is the standard larynx-preserving treatment for advanced laryngeal cancer where the larynx is still functioning; laryngectomy is reserved for extensive disease or salvage.","caveats":["Long-term follow-up showed more non-cancer deaths in the concurrent arm.","T4 tumours with cartilage invasion were excluded."],"changedPractice":true,"participants":547},{"id":"paper-rtog-9402-cairncross-jco-2013","kind":"paper","name":"RTOG 9402: PCV chemotherapy before radiotherapy for anaplastic oligodendroglioma, long-term results","aka":[],"tldr":"Long follow-up of this trial showed that adding PCV chemotherapy to radiotherapy roughly doubled survival, from about seven to fourteen years, in anaplastic oligodendroglioma with loss of chromosomes 1p and 19q, while tumours without the codeletion gained nothing.","summary":"Phase 3 trial of 291 patients with anaplastic oligodendroglioma or oligoastrocytoma randomised to intensive PCV followed by radiotherapy or radiotherapy alone, reported at a median follow-up of 11.3 years.\n\nOverall survival did not differ in the whole cohort, but in 1p/19q-codeleted tumours median survival was 14.7 years with PCV against 7.3 years without (hazard ratio 0.59), while non-codeleted tumours had a median of 2.6 versus 2.7 years.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2013","url":"https://doi.org/10.1200/JCO.2012.43.2674"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23071247/"}],"tags":[],"related":[],"cancers":["oligodendroglioma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["rtog-9402"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2013,"doi":"10.1200/JCO.2012.43.2674","pmid":"23071247","authors":"Cairncross G, Wang M, Shaw E, et al.","paperType":"rct","findings":["Codeleted tumours: median overall survival 14.7 vs 7.3 years; hazard ratio 0.59.","Non-codeleted tumours: no benefit (2.6 vs 2.7 years)."],"whatItMeans":"1p/19q codeletion is a predictive marker: codeleted oligodendroglioma is treated with radiotherapy plus PCV, and the finding helped make the codeletion part of the tumour's definition.","caveats":["Retrospective molecular subgrouping of a trial designed before codeletion was known to matter.","Intensive PCV schedule was poorly tolerated."],"changedPractice":true,"participants":291},{"id":"paper-rtog-9408-short-term-adt-jones-nejm-2011","kind":"paper","name":"RTOG 9408: radiotherapy with short-term androgen deprivation for localised prostate cancer","aka":[],"tldr":"Four months of hormone therapy around radiotherapy improved survival in men with early prostate cancer, with the benefit confined to intermediate-risk disease, so short-course androgen deprivation became standard for that group.","summary":"Phase 3 trial of 1,979 men with T1b to T2b prostate cancer and PSA of 20 or less randomised to radiotherapy alone or with four months of androgen deprivation beginning two months before radiotherapy.\n\nTen-year overall survival was 62 versus 57 percent and prostate cancer mortality 4 versus 8 percent with androgen deprivation; the benefit was seen in intermediate-risk men (ten-year survival 61 versus 54 percent) and not in low-risk men.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2011","url":"https://doi.org/10.1056/NEJMoa1012348"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21751904/"}],"tags":[],"related":[],"cancers":["prostate-intermediate-risk"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2011,"doi":"10.1056/NEJMoa1012348","pmid":"21751904","authors":"Jones CU, Hunt D, McGowan DG, et al.","paperType":"rct","findings":["Ten-year overall survival 62 percent vs 57 percent.","Intermediate risk: ten-year overall survival 61 percent vs 54 percent; no benefit in low risk."],"whatItMeans":"Short-term androgen deprivation with radiotherapy is standard for unfavourable intermediate-risk prostate cancer; low-risk men do not need it.","caveats":["Radiotherapy dose (66.6 Gy) was lower than current practice; whether hormones are needed with dose-escalated radiotherapy is debated."],"changedPractice":true,"participants":1979},{"id":"paper-cooper-rtog-9501-nejm-2004","kind":"paper","name":"RTOG 9501: postoperative concurrent radiotherapy and chemotherapy for high-risk head and neck squamous cell carcinoma","aka":[],"tldr":"In this American trial, adding cisplatin to postoperative radiotherapy for high-risk head and neck cancer improved local control and disease-free survival but not overall survival, and doubled severe toxicity.","summary":"Phase 3 trial of 459 patients with resected high-risk head and neck squamous cell carcinoma (two or more involved nodes, extracapsular extension or positive margins) randomised to postoperative radiotherapy alone or with concurrent cisplatin.\n\nLocoregional control at two years was 82 versus 72 percent (hazard ratio 0.61) and disease-free survival was improved (hazard ratio 0.78), but overall survival did not differ significantly; grade 3 or worse adverse events were 77 versus 34 percent. Long-term follow-up confirmed benefit only in patients with extracapsular extension or positive margins.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2004","url":"https://doi.org/10.1056/NEJMoa032646"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/15128893/"}],"tags":[],"related":[],"cancers":["hpv-negative-head-and-neck-cancer","oral-cavity-cancer","buccal-mucosa-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2004,"doi":"10.1056/NEJMoa032646","pmid":"15128893","authors":"Cooper JS, Pajak TF, Forastiere AA, et al.","paperType":"rct","findings":["Two-year locoregional control 82 percent vs 72 percent.","Grade 3 or greater adverse events 77 percent vs 34 percent."],"whatItMeans":"With EORTC 22931, this trial defines who receives postoperative chemoradiation: patients with extranodal extension or positive margins, not those whose only risk factor is multiple nodes.","caveats":["No overall survival benefit in the whole population.","Different high-risk definitions from the EORTC trial."],"changedPractice":true,"participants":459},{"id":"paper-rtog-9802-buckner-nejm-2016","kind":"paper","name":"RTOG 9802: radiation plus procarbazine, lomustine and vincristine in high-risk low-grade glioma","aka":[],"tldr":"Adding PCV chemotherapy after radiotherapy for grade 2 glioma in adults who were over 40 or had residual tumour lengthened median survival from about eight to over thirteen years, one of the largest gains ever seen in neuro-oncology.","summary":"Phase 3 trial of 251 patients with grade 2 astrocytoma, oligodendroglioma or oligoastrocytoma who were either aged 40 or over or had undergone subtotal resection, randomised to radiotherapy alone or radiotherapy followed by six cycles of procarbazine, lomustine and vincristine (PCV).\n\nMedian overall survival was 13.3 years with PCV against 7.8 years with radiotherapy alone (hazard ratio 0.59), with benefit across histologies in later molecular analyses, strongest in IDH-mutant tumours.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2016","url":"https://doi.org/10.1056/NEJMoa1500925"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27050206/"}],"tags":[],"related":[],"cancers":["idh-mutant-astrocytoma","oligodendroglioma"],"sections":[],"technologies":[],"targets":[],"drugs":["procarbazine","vincristine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["jan-buckner"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2016,"doi":"10.1056/NEJMoa1500925","pmid":"27050206","authors":"Buckner JC, Shaw EG, Pugh SL, et al.","paperType":"rct","findings":["Median overall survival 13.3 vs 7.8 years; hazard ratio for death 0.59.","Ten-year progression-free survival 51 percent vs 21 percent."],"whatItMeans":"Radiotherapy followed by PCV is the standard for high-risk grade 2 IDH-mutant glioma; whether temozolomide can replace PCV, and whether vorasidenib can defer both, are the current questions.","caveats":["Small trial that took two decades to report.","PCV toxicity limits completion of all six cycles."],"changedPractice":true,"participants":251},{"id":"paper-ruby-nejm-2023","kind":"paper","name":"RUBY: dostarlimab with chemotherapy for advanced or recurrent endometrial cancer","aka":[],"tldr":"Adding the PD-1 antibody dostarlimab to first-line chemotherapy for advanced endometrial cancer cut progression by 72% in tumours with defective mismatch repair and by about a third overall, and later improved survival.","summary":"Double-blind, placebo-controlled phase 3 trial of 494 patients with primary advanced (stage III-IV) or first recurrent endometrial cancer randomised to dostarlimab or placebo with carboplatin-paclitaxel for six cycles, then dostarlimab or placebo maintenance for up to three years. Primary endpoints were PFS in the dMMR/MSI-high population and in the overall population, and OS.\n\nIn dMMR tumours (about 24% of patients), 24-month PFS was 61.4% vs 15.7% (HR 0.28); overall, 36.1% vs 18.1% (HR 0.64). Overall survival was improved in the whole population (HR 0.69 in the 2024 analysis). Together with NRG-GY018 (pembrolizumab), it made chemo-immunotherapy the first-line standard for advanced endometrial cancer and mismatch repair testing routine.","asOf":"2026-09-08","links":[{"label":"NEJM 2023","url":"https://doi.org/10.1056/NEJMoa2216334"},{"label":"ClinicalTrials.gov NCT03981796","url":"https://clinicaltrials.gov/study/NCT03981796"}],"tags":[],"related":[],"cancers":["endometrial"],"sections":[],"technologies":["checkpoint-inhibitor","cytotoxic-chemotherapy","histopathology-ihc"],"targets":["pd1"],"drugs":["dostarlimab","carboplatin","paclitaxel"],"companies":["gsk"],"institutions":[],"pathways":[],"terms":["msi","pfs","os","first-line"],"trials":[],"people":[],"bottlenecks":["b-immunotherapy-response","b-biomarker-validation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/NEJMoa2216334","authors":"Mirza MR, Chase DM, Slomovitz BM, et al.","paperType":"rct","findings":["dMMR/MSI-high: 24-month PFS 61.4% vs 15.7%; HR 0.28 (95% CI 0.16-0.50).","Overall population: 24-month PFS 36.1% vs 18.1%; HR 0.64 (95% CI 0.51-0.80).","Overall survival (Annals of Oncology 2024): HR 0.69 in the overall population; HR 0.32 in dMMR.","Mismatch-repair-proficient tumours had a smaller benefit (PFS HR about 0.76), concentrated in TP53-mutated and PD-L1-positive subgroups in exploratory analyses.","Grade 3 or higher adverse events 70.5% vs 59.8%; immune-related events, mainly hypothyroidism and rash, were more frequent with dostarlimab."],"whatItMeans":"Women with newly diagnosed advanced or recurrent endometrial cancer should receive a PD-1 antibody (dostarlimab or pembrolizumab) with their chemotherapy, and mismatch repair testing is now essential because women with dMMR tumours gain a very large and durable benefit. The gain in mismatch-repair-proficient tumours is real but smaller, and molecular classification (POLE, p53, MMR) is increasingly used to decide who benefits most.","caveats":["The dMMR benefit dominates; the pMMR benefit is modest and debated for the p53-wild-type, non-specific-molecular-profile subgroup.","Up to three years of maintenance immunotherapy adds cost and cumulative immune toxicity.","Recurrent disease after prior adjuvant chemotherapy was included but patients with prior immunotherapy were not.","The parallel DUO-E trial suggests adding olaparib may help pMMR tumours, but the optimal combination is unsettled."],"changedPractice":true,"participants":494},{"id":"paper-russell-mv-nis-myeloma-mayo-2014","kind":"paper","name":"Russell 2014: a measles virus given into the vein put one patient's myeloma into complete remission","aka":[],"tldr":"Two people with drug-resistant myeloma were given an enormous dose of engineered measles virus into a vein; both responded and one went into a lasting complete remission.","summary":"MV-NIS is an engineered measles virus that is selectively destructive to myeloma plasma cells and carries the sodium iodide symporter gene, so that where the virus is replicating can be imaged non-invasively with radioiodine. Two measles-seronegative patients with relapsing, drug-refractory myeloma and multiple glucose-avid plasmacytomas were given a single intravenous infusion of 10^11 tissue culture infectious doses.\n\nBoth responded, with reduction in M protein and resolution of bone marrow plasmacytosis, and one had a durable complete remission at all disease sites. Symporter-mediated radioiodine uptake in virus-infected plasmacytomas documented that the virus had reached and was replicating in the tumours. Toxicities resolved within the first week.\n\nThe two patients were selected for being measles-seronegative, which almost nobody is, and the dose is at the edge of what can be manufactured. That is the paper's real content: proof that intravenous oncolytic virotherapy can work, and a demonstration of exactly why it usually cannot.","asOf":"2026-09-25","links":[{"label":"Mayo Clin Proc 2014","url":"https://doi.org/10.1016/j.mayocp.2014.04.003"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24835528/"}],"tags":[],"related":[],"cancers":["multiple-myeloma"],"sections":["immunotherapy"],"technologies":["oncolytic-virus"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["stephen-russell","evanthia-galanis"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Mayo Clinic Proceedings","year":2014,"doi":"10.1016/j.mayocp.2014.04.003","pmid":"24835528","authors":"Russell SJ, Federspiel MJ, Peng KW, et al.","paperType":"translational","findings":["Two measles-seronegative patients with relapsing drug-refractory myeloma received a single intravenous infusion of 10^11 tissue culture infectious doses of MV-NIS.","Both responded with reduction in M protein and resolution of bone marrow plasmacytosis; one had a durable complete remission at all disease sites.","Sodium iodide symporter-mediated radioiodine imaging documented virus replication inside the plasmacytomas, confirming tumour targeting.","Toxicities resolved within the first week after therapy."],"whatItMeans":"This is the case most often cited to argue that oncolytic viruses can cure. It should be cited with its conditions: two patients, both chosen because they had no pre-existing measles antibodies, and a dose so large that manufacturing it is itself a research problem. It proves the biology is real and simultaneously explains why the approach has not generalised.","caveats":["Two patients, one durable remission. This is a case report, not evidence of efficacy.","Both patients were measles-seronegative, which excludes nearly everyone vaccinated or previously infected; pre-existing neutralising antibody is the main barrier to intravenous delivery.","The dose, 10^11 infectious units, is at the limit of what current manufacturing can supply.","Later trials of MV-NIS in larger, unselected populations have not reproduced this result."],"participants":2},{"id":"paper-russell-peng-bell-oncolytic-virotherapy-natbiotech-2012","kind":"paper","name":"Russell, Peng and Bell 2012: the field states its own problems","aka":[],"tldr":"The review that set the modern agenda for cancer-killing viruses, and named the four things that had to be solved.","summary":"Russell, Peng and Bell review oncolytic virotherapy as replication-competent viruses used to destroy cancers. They summarise preclinical proof of feasibility for a single-shot cure, drugs that accelerate spread of virus within a tumour, strategies to maximise the immunotherapeutic action of the virus, and clinical confirmation of a critical concentration of virus in the blood below which vascular delivery and intratumoural replication do not happen.\n\nThe value of the paper is that it states the field's problems rather than its promise: choosing between a proliferating number of platforms and engineered derivatives, transiently suppressing and then unleashing the immune system so that both virus spread and antitumour immunity are maximised, building preclinical models that mean something, and manufacturing virus at yields orders of magnitude higher than were then possible. Every one of those four remains open.","asOf":"2026-09-25","links":[{"label":"Nat Biotechnol 2012","url":"https://doi.org/10.1038/nbt.2287"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22781695/"}],"tags":[],"related":[],"cancers":[],"sections":["immunotherapy"],"technologies":["oncolytic-virus"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["stephen-russell","john-bell"],"bottlenecks":[],"keyPapers":[],"journals":["nature-biotechnology"],"dependsOn":[],"notes":[],"journal":"Nature Biotechnology","year":2012,"doi":"10.1038/nbt.2287","pmid":"22781695","authors":"Russell SJ, Peng KW, Bell JC","paperType":"review","findings":["Vascular delivery and intratumoural replication depend on exceeding a threshold concentration of virus in the blood, confirmed clinically.","The immune response has to be suppressed transiently to let the virus spread, then unleashed to produce antitumour immunity; the two requirements conflict.","Manufacturing yields needed to rise by orders of magnitude for intravenous dosing to be practical.","The number of oncolytic platforms and engineered derivatives had already outgrown the field's ability to test them properly."],"whatItMeans":"Read against what happened next, this review is a fair scorecard. The immune timing problem, the delivery threshold and the manufacturing yield are still the reasons most programmes fail, and the proliferation of platforms the authors warned about is still the reason the field has many products and few randomised wins.","caveats":["A review, so the numbers in it belong to the studies it cites rather than to this paper.","Written before the 2015 approval of talimogene laherparepvec and before the randomised failures that followed, so its optimism about combination with checkpoint blockade has not been borne out."]},{"id":"paper-harrison-j-clin-oncol","kind":"paper","name":"Ruxolitinib Versus Best Available Therapy for Polycythemia Vera Intolerant or Resistant to Hydroxycarbamide in a Randomized Trial","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 37126762 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: Polycythemia vera (PV) is characterized by JAK/STAT activation, thrombotic/hemorrhagic events, systemic symptoms, and disease transformation. In high-risk PV, ruxolitinib controls blood counts and improves symptoms.\n\nPatients and methods: MAJIC-PV is a randomized phase II trial of ruxolitinib versus best available therapy (BAT) in patients resistant/intolerant to hydroxycarbamide (HC-INT/RES). Primary outcome was complete response (CR) within 1 year. Secondary outcomes included duration of response, event-free survival (EFS), symptom, and molecular response.\n\nResults: One hundred eighty patients were randomly assigned. CR was achieved in 40 (43%) patients on ruxolitinib versus 23 (26%) on BAT (odds ratio, 2.12; 90% CI, 1.25 to 3.60; P =.02). Duration of CR was superior for ruxolitinib (hazard ratio [HR], 0.38; 95% CI, 0.24 to 0.61; P <.001). Symptom responses were better with ruxolitinib and durable. EFS (major thrombosis, hemorrhage, transformation, and death) was superior for patients attaining CR within 1 year (HR, 0.41; 95% CI, 0.21 to 0.78; P =.01); and those on ruxolitinib (HR, 0.58; 95% CI, 0.35 to 0.94; P =.03). Serial analysis of JAK2 V617F variant allele fraction revealed molecular response was more frequent with ruxolitinib and was associated with improved outcomes (progression-free survival [PFS] P =.001, EFS P =.001, overall survival P =.01) and clearance of JAK2 V617F stem/progenitor cells. ASXL 1 mutations predicted for adverse EFS (HR, 3.02; 95% CI, 1.47 to 6.17; P =.003). The safety profile of ruxolitinib was as previously reported.\n\nConclusion: The MAJIC-PV study demonstrates ruxolitinib treatment benefits HC-INT/RES PV patients with superior CR, and EFS as well as molecular response; importantly also demonstrating for the first time, to our knowledge, that molecular response is linked to EFS, PFS, and OS.\n\nIndexed on Europe PMC as PubMed record 37126762 (DOI 10.1200/jco.22.01935). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2023","url":"https://doi.org/10.1200/jco.22.01935"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37126762/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37126762"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["majic-pv"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2023,"doi":"10.1200/jco.22.01935","pmid":"37126762","authors":"Harrison CN, Nangalia J, Boucher R, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-zeidan-lancet-haematol","kind":"paper","name":"Sabatolimab plus hypomethylating agents in previously untreated patients with higher-risk myelodysplastic syndromes (STIMULUS-MDS1): a randomised, double-blind, placebo-controlled, phase 2 trial","aka":[],"tldr":"Paper cited by one target page, indexed on Europe PMC as PubMed record 38065203 and published in The Lancet Haematology; the citing page links this DOI, which is how the record was matched.","summary":"Background: Sabatolimab is an immunotherapy targeting T-cell immunoglobulin domain and mucin domain-3 (TIM-3), an immuno-myeloid regulator expressed on immune cells and leukaemic stem cells. In this trial, we compared the efficacy and safety of sabatolimab plus hypomethylating agent with placebo plus hypomethylating agents in previously untreated patients with higher-risk myelodysplastic syndromes.\n\nMethods: STIMULUS-MDS1 was a multicentre, randomised, double-blind, placebo-controlled, phase 2 study done at 54 investigational sites in 17 countries. Adult patients (aged ≥18 years) with intermediate-risk, high-risk, and very high-risk myelodysplastic syndromes (according to Revised International Prognostic Scoring System criteria) who had not received previous treatment were included. Patients were randomly assigned (1:1) to intravenous sabatolimab (400 mg on day 8 and 22) or placebo plus a hypomethylating agent (intravenous decitabine 20 mg/m 2 on day 1-5 or intravenous or subcutaneous azacitidine 75 mg/m 2 on day 1-7 or day 1-5 and day 8 and 9) every 28 days until treatment discontinuation. The two primary endpoints were complete response rate and progression-free survival, assessed in the full analysis set, which included all randomly assigned patients. Complete response was analysed, as prespecified, 7 months after the last patient was randomly assigned. All other analyses presented, including progression-free survival, were done at the final data cutoff prespecified via a protocol amendment on Sept 2, 2021. Safety was assessed in in all patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT03946670, and is ongoing.\n\nFindings: Between July 29, 2019, and Aug 10, 2020, 127 patients were randomly assigned to sabatolimab plus a hypomethylating agent group (sabatolimab group; n=65) or placebo plus a hypomethylating agent (placebo group; n=62). The median age of participants was 73 years (IQR 69-77), of whom 86 (68%) of 127 patients were male and 77 (61%) were White. The primary endpoints were not met. Complete response (cutoff date of March 10, 2021) was achieved in 14 (22%; 95% CI 12·3-33·5) of 65 patients in the sabatolimab group vs 11 (18%; 9·2-29·5) of 62 patients in the placebo group (p=0·77). At the cutoff date of the final analysis (March 1, 2022), median follow-up for progression-free survival was 17·8 months (IQR 16·6-19·4) in the sabatolimab group and 19·2 months (17·7-22·3) in the placebo group, and the median progression-free survival was 11·1 months (95% CI 7·6-17·6) in the sabatolimab group vs 8·5 months (6·9-11·3) in the placebo group (hazard ratio 0·75 [95% CI 0·48-1·17]; p=0·1022). The most common adverse events of any grade were neutropenia (35 [56%] of 62 patients in the sabatolimab group vs 43 [68%] of 63 patients in the placebo group), thrombocytopenia (30 [48%] vs 32 [51%]), constipation (29 [47%] vs 24 [38%]), diarrhoea (27 [44%] vs 14 [22%]), anaemia (22 [35%] vs 34 [54%]), febrile neutropenia (22 [35%] vs 15 [24%]), and leukopenia (15 [24%] vs 20 [32%]). One patient developed a serious potential treatment-related immune-mediated adverse event in the sabatolimab group. There was one treatment-related death in the sabatolimab group due to pneumonitis.\n\nInterpretation: The addition of sabatolimab to hypomethylating agents in this study did not result in a significant improvement in complete response rates or progression-free survival. Sabatolimab had a manageable safety in most patients with higher-risk myelodysplastic syndromes. A randomised phase 3 trial is ongoing to assess the potential benefit of sabatolimab plus azacitidine on overall survival in this setting.\n\nFunding: Novartis Pharmaceuticals.\n\nIndexed on Europe PMC as PubMed record 38065203 (DOI 10.1016/s2352-3026(23)00333-2). Matched by DOI alone: one target page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Haematol 2024","url":"https://doi.org/10.1016/s2352-3026(23)00333-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38065203/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38065203"}],"tags":["europepmc-ingest"],"related":["tim3"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-haematology"],"dependsOn":[],"notes":[],"journal":"The Lancet Haematology","year":2024,"doi":"10.1016/s2352-3026(23)00333-2","pmid":"38065203","authors":"Zeidan AM, Ando K, Rauzy O, et al.","paperType":"rct","findings":[],"whatItMeans":"One target page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-trastuzumab-deruxtecan-tnbc-esmo-open-2021","kind":"paper","name":"Sacituzumab govitecan and trastuzumab deruxtecan: two new antibody-drug conjugates in the breast cancer treatment landscape","aka":[],"tldr":"Review on Trastuzumab deruxtecan in Triple-negative breast cancer, in ESMO Open (2021), one of the most cited Europe PMC records with Trastuzumab deruxtecan in its title.","summary":"Background: Two new antibody-drug conjugates (ADCs) containing a topoisomerase I inhibitor payload have recently emerged in the breast cancer (BC) treatment landscape. Sacituzumab govitecan-hziy (SG) is a first-in-class anti-trophoblast cell-surface antigen 2 ADC approved for pretreated metastatic triple-negative breast cancer (mTNBC) and trastuzumab deruxtecan (T-DXd) gained approval for human epidermal growth factor receptor-2 (HER2)-positive advanced BC (aBC). We aim to provide a contemporary review and the current clinical trial landscape of SG and T-DXd in BC.\n\nMaterials and methods: We conducted a literature search from Medline database through PubMed, major conference proceedings [abstracts from European Society for Medical Oncology (Breast) Congress, American Society of Clinical Oncology annual meeting, San Antonio Breast Cancer Symposium] and ClinicalTrials.gov with search terms 'sacituzumab govitecan', 'IMMU-132', 'trastuzumab deruxtecan' and 'DS-8201a' up to 21 March 2021.\n\nResults: We assessed 293 records for eligibility, of which 153 were included in this review after screening and exclusion. For SG, efficacy and safety data are available from a phase III trial in pretreated mTNBC and from a phase I/II basket study in mTNBC and hormone receptor-positive/HER2-negative aBC. Thirteen trials with pending primary analysis are ongoing with SG as single agent or in combination, of which 11 are enrolling (2/11 in the early setting). For T-DXd, efficacy/safety data are available as single agent in pretreated HER2-positive (phase Ib and phase II) and in HER2-low aBC (phase Ib), and in combination with nivolumab in HER2-low/positive aBC (phase Ib). Of 23 ongoing trials with T-DXd, 12 are open for enrollment and 3 phase III trials have completed recruitment. The distinct safety profiles of both drugs and their management are discussed.\n\nConclusion: Given their robust single-agent activity, SG and T-DXd are expected to substantially impact treatment standards, both in and far beyond the currently approved indications. Several trials are investigating new treatment settings for both drugs, including a transition to earlier lines and combinations with other anticancer treatments such as immune checkpoint inhibitors.\n\nIndexed on Europe PMC as PubMed record 34225076 (DOI 10.1016/j.esmoop.2021.100204). Its title names Trastuzumab deruxtecan and its text names Triple-negative breast cancer; PubMed types it as a review (review-article, Review). It was matched automatically to the idea \"AI quantification of HER2-low and HER2-ultralow\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"ESMO Open 2021","url":"https://doi.org/10.1016/j.esmoop.2021.100204"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34225076/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34225076"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["esmo-open"],"dependsOn":[],"notes":[],"journal":"ESMO Open","year":2021,"doi":"10.1016/j.esmoop.2021.100204","pmid":"34225076","authors":"Adams E, Wildiers H, Neven P, et al.","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for Trastuzumab deruxtecan in Triple-negative breast cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Trastuzumab deruxtecan in the title and Triple-negative breast cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-ascent-03-n-engl-j-med-2025","kind":"paper","name":"Sacituzumab Govitecan in Untreated, Advanced Triple-Negative Breast Cancer","aka":[],"tldr":"Published report from the ASCENT-03 trial registered as NCT05382299, in New England Journal of Medicine (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Patients with previously untreated, locally advanced, unresectable or metastatic triple-negative breast cancer who are not candidates for inhibitors of programmed cell death protein 1 (PD-1) or programmed death ligand 1 (PD-L1) have limited treatment options.\n\nMethods: In this international, phase 3, open-label, randomized trial, we enrolled patients with previously untreated, advanced triple-negative breast cancer who were not candidates for PD-1 or PD-L1 inhibitors owing to previous use or coexisting conditions. Patients had either PD-L1-negative tumors with a combined positive score (CPS; the number of PD-L1-staining tumor cells, lymphocytes, and macrophages divided by the total number of viable tumor cells, multiplied by 100) of less than 10 or PD-L1-positive tumors with a CPS of 10 or higher and were assigned in a 1:1 ratio to receive sacituzumab govitecan or chemotherapy (paclitaxel, nanoparticle albumin-bound paclitaxel, or gemcitabine plus carboplatin). The primary end point was progression-free survival, assessed by blinded independent central review. Secondary end points included overall survival, objective response, the duration of response, and safety.\n\nResults: Among 558 patients, median progression-free survival was 9.7 months (95% confidence interval [CI], 8.1 to 11.1) with sacituzumab govitecan and 6.9 months (95% CI, 5.6 to 8.2) with chemotherapy (stratified hazard ratio for disease progression or death, 0.62; 95% CI, 0.50 to 0.77; P<0.001). An objective response was confirmed in 48% of patients (95% CI, 42 to 54) who received sacituzumab govitecan and 46% (95% CI, 40 to 52) who received chemotherapy; the median response duration was 12.2 months (95% CI, 9.7 to 13.8) and 7.2 months (95% CI, 5.7 to 8.4), respectively. Adverse events of grade 3 or higher occurred in 66% of patients who received sacituzumab govitecan (most frequently neutropenia [in 43%], diarrhea [in 9%], and leukopenia [in 7%]) and in 62% of patients who received chemotherapy (most frequently neutropenia [in 41%], anemia [in 16%], and leukopenia [in 13%]). The incidence of adverse events that led to discontinuation of sacituzumab govitecan or at least one chemotherapy drug was 4% and 12%, respectively.\n\nConclusions: Sacituzumab govitecan led to significantly longer progression-free survival than chemotherapy among patients with advanced triple-negative breast cancer who were not candidates for treatment with PD-1 or PD-L1 inhibitors. The incidence of adverse events of grade 3 or higher with sacituzumab govitecan was similar to that with chemotherapy, but adverse events were common. (Funded by Gilead Sciences; ASCENT-03 ClinicalTrials.gov number, NCT05382299.).\n\nIndexed on Europe PMC as PubMed record 41124233 (DOI 10.1056/nejmoa2511734). Its abstract cites the registry id NCT05382299, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2025","url":"https://doi.org/10.1056/nejmoa2511734"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41124233/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41124233"},{"label":"ClinicalTrials.gov NCT05382299","url":"https://clinicaltrials.gov/study/NCT05382299"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["ascent-03"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2025,"doi":"10.1056/nejmoa2511734","pmid":"41124233","authors":"Cortés J, Punie K, Barrios C, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05382299 with the most citations, so it is the natural first reading for anyone following the ASCENT-03 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-ascent-04-n-engl-j-med-2026","kind":"paper","name":"Sacituzumab Govitecan plus Pembrolizumab for Advanced Triple-Negative Breast Cancer","aka":[],"tldr":"Published report from the ASCENT-04 trial registered as NCT05382286, in New England Journal of Medicine (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Triple-negative breast cancer is an aggressive breast cancer subtype, and there remains an unmet need to improve outcomes in patients with previously untreated, programmed death ligand 1 (PD-L1)-positive, locally advanced unresectable or metastatic triple-negative breast cancer.\n\nMethods: In this phase 3, open-label, international trial, we randomly assigned patients in a 1:1 ratio to receive sacituzumab govitecan plus pembrolizumab or chemotherapy plus pembrolizumab. The primary end point was progression-free survival as assessed by blinded independent central review. Secondary end points included overall survival, objective response (complete or partial response) and duration of response as assessed by blinded independent central review, and safety.\n\nResults: A total of 443 patients were randomly assigned to receive sacituzumab govitecan plus pembrolizumab (221 patients) or chemotherapy plus pembrolizumab (222 patients). The median progression-free survival was 11.2 months (95% confidence interval [CI], 9.3 to 16.7) with sacituzumab govitecan plus pembrolizumab and 7.8 months (95% CI, 7.3 to 9.3) with chemotherapy plus pembrolizumab (hazard ratio for disease progression or death, 0.65; 95% CI, 0.51 to 0.84; two-sided P<0.001). Data for overall survival were immature. The percentage of patients with an objective response was 60% (95% CI, 53 to 66) with sacituzumab govitecan plus pembrolizumab and 53% (95% CI, 46 to 60) with chemotherapy plus pembrolizumab; among patients with a response, the median duration of response was 16.5 months (95% CI, 12.7 to 19.5) and 9.2 months (95% CI, 7.6 to 11.3), respectively. Adverse events of grade 3 or higher occurred in 71% of the patients receiving sacituzumab govitecan plus pembrolizumab and in 70% of those receiving chemotherapy plus pembrolizumab; the incidence of treatment discontinuation due to adverse events was 12% and 31%, respectively. Adverse events leading to death occurred in 3% of the patients in each group.\n\nConclusions: Sacituzumab govitecan plus pembrolizumab led to significantly longer progression-free survival than chemotherapy plus pembrolizumab among patients with previously untreated, PD-L1-positive, advanced triple-negative breast cancer. (Funded by Gilead Sciences; ASCENT-04/KEYNOTE-D19 ClinicalTrials.gov number, NCT05382286.).\n\nIndexed on Europe PMC as PubMed record 41564397 (DOI 10.1056/nejmoa2508959). Its abstract cites the registry id NCT05382286, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2026","url":"https://doi.org/10.1056/nejmoa2508959"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41564397/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41564397"},{"label":"ClinicalTrials.gov NCT05382286","url":"https://clinicaltrials.gov/study/NCT05382286"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["ascent-04"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2026,"doi":"10.1056/nejmoa2508959","pmid":"41564397","authors":"Tolaney SM, de Azambuja E, Kalinsky K, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05382286 with the most citations, so it is the natural first reading for anyone following the ASCENT-04 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-sacituzumab-govitecan-tnbc-n-engl-j-med-2019","kind":"paper","name":"Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer","aka":[],"tldr":"Phase 2 or 3 results paper on Sacituzumab govitecan in Triple-negative breast cancer, in New England Journal of Medicine (2019), one of the most cited Europe PMC records with Sacituzumab govitecan in its title.","summary":"Background: Standard chemotherapy is associated with low response rates and short progression-free survival among patients with pretreated metastatic triple-negative breast cancer. Sacituzumab govitecan-hziy is an antibody-drug conjugate that combines a humanized monoclonal antibody, which targets the human trophoblast cell-surface antigen 2 (Trop-2), with SN-38, which is conjugated to the antibody by a cleavable linker. Sacituzumab govitecan-hziy enables delivery of high concentrations of SN-38 to tumors.\n\nMethods: We conducted a phase 1/2 single-group, multicenter trial involving patients with advanced epithelial cancers who received sacituzumab govitecan-hziy intravenously on days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxic effects. A total of 108 patients received sacituzumab govitecan-hziy at a dose of 10 mg per kilogram of body weight after receiving at least two previous anticancer therapies for metastatic triple-negative breast cancer. The end points included safety; the objective response rate (according to Response Evaluation Criteria in Solid Tumors, version 1.1), which was assessed locally; the duration of response; the clinical benefit rate (defined as a complete or partial response or stable disease for at least 6 months); progression-free survival; and overall survival. Post hoc analyses determined the response rate and duration, which were assessed by blinded independent central review.\n\nResults: The 108 patients with triple-negative breast cancer had received a median of 3 previous therapies (range, 2 to 10). Four deaths occurred during treatment; 3 patients (2.8%) discontinued treatment because of adverse events. Grade 3 or 4 adverse events (in ≥10% of the patients) included anemia and neutropenia; 10 patients (9.3%) had febrile neutropenia. The response rate (3 complete and 33 partial responses) was 33.3% (95% confidence interval [CI], 24.6 to 43.1), and the median duration of response was 7.7 months (95% CI, 4.9 to 10.8); as assessed by independent central review, these values were 34.3% and 9.1 months, respectively. The clinical benefit rate was 45.4%. Median progression-free survival was 5.5 months (95% CI, 4.1 to 6.3), and overall survival was 13.0 months (95% CI, 11.2 to 13.7).\n\nConclusions: Sacituzumab govitecan-hziy was associated with durable objective responses in patients with heavily pretreated metastatic triple-negative breast cancer. Myelotoxic effects were the main adverse reactions. (Funded by Immunomedics; IMMU-132-01 ClinicalTrials.gov number, NCT01631552.).\n\nIndexed on Europe PMC as PubMed record 30786188 (DOI 10.1056/nejmoa1814213). Its title names Sacituzumab govitecan and its text names Triple-negative breast cancer; PubMed types it as a clinical trial report (Clinical Trial, Phase II, Research Support, Non-U.S. Gov't, Multicenter Study, Clinical Trial, Phase I). It was matched automatically to the idea \"TROP2 PET to choose and sequence TROP2 ADCs\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2019","url":"https://doi.org/10.1056/nejmoa1814213"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30786188/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30786188"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2019,"doi":"10.1056/nejmoa1814213","pmid":"30786188","authors":"Bardia A, Mayer IA, Vahdat LT, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Sacituzumab govitecan in Triple-negative breast cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Sacituzumab govitecan in the title and Triple-negative breast cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-nct05870319-n-engl-j-med-2026","kind":"paper","name":"Sacituzumab Tirumotecan in EGFR-TKI-Resistant, EGFR -Mutated Advanced NSCLC","aka":[],"tldr":"Published report from the trial registered as NCT05870319, in New England Journal of Medicine (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Sacituzumab tirumotecan (sac-TMT) is an antibody-drug conjugate targeting trophoblast cell-surface antigen 2 that has shown significant survival benefits in patients with EGFR -mutated non-small-cell lung cancer (NSCLC) that has progressed after epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy and platinum-based chemotherapy.\n\nMethods: In this phase 3 trial, we enrolled patients with EGFR -mutated locally advanced or metastatic nonsquamous NSCLC that had progressed after EGFR-TKI therapy. The patients were randomly assigned, in a 1:1 ratio, to receive sac-TMT monotherapy or pemetrexed plus platinum-based chemotherapy. The primary end point was progression-free survival as assessed by blinded independent review. Overall survival was a hierarchically tested key secondary end point. In the interim analysis of progression-free survival as assessed by blinded independent review, sac-TMT monotherapy met the prespecified criterion for significance (two-sided P<0.0001); we report here the prespecified final analysis of progression-free survival and the preplanned interim analysis of overall survival.\n\nResults: Overall, 376 patients underwent randomization, with 188 assigned to each group. After a median follow-up of 18.9 months, the median progression-free survival was 8.3 months in the sac-TMT group and 4.3 months in the chemotherapy group (hazard ratio for disease progression or death, 0.49; 95% confidence interval [CI], 0.39 to 0.62). Overall survival was significantly longer with sac-TMT than with chemotherapy (hazard ratio for death, 0.60; 95% CI, 0.44 to 0.82; two-sided P = 0.001); 18-month overall survival was 65.8% and 48.0%, respectively. Treatment-related adverse events of grade 3 or higher occurred in 58.0% of patients receiving sac-TMT and in 53.8% of those receiving chemotherapy, with the most common being a decreased neutrophil count (39.9% vs. 33.0%); treatment-related serious adverse events occurred in 9.0% and 17.6%, respectively.\n\nConclusions: In patients with EGFR -mutated advanced or metastatic NSCLC that had progressed after previous EGFR-TKI therapy, progression-free survival and overall survival outcomes were significantly better with sac-TMT than with platinum-based chemotherapy. (Funded by Sichuan Kelun-Biotech Biopharmaceutical; OptiTROP-Lung04 ClinicalTrials.gov number, NCT05870319.).\n\nIndexed on Europe PMC as PubMed record 41124220 (DOI 10.1056/nejmoa2512071). Its abstract cites the registry id NCT05870319, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2026","url":"https://doi.org/10.1056/nejmoa2512071"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41124220/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41124220"},{"label":"ClinicalTrials.gov NCT05870319","url":"https://clinicaltrials.gov/study/NCT05870319"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05870319"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2026,"doi":"10.1056/nejmoa2512071","pmid":"41124220","authors":"Fang W, Wu L, Meng X, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05870319 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-nct05347134-nat-med-2025","kind":"paper","name":"Sacituzumab tirumotecan in previously treated metastatic triple-negative breast cancer: a randomized phase 3 trial","aka":[],"tldr":"Published report from the trial registered as NCT05347134, in Nature Medicine (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Chemotherapy remains a standard treatment option for metastatic triple-negative breast cancer (TNBC) but is associated with limited survival. Although some targeted antibody-drug conjugates have demonstrated clinical benefits and are considered standard therapy, persistent unmet medical needs remain due to varying accessibility. The OptiTROP-Breast01 phase 3 trial assessed sacituzumab tirumotecan (sac-TMT) versus chemotherapy in patients with locally recurrent or metastatic TNBC who had received two or more prior therapies, including at least one for metastatic disease. Patients were randomized to sac-TMT (n = 130) or chemotherapy (n = 133). The primary endpoint of progression-free survival (PFS) by blinded independent central review (BICR) was met based on the protocol-specified interim analysis. At final analysis, the median PFS by BICR was 6.7 (95% confidence interval (CI), 5.5-8.0) months with sac-TMT and 2.5 (95% CI, 1.7-2.7) months with chemotherapy (hazard ratio (HR), 0.32; 95% CI, 0.24-0.44; P < 0.00001). Concurrently, at the protocol-specified interim analysis for overall survival (OS), the median OS was not reached (95% CI, 11.2 months to not estimable (NE)) with sac-TMT and 9.4 (95% CI, 8.5-11.7) months with chemotherapy (HR, 0.53; 95% CI, 0.36-0.78; P = 0.0005). The percentage of patients with an objective response was 45.4% with sac-TMT and 12.0% with chemotherapy. The median duration of response was 7.1 (95% CI, 5.6-NE) months with sac-TMT and 3.0 (95% CI, 2.5-NE) months with chemotherapy. The most common treatment-related adverse event with sac-TMT was hematologic toxicity. Sac-TMT demonstrated statistically significant and clinically meaningful improvements in PFS compared to chemotherapy, with a manageable safety profile. The study findings support sac-TMT as an additional effective treatment option for pretreated metastatic TNBC. ClinicalTrials.gov identifier: NCT05347134.\n\nIndexed on Europe PMC as PubMed record 40217078 (DOI 10.1038/s41591-025-03630-w). Its abstract cites the registry id NCT05347134, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Nat Med 2025","url":"https://doi.org/10.1038/s41591-025-03630-w"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40217078/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40217078"},{"label":"ClinicalTrials.gov NCT05347134","url":"https://clinicaltrials.gov/study/NCT05347134"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05347134"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2025,"doi":"10.1038/s41591-025-03630-w","pmid":"40217078","authors":"Yin Y, Fan Y, Ouyang Q, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05347134 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-nct06448312-lancet-2026","kind":"paper","name":"Sacituzumab tirumotecan plus pembrolizumab versus pembrolizumab in PD-L1-positive advanced non-small-cell lung cancer (OptiTROP-Lung05): interim analysis of a randomised, open-label, phase 3 trial","aka":[],"tldr":"Published report from the trial registered as NCT06448312, in The Lancet (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Sacituzumab tirumotecan (sac-TMT), a trophoblast cell-surface antigen 2-targeting antibody-drug conjugate, combined with programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitors, has shown promising antitumour activity as first-line therapy for non-small-cell lung cancer (NSCLC) in early-phase studies. Our aim was to evaluate the efficacy and safety of sac-TMT plus pembrolizumab as first-line treatment for patients with PD-L1-positive advanced NSCLC without targetable genomic alterations.\n\nMethods: In this randomised, open-label, phase 3 trial (OptiTROP-Lung05) conducted across 68 hospitals in China, eligible patients had locally advanced or metastatic NSCLC without targetable genomic alterations and a PD-L1 tumour proportion score (TPS) of 1% or greater. Patients were randomly assigned (1:1) to receive sac-TMT (4 mg/kg on days 1, 15, and 29) plus pembrolizumab (400 mg fixed dose on day 1), or pembrolizumab alone, administered intravenously every 6 weeks. The primary endpoint was progression-free survival, as assessed by blinded independent central review in the intention-to-treat population. This trial was registered with ClinicalTrials.gov (NCT06448312). Recruitment is complete, with the trial ongoing and the final analysis to be reported later.\n\nFindings: Between June 7, 2024, and March 27, 2025, 741 patients were screened and 413 eligible patients were randomly assigned to receive sac-TMT plus pembrolizumab (n=208) or pembrolizumab alone (n=205). At the prespecified interim analysis, conducted after a median follow-up of 10·5 months (IQR 8·7-12·5), median progression-free survival was significantly longer with sac-TMT plus pembrolizumab than with pembrolizumab alone (not reached vs 5·7 months; stratified hazard ratio [HR] 0·35 [95% CI 0·26-0·47]; p<0·0001). The progression-free survival benefit was broadly consistent across subgroups, including patients with PD-L1 TPS of 1-49% (HR 0·28 [95% CI 0·19-0·41]) and those with PD-L1 TPS of 50% or greater (HR 0·47 [0·29-0·77]). Grade 3 or higher treatment-emergent adverse events occurred in 115 (55%) of 208 patients in the sac-TMT plus pembrolizumab group and 64 (31%) of 204 patients in the pembrolizumab group.\n\nInterpretation: Among patients with PD-L1-positive advanced NSCLC without targetable genomic alterations, first-line treatment with sac-TMT plus pembrolizumab significantly prolonged progression-free survival compared with pembrolizumab alone. Therefore, sac-TMT plus pembrolizumab has the potential to redefine first-line treatment for patients with PD-L1-positive advanced NSCLC without targetable genomic alterations.\n\nFunding: Sichuan Kelun-Biotech Biopharmaceutical.\n\nIndexed on Europe PMC as PubMed record 42214392 (DOI 10.1016/s0140-6736(26)00968-2). Its abstract cites the registry id NCT06448312, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet 2026","url":"https://doi.org/10.1016/s0140-6736(26)00968-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42214392/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42214392"},{"label":"ClinicalTrials.gov NCT06448312","url":"https://clinicaltrials.gov/study/NCT06448312"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct06448312"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2026,"doi":"10.1016/s0140-6736(26)00968-2","pmid":"42214392","authors":"Xiong A, Yao W, Zheng W, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT06448312 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-brahmer-anti-pd-l1-phase-1-nejm-2012","kind":"paper","name":"Safety and activity of anti-PD-L1 antibody in patients with advanced cancer","aka":[],"tldr":"The first PD-L1 antibody trial treated 207 people across several cancers; melanoma, kidney and lung cancers responded, and none of the 14 pancreatic cancer patients did.","summary":"In a multicentre phase 1 trial, intravenous anti-PD-L1 antibody at 0.3 to 10 mg/kg was given every 14 days in 6-week cycles for up to 16 cycles to patients with selected advanced cancers. Of 207 patients, 75 had non-small-cell lung cancer, 55 melanoma, 18 colorectal, 17 renal cell, 17 ovarian, 14 pancreatic, 7 gastric and 4 breast cancer. Grade 3 or 4 treatment-related toxicity occurred in 9%. Objective responses were seen in 9 of 52 melanoma, 2 of 17 renal cell, 5 of 49 lung and 1 of 17 ovarian patients; no pancreatic responses were reported.","asOf":"2026-09-24","links":[{"label":"Brahmer et al., N Engl J Med 2012: anti-PD-L1 in 207 patients, none of 14 pancreatic responded","url":"https://doi.org/10.1056/NEJMoa1200694"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22658128/"}],"tags":[],"related":[],"cancers":["pancreatic","metastatic-pdac"],"sections":[],"technologies":[],"targets":["pdl1"],"drugs":[],"companies":[],"institutions":[],"pathways":["pd1-checkpoint"],"terms":["cold-vs-hot"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2012,"doi":"10.1056/NEJMoa1200694","pmid":"22658128","authors":"Brahmer JR, Tykodi SS, Chow LQ, et al.","paperType":"rct","findings":["Objective responses in melanoma, renal cell, lung and ovarian cancer.","None of the 14 pancreatic cancer patients responded."],"whatItMeans":"The trial that opened the PD-L1 era for other cancers is also the first evidence that pancreatic cancer would be left out of it.","caveats":["Fourteen pancreatic patients, unselected.","Early dose-finding design."],"changedPractice":true,"participants":207},{"id":"paper-blinatumomab-all-leukemia-lancet-oncol-2015","kind":"paper","name":"Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study","aka":[],"tldr":"Phase 2 or 3 results paper on Blinatumomab in Acute lymphoblastic leukaemia, in The Lancet Oncology (2015), one of the most cited Europe PMC records with Blinatumomab in its title.","summary":"Background: Adults with relapsed or refractory B-precursor acute lymphoblastic leukaemia have an unfavourable prognosis. Blinatumomab is a bispecific T-cell engager antibody construct targeting CD19, an antigen consistently expressed on B-lineage acute lymphoblastic leukaemia cells. We aimed to confirm the activity and safety profile of blinatumomab for acute lymphoblastic leukaemia.\n\nMethods: In a multicentre, single-arm, open-label phase 2 study, we enrolled adult patients with Philadelphia-chromosome-negative, primary refractory or relapsed (first relapse within 12 months of first remission, relapse within 12 months after allogeneic haemopoietic stem-cell transplantation [HSCT], or no response to or relapse after first salvage therapy or beyond) leukaemia. Patients received blinatumomab (9 μg/day for the first 7 days and 28 μg/day thereafter) by continuous intravenous infusion over 4 weeks every 6 weeks (up to five cycles), per protocol. The primary endpoint was complete remission (CR) or CR with partial haematological recovery of peripheral blood counts (CRh) within the first two cycles. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT01466179.\n\nFindings: Between Jan 13, 2012, and Oct 10, 2013, 189 patients were enrolled and treated with blinatumomab. After two cycles, 81 (43%, 95% CI 36-50) patients had achieved a CR or CRh: 63 (33%) patients had a CR and 18 (10%) patients had a CRh. 32 (40%) of patients who achieved CR/CRh underwent subsequent allogeneic HSCT. The most frequent grade 3 or worse adverse events were febrile neutropenia (48 patients, 25%), neutropenia (30 patients, 16%), and anaemia (27 patients, 14%). Three (2%) patients had grade 3 cytokine release syndrome. Neurologic events of worst grade 3 or 4 occurred in 20 (11%) and four (2%) patients, respectively. Three deaths (due to sepsis, Escherichia coli sepsis, and Candida infection) were thought to be treatment-related by the investigators.\n\nInterpretation: Single-agent blinatumomab showed antileukaemia activity in adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia characterised by negative prognostic factors. Further assessment of blinatumomab treatment earlier in the course of the disease and in combination with other treatment approaches is warranted.\n\nFunding: Amgen.\n\nIndexed on Europe PMC as PubMed record 25524800 (DOI 10.1016/s1470-2045(14)71170-2). Its title names Blinatumomab and its text names Acute lymphoblastic leukaemia; PubMed types it as a clinical trial report (Clinical Trial, Phase II, Research Support, Non-U.S. Gov't, Multicenter Study). It was matched automatically to the idea \"Menin inhibitors for infant KMT2A-rearranged ALL\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2015","url":"https://doi.org/10.1016/s1470-2045(14)71170-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25524800/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25524800"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2015,"doi":"10.1016/s1470-2045(14)71170-2","pmid":"25524800","authors":"Topp MS, Gökbuget N, Stein AS, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Blinatumomab in Acute lymphoblastic leukaemia, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Blinatumomab in the title and Acute lymphoblastic leukaemia in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-nct03330847-clin-cancer-res-2026","kind":"paper","name":"Safety and Efficacy of Ceralasertib plus Olaparib for Advanced/Metastatic Triple-Negative Breast Cancer in Three Molecular Strata: The Phase II VIOLETTE Study","aka":[],"tldr":"Published report from the VIOLETTE trial registered as NCT03330847, in Clinical Cancer Research (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Purpose: VIOLETTE (NCT03330847) assessed olaparib alone or with ceralasertib (ATR inhibitor) or adavosertib (WEE1 inhibitor) as second-/third-line treatment in three molecular strata of patients with previously treated, PARP inhibitor-naïve, advanced triple-negative breast cancer (TNBC).\n\nPatients and methods: Patients were randomized 1:1:1 to olaparib 300 mg twice daily (BD), ceralasertib 160 mg once daily (Days 1-7; 28-day cycles) + olaparib 300 mg BD, or adavosertib 150 mg BD (Days 1-3, 8-10; 21-day cycles) + olaparib 200 mg BD. Patients were stratified by presence of tumoral homologous recombination repair (HRR) pathway mutations (m): BRCA1/2m, non-BRCA1/2m HRRm, or non-HRRm. Primary endpoint was progression-free survival (PFS) by blinded independent central review.\n\nResults: 273 patients were randomized: 114, 112, and 47 to the olaparib, ceralasertib + olaparib, and adavosertib + olaparib arms, respectively. The adavosertib + olaparib arm was terminated early due to unacceptable toxicity. Median PFS of ceralasertib + olaparib was 7.4, 3.9, and 3.6 months in the BRCA1/2m, non-BRCA1/2m HRRm, and non-HRRm strata, respectively, and did not differ significantly from olaparib (HR 1.02 [90% CI, 0.63-1.66], 0.54 [90% CI, 0.28-1.03], and 0.76 [90% CI, 0.50-1.14], respectively). In the non-HRRm group objective response rates (ORR) were significantly improved for ceralasertib + olaparib (15.4%) vs. olaparib (3.9%; OR, 4.45; 90% CI, 1.30‒21.20; P = 0.0425). No unexpected safety signals were reported for ceralasertib or olaparib.\n\nConclusions: In patients with advanced PARP inhibitor-naïve non-HRRm TNBC, ceralasertib + olaparib significantly improved ORR versus olaparib. However, clinical significance is limited without improvement in PFS.\n\nIndexed on Europe PMC as PubMed record 42765908 (DOI 10.1158/1078-0432.ccr-26-1066). Its abstract cites the registry id NCT03330847, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Clin Cancer Res 2026","url":"https://doi.org/10.1158/1078-0432.ccr-26-1066"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42765908/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42765908"},{"label":"ClinicalTrials.gov NCT03330847","url":"https://clinicaltrials.gov/study/NCT03330847"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct03330847"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2026,"doi":"10.1158/1078-0432.ccr-26-1066","pmid":"42765908","authors":"Tutt A, Nowecki Z, Szoszkiewicz R, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03330847 with the most citations, so it is the natural first reading for anyone following the VIOLETTE trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-checkmate-358-j-clin-oncol-2019","kind":"paper","name":"Safety and Efficacy of Nivolumab Monotherapy in Recurrent or Metastatic Cervical, Vaginal, or Vulvar Carcinoma: Results From the Phase I/II CheckMate 358 Trial","aka":[],"tldr":"Published report from the CheckMate 358 trial registered as NCT02488759, in Journal of Clinical Oncology (2019), chosen as the most cited paper whose own text cites the registry id.","summary":"Purpose: Nivolumab was assessed in patients with virus-associated tumors in the phase I/II CheckMate 358 trial (ClinicalTrials.gov identifier: NCT02488759). We report on patients with recurrent/metastatic cervical, vaginal, or vulvar cancers.\n\nPatients and methods: Patients received nivolumab 240 mg every 2 weeks. Although patients with unknown human papillomavirus status were enrolled, patients known to have human papillomavirus-negative tumors were ineligible. The primary end point was objective response rate. Duration of response (DOR), progression-free survival, and overall survival were secondary end points. Safety and patient-reported outcomes were exploratory end points.\n\nResults: Twenty-four patients (cervical, n = 19; vaginal/vulvar, n = 5) were enrolled. Most patients had received prior systemic therapy for metastatic disease (cervical, 78.9%; vaginal/vulvar, 80.0%). Objective response rates were 26.3% (95% CI, 9.1 to 51.2) for cervical cancer and 20.0% (95% CI, 0.5 to 71.6) for vaginal/vulvar cancers. At a median follow-up of 19.2 months, median DOR was not reached (range, 23.3 to 29.5+ months; + indicates a censored observation) in the five responding patients in the cervical cohort; the DOR was 5.0 months in the single responding patient in the vaginal/vulvar cohort. Median overall survival was 21.9 months (95% CI, 15.1 months to not reached) among patients with cervical cancer. Any-grade treatment-related adverse events were reported in 12 of 19 patients (63.2%) in the cervical cohort and all five patients in the vaginal/vulvar cohort; there were no treatment-related deaths. In the cervical cohort, nivolumab treatment generally resulted in stabilization of patient-reported outcomes associated with health status and health-related quality of life.\n\nConclusion: The efficacy of nivolumab in patients with recurrent/metastatic cervical and vaginal or vulvar cancers is promising and warrants additional investigation. No new safety signals were identified with nivolumab treatment in this population.\n\nIndexed on Europe PMC as PubMed record 31487218 (DOI 10.1200/jco.19.00739). Its abstract cites the registry id NCT02488759, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2019","url":"https://doi.org/10.1200/jco.19.00739"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31487218/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31487218"},{"label":"ClinicalTrials.gov NCT02488759","url":"https://clinicaltrials.gov/study/NCT02488759"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-358"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2019,"doi":"10.1200/jco.19.00739","pmid":"31487218","authors":"Naumann RW, Hollebecque A, Meyer T, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02488759 with the most citations, so it is the natural first reading for anyone following the CheckMate 358 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-elm-2-odronextamab-follicular-ann-oncol-2024","kind":"paper","name":"Safety and efficacy of odronextamab in patients with relapsed or refractory follicular lymphoma","aka":["ELM-2","Kim 2024","Odronextamab in follicular lymphoma"],"tldr":"A two-headed antibody given alone put nearly three quarters of people with repeatedly relapsed follicular lymphoma into complete remission, lasting a median of two years.","summary":"The follicular lymphoma cohort of the phase 2 ELM-2 study of odronextamab, a CD20 by CD3 bispecific antibody, in patients with relapsed or refractory disease after two or more lines of systemic therapy. Odronextamab was given intravenously in 21-day cycles with step-up dosing in cycle 1 to mitigate cytokine release syndrome, until disease progression or unacceptable toxicity. The primary endpoint was objective response rate by independent central review.\n\n128 patients were evaluated, of whom 95 per cent completed cycle 1 and 85 per cent four or more cycles. At 20.1 months of efficacy follow-up, the objective response rate was 80.0 per cent and the complete response rate 73.4 per cent. Median duration of complete response was 25.1 months, median progression-free survival 20.7 months, and median overall survival was not reached. Discontinuation for adverse events occurred in 16 per cent. The commonest treatment-emergent adverse events were cytokine release syndrome in 56 per cent, with grade 3 or above in 1.7 per cent (one of 60 patients) using the 0.7, 4 and 20 milligram step-up, neutropenia in 39 per cent and pyrexia in 38 per cent.","asOf":"2026-10-01","links":[{"label":"Annals of Oncology 2024","url":"https://doi.org/10.1016/j.annonc.2024.08.2239"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39147364/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39147364"}],"tags":["lymphoma-evidence"],"related":["lymphoma-roadmap"],"cancers":["follicular-lymphoma","non-hodgkin-lymphoma"],"sections":["immunotherapy"],"technologies":["bispecific-antibody","t-cell-engager"],"targets":["cd20","cd3"],"drugs":["odronextamab"],"companies":["regeneron"],"institutions":[],"pathways":[],"terms":["crs","orr","complete-response"],"trials":["nct03888105"],"people":[],"bottlenecks":["b-manufacturing-cell-therapy","b-global-access"],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2024,"doi":"10.1016/j.annonc.2024.08.2239","pmid":"39147364","authors":"Kim TM, Taszner M, Novelli S, et al.","paperType":"rct","findings":["The objective response rate was 80.0 per cent and the complete response rate 73.4 per cent among 128 evaluated patients.","Median duration of complete response was 25.1 months and median progression-free survival 20.7 months; median overall survival was not reached.","Cytokine release syndrome occurred in 56 per cent, with grade 3 or above in 1.7 per cent using the 0.7, 4 and 20 milligram step-up schedule.","16 per cent discontinued odronextamab because of adverse events.","95 per cent of patients completed cycle 1 and 85 per cent completed four or more cycles."],"whatItMeans":"An off-the-shelf alternative to CAR-T for repeatedly relapsed follicular lymphoma: no apheresis, no manufacturing wait, and a complete response rate in the same range, at the cost of continued treatment rather than a single infusion.","caveats":["Single-arm, so the comparison with CAR-T and with the other bispecific antibodies is cross-trial.","The cytokine release syndrome figures depend on the step-up schedule used, which changed during the study.","Treatment continues until progression or toxicity, rather than for a fixed duration as with mosunetuzumab, which matters for cost and for time spent in hospital."],"changedPractice":true,"participants":128},{"id":"paper-idbaih-clin-cancer-res","kind":"paper","name":"Safety and Feasibility of Repeated and Transient Blood-Brain Barrier Disruption by Pulsed Ultrasound in Patients with Recurrent Glioblastoma","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 30890548 and published in Clinical Cancer Research; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: The blood-brain barrier (BBB) limits the efficacy of drug therapies for glioblastoma (GBM). Preclinical data indicate that low-intensity pulsed ultrasound (LIPU) can transiently disrupt the BBB and increase intracerebral drug concentrations.\n\nPatients and methods: A first-in-man, single-arm, single-center trial (NCT02253212) was initiated to investigate the transient disruption of the BBB in patients with recurrent GBM. Patients were implanted with a 1-MHz, 11.5-mm diameter cranial ultrasound device (SonoCloud-1, CarThera). The device was activated monthly to transiently disrupt the BBB before intravenous carboplatin chemotherapy.\n\nResults: Between 2014 and 2016, 21 patients were registered for the study and implanted with the SonoCloud-1; 19 patients received at least one sonication. In 65 ultrasound sessions, BBB disruption was visible on T1w MRI for 52 sonications. Treatment-related adverse events observed were transient and manageable: a transient edema at H1 and at D15. No carboplatin-related neurotoxicity was observed. Patients with no or poor BBB disruption ( n = 8) visible on MRI had a median progression-free survival (PFS) of 2.73 months, and a median overall survival (OS) of 8.64 months. Patients with clear BBB disruption ( n = 11) had a median PFS of 4.11 months, and a median OS of 12.94 months.\n\nConclusions: SonoCloud-1 treatments were well tolerated and may increase the effectiveness of systemic drug therapies, such as carboplatin, in the brain without inducing neurotoxicity. See related commentary by Sonabend and Stupp, p. 3750.\n\nIndexed on Europe PMC as PubMed record 30890548 (DOI 10.1158/1078-0432.ccr-18-3643). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Clin Cancer Res 2019","url":"https://doi.org/10.1158/1078-0432.ccr-18-3643"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30890548/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30890548"}],"tags":["europepmc-ingest"],"related":["transcranial-focused-ultrasound-systems"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2019,"doi":"10.1158/1078-0432.ccr-18-3643","pmid":"30890548","authors":"Idbaih A, Canney M, Belin L, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-van-herpen-esmo-open","kind":"paper","name":"Salivary gland cancer: ESMO-European Reference Network on Rare Adult Solid Cancers (EURACAN) Clinical Practice Guideline for diagnosis, treatment and follow-up","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 36567082 and published in ESMO Open; the citing page links this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 36567082 (DOI 10.1016/j.esmoop.2022.100602). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"ESMO Open 2022","url":"https://doi.org/10.1016/j.esmoop.2022.100602"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36567082/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36567082"}],"tags":["europepmc-ingest"],"related":["salivary-gland"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["esmo-open"],"dependsOn":[],"notes":[],"journal":"ESMO Open","year":2022,"doi":"10.1016/j.esmoop.2022.100602","pmid":"36567082","authors":"van Herpen C, Vander Poorten V, Skalova A, et al.","paperType":"guideline","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-koshiol-salmonella-typhi-gallbladder-cancer-cancer-med-2016","kind":"paper","name":"Salmonella enterica serovar Typhi and gallbladder cancer: a case-control study and meta-analysis","aka":[],"tldr":"Pooling more than a thousand cases, people with signs of past or chronic typhoid infection were four to five times more likely to have gallbladder cancer, though the bacterium itself was not recovered from the Chilean patients studied.","summary":"In Chile, where typhoid was endemic until the 1990s, 39 gallbladder cancer cases, 40 gallstone controls and 39 population controls were tested for Salmonella Typhi Vi antibodies, with culture and quantitative PCR on available bile, stone, tissue and stool. Cases were more likely to have high Vi titres (odds ratio 4.0, 95 percent CI 0.9 to 18.3), but S. Typhi was not recovered from any sample. A meta-analysis combining these with previous studies (over 1,000 cases) gave a summary relative risk of 4.6 (3.1 to 6.8) for anti-Vi antibodies and 5.0 (2.7 to 9.3) for bile or stool culture. The mechanism remains to be established.","asOf":"2026-09-24","links":[{"label":"Cancer Med 2016","url":"https://doi.org/10.1002/cam4.915"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27726295/"}],"tags":["gallbladder-evidence"],"related":["paper-nagaraja-eslick-typhi-carrier-gallbladder-cancer-meta-analysis-apt-2014"],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nci"],"pathways":[],"terms":["prophylactic-cholecystectomy","inflammation","salmonella-typhi-gallbladder-cancer"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-medicine"],"dependsOn":[],"notes":[],"journal":"Cancer Medicine","year":2016,"doi":"10.1002/cam4.915","pmid":"27726295","authors":"Koshiol J, Wozniak A, Cook P, et al.","paperType":"meta-analysis","findings":["Meta-analysis summary relative risk 4.6 (95 percent CI 3.1 to 6.8) for anti-Vi antibodies and 5.0 (2.7 to 9.3) for bile or stool culture.","Chilean case-control odds ratio 4.0 (0.9 to 18.3) for high Vi titre; no S. Typhi recovered from samples."],"whatItMeans":"Typhoid carriage is one of the few modifiable risk factors for gallbladder cancer. In the UK it is rare, but it matters for people who grew up where typhoid is endemic and for the question of whether chronic carriers should be offered cholecystectomy.","caveats":["Small Chilean sample; the association rests mainly on the meta-analysis.","Serology cannot distinguish past infection from chronic carriage."],"changedPractice":false},{"id":"paper-scanu-salmonella-gallbladder-transformation-cell-host-microbe-2015","kind":"paper","name":"Salmonella manipulation of host signaling pathways provokes cellular transformation associated with gallbladder carcinoma","aka":[],"tldr":"Typhoid bacteria can push already-damaged gallbladder cells into becoming cancerous: in mice, gallbladder organoids and cells with faulty TP53 and extra MYC, Salmonella infection switched on growth signalling that started and maintained the transformation.","summary":"Gallbladder carcinoma is frequent in the Indian subcontinent, where chronic Salmonella enterica serovar Typhi infection is a reported risk factor, but a causal mechanism had not been established. Deconstructing the epidemiological association, the authors showed that Salmonella enterica induces malignant transformation in predisposed mice, murine gallbladder organoids and fibroblasts carrying TP53 mutations and c-MYC amplification.\n\nMechanistically, activation of MAPK and AKT pathways, mediated by Salmonella effectors secreted during infection, was critical both to ignite and to sustain transformation, consistent with observations in gallbladder cancer patients from India. The findings indicate that Salmonella enterica can promote transformation of genetically predisposed cells and is a causative agent of gallbladder carcinoma.","asOf":"2026-09-24","links":[{"label":"Scanu et al., Cell Host Microbe 2015: Salmonella infection transforms predisposed gallbladder cells","url":"https://doi.org/10.1016/j.chom.2015.05.002"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26028364/"}],"tags":[],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":["tp53"],"drugs":[],"companies":[],"institutions":[],"pathways":["ras-mapk","pi3k-akt-mtor"],"terms":["salmonella-typhi-gallbladder-cancer"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Cell Host and Microbe","year":2015,"doi":"10.1016/j.chom.2015.05.002","pmid":"26028364","authors":"Scanu T, Spaapen RM, Bakker JM, et al.","paperType":"basic","findings":["Salmonella enterica transformed predisposed (TP53-mutant, c-MYC-amplified) mouse cells, gallbladder organoids and fibroblasts.","Bacterial effectors activated MAPK and AKT signalling, required to start and sustain transformation.","Findings were consistent with tumours from Indian patients."],"whatItMeans":"A mechanism for the oldest epidemiological clue in gallbladder cancer, and a reason the disease appears so early in India. It frames typhoid control and cholecystectomy in chronic carriers as cancer prevention, and MAPK and AKT as pathways worth watching in infection-associated tumours.","caveats":["Mouse and organoid work; the human evidence is epidemiological and immunohistochemical.","Predisposing mutations were engineered, so the sequence of events in patients is inferred."],"changedPractice":false},{"id":"paper-cd19-dlbcl-clin-cancer-res-2011","kind":"paper","name":"SAR3419: an anti-CD19-Maytansinoid Immunoconjugate for the treatment of B-cell malignancies","aka":[],"tldr":"Review on CD19 in Diffuse large B-cell lymphoma, in Clinical Cancer Research (2011), one of the most cited Europe PMC records with CD19 in its title.","summary":"SAR3419 is a novel anti-CD19 humanized monoclonal antibody conjugated to a maytansine derivate through a cleavable linker for the treatment of B-cell malignancies. SAR3419 combines the strengths of a high-potency tubulin inhibitor and the exquisite B-cell selectivity of an anti-CD19 antibody. The internalization and processing of SAR3419, following its binding at the surface of CD19-positive human lymphoma cell lines and xenograft models, release active metabolites that trigger cell-cycle arrest and apoptosis, leading to cell death and tumor regression. SAR3419 has also been shown to be active in different lymphoma xenograft models, including aggressive diffuse large B-cell lymphoma, resulting in complete regressions and tumor-free survival. In these models, the activity of SAR3419 compared favorably with rituximab and lymphoma standard of care chemotherapy. Two phase I trials with 2 different schedules of SAR3419 as a single agent were conducted in refractory/relapsed B-cell non-Hodgkin lymphoma. Activity was reported in both schedules, in heavily pretreated patients of both follicular and diffuse large B-cell lymphoma subtypes, with a notable lack of significant hematological toxicity, validating SAR3419 as an effective antibody-drug conjugate and opening opportunities in the future. Numerous B-cell-specific anti-CD19 biologics are available to treat B-cell non-Hodgkin lymphoma, and early phase I results obtained with SAR3419 suggest that it is a promising candidate for further development in this disease. In addition, thanks to the broad expression of CD19, SAR3419 may provide treatment options for B-cell leukemias that are often CD20-negative.\n\nIndexed on Europe PMC as PubMed record 22003072 (DOI 10.1158/1078-0432.ccr-11-0485). Its title names CD19 and its text names Diffuse large B-cell lymphoma; PubMed types it as a review (Review). It was matched automatically to the idea \"In vivo CAR-T as a vial on the shelf: a cost and access trial in lymphoma\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Clin Cancer Res 2011","url":"https://doi.org/10.1158/1078-0432.ccr-11-0485"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22003072/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/22003072"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2011,"doi":"10.1158/1078-0432.ccr-11-0485","pmid":"22003072","authors":"Blanc V, Bousseau A, Caron A, et al.","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for CD19 in Diffuse large B-cell lymphoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by CD19 in the title and Diffuse large B-cell lymphoma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-sarc028-pembrolizumab-sarcoma-tawbi-lancet-oncol-2017","kind":"paper","name":"SARC028: pembrolizumab in advanced soft tissue and bone sarcoma","aka":[],"tldr":"Pembrolizumab had little effect in most sarcomas, but it shrank tumours in about 40 percent of patients with undifferentiated pleomorphic sarcoma and some with dedifferentiated liposarcoma, singling out these subtypes for immunotherapy.","summary":"Phase 2 study of 86 patients with advanced soft tissue sarcoma (undifferentiated pleomorphic sarcoma, dedifferentiated liposarcoma, synovial sarcoma, leiomyosarcoma) or bone sarcoma treated with pembrolizumab.\n\nObjective response was 18 percent in soft tissue sarcoma, driven by 40 percent in undifferentiated pleomorphic sarcoma and 20 percent in dedifferentiated liposarcoma, with no responses in leiomyosarcoma and one in synovial sarcoma; bone sarcoma response was 5 percent.","asOf":"2026-09-17","links":[{"label":"Lancet Oncol 2017","url":"https://doi.org/10.1016/S1470-2045(17)30624-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28988646/"}],"tags":[],"related":[],"cancers":["undifferentiated-pleomorphic-sarcoma"],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["sarc028"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2017,"doi":"10.1016/S1470-2045(17)30624-1","pmid":"28988646","authors":"Tawbi HA, Burgess M, Bolejack V, et al.","paperType":"observational","findings":["Objective response 40 percent in undifferentiated pleomorphic sarcoma; 20 percent in dedifferentiated liposarcoma.","0 percent in leiomyosarcoma; 5 percent in bone sarcomas."],"whatItMeans":"PD-1 blockade is an off-label or trial option specifically for undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma, not for sarcoma in general.","caveats":["Small cohorts of about 10 patients per histology; expansion cohorts confirmed lower rates (about 23 percent) in undifferentiated pleomorphic sarcoma."],"changedPractice":true,"participants":86},{"id":"paper-koelsche-nat-commun","kind":"paper","name":"Sarcoma classification by DNA methylation profiling","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 33479225 and published in Nature Communications; the citing page links this DOI, which is how the record was matched.","summary":"Sarcomas are malignant soft tissue and bone tumours affecting adults, adolescents and children. They represent a morphologically heterogeneous class of tumours and some entities lack defining histopathological features. Therefore, the diagnosis of sarcomas is burdened with a high inter-observer variability and misclassification rate. Here, we demonstrate classification of soft tissue and bone tumours using a machine learning classifier algorithm based on array-generated DNA methylation data. This sarcoma classifier is trained using a dataset of 1077 methylation profiles from comprehensively pre-characterized cases comprising 62 tumour methylation classes constituting a broad range of soft tissue and bone sarcoma subtypes across the entire age spectrum. The performance is validated in a cohort of 428 sarcomatous tumours, of which 322 cases were classified by the sarcoma classifier. Our results demonstrate the potential of the DNA methylation-based sarcoma classification for research and future diagnostic applications.\n\nIndexed on Europe PMC as PubMed record 33479225 (DOI 10.1038/s41467-020-20603-4). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Commun 2021","url":"https://doi.org/10.1038/s41467-020-20603-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33479225/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33479225"}],"tags":["europepmc-ingest"],"related":["sarcoma-methylation-classifier"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-communications"],"dependsOn":[],"notes":[],"journal":"Nature Communications","year":2021,"doi":"10.1038/s41467-020-20603-4","pmid":"33479225","authors":"Koelsche C, Schrimpf D, Stichel D, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-sato-lgr5-organoids-nature-2009","kind":"paper","name":"Sato 2009: single Lgr5 stem cells build crypt-villus organoids","aka":[],"tldr":"The experiment that invented organoids: a single intestinal stem cell, given three growth factors in a gel, grew into a miniature gut lining that could be kept alive indefinitely, a method since extended to tumours from individual patients.","summary":"Sato, Clevers and colleagues at the Hubrecht Institute showed that single Lgr5-positive stem cells from the mouse small intestine, embedded in Matrigel with EGF, Noggin and R-spondin 1 and no supporting mesenchyme, form self-organising structures with crypt and villus domains containing all the differentiated cell types of the gut. The organoids could be passaged for over eight months without losing their properties. The method was soon adapted to human tissue and to tumours, creating patient-derived organoids for drug testing.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1038/nature07935"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["organoids","organoid-guided-therapy-scale"],"targets":[],"drugs":[],"companies":[],"institutions":["umc-utrecht"],"pathways":[],"terms":["stem-cell"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature","year":2009,"doi":"10.1038/nature07935","authors":"Sato T, Vries RG, Snippert HJ, et al.","paperType":"methods","findings":["Single Lgr5-positive intestinal stem cells formed crypt-villus organoids in Matrigel with EGF, Noggin and R-spondin 1, without a mesenchymal niche.","Organoids contained all differentiated intestinal cell types and could be maintained for more than eight months.","The defined culture conditions were the basis for later human and tumour organoid systems."],"whatItMeans":"Organoids from patients' tumours are now used to test drugs before treatment, to model rare cancers and to study resistance. Every one of those systems descends from this culture method.","caveats":["Mouse intestine only in this paper; human and tumour organoids came in later work.","Organoids lack blood vessels, immune cells and stroma unless these are added."],"changedPractice":false},{"id":"paper-sauer-preoperative-chemoradiotherapy-rectal-nejm-2004","kind":"paper","name":"Sauer 2004: chemoradiotherapy before rather than after surgery for rectal cancer (CAO/ARO/AIO-94)","aka":[],"tldr":"Giving chemotherapy and radiotherapy before surgery rather than after halved local recurrences of rectal cancer, caused less toxicity and let more patients keep their anal sphincter, without changing overall survival.","summary":"The German Rectal Cancer Study Group randomised 823 patients with locally advanced rectal cancer (clinical stage T3 or T4 or node-positive) to fluorouracil-based chemoradiotherapy either before or after total mesorectal excision, with both groups receiving further chemotherapy. Preoperative treatment reduced five-year local recurrence, lowered acute and long-term toxicity and increased sphincter-preserving surgery among patients whose tumours had been judged to need an abdominoperineal resection, while overall survival was the same in both arms.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa040694"}],"tags":[],"related":["colorectal-roadmap","paper-sebag-montefiore-cr07-preoperative-radiotherapy-lancet-2009","paper-kapiteijn-dutch-tme-preoperative-radiotherapy-nejm-2001"],"cancers":["colorectal"],"sections":[],"technologies":[],"targets":[],"drugs":["fluorouracil"],"companies":[],"institutions":[],"pathways":[],"terms":["chemoradiation","neoadjuvant-adjuvant","total-neoadjuvant-therapy","organ-preservation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2004,"doi":"10.1056/NEJMoa040694","authors":"Sauer R, Becker H, Hohenberger W, et al.","paperType":"rct","findings":["823 patients with locally advanced rectal cancer; chemoradiotherapy before or after total mesorectal excision.","Five-year local recurrence 6% with preoperative vs 13% with postoperative treatment.","Five-year overall survival 76% vs 74%, not significantly different.","Grade 3 or 4 acute toxicity 27% vs 40%; long-term toxicity 14% vs 24%; sphincter preservation rose in patients initially judged to need an abdominoperineal resection."],"whatItMeans":"This trial made preoperative chemoradiotherapy the standard for locally advanced rectal cancer worldwide and is the foundation on which total neoadjuvant therapy and watch-and-wait organ preservation were later built.","caveats":["Overall survival was unchanged; the gain is in local control, toxicity and function.","Chemotherapy was fluorouracil alone by the standards of 2004.","Staging relied on endorectal ultrasound and CT rather than modern MRI."],"changedPractice":true,"participants":823},{"id":"paper-nct03778229-ann-oncol-2025","kind":"paper","name":"Savolitinib plus osimertinib in epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer with MET overexpression and/or amplification following disease progression on osimertinib: primary results from the phase II SAVANNAH study","aka":[],"tldr":"Published report from the SAVANNAH trial registered as NCT03778229, in Annals of Oncology (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: MET-based resistance following osimertinib treatment for epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC) is common. We report the primary analysis of the phase II SAVANNAH study (NCT03778229) evaluating savolitinib plus osimertinib in this setting.\n\nPatients and methods: Patients had EGFR-mutated, advanced NSCLC with MET overexpression and/or amplification. MET cut-offs were initially MET immunohistochemistry (IHC)3+/≥50% (3+ intensity in ≥50% of tumor cells) and/or FISH5+ (≥5 MET gene copies or MET/chromosome 7 centromere ratio ≥2), and increased to MET IHC3+/≥90% and/or FISH10+ after a preliminary analysis. Patients received oral savolitinib [300 mg twice daily (b.i.d.) or once daily (o.d.), or 600 mg o.d.] plus osimertinib 80 mg o.d., or savolitinib 300 mg b.i.d. plus placebo. A primary endpoint was investigator-assessed objective response rate (ORR) in patients with progression on first-line osimertinib and MET IHC3+/≥90% and/or FISH10+ status receiving savolitinib 300 mg b.i.d. plus osimertinib (primary efficacy population). Safety was analyzed in all patients receiving savolitinib plus osimertinib.\n\nResults: Of the 365 patients treated, 341 received savolitinib plus osimertinib, with 80 of these included in the primary efficacy population. Investigator-assessed confirmed ORR in the primary efficacy population was 56.3% [95% confidence interval (CI) 44.7% to 67.3%]; the median duration of response (mDoR) was 7.1 months (95% CI 5.6-9.6 months); the median progression-free survival (PFS) was 7.4 months (95% CI 5.5-7.6 months). Blinded independent central review was consistent: confirmed ORR 55.0% (95% CI 43.5% to 66.2%); mDoR 9.9 months (95% CI 6.0-13.7 months); median PFS 7.5 months (95% CI 6.4-11.3 months). The most common any grade adverse events in patients receiving savolitinib plus osimertinib were peripheral edema (46.0%), nausea (40.5%), and diarrhea (23.2%).\n\nConclusions: Savolitinib 300 mg b.i.d. plus osimertinib demonstrated high, clinically meaningful and durable responses in patients with EGFR-mutated, advanced NSCLC with MET IHC3+/≥90% and/or FISH10+ status following progression on first-line osimertinib. The combination was well tolerated and may provide a new oral targeted treatment approach in this setting.\n\nIndexed on Europe PMC as PubMed record 40461383 (DOI 10.1016/j.annonc.2025.04.003). Its abstract cites the registry id NCT03778229, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2025","url":"https://doi.org/10.1016/j.annonc.2025.04.003"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40461383/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40461383"},{"label":"ClinicalTrials.gov NCT03778229","url":"https://clinicaltrials.gov/study/NCT03778229"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct03778229"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2025,"doi":"10.1016/j.annonc.2025.04.003","pmid":"40461383","authors":"de Marinis F, Kim TM, Bonanno L, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03778229 with the most citations, so it is the natural first reading for anyone following the SAVANNAH trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-lewis-science","kind":"paper","name":"Scalable emulation of protein equilibrium ensembles with generative deep learning","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 40638710 and published in Science; the citing page links this DOI, which is how the record was matched.","summary":"Following the sequence and structure revolutions, predicting functionally relevant protein structure changes at scale remains an outstanding challenge. We introduce BioEmu, a deep learning system that emulates protein equilibrium ensembles by generating thousands of statistically independent structures per hour on a single graphics processing unit (GPU). BioEmu integrates more than 200 milliseconds of molecular dynamics (MD) simulations, static structures, and experimental protein stabilities using new training algorithms. It captures diverse functional motions-including cryptic pocket formation, local unfolding, and domain rearrangements-and predicts relative free energies with 1 kilocalorie per mole accuracy compared with millisecond-scale MD and experimental data. BioEmu provides mechanistic insights by jointly modeling structural ensembles and thermodynamic properties. This approach amortizes the cost of MD and experimental data generation, demonstrating a scalable path toward understanding and designing protein function.\n\nIndexed on Europe PMC as PubMed record 40638710 (DOI 10.1126/science.adv9817). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Science 2025","url":"https://doi.org/10.1126/science.adv9817"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40638710/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40638710"}],"tags":["europepmc-ingest"],"related":["bioemu"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2025,"doi":"10.1126/science.adv9817","pmid":"40638710","authors":"Lewis S, Hempel T, Jiménez-Luna J, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-scalp-trial-jama-2017","kind":"paper","name":"SCALP: scalp cooling to prevent hair loss during chemotherapy for early breast cancer","aka":[],"tldr":"In the first randomised trial of a modern scalp cooling system, half the women who used the Paxman device during taxane or anthracycline chemotherapy for early breast cancer kept most of their hair, compared with none of those who did not.","summary":"SCALP was a multicentre randomised trial at seven US centres of the Paxman Orbis scalp cooling system in women with stage I or II breast cancer receiving at least four cycles of taxane-based, anthracycline-based or combined chemotherapy, randomised 2:1 to cooling or no cooling. The primary endpoint was hair preservation, defined as Dean scale grade 0 or 1 (less than 50 percent hair loss without the need for a wig) after four cycles.\n\nAt the planned interim analysis of 142 evaluable women, 48 of 95 (50.5 percent) in the cooling group preserved their hair compared with 0 of 47 in the control group, and the trial stopped early for efficacy. Preservation was better with taxane-only regimens than with anthracycline-containing regimens. Adverse events were mild (headache, chills, scalp pain) and there were no scalp metastases during follow-up. Quality-of-life measures did not differ significantly at four cycles. A companion single-arm study of the DigniCap system (Rugo et al., same issue) reported hair preservation in 66.3 percent of women on non-anthracycline taxane regimens versus none of 16 concurrent controls. Together the two studies underpinned FDA clearance of both devices for solid tumours.","asOf":"2026-09-10","links":[{"label":"SCALP randomised trial (JAMA 2017)","url":"https://doi.org/10.1001/jama.2016.20939"},{"label":"DigniCap prospective cohort with concurrent controls (JAMA 2017)","url":"https://doi.org/10.1001/jama.2016.21038"},{"label":"Scalp cooling and the risk of scalp metastases: systematic review (Breast Cancer Res Treat 2017)","url":"https://doi.org/10.1007/s10549-017-4185-9"}],"tags":["complementary","hair-loss"],"related":[],"cancers":["breast-hr-positive","tnbc","breast-her2-positive"],"sections":[],"technologies":["scalp-cooling"],"targets":[],"drugs":["docetaxel","paclitaxel","doxorubicin","cyclophosphamide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2017,"doi":"10.1001/jama.2016.20939","authors":"Nangia J, Wang T, Osborne C, et al.","paperType":"rct","findings":["182 women randomised; interim analysis of 142 evaluable: hair preservation 50.5% (48/95) with scalp cooling versus 0% (0/47) without.","Preservation higher with taxane-only than anthracycline-containing chemotherapy.","Adverse events limited to grade 1-2 headache, chills and scalp discomfort; no scalp metastases.","Companion DigniCap study: 66.3% hair preservation on non-anthracycline taxane regimens versus 0% in controls."],"whatItMeans":"Scalp cooling works, especially for taxane-based regimens, and is safe. The question moved from whether to how to make it available: device time in the chemotherapy chair, staff training, and who pays.","caveats":["Open-label; the outcome was assessed by clinicians and patients who knew the allocation.","Stopped early at interim analysis, which can overestimate effect size.","Anthracycline-containing regimens, common in breast cancer, had lower preservation rates."],"changedPractice":true,"participants":182},{"id":"paper-cui-nat-methods","kind":"paper","name":"scGPT: toward building a foundation model for single-cell multi-omics using generative AI","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 38409223 and published in Nature methods; the citing page links this DOI, which is how the record was matched.","summary":"Generative pretrained models have achieved remarkable success in various domains such as language and computer vision. Specifically, the combination of large-scale diverse datasets and pretrained transformers has emerged as a promising approach for developing foundation models. Drawing parallels between language and cellular biology (in which texts comprise words; similarly, cells are defined by genes), our study probes the applicability of foundation models to advance cellular biology and genetic research. Using burgeoning single-cell sequencing data, we have constructed a foundation model for single-cell biology, scGPT, based on a generative pretrained transformer across a repository of over 33 million cells. Our findings illustrate that scGPT effectively distills critical biological insights concerning genes and cells. Through further adaptation of transfer learning, scGPT can be optimized to achieve superior performance across diverse downstream applications. This includes tasks such as cell type annotation, multi-batch integration, multi-omic integration, perturbation response prediction and gene network inference.\n\nIndexed on Europe PMC as PubMed record 38409223 (DOI 10.1038/s41592-024-02201-0). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Methods 2024","url":"https://doi.org/10.1038/s41592-024-02201-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38409223/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38409223"}],"tags":["europepmc-ingest"],"related":["scgpt"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature methods","year":2024,"doi":"10.1038/s41592-024-02201-0","pmid":"38409223","authors":"Cui H, Wang C, Maan H, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-schreiber-cancer-immunoediting-science-2011","kind":"paper","name":"Schreiber, Old and Smyth 2011: cancer immunoediting","aka":[],"tldr":"The review that set out the three Es of how the immune system shapes a cancer: elimination of many early tumours, an equilibrium in which growth is held in check, and escape when the tumour evolves ways to evade attack.","summary":"Schreiber, Old and Smyth summarised two decades of evidence, much of it from genetically modified mice, that the immune system both suppresses and sculpts tumours. In the elimination phase innate and adaptive immunity destroy many nascent cancers; in equilibrium, adaptive immunity holds surviving tumour cells dormant while editing their immunogenicity; in escape, variants that have lost antigens, upregulated PD-L1 or recruited suppressive cells grow out. The framework explained why clinically apparent cancers are poorly immunogenic and why checkpoint blockade can work.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1126/science.1203486"}],"tags":[],"related":["paper-pardoll-immune-checkpoint-blockade-nrc-2012"],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["pdl1"],"drugs":[],"companies":[],"institutions":["wustl-siteman"],"pathways":[],"terms":["immune-system","immune-checkpoint"],"trials":[],"people":["robert-schreiber"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Science","year":2011,"doi":"10.1126/science.1203486","authors":"Schreiber RD, Old LJ, Smyth MJ.","paperType":"review","findings":["Immune-deficient mice develop more spontaneous and carcinogen-induced cancers, showing immune surveillance is real.","Tumours can persist in an equilibrium state controlled by adaptive immunity, as shown by outgrowth when T cells are depleted.","Escape occurs through loss of antigen presentation, immunosuppressive cytokines and ligands such as PD-L1, and recruitment of regulatory cells."],"whatItMeans":"Immunoediting is the conceptual backbone of modern immuno-oncology: it explains tumour heterogeneity, dormancy and late relapse, and why immunotherapy works by releasing pre-existing but suppressed immunity.","caveats":["Largely based on mouse models; human equilibrium is inferred rather than observed.","A review, so it synthesises rather than tests."],"changedPractice":false},{"id":"paper-baine-sclc-subtype-immunohistochemistry-jto-2020","kind":"paper","name":"SCLC subtypes defined by ASCL1, NEUROD1, POU2F3, and YAP1: a comprehensive immunohistochemical and histopathologic characterization","aka":[],"tldr":"The four kinds of small-cell lung cancer were defined in laboratory models. Staining 174 real patient samples showed the picture is messier: more than a third of tumours switch on two of the control proteins at once.","summary":"Expression of ASCL1, NEUROD1, POU2F3 and YAP1 was analysed by immunohistochemistry in 174 patient samples of small-cell lung carcinoma and correlated with histological characteristics, classic neuroendocrine markers and other markers including TTF-1 and DLL3. ASCL1 and NEUROD1 expression distributed as 41% ASCL1-positive and NEUROD1-negative, 37% positive for both, 8% ASCL1-negative and NEUROD1-positive, and 14% negative for both; on relative expression, 69% were ASCL1-dominant and 17% NEUROD1-dominant. POU2F3 was expressed in 7% and was mutually exclusive of ASCL1 and NEUROD1. YAP1 was expressed at low levels, primarily in combined small-cell carcinomas, and was not exclusive of other subtypes. ASCL1-dominant and NEUROD1-dominant tumours had a neuroendocrine marker high, TTF-1 high and DLL3 high profile, whereas POU2F3 and other double-negative tumours were low for all three.","asOf":"2026-09-25","links":[{"label":"Baine et al., J Thorac Oncol 2020: immunohistochemical characterisation of the small-cell subtypes in 174 patient samples","url":"https://doi.org/10.1016/j.jtho.2020.09.009"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33011388/"}],"tags":[],"related":["dll3-expression"],"cancers":["sclc"],"sections":[],"technologies":["histopathology-ihc"],"targets":["ascl1","yap1","dll3","nkx2-1"],"drugs":[],"companies":[],"institutions":["mskcc"],"pathways":["sclc-signalling","lineage-plasticity-neuroendocrine","notch"],"terms":["ihc"],"trials":[],"people":["charles-rudin"],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-thoracic-oncology"],"dependsOn":[],"notes":[],"journal":"Journal of Thoracic Oncology","year":2020,"doi":"10.1016/j.jtho.2020.09.009","pmid":"33011388","authors":"Baine MK, Hsieh MS, Lai WV, et al.","paperType":"observational","findings":["69% of tumours are ASCL1-dominant and 17% NEUROD1-dominant, with 37% expressing both.","POU2F3 is expressed in 7% and is mutually exclusive of the other two.","YAP1 is low and not exclusive, mostly in combined small-cell carcinomas.","POU2F3 and double-negative tumours are low for neuroendocrine markers, TTF-1 and DLL3."],"whatItMeans":"It is the reality check on the subtype model and it has a direct consequence for treatment: the DLL3-directed medicines are aimed at the neuroendocrine-high subtypes, and the POU2F3 and double-negative tumours will not express the target.","caveats":["Immunohistochemistry is a coarse readout of a transcriptional state.","Single-institution samples, many from small biopsies.","Co-expression of ASCL1 and NEUROD1 in 37% means dominance has to be defined by relative intensity, which is subjective."],"changedPractice":false,"participants":174},{"id":"paper-plco-chest-radiograph-lung-cancer-mortality-jama-2011","kind":"paper","name":"Screening by chest radiograph and lung cancer mortality: the Prostate, Lung, Colorectal, and Ovarian (PLCO) randomized trial","aka":[],"tldr":"154,901 people were randomised to yearly chest X-rays or usual care. After 13 years the number who died of lung cancer was the same in both groups. The test that had been used for decades did not work.","summary":"The lung arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, reported by Oken, Hocking, Kvale and colleagues: 154,901 participants aged 55 to 74 randomised between November 1993 and July 2001 at ten United States centres, 77,445 offered annual posteroanterior chest radiographs for four years and 77,456 to usual care, followed for up to 13 years.\n\nPLCO is the control that makes NLST interpretable. NLST compared low-dose computed tomography against chest radiography rather than against nothing, and the reason that was an acceptable design is that PLCO had already established radiography to be no better than usual care.","asOf":"2026-09-25","links":[{"label":"JAMA 2011","url":"https://doi.org/10.1001/jama.2011.1591"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22031728/"},{"label":"ClinicalTrials.gov NCT00002540","url":"https://clinicaltrials.gov/study/NCT00002540"}],"tags":["lung-evidence"],"related":["paper-nlst-nejm-2011","paper-nelson-nejm-2020","early-detection-roadmap"],"cancers":["lung-cancer","nsclc"],"sections":["early-detection"],"technologies":["low-dose-ct-screening"],"targets":[],"drugs":[],"companies":[],"institutions":["nci"],"pathways":[],"terms":["overdiagnosis"],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-overdiagnosis","b-negative-results"],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2011,"doi":"10.1001/jama.2011.1591","pmid":"22031728","authors":"Oken MM, Hocking WG, Kvale PA, et al.","paperType":"rct","findings":["Cumulative lung cancer incidence through 13 years was 20.1 per 10,000 person-years in the screened group and 19.2 in usual care (rate ratio 1.05, 95 percent confidence interval 0.98 to 1.12).","1,213 lung cancer deaths in the intervention group against 1,230 in usual care through 13 years (mortality rate ratio 0.99, 0.87 to 1.22).","Stage and histology were similar between the two groups.","Screening adherence was 86.6 percent at baseline and 79 to 84 percent in years 1 to 3; screening use in the usual care group was 11 percent.","In the subset eligible for NLST, over the same 6-year follow-up, the mortality rate ratio was 0.94 (0.81 to 1.10)."],"whatItMeans":"A negative screening trial that saved a generation from a useless test, and the reason low-dose computed tomography had to be proved separately rather than assumed to work because it saw more.","caveats":["Four annual screens only; a longer programme was not tested.","11 percent contamination in the usual care group would dilute any true effect.","Chest radiography as practised in the 1990s; it says nothing about the modern reads of those films by machine."],"changedPractice":true,"participants":154901},{"id":"paper-uspstf-lung-cancer-screening-jama-2021","kind":"paper","name":"Screening for Lung Cancer: US Preventive Services Task Force Recommendation Statement","aka":[],"tldr":"In 2021 the United States task force lowered the age at which lung screening starts from 55 to 50 and halved the smoking history needed from 30 to 20 pack-years, roughly doubling the number of people eligible.","summary":"The 2021 update of the United States Preventive Services Task Force recommendation on lung cancer screening, replacing the 2013 statement. It recommends annual low-dose computed tomography in adults aged 50 to 80 years with a 20 pack-year smoking history who currently smoke or have quit within the past 15 years, a B recommendation, and says screening should stop once a person has not smoked for 15 years or develops a problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery.\n\nThe widened criteria were driven by a commissioned systematic review and a collaborative modelling study, and by evidence that the 2013 thresholds excluded groups at high risk, Black smokers in particular (paper-aldrich-uspstf-screening-african-american-smokers-jama-oncol-2019).","asOf":"2026-09-25","links":[{"label":"JAMA 2021","url":"https://doi.org/10.1001/jama.2021.1117"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33687470/"},{"label":"USPSTF recommendation: lung cancer screening","url":"https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/lung-cancer-screening"}],"tags":["lung-evidence"],"related":["paper-nlst-nejm-2011","paper-nelson-nejm-2020","paper-aldrich-uspstf-screening-african-american-smokers-jama-oncol-2019","early-detection-roadmap","idea-prev-lung-screening-risk-model-eligibility"],"cancers":["lung-cancer","nsclc"],"sections":["early-detection","prevention"],"technologies":["low-dose-ct-screening"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["overdiagnosis"],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-prevention-adoption","b-trial-diversity","b-global-access"],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2021,"doi":"10.1001/jama.2021.1117","pmid":"33687470","authors":"US Preventive Services Task Force, Krist AH, Davidson KW, et al.","paperType":"guideline","findings":["Annual low-dose computed tomography is recommended for adults aged 50 to 80 with a 20 pack-year smoking history who currently smoke or quit within the past 15 years (B recommendation).","This replaces the 2013 statement, which recommended screening from age 55 with a 30 pack-year history.","The task force concludes with moderate certainty that annual low-dose computed tomography has a moderate net benefit in people at high risk based on age, cumulative tobacco exposure and years since quitting.","The statement quotes an estimated 228,820 lung cancer diagnoses and 135,720 deaths in the United States in 2020, and an overall five-year survival of 20.5 percent."],"whatItMeans":"The document that defines who is offered a scan in the United States, and therefore the document any argument about the screening eligibility gap has to engage with. Eligibility is still defined by pack-years and years since quitting rather than by an individual risk estimate.","caveats":["Pack-year thresholds are a crude proxy for risk and perform differently across populations; risk-model eligibility was considered in the modelling but not adopted.","Never-smokers are outside the recommendation entirely, so the growing never-smoker disease is not addressed.","A recommendation is not delivery: uptake among eligible people in the United States has remained a small fraction of those covered.","United Kingdom eligibility, the Targeted Lung Health Check programme and NICE positions are on the UK and NHS page for lung cancer and are not restated here."],"changedPractice":true},{"id":"paper-bellera-ann-oncol","kind":"paper","name":"Screening older cancer patients: first evaluation of the G-8 geriatric screening tool","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 22250183 and published in Annals of Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background: Development of a geriatric screening tool is necessary to identify elderly cancer patients who would benefit from comprehensive geriatric assessment (CGA). We develop and evaluate the G-8 screening tool against various reference tests.\n\nPatients and methods: Analyses were based on 364 cancer patients aged>70 years scheduled to receive first-line chemotherapy included in a multicenter prospective study. The G-8 consists of seven items from the Mini Nutritional Assessment (MNA) questionnaire and age. Our primary reference test is based on a set of seven CGA scales: Activities Daily Living (ADL), Instrumental ADL, MNA, Mini-Mental State Exam, Geriatric Depression Scale, Cumulative Illness Rating Scale-Geriatrics, and Timed Get Up and Go. We considered the presence of at least one questionnaire with an impaired score as an abnormal reference exam. Additional reference exams are also discussed.\n\nResults: The prevalence of being at risk varied from 60% to 94% according to the various definitions of the reference test. When considering the primary reference test, a cut-off value of 14 for the G-8 tool provided a good sensitivity estimate (85%) without deteriorating the specificity excessively (65%).\n\nConclusion: The G-8 shows good screening properties for identifying elderly cancer patients who could benefit from CGA.\n\nIndexed on Europe PMC as PubMed record 22250183 (DOI 10.1093/annonc/mdr587). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Ann Oncol 2012","url":"https://doi.org/10.1093/annonc/mdr587"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22250183/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/22250183"}],"tags":["europepmc-ingest"],"related":["g8-geriatric-screening"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2012,"doi":"10.1093/annonc/mdr587","pmid":"22250183","authors":"Bellera CA, Rainfray M, Mathoulin-Pélissier S, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-masai-lancet-digit-health-2025","kind":"paper","name":"Screening performance and characteristics of breast cancer detected in the Mammography Screening with Artificial Intelligence trial (MASAI): a randomised, controlled, parallel-group, non-inferiority, single-blinded, screening accuracy study","aka":[],"tldr":"Published report from the MASAI trial registered as NCT04838756, in The Lancet Digital Health (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Emerging evidence suggests that artificial intelligence (AI) can increase cancer detection in mammography screening while reducing screen-reading workload, but further understanding of the clinical impact is needed.\n\nMethods: In this randomised, controlled, parallel-group, non-inferiority, single-blinded, screening-accuracy study, done within the Swedish national screening programme, women recruited at four screening sites in southwest Sweden (Malmö, Lund, Landskrona, and Trelleborg) who were eligible for mammography screening were randomly allocated (1:1) to AI-supported screening or standard double reading. The AI system (Transpara version 1.7.0 ScreenPoint Medical, Nijmegen, Netherlands) was used to triage screening examinations to single or double reading and as detection support highlighting suspicious findings. This is a protocol-defined analysis of the secondary outcome measures of recall, cancer detection, false-positive rates, positive predictive value of recall, type and stage of cancer detected, and screen-reading workload. This trial is registered at ClinicalTrials.gov, NCT04838756 and is closed to accrual.\n\nFindings: Between April 12, 2021, and Dec 7, 2022, 105 934 women were randomly assigned to the intervention or control group. 19 women were excluded from the analysis. The median age was 53·7 years (IQR 46·5-63·2). AI-supported screening among 53 043 participants resulted in 338 detected cancers and 1110 recalls. Standard screening among 52 872 participants resulted in 262 detected cancers and 1027 recalls. Cancer-detection rates were 6·4 per 1000 (95% CI 5·7-7·1) screened participants in the intervention group and 5·0 per 1000 (4·4-5·6) in the control group, a ratio of 1·29 (95% CI 1·09-1·51; p=0·0021). AI-supported screening resulted in an increased detection of invasive cancers (270 vs 217, a proportion ratio of 1·24 [95% CI 1·04-1·48]), wich were mainly small lymph-node negative cancers (58 more T1, 46 more lymph-node negative, and 21 more non-luminal A). AI-supported screening also resulted in an increased detection of in situ cancers (68 vs 45, a proportion ratio of 1·51 [1·03-2·19]), with about half of the increased detection being high-grade in situ cancer (12 more nuclear grade III, and no increase in nuclear grade I). The recall and false-positive rate were not significantly higher in the intervention group (a ratio of 1·08 [95% CI 0·99-1·17; p=0·084] and 1·01 [0·91-1·11; p=0·92], respectively). The positive predictive value of recall was significantly higher in the intervention group compared with the control group, with a ratio of 1·19 (95% CI 1·04-1·37; p=0·012). There were 61 248 screen readings in the intervention group and 109 692 in the control group, resulting in a 44·2% reduction in the screen-reading workload.\n\nInterpretation: The findings suggest that AI contributes to the early detection of clinically relevant breast cancer and reduces screen-reading workload without increasing false positives.\n\nFunding: Swedish Cancer Society, Confederation of Regional Cancer Centres, and Swedish governmental funding for clinical research.\n\nIndexed on Europe PMC as PubMed record 39904652 (DOI 10.1016/s2589-7500(24)00267-x). Its abstract cites the registry id NCT04838756, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Digit Health 2025","url":"https://doi.org/10.1016/s2589-7500(24)00267-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39904652/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39904652"},{"label":"ClinicalTrials.gov NCT04838756","url":"https://clinicaltrials.gov/study/NCT04838756"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["masai"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-digital-health"],"dependsOn":[],"notes":[],"journal":"The Lancet Digital Health","year":2025,"doi":"10.1016/s2589-7500(24)00267-x","pmid":"39904652","authors":"Hernström V, Josefsson V, Sartor H, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04838756 with the most citations, so it is the natural first reading for anyone following the MASAI trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-schaapveld-second-cancer-risk-40-years-hodgkin-nejm-2015","kind":"paper","name":"Second cancer risk up to 40 years after treatment for Hodgkin's lymphoma","aka":["Schaapveld 2015","Dutch Hodgkin late-effects cohort","Second malignancy after Hodgkin lymphoma"],"tldr":"Of nearly 4,000 Dutch people cured of Hodgkin lymphoma, almost half developed another cancer within forty years, and the gentler treatments introduced in the late 1980s had not reduced that risk.","summary":"This is the cohort that defines the cost of curing Hodgkin lymphoma. 3,905 people in the Netherlands who had survived at least five years after starting treatment between 1965 and 2000, aged 15 to 50 at the time, were followed and compared with cancer incidence in the general population.\n\nAt a median follow-up of 19.1 years, 1,055 second cancers were diagnosed in 908 patients, a standardised incidence ratio of 4.6 (95 per cent confidence interval 4.3 to 4.9). The risk was still raised 35 years or more after treatment (3.9, 2.8 to 5.4), and the cumulative incidence of a second cancer at 40 years was 48.5 per cent (45.4 to 51.5).\n\nThe finding that mattered most was the one the authors did not expect. The cumulative incidence of second solid cancers did not differ between the 1965 to 1976, 1977 to 1988 and 1989 to 2000 treatment periods (p = 0.71 for heterogeneity), despite the less toxic protocols introduced in the late 1980s. Breast cancer risk was lower in patients treated with supradiaphragmatic radiotherapy that spared the axilla than with mantle-field irradiation (hazard ratio 0.37, 0.19 to 0.72), but not lower in the most recent period. A cumulative procarbazine dose of 4.3 grams per square metre or more, which is associated with premature menopause, was associated with lower breast cancer risk (hazard ratio 0.57, 0.39 to 0.84) and higher gastrointestinal cancer risk (2.70, 1.69 to 4.30).","asOf":"2026-10-01","links":[{"label":"New England Journal of Medicine 2015","url":"https://doi.org/10.1056/NEJMoa1505949"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26699166/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26699166"}],"tags":["lymphoma-evidence"],"related":["paper-van-nimwegen-cardiovascular-disease-after-hodgkin-jama-intern-med-2015","paper-travis-breast-cancer-after-hodgkin-radiotherapy-jama-2003","lymphoma-roadmap"],"cancers":["hodgkin-lymphoma","early-stage-classical-hodgkin-lymphoma","advanced-stage-classical-hodgkin-lymphoma"],"sections":["radiation","supportive-care","prevention"],"technologies":["radiotherapy","proton-therapy"],"targets":[],"drugs":["procarbazine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["hd10","hd16","radar-hodgkin"],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol","b-overdiagnosis"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2015,"doi":"10.1056/NEJMoa1505949","pmid":"26699166","authors":"Schaapveld M, Aleman BM, van Eggermond AM, et al.","paperType":"observational","findings":["Among 3,905 five-year survivors of Hodgkin lymphoma, 1,055 second cancers occurred in 908 patients, a standardised incidence ratio of 4.6 (95 per cent confidence interval 4.3 to 4.9) against the general population.","The cumulative incidence of a second cancer at 40 years was 48.5 per cent (45.4 to 51.5).","Risk remained raised 35 years or more after treatment, with a standardised incidence ratio of 3.9 (2.8 to 5.4).","The cumulative incidence of second solid cancers did not differ between the 1965 to 1976, 1977 to 1988 and 1989 to 2000 treatment periods (p = 0.71 for heterogeneity).","A cumulative procarbazine dose of 4.3 grams per square metre or more was associated with lower breast cancer risk (hazard ratio 0.57, 0.39 to 0.84) and higher gastrointestinal cancer risk (2.70, 1.69 to 4.30)."],"whatItMeans":"The reason every current Hodgkin lymphoma trial is a de-escalation trial, and the reason survivors need lifelong surveillance rather than discharge at five years. It is also a warning about assuming that a gentler protocol is a safer one until a cohort has been followed long enough to say.","caveats":["Patients treated up to 2000, so the cohort does not include modern involved-site radiotherapy fields, proton therapy, or the brentuximab and checkpoint inhibitor regimens; the risks for people treated today are unknown and may be lower.","An observational cohort compared with population rates, not a randomised comparison of treatment eras.","The absence of a difference between treatment periods may partly reflect insufficient follow-up in the most recent group.","Dutch population rates may not transfer to populations with different background cancer incidence."],"changedPractice":true,"participants":3905},{"id":"paper-abc-06-folfox-second-line-lancet-oncol-2021","kind":"paper","name":"Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): a phase 3, open-label, randomised, controlled trial","aka":[],"tldr":"The UK trial that showed a second chemotherapy, FOLFOX, helps people with advanced bile duct or gallbladder cancer live about a month longer on average once gemcitabine and cisplatin stop working, with one in four alive at a year instead of one in nine.","summary":"ABC-06 randomised 162 patients at 20 UK sites between March 2014 and January 2018, after progression on cisplatin and gemcitabine, to active symptom control with or without FOLFOX for up to 12 cycles. Median overall survival was 6.2 months (95 percent CI 5.4 to 7.6) with FOLFOX against 5.3 months (4.1 to 5.8); adjusted hazard ratio 0.69 (0.50 to 0.97), p=0.031. Survival at 6 and 12 months was 50.6 and 25.9 percent with FOLFOX against 35.5 and 11.4 percent. Grade 3 to 5 adverse events occurred in 69 versus 52 percent, with three chemotherapy-related deaths.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2021","url":"https://doi.org/10.1016/S1470-2045(21)00027-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33798493/"},{"label":"ClinicalTrials.gov NCT01926236","url":"https://clinicaltrials.gov/study/NCT01926236"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder","cholangiocarcinoma","biliary-tract-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["folfox"],"companies":[],"institutions":["the-christie"],"pathways":[],"terms":["os"],"trials":["abc-06"],"people":["angela-lamarca","juan-valle"],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2021,"doi":"10.1016/S1470-2045(21)00027-9","pmid":"33798493","authors":"Lamarca A, Palmer DH, Wasan HS, et al.","paperType":"rct","findings":["Median overall survival 6.2 vs 5.3 months; adjusted hazard ratio 0.69 (95 percent CI 0.50 to 0.97), p=0.031.","Overall survival at 12 months 25.9 vs 11.4 percent; at 6 months 50.6 vs 35.5 percent.","Grade 3 to 5 adverse events 69 vs 52 percent; three chemotherapy-related deaths."],"whatItMeans":"FOLFOX became the guideline second-line option for gallbladder cancer on this trial. The gain is real but small, which is why later-line care now starts with a search for a HER2 or other targetable alteration.","caveats":["Open-label trial with a symptom-control comparator.","Gallbladder and ampullary cancers were included but not analysed as separate populations in the abstract."],"changedPractice":true,"participants":162},{"id":"paper-belinda-tisagenlecleucel-second-line-nejm-2022","kind":"paper","name":"Second-line tisagenlecleucel or standard care in aggressive B-cell lymphoma","aka":["BELINDA","Bishop 2022"],"tldr":"The one second-line CAR-T trial that failed. Its result is best explained by how long the cells took to make and what patients received while they waited.","summary":"An international phase 3 trial in patients whose aggressive B-cell lymphoma was refractory to, or progressed within 12 months of, first-line therapy. 322 patients were randomised to tisagenlecleucel with optional bridging therapy or to salvage chemotherapy and autologous haematopoietic stem-cell transplantation, with crossover allowed if a defined event occurred at or after the week 12 assessment.\n\nMedian event-free survival was 3.0 months in both groups (hazard ratio 1.07, 95 per cent confidence interval 0.82 to 1.40, p = 0.61), and response occurred in 46.3 per cent against 42.5 per cent. 95.7 per cent of the tisagenlecleucel group received the product and 32.5 per cent of the standard-care group received an autologous transplant. The median time from leukapheresis to infusion was 52 days, and 25.9 per cent of the tisagenlecleucel group had lymphoma progression by week 6 against 13.8 per cent of the standard-care group. Baseline imbalances favoured the standard-care group: 24.1 against 16.9 per cent had high-grade lymphoma and 65.4 against 57.5 per cent an International Prognostic Index of 2 or more. Ten patients in the tisagenlecleucel group and 13 in the standard-care group died from adverse events.","asOf":"2026-10-01","links":[{"label":"New England Journal of Medicine 2022","url":"https://doi.org/10.1056/NEJMoa2116596"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34904798/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34904798"}],"tags":["lymphoma-evidence"],"related":["lymphoma-roadmap"],"cancers":["dlbcl","non-hodgkin-lymphoma"],"sections":["cell-therapy"],"technologies":["car-t"],"targets":["cd19"],"drugs":["tisagenlecleucel"],"companies":["novartis"],"institutions":[],"pathways":[],"terms":["bridging-therapy","autologous-transplant","ipi-score","lymphoma-tx-car-t-pathway"],"trials":["belinda","zuma-7","transform","juliet"],"people":["michael-dickinson","jason-westin"],"bottlenecks":["b-manufacturing-cell-therapy","b-negative-results","b-trial-design"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/NEJMoa2116596","pmid":"34904798","authors":"Bishop MR, Dickinson M, Purtill D, et al.","paperType":"rct","findings":["Median event-free survival was 3.0 months in both groups (hazard ratio 1.07, 95 per cent confidence interval 0.82 to 1.40, p = 0.61).","Response occurred in 46.3 per cent of the tisagenlecleucel group and 42.5 per cent of the standard-care group.","The median time from leukapheresis to tisagenlecleucel infusion was 52 days.","25.9 per cent of the tisagenlecleucel group had lymphoma progression at week 6 against 13.8 per cent of the standard-care group.","At baseline the tisagenlecleucel group had more high-grade lymphoma (24.1 against 16.9 per cent) and more patients with an International Prognostic Index of 2 or higher (65.4 against 57.5 per cent).","32.5 per cent of patients in the standard-care group received an autologous transplant."],"whatItMeans":"The reason second-line CAR-T is offered with axicabtagene ciloleucel or lisocabtagene maraleucel rather than tisagenlecleucel. The trial is also the strongest evidence in the field that the interval between apheresis and infusion, and what is given during it, is part of the treatment rather than logistics around it.","caveats":["The baseline imbalance in high-grade histology and prognostic index favoured the standard-care group and was not adjusted for in the primary analysis.","Extensive bridging chemotherapy was permitted and widely used, which blurs the comparison with the salvage arm.","A 52-day median manufacturing interval is longer than in ZUMA-7 and TRANSFORM, which is the explanation most often offered for the difference in result, but it is a cross-trial comparison and not a tested hypothesis.","The event-free survival definition, which counted stable or progressive disease at or after week 12, differed from those used in the other two trials."],"changedPractice":true,"participants":322},{"id":"paper-karius-radiother-oncol","kind":"paper","name":"Seed-displacements in the immediate post-implant phase in permanent prostate brachytherapy","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 36858202 and published in Radiotherapy and Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: To investigate differences in seed-displacements between the immediate post-implant phase (day 0-1) and the time to post-plan computed tomography (CT) (day 1-30) in seed prostate brachytherapy.\n\nMaterials and methods: Seed positions were identified on the intra-operatively created ultrasound-based treatment plan (day 0) and CT scans of day 1 and 30 for 33 patients. The day 1 (30) seed arrangement was registered onto the day 0 (1) arrangement using a seed-only approach. Based on a 1:1 assignment of seeds via the Kuhn-Munkres algorithm, seed-displacements were analyzed. Displacements were evaluated depending on strand-length and anatomical implant location. Resulting dosimetric effects were calculated.\n\nResults: Seed-displacements in the immediate post-implant phase (median displacements: 3.8 ± 3.6 mm) were stronger than in the time to post-plan CT (2.1 ± 2.6 mm) and enhanced along the superior-inferior direction. From day 0 to 1, strands containing one (7.3 ± 5.4 mm) or two (8.1 ± 5.8 mm) seeds showed larger displacements than strands of higher lengths (up to 4.2 ± 7.0 mm), whereas no length-dependency was found to day 30. Seeds implanted in base and apex tended to move towards the prostate midzone during both time periods. D 90 (dose that 90% of prostate receives) was with variations of 2 ± 15 Gy more stable from day 1 to 30 than in the immediate post-implant phase (-18 ± 11 Gy).\n\nConclusion: Seed-displacements in the immediate post-implant phase was enhanced compared to day 1-30. This may result from uncertainties in the gold-standard ultrasound-based treatment planning and implantation. Adaptive implantation workflows appear useful for ensuring high implant stability from the beginning.\n\nIndexed on Europe PMC as PubMed record 36858202 (DOI 10.1016/j.radonc.2023.109590). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Radiother Oncol 2023","url":"https://doi.org/10.1016/j.radonc.2023.109590"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36858202/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36858202"}],"tags":["europepmc-ingest"],"related":["vaginal"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["radiotherapy-and-oncology"],"dependsOn":[],"notes":[],"journal":"Radiotherapy and Oncology","year":2023,"doi":"10.1016/j.radonc.2023.109590","pmid":"36858202","authors":"Karius A, Schweizer C, Strnad V, et al.","paperType":"observational","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-ma-nat-commun","kind":"paper","name":"Segment anything in medical images","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 38253604 and published in Nature Communications; the citing page links this DOI, which is how the record was matched.","summary":"Medical image segmentation is a critical component in clinical practice, facilitating accurate diagnosis, treatment planning, and disease monitoring. However, existing methods, often tailored to specific modalities or disease types, lack generalizability across the diverse spectrum of medical image segmentation tasks. Here we present MedSAM, a foundation model designed for bridging this gap by enabling universal medical image segmentation. The model is developed on a large-scale medical image dataset with 1,570,263 image-mask pairs, covering 10 imaging modalities and over 30 cancer types. We conduct a comprehensive evaluation on 86 internal validation tasks and 60 external validation tasks, demonstrating better accuracy and robustness than modality-wise specialist models. By delivering accurate and efficient segmentation across a wide spectrum of tasks, MedSAM holds significant potential to expedite the evolution of diagnostic tools and the personalization of treatment plans.\n\nIndexed on Europe PMC as PubMed record 38253604 (DOI 10.1038/s41467-024-44824-z). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Commun 2024","url":"https://doi.org/10.1038/s41467-024-44824-z"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38253604/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38253604"}],"tags":["europepmc-ingest"],"related":["medsam"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-communications"],"dependsOn":[],"notes":[],"journal":"Nature Communications","year":2024,"doi":"10.1038/s41467-024-44824-z","pmid":"38253604","authors":"Ma J, He Y, Li F, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-select-lenvatinib-nejm-2015","kind":"paper","name":"SELECT: lenvatinib versus placebo in radioiodine-refractory differentiated thyroid cancer","aka":[],"tldr":"The multikinase inhibitor lenvatinib delayed progression by almost fifteen months compared with placebo in iodine-refractory differentiated thyroid cancer and shrank tumours in two thirds of patients, becoming the preferred drug for this disease.","summary":"Phase 3 placebo-controlled trial of 392 patients with progressive radioiodine-refractory differentiated thyroid cancer randomised 2:1 to lenvatinib 24 mg daily or placebo.\n\nMedian progression-free survival was 18.3 versus 3.6 months (hazard ratio 0.21) and response 64.8 versus 1.5 percent; hypertension, diarrhoea, fatigue and proteinuria led to dose reductions in most patients, and there were six treatment-related deaths.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2015","url":"https://doi.org/10.1056/NEJMoa1406470"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25671254/"}],"tags":[],"related":[],"cancers":["follicular-thyroid-cancer","papillary-thyroid-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["lenvatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["select-lenvatinib"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2015,"doi":"10.1056/NEJMoa1406470","pmid":"25671254","authors":"Schlumberger M, Tahara M, Wirth LJ, et al.","paperType":"rct","findings":["Median progression-free survival 18.3 vs 3.6 months; hazard ratio 0.21.","Objective response 64.8 percent vs 1.5 percent."],"whatItMeans":"Lenvatinib is the first-choice kinase inhibitor for progressive iodine-refractory papillary and follicular thyroid cancer, reserved for symptomatic or rapidly progressing disease because of its toxicity.","caveats":["No overall survival benefit because of crossover.","Starting dose debate; 18 mg was not non-inferior in a later study."],"changedPractice":true,"participants":392},{"id":"paper-filippakopoulos-nature","kind":"paper","name":"Selective inhibition of BET bromodomains","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 20871596 and published in Nature; the citing page links this DOI, which is how the record was matched.","summary":"Epigenetic proteins are intently pursued targets in ligand discovery. So far, successful efforts have been limited to chromatin modifying enzymes, or so-called epigenetic 'writers' and 'erasers'. Potent inhibitors of histone binding modules have not yet been described. Here we report a cell-permeable small molecule (JQ1) that binds competitively to acetyl-lysine recognition motifs, or bromodomains. High potency and specificity towards a subset of human bromodomains is explained by co-crystal structures with bromodomain and extra-terminal (BET) family member BRD4, revealing excellent shape complementarity with the acetyl-lysine binding cavity. Recurrent translocation of BRD4 is observed in a genetically-defined, incurable subtype of human squamous carcinoma. Competitive binding by JQ1 displaces the BRD4 fusion oncoprotein from chromatin, prompting squamous differentiation and specific antiproliferative effects in BRD4-dependent cell lines and patient-derived xenograft models. These data establish proof-of-concept for targeting protein-protein interactions of epigenetic 'readers', and provide a versatile chemical scaffold for the development of chemical probes more broadly throughout the bromodomain family.\n\nIndexed on Europe PMC as PubMed record 20871596 (DOI 10.1038/nature09504). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2010","url":"https://doi.org/10.1038/nature09504"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20871596/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/20871596"}],"tags":["europepmc-ingest"],"related":["nut-carcinoma"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2010,"doi":"10.1038/nature09504","pmid":"20871596","authors":"Filippakopoulos P, Qi J, Picaud S, et al.","paperType":"basic","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-hpv-self-sampling-bmj-2018","kind":"paper","name":"Self-collected HPV samples are as accurate as clinician samples and reach women who never attend screening","aka":[],"tldr":"A meta-analysis of 56 accuracy studies and 25 randomised trials found that self-sampled swabs tested with PCR detect precancer as well as clinician-taken samples, and mailing kits to under-screened women roughly doubles participation.","summary":"Arbyn and colleagues pooled diagnostic accuracy studies comparing HPV testing on self-collected versus clinician-collected samples, and randomised trials comparing strategies to reach under-screened women.\n\nWith PCR-based assays, sensitivity for CIN2+ and CIN3+ on self samples was equivalent to clinician samples (relative sensitivity 0.99) and specificity was marginally lower (0.98). Signal-amplification assays performed worse on self samples. Mailing self-sampling kits to all under-screened women increased participation more than twofold compared with an invitation letter, as did door-to-door offers; opt-in kits produced smaller gains.\n\nThe findings underpin WHO and national guidance that self-sampling is an acceptable primary screening method.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1136/bmj.k4823"}],"tags":[],"related":["idea-prev-hpv-self-sampling-mailed-default","idea-prev-hpv-same-day-screen-and-treat","idea-acc-hpv-self-sample-same-day-ablation"],"cancers":["cervical"],"sections":["early-detection","prevention"],"technologies":["hpv-testing","hpv-vaccine"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-global-access","b-early-detection"],"keyPapers":[],"journals":["bmj"],"dependsOn":[],"notes":[],"journal":"BMJ","year":2018,"doi":"10.1136/bmj.k4823","pmid":"30518635","authors":"Arbyn M, Smith SB, Temin S, Sultana F, Castle P","paperType":"meta-analysis","findings":["PCR-based assays: pooled relative sensitivity of self vs clinician samples 0.99 for CIN2+, relative specificity 0.98","Signal-amplification assays were less sensitive on self samples (relative sensitivity 0.85 for CIN2+)","Mailing kits to under-screened women increased participation about 2.3-fold versus invitation letters","Opt-in approaches (women must request a kit) gave only modest participation gains"],"whatItMeans":"Women can collect their own screening sample at home with no loss of accuracy if the laboratory uses a PCR test. Sending kits directly is the most effective way to reach women who do not attend, which matters because most cervical cancers occur in under-screened women.","caveats":["Accuracy equivalence holds only for PCR-based assays validated for self samples","Triage of positive self-samples still requires a clinic visit; follow-up completion is the weak point","Participation trials were heterogeneous in setting and delivery","Self-sampling for cytology (rather than HPV) is not supported"],"changedPractice":true},{"id":"paper-nct04819100-n-engl-j-med-2026","kind":"paper","name":"Selpercatinib in Early-Stage RET Fusion-Positive Non-Small-Cell Lung Cancer","aka":[],"tldr":"Published report from the LIBRETTO-432 trial registered as NCT04819100, in New England Journal of Medicine (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Selpercatinib, a highly selective, potent, and central nervous system-penetrant RET inhibitor, is approved for RET fusion-positive advanced or metastatic non-small-cell lung cancer (NSCLC). The efficacy and safety of selpercatinib in early-stage NSCLC are unknown.\n\nMethods: We conducted a phase 3, double-blind trial involving patients with RET fusion-positive NSCLC who had received definitive therapy with curative intent (surgery or radiotherapy with adjuvant systemic anticancer therapy, if applicable). Patients were randomly assigned to receive adjuvant selpercatinib or placebo for up to 3 years. The primary end point was investigator-assessed event-free survival in patients with stage II or IIIA disease. Secondary end points were investigator-assessed event-free survival in patients with stage IB, II, or IIIA disease; event-free survival as assessed by blinded independent central review; overall survival; and safety.\n\nResults: A total of 151 patients were assigned to receive selpercatinib (75 patients) or placebo (76 patients). Median follow-up was 24 months and 27 months in the respective groups. Among 109 patients with stage II or IIIA disease, 2-year investigator-assessed event-free survival was 92% with selpercatinib and 61% with placebo (hazard ratio for disease recurrence, progression, or death, 0.17; 95% confidence interval [CI], 0.06 to 0.51; P<0.001). Event-free survival as assessed by blinded independent central review was consistent with investigator-assessed event-free survival. Among the 151 patients with stage IB, II, or IIIA NSCLC, investigator-assessed event-free survival at 2 years was 94% with selpercatinib and 70% with placebo (hazard ratio for disease recurrence, progression, or death, 0.16; 95% CI, 0.06 to 0.48; P<0.001). The most common adverse events during the treatment period were increased levels of alanine aminotransferase and aspartate aminotransferase (grade ≥3 in 17% and 19% of patients, respectively, in the selpercatinib group). Three deaths occurred, all in the placebo group, owing to disease progression.\n\nConclusions: Among patients with stage II or IIIA RET fusion-positive NSCLC, event-free survival was significantly longer with adjuvant selpercatinib than with placebo. (Funded by Lilly; LIBRETTO-432 ClinicalTrials.gov number, NCT04819100.).\n\nIndexed on Europe PMC as PubMed record 42223087 (DOI 10.1056/nejmoa2602628). Its abstract cites the registry id NCT04819100, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2026","url":"https://doi.org/10.1056/nejmoa2602628"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42223087/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42223087"},{"label":"ClinicalTrials.gov NCT04819100","url":"https://clinicaltrials.gov/study/NCT04819100"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04819100"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2026,"doi":"10.1056/nejmoa2602628","pmid":"42223087","authors":"Wu YL, Hochmair M, Yang Y, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04819100 with the most citations, so it is the natural first reading for anyone following the LIBRETTO-432 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-nct01933932-jama-2017","kind":"paper","name":"Selumetinib Plus Docetaxel Compared With Docetaxel Alone and Progression-Free Survival in Patients With KRAS-Mutant Advanced Non-Small Cell Lung Cancer: The SELECT-1 Randomized Clinical Trial","aka":[],"tldr":"Published report from the SELECT 1 trial registered as NCT01933932, in JAMA (2017), chosen as the most cited paper whose own text cites the registry id.","summary":"Importance: There are no specifically approved targeted therapies for the most common genomically defined subset of non-small cell lung cancer (NSCLC), KRAS-mutant lung cancer.\n\nObjective: To compare efficacy of the mitogen-activated protein kinase kinase (MEK) inhibitor selumetinib + docetaxel with docetaxel alone as a second-line therapy for advanced KRAS-mutant NSCLC.\n\nDesign, setting, and participants: Multinational, randomized clinical trial conducted at 202 sites across 25 countries from October 2013 through January 2016. Of 3323 patients with advanced NSCLC and disease progression following first-line anticancer therapy tested for a KRAS mutation, 866 were enrolled and 510 randomized. Primary reason for exclusion was ineligibility. The data cutoff date for analysis was June 7, 2016.\n\nInterventions: Patients were randomized 1:1; 254 to receive selumetinib + docetaxel and 256 to receive placebo + docetaxel.\n\nMain outcomes and measures: Primary end point was investigator assessed progression-free survival. Secondary end points included overall survival, objective response rate, duration of response, effects on disease-related symptoms, safety, and tolerability.\n\nResults: Of 510 randomized patients (mean age, 61.4 years [SD, 8.3]; women, 207 [41%]), 505 patients (99%) received treatment and completed the study (251 received selumetinib + docetaxel; 254 received placebo + docetaxel). At the time of data cutoff, 447 patients (88%) had experienced a progression event and 346 deaths (68%) had occurred. Median progression-free survival was 3.9 months (interquartile range [IQR], 1.5-5.9) with selumetinib + docetaxel and 2.8 months (IQR, 1.4-5.5) with placebo + docetaxel (difference, 1.1 months; hazard ratio [HR], 0.93 [95% CI, 0.77-1.12]; P =.44). Median overall survival was 8.7 months (IQR, 3.6-16.8) with selumetinib + docetaxel and 7.9 months (IQR, 3.8-20.1) with placebo + docetaxel (difference, 0.9 months; HR, 1.05 [95% CI, 0.85-1.30]; P =.64). Objective response rate was 20.1% with selumetinib + docetaxel and 13.7% with placebo + docetaxel (difference, 6.4%; odds ratio, 1.61 [95% CI, 1.00-2.62]; P =.05). Median duration of response was 2.9 months (IQR, 1.7-4.8; 95% CI, 2.7-4.1) with selumetinib + docetaxel and 4.5 months (IQR, 2.3-7.3; 95% CI, 2.8-5.6) with placebo + docetaxel. Adverse events of grade 3 or higher were more frequent with selumetinib + docetaxel (169 adverse events [67%] for selumetinib + docetaxel vs 115 adverse events [45%] for placebo + docetaxel; difference, 22%).\n\nConclusions and relevance: Among patients with previously treated advanced KRAS-mutant non-small cell lung cancer, addition of selumetinib to docetaxel did not improve progression-free survival compared with docetaxel alone.\n\nTrial registration: clinicaltrials.gov: NCT01933932.\n\nIndexed on Europe PMC as PubMed record 28492898 (DOI 10.1001/jama.2017.3438). Its abstract cites the registry id NCT01933932, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"JAMA 2017","url":"https://doi.org/10.1001/jama.2017.3438"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28492898/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28492898"},{"label":"ClinicalTrials.gov NCT01933932","url":"https://clinicaltrials.gov/study/NCT01933932"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct01933932"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2017,"doi":"10.1001/jama.2017.3438","pmid":"28492898","authors":"Jänne PA, van den Heuvel MM, Barlesi F, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT01933932 with the most citations, so it is the natural first reading for anyone following the SELECT 1 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-lincoff-n-engl-j-med","kind":"paper","name":"Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 37952131 and published in New England Journal of Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Background: Semaglutide, a glucagon-like peptide-1 receptor agonist, has been shown to reduce the risk of adverse cardiovascular events in patients with diabetes. Whether semaglutide can reduce cardiovascular risk associated with overweight and obesity in the absence of diabetes is unknown.\n\nMethods: In a multicenter, double-blind, randomized, placebo-controlled, event-driven superiority trial, we enrolled patients 45 years of age or older who had preexisting cardiovascular disease and a body-mass index (the weight in kilograms divided by the square of the height in meters) of 27 or greater but no history of diabetes. Patients were randomly assigned in a 1:1 ratio to receive once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo. The primary cardiovascular end point was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke in a time-to-first-event analysis. Safety was also assessed.\n\nResults: A total of 17,604 patients were enrolled; 8803 were assigned to receive semaglutide and 8801 to receive placebo. The mean (±SD) duration of exposure to semaglutide or placebo was 34.2±13.7 months, and the mean duration of follow-up was 39.8±9.4 months. A primary cardiovascular end-point event occurred in 569 of the 8803 patients (6.5%) in the semaglutide group and in 701 of the 8801 patients (8.0%) in the placebo group (hazard ratio, 0.80; 95% confidence interval, 0.72 to 0.90; P<0.001). Adverse events leading to permanent discontinuation of the trial product occurred in 1461 patients (16.6%) in the semaglutide group and 718 patients (8.2%) in the placebo group (P<0.001).\n\nConclusions: In patients with preexisting cardiovascular disease and overweight or obesity but without diabetes, weekly subcutaneous semaglutide at a dose of 2.4 mg was superior to placebo in reducing the incidence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke at a mean follow-up of 39.8 months. (Funded by Novo Nordisk; SELECT ClinicalTrials.gov number, NCT03574597.).\n\nIndexed on Europe PMC as PubMed record 37952131 (DOI 10.1056/nejmoa2307563). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2023","url":"https://doi.org/10.1056/nejmoa2307563"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37952131/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37952131"}],"tags":["europepmc-ingest"],"related":["glp1-agonists-cancer-risk"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/nejmoa2307563","pmid":"37952131","authors":"Lincoff AM, Brown-Frandsen K, Colhoun HM, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-widdison-j-med-chem","kind":"paper","name":"Semisynthetic maytansine analogues for the targeted treatment of cancer","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 16821799 and published in Journal of medicinal chemistry; the citing page links this DOI, which is how the record was matched.","summary":"Maytansine, a highly cytotoxic natural product, failed as an anticancer agent in human clinical trials because of unacceptable systemic toxicity. The potent cell killing ability of maytansine can be used in a targeted delivery approach for the selective destruction of cancer cells. A series of new maytansinoids, bearing a disulfide or thiol substituent were synthesized. The chain length of the ester side chain and the degree of steric hindrance on the carbon atom bearing the thiol substituent were varied. Several of these maytansinoids were found to be even more potent in vitro than maytansine. The targeted delivery of these maytansinoids, using monoclonal antibodies, resulted in a high, specific killing of the targeted cells in vitro and remarkable antitumor activity in vivo.\n\nIndexed on Europe PMC as PubMed record 16821799 (DOI 10.1021/jm060319f). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Med Chem 2006","url":"https://doi.org/10.1021/jm060319f"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/16821799/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/16821799"}],"tags":["europepmc-ingest"],"related":["dm4"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of medicinal chemistry","year":2006,"doi":"10.1021/jm060319f","pmid":"16821799","authors":"Widdison WC, Wilhelm SD, Cavanagh EE, et al.","paperType":"basic","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-sempet-de-santis-jco-2004","kind":"paper","name":"SEMPET: FDG-PET as a predictor of viable tumour in post-chemotherapy seminoma residuals","aka":[],"tldr":"A PET scan reliably told apart residual masses that still contained living seminoma from scar tissue after chemotherapy, allowing surgeons to leave PET-negative masses alone rather than operating on all masses over 3 cm.","summary":"Prospective multicentre study of 51 patients with metastatic seminoma and residual masses after chemotherapy who underwent FDG-PET, with results validated against histology or clinical follow-up.\n\nPET had a sensitivity of 80 percent and specificity of 100 percent for viable tumour, and for residual lesions over 3 cm specificity and sensitivity were both 100 percent, outperforming CT size criteria.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2004","url":"https://doi.org/10.1200/JCO.2004.07.188"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/15020605/"}],"tags":[],"related":[],"cancers":["seminoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["maria-de-santis"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2004,"doi":"10.1200/JCO.2004.07.188","pmid":"15020605","authors":"De Santis M, Becherer A, Bokemeyer C, et al.","paperType":"observational","findings":["Specificity 100 percent, sensitivity 80 percent for viable residual seminoma.","Sensitivity and specificity 100 percent for lesions over 3 cm."],"whatItMeans":"FDG-PET is standard for residual seminoma masses larger than 3 cm after chemotherapy, sparing most men surgery.","caveats":["Small study; false positives occur when PET is done too soon after chemotherapy, so scans are delayed at least six weeks."],"changedPractice":true,"participants":51},{"id":"paper-schmitt-nat-rev-clin-oncol","kind":"paper","name":"Senescence and cancer - role and therapeutic opportunities","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 36045302 and published in Nature Reviews Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Cellular senescence is a state of stable, terminal cell cycle arrest associated with various macromolecular changes and a hypersecretory, pro-inflammatory phenotype. Entry of cells into senescence can act as a barrier to tumorigenesis and, thus, could in principle constitute a desired outcome for any anticancer therapy. Paradoxically, studies published in the past decade have demonstrated that, in certain conditions and contexts, malignant and non-malignant cells with lastingly persistent senescence can acquire pro-tumorigenic properties. In this Review, we first discuss the major mechanisms involved in the antitumorigenic functions of senescent cells and then consider the cell-intrinsic and cell-extrinsic factors that participate in their switch towards a tumour-promoting role, providing an overview of major translational and emerging clinical findings. Finally, we comprehensively describe various senolytic and senomorphic therapies and their potential to benefit patients with cancer.\n\nIndexed on Europe PMC as PubMed record 36045302 (DOI 10.1038/s41571-022-00668-4). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Clin Oncol 2022","url":"https://doi.org/10.1038/s41571-022-00668-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36045302/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36045302"}],"tags":["europepmc-ingest"],"related":["senescence"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-clinical-oncology"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Clinical Oncology","year":2022,"doi":"10.1038/s41571-022-00668-4","pmid":"36045302","authors":"Schmitt CA, Wang B, Demaria M","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-lutetium-177-vipivotide-tetrax-prostate-oncol-ther-2025","kind":"paper","name":"Sequencing of Radium-223 and Lutetium-177 Vipivotide Tetraxetan: Maximizing the Benefit of Systemic Targeted Radiation Therapy in Metastatic Castration-Resistant Prostate Cancer","aka":[],"tldr":"Review on Lutetium-177 vipivotide tetraxetan in Prostate cancer, in Oncology and therapy (2025), one of the most cited Europe PMC records with Lutetium-177 vipivotide tetraxetan in its title.","summary":"Introduction: The goals of treatment for metastatic castration-resistant prostate cancer are disease management, improving quality of life, and prolonging life. Although androgen-receptor blockade and chemotherapy can control the disease for several years in most patients, resistance to treatment and continued disease progression are inevitable. Radionuclides have emerged as important tools in the therapeutic arsenal against prostate cancer. Appropriate sequencing with existing standards of care is paramount to ensure that patients get the maximum clinical benefit from as many life-prolonging therapies as possible during the treatment journey.\n\nMethods: We review radionuclide therapy for men with metastatic castration-resistant prostate cancer and present a treatment algorithm used in our specialist center to provide optimal care.\n\nResults: The goal of the treatment algorithm employed in our specialist center is to provide optimal patient care by using and sequencing appropriate systemic radionuclide therapy. The first step is to determine the extent of disease and metastases to offer personalized treatment to extend survival. Appropriate treatment sequencing can allow men to receive the life-prolonging benefits of radium-223 immediately upon bone-only progression, while remaining eligible to benefit from chemotherapy and/or lutetium-177 vipivotide tetraxetan ( 177 Lu-PSMA) upon further disease progression. Importantly, although prostate-specific antigen (PSA) is frequently perceived as a marker for prostatic disease burden, survival benefits of radionuclide therapy may be independent of change in PSA.\n\nConclusions: As the majority of men with metastatic castration-resistant prostate cancer first present with bone-only metastases, they may be treated initially with radium-223, while still remaining eligible to benefit from chemotherapy and 177 Lu-PSMA upon subsequent progression of skeletal metastatic disease and/or the emergence of lymph node or visceral metastases. Graphical abstract available for this article.\n\nIndexed on Europe PMC as PubMed record 41060609 (DOI 10.1007/s40487-025-00377-9). Its title names Lutetium-177 vipivotide tetraxetan and its text names Prostate cancer; PubMed types it as a review (review-article, Review). It was matched automatically to the idea \"Alpha-emitting PSMA therapy at first metastatic diagnosis\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Oncol Ther 2025","url":"https://doi.org/10.1007/s40487-025-00377-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41060609/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41060609"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Oncology and therapy","year":2025,"doi":"10.1007/s40487-025-00377-9","pmid":"41060609","authors":"Mehr S, Hauke R","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for Lutetium-177 vipivotide tetraxetan in Prostate cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Lutetium-177 vipivotide tetraxetan in the title and Prostate cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-trappe-lancet-oncol","kind":"paper","name":"Sequential treatment with rituximab followed by CHOP chemotherapy in adult B-cell post-transplant lymphoproliferative disorder (PTLD): the prospective international multicentre phase 2 PTLD-1 trial","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 22173060 and published in The Lancet Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background: Post-transplantation lymphoproliferative disorder (PTLD) develops in 1-10% of transplant recipients and can be Epstein-Barr virus (EBV) associated. To improve long-term efficacy after rituximab monotherapy and to avoid the toxic effects of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy seen in first-line treatment, we initiated a phase 2 trial to test whether the subsequent use of rituximab and CHOP would improve the outcome of patients with PTLD.\n\nMethods: In this international multicentre open-label phase 2 trial, treatment-naive adult solid-organ transplant recipients diagnosed with CD20-positive PTLD who had failed to respond to upfront immunosuppression reduction received four courses of rituximab (375 mg/m(2) intravenously) once a week followed by 4 weeks without treatment and four cycles of CHOP every 3 weeks. In case of disease progression during rituximab monotherapy, CHOP was started immediately. Supportive therapy with granulocyte-colony stimulating factor after chemotherapy was mandatory and antibiotic prophylaxis was recommended. The primary endpoint was treatment efficacy measured as response rates in all patients who completed treatment with rituximab and CHOP, per protocol, and response duration, in all patients who completed all planned therapy and responded. Secondary endpoints were frequency of infections, treatment-related mortality, and overall survival. This study is registered at ClinicalTrials.gov, number NCT01458548.\n\nFindings: 74 patients were enrolled between Dec 12, 2002 and May 5, 2008, of whom 70 patients were eligible to receive treatment. PTLD was of late type in 53 (76%) of 70 patients, monomorphic in 67 (96%) of 70, and histologically EBV associated in 29 (44%) of 66 cases. Four of 70 patients did not receive CHOP. 53 of 59 patients had a complete or partial response (90%, 95% CI 79-96), of which 40 (68%, 55-78) were complete responses. At data cutoff (June 1, 2011) median response duration in the 53 patients who had responded to treatment had not yet been reached (>79·1 months). The main adverse events were grade 3-4 leucopenia in 42 of 62 patients (68%, 55-78) and infections of grade 3-4 in 26 of 64 patients (41%, 29-53). Seven of 66 patients (11%, 5-21) had CHOP-associated treatment-related mortality. Median overall survival was 6·6 years (95% CI 2·8-10·4; n=70).\n\nInterpretation: Our results support the use of sequential immunochemotherapy with rituximab and CHOP in PTLD.\n\nFunding: F Hoffmann-La Roche, Amgen Germany, Chugaï France.\n\nIndexed on Europe PMC as PubMed record 22173060 (DOI 10.1016/s1470-2045(11)70300-x). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2012","url":"https://doi.org/10.1016/s1470-2045(11)70300-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22173060/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/22173060"}],"tags":["europepmc-ingest"],"related":["post-transplant-lymphoproliferative-disorder"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2012,"doi":"10.1016/s1470-2045(11)70300-x","pmid":"22173060","authors":"Trappe R, Oertel S, Leblond V, et al.","paperType":"observational","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-transcend-miller-nejm-2026","kind":"paper","name":"Setmelanotide for the treatment of acquired hypothalamic obesity (TRANSCEND)","aka":[],"tldr":"In children and adults whose severe weight gain followed damage to the hypothalamus, a year of daily setmelanotide injections cut body-mass index by 16.5 percent while placebo recipients gained 3.3 percent, and hunger fell more too.","summary":"Primary publication of TRANSCEND (NCT05774756). Participants aged 4 years and older with acquired hypothalamic obesity, defined by a body-mass index at or above the 95th percentile for age and sex (under 18) or at least 30 (18 and over) and a history of a hypothalamic tumour, lesion or injury, were randomly assigned 2:1 to setmelanotide 1.5 to 3.0 mg or placebo, given subcutaneously once daily for 52 weeks after dose escalation. The primary endpoint was the mean percent change in body-mass index from baseline to 52 weeks after the end of dose escalation; the weekly average of maximal daily hunger scores (0 to 10) in participants aged 12 and older was a secondary endpoint.\n\nFrom 26 April 2023 to 18 March 2025, 120 participants were assigned to setmelanotide (81) or placebo (39); mean age 19.9 years (range 4 to 66). The least-squares mean change in body-mass index at 52 weeks was minus 16.5 percent (95 percent CI minus 19.3 to minus 13.8) with setmelanotide and 3.3 percent (minus 0.6 to 7.2) with placebo (P less than 0.001); the hunger score changed by minus 2.73 (minus 3.28 to minus 2.18) versus minus 1.45 (minus 2.23 to minus 0.67) (P = 0.009). Adverse events were reported in 100 percent and 90 percent of participants and serious adverse events in 28 percent and 8 percent; skin hyperpigmentation, nausea, vomiting and headache were the commonest events with setmelanotide.","asOf":"2026-09-24","links":[{"label":"NEJM 2026","url":"https://doi.org/10.1056/NEJMoa2512275"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42418774/"},{"label":"ClinicalTrials.gov NCT05774756","url":"https://clinicaltrials.gov/study/NCT05774756"}],"tags":[],"related":[],"cancers":["craniopharyngioma"],"sections":["supportive-care"],"technologies":[],"targets":[],"drugs":["setmelanotide"],"companies":["rhythm-pharmaceuticals"],"institutions":[],"pathways":[],"terms":[],"trials":["transcend"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2026,"doi":"10.1056/NEJMoa2512275","pmid":"42418774","authors":"Miller JL, van Santen HM, Phillips SA, et al.","paperType":"rct","findings":["Least-squares mean change in body-mass index at 52 weeks: minus 16.5 percent with setmelanotide vs plus 3.3 percent with placebo (P<0.001).","Hunger score (participants aged 12 and older): minus 2.73 vs minus 1.45 (P = 0.009).","Serious adverse events in 28 percent vs 8 percent; skin hyperpigmentation, nausea, vomiting and headache were the commonest events with setmelanotide."],"whatItMeans":"For survivors of craniopharyngioma and other hypothalamic injuries, whose weight gain has resisted diet and conventional drugs, this is the first randomised evidence of a treatment that works on the damaged satiety pathway itself. The FDA extended the Imcivree label to acquired hypothalamic obesity in March 2026 on this trial.","caveats":["One year of follow-up; durability beyond 52 weeks and effects on cardiometabolic outcomes are not yet reported.","Serious adverse events were more than three times as frequent with setmelanotide (28 percent vs 8 percent).","The abstract does not give the size of the age 12 and older subgroup used for the hunger endpoint."],"changedPractice":true,"participants":120},{"id":"paper-soho-01-n-engl-j-med-2025","kind":"paper","name":"Sevabertinib in Advanced HER2 -Mutant Non-Small-Cell Lung Cancer","aka":[],"tldr":"Published report from the SOHO-01 trial registered as NCT05099172, in New England Journal of Medicine (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: HER2 gene mutations occur in 2 to 4% of patients with non-small-cell lung cancer (NSCLC). Sevabertinib is an oral, reversible tyrosine kinase inhibitor that has shown anti-HER2 activity in preclinical models.\n\nMethods: We conducted an open-label, multicenter, multicohort, phase 1-2 study to evaluate sevabertinib at a twice-daily dose of 20 mg in patients with locally advanced or metastatic HER2 -mutant NSCLC. Three cohorts were defined according to previous therapy: cohort D comprised previously treated patients who had not received HER2-targeted therapy; cohort E, patients who had previously received HER2-directed antibody-drug conjugates; and cohort F, patients who had not previously received treatment. The primary end point was an objective response, as assessed by blinded independent central review. Secondary end points were duration of response and progression-free survival.\n\nResults: A total of 209 patients received sevabertinib (at June 27, 2025, the data-cutoff date); the median duration of follow-up was 13.8 months in cohort D, 11.7 months in cohort E, and 9.9 months in cohort F. Among 81 patients in cohort D, an objective response was observed in 64% (95% confidence interval [CI], 53 to 75); the median duration of response was 9.2 months (95% CI, 6.3 to 13.5), and the median progression-free survival was 8.3 months (95% CI, 6.9 to 12.3). Among 55 patients in cohort E, an objective response was observed in 38% (95% CI, 25 to 52); the median duration of response was 8.5 months, and the median progression-free survival was 5.5 months. Among 73 patients in cohort F, an objective response was observed in 71% (95% CI, 59 to 81), and the median duration of response was 11.0 months; data on progression-free survival were immature. Grade 3 or higher drug-related adverse events occurred in 31% of the patients. The most common adverse event was diarrhea (in 84 to 91%), with diarrhea of grade 3 or higher occurring in 5 to 23%. Treatment was discontinued by 3% of the patients owing to drug-related adverse events.\n\nConclusions: Sevabertinib showed antitumor activity in patients with locally advanced or metastatic HER2 -mutant NSCLC. Diarrhea was the most common adverse event. (Funded by Bayer; SOHO-01 ClinicalTrials.gov number, NCT05099172.).\n\nIndexed on Europe PMC as PubMed record 41104928 (DOI 10.1056/nejmoa2511065). Its abstract cites the registry id NCT05099172, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2025","url":"https://doi.org/10.1056/nejmoa2511065"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41104928/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41104928"},{"label":"ClinicalTrials.gov NCT05099172","url":"https://clinicaltrials.gov/study/NCT05099172"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["soho-01"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2025,"doi":"10.1056/nejmoa2511065","pmid":"41104928","authors":"Le X, Kim TM, Loong HH, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05099172 with the most citations, so it is the natural first reading for anyone following the SOHO-01 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-thakurdesai-fenbendazole-liver-injury-2024","kind":"paper","name":"Severe drug-induced liver injury due to self-administration of the veterinary anthelmintic medication fenbendazole","aka":[],"tldr":"The first biopsy-confirmed case of severe liver injury from a dog dewormer taken for cancer: a 67-year-old woman with two weeks of jaundice whose liver tests took three months to recover.","summary":"Fenbendazole is approved for veterinary use only, and its human use appears to be increasing because social media popularises its potential anticancer effects (Thakurdesai case report 2024). The authors describe the first case of histologically confirmed severe drug-induced liver injury, hepatocellular pattern, in a 67-year-old woman who presented with two weeks of jaundice after self-administering fenbendazole; liver function tests normalised three months after she stopped (Thakurdesai case report 2024).","asOf":"2026-09-24","links":[{"label":"Thakurdesai case report 2024","url":"https://doi.org/10.14309/crj.0000000000001354"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38706451/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["fenbendazole"],"companies":[],"institutions":[],"pathways":[],"terms":["hepatotoxicity"],"trials":[],"people":[],"bottlenecks":["b-misinformation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo agent (Claude Fable 5.1)","editedOn":"2026-09-24","note":"Written from cached ClinicalTrials.gov v2, Europe PMC, DailyMed, Drugs@FDA and WHO eEML responses; no figure appears without its source link."},"journal":"ACG Case Reports Journal","year":2024,"doi":"10.14309/crj.0000000000001354","pmid":"38706451","authors":"Thakurdesai A, Rivera-Matos L, Nagra N, Busch B, Mais DD, Cave MC.","paperType":"observational","findings":["Histologically confirmed hepatocellular liver injury from self-administered fenbendazole; recovery over three months."],"whatItMeans":"Fenbendazole has never been tested for safety in people. This is what that absence means in practice.","caveats":["Single case."],"changedPractice":false,"participants":1},{"id":"paper-shalhout-oncolytic-progress-challenges-natrevclinonc-2023","kind":"paper","name":"Shalhout 2023: what the approved oncolytic viruses actually do in practice","aka":[],"tldr":"A review of where cancer-killing viruses stand in the clinic, written around the accumulated experience of the one product that is widely approved.","summary":"Shalhout, Miller, Emerick and Kaufman review oncolytic viruses as a class: selective replication in tumour cells, delivery of several transgene payloads, induction of immunogenic cell death, promotion of antitumour immunity, and a safety profile that largely does not overlap with other cancer therapeutics. They note that four oncolytic viruses and one non-oncolytic virus had been approved for cancer globally, while talimogene laherparepvec remained the only widely approved therapy, indicated for recurrent melanoma after initial surgery and first approved in 2015.\n\nThe review is written as practical guidance on using these agents rather than as advocacy, and sets out the preclinical, clinical and regulatory obstacles that have limited their development. Howard Kaufman, one of the authors, was a lead investigator of the trial that produced the first approval.","asOf":"2026-09-25","links":[{"label":"Nat Rev Clin Oncol 2023","url":"https://doi.org/10.1038/s41571-022-00719-w"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36631681/"}],"tags":[],"related":[],"cancers":[],"sections":["immunotherapy"],"technologies":["oncolytic-virus"],"targets":[],"drugs":["talimogene-laherparepvec"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["howard-kaufman"],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-clinical-oncology"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Clinical Oncology","year":2023,"doi":"10.1038/s41571-022-00719-w","pmid":"36631681","authors":"Shalhout SZ, Miller DM, Emerick KS, Kaufman HL","paperType":"review","findings":["Four oncolytic viruses and one non-oncolytic virus had been approved for cancer somewhere in the world; only talimogene laherparepvec was widely approved.","The class safety profile largely does not overlap with that of other cancer therapeutics, which is the main argument for combination.","The obstacles named are preclinical model quality, clinical trial design and regulation, not a lack of candidate viruses."],"whatItMeans":"The honest summary of the field after its first approval: a tolerable class of agents, a large number of candidates, and one product in routine use in one disease. The distinction the review keeps making, between viruses that replicate in the tumour and viruses used only to deliver a gene, is the distinction most coverage of this field drops.","caveats":["A narrative review by authors with commercial and trial involvement in the field; the conflict-of-interest statement should be read with it.","Approval counts change, and the review does not include the products approved since it was written."]},{"id":"paper-shape-nejm-2024","kind":"paper","name":"SHAPE: simple versus radical hysterectomy in low-risk early cervical cancer","aka":[],"tldr":"For small, low-risk cervical cancers, a simple hysterectomy gave the same very low pelvic recurrence rate as a radical hysterectomy with fewer urinary and sexual complications, so less extensive surgery is now acceptable.","summary":"Phase 3 non-inferiority trial of 700 women with low-risk cervical cancer (up to 2 cm, limited stromal invasion) randomised to simple hysterectomy or radical hysterectomy, both with pelvic node assessment.\n\nThree-year pelvic recurrence was 2.52 percent with simple hysterectomy and 2.17 percent with radical hysterectomy, within the non-inferiority margin, with fewer urinary incontinence and retention problems and better sexual health after simple hysterectomy.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2024","url":"https://doi.org/10.1056/NEJMoa2308900"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38416430/"}],"tags":[],"related":[],"cancers":["early-cervical-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["shape"],"people":["marie-plante"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2024,"doi":"10.1056/NEJMoa2308900","pmid":"38416430","authors":"Plante M, Kwon JS, Ferguson S, et al.","paperType":"rct","findings":["Three-year pelvic recurrence 2.52 percent vs 2.17 percent (non-inferior).","Urinary incontinence 2.4 percent vs 5.5 percent within four weeks; urinary retention 0.6 percent vs 11.0 percent."],"whatItMeans":"Women with low-risk early cervical cancer can be offered simple hysterectomy, sparing them the bladder and sexual morbidity of parametrectomy, provided strict eligibility criteria are applied.","caveats":["Strict imaging and pathology criteria define low risk; misapplication to larger tumours would be unsafe.","Longer follow-up is pending."],"changedPractice":true,"participants":700},{"id":"paper-sharp-sorafenib-nejm-2008","kind":"paper","name":"SHARP: sorafenib in advanced hepatocellular carcinoma","aka":[],"tldr":"Sorafenib was the first systemic drug to lengthen survival in advanced liver cancer, adding almost three months compared with placebo, and remained the only option for a decade.","summary":"Phase 3 placebo-controlled trial of 602 patients with advanced hepatocellular carcinoma and preserved liver function (Child-Pugh A) randomised to sorafenib 400 mg twice daily or placebo.\n\nMedian overall survival was 10.7 versus 7.9 months (hazard ratio 0.69), time to radiological progression 5.5 versus 2.8 months, with response in only 2 percent; diarrhoea, weight loss and hand-foot skin reaction were the main toxicities.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2008","url":"https://doi.org/10.1056/NEJMoa0708857"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/18650514/"}],"tags":[],"related":[],"cancers":["hcc-advanced"],"sections":[],"technologies":[],"targets":[],"drugs":["sorafenib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["sharp"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2008,"doi":"10.1056/NEJMoa0708857","pmid":"18650514","authors":"Llovet JM, Ricci S, Mazzaferro V, et al.","paperType":"rct","findings":["Median overall survival 10.7 vs 7.9 months; hazard ratio 0.69.","Time to radiological progression 5.5 vs 2.8 months."],"whatItMeans":"Sorafenib became the reference standard against which lenvatinib, atezolizumab-bevacizumab and durvalumab-tremelimumab were tested, and remains an option where immunotherapy is unsuitable.","caveats":["Benefit confined to patients with good liver function.","Very low response rate; benefit is disease stabilisation."],"changedPractice":true,"participants":602},{"id":"paper-sherr-roberts-cdk-inhibitors-genesdev-1999","kind":"paper","name":"Sherr and Roberts 1999: CDK inhibitors as regulators of the G1 phase","aka":[],"tldr":"The classic review of the brakes on the cell cycle, the proteins that hold back the cyclin-dependent kinases which commit a cell to dividing, and how cancers lose them, the biology behind today's CDK4/6 inhibitors.","summary":"Sherr and Roberts described the two families of cyclin-dependent kinase inhibitors that govern passage through G1: the INK4 proteins (p16, p15, p18 and p19), which specifically block cyclin D-CDK4 and CDK6, and the Cip/Kip proteins (p21, p27 and p57), which act on a broader range of cyclin-CDK complexes. They explained how these inhibitors integrate mitogenic and anti-proliferative signals to control the restriction point, how p21 links p53 to arrest and p27 mediates contact inhibition and TGF-beta responses, and how loss of p16 or p27 and overexpression of cyclin D contribute to cancer.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1101/gad.13.12.1501"}],"tags":[],"related":["paper-el-deiry-waf1-p21-cell-1993"],"cancers":[],"sections":[],"technologies":["cdk46-inhibitor"],"targets":["cdk4-6"],"drugs":[],"companies":[],"institutions":["st-jude"],"pathways":["cell-cycle-engine-cdks","p53-cell-cycle"],"terms":["cell-cycle","tumour-suppressor-gene"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Genes and Development","year":1999,"doi":"10.1101/gad.13.12.1501","authors":"Sherr CJ, Roberts JM.","paperType":"review","findings":["INK4 inhibitors (p16, p15, p18, p19) specifically restrain cyclin D-dependent CDK4 and CDK6; Cip/Kip inhibitors (p21, p27, p57) act more broadly.","These inhibitors integrate growth-promoting and growth-inhibitory signals at the G1 restriction point.","Loss of p16 (CDKN2A) or p27 and cyclin D overexpression are common in cancer and remove the G1 brake."],"whatItMeans":"This review is the textbook basis for the cyclin D-CDK4/6-RB axis that palbociclib, ribociclib and abemaciclib target in breast cancer, and for reading CDKN2A loss and cyclin D1 amplification in tumour genomes.","caveats":["Written before the clinical development of CDK4/6 inhibitors.","Later work showed CDK2 and cyclin E can bypass the CDK4/6 brake, which underlies resistance."],"changedPractice":false},{"id":"paper-perry-n-engl-j-med","kind":"paper","name":"Short-Course Radiation plus Temozolomide in Elderly Patients with Glioblastoma","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 28296618 and published in New England Journal of Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Background: Glioblastoma is associated with a poor prognosis in the elderly. Survival has been shown to increase among patients 70 years of age or younger when temozolomide chemotherapy is added to standard radiotherapy (60 Gy over a period of 6 weeks). In elderly patients, more convenient shorter courses of radiotherapy are commonly used, but the benefit of adding temozolomide to a shorter course of radiotherapy is unknown.\n\nMethods: We conducted a trial involving patients 65 years of age or older with newly diagnosed glioblastoma. Patients were randomly assigned to receive either radiotherapy alone (40 Gy in 15 fractions) or radiotherapy with concomitant and adjuvant temozolomide.\n\nResults: A total of 562 patients underwent randomization, 281 to each group. The median age was 73 years (range, 65 to 90). The median overall survival was longer with radiotherapy plus temozolomide than with radiotherapy alone (9.3 months vs. 7.6 months; hazard ratio for death, 0.67; 95% confidence interval [CI], 0.56 to 0.80; P<0.001), as was the median progression-free survival (5.3 months vs. 3.9 months; hazard ratio for disease progression or death, 0.50; 95% CI, 0.41 to 0.60; P<0.001). Among 165 patients with methylated O 6 -methylguanine-DNA methyltransferase (MGMT) status, the median overall survival was 13.5 months with radiotherapy plus temozolomide and 7.7 months with radiotherapy alone (hazard ratio for death, 0.53; 95% CI, 0.38 to 0.73; P<0.001). Among 189 patients with unmethylated MGMT status, the median overall survival was 10.0 months with radiotherapy plus temozolomide and 7.9 months with radiotherapy alone (hazard ratio for death, 0.75; 95% CI, 0.56 to 1.01; P=0.055; P=0.08 for interaction). Quality of life was similar in the two trial groups.\n\nConclusions: In elderly patients with glioblastoma, the addition of temozolomide to short-course radiotherapy resulted in longer survival than short-course radiotherapy alone. (Funded by the Canadian Cancer Society Research Institute and others; ClinicalTrials.gov number, NCT00482677.).\n\nIndexed on Europe PMC as PubMed record 28296618 (DOI 10.1056/nejmoa1611977). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2017","url":"https://doi.org/10.1056/nejmoa1611977"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28296618/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28296618"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["cctg-ce6"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2017,"doi":"10.1056/nejmoa1611977","pmid":"28296618","authors":"Perry JR, Laperriere N, O'Callaghan CJ, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-bahadoer-rapido-short-course-radiotherapy-lancet-oncol-2021","kind":"paper","name":"Short-course radiotherapy followed by chemotherapy before total mesorectal excision versus preoperative chemoradiotherapy in locally advanced rectal cancer (RAPIDO)","aka":[],"tldr":"Moving all the chemotherapy in front of the operation, after one week of radiotherapy, cut three-year treatment failure from 30.4 to 23.7 percent in high-risk rectal cancer.","summary":"RAPIDO recruited from 54 centres in the Netherlands, Sweden, Spain, Slovenia, Denmark, Norway and the United States. Patients aged 18 or older with biopsy-proven, newly diagnosed, primary locally advanced rectal adenocarcinoma classified as high risk on pelvic MRI (cT4a or cT4b, extramural vascular invasion, cN2, involved mesorectal fascia, or enlarged lateral lymph nodes) were randomised 1:1. The experimental group received short-course radiotherapy (5 x 5 Gy over a maximum of eight days) followed by six cycles of CAPOX or nine of FOLFOX4 and then total mesorectal excision; the standard of care group received 28 daily fractions of 1.8 Gy to 50.4 Gy or 25 of 2.0 Gy to 50.0 Gy with concomitant capecitabine, then total mesorectal excision and, where hospital policy stipulated, adjuvant chemotherapy.\n\nThe primary endpoint was three-year disease-related treatment failure, defined as the first occurrence of locoregional failure, distant metastasis, new primary colorectal tumour or treatment-related death.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2021","url":"https://doi.org/10.1016/S1470-2045(20)30555-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33301740/"}],"tags":["colorectal-evidence"],"related":["paper-conroy-prodige-23-neoadjuvant-folfirinox-rectal-lancet-oncol-2021","paper-garcia-aguilar-opra-organ-preservation-jco-2022","paper-esmo-rectal-cancer-guideline-ann-oncol-2017"],"cancers":["colorectal","rectal-cancer"],"sections":["radiation","chemotherapy","surgery"],"technologies":["radiotherapy","mri","imrt-igrt"],"targets":[],"drugs":["capox","folfox","capecitabine","oxaliplatin"],"companies":[],"institutions":[],"pathways":[],"terms":["total-neoadjuvant-therapy","total-mesorectal-excision","chemoradiation"],"trials":["rapido"],"people":["cornelis-van-de-velde"],"bottlenecks":["b-surgery-radiation-innovation"],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2021,"doi":"10.1016/S1470-2045(20)30555-6","pmid":"33301740","authors":"Bahadoer RR, Dijkstra EA, van Etten B, et al.","paperType":"rct","findings":["912 eligible patients (462 experimental, 450 standard of care); median follow-up 4.6 years.","Three-year disease-related treatment failure 23.7 percent (95 percent CI 19.8 to 27.6) against 30.4 percent (26.1 to 34.6): hazard ratio 0.75 (0.60 to 0.95, p=0.019).","Grade 3 or higher diarrhoea during preoperative therapy in 81 of 460 (18 percent) experimental patients against 41 of 441 (9 percent) standard-of-care patients.","Four treatment-related deaths in each group."],"whatItMeans":"The first total neoadjuvant therapy trial to change practice in high-risk rectal cancer, and the schedule that makes organ preservation possible by giving the tumour months rather than weeks to respond.","caveats":["Longer follow-up showed more locoregional recurrence in the experimental arm, which the authors attributed in part to the surgery and pathology; the balance between distant and local control is still argued.","Adjuvant chemotherapy in the control arm depended on hospital policy, so the comparator was not uniform.","More grade 3 diarrhoea during preoperative treatment."],"changedPractice":true,"participants":920},{"id":"paper-siegel-cancer-statistics-2012-cacancer-2012","kind":"paper","name":"Siegel 2012: Cancer statistics, 2012","aka":[],"tldr":"The American Cancer Society's annual US report for 2012 projected about 1.64 million new cancer cases and reported that death rates had fallen steadily since the early 1990s in both men and women, sparing more than a million lives.","summary":"Siegel, Naishadham and Jemal projected 1,638,910 new cancer cases and 577,190 cancer deaths in the United States for 2012. Cancer death rates had declined from their peaks by 22.9% in men (from 1990) and 15.3% in women (from 1991) to 2008, which the authors estimated had averted more than a million cancer deaths. The report noted the largest declines in lung, colorectal, breast and prostate cancer mortality and highlighted persistent differences by race and education.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.3322/caac.20138"},{"label":"ACS Cancer Facts and Figures","url":"https://www.cancer.org/research/cancer-facts-statistics.html"}],"tags":[],"related":["paper-siegel-cancer-statistics-2024-cacancer-2024"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["incidence-vs-prevalence","mortality"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"CA: A Cancer Journal for Clinicians","year":2012,"doi":"10.3322/caac.20138","authors":"Siegel R, Naishadham D, Jemal A.","paperType":"observational","findings":["Projected 1,638,910 new cancer cases and 577,190 cancer deaths in the United States in 2012.","Death rates down 22.9% in men and 15.3% in women from their early-1990s peaks to 2008, more than a million deaths averted.","Largest mortality declines in lung, colorectal, breast and prostate cancers."],"whatItMeans":"An early edition of the series that established the now-standard framing of deaths averted since the 1991 peak.","caveats":["Projections rather than counts.","US-specific."],"changedPractice":false},{"id":"paper-siegel-cancer-statistics-2013-cacancer-2013","kind":"paper","name":"Siegel 2013: Cancer statistics, 2013","aka":[],"tldr":"The American Cancer Society's 2013 report projected about 1.66 million new US cancer cases and put the overall cancer death rate 20 percent below its 1991 peak, with chronic myeloid leukaemia showing the fastest fall in deaths of any cancer.","summary":"Siegel, Naishadham and Jemal projected 1,660,290 new cancer cases and 580,350 cancer deaths in the United States for 2013. Over 2005 to 2009 incidence declined slightly in men (0.6 percent a year) and was stable in women, while death rates fell 1.8 percent a year in men and 1.5 percent a year in women. The overall cancer death rate had dropped 20 percent from its 1991 peak of 215.1 per 100,000 to 173.1 in 2009, with continuing declines in lung, colorectal, breast and prostate cancer. Over 2000 to 2009 the largest annual falls in death rates were for chronic myeloid leukaemia (8.4 percent, the imatinib era), stomach cancer (3.1 percent), colorectal cancer (3.0 percent) and non-Hodgkin lymphoma (3.0 percent).","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.3322/caac.21166"},{"label":"ACS Cancer Facts and Figures","url":"https://www.cancer.org/research/cancer-facts-statistics.html"}],"tags":[],"related":["paper-siegel-cancer-statistics-2023-cacancer-2023","paper-siegel-cancer-statistics-2024-cacancer-2024"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["incidence-vs-prevalence","mortality"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"CA: A Cancer Journal for Clinicians","year":2013,"doi":"10.3322/caac.21166","authors":"Siegel R, Naishadham D, Jemal A.","paperType":"observational","findings":["Projected 1,660,290 new cancer cases and 580,350 cancer deaths in the United States in 2013.","Overall cancer death rate down 20 percent from 215.1 per 100,000 in 1991 to 173.1 in 2009.","Fastest annual falls in death rates for chronic myeloid leukaemia (8.4 percent), stomach cancer, colorectal cancer and non-Hodgkin lymphoma."],"whatItMeans":"The clearest population-level signature of a targeted drug: the fall in chronic myeloid leukaemia deaths after imatinib.","caveats":["Projections rather than counts.","US-specific."],"changedPractice":false},{"id":"paper-siegel-cancer-statistics-2014-cacancer-2014","kind":"paper","name":"Siegel 2014: Cancer statistics, 2014","aka":[],"tldr":"The American Cancer Society's 2014 report projected about 1.67 million new US cancer cases and estimated that two decades of falling death rates had avoided about 1.34 million cancer deaths, with the gains very unevenly spread by age, race and sex.","summary":"Siegel, Ma, Zou and Jemal projected 1,665,540 new cancer cases and 585,720 cancer deaths in the United States for 2014. Over 2006 to 2010 incidence declined slightly in men (0.6 percent a year) and was stable in women, while death rates fell 1.8 percent a year in men and 1.4 percent a year in women. The combined death rate had fallen for two decades, from 215.1 per 100,000 in 1991 to 171.8 in 2010, a 20 percent decline that translated into about 1,340,400 deaths avoided (952,700 in men and 387,700 in women). The size of the decline ranged from none among white women aged 80 and over to 55 percent among black men aged 40 to 49.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.3322/caac.21208"},{"label":"ACS Cancer Facts and Figures","url":"https://www.cancer.org/research/cancer-facts-statistics.html"}],"tags":[],"related":["paper-siegel-cancer-statistics-2023-cacancer-2023","paper-siegel-cancer-statistics-2024-cacancer-2024"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["incidence-vs-prevalence","mortality"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"CA: A Cancer Journal for Clinicians","year":2014,"doi":"10.3322/caac.21208","authors":"Siegel R, Ma J, Zou Z, Jemal A.","paperType":"observational","findings":["Projected 1,665,540 new cancer cases and 585,720 cancer deaths in the United States in 2014.","Combined death rate down from 215.1 per 100,000 in 1991 to 171.8 in 2010, about 1,340,400 deaths avoided.","Decline ranged from none in white women aged 80 and over to 55 percent in black men aged 40 to 49."],"whatItMeans":"Introduced the breakdown of progress by age, race and sex that exposed how unequally the decline in cancer deaths had been shared.","caveats":["Projections rather than counts.","US-specific."],"changedPractice":false},{"id":"paper-siegel-cancer-statistics-2015-cacancer-2015","kind":"paper","name":"Siegel 2015: Cancer statistics, 2015","aka":[],"tldr":"The American Cancer Society's annual US report for 2015 projected about 1.66 million new cancer cases and recorded a cancer death rate 22% below its 1991 peak, the year the series began reporting deaths averted in the millions.","summary":"Siegel and colleagues projected 1,658,370 new cancer cases and 589,430 cancer deaths in the United States for 2015. The cancer death rate had fallen 22% from its 1991 peak to 2011, which the authors translated into about 1.5 million fewer cancer deaths than if rates had stayed at the peak.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.3322/caac.21254"},{"label":"ACS Cancer Facts and Figures","url":"https://www.cancer.org/research/cancer-facts-statistics.html"}],"tags":[],"related":["paper-siegel-cancer-statistics-2024-cacancer-2024"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["incidence-vs-prevalence","mortality"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"CA: A Cancer Journal for Clinicians","year":2015,"doi":"10.3322/caac.21254","authors":"Siegel RL, Miller KD, Jemal A.","paperType":"observational","findings":["Projected 1,658,370 new cancer cases and 589,430 cancer deaths in the United States in 2015.","Cancer death rate down 22% from 1991 to 2011, about 1.5 million deaths averted."],"whatItMeans":"This edition marked twenty years of falling US cancer mortality and is cited for the estimate that more than 1.5 million deaths had been averted.","caveats":["Projections rather than counts; registrations arrive years later.","US-specific."],"changedPractice":false},{"id":"paper-siegel-cancer-statistics-2016-cacancer-2016","kind":"paper","name":"Siegel 2016: Cancer statistics, 2016","aka":[],"tldr":"The American Cancer Society's annual US report for 2016 projected about 1.69 million new cancer cases and recorded a cancer death rate 23% below its 1991 peak, with the report noting that cancer had overtaken heart disease as the leading cause of death in many US states.","summary":"Siegel and colleagues projected 1,685,210 new cancer cases and 595,690 cancer deaths in the United States for 2016. The cancer death rate had fallen 23% from its 1991 peak to 2012, which the authors translated into about 1.7 million fewer cancer deaths than if rates had stayed at the peak. The report noted that cancer had become the leading cause of death in 21 states and among Hispanic and Asian Americans, and it documented persistent racial gaps in mortality.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.3322/caac.21332"},{"label":"ACS Cancer Facts and Figures","url":"https://www.cancer.org/research/cancer-facts-statistics.html"}],"tags":[],"related":["paper-siegel-cancer-statistics-2024-cacancer-2024"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["incidence-vs-prevalence","mortality"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"CA: A Cancer Journal for Clinicians","year":2016,"doi":"10.3322/caac.21332","authors":"Siegel RL, Miller KD, Jemal A.","paperType":"observational","findings":["Projected 1,685,210 new cancer cases and 595,690 cancer deaths in the United States in 2016.","Cancer death rate down 23% from 1991 to 2012, about 1.7 million deaths averted.","Cancer was the leading cause of death in 21 states and among Hispanic and Asian American populations."],"whatItMeans":"This edition is cited for the shift of cancer to the leading cause of death in a large part of the United States as heart disease mortality fell faster.","caveats":["Projections rather than counts; registrations arrive years later.","US-specific."],"changedPractice":false},{"id":"paper-siegel-cancer-statistics-2017-cacancer-2017","kind":"paper","name":"Siegel 2017: Cancer statistics, 2017","aka":[],"tldr":"The American Cancer Society's annual US report for 2017 projected about 1.69 million new cancer cases and recorded a cancer death rate 25% below its 1991 peak.","summary":"Siegel and colleagues projected 1,688,780 new cancer cases and 600,920 cancer deaths in the United States for 2017. The cancer death rate had fallen 25% from its 1991 peak to 2014, which the authors translated into about 2.1 million fewer cancer deaths than if rates had stayed at the peak. The report highlighted that the gender gap in cancer incidence had narrowed and that the racial gap in mortality had shrunk substantially since the early 1990s.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.3322/caac.21387"},{"label":"ACS Cancer Facts and Figures","url":"https://www.cancer.org/research/cancer-facts-statistics.html"}],"tags":[],"related":["paper-siegel-cancer-statistics-2024-cacancer-2024"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["incidence-vs-prevalence","mortality"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"CA: A Cancer Journal for Clinicians","year":2017,"doi":"10.3322/caac.21387","authors":"Siegel RL, Miller KD, Jemal A.","paperType":"observational","findings":["Projected 1,688,780 new cancer cases and 600,920 cancer deaths in the United States in 2017.","Cancer death rate down 25% from 1991 to 2014, about 2.1 million deaths averted."],"whatItMeans":"One of the most cited editions of the series, used as the reference for US cancer numbers in the mid-2010s.","caveats":["Projections rather than counts; registrations arrive years later.","US-specific."],"changedPractice":false},{"id":"paper-siegel-cancer-statistics-2018-cacancer-2018","kind":"paper","name":"Siegel 2018: Cancer statistics, 2018","aka":[],"tldr":"The American Cancer Society's annual US report for 2018 projected about 1.74 million new cancer cases and recorded a cancer death rate 26% below its 1991 peak.","summary":"Siegel and colleagues projected 1,735,350 new cancer cases and 609,640 cancer deaths in the United States for 2018. The cancer death rate had fallen 26% from its 1991 peak to 2015, which the authors translated into about 2.4 million fewer cancer deaths than if rates had stayed at the peak. The report documented declining incidence in men, stable incidence in women, and a narrowing racial gap in mortality, while flagging rising incidence of liver cancer and of colorectal cancer in younger adults.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.3322/caac.21442"},{"label":"ACS Cancer Facts and Figures","url":"https://www.cancer.org/research/cancer-facts-statistics.html"}],"tags":[],"related":["paper-siegel-cancer-statistics-2024-cacancer-2024"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["incidence-vs-prevalence","mortality"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"CA: A Cancer Journal for Clinicians","year":2018,"doi":"10.3322/caac.21442","authors":"Siegel RL, Miller KD, Jemal A.","paperType":"observational","findings":["Projected 1,735,350 new cancer cases and 609,640 cancer deaths in the United States in 2018.","Cancer death rate down 26% from 1991 to 2015, about 2.4 million deaths averted.","Rising incidence of liver cancer and of colorectal cancer in adults under 55 were flagged as concerns."],"whatItMeans":"This edition is widely cited for the early warning about colorectal cancer in younger adults, which later editions confirmed.","caveats":["Projections rather than counts; registrations arrive years later.","US-specific."],"changedPractice":false},{"id":"paper-siegel-cancer-statistics-2019-cacancer-2019","kind":"paper","name":"Siegel 2019: Cancer statistics, 2019","aka":[],"tldr":"The American Cancer Society's annual US report for 2019 projected about 1.76 million new cancer cases, recorded a quarter-century of falling cancer death rates, and drew attention to widening gaps between rich and poor counties.","summary":"Siegel, Miller and Jemal projected 1,762,450 new cancer cases and 606,880 cancer deaths in the United States for 2019. The cancer death rate had fallen continuously since 1991, by 27% to 2016, which the authors translated into about 2.6 million fewer cancer deaths than if rates had stayed at their peak. The report highlighted that the racial gap in cancer mortality was narrowing while the socioeconomic gap was widening, with the poorest counties carrying the highest death rates for the most preventable cancers.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.3322/caac.21551"},{"label":"ACS Cancer Facts and Figures","url":"https://www.cancer.org/research/cancer-facts-statistics.html"}],"tags":[],"related":["paper-siegel-cancer-statistics-2024-cacancer-2024"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["incidence-vs-prevalence","mortality"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"CA: A Cancer Journal for Clinicians","year":2019,"doi":"10.3322/caac.21551","authors":"Siegel RL, Miller KD, Jemal A.","paperType":"observational","findings":["Projected 1,762,450 new cancer cases and 606,880 cancer deaths in the United States in 2019.","Cancer death rate down 27% from 1991 to 2016, about 2.6 million deaths averted.","Socioeconomic disparities in cancer mortality were widening even as racial disparities narrowed."],"whatItMeans":"This edition is often cited for the disparities finding: progress against cancer in the United States was reaching some communities much more than others.","caveats":["Projections rather than counts.","US-specific."],"changedPractice":false},{"id":"paper-siegel-cancer-statistics-2021-cacancer-2021","kind":"paper","name":"Siegel 2021: Cancer statistics, 2021","aka":[],"tldr":"The American Cancer Society's annual US report for 2021 projected about 1.9 million new cancer cases and recorded a cancer death rate 31% below its 1991 peak, with the largest single-year drop yet recorded, driven by lung cancer.","summary":"Siegel and colleagues projected 1,898,160 new cancer cases and 608,570 cancer deaths in the United States for 2021. The cancer death rate had fallen 31% from its 1991 peak to 2018, which the authors translated into about 3.2 million fewer cancer deaths than if rates had stayed at the peak. The decline from 2017 to 2018 was 2.4%, the largest single-year drop recorded, driven by accelerating falls in lung cancer mortality attributed to reduced smoking and to new treatments, and the report noted that the pandemic's effect on diagnoses would only appear in later data.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.3322/caac.21654"},{"label":"ACS Cancer Facts and Figures","url":"https://www.cancer.org/research/cancer-facts-statistics.html"}],"tags":[],"related":["paper-siegel-cancer-statistics-2024-cacancer-2024"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["incidence-vs-prevalence","mortality"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"CA: A Cancer Journal for Clinicians","year":2021,"doi":"10.3322/caac.21654","authors":"Siegel RL, Miller KD, Fuchs HE, Jemal A.","paperType":"observational","findings":["Projected 1,898,160 new cancer cases and 608,570 cancer deaths in the United States in 2021.","Cancer death rate down 31% from 1991 to 2018, about 3.2 million deaths averted.","A 2.4% fall in the death rate from 2017 to 2018, the largest single-year drop recorded, driven by lung cancer."],"whatItMeans":"This edition documented the fastest ever annual fall in US cancer mortality and attributed it in part to targeted therapy and immunotherapy for lung cancer, one of the clearest links between new drugs and national statistics.","caveats":["Projections rather than counts; registrations arrive years later.","US-specific."],"changedPractice":false},{"id":"paper-siegel-cancer-statistics-2022-cacancer-2022","kind":"paper","name":"Siegel 2022: Cancer statistics, 2022","aka":[],"tldr":"The American Cancer Society's annual US report for 2022 projected about 1.9 million new cancer cases and reported that the cancer death rate had fallen by about a third since 1991, with declines in lung cancer deaths accelerating as treatment improved.","summary":"Siegel, Miller, Fuchs and Jemal projected 1,918,030 new cancer cases and 609,360 cancer deaths in the United States for 2022. The cancer death rate had fallen 32% from 1991 to 2019, an estimated 3.5 million deaths averted. The report attributed the accelerating decline in lung cancer mortality to falling smoking, earlier diagnosis and better treatment, and it noted that the pandemic's effect on diagnoses was not yet visible in the data.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.3322/caac.21708"},{"label":"ACS Cancer Facts and Figures","url":"https://www.cancer.org/research/cancer-facts-statistics.html"}],"tags":[],"related":["paper-siegel-cancer-statistics-2024-cacancer-2024"],"cancers":["nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["incidence-vs-prevalence","mortality"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"CA: A Cancer Journal for Clinicians","year":2022,"doi":"10.3322/caac.21708","authors":"Siegel RL, Miller KD, Fuchs HE, Jemal A.","paperType":"observational","findings":["Projected 1,918,030 new cancer cases and 609,360 cancer deaths in the United States in 2022.","Cancer death rate down 32% from 1991 to 2019, about 3.5 million deaths averted.","Lung cancer mortality declines were accelerating, reflecting reduced smoking and advances in treatment."],"whatItMeans":"This edition documented the treatment-driven fall in lung cancer deaths that followed targeted therapy and immunotherapy, a rare case of new drugs visibly moving national mortality statistics.","caveats":["Projections rather than counts, based on data through 2018 and 2019.","US-specific."],"changedPractice":false},{"id":"paper-siegel-cancer-statistics-2023-cacancer-2023","kind":"paper","name":"Siegel 2023: Cancer statistics, 2023","aka":[],"tldr":"The American Cancer Society's annual US report for 2023 projected about 1.96 million new cancer cases, reported a continued fall in the cancer death rate, and flagged rising prostate cancer diagnoses at advanced stage alongside a steep fall in cervical cancer among young women vaccinated against HPV.","summary":"Siegel, Miller, Wagle and Jemal projected 1,958,310 new cancer cases and 609,820 cancer deaths in the United States for 2023. The cancer death rate had fallen 33% since 1991, an estimated 3.8 million deaths averted. The report noted that prostate cancer incidence had risen by about 3% a year from 2014 to 2019 after a decade of decline, driven by advanced-stage disease, and that cervical cancer incidence in women aged 20 to 24 had fallen by 65% from 2012 to 2019, consistent with HPV vaccination.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.3322/caac.21763"},{"label":"ACS Cancer Facts and Figures","url":"https://www.cancer.org/research/cancer-facts-statistics.html"}],"tags":[],"related":["paper-siegel-cancer-statistics-2024-cacancer-2024"],"cancers":["prostate","cervical"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["incidence-vs-prevalence","mortality"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"CA: A Cancer Journal for Clinicians","year":2023,"doi":"10.3322/caac.21763","authors":"Siegel RL, Miller KD, Wagle NS, Jemal A.","paperType":"observational","findings":["Projected 1,958,310 new cancer cases and 609,820 cancer deaths in the United States in 2023.","Cancer death rate down 33% since 1991, about 3.8 million deaths averted.","Prostate cancer incidence rising about 3% a year from 2014 to 2019, mostly advanced-stage disease.","Cervical cancer incidence in women aged 20 to 24 down 65% from 2012 to 2019."],"whatItMeans":"This edition supplied two widely quoted signals: the first population-level evidence of HPV vaccination preventing cervical cancer in the United States, and the warning that reduced PSA screening was shifting prostate cancer towards later diagnosis.","caveats":["Projections rather than counts.","US-specific; the prostate finding relates to US screening practice."],"changedPractice":false},{"id":"paper-siegel-cancer-statistics-2024-cacancer-2024","kind":"paper","name":"Siegel 2024: Cancer statistics, 2024, the American Cancer Society's annual US report","aka":[],"tldr":"The American Cancer Society's yearly count projected that the United States would pass two million new cancer diagnoses in 2024 for the first time, while the cancer death rate kept falling and colorectal cancer rose to become the leading cause of cancer death in men under 50.","summary":"Each January the American Cancer Society projects the number of new cancer cases and deaths in the United States and reviews trends in incidence, mortality and survival from national registries. The 2024 report projected 2,001,140 new cancer cases and 611,720 cancer deaths. It reported that the cancer mortality rate had fallen by a third since 1991, averting more than four million deaths, but that incidence was rising for six of the ten most common cancers and shifting towards younger adults, with colorectal cancer now the leading cause of cancer death in men under 50 and the second in women under 50.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.3322/caac.21820"},{"label":"ACS Cancer Facts and Figures","url":"https://www.cancer.org/research/cancer-facts-statistics.html"}],"tags":[],"related":["paper-bray-globocan-2022-cacancer-2024"],"cancers":["colorectal","prostate","breast-hr-positive","pancreatic","endometrial","melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["incidence-vs-prevalence","mortality"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"CA: A Cancer Journal for Clinicians","year":2024,"doi":"10.3322/caac.21820","authors":"Siegel RL, Giaquinto AN, Jemal A.","paperType":"observational","findings":["Projected 2,001,140 new cancer cases and 611,720 cancer deaths in the United States in 2024, the first year above two million cases.","Cancer mortality down by about a third since 1991, an estimated 4.1 million deaths averted.","Incidence rising for six of the ten most common cancers, including breast, prostate, endometrial, pancreatic, kidney and melanoma.","Colorectal cancer the leading cause of cancer death in men under 50 and the second in women under 50."],"whatItMeans":"This series is the standard reference for US cancer numbers and the source of most headlines about cancer in younger adults. The gap between falling mortality and rising incidence is the argument for both continued treatment advances and stronger prevention and screening.","caveats":["Projections, not counts; actual registrations arrive years later.","US-specific patterns do not transfer directly to other countries."],"changedPractice":false},{"id":"paper-hayes-science","kind":"paper","name":"Simulating 500 million years of evolution with a language model","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 39818825 and published in Science; the citing page links this DOI, which is how the record was matched.","summary":"More than 3 billion years of evolution have produced an image of biology encoded into the space of natural proteins. Here, we show that language models trained at scale on evolutionary data can generate functional proteins that are far away from known proteins. We present ESM3, a frontier multimodal generative language model that reasons over the sequence, structure, and function of proteins. ESM3 can follow complex prompts combining its modalities and is highly responsive to alignment to improve its fidelity. We have prompted ESM3 to generate fluorescent proteins. Among the generations that we synthesized, we found a bright fluorescent protein at a far distance (58% sequence identity) from known fluorescent proteins, which we estimate is equivalent to simulating 500 million years of evolution.\n\nIndexed on Europe PMC as PubMed record 39818825 (DOI 10.1126/science.ads0018). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Science 2025","url":"https://doi.org/10.1126/science.ads0018"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39818825/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39818825"}],"tags":["europepmc-ingest"],"related":["esm3"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2025,"doi":"10.1126/science.ads0018","pmid":"39818825","authors":"Hayes T, Rao R, Akin H, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-singh-brain-tumour-initiating-cells-nature-2004","kind":"paper","name":"Singh 2004: identification of human brain tumour initiating cells","aka":[],"tldr":"The first proof that human brain tumours are driven by a small population of stem-like cells: a hundred cells carrying the CD133 marker could regrow a patient's tumour in a mouse brain while a hundred thousand cells without it could not.","summary":"Singh, Dirks and colleagues at the Hospital for Sick Children in Toronto isolated CD133-positive cells from human medulloblastomas and glioblastomas and transplanted them into the brains of immunodeficient mice. As few as 100 CD133-positive cells produced tumours that reproduced the histology of the patient's original cancer and could be serially transplanted, whereas up to 100,000 CD133-negative cells did not form tumours. The paper established the brain tumour initiating cell and made CD133 the working marker for glioma stem cells.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1038/nature03128"}],"tags":[],"related":["paper-bao-glioma-stem-cells-radioresistance-nature-2006","paper-reya-cancer-stem-cells-nature-2001"],"cancers":["glioblastoma","medulloblastoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["sickkids"],"pathways":[],"terms":["stem-cell"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature","year":2004,"doi":"10.1038/nature03128","authors":"Singh SK, Hawkins C, Clarke ID, et al.","paperType":"basic","findings":["CD133-positive cells from human medulloblastoma and glioblastoma initiated tumours in mouse brains from as few as 100 cells.","CD133-negative cells did not form tumours even at 100,000 cells.","Xenografts reproduced the original tumour's phenotype and could be passaged serially."],"whatItMeans":"This paper extended the cancer stem cell model to brain tumours and set up the later finding that these cells resist radiotherapy. It is the basis for treatment strategies aimed at the cells that regrow glioblastoma after surgery and chemoradiation.","caveats":["CD133-negative cells were later shown to initiate tumours in some gliomas, so the marker is imperfect.","Transplantation assays in mice may select for cells that survive the assay."],"changedPractice":false},{"id":"paper-raajit-rampal-nature-2020","kind":"paper","name":"Single-cell mutation analysis of clonal evolution in myeloid malignancies","aka":[],"tldr":"Paper by Raajit K. Rampal indexed on Europe PMC as PubMed record 33116311, in Nature (2020), one of the most cited records naming an author with this name at Memorial Sloan Kettering Cancer Center.","summary":"Myeloid malignancies, including acute myeloid leukaemia (AML), arise from the expansion of haematopoietic stem and progenitor cells that acquire somatic mutations. Bulk molecular profiling has suggested that mutations are acquired in a stepwise fashion: mutant genes with high variant allele frequencies appear early in leukaemogenesis, and mutations with lower variant allele frequencies are thought to be acquired later 1-3. Although bulk sequencing can provide information about leukaemia biology and prognosis, it cannot distinguish which mutations occur in the same clone(s), accurately measure clonal complexity, or definitively elucidate the order of mutations. To delineate the clonal framework of myeloid malignancies, we performed single-cell mutational profiling on 146 samples from 123 patients. Here we show that AML is dominated by a small number of clones, which frequently harbour co-occurring mutations in epigenetic regulators. Conversely, mutations in signalling genes often occur more than once in distinct subclones, consistent with increasing clonal diversity. We mapped clonal trajectories for each sample and uncovered combinations of mutations that synergized to promote clonal expansion and dominance. Finally, we combined protein expression with mutational analysis to map somatic genotype and clonal architecture with immunophenotype. Our findings provide insights into the pathogenesis of myeloid transformation and how clonal complexity evolves with disease progression.\n\nIndexed on Europe PMC as PubMed record 33116311 (DOI 10.1038/s41586-020-2864-x). Its author list gives \"Rampal R\" with the affiliation \"Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY, USA\", which names Memorial Sloan Kettering Cancer Center; that is how the record was matched to Raajit K. Rampal, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2020","url":"https://doi.org/10.1038/s41586-020-2864-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33116311/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33116311"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["raajit-rampal"],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2020,"doi":"10.1038/s41586-020-2864-x","pmid":"33116311","authors":"Miles LA, Bowman RL, Merlinsky TR, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Raajit K. Rampal at Memorial Sloan Kettering Cancer Center, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-badwe-progesterone-jco-2011","kind":"paper","name":"Single-injection depot progesterone before surgery and survival in operable breast cancer","aka":[],"tldr":"A single cheap hormone injection given days before breast surgery did not help every patient, but among women whose cancer had spread to lymph nodes it improved five-year survival, a result that seeded twenty years of low-cost perioperative trials in India.","summary":"976 women with operable breast cancer at Tata Memorial were randomised to one intramuscular injection of depot hydroxyprogesterone 5 to 14 days before surgery or to surgery alone, with a median follow-up of 65 months. Disease-free and overall survival were not significantly different overall. In node-positive women, 5-year disease-free survival was 65.3% versus 54.7% (hazard ratio 0.72; 95% CI 0.54-0.97; P=0.02) and overall survival 75.7% versus 66.8% (hazard ratio 0.70; 95% CI 0.49-0.99; P=0.04).","asOf":"2026-09-10","links":[{"label":"JCO 2011","url":"https://doi.org/10.1200/JCO.2010.33.0738"}],"tags":[],"related":[],"cancers":["breast-hr-positive"],"sections":[],"technologies":["endocrine-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":["tata-memorial"],"pathways":[],"terms":[],"trials":["progesterone-preop-tmh","lidocaine-peritumoral-tmh"],"people":["badwe-rajendra"],"bottlenecks":["b-generic-repurposing"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2011,"doi":"10.1200/JCO.2010.33.0738","authors":"Badwe R, Hawaldar R, Parmar V, et al.","paperType":"rct","findings":["No significant overall improvement in disease-free or overall survival.","Node-positive subgroup: 5-year disease-free survival 65.3% versus 54.7% (HR 0.72).","Node-positive subgroup: 5-year overall survival 75.7% versus 66.8% (HR 0.70).","Intervention cost is a single injection of a generic hormone."],"whatItMeans":"The trial did not change practice, but it established the idea that the days around surgery are a window in which cheap interventions might reduce metastasis, a line the same group pursued to a positive result with peritumoral lidocaine in 2023. It is a reminder that subgroup findings need confirmation, which is still awaited.","caveats":["The benefit is a subgroup finding in a trial whose primary analysis was negative.","Mechanism (progesterone-driven changes in tumour gene expression) is plausible but unproven in humans.","No confirmatory trial has yet reported."],"changedPractice":false,"participants":976},{"id":"paper-caldecott-nat-rev-genet","kind":"paper","name":"Single-strand break repair and genetic disease","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 18626472 and published in Nature reviews. Genetics; the citing page links this DOI, which is how the record was matched.","summary":"Hereditary defects in the repair of DNA damage are implicated in a variety of diseases, many of which are typified by neurological dysfunction and/or increased genetic instability and cancer. Of the different types of DNA damage that arise in cells, single-strand breaks (SSBs) are the most common, arising at a frequency of tens of thousands per cell per day from direct attack by intracellular metabolites and from spontaneous DNA decay. Here, the molecular mechanisms and organization of the DNA-repair pathways that remove SSBs are reviewed and the connection between defects in these pathways and hereditary neurodegenerative disease are discussed.\n\nIndexed on Europe PMC as PubMed record 18626472 (DOI 10.1038/nrg2380). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Genet 2008","url":"https://doi.org/10.1038/nrg2380"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/18626472/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/18626472"}],"tags":["europepmc-ingest"],"related":["base-excision-repair-parp"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature reviews. Genetics","year":2008,"doi":"10.1038/nrg2380","pmid":"18626472","authors":"Caldecott KW","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-ren-lancet-oncol","kind":"paper","name":"Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32): a randomised, open-label, phase 2-3 study","aka":[],"tldr":"Paper cited by one trial page and one treatment page, indexed on Europe PMC as PubMed record 34143971 and published in The Lancet Oncology; the citing pages link this DOI, which is how the record was matched.","summary":"Background: China has a high burden of hepatocellular carcinoma, and hepatitis B virus (HBV) infection is the main causative factor. Patients with hepatocellular carcinoma have a poor prognosis and a substantial unmet clinical need. The phase 2-3 ORIENT-32 study aimed to assess sintilimab (a PD-1 inhibitor) plus IBI305, a bevacizumab biosimilar, versus sorafenib as a first-line treatment for unresectable HBV-associated hepatocellular carcinoma.\n\nMethods: This randomised, open-label, phase 2-3 study was done at 50 clinical sites in China. Patients aged 18 years or older with histologically or cytologically diagnosed or clinically confirmed unresectable or metastatic hepatocellular carcinoma, no previous systemic treatment, and a baseline Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 were eligible for inclusion. In the phase 2 part of the study, patients received intravenous sintilimab (200 mg every 3 weeks) plus intravenous IBI305 (15 mg/kg every 3 weeks). In the phase 3 part, patients were randomly assigned (2:1) to receive either sintilimab plus IBI305 (sintilimab-bevacizumab biosimilar group) or sorafenib (400 mg orally twice daily; sorafenib group), until disease progression or unacceptable toxicity. Randomisation was done using permuted block randomisation, with a block size of six, via an interactive web response system, and stratified by macrovascular invasion or extrahepatic metastasis, baseline α-fetoprotein, and ECOG performance status. The primary endpoint of the phase 2 part of the study was safety, assessed in all patients who received at least one dose of study drug. The co-primary endpoints of the phase 3 part of the study were overall survival and independent radiological review committee (IRRC)-assessed progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT03794440. The study is closed to new participants and follow-up is ongoing for long-term outcomes.\n\nFindings: Between Feb 11, 2019 and Jan 15, 2020, we enrolled 595 patients: 24 were enrolled directly into the phase 2 safety run-in and 571 were randomly assigned to sintilimab-bevacizumab biosimilar (n=380) or sorafenib (n=191). In the phase 2 part of the trial, 24 patients received at least one dose of the study drug, with an objective response rate of 25·0% (95% CI 9·8-46·7). Based on the preliminary safety and activity data of the phase 2 part, in which grade 3 or worse treatment-related adverse events occurred in seven (29%) of 24 patients, the randomised phase 3 part was started. At data cutoff (Aug 15, 2020), the median follow-up was 10·0 months (IQR 8·5-11·7) in the sintilimab-bevacizumab biosimilar group and 10·0 months (8·4-11·7) in the sorafenib group. Patients in the sintilimab-bevacizumab biosimilar group had a significantly longer IRRC-assessed median progression-free survival (4·6 months [95% CI 4·1-5·7]) than did patients in the sorafenib group (2·8 months [2·7-3·2]; stratified hazard ratio [HR] 0·56, 95% CI 0·46-0·70; p<0·0001). In the first interim analysis of overall survival, sintilimab-bevacizumab biosimilar showed a significantly longer overall survival than did sorafenib (median not reached [95% CI not reached-not reached] vs 10·4 months [8·5-not reached]; HR 0·57, 95% CI 0·43-0·75; p<0·0001). The most common grade 3-4 treatment-emergent adverse events were hypertension (55 [14%] of 380 patients in the sintilimab-bevacizumab biosimilar group vs 11 [6%] of 185 patients in the sorafenib group) and palmar-plantar erythrodysaesthesia syndrome (none vs 22 [12%]). 123 (32%) patients in the sintilimab-bevacizumab biosimilar group and 36 (19%) patients in the sorafenib group had serious adverse events. Treatment-related adverse events that led to death occurred in six (2%) patients in the sintilimab-bevacizumab biosimilar group (one patient with abnormal liver function, one patient with both hepatic failure and gastrointestinal haemorrhage, one patient with interstitial lung disease, one patient with both hepatic faliure and hyperkalemia, one patient with upper gastrointestinal haemorrhage, and one patient with intestinal volvulus) and two (1%) patients in the sorafenib group (one patient with gastrointestinal haemorrhage and one patient with death of unknown cause).\n\nInterpretation: Sintilimab plus IBI305 showed a significant overall survival and progression-free survival benefit versus sorafenib in the first-line setting for Chinese patients with unresectable, HBV-associated hepatocellular carcinoma, with an acceptable safety profile. This combination regimen could provide a novel treatment option for such patients.\n\nFunding: Innovent Biologics.\n\nTranslation: For the Chinese translation of the abstract see Supplementary Materials section.\n\nIndexed on Europe PMC as PubMed record 34143971 (DOI 10.1016/s1470-2045(21)00252-7). Matched by DOI alone: one trial page and one treatment page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2021","url":"https://doi.org/10.1016/s1470-2045(21)00252-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34143971/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34143971"}],"tags":["europepmc-ingest"],"related":["sintilimab"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["orient-32"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2021,"doi":"10.1016/s1470-2045(21)00252-7","pmid":"34143971","authors":"Ren Z, Xu J, Bai Y, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page and one treatment page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-xu-jama","kind":"paper","name":"Sintilimab Plus Chemotherapy for Unresectable Gastric or Gastroesophageal Junction Cancer: The ORIENT-16 Randomized Clinical Trial","aka":[],"tldr":"Paper cited by one trial page and one treatment page, indexed on Europe PMC as PubMed record 38051328 and published in JAMA; the citing pages link this DOI, which is how the record was matched.","summary":"Importance: Gastric and gastroesophageal junction cancers are diagnosed in more than 1 million people worldwide annually, and few effective treatments are available. Sintilimab, a recombinant human IgG4 monoclonal antibody that binds to programmed cell death 1 (PD-1), in combination with chemotherapy, has demonstrated promising efficacy.\n\nObjective: To compare overall survival of patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction cancers who were treated with sintilimab with chemotherapy vs placebo with chemotherapy. Also compared were a subset of patients with a PD ligand 1 (PD-L1) combined positive score (CPS) of 5 or more (range, 1-100).\n\nDesign, setting, and participants: Randomized, double-blind, placebo-controlled, phase 3 clinical trial conducted at 62 hospitals in China that enrolled 650 patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma between January 3, 2019, and August 5, 2020. Final follow-up occurred on June 20, 2021.\n\nInterventions: Patients were randomized 1:1 to either sintilimab (n = 327) or placebo (n = 323) combined with capecitabine and oxaliplatin (the XELOX regimen) every 3 weeks for a maximum of 6 cycles. Maintenance therapy with sintilimab or placebo plus capecitabine continued for up to 2 years.\n\nMain outcomes and measures: The primary end point was overall survival time from randomization.\n\nResults: Of the 650 patients (mean age, 59 years; 483 [74.3%] men), 327 were randomized to sintilimab plus chemotherapy and 323 to placebo plus chemotherapy. Among the randomized patients, 397 (61.1%) had tumors with a PD-L1 CPS of 5 or more; 563 (86.6%) discontinued study treatment and 388 (59.7%) died; 1 patient (<0.1%) was lost to follow-up. Among all randomized patients, sintilimab improved overall survival compared with placebo (median, 15.2 vs 12.3 months; stratified hazard ratio [HR], 0.77 [95% CI, 0.63-0.94]; P =.009). Among patients with a CPS of 5 or more, sintilimab improved overall survival compared with placebo (median, 18.4 vs 12.9 months; HR, 0.66 [95% CI, 0.50-0.86]; P =.002). The most common grade 3 or higher treatment-related adverse events were decreased platelet count (sintilimab, 24.7% vs placebo, 21.3%), decreased neutrophil count (sintilimab, 20.1% vs placebo, 18.8%), and anemia (sintilimab, 12.5% vs placebo, 8.8%).\n\nConclusions and relevance: Among patients with unresectable locally advanced or metastatic gastric and gastroesophageal junction adenocarcinoma treated with first-line chemotherapy, sintilimab significantly improved overall survival for all patients and for patients with a CPS of 5 or more compared with placebo.\n\nTrial registration: ClinicalTrials.gov Identifier: NCT03745170.\n\nIndexed on Europe PMC as PubMed record 38051328 (DOI 10.1001/jama.2023.19918). Matched by DOI alone: one trial page and one treatment page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA 2023","url":"https://doi.org/10.1001/jama.2023.19918"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38051328/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38051328"}],"tags":["europepmc-ingest"],"related":["sintilimab"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["orient-16"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2023,"doi":"10.1001/jama.2023.19918","pmid":"38051328","authors":"Xu J, Jiang H, Pan Y, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page and one treatment page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-siop-cns-gct-96-calaminus-neuro-oncology-2013","kind":"paper","name":"SIOP CNS GCT 96: outcomes for children and adults with intracranial germinoma treated with radiotherapy alone or chemotherapy plus reduced radiotherapy","aka":[],"tldr":"This large European trial showed that localised intracranial germinoma can be cured in almost every patient either with craniospinal radiotherapy or with chemotherapy followed by smaller-field radiotherapy, but that the reduced field must cover the ventricles to avoid relapse.","summary":"Prospective non-randomised trial of 235 patients with intracranial germinoma treated by choice with craniospinal irradiation (24 Gy plus boost) or two cycles of carboplatin, etoposide and ifosfamide followed by focal radiotherapy (40 Gy); metastatic disease received craniospinal irradiation.\n\nFive-year event-free survival was 97 percent with craniospinal irradiation and 88 percent with the combined approach; relapses after focal radiotherapy occurred mainly in the ventricles, prompting whole-ventricular irradiation in the successor trial.","asOf":"2026-09-17","links":[{"label":"Neuro Oncol 2013","url":"https://doi.org/10.1093/neuonc/not019"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23460321/"}],"tags":[],"related":[],"cancers":["cns-germ-cell-tumours"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["neuro-oncology"],"dependsOn":[],"notes":[],"journal":"Neuro-Oncology","year":2013,"doi":"10.1093/neuonc/not019","pmid":"23460321","authors":"Calaminus G, Kortmann R, Worch J, et al.","paperType":"observational","findings":["Five-year event-free survival 97 percent with craniospinal irradiation vs 88 percent with chemotherapy and focal radiotherapy.","Ventricular relapses after focal fields led to adoption of whole-ventricular irradiation."],"whatItMeans":"Chemotherapy followed by whole-ventricular irradiation with a tumour boost, rather than craniospinal irradiation, is the standard for localised germinoma, sparing children the neurocognitive and endocrine cost of wider fields.","caveats":["Treatment was allocated by institutional preference rather than randomisation."],"changedPractice":true,"participants":235},{"id":"paper-siopel-3-cisplatin-vs-plado-standard-risk-hepatoblastoma-perilongo-nejm-2009","kind":"paper","name":"SIOPEL-3: cisplatin versus cisplatin plus doxorubicin for standard-risk hepatoblastoma","aka":[],"tldr":"Children with standard-risk hepatoblastoma were cured just as often with cisplatin alone as with cisplatin plus doxorubicin, and had far fewer severe side effects, so doxorubicin can be left out.","summary":"International randomised trial of the SIOPEL group: 255 children with standard-risk hepatoblastoma were randomised to pre- and post-operative cisplatin alone (n 126) or cisplatin plus doxorubicin (n 129) with delayed resection.\n\nComplete resection was achieved in 95 and 93 percent; three-year event-free survival was 83 and 85 percent and overall survival 95 and 93 percent (median follow-up 46 months). Acute grade 3 or 4 adverse events occurred in 20.6 percent with cisplatin alone against 74.4 percent with the combination.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2009","url":"https://doi.org/10.1056/NEJMoa0810613"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19846851/"}],"tags":[],"related":[],"cancers":["hepatoblastoma"],"sections":[],"technologies":[],"targets":[],"drugs":["cisplatin","doxorubicin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["siopel-3"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2009,"doi":"10.1056/NEJMoa0810613","pmid":"19846851","authors":"Perilongo G, Maibach R, Shafford E, et al.","paperType":"rct","findings":["Complete resection 95 percent with cisplatin versus 93 percent with cisplatin plus doxorubicin (difference 1.4 percent, 95% CI -4.1 to 7.0).","Three-year event-free survival 83 versus 85 percent; overall survival 95 versus 93 percent.","Grade 3 or 4 acute adverse events 20.6 versus 74.4 percent."],"whatItMeans":"Cisplatin monotherapy with delayed surgery is the standard for standard-risk hepatoblastoma; later SIOPEL-6 added sodium thiosulfate to protect hearing.","caveats":["Standard-risk disease only; high-risk patients need intensified regimens such as SIOPEL-4."],"changedPractice":true,"participants":255},{"id":"paper-siopel-4-dose-dense-cisplatin-high-risk-hepatoblastoma-zsiros-lancet-oncol-2013","kind":"paper","name":"SIOPEL-4: dose-dense cisplatin-based chemotherapy and surgery for high-risk hepatoblastoma","aka":[],"tldr":"Weekly cisplatin with doxorubicin before surgery got almost every child with high-risk hepatoblastoma to respond and three quarters to complete removal of the tumour, with three-year survival of 83 percent in a group that previously did poorly.","summary":"Prospective single-arm feasibility study of the SIOPEL group in 62 children with high-risk hepatoblastoma (39 with lung metastases): dose-dense cisplatin with doxorubicin before surgery (including transplantation and metastasectomy where needed), then carboplatin and doxorubicin.\n\n60 of 61 evaluable patients had a partial response to pre-operative chemotherapy, 46 (74 percent) had complete resection and 49 (79 percent) were in complete remission at the end of therapy. Three-year event-free survival was 76 percent and overall survival 83 percent at a median follow-up of 52 months; 97 percent had grade 3 or 4 haematological toxicity and 71 percent febrile neutropenia.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2013","url":"https://doi.org/10.1016/S1470-2045(13)70272-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23831416/"}],"tags":[],"related":[],"cancers":["hepatoblastoma"],"sections":[],"technologies":[],"targets":[],"drugs":["cisplatin","doxorubicin","carboplatin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["siopel-4"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2013,"doi":"10.1016/S1470-2045(13)70272-9","pmid":"23831416","authors":"Zsiros J, Brugieres L, Brock P, et al.","paperType":"observational","findings":["Complete remission at the end of therapy 79 percent (95% CI 67 to 88).","Partial response to pre-operative chemotherapy in 98 percent; complete resection in 74 percent.","Three-year event-free survival 76 percent (65 to 87) and overall survival 83 percent (73 to 93)."],"whatItMeans":"Dose-dense cisplatin became the SIOPEL standard for high-risk hepatoblastoma and one arm of the international PHITT trial.","caveats":["Single-arm feasibility design with heavy haematological toxicity; hearing loss from cumulative cisplatin is a long-term concern."],"changedPractice":true,"participants":62},{"id":"paper-kantoff-n-engl-j-med","kind":"paper","name":"Sipuleucel-T immunotherapy for castration-resistant prostate cancer","aka":[],"tldr":"Paper cited by one treatment page, indexed on Europe PMC as PubMed record 20818862 and published in New England Journal of Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Background: Sipuleucel-T, an autologous active cellular immunotherapy, has shown evidence of efficacy in reducing the risk of death among men with metastatic castration-resistant prostate cancer.\n\nMethods: In this double-blind, placebo-controlled, multicenter phase 3 trial, we randomly assigned 512 patients in a 2:1 ratio to receive either sipuleucel-T (341 patients) or placebo (171 patients) administered intravenously every 2 weeks, for a total of three infusions. The primary end point was overall survival, analyzed by means of a stratified Cox regression model adjusted for baseline levels of serum prostate-specific antigen (PSA) and lactate dehydrogenase.\n\nResults: In the sipuleucel-T group, there was a relative reduction of 22% in the risk of death as compared with the placebo group (hazard ratio, 0.78; 95% confidence interval [CI], 0.61 to 0.98; P=0.03). This reduction represented a 4.1-month improvement in median survival (25.8 months in the sipuleucel-T group vs. 21.7 months in the placebo group). The 36-month survival probability was 31.7% in the sipuleucel-T group versus 23.0% in the placebo group. The treatment effect was also observed with the use of an unadjusted Cox model and a log-rank test (hazard ratio, 0.77; 95% CI, 0.61 to 0.97; P=0.02) and after adjustment for use of docetaxel after the study therapy (hazard ratio, 0.78; 95% CI, 0.62 to 0.98; P=0.03). The time to objective disease progression was similar in the two study groups. Immune responses to the immunizing antigen were observed in patients who received sipuleucel-T. Adverse events that were more frequently reported in the sipuleucel-T group than in the placebo group included chills, fever, and headache.\n\nConclusions: The use of sipuleucel-T prolonged overall survival among men with metastatic castration-resistant prostate cancer. No effect on the time to disease progression was observed. (Funded by Dendreon; ClinicalTrials.gov number, NCT00065442.)\n\nIndexed on Europe PMC as PubMed record 20818862 (DOI 10.1056/nejmoa1001294). Matched by DOI alone: one treatment page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2010","url":"https://doi.org/10.1056/nejmoa1001294"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20818862/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/20818862"}],"tags":["europepmc-ingest"],"related":["sipuleucel-t","prostate-roadmap","paper-antonarakis-keynote-199-pembrolizumab-jco-2020"],"cancers":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2010,"doi":"10.1056/nejmoa1001294","pmid":"20818862","authors":"Kantoff PW, Higano CS, Shore ND, et al.","paperType":"rct","findings":[],"whatItMeans":"One treatment page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-lin-tnbc-cns-metastases-dfci-cancer-2008","kind":"paper","name":"Sites of distant recurrence and clinical outcomes in patients with metastatic triple-negative breast cancer: high incidence of central nervous system metastases","aka":[],"tldr":"A 2008 Dana-Farber series of 116 women with metastatic triple-negative breast cancer in which 46 percent developed brain metastases before death, median survival after spread was 13.3 months and after a brain diagnosis 4.9 months.","summary":"Lin, Claus, Sohl, Razzak and colleagues identified 116 patients treated for metastatic triple-negative breast cancer at Dana-Farber Cancer Institute between January 2000 and June 2006 from pharmacy and pathology records. Median survival from metastatic diagnosis was 13.3 months. Sixteen patients (14 percent) had central nervous system involvement at first metastatic diagnosis and 46 percent were diagnosed with central nervous system metastases before death; median survival after that diagnosis was 4.9 months, and the adjusted death rate for patients whose first presentation included a central nervous system metastasis was 3.4 times (95 percent confidence interval 1.9 to 6.1) that of others. Of 53 patients with brain metastases only 3 had stable or responding systemic disease at last follow-up, so the authors attribute the high rate to a lack of effective therapies rather than a sanctuary effect.","asOf":"2026-09-24","links":[{"label":"Cancer 2008","url":"https://doi.org/10.1002/cncr.23930"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/18833576/"}],"tags":["tnbc-evidence"],"related":[],"cancers":["tnbc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["dana-farber"],"pathways":[],"terms":["brain-metastases","os"],"trials":[],"people":["nancy-lin"],"bottlenecks":["b-brain-delivery","b-metastasis-biology"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Cancer","year":2008,"doi":"10.1002/cncr.23930","pmid":"18833576","authors":"Lin NU, Claus E, Sohl J, et al.","paperType":"observational","findings":["Median survival from metastatic diagnosis 13.3 months (2000 to 2006).","Central nervous system metastases in 14 percent at first metastatic diagnosis and 46 percent before death; median survival after brain diagnosis 4.9 months.","Only 3 of 53 patients with brain metastases had controlled systemic disease at last follow-up."],"whatItMeans":"The 13.3-month median is the pre-immunotherapy, pre-antibody-drug conjugate benchmark against which first-line trials now reporting medians near two years are measured; the brain metastasis rate is why trials that exclude active brain disease leave the question unanswered.","caveats":["Single-centre, retrospective, small.","Era before systematic brain imaging in asymptomatic patients."],"changedPractice":false,"participants":116},{"id":"paper-peters-j-clin-oncol","kind":"paper","name":"SKYSCRAPER-01: Tiragolumab in Combination With Atezolizumab in Previously Untreated PD-L1-High, Locally Advanced, Unresectable or Metastatic Non-Small Cell Lung Cancer","aka":[],"tldr":"Paper cited by one pairing page, indexed on Europe PMC as PubMed record 42507968 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: Tiragolumab plus atezolizumab has shown encouraging survival outcomes in metastatic non-small cell lung cancer (NSCLC), primarily in patients with PD-L1-high tumors. We further evaluated the combination of tiragolumab plus atezolizumab in the phase III SKYSCRAPER-01 study.\n\nMethods: Patients with untreated, locally advanced unresectable/metastatic PD-L1-high (by central laboratory testing) NSCLC were randomly assigned 1:1 to receive either tiragolumab (600 mg) plus atezolizumab (1,200 mg) or placebo plus atezolizumab (1,200 mg) intravenously in 21-day cycles until disease progression, loss of clinical benefit, or unacceptable toxicity. Primary end points were investigator-assessed progression-free survival (INV-PFS) and overall survival (OS) in the primary analysis set (PD-L1-high per 22C3 assay).\n\nResults: Five hundred twenty-one patients were randomly assigned to either the tiragolumab plus atezolizumab group (n = 262) or the placebo plus atezolizumab group (n = 259). At the primary PFS analysis (Mar 12, 2022; median follow-up 9.9 months [IQR, 6.2-13.8]), median INV-PFS was 7.0 months (95% CI, 5.6 to 9.8) with tiragolumab plus atezolizumab and 5.6 months (95% CI, 4.4 to 7.0) with placebo plus atezolizumab (hazard ratio [HR], 0.78 [95% CI, 0.63 to 0.97]; P =.02 [nonsignificant]). At the final OS analysis (Sept 24, 2024; median follow-up 17.9 months [IQR, 6.7-39.0]), median OS was 23.1 months (95% CI, 17.7 to 28.8) with tiragolumab plus atezolizumab and 16.9 months (95% CI, 14.6 to 21.3) with placebo plus atezolizumab (HR, 0.87 [95% CI, 0.7 to 1.1]; P =.22 [nonsignificant]). Overall, 41.2% (n = 110/267) and 33.8% (n = 89/263) of patients experienced grade 3-4 adverse events with tiragolumab plus atezolizumab and placebo plus atezolizumab, respectively. Four and two treatment-related deaths occurred in each group, respectively.\n\nConclusion: Tiragolumab plus atezolizumab did not demonstrate a statistically significant INV-PFS or OS benefit over atezolizumab in patients with previously untreated PD-L1-high NSCLC.\n\nIndexed on Europe PMC as PubMed record 42507968 (DOI 10.1200/jco-25-02777). Matched by DOI alone: one pairing page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2026","url":"https://doi.org/10.1200/jco-25-02777"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42507968/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42507968"}],"tags":["europepmc-ingest"],"related":["tigit-plus-pd1-caution"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2026,"doi":"10.1200/jco-25-02777","pmid":"42507968","authors":"Peters S, Herbst R, Horinouchi H, et al.","paperType":"rct","findings":[],"whatItMeans":"One pairing page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nct04665856-j-thorac-oncol-2026","kind":"paper","name":"SKYSCRAPER-02C: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Atezolizumab Plus Carboplatin and Etoposide With or Without Tiragolumab in Patients With Untreated Extensive-Stage SCLC in China","aka":[],"tldr":"Published report from the SKYSCRAPER-02C trial registered as NCT04665856, in Journal of Thoracic Oncology (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Introduction: Tiragolumab may synergize with other immunotherapies to enhance antitumor immune responses. We report efficacy, safety, and biomarker findings from SKYSCRAPER-02C (NCT04665856), comparing tiragolumab plus atezolizumab plus carboplatin and etoposide (CE; experimental arm) with atezolizumab plus CE (control arm) in patients with untreated extensive-stage SCLC (ES-SCLC) in China.\n\nMethods: Patients were randomized (1:1) to tiragolumab 600 mg or placebo, plus atezolizumab 1200 mg and CE (four cycles), then maintenance tiragolumab or placebo plus atezolizumab. Primary end points were investigator-assessed progression-free survival (PFS) and overall survival (OS) in patients without history or presence of brain metastases at baseline (primary analysis set).\n\nResults: The primary analysis set comprised 54 patients in the experimental arm and 56 in the control arm. Median PFS was 5.6 months (experimental) and 5.4 months (control; unstratified hazard ratio = 0.65, 95% confidence interval: 0.43‒0.97; median follow-up 26.7 months); median OS was 18.7 and 13.5 months, respectively (unstratified hazard ratio 0.89, 95% confidence interval: 0.56‒1.40). The biomarker-evaluable population comprised 69 patients with immunohistochemistry data and 66 with RNA sequencing data. RNA sequencing survival analysis found that patients with non-negative matrix factorization 3 (SCLC-inflamed-neuroendocrine) or non-negative matrix factorization 4 (SCLC-inflamed-non-neuroendocrine) molecular subtypes, and those with high T-effector and tumor-associated macrophage immune signatures, benefited from tiragolumab plus atezolizumab plus CE treatment. Tiragolumab was well tolerated, with no new safety signals.\n\nConclusions: Although results from the global SKYSCRAPER-02 study were not statistically significant, numerical improvements in PFS and OS were observed with tiragolumab plus atezolizumab plus CE versus atezolizumab plus CE in Chinese patients with ES-SCLC. Biomarker analysis identified immune-inflamed signatures that may guide future tyrosine-based inhibitory motif domain-based strategies.\n\nIndexed on Europe PMC as PubMed record 41950998 (DOI 10.1016/j.jtho.2026.103713). Its abstract cites the registry id NCT04665856, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Thorac Oncol 2026","url":"https://doi.org/10.1016/j.jtho.2026.103713"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41950998/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41950998"},{"label":"ClinicalTrials.gov NCT04665856","url":"https://clinicaltrials.gov/study/NCT04665856"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04665856"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-thoracic-oncology"],"dependsOn":[],"notes":[],"journal":"Journal of Thoracic Oncology","year":2026,"doi":"10.1016/j.jtho.2026.103713","pmid":"41950998","authors":"Lu S, Fang J, Yu Y, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04665856 with the most citations, so it is the natural first reading for anyone following the SKYSCRAPER-02C trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-slamon-her2-amplification-science-1987","kind":"paper","name":"Slamon 1987: HER2 gene amplification marks an aggressive form of breast cancer","aka":[],"tldr":"Extra copies of the HER2 gene were found in about a quarter to a third of breast cancers and picked out the patients most likely to relapse, the discovery that made HER2 a drug target and a test.","summary":"Slamon and colleagues measured copies of the HER2/neu gene in 189 primary human breast cancers and found amplification in 53 of them, about 28%, with amplification ranging from 2- to more than 20-fold. In node-positive patients, amplification was a strong and independent predictor of both time to relapse and survival, stronger than most conventional factors. The paper established HER2 as a marker of aggressive disease and, with later work showing the receptor's role in growth signalling, as the target that trastuzumab would hit a decade later.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1126/science.3798106"}],"tags":[],"related":["paper-slamon-trastuzumab-nejm-2001","paper-asco-cap-er-pr-testing-guideline-jco-2010"],"cancers":["breast-her2-positive","tnbc"],"sections":[],"technologies":[],"targets":["her2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["dennis-slamon"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Science","year":1987,"doi":"10.1126/science.3798106","pmid":"3798106","authors":"Slamon DJ, Clark GM, Wong SG, et al.","paperType":"translational","findings":["HER2/neu amplification in 53 of 189 primary breast cancers (about 28%).","Amplification correlated with the number of positive lymph nodes and, in node-positive patients, with shorter time to relapse and shorter survival.","Amplification was an independent prognostic factor in multivariate analysis, stronger than tumour size or hormone receptor status."],"whatItMeans":"Every HER2 test, every trastuzumab prescription and the whole HER2-positive breast cancer category trace back to this observation. It is the model for how a genomic marker of bad prognosis became a drug target and then the basis for one of the largest survival gains in solid tumour oncology.","caveats":["Prognostic effect was clearest in node-positive disease; the node-negative signal was weaker in this dataset.","Measured gene copies by Southern blot; clinical testing later moved to immunohistochemistry and in situ hybridisation with their own cut-offs."],"changedPractice":true},{"id":"paper-slamon-her2-breast-ovarian-science-1989","kind":"paper","name":"Slamon 1989: HER2/neu in human breast and ovarian cancer","aka":[],"tldr":"The follow-up to the 1987 discovery: extra copies of the HER2 gene were found in about a quarter to a third of breast cancers and also in ovarian cancers, they led to overproduction of the HER2 protein, and they marked patients with worse outcomes in both diseases.","summary":"Slamon and colleagues examined HER2/neu gene amplification and expression in 526 breast cancers and 120 ovarian cancers. Amplification was present in about a quarter to a third of the breast tumours and was tightly linked to overexpression of HER2 messenger RNA and protein, so measuring the protein could stand in for measuring the gene. Amplification and overexpression were associated with poorer survival in breast cancer and, for the first time, were shown in ovarian cancer with a similar prognostic effect.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1126/science.2470152"}],"tags":[],"related":["paper-slamon-her2-amplification-science-1987","paper-slamon-trastuzumab-nejm-2001"],"cancers":["breast-her2-positive","ovarian"],"sections":[],"technologies":[],"targets":["her2"],"drugs":[],"companies":[],"institutions":["ucla-jonsson"],"pathways":[],"terms":[],"trials":[],"people":["dennis-slamon"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Science","year":1989,"doi":"10.1126/science.2470152","authors":"Slamon DJ, Godolphin W, Jones LA, et al.","paperType":"translational","findings":["HER2/neu amplification in about 25 to 30% of 526 breast cancers, correlating with mRNA and protein overexpression.","HER2 amplification and overexpression also found in ovarian cancers, associated with poorer survival.","Protein overexpression by immunohistochemistry tracked gene amplification, supporting a tissue test."],"whatItMeans":"This study confirmed HER2 as a prognostic marker and a therapeutic target, showed that immunohistochemistry could identify the patients, and extended the target to ovarian cancer. It set up the clinical development of trastuzumab and the HER2 testing that every breast cancer now receives.","caveats":["Retrospective tumour bank study.","Ovarian findings were smaller in scale and HER2-directed therapy has had less success in ovarian cancer than in breast cancer."],"changedPractice":true},{"id":"paper-slamon-trastuzumab-nejm-2001","kind":"paper","name":"Slamon 2001: adding trastuzumab to chemotherapy for HER2-positive metastatic breast cancer","aka":[],"tldr":"The trial that made trastuzumab standard: adding the HER2 antibody to chemotherapy slowed progression and prolonged life in women whose breast cancers overexpressed HER2, at the cost of heart weakening when it was paired with anthracyclines.","summary":"This phase 3 trial randomised 469 women with previously untreated HER2-overexpressing metastatic breast cancer to chemotherapy (an anthracycline plus cyclophosphamide, or paclitaxel for those who had received adjuvant anthracycline) with or without trastuzumab. Adding trastuzumab lengthened the time to progression and raised the response rate, and it improved overall survival despite two thirds of the chemotherapy-alone group receiving trastuzumab after progression. Cardiac dysfunction was markedly more frequent when trastuzumab was combined with the anthracycline, which is why the two are not given together today.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJM200103153441101"}],"tags":[],"related":["paper-slamon-her2-amplification-science-1987"],"cancers":["breast-her2-positive"],"sections":[],"technologies":[],"targets":["her2"],"drugs":["trastuzumab","paclitaxel"],"companies":["roche-genentech"],"institutions":[],"pathways":[],"terms":["os","orr"],"trials":[],"people":["dennis-slamon"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2001,"doi":"10.1056/NEJM200103153441101","authors":"Slamon DJ, Leyland-Jones B, Shak S, et al.","paperType":"rct","findings":["469 women with HER2-overexpressing metastatic breast cancer; chemotherapy with or without trastuzumab.","Time to progression 7.4 vs 4.6 months; objective response 50% vs 32%.","Median overall survival 25.1 vs 20.3 months, hazard ratio for death 0.80.","Cardiac dysfunction in 27% of patients given anthracycline plus trastuzumab versus 8% with anthracycline alone, and 13% with paclitaxel plus trastuzumab."],"whatItMeans":"This was the first proof that a monoclonal antibody against a growth receptor could extend life in a common solid tumour, and it created HER2-positive breast cancer as a disease treated differently from the rest. Its cardiac finding shaped every later HER2 regimen, which pair trastuzumab with taxanes rather than anthracyclines.","caveats":["Crossover to trastuzumab after progression diluted the survival difference.","HER2 positivity was defined by immunohistochemistry 2+ or 3+, broader than the 3+ or amplified definition used now.","Open-label design."],"changedPractice":true,"participants":469},{"id":"paper-rudin-nat-rev-dis-primers","kind":"paper","name":"Small-cell lung cancer","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 33446664 and published in Nature reviews. Disease primers; the citing page links this DOI, which is how the record was matched.","summary":"Small-cell lung cancer (SCLC) represents about 15% of all lung cancers and is marked by an exceptionally high proliferative rate, strong predilection for early metastasis and poor prognosis. SCLC is strongly associated with exposure to tobacco carcinogens. Most patients have metastatic disease at diagnosis, with only one-third having earlier-stage disease that is amenable to potentially curative multimodality therapy. Genomic profiling of SCLC reveals extensive chromosomal rearrangements and a high mutation burden, almost always including functional inactivation of the tumour suppressor genes TP53 and RB1. Analyses of both human SCLC and murine models have defined subtypes of disease based on the relative expression of dominant transcriptional regulators and have also revealed substantial intratumoural heterogeneity. Aspects of this heterogeneity have been implicated in tumour evolution, metastasis and acquired therapeutic resistance. Although clinical progress in SCLC treatment has been notoriously slow, a better understanding of the biology of disease has uncovered novel vulnerabilities that might be amenable to targeted therapeutic approaches. The recent introduction of immune checkpoint blockade into the treatment of patients with SCLC is offering new hope, with a small subset of patients deriving prolonged benefit. Strategies to direct targeted therapies to those patients who are most likely to respond and to extend the durable benefit of effective antitumour immunity to a greater fraction of patients are urgently needed and are now being actively explored.\n\nIndexed on Europe PMC as PubMed record 33446664 (DOI 10.1038/s41572-020-00235-0). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Dis Primers 2021","url":"https://doi.org/10.1038/s41572-020-00235-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33446664/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33446664"}],"tags":["europepmc-ingest"],"related":["sclc-signalling"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature reviews. Disease primers","year":2021,"doi":"10.1038/s41572-020-00235-0","pmid":"33446664","authors":"Rudin CM, Brambilla E, Faivre-Finn C, et al.","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-peto-smoking-cessation-lung-cancer-uk-bmj-2000","kind":"paper","name":"Smoking, smoking cessation, and lung cancer in the UK since 1950: combination of national statistics with two case-control studies","aka":[],"tldr":"Quitting works, and it works even in middle age. Men who stopped at 30 had a 2 percent lifetime risk of dying of lung cancer, at 40 it was 3 percent, at 50 it was 6 percent, and those who carried on had 16 percent.","summary":"Peto, Darby, Deo, Silcocks, Whitley and Doll related United Kingdom national trends in smoking, cessation and lung cancer since 1950 to two large case-control studies, one centred around 1950 and one around 1990: 1,465 case-control pairs in the 1950 study, and 982 cases with 3,185 controls in 1990.\n\nThe paper is the reason cessation, rather than prevention alone, became a health service activity. It is also the cleanest demonstration in the literature that the risk from a cumulative exposure is not fixed at the moment of exposure: stopping changes the future even after decades of smoking.","asOf":"2026-09-25","links":[{"label":"BMJ 2000","url":"https://doi.org/10.1136/bmj.321.7257.323"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/10926586/"}],"tags":["lung-evidence"],"related":["paper-doll-peto-50-year-doctors-bmj-2004","smoking-cessation-after-diagnosis","prevention-roadmap"],"cancers":["lung-cancer","nsclc","sclc"],"sections":["prevention","early-detection"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["richard-peto"],"bottlenecks":["b-prevention-adoption","b-global-access"],"keyPapers":[],"journals":["bmj"],"dependsOn":[],"notes":[],"journal":"BMJ","year":2000,"doi":"10.1136/bmj.321.7257.323","pmid":"10926586","authors":"Peto R, Darby S, Deo H, et al.","paperType":"observational","findings":["Cumulative risk of death from lung cancer by age 75 rose from 6 percent at 1950 rates to 16 percent at 1990 rates in male cigarette smokers, and from 1 percent to 10 percent in female smokers.","For men who stopped at ages 60, 50, 40 and 30, the cumulative risks of lung cancer by age 75 were 10, 6, 3 and 2 percent.","By 1990 cessation had almost halved the number of lung cancers that would have been expected if the former smokers had continued.","Stopping before middle age avoids more than 90 percent of the risk attributable to tobacco.","For men in early middle age the prevalence of smoking halved between 1950 and 1990 but the death rate from lung cancer at ages 35 to 54 fell faster still, indicating some reduction in risk among continuing smokers."],"whatItMeans":"The single most quotable number in tobacco control: quitting at 30 avoids almost all the risk, quitting at 50 avoids half of it, and it is never not worth stopping. It is also the argument for putting cessation support inside a lung screening appointment rather than beside it.","caveats":["National statistics combined with two case-control studies forty years apart, not a randomised comparison of quitting against continuing.","Risks are quoted in the absence of other causes of death, which overstates what an individual smoker experiences.","United Kingdom figures; the shape holds elsewhere but the absolute risks track each country's smoking history."],"changedPractice":true},{"id":"paper-morrow-j-clin-oncol","kind":"paper","name":"Society of Surgical Oncology-American Society for Radiation Oncology-American Society of Clinical Oncology Consensus Guideline on Margins for Breast-Conserving Surgery With Whole-Breast Irradiation in Ductal Carcinoma In Situ","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 27528719 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background Controversy exists regarding the optimal negative margin width for ductal carcinoma in situ (DCIS) treated with breast-conserving surgery and whole-breast irradiation (WBRT). Methods A multidisciplinary consensus panel used a meta-analysis of margin width and ipsilateral breast tumor recurrence (IBTR) from a systematic review of 20 studies including 7883 patients and other published literature as the evidence base for consensus. Results Negative margins halve the risk of IBTR compared with positive margins defined as ink on DCIS. A 2 mm margin minimizes the risk of IBTR compared with smaller negative margins. More widely clear margins do not significantly decrease IBTR compared with 2 mm margins. Negative margins less than 2 mm alone are not an indication for mastectomy, and factors known to impact rates of IBTR should be considered in determining the need for re-excision. Conclusion The use of a 2 mm margin as the standard for an adequate margin in DCIS treated with WBRT is associated with low rates of IBTR and has the potential to decrease re-excision rates, improve cosmetic outcome, and decrease health care costs. Clinical judgment should be used in determining the need for further surgery in patients with negative margins < 2 mm.\n\nIndexed on Europe PMC as PubMed record 27528719 (DOI 10.1200/jco.2016.68.3573). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2016","url":"https://doi.org/10.1200/jco.2016.68.3573"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27528719/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27528719"}],"tags":["europepmc-ingest"],"related":["ductal-carcinoma-in-situ"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2016,"doi":"10.1200/jco.2016.68.3573","pmid":"27528719","authors":"Morrow M, Van Zee KJ, Solin LJ, et al.","paperType":"meta-analysis","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-forrest-socioeconomic-inequalities-lung-cancer-treatment-plos-med-2013","kind":"paper","name":"Socioeconomic inequalities in lung cancer treatment: systematic review and meta-analysis","aka":[],"tldr":"Poorer patients with lung cancer are less likely to be given any treatment at all, and the gap is not explained by them being diagnosed later or by which country's health system they are in.","summary":"Forrest, Adams, Wareham, Rubin and White searched MEDLINE, EMBASE and Scopus to September 2012 for cohort studies in which receipt of lung cancer treatment was reported by a measure of socioeconomic position. Forty-six papers met the inclusion criteria and 23 entered the meta-analysis.\n\nThe framing matters as much as the result: the authors call this an intervention-generated inequality, a variation in outcome produced by how care is organised and delivered rather than by the disease. The gap survived adjustment for stage at presentation and was present across health care systems, including systems free at the point of use.","asOf":"2026-09-25","links":[{"label":"PLoS Med 2013","url":"https://doi.org/10.1371/journal.pmed.1001376"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23393428/"}],"tags":["lung-evidence"],"related":["paper-uspstf-lung-cancer-screening-jama-2021","global-access-roadmap","idea-prev-mobile-lung-screening-deprived-areas"],"cancers":["lung-cancer","nsclc","sclc"],"sections":["early-detection"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["performance-status"],"trials":[],"people":[],"bottlenecks":["b-global-access","b-care-fragmentation","b-trial-diversity","b-workforce"],"keyPapers":[],"journals":["plos-medicine"],"dependsOn":[],"notes":[],"journal":"PLoS Medicine","year":2013,"doi":"10.1371/journal.pmed.1001376","pmid":"23393428","authors":"Forrest LF, Adams J, Wareham H, et al.","paperType":"meta-analysis","findings":["Lower socioeconomic position was associated with a reduced likelihood of receiving any treatment (odds ratio 0.79, 95 percent confidence interval 0.73 to 0.86).","Patients in more deprived circumstances were less likely to receive surgery and less likely to receive chemotherapy.","The inequalities were not accounted for by socioeconomic differences in stage at presentation or by differences in health care system.","46 papers met the inclusion criteria; 23 were included in the meta-analysis."],"whatItMeans":"The deprivation gradient in lung cancer is not only about who gets the disease. Among people who already have it, and at the same stage, poorer patients are less likely to be offered the treatment that works.","caveats":["Observational cohorts with heterogeneous measures of socioeconomic position, pooled; residual confounding by comorbidity and performance status cannot be excluded.","Literature to 2012, before immunotherapy and before most perioperative treatment; whether the gap has widened or narrowed since is untested here.","United Kingdom-specific figures, audit indicators and NHS pathway detail belong to the UK and NHS page for lung cancer."],"changedPractice":false},{"id":"paper-brock-n-engl-j-med","kind":"paper","name":"Sodium Thiosulfate for Protection from Cisplatin-Induced Hearing Loss","aka":[],"tldr":"Paper cited by two cancer pages and one treatment page, indexed on Europe PMC as PubMed record 29924955 and published in New England Journal of Medicine; the citing pages link this DOI, which is how the record was matched.","summary":"Background: Cisplatin chemotherapy and surgery are effective treatments for children with standard-risk hepatoblastoma but may cause considerable and irreversible hearing loss. This trial compared cisplatin with cisplatin plus delayed administration of sodium thiosulfate, aiming to reduce the incidence and severity of cisplatin-related ototoxic effects without jeopardizing overall and event-free survival.\n\nMethods: We randomly assigned children older than 1 month and younger than 18 years of age who had standard-risk hepatoblastoma (≤3 involved liver sectors, no metastatic disease, and an alpha-fetoprotein level of >100 ng per milliliter) to receive cisplatin alone (at a dose of 80 mg per square meter of body-surface area, administered over a period of 6 hours) or cisplatin plus sodium thiosulfate (at a dose of 20 g per square meter, administered intravenously over a 15-minute period, 6 hours after the discontinuation of cisplatin) for four preoperative and two postoperative courses. The primary end point was the absolute hearing threshold, as measured by pure-tone audiometry, at a minimum age of 3.5 years. Hearing loss was assessed according to the Brock grade (on a scale from 0 to 4, with higher grades indicating greater hearing loss). The main secondary end points were overall survival and event-free survival at 3 years.\n\nResults: A total of 109 children were randomly assigned to receive cisplatin plus sodium thiosulfate (57 children) or cisplatin alone (52) and could be evaluated. Sodium thiosulfate was associated with few high-grade toxic effects. The absolute hearing threshold was assessed in 101 children. Hearing loss of grade 1 or higher occurred in 18 of 55 children (33%) in the cisplatin-sodium thiosulfate group, as compared with 29 of 46 (63%) in the cisplatin-alone group, indicating a 48% lower incidence of hearing loss in the cisplatin-sodium thiosulfate group (relative risk, 0.52; 95% confidence interval [CI], 0.33 to 0.81; P=0.002). At a median of 52 months of follow-up, the 3-year rates of event-free survival were 82% (95% CI, 69 to 90) in the cisplatin-sodium thiosulfate group and 79% (95% CI, 65 to 88) in the cisplatin-alone group, and the 3-year rates of overall survival were 98% (95% CI, 88 to 100) and 92% (95% CI, 81 to 97), respectively.\n\nConclusions: The addition of sodium thiosulfate, administered 6 hours after cisplatin chemotherapy, resulted in a lower incidence of cisplatin-induced hearing loss among children with standard-risk hepatoblastoma, without jeopardizing overall or event-free survival. (Funded by Cancer Research UK and others; SIOPEL 6 ClinicalTrials.gov number, NCT00652132; EudraCT number, 2007-002402-21.).\n\nIndexed on Europe PMC as PubMed record 29924955 (DOI 10.1056/nejmoa1801109). Matched by DOI alone: two cancer pages and one treatment page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2018","url":"https://doi.org/10.1056/nejmoa1801109"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29924955/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29924955"}],"tags":["europepmc-ingest"],"related":["paediatric-germ-cell-tumours","hepatoblastoma","sodium-thiosulfate"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2018,"doi":"10.1056/nejmoa1801109","pmid":"29924955","authors":"Brock PR, Maibach R, Childs M, et al.","paperType":"rct","findings":[],"whatItMeans":"Two cancer pages and one treatment page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-robin-jones-ann-oncol-2018","kind":"paper","name":"Soft tissue and visceral sarcomas: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up","aka":[],"tldr":"Paper by Robin L. Jones indexed on Europe PMC as PubMed record 29846498, in Annals of Oncology (2018), one of the most cited records naming an author with this name at The Royal Marsden.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 29846498 (DOI 10.1093/annonc/mdy096). Its author list gives \"Jones RL\" with the affiliation \"Royal Marsden Hospital, London\", which names The Royal Marsden; that is how the record was matched to Robin L. Jones, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Ann Oncol 2018","url":"https://doi.org/10.1093/annonc/mdy096"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29846498/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29846498"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["robin-jones"],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2018,"doi":"10.1093/annonc/mdy096","pmid":"29846498","authors":"Casali PG, Abecassis N, Aro HT, et al.","paperType":"guideline","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Robin L. Jones at The Royal Marsden, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-esmo-sts-guideline-gronchi-ann-oncol-2021","kind":"paper","name":"Soft tissue and visceral sarcomas: ESMO-EURACAN-GENTURIS clinical practice guideline","aka":[],"tldr":"The European sarcoma guideline sets out referral to reference centres, biopsy and molecular diagnosis, surgery with radiotherapy for localised disease, the selective use of chemotherapy, and histology-driven treatment of advanced disease.","summary":"Joint European guideline covering the diagnosis, staging, multidisciplinary management and follow-up of soft tissue and visceral sarcomas in adults, including limb and trunk sarcomas, retroperitoneal sarcoma, gastrointestinal stromal tumour, desmoid tumours and subtype-specific systemic therapy recommendations.","asOf":"2026-09-17","links":[{"label":"Ann Oncol 2021","url":"https://doi.org/10.1016/j.annonc.2021.07.006"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34303806/"}],"tags":[],"related":[],"cancers":["myxofibrosarcoma","undifferentiated-pleomorphic-sarcoma","extremity-soft-tissue-sarcoma","retroperitoneal-sarcoma","leiomyosarcoma","liposarcoma","pecoma","malignant-peripheral-nerve-sheath-tumour"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2021,"doi":"10.1016/j.annonc.2021.07.006","pmid":"34303806","authors":"Gronchi A, Miah AB, Dei Tos AP, et al.","paperType":"guideline","findings":[],"whatItMeans":"The general principles on the sarcoma subtype pages (reference centre surgery, radiotherapy for high-grade deep tumours, doxorubicin first line, histology-directed later lines) follow this guideline.","caveats":["Updated periodically; drug approvals since 2021 (for example nab-sirolimus, afamitresgene) are not covered."],"changedPractice":true},{"id":"paper-trojani-int-j-cancer","kind":"paper","name":"Soft-tissue sarcomas of adults; study of pathological prognostic variables and definition of a histopathological grading system","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 6693192 and published in International journal of cancer; the citing page links this DOI, which is how the record was matched.","summary":"The pathological features of 155 adult patients with soft-tissue sarcomas were studied retrospectively, in an attempt to set up a grading system for these tumors. As the first step, seven histological criteria (tumor differentiation, cellularity, importance of nuclear atypia, presence of malignant giant cells, mitosis count, pattern of tumor necrosis and presence of vascular emboli) were evaluated in a monofactorial analysis. Five of these (tumor differentiation, cellularity, mitosis count, tumor necrosis, and vascular emboli) were correlated with the advent of metastases and with survival. A multivariate analysis, using a Cox model, selected a minimal set of three factors (tumor differentiation, mitosis count, and tumor necrosis) the combination of which was necessary and sufficient to retain all the prognostic information. A grading system was elaborated, which turned out to be correlated with the advent of metastasis and with patients' survival. A second multivariate analysis introducing clinical prognostic features showed that the histological grade was the most important prognostic factor for soft-tissue sarcomas. Thus, this grading system appears to be highly interesting because of its prognostic value and the facility of its elaboration. However, its reproducibility should be tested.\n\nIndexed on Europe PMC as PubMed record 6693192 (DOI 10.1002/ijc.2910330108). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Int J Cancer 1984","url":"https://doi.org/10.1002/ijc.2910330108"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/6693192/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/6693192"}],"tags":["europepmc-ingest"],"related":["fnclcc-grade"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["international-journal-of-cancer"],"dependsOn":[],"notes":[],"journal":"International journal of cancer","year":1984,"doi":"10.1002/ijc.2910330108","pmid":"6693192","authors":"Trojani M, Contesso G, Coindre JM, et al.","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-solar-1-alpelisib-nejm-2019","kind":"paper","name":"SOLAR-1: alpelisib plus fulvestrant for PIK3CA-mutated hormone receptor-positive advanced breast cancer","aka":[],"tldr":"Alpelisib, a pill blocking the mutated PI3K-alpha enzyme, nearly doubled the time to progression when added to fulvestrant in advanced breast cancer carrying a PIK3CA mutation, at the cost of high blood sugar and rash.","summary":"Phase 3 placebo-controlled trial of 572 patients with hormone receptor-positive, HER2-negative advanced breast cancer after an aromatase inhibitor, randomised to alpelisib or placebo with fulvestrant, stratified by PIK3CA mutation status.\n\nIn the 341 patients with PIK3CA-mutated tumours, median progression-free survival was 11.0 versus 5.7 months (hazard ratio 0.65); no benefit was seen without the mutation. Hyperglycaemia, rash and diarrhoea led to frequent dose changes.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2019","url":"https://doi.org/10.1056/NEJMoa1813904"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31091374/"}],"tags":[],"related":[],"cancers":["hr-positive-metastatic-post-cdk46"],"sections":[],"technologies":[],"targets":[],"drugs":["alpelisib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["solar-1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2019,"doi":"10.1056/NEJMoa1813904","pmid":"31091374","authors":"André F, Ciruelos E, Rubovszky G, et al.","paperType":"rct","findings":["Median progression-free survival 11.0 vs 5.7 months in PIK3CA-mutated disease; hazard ratio 0.65.","Grade 3 or worse hyperglycaemia in 36.6 percent of alpelisib patients."],"whatItMeans":"PIK3CA testing became routine in advanced hormone receptor-positive breast cancer, with alpelisib-fulvestrant the first approved PI3K-targeted regimen; capivasertib and inavolisib now offer alternatives.","caveats":["Few patients had received a prior CDK4/6 inhibitor.","Toxicity leads to discontinuation in a meaningful minority."],"changedPractice":true,"participants":572},{"id":"paper-english-cancer","kind":"paper","name":"Solitomab, an epithelial cell adhesion molecule/CD3 bispecific antibody (BiTE), is highly active against primary chemotherapy-resistant ovarian cancer cell lines in vitro and fresh tumor cells ex vivo","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 25251053 and published in Cancer; the citing page links this DOI, which is how the record was matched.","summary":"Background: Solitomab is a novel, bispecific, single-chain antibody that targets epithelial cell adhesion molecule (EpCAM) on tumor cells and also contains a cluster of differentiation 3 (CD3) (T-cell coreceptor) binding region. The authors evaluated the in vitro activity of solitomab against primary chemotherapy-resistant epithelial ovarian carcinoma cell lines as well as malignant cells in ascites.\n\nMethods: EpCAM expression was evaluated by flow cytometry in 5 primary ovarian cancer cell lines and in 42 fresh ovarian tumor cell cultures in ascites from patients with mainly advanced or recurrent, chemotherapy-resistant disease. The potential activity of solitomab against EpCAM-positive tumor cells was evaluated by flow cytometry, proliferation, and 4-hour chromium-release, cell-mediated cytotoxicity assays.\n\nResults: EpCAM expression was detected by flow cytometry in approximately 80% of the fresh ovarian tumors and primary ovarian tumor cell lines tested. EpCAM-positive, chemotherapy-resistant cell lines were identified as resistant to natural killer cell-mediated or T-cell-mediated killing after exposure to peripheral blood lymphocytes in 4-hour chromium-release assays (mean±standard error of the mean, 3.6%±0.7% of cells killed after incubation of EpCAM-positive cell lines with control bispecific antibody). In contrast, after incubation with solitomab, EpCAM-positive, chemotherapy-resistant cells became highly sensitive to T-cell cytotoxicity (mean±standard error of the mean, 28.2%±2.05% of cells killed; P<.0001) after exposure to peripheral blood lymphocytes. Ex vivo incubation of autologous tumor-associated lymphocytes with EpCAM-expressing malignant cells in ascites with solitomab resulted in a significant increase in T-cell activation markers and a reduction in the number of viable ovarian tumor cells in ascites (P<.001).\n\nConclusions: Solitomab may represent a novel, potentially effective agent for the treatment of chemotherapy-resistant ovarian cancers that overexpress EpCAM.\n\nIndexed on Europe PMC as PubMed record 25251053 (DOI 10.1002/cncr.29062). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer 2015","url":"https://doi.org/10.1002/cncr.29062"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25251053/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25251053"}],"tags":["europepmc-ingest"],"related":["pleuropulmonary-blastoma"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-wiley"],"dependsOn":[],"notes":[],"journal":"Cancer","year":2015,"doi":"10.1002/cncr.29062","pmid":"25251053","authors":"English DP, Bellone S, Schwab CL, et al.","paperType":"basic","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-solo-1-nejm-2018","kind":"paper","name":"SOLO-1: two years of olaparib maintenance after first-line chemotherapy for BRCA-mutated ovarian cancer","aka":[],"tldr":"In women with newly diagnosed advanced BRCA-mutated ovarian cancer who had responded to chemotherapy, two years of the PARP inhibitor olaparib kept far more of them free of progression than placebo, and the effect persisted for years after the tablets stopped. It moved PARP inhibitors into first-line maintenance and made BRCA testing at diagnosis routine.","summary":"Double-blind, placebo-controlled phase 3 trial of 391 patients with newly diagnosed advanced high-grade ovarian cancer and a BRCA1/2 mutation who had responded to platinum-based chemotherapy, randomised 2:1 to two years of olaparib or placebo maintenance. Primary endpoint was investigator-assessed PFS.\n\nPFS HR was 0.30, with 3-year PFS 60% vs 27%. Long-term follow-up showed a durable effect after treatment stopped: 7-year OS 67% vs 46.5% (HR 0.55) and about 45% of olaparib patients progression-free at seven years, suggesting a fraction were cured. It moved PARP inhibitors from recurrent disease to first-line maintenance and made BRCA testing at diagnosis mandatory.","asOf":"2026-09-08","links":[{"label":"NEJM 2018","url":"https://doi.org/10.1056/NEJMoa1810858"},{"label":"ClinicalTrials.gov NCT01844986","url":"https://clinicaltrials.gov/study/NCT01844986"}],"tags":[],"related":[],"cancers":["ovarian"],"sections":[],"technologies":["parp-inhibitor","germline-testing","synthetic-lethality-approaches"],"targets":["parp","brca"],"drugs":["olaparib"],"companies":["astrazeneca","merck"],"institutions":[],"pathways":[],"terms":["synthetic-lethality","pfs","os","germline-vs-somatic","hrd"],"trials":[],"people":["giovanni-scambia","amit-oza"],"bottlenecks":["b-hereditary-risk","b-dormancy-mrd","b-resistance"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2018,"doi":"10.1056/NEJMoa1810858","authors":"Moore K, Colombo N, Scambia G, et al.","paperType":"rct","findings":["Progression-free survival HR 0.30 (95% CI 0.23-0.41); 3-year PFS 60% vs 27%.","Median PFS 56.0 vs 13.8 months at five-year follow-up (Lancet Oncology 2021); 5-year PFS 48% vs 21%.","Overall survival at seven years (JCO 2023): 67.0% vs 46.5%; HR 0.55 (95% CI 0.40-0.76), despite 44% of placebo patients later receiving a PARP inhibitor.","Grade 3 or higher adverse events 39% vs 18%, mainly anaemia; 12% discontinued olaparib for toxicity.","Myelodysplastic syndrome or acute myeloid leukaemia in about 1.5% of olaparib patients at long follow-up, similar to placebo."],"whatItMeans":"Every woman diagnosed with advanced high-grade ovarian cancer should be tested for BRCA mutations at diagnosis, because those who carry one should receive two years of olaparib after chemotherapy, which greatly extends the time in remission and improves long-term survival. The plateau in the survival curves suggests some patients are cured by this approach. Toxicity is mostly anaemia, fatigue and nausea, and the two-year limit appears sufficient.","caveats":["The OS analysis did not formally meet its stringent statistical threshold (p<0.0001) though the effect is large and consistent.","Only BRCA-mutated patients; PRIMA and PAOLA-1 extended maintenance PARP inhibition to HRD-positive non-BRCA tumours.","Long-term surveillance for secondary leukaemia is warranted.","Patients who progress on a PARP inhibitor respond poorly to subsequent platinum, complicating later treatment."],"changedPractice":true,"participants":391},{"id":"paper-curtin-kit-melanoma-jco-2006","kind":"paper","name":"Somatic activation of KIT in distinct subtypes of melanoma","aka":[],"tldr":"This study found KIT mutations and amplifications in a substantial minority of mucosal, acral and chronically sun-damaged skin melanomas but almost never in ordinary skin melanoma, identifying a targetable driver for these rarer subtypes.","summary":"Analysis of 102 primary melanomas from mucosal, acral, chronically sun-damaged and non-sun-damaged sites for KIT copy number and mutations, finding KIT alterations in 39 percent of mucosal, 36 percent of acral and 28 percent of chronically sun-damaged melanomas, and none in non-sun-damaged skin melanomas.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2006","url":"https://doi.org/10.1200/JCO.2006.06.2984"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/16908931/"}],"tags":[],"related":[],"cancers":["mucosal-melanoma","acral-melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2006,"doi":"10.1200/JCO.2006.06.2984","pmid":"16908931","authors":"Curtin JA, Busam K, Pinkel D, et al.","paperType":"translational","findings":["KIT aberrations in 39 percent of mucosal, 36 percent of acral and 28 percent of chronically sun-damaged melanomas.","Absent in melanomas on skin without chronic sun damage."],"whatItMeans":"KIT joined BRAF and NRAS as a melanoma driver and became the rationale for imatinib and nilotinib in mucosal and acral melanoma.","caveats":["Later series found lower mutation frequencies (about 10 to 15 percent) in mucosal and acral melanoma."],"changedPractice":true,"participants":102},{"id":"paper-shattuck-n-engl-j-med","kind":"paper","name":"Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 14585940 and published in New England Journal of Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Background: We looked for mutations of the HRPT2 gene, which encodes the parafibromin protein, in sporadic parathyroid carcinoma because germ-line inactivating HRPT2 mutations have been found in a type of familial hyperparathyroidism--hyperparathyroidism-jaw tumor (HPT-JT) syndrome--that carries an increased risk of parathyroid cancer.\n\nMethods: We directly sequenced the full coding and flanking splice-junctional regions of the HRPT2 gene in 21 parathyroid carcinomas from 15 patients who had no known family history of primary hyperparathyroidism or the HPT-JT syndrome at presentation. We also sought to confirm the somatic nature of the identified mutations and tested the carcinomas for tumor-specific loss of heterozygosity at HRPT2.\n\nResults: Parathyroid carcinomas from 10 of the 15 patients had HRPT2 mutations, all of which were predicted to inactivate the encoded parafibromin protein. Two distinct HRPT2 mutations were found in tumors from five patients, and biallelic inactivation as a result of a mutation and loss of heterozygosity was found in one tumor. At least one HRPT2 mutation was demonstrably somatic in carcinomas from six patients. Unexpectedly, HRPT2 mutations in the parathyroid carcinomas of three patients were identified as germ-line mutations.\n\nConclusions: Sporadic parathyroid carcinomas frequently have HRPT2 mutations that are likely to be of pathogenetic importance. Certain patients with apparently sporadic parathyroid carcinoma carry germ-line mutations in HRPT2 and may have the HPT-JT syndrome or a phenotypic variant.\n\nIndexed on Europe PMC as PubMed record 14585940 (DOI 10.1056/nejmoa031237). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2003","url":"https://doi.org/10.1056/nejmoa031237"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/14585940/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/14585940"}],"tags":["europepmc-ingest"],"related":["parathyroid-carcinoma"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2003,"doi":"10.1056/nejmoa031237","pmid":"14585940","authors":"Shattuck TM, Välimäki S, Obara T, et al.","paperType":"observational","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-martincorena-science","kind":"paper","name":"Somatic mutant clones colonize the human esophagus with age","aka":[],"tldr":"Paper cited by one pathway page and one term page, indexed on Europe PMC as PubMed record 30337457 and published in Science; the citing pages link this DOI, which is how the record was matched.","summary":"The extent to which cells in normal tissues accumulate mutations throughout life is poorly understood. Some mutant cells expand into clones that can be detected by genome sequencing. We mapped mutant clones in normal esophageal epithelium from nine donors (age range, 20 to 75 years). Somatic mutations accumulated with age and were caused mainly by intrinsic mutational processes. We found strong positive selection of clones carrying mutations in 14 cancer genes, with tens to hundreds of clones per square centimeter. In middle-aged and elderly donors, clones with cancer-associated mutations covered much of the epithelium, with NOTCH1 and TP53 mutations affecting 12 to 80% and 2 to 37% of cells, respectively. Unexpectedly, the prevalence of NOTCH1 mutations in normal esophagus was several times higher than in esophageal cancers. These findings have implications for our understanding of cancer and aging.\n\nIndexed on Europe PMC as PubMed record 30337457 (DOI 10.1126/science.aau3879). Matched by DOI alone: one pathway page and one term page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Science 2018","url":"https://doi.org/10.1126/science.aau3879"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30337457/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30337457"}],"tags":["europepmc-ingest"],"related":["field-cancerisation","ageing-tissue-field-theory"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2018,"doi":"10.1126/science.aau3879","pmid":"30337457","authors":"Martincorena I, Fowler JC, Wabik A, et al.","paperType":"observational","findings":[],"whatItMeans":"One pathway page and one term page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-treon-blood","kind":"paper","name":"Somatic mutations in MYD88 and CXCR4 are determinants of clinical presentation and overall survival in Waldenstrom macroglobulinemia","aka":[],"tldr":"Paper cited by one target page, indexed on Europe PMC as PubMed record 24553177 and published in Blood; the citing page links this DOI, which is how the record was matched.","summary":"Whole genome sequencing has revealed activating somatic mutations in MYD88 (L265P) and CXCR4 in Waldenström macroglobulinemia (WM). CXCR4 somatic mutations in WM are the first ever reported in human cancer and are similar to nonsense (NS) and frameshift (FS) germline mutations found in warts, hypogammaglobulinemia, infections and myelokathexis (WHIM) syndrome. We genotyped lymphoplasmacytic cells from 175 WM patients and observed significantly higher bone marrow (BM) disease involvement, serum immunoglobulin-M levels, and symptomatic disease requiring therapy, including hyperviscosity syndrome in those patients with MYD88(L265P)CXCR4(WHIM/NS) mutations (P <.03). Patients with MYD88(L265P)CXCR4(WHIM/FS) or MYD88(L265P)CXCR4(WILDTYPE (WT)) had intermediate BM and serum immunoglobulin-M levels; those with MYD88(WT)CXCR4(WT) showed lowest BM disease burden. Fewer patients with MYD88(L265P) and CXCR4(WHIM/FS or NS) vs MYD88(L265P)CXCR4(WT) presented with adenopathy (P <.01), further delineating differences in disease tropism based on CXCR4 status. Neither MYD88 nor CXCR4 mutations correlated with SDF-1a (RS1801157) polymorphisms in 54 patients who were genotyped for these variants. Unexpectedly, risk of death was not impacted by CXCR4 mutation status, but by MYD88(WT) status (hazard ratio 10.54; 95% confidence interval 2.4-46.2, P =.0018). Somatic mutations in MYD88 and CXCR4 are important determinants of clinical presentation and impact overall survival in WM. Targeted therapies directed against MYD88 and/or CXCR4 signaling may provide a personalized treatment approach to WM.\n\nIndexed on Europe PMC as PubMed record 24553177 (DOI 10.1182/blood-2014-01-550905). Matched by DOI alone: one target page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Blood 2014","url":"https://doi.org/10.1182/blood-2014-01-550905"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24553177/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/24553177"}],"tags":["europepmc-ingest"],"related":["cxcr4"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["blood"],"dependsOn":[],"notes":[],"journal":"Blood","year":2014,"doi":"10.1182/blood-2014-01-550905","pmid":"24553177","authors":"Treon SP, Cao Y, Xu L, et al.","paperType":"observational","findings":[],"whatItMeans":"One target page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-domingo-somatic-pole-proofreading-colorectal-lancet-gastro-2016","kind":"paper","name":"Somatic POLE proofreading domain mutation, immune response, and prognosis in colorectal cancer","aka":[],"tldr":"Pooling trials and cohorts covering 6,517 bowel cancers found that one in a hundred has a broken proofreading enzyme. Those tumours carry far more mutations than any other, attract as many immune cells as the mismatch repair deficient ones, and relapse far less often.","summary":"The association of POLE proofreading domain mutation with clinicopathological variables and immune response was examined in colorectal cancers from the VICTOR, QUASAR2 and PETACC-3 trials and eight cohorts, with prognosis in stage II and III disease assessed by Cox regression on pooled individual patient data from more than 4,500 cases. Pathogenic somatic POLE mutations were detected in 66 of 6,517 colorectal cancers (1.0%) and were mutually exclusive with mismatch repair deficiency (none of 66 against 833 of 6,211 determined for both). Compared with POLE wild-type cases, POLE-mutant patients were younger (median 54.5 against 67.2 years), more often male (75.8% against 55.5%), more often had right-sided tumours (68.8% against 39.8%) and were diagnosed at an earlier stage. POLE-mutant tumours displayed increased CD8-positive lymphocyte infiltration and expression of cytotoxic T-cell markers and effector cytokines, similar to mismatch repair deficient cancers. Both POLE mutation and mismatch repair deficiency were associated with reduced recurrence risk against mismatch repair proficient cancers (hazard ratios 0.34 and 0.72).","asOf":"2026-09-24","links":[{"label":"Domingo et al., Lancet Gastroenterol Hepatol 2016: somatic POLE proofreading mutation, immune response and prognosis in 6,517 colorectal cancers","url":"https://doi.org/10.1016/S2468-1253(16)30014-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28404093/"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["wes-wgs","tmb-testing"],"targets":["pole","mmr"],"drugs":[],"companies":[],"institutions":["oxford-cancer"],"pathways":["replication-stress","mismatch-repair-msi","cancer-immunity-cycle"],"terms":["pole-ultramutation","tmb","mss-pmmr","neoantigen"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"Lancet Gastroenterology and Hepatology","year":2016,"doi":"10.1016/S2468-1253(16)30014-0","pmid":"28404093","authors":"Domingo E, Freeman-Mills L, Rayner E, et al.","paperType":"meta-analysis","findings":["Pathogenic somatic POLE mutation in 66 of 6,517 colorectal cancers (1.0%), mutually exclusive with mismatch repair deficiency.","POLE-mutant patients younger (median 54.5 years) and more often male.","Recurrence hazard ratio 0.34 against mismatch repair proficient disease, with CD8 infiltration matching deficient tumours."],"whatItMeans":"It defines a small group with an excellent prognosis that no repair immunohistochemistry panel or MSI assay will find, and it is the main argument for sequencing rather than staining alone in younger patients.","caveats":["Retrospective and pooled, with varied POLE calling methods.","Only 66 cases, so the prognostic estimate is wide.","Checkpoint inhibitors were not used; the immunotherapy case in POLE-mutant colorectal cancer rests on case series."],"changedPractice":false,"participants":6517},{"id":"paper-kras-nsclc-n-engl-j-med-2021","kind":"paper","name":"Sotorasib for Lung Cancers with KRAS p.G12C Mutation","aka":[],"tldr":"Phase 2 or 3 results paper on KRAS in Non-small-cell lung cancer, in New England Journal of Medicine (2021), one of the most cited Europe PMC records with KRAS in its title.","summary":"Background: Sotorasib showed anticancer activity in patients with KRAS p.G12C-mutated advanced solid tumors in a phase 1 study, and particularly promising anticancer activity was observed in a subgroup of patients with non-small-cell lung cancer (NSCLC).\n\nMethods: In a single-group, phase 2 trial, we investigated the activity of sotorasib, administered orally at a dose of 960 mg once daily, in patients with KRAS p.G12C-mutated advanced NSCLC previously treated with standard therapies. The primary end point was objective response (complete or partial response) according to independent central review. Key secondary end points included duration of response, disease control (defined as complete response, partial response, or stable disease), progression-free survival, overall survival, and safety. Exploratory biomarkers were evaluated for their association with response to sotorasib therapy.\n\nResults: Among the 126 enrolled patients, the majority (81.0%) had previously received both platinum-based chemotherapy and inhibitors of programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1). According to central review, 124 patients had measurable disease at baseline and were evaluated for response. An objective response was observed in 46 patients (37.1%; 95% confidence interval [CI], 28.6 to 46.2), including in 4 (3.2%) who had a complete response and in 42 (33.9%) who had a partial response. The median duration of response was 11.1 months (95% CI, 6.9 to could not be evaluated). Disease control occurred in 100 patients (80.6%; 95% CI, 72.6 to 87.2). The median progression-free survival was 6.8 months (95% CI, 5.1 to 8.2), and the median overall survival was 12.5 months (95% CI, 10.0 to could not be evaluated). Treatment-related adverse events occurred in 88 of 126 patients (69.8%), including grade 3 events in 25 patients (19.8%) and a grade 4 event in 1 (0.8%). Responses were observed in subgroups defined according to PD-L1 expression, tumor mutational burden, and co-occurring mutations in STK11, KEAP1, or TP53.\n\nConclusions: In this phase 2 trial, sotorasib therapy led to a durable clinical benefit without new safety signals in patients with previously treated KRAS p.G12C-mutated NSCLC. (Funded by Amgen and the National Institutes of Health; CodeBreaK100 ClinicalTrials.gov number, NCT03600883.).\n\nIndexed on Europe PMC as PubMed record 34096690 (DOI 10.1056/nejmoa2103695). Its title names KRAS and its text names Non-small-cell lung cancer; PubMed types it as a clinical trial report (Clinical Trial, Phase II, Research Support, Non-U.S. Gov't, research-article, Multicenter Study, Research Support, N.I.H., Extramural). It was matched automatically to the idea \"Turn a brake back on: drugs that reactivate the PP2A phosphatase\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2021","url":"https://doi.org/10.1056/nejmoa2103695"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34096690/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34096690"}],"tags":["europepmc-ingest"],"related":["lung-cancer-evidence-roadmap","paper-codebreak-200-lancet-2023"],"cancers":["lung-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2021,"doi":"10.1056/nejmoa2103695","pmid":"34096690","authors":"Skoulidis F, Li BT, Dy GK, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for KRAS in Non-small-cell lung cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by KRAS in the title and Non-small-cell lung cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-mu-sox2-lineage-plasticity-science-2017","kind":"paper","name":"SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer","aka":["Mu 2017","SOX2 lineage plasticity prostate","enzalutamide resistance by lineage switching"],"tldr":"Some prostate cancers escape hormone drugs not by changing the receptor but by becoming a different kind of cell that does not need it. This paper showed how: losing two tumour suppressors lets the cell switch on SOX2 and change identity, and restoring them reverses it.","summary":"Ping Mu, Charles Sawyers and colleagues used human prostate cancer models in vitro and in vivo to show that tumours can develop resistance to enzalutamide by a phenotypic shift from androgen receptor-dependent luminal epithelial cells to androgen receptor-independent basal-like cells.\n\nThe chain is specific and, unusually, reversible. Loss of TP53 and RB1 function enables the plasticity; increased expression of the reprogramming transcription factor SOX2 mediates it; restoring TP53 and RB1 function or inhibiting SOX2 reverses it. Published back to back with Ku and colleagues in the same issue of Science, it supplies the mechanism behind the clinical observation that treatment-emergent small-cell neuroendocrine prostate cancer appears in men treated hard with androgen receptor drugs, and it says that the enabling lesions are detectable before the switch happens.","asOf":"2026-09-25","links":[{"label":"Science 2017","url":"https://doi.org/10.1126/science.aah4307"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28059768/"}],"tags":["prostate-evidence"],"related":["paper-ku-rb1-trp53-lineage-plasticity-science-2017","paper-beltran-nepc-divergent-evolution-nat-med-2016","paper-aggarwal-t-sccpc-jco-2018","paper-rubin-mol-cell","idea-bio1-cfrna-plasticity-tracking","prostate-roadmap"],"cancers":["prostate","prostate-mcrpc","prostate-nepc"],"sections":["targeted-therapy","epigenetics"],"technologies":[],"targets":["tp53","rb1","androgen-receptor","sox2"],"drugs":[],"companies":[],"institutions":["mskcc"],"pathways":["lineage-plasticity-neuroendocrine","epigenetic-reprogramming","ar-signaling","cancer-stem-cells-plasticity"],"terms":["castration-resistance","neuroendocrine-differentiation","histologic-transformation","resistance"],"trials":[],"people":["charles-sawyers"],"bottlenecks":["b-resistance","b-undruggable-targets","b-tumor-heterogeneity"],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2017,"doi":"10.1126/science.aah4307","pmid":"28059768","authors":"Mu P, Zhang Z, Benelli M, et al.","paperType":"basic","findings":["Human prostate cancer models developed resistance to enzalutamide by a phenotypic shift from androgen receptor-dependent luminal epithelial cells to androgen receptor-independent basal-like cells.","The lineage plasticity is enabled by the loss of TP53 and RB1 function.","It is mediated by increased expression of the reprogramming transcription factor SOX2.","It can be reversed by restoring TP53 and RB1 function or by inhibiting SOX2 expression.","Mutations in tumour suppressor genes can therefore create a state of increased cellular plasticity that, when challenged with antiandrogen therapy, promotes resistance through lineage switching."],"whatItMeans":"A mechanism for the most feared form of treatment resistance in prostate cancer, and the reason combined TP53 and RB1 loss is worth knowing about before a man starts an androgen receptor drug rather than after his biopsy comes back neuroendocrine. Reversibility in the laboratory is also an argument that the switch is a target and not just a prognosis.","caveats":["Cell line and mouse models; no drug that restores TP53 or RB1 function or inhibits SOX2 exists for patients.","Combined TP53 and RB1 loss is necessary but not sufficient in these models, and most men with both lesions do not develop neuroendocrine disease.","The clinical frequency of lineage switching is measured elsewhere: Aggarwal and colleagues found treatment-emergent small-cell neuroendocrine carcinoma in 17 percent of metastatic biopsies in their cohort (paper-aggarwal-t-sccpc-jco-2018)."],"changedPractice":false},{"id":"paper-nechuta-am-j-clin-nutr","kind":"paper","name":"Soy food intake after diagnosis of breast cancer and survival: an in-depth analysis of combined evidence from cohort studies of US and Chinese women","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 22648714 and published in The American journal of clinical nutrition; the citing page links this DOI, which is how the record was matched.","summary":"Background: Soy isoflavones have antiestrogenic and anticancer properties but also possess estrogen-like properties, which has raised concern about soy food consumption among breast cancer survivors.\n\nObjective: We prospectively evaluated the association between postdiagnosis soy food consumption and breast cancer outcomes among US and Chinese women by using data from the After Breast Cancer Pooling Project.\n\nDesign: The analysis included 9514 breast cancer survivors with a diagnosis of invasive breast cancer between 1991 and 2006 from 2 US cohorts and 1 Chinese cohort. Soy isoflavone intake (mg/d) was measured with validated food-frequency questionnaires. HRs and 95% CIs were estimated by using delayed-entry Cox regression models, adjusted for sociodemographic, clinical, and lifestyle factors.\n\nResults: After a mean follow-up of 7.4 y, we identified 1171 total deaths (881 from breast cancer) and 1348 recurrences. Despite large differences in soy isoflavone intake by country, isoflavone consumption was inversely associated with recurrence among both US and Chinese women, regardless of whether data were analyzed separately by country or combined. No heterogeneity was observed. In the pooled analysis, consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of all-cause (HR: 0.87; 95% CI: 0.70, 1.10) and breast cancer-specific (HR: 0.83; 95% CI: 0.64, 1.07) mortality and a statistically significant reduced risk of recurrence (HR: 0.75; 95% CI: 0.61, 0.92).\n\nConclusion: In this large study of combined data on US and Chinese women, postdiagnosis soy food consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of breast cancer-specific mortality and a statistically significant reduced risk of recurrence.\n\nIndexed on Europe PMC as PubMed record 22648714 (DOI 10.3945/ajcn.112.035972). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Am J Clin Nutr 2012","url":"https://doi.org/10.3945/ajcn.112.035972"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22648714/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/22648714"}],"tags":["europepmc-ingest"],"related":["soy-breast-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The American journal of clinical nutrition","year":2012,"doi":"10.3945/ajcn.112.035972","pmid":"22648714","authors":"Nechuta SJ, Caan BJ, Chen WY, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-spartan-nejm-2018","kind":"paper","name":"SPARTAN: apalutamide for non-metastatic castration-resistant prostate cancer","aka":[],"tldr":"In men whose PSA was rising rapidly on hormone therapy but who had no visible metastases, apalutamide delayed the appearance of metastases by two years and later showed a survival benefit.","summary":"Phase 3 placebo-controlled trial of 1,207 men with non-metastatic castration-resistant prostate cancer and PSA doubling time of ten months or less randomised 2:1 to apalutamide or placebo with continued androgen deprivation.\n\nMedian metastasis-free survival was 40.5 versus 16.2 months (hazard ratio 0.28), and the final analysis showed median overall survival of 73.9 versus 59.9 months (hazard ratio 0.78); rash, fracture and hypothyroidism were more common with apalutamide.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2018","url":"https://doi.org/10.1056/NEJMoa1715546"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29420164/"}],"tags":[],"related":[],"cancers":["prostate-nmcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":["apalutamide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2018,"doi":"10.1056/NEJMoa1715546","pmid":"29420164","authors":"Smith MR, Saad F, Chowdhury S, et al.","paperType":"rct","findings":["Median metastasis-free survival 40.5 vs 16.2 months; hazard ratio 0.28.","Median overall survival 73.9 vs 59.9 months; hazard ratio 0.78."],"whatItMeans":"Apalutamide, enzalutamide or darolutamide are standard for high-risk non-metastatic castration-resistant prostate cancer, a setting largely defined by conventional imaging.","caveats":["Most of these men would show metastases on PSMA PET.","Rash in about a quarter of patients."],"changedPractice":true,"participants":1207},{"id":"paper-grunwald-subtme-pancreatic-cell-2021","kind":"paper","name":"Spatially confined sub-tumor microenvironments in pancreatic cancer","aka":[],"tldr":"Mapping pancreatic tumours region by region found that the tissue organises itself into two recurring neighbourhoods: reactive ones full of active fibroblasts and immune cells beside aggressive tumour cells, and deserted matrix-rich ones that protect the cancer from chemotherapy.","summary":"The human pancreatic tumour microenvironment was deconvoluted through large-scale integration of histology-guided regional multi-omics with clinical data and patient-derived preclinical models. Histologically definable tissue states anchored in fibroblast plasticity, termed subTMEs, showed regional relationships to tumour immunity, subtypes, differentiation and treatment response. Reactive subTMEs rich in coordinated fibroblast communities were immune hot and inhabited by aggressive tumour phenotypes; matrix-rich deserted subTMEs had fewer activated fibroblasts and tumour-suppressive features yet were markedly chemoprotective and enriched after chemotherapy. SubTMEs originated in fibroblast differentiation trajectories, and their intratumoural co-occurrence produced patient-specific, computationally predictable heterogeneity.","asOf":"2026-09-24","links":[{"label":"Grunwald et al., Cell 2021: spatially confined sub-tumour microenvironments","url":"https://doi.org/10.1016/j.cell.2021.09.022"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34644529/"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":["spatial-transcriptomics","single-cell-spatial","organoids"],"targets":[],"drugs":[],"companies":[],"institutions":["princess-margaret","oicr"],"pathways":["tumor-microenvironment","caf-activation-desmoplasia"],"terms":["desmoplasia"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Cell","year":2021,"doi":"10.1016/j.cell.2021.09.022","pmid":"34644529","authors":"Grunwald BT, Devisme A, Andrieux G, et al.","paperType":"translational","findings":["Two recurring tissue states: reactive (immune hot, aggressive) and deserted (matrix-rich, chemoprotective).","Deserted regions are enriched after chemotherapy; subTMEs arise from fibroblast differentiation trajectories."],"whatItMeans":"It explains why one biopsy can mislead and why chemotherapy selects for the protective neighbourhood, an argument for spatial rather than bulk profiling.","caveats":["Retrospective, histology-guided sampling.","No therapeutic intervention tested."],"changedPractice":false},{"id":"paper-gruosso-tnbc-spatial-immune-microenvironments-jci-2019","kind":"paper","name":"Spatially distinct tumor immune microenvironments stratify triple-negative breast cancers","aka":[],"tldr":"Where the immune cells sit matters: triple-negative tumours with killer T cells inside the tumour did well, tumours with no T cells and fibrotic B7-H4-rich stroma did badly, and a third group kept T cells trapped in the stroma with PD-L1 on stromal cells.","summary":"Spatial resolution of immune cells was integrated with laser-capture microdissection expression profiles of tumour and stroma. Immunoreactive TNBCs had tumoural granzyme B-positive CD8 T cells, a type 1 interferon signature and elevated IDO and PD-L1, with good outcome. An immune-cold microenvironment lacking tumoural CD8 cells was defined by high B7-H4, fibrotic stroma signatures and poor outcome. A distinct poor-outcome immunomodulatory microenvironment showed stromal restriction of CD8 cells, stromal PD-L1 and cholesterol biosynthesis signatures. Metasignatures stratified TNBC outcome and suggested targets.","asOf":"2026-09-24","links":[{"label":"Gruosso et al., J Clin Invest 2019: spatially distinct immune microenvironments stratify TNBC","url":"https://doi.org/10.1172/JCI96313"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30753167/"}],"tags":[],"related":[],"cancers":["tnbc"],"sections":[],"technologies":["digital-pathology-ai"],"targets":["pdl1","b7h4","ido1"],"drugs":[],"companies":[],"institutions":[],"pathways":["immune-desert-exclusion","tumor-microenvironment"],"terms":["tils"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jci"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Investigation","year":2019,"doi":"10.1172/JCI96313","pmid":"30753167","authors":"Gruosso T, Gigoux M, Manem VSK, et al.","paperType":"translational","findings":["Three spatial immune classes: immunoreactive (good outcome), immune-cold with B7-H4 and fibrosis (poor), stroma-restricted with stromal PD-L1 (poor).","Metasignatures stratify outcome and nominate IDO, PD-L1 and B7-H4 as class-specific targets."],"whatItMeans":"It explains why a PD-L1 score alone predicts imperfectly: PD-L1 on stromal cells with excluded T cells is a poor-outcome pattern, and B7-H4 marks the cold tumours now being targeted by antibody-drug conjugates.","caveats":["Discovery cohort of modest size; classes were defined retrospectively.","Spatial patterns need standardised digital pathology to be used clinically."],"changedPractice":false},{"id":"paper-bill-axelson-spcg-4-29-year-nejm-2018","kind":"paper","name":"SPCG-4: radical prostatectomy or watchful waiting in prostate cancer, 29-year follow-up","aka":["SPCG-4","Bill-Axelson 2018","Scandinavian Prostate Cancer Group Study Number 4"],"tldr":"Men with prostate cancer found because it caused a lump or symptoms, randomised in the years before PSA testing, were followed for nearly thirty years. Surgery roughly halved the chance of dying of prostate cancer and added an average of 2.9 years of life.","summary":"Anna Bill-Axelson and the Scandinavian Prostate Cancer Group randomised 695 men with clinically detected localised prostate cancer to watchful waiting or radical prostatectomy between October 1989 and February 1999, and followed them through 2017.\n\nThe critical word is clinically detected. These men were found because something was abnormal, not because a blood test was raised, so their cancers were larger and more advanced than the ones a screening programme finds. That is why SPCG-4 is positive and PIVOT, which enrolled a largely prostate-specific antigen-detected population five years later, is not. Read together, the two trials say that the benefit of radical treatment depends on how the cancer was found, which is the single most useful thing a man with newly diagnosed localised disease can be told.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2018","url":"https://doi.org/10.1056/nejmoa1807801"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30575473/"}],"tags":["prostate-evidence"],"related":["paper-wilt-pivot-prostatectomy-observation-nejm-2017","paper-protect-nejm-2016","paper-protect-15-year-nejm-2023","surgery-roadmap","prostate-roadmap"],"cancers":["prostate","prostate-intermediate-risk","prostate-high-risk"],"sections":["surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["prostatectomy","gleason-grade-group","overdiagnosis","other-cause-mortality","overtreatment"],"trials":[],"people":[],"bottlenecks":["b-overdiagnosis","b-surgery-radiation-innovation","b-toxicity-qol"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2018,"doi":"10.1056/nejmoa1807801","pmid":"30575473","authors":"Bill-Axelson A, Holmberg L, Garmo H, et al.","paperType":"rct","findings":["By 31 December 2017, 261 of 347 men in the radical prostatectomy group and 292 of 348 in the watchful waiting group had died.","71 deaths in the prostatectomy group and 110 in the watchful waiting group were from prostate cancer: relative risk 0.55 (95 percent confidence interval 0.41 to 0.74; P less than 0.001), an absolute difference of 11.7 percentage points (5.2 to 18.2).","The number needed to treat to avert one death from any cause was 8.4.","At 23 years, a mean of 2.9 extra years of life were gained with radical prostatectomy.","Among men who had surgery, extracapsular extension carried 5 times the risk of prostate cancer death, and a Gleason score above 7 carried 10 times the risk of a score of 6 or lower."],"whatItMeans":"The clearest evidence that radical treatment of localised prostate cancer saves lives when the cancer was found clinically rather than by a blood test, and the clearest single statement of what grade does: a Gleason score above 7 carried ten times the risk of death of a score of 6 or lower in the same trial.","caveats":["Enrolment ran from 1989 to 1999 and the population was clinically detected, with a median prostate-specific antigen far above what a screening programme produces; the result does not transfer to screen-detected low-risk disease.","Watchful waiting in this trial is not modern active surveillance, which uses magnetic resonance imaging and repeat biopsy and treats radically when the cancer progresses.","Surgical technique, staging and adjuvant treatment have all changed in the intervening thirty years."],"changedPractice":true,"participants":695},{"id":"paper-spearhead-1-lancet-2024","kind":"paper","name":"SPEARHEAD-1: afamitresgene autoleucel, the first engineered T-cell receptor therapy approved for a solid tumour, in synovial sarcoma","aka":[],"tldr":"T cells taken from patients and engineered to recognise the MAGE-A4 protein shrank tumours in about four in ten patients with advanced synovial sarcoma, leading to the first approval of a TCR T-cell therapy for any solid cancer.","summary":"Single-arm phase 2 trial of 52 patients (44 with synovial sarcoma, 8 with myxoid/round cell liposarcoma) who were HLA-A*02 positive with MAGE-A4-expressing tumours, previously treated with anthracycline or ifosfamide, treated with a single infusion of afamitresgene autoleucel (afami-cel), autologous T cells expressing an affinity-enhanced MAGE-A4-specific T-cell receptor, after lymphodepleting chemotherapy. Primary endpoint was objective response rate.\n\nThe response rate was 37% overall and 39% in synovial sarcoma, with a median duration of response of about 12 months. Cytokine release syndrome occurred in about 70% but was mostly low grade. It led to FDA accelerated approval in 2024 (Tecelra), the first TCR-T and the first engineered cell therapy approved for a solid tumour.","asOf":"2026-09-08","links":[{"label":"PubMed search: SPEARHEAD-1 afamitresgene autoleucel Lancet","url":"https://pubmed.ncbi.nlm.nih.gov/?term=SPEARHEAD-1+afamitresgene+autoleucel+synovial+sarcoma+Lancet"},{"label":"ClinicalTrials.gov NCT04044768","url":"https://clinicaltrials.gov/study/NCT04044768"},{"label":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=SPEARHEAD-1%20afamitresgene%20autoleucel%20synovial%20sarcoma%20D'Angelo%20Lancet%202024"}],"tags":[],"related":["paper-c-144-01-lifileucel-melanoma-jco-2021"],"cancers":["sarcoma"],"sections":[],"technologies":["tcr-t"],"targets":["mage-a4"],"drugs":["afamitresgene-autoleucel","letetresgene-autoleucel"],"companies":["adaptimmune"],"institutions":[],"pathways":[],"terms":["orr","crs","accelerated-approval"],"trials":[],"people":["jean-yves-blay"],"bottlenecks":["b-rare-cancers","b-manufacturing-cell-therapy","b-trial-diversity"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2024,"doi":"10.1016/S0140-6736(24)00319-2","pmid":"38554725","authors":"D'Angelo SP, Araujo DM, Abdul Razak AR, et al.","paperType":"rct","findings":["Objective response 37% overall (19 of 52); 39% in synovial sarcoma and 25% in myxoid/round cell liposarcoma.","Median duration of response about 12 months; median PFS about 3.8 months and median OS about 15 months in a heavily pretreated population.","Cytokine release syndrome in about 70% of patients, grade 3 in around 2%; cytopenias were common after lymphodepletion.","Eligibility required both HLA-A*02 genotype and MAGE-A4 expression, satisfied by roughly a third of screened synovial sarcoma patients.","Manufacturing success was high but the process took several weeks per patient."],"whatItMeans":"Patients with advanced synovial sarcoma, a rare cancer of young adults with few effective drugs, now have an approved cell therapy that produces responses lasting about a year in a substantial minority, if their tissue type and tumour antigen match. It proves that engineered T cells can work against a solid tumour when a good target is present, which had been elusive. It is not a cure for most, requires specialised centres, and only a minority of patients are eligible.","caveats":["Single-arm trial with a response-rate endpoint; no randomised comparison and OS benefit is unproven.","Restricted to HLA-A*02-positive patients, which excludes many people of non-European ancestry.","Responses are usually not durable beyond a year; mechanisms of relapse (antigen loss, T-cell exhaustion) are being studied.","Very high cost and complex logistics for a rare indication."],"changedPractice":true,"participants":52},{"id":"paper-spotlight-lancet-2023","kind":"paper","name":"SPOTLIGHT: zolbetuximab, the first Claudin 18.2 antibody, added to chemotherapy in gastric cancer","aka":[],"tldr":"In stomach cancers that express the protein Claudin 18.2, adding the antibody zolbetuximab to chemotherapy extended survival by nearly three months, making Claudin 18.2 a new biomarker to test for.","summary":"Double-blind phase 3 trial of 565 patients with untreated, HER2-negative, Claudin 18.2-positive (moderate-to-strong staining in 75% or more of tumour cells) locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma, randomised to zolbetuximab or placebo plus mFOLFOX6. Primary endpoint was PFS.\n\nMedian PFS was 10.6 vs 8.7 months (HR 0.75) and median OS 18.2 vs 15.5 months (HR 0.75). Together with the GLOW trial (zolbetuximab plus CAPOX) it led to approvals in 2024 and made Claudin 18.2 testing routine for HER2-negative gastric cancer, while opening a target now pursued by ADCs and CAR-T cells.","asOf":"2026-09-08","links":[{"label":"PubMed search: SPOTLIGHT zolbetuximab Lancet 2023","url":"https://pubmed.ncbi.nlm.nih.gov/?term=SPOTLIGHT+zolbetuximab+mFOLFOX6+Shitara+Lancet"},{"label":"ClinicalTrials.gov NCT03504397","url":"https://clinicaltrials.gov/study/NCT03504397"}],"tags":[],"related":[],"cancers":["gastric","esophageal"],"sections":[],"technologies":["monoclonal-antibody","histopathology-ihc","companion-diagnostic"],"targets":["cldn18-2"],"drugs":[],"companies":["astellas"],"institutions":["ncc-japan"],"pathways":[],"terms":["ihc","pfs","os","adcc","first-line"],"trials":[],"people":["shitara-kohei","bang-yung-jue","xu-rui-hua","kang-yoon-koo"],"bottlenecks":["b-biomarker-validation","b-combination-space"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2023,"doi":"10.1016/S0140-6736(23)00620-7","pmid":"37068504","authors":"Shitara K, Lordick F, Bang YJ, et al.","paperType":"rct","findings":["Median PFS 10.61 vs 8.67 months; HR 0.751 (95% CI 0.598-0.942).","Median overall survival 18.23 vs 15.54 months; HR 0.750 (95% CI 0.601-0.936).","About 38% of screened patients were Claudin 18.2-positive by the trial definition.","Nausea (81% vs 61%) and vomiting (65% vs 35%) were much more common with zolbetuximab, particularly during the first infusions.","GLOW (Nature Medicine 2023) confirmed the result with CAPOX: PFS 8.2 vs 6.8 months (HR 0.69), OS 14.4 vs 12.2 months (HR 0.77)."],"whatItMeans":"Patients with newly diagnosed advanced stomach cancer should now have Claudin 18.2 tested alongside HER2, PD-L1 and mismatch repair, because roughly a third will be eligible for zolbetuximab, which adds about three months of median survival. The main practical problem is nausea and vomiting during infusions, which needs aggressive prophylaxis. How to sequence or combine it with immunotherapy in PD-L1-positive tumours is unresolved.","caveats":["The PD-L1-positive population, who would now receive nivolumab or pembrolizumab with chemotherapy, was not addressed; the trials predate that standard.","Claudin 18.2 immunohistochemistry cut-off (75% of cells at 2+/3+) is stringent and assay standardisation is incomplete.","Gastrointestinal toxicity leads to infusion interruptions in many patients.","Modest absolute gains for a costly antibody."],"changedPractice":true,"participants":565},{"id":"paper-jean-pascal-machiels-ann-oncol-2020","kind":"paper","name":"Squamous cell carcinoma of the oral cavity, larynx, oropharynx and hypopharynx: EHNS-ESMO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up","aka":[],"tldr":"Paper by Jean-Pascal Machiels indexed on Europe PMC as PubMed record 33239190, in Annals of Oncology (2020), one of the most cited records naming an author with this name at King Albert II Cancer Institute, Cliniques universitaires Saint-Luc.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 33239190 (DOI 10.1016/j.annonc.2020.07.011). Its author list gives \"Machiels JP\" with the affiliation \"Service d'Oncologie Médicale, Institut Roi Albert II, Cliniques Universitaires Saint-Luc, Brussels, Belgium; Institut de Recherche Clinique et Expérimentale, Université Catholique de Louvain (UCLouvain), Brussels, Belgium\", which names King Albert II Cancer Institute, Cliniques universitaires Saint-Luc; that is how the record was matched to Jean-Pascal Machiels, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Ann Oncol 2020","url":"https://doi.org/10.1016/j.annonc.2020.07.011"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33239190/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33239190"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["jean-pascal-machiels"],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2020,"doi":"10.1016/j.annonc.2020.07.011","pmid":"33239190","authors":"Machiels JP, René Leemans C, Golusinski W, et al.","paperType":"guideline","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Jean-Pascal Machiels at King Albert II Cancer Institute, Cliniques universitaires Saint-Luc, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-ssg-xviii-adjuvant-imatinib-joensuu-jama-2012","kind":"paper","name":"SSG XVIII/AIO: one versus three years of adjuvant imatinib for operable gastrointestinal stromal tumour","aka":[],"tldr":"Three years of imatinib after surgery for high-risk gastrointestinal stromal tumour reduced recurrences and deaths compared with one year, setting the standard duration of adjuvant therapy.","summary":"Phase 3 trial of 400 patients with resected KIT-positive GIST at high risk of recurrence randomised to 12 or 36 months of adjuvant imatinib 400 mg daily.\n\nFive-year recurrence-free survival was 65.6 versus 47.9 percent (hazard ratio 0.46) and five-year overall survival 92.0 versus 81.7 percent (hazard ratio 0.45); ten-year follow-up confirmed the survival benefit, and discontinuation for adverse events was more common with longer treatment.","asOf":"2026-09-17","links":[{"label":"JAMA 2012","url":"https://doi.org/10.1001/jama.2012.347"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22453568/"}],"tags":[],"related":[],"cancers":["gist-kit-exon-11"],"sections":[],"technologies":[],"targets":[],"drugs":["imatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["heikki-joensuu"],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2012,"doi":"10.1001/jama.2012.347","pmid":"22453568","authors":"Joensuu H, Eriksson M, Sundby Hall K, et al.","paperType":"rct","findings":["Five-year recurrence-free survival 65.6 percent vs 47.9 percent; hazard ratio 0.46.","Five-year overall survival 92.0 percent vs 81.7 percent; hazard ratio 0.45."],"whatItMeans":"Three years of adjuvant imatinib is standard for high-risk resected GIST with imatinib-sensitive mutations; longer courses are being tested.","caveats":["Patients with PDGFRA D842V mutations, which are imatinib-resistant, do not benefit.","Recurrences resume after imatinib is stopped."],"changedPractice":true,"participants":400},{"id":"paper-stampede-abiraterone-high-risk-attard-lancet-2022","kind":"paper","name":"STAMPEDE: abiraterone with or without enzalutamide added to androgen deprivation for high-risk non-metastatic prostate cancer","aka":[],"tldr":"Adding two years of abiraterone to hormone therapy and radiotherapy for high-risk localised or node-positive prostate cancer halved the risk of metastases and cut deaths by 40 percent, while adding enzalutamide on top brought only extra toxicity.","summary":"Meta-analysis of two STAMPEDE comparisons including 1,974 men with high-risk non-metastatic prostate cancer (node-positive, or node-negative with at least two of T3/4, Gleason 8 to 10, PSA 40 or more) randomised to androgen deprivation with or without two years of abiraterone (with enzalutamide in the second comparison).\n\nSix-year metastasis-free survival was 82 versus 69 percent (hazard ratio 0.53) and overall survival 86 versus 77 percent (hazard ratio 0.60); enzalutamide added toxicity without efficacy.","asOf":"2026-09-17","links":[{"label":"Lancet 2022","url":"https://doi.org/10.1016/S0140-6736(21)02437-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34953525/"}],"tags":[],"related":[],"cancers":["prostate-high-risk"],"sections":[],"technologies":[],"targets":[],"drugs":["abiraterone","enzalutamide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["stampede"],"people":["gerhardt-attard"],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2022,"doi":"10.1016/S0140-6736(21)02437-5","pmid":"34953525","authors":"Attard G, Murphy L, Clarke NW, et al.","paperType":"rct","findings":["Six-year metastasis-free survival 82 percent vs 69 percent; hazard ratio 0.53.","Six-year overall survival 86 percent vs 77 percent; hazard ratio 0.60."],"whatItMeans":"Two years of abiraterone with androgen deprivation and radiotherapy is the standard for very high-risk and node-positive localised prostate cancer.","caveats":["Most men received radiotherapy; benefit after prostatectomy is less certain.","Staging was by conventional imaging."],"changedPractice":true,"participants":1974},{"id":"paper-stampede-abiraterone-nejm-2017","kind":"paper","name":"STAMPEDE: adding abiraterone to hormone therapy at diagnosis of advanced prostate cancer","aka":[],"tldr":"Giving the hormone-pathway drug abiraterone from the start, alongside standard testosterone suppression, cut deaths by more than a third in men newly diagnosed with high-risk or metastatic prostate cancer.","summary":"STAMPEDE is a multi-arm, multi-stage platform trial. This comparison randomised 1,917 men with newly diagnosed locally advanced or metastatic prostate cancer starting androgen deprivation therapy (ADT) to ADT alone or ADT plus abiraterone and prednisolone. Primary endpoint was overall survival.\n\nOverall survival HR was 0.63 (3-year OS 83% vs 76%) and failure-free survival HR 0.29. Alongside LATITUDE, published the same day, it made early intensification of hormone therapy the standard for metastatic hormone-sensitive prostate cancer, and later STAMPEDE analyses extended this to high-risk non-metastatic disease. The platform design itself, testing many questions against one shared control arm, became a model for trial efficiency.","asOf":"2026-09-08","links":[{"label":"NEJM 2017","url":"https://doi.org/10.1056/NEJMoa1702900"},{"label":"ClinicalTrials.gov NCT00268476","url":"https://clinicaltrials.gov/study/NCT00268476"}],"tags":[],"related":["prostate-roadmap","paper-vale-stopcap-docetaxel-bisphosphonates-lancet-oncol-2016"],"cancers":["prostate"],"sections":[],"technologies":["androgen-deprivation","endocrine-therapy"],"targets":["androgen-receptor"],"drugs":[],"companies":["johnson-johnson"],"institutions":["icr-london","royal-marsden","cruk"],"pathways":[],"terms":["basket-umbrella-platform","os","standard-of-care"],"trials":[],"people":["nicholas-james","johann-de-bono"],"bottlenecks":["b-trial-design","b-drug-pricing","b-generic-repurposing"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2017,"doi":"10.1056/NEJMoa1702900","authors":"James ND, de Bono JS, Spears MR, et al.","paperType":"rct","findings":["Overall survival HR 0.63 (95% CI 0.52-0.76); 3-year OS 83% vs 76%.","Failure-free survival HR 0.29 (95% CI 0.25-0.34).","Benefit consistent in metastatic (M1) and high-risk non-metastatic (M0) subgroups at the primary analysis.","Grade 3-5 adverse events 47% vs 33%, driven by hypertension, liver enzyme elevation and cardiovascular events.","Later STAMPEDE analysis (Lancet 2022) showed abiraterone for two years in high-risk M0 disease improved 6-year metastasis-free survival from 69% to 82% (HR 0.53)."],"whatItMeans":"Men diagnosed with prostate cancer that has already spread, or that is locally advanced and high risk, should start abiraterone (or another androgen-receptor pathway inhibitor) at the same time as testosterone suppression rather than waiting for resistance. This roughly halves the risk of death over several years. The same platform later showed that docetaxel chemotherapy and, in high-volume metastatic disease, triple therapy also help, and that abiraterone benefits men with high-risk disease treated with radiotherapy.","caveats":["Abiraterone requires prednisolone and monitoring for hypertension, hypokalaemia and liver toxicity; cardiovascular risk is higher in older men.","Direct comparison with docetaxel (also in STAMPEDE) showed similar OS in metastatic disease, leaving the choice to toxicity and cost.","Cost of abiraterone was a barrier until generic versions became available.","Optimal duration in non-metastatic disease (two years in STAMPEDE) was chosen empirically."],"changedPractice":true,"participants":1917},{"id":"paper-rtog-0617-lancet-oncol-2015","kind":"paper","name":"Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study","aka":[],"tldr":"Published report from the RTOG 0617 trial registered as NCT00533949, in The Lancet Oncology (2015), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: We aimed to compare overall survival after standard-dose versus high-dose conformal radiotherapy with concurrent chemotherapy and the addition of cetuximab to concurrent chemoradiation for patients with inoperable stage III non-small-cell lung cancer.\n\nMethods: In this open-label randomised, two-by-two factorial phase 3 study in 185 institutions in the USA and Canada, we enrolled patients (aged ≥ 18 years) with unresectable stage III non-small-cell lung cancer, a Zubrod performance status of 0-1, adequate pulmonary function, and no evidence of supraclavicular or contralateral hilar adenopathy. We randomly assigned (1:1:1:1) patients to receive either 60 Gy (standard dose), 74 Gy (high dose), 60 Gy plus cetuximab, or 74 Gy plus cetuximab. All patients also received concurrent chemotherapy with 45 mg/m(2) paclitaxel and carboplatin once a week (AUC 2); 2 weeks after chemoradiation, two cycles of consolidation chemotherapy separated by 3 weeks were given consisting of paclitaxel (200 mg/m(2)) and carboplatin (AUC 6). Randomisation was done with permuted block randomisation methods, stratified by radiotherapy technique, Zubrod performance status, use of PET during staging, and histology; treatment group assignments were not masked. Radiation dose was prescribed to the planning target volume and was given in 2 Gy daily fractions with either intensity-modulated radiation therapy or three-dimensional conformal radiation therapy. The use of four-dimensional CT and image-guided radiation therapy were encouraged but not necessary. For patients assigned to receive cetuximab, 400 mg/m(2) cetuximab was given on day 1 followed by weekly doses of 250 mg/m(2), and was continued through consolidation therapy. The primary endpoint was overall survival. All analyses were done by modified intention-to-treat. The study is registered with ClinicalTrials.gov, number NCT00533949.\n\nFindings: Between Nov 27, 2007, and Nov 22, 2011, 166 patients were randomly assigned to receive standard-dose chemoradiotherapy, 121 to high-dose chemoradiotherapy, 147 to standard-dose chemoradiotherapy and cetuximab, and 110 to high-dose chemoradiotherapy and cetuximab. Median follow-up for the radiotherapy comparison was 22.9 months (IQR 27.5-33.3). Median overall survival was 28.7 months (95% CI 24.1-36.9) for patients who received standard-dose radiotherapy and 20.3 months (17.7-25.0) for those who received high-dose radiotherapy (hazard ratio [HR] 1.38, 95% CI 1.09-1.76; p=0.004). Median follow-up for the cetuximab comparison was 21.3 months (IQR 23.5-29.8). Median overall survival in patients who received cetuximab was 25.0 months (95% CI 20.2-30.5) compared with 24.0 months (19.8-28.6) in those who did not (HR 1.07, 95% CI 0.84-1.35; p=0.29). Both the radiation-dose and cetuximab results crossed protocol-specified futility boundaries. We recorded no statistical differences in grade 3 or worse toxic effects between radiotherapy groups. By contrast, the use of cetuximab was associated with a higher rate of grade 3 or worse toxic effects (205 [86%] of 237 vs 160 [70%] of 228 patients; p<0.0001). There were more treatment-related deaths in the high-dose chemoradiotherapy and cetuximab groups (radiotherapy comparison: eight vs three patients; cetuximab comparison: ten vs five patients). There were no differences in severe pulmonary events between treatment groups. Severe oesophagitis was more common in patients who received high-dose chemoradiotherapy than in those who received standard-dose treatment (43 [21%] of 207 patients vs 16 [7%] of 217 patients; p<0.0001).\n\nInterpretation: 74 Gy radiation given in 2 Gy fractions with concurrent chemotherapy was not better than 60 Gy plus concurrent chemotherapy for patients with stage III non-small-cell lung cancer, and might be potentially harmful. Addition of cetuximab to concurrent chemoradiation and consolidation treatment provided no benefit in overall survival for these patients.\n\nFunding: National Cancer Institute and Bristol-Myers Squibb.\n\nIndexed on Europe PMC as PubMed record 25601342 (DOI 10.1016/s1470-2045(14)71207-0). Its abstract cites the registry id NCT00533949, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2015","url":"https://doi.org/10.1016/s1470-2045(14)71207-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25601342/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25601342"},{"label":"ClinicalTrials.gov NCT00533949","url":"https://clinicaltrials.gov/study/NCT00533949"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["rtog-0617"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2015,"doi":"10.1016/s1470-2045(14)71207-0","pmid":"25601342","authors":"Bradley JD, Paulus R, Komaki R, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT00533949 with the most citations, so it is the natural first reading for anyone following the RTOG 0617 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-li-j-mol-diagn","kind":"paper","name":"Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 27993330 and published in The Journal of molecular diagnostics; the citing page links this DOI, which is how the record was matched.","summary":"Widespread clinical laboratory implementation of next-generation sequencing-based cancer testing has highlighted the importance and potential benefits of standardizing the interpretation and reporting of molecular results among laboratories. A multidisciplinary working group tasked to assess the current status of next-generation sequencing-based cancer testing and establish standardized consensus classification, annotation, interpretation, and reporting conventions for somatic sequence variants was convened by the Association for Molecular Pathology with liaison representation from the American College of Medical Genetics and Genomics, American Society of Clinical Oncology, and College of American Pathologists. On the basis of the results of professional surveys, literature review, and the Working Group's subject matter expert consensus, a four-tiered system to categorize somatic sequence variations based on their clinical significances is proposed: tier I, variants with strong clinical significance; tier II, variants with potential clinical significance; tier III, variants of unknown clinical significance; and tier IV, variants deemed benign or likely benign. Cancer genomics is a rapidly evolving field; therefore, the clinical significance of any variant in therapy, diagnosis, or prognosis should be reevaluated on an ongoing basis. Reporting of genomic variants should follow standard nomenclature, with testing method and limitations clearly described. Clinical recommendations should be concise and correlate with histological and clinical findings.\n\nIndexed on Europe PMC as PubMed record 27993330 (DOI 10.1016/j.jmoldx.2016.10.002). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Mol Diagn 2017","url":"https://doi.org/10.1016/j.jmoldx.2016.10.002"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27993330/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27993330"}],"tags":["europepmc-ingest"],"related":["vaf"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Journal of molecular diagnostics","year":2017,"doi":"10.1016/j.jmoldx.2016.10.002","pmid":"27993330","authors":"Li MM, Datto M, Duncavage EJ, et al.","paperType":"review","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-palma-j-clin-oncol","kind":"paper","name":"Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastatic Cancers: Long-Term Results of the SABR-COMET Phase II Randomized Trial","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 32484754 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: The oligometastatic paradigm hypothesizes that patients with a limited number of metastases may achieve long-term disease control, or even cure, if all sites of disease can be ablated. However, long-term randomized data that test this paradigm are lacking.\n\nMethods: We enrolled patients with a controlled primary malignancy and 1-5 metastatic lesions, with all metastases amenable to stereotactic ablative radiotherapy (SABR). We stratified by the number of metastases (1-3 v 4-5) and randomized in a 1:2 ratio between palliative standard-of-care (SOC) treatments (arm 1) and SOC plus SABR (arm 2). We used a randomized phase II screening design with a primary end point of overall survival (OS), using an α of.20 (wherein P <.20 indicates a positive trial). Secondary end points included progression-free survival (PFS), toxicity, and quality of life (QOL). Herein, we present long-term outcomes from the trial.\n\nResults: Between 2012 and 2016, 99 patients were randomly assigned at 10 centers internationally. The most common primary tumor types were breast (n = 18), lung (n = 18), colorectal (n = 18), and prostate (n = 16). Median follow-up was 51 months. The 5-year OS rate was 17.7% in arm 1 (95% CI, 6% to 34%) versus 42.3% in arm 2 (95% CI, 28% to 56%; stratified log-rank P =.006). The 5-year PFS rate was not reached in arm 1 (3.2%; 95% CI, 0% to 14% at 4 years with last patient censored) and 17.3% in arm 2 (95% CI, 8% to 30%; P =.001). There were no new grade 2-5 adverse events and no differences in QOL between arms.\n\nConclusion: With extended follow-up, the impact of SABR on OS was larger in magnitude than in the initial analysis and durable over time. There were no new safety signals, and SABR had no detrimental impact on QOL.\n\nIndexed on Europe PMC as PubMed record 32484754 (DOI 10.1200/jco.20.00818). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2020","url":"https://doi.org/10.1200/jco.20.00818"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32484754/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32484754"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["sabr-comet"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/jco.20.00818","pmid":"32484754","authors":"Palma DA, Olson R, Harrow S, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-sabr-comet-lancet-2019","kind":"paper","name":"Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): a randomised, phase 2, open-label trial","aka":[],"tldr":"Published report from the trial registered as NCT01446744, in The Lancet (2019), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: The oligometastatic paradigm suggests that some patients with a limited number of metastases might be cured if all lesions are eradicated. Evidence from randomised controlled trials to support this paradigm is scarce. We aimed to assess the effect of stereotactic ablative radiotherapy (SABR) on survival, oncological outcomes, toxicity, and quality of life in patients with a controlled primary tumour and one to five oligometastatic lesions.\n\nMethods: This randomised, open-label phase 2 study was done at 10 hospitals in Canada, the Netherlands, Scotland, and Australia. Patients aged 18 or older with a controlled primary tumour and one to five metastatic lesions, Eastern Cooperative Oncology Group score of 0-1, and a life expectancy of at least 6 months were eligible. After stratifying by the number of metastases (1-3 vs 4-5), we randomly assigned patients (1:2) to receive either palliative standard of care treatments alone (control group), or standard of care plus SABR to all metastatic lesions (SABR group), using a computer-generated randomisation list with permuted blocks of nine. Neither patients nor physicians were masked to treatment allocation. The primary endpoint was overall survival. We used a randomised phase 2 screening design with a two-sided α of 0·20 (wherein p<0·20 designates a positive trial). All analyses were intention to treat. This study is registered with ClinicalTrials.gov, number NCT01446744.\n\nFindings: 99 patients were randomised between Feb 10, 2012, and Aug 30, 2016. Of 99 patients, 33 (33%) were assigned to the control group and 66 (67%) to the SABR group. Two (3%) patients in the SABR group did not receive allocated treatment and withdrew from the trial; two (6%) patients in the control group also withdrew from the trial. Median follow-up was 25 months (IQR 19-54) in the control group versus 26 months (23-37) in the SABR group. Median overall survival was 28 months (95% CI 19-33) in the control group versus 41 months (26-not reached) in the SABR group (hazard ratio 0·57, 95% CI 0·30-1·10; p=0·090). Adverse events of grade 2 or worse occurred in three (9%) of 33 controls and 19 (29%) of 66 patients in the SABR group (p=0·026), an absolute increase of 20% (95% CI 5-34). Treatment-related deaths occurred in three (4·5%) of 66 patients after SABR, compared with none in the control group.\n\nInterpretation: SABR was associated with an improvement in overall survival, meeting the primary endpoint of this trial, but three (4·5%) of 66 patients in the SABR group had treatment-related death. Phase 3 trials are needed to conclusively show an overall survival benefit, and to determine the maximum number of metastatic lesions wherein SABR provides a benefit.\n\nFunding: Ontario Institute for Cancer Research and London Regional Cancer Program Catalyst Grant.\n\nIndexed on Europe PMC as PubMed record 30982687 (DOI 10.1016/s0140-6736(18)32487-5). Its abstract cites the registry id NCT01446744, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet 2019","url":"https://doi.org/10.1016/s0140-6736(18)32487-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30982687/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30982687"},{"label":"ClinicalTrials.gov NCT01446744","url":"https://clinicaltrials.gov/study/NCT01446744"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["sabr-comet"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2019,"doi":"10.1016/s0140-6736(18)32487-5","pmid":"30982687","authors":"Palma DA, Olson R, Harrow S, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT01446744 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-chisel-lancet-oncol-2019","kind":"paper","name":"Stereotactic ablative radiotherapy versus standard radiotherapy in stage 1 non-small-cell lung cancer (TROG 09.02 CHISEL): a phase 3, open-label, randomised controlled trial","aka":[],"tldr":"Published report from the CHISEL trial registered as NCT01014130, in The Lancet Oncology (2019), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Stereotactic ablative body radiotherapy (SABR) is widely used to treat inoperable stage 1 non-small-cell lung cancer (NSCLC), despite the absence of prospective evidence that this type of treatment improves local control or prolongs overall survival compared with standard radiotherapy. We aimed to compare the two treatment techniques.\n\nMethods: We did this multicentre, phase 3, randomised, controlled trial in 11 hospitals in Australia and three hospitals in New Zealand. Patients were eligible if they were aged 18 years or older, had biopsy-confirmed stage 1 (T1-T2aN0M0) NSCLC diagnosed on the basis of 18 F-fluorodeoxyglucose PET, and were medically inoperable or had refused surgery. Patients had to have an Eastern Cooperative Oncology Group performance status of 0 or 1, and the tumour had to be peripherally located. Patients were randomly assigned after stratification for T stage and operability in a 2:1 ratio to SABR (54 Gy in three 18 Gy fractions, or 48 Gy in four 12 Gy fractions if the tumour was <2 cm from the chest wall) or standard radiotherapy (66 Gy in 33 daily 2 Gy fractions or 50 Gy in 20 daily 2·5 Gy fractions, depending on institutional preference) using minimisation, so no sequence was pre-generated. Clinicians, patients, and data managers had no previous knowledge of the treatment group to which patients would be assigned; however, the treatment assignment was subsequently open label (because of the nature of the interventions). The primary endpoint was time to local treatment failure (assessed according to Response Evaluation Criteria in Solid Tumors version 1.0), with the hypothesis that SABR would result in superior local control compared with standard radiotherapy. All efficacy analyses were based on the intention-to-treat analysis. Safety analyses were done on a per-protocol basis, according to treatment that the patients actually received. The trial is registered with ClinicalTrials.gov (NCT01014130) and the Australia and New Zealand Clinical Trials Registry (ACTRN12610000479000). The trial is closed to new participants.\n\nFindings: Between Dec 31, 2009, and June 22, 2015, 101 eligible patients were enrolled and randomly assigned to receive SABR (n=66) or standard radiotherapy (n=35). Five (7·6%) patients in the SABR group and two (6·5%) in the standard radiotherapy group did not receive treatment, and a further four in each group withdrew before study end. at data cutoff (July 31, 2017), median follow-up for local treatment failure was 2·1 years (IQR 1·2-3·6) for patients randomly assigned to standard radiotherapy and 2·6 years (IQR 1·6-3·6) for patients assigned to SABR. 20 (20%) of 101 patients had progressed locally: nine (14%) of 66 patients in the SABR group and 11 (31%) of 35 patients in the standard radiotherapy group, and freedom from local treatment failure was improved in the SABR group compared with the standard radiotherapy group (hazard ratio 0·32, 95% CI 0·13-0·77, p=0·0077). Median time to local treatment failure was not reached in either group. In patients treated with SABR, there was one grade 4 adverse event (dyspnoea) and seven grade 3 adverse events (two cough, one hypoxia, one lung infection, one weight loss, one dyspnoea, and one fatigue) related to treatment compared with two grade 3 events (chest pain) in the standard treatment group.\n\nInterpretation: In patients with inoperable peripherally located stage 1 NSCLC, compared with standard radiotherapy, SABR resulted in superior local control of the primary disease without an increase in major toxicity. The findings of this trial suggest that SABR should be the treatment of choice for this patient group.\n\nFunding: The Radiation and Optometry Section of the Australian Government Department of Health with the assistance of Cancer Australia, and the Cancer Society of New Zealand and the Cancer Research Trust New Zealand (formerly Genesis Oncology Trust).\n\nIndexed on Europe PMC as PubMed record 30770291 (DOI 10.1016/s1470-2045(18)30896-9). Its abstract cites the registry id NCT01014130, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2019","url":"https://doi.org/10.1016/s1470-2045(18)30896-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30770291/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30770291"},{"label":"ClinicalTrials.gov NCT01014130","url":"https://clinicaltrials.gov/study/NCT01014130"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["chisel"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2019,"doi":"10.1016/s1470-2045(18)30896-9","pmid":"30770291","authors":"Ball D, Mai GT, Vinod S, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT01014130 with the most citations, so it is the natural first reading for anyone following the CHISEL trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-kras-nsclc-cancer-discov-2018","kind":"paper","name":"STK11/LKB1 Mutations and PD-1 Inhibitor Resistance in KRAS -Mutant Lung Adenocarcinoma","aka":[],"tldr":"Phase 2 or 3 results paper on KRAS in Non-small-cell lung cancer, in Cancer Discovery (2018), one of the most cited Europe PMC records with KRAS in its title.","summary":"KRAS is the most common oncogenic driver in lung adenocarcinoma (LUAC). We previously reported that STK11/LKB1 (KL) or TP53 (KP) comutations define distinct subgroups of KRAS -mutant LUAC. Here, we examine the efficacy of PD-1 inhibitors in these subgroups. Objective response rates to PD-1 blockade differed significantly among KL (7.4%), KP (35.7%), and K-only (28.6%) subgroups ( P < 0.001) in the Stand Up To Cancer (SU2C) cohort (174 patients) with KRAS -mutant LUAC and in patients treated with nivolumab in the CheckMate-057 phase III trial (0% vs. 57.1% vs. 18.2%; P = 0.047). In the SU2C cohort, KL LUAC exhibited shorter progression-free ( P < 0.001) and overall ( P = 0.0015) survival compared with KRAS MUT; STK11/LKB1 WT LUAC. Among 924 LUACs, STK11/LKB1 alterations were the only marker significantly associated with PD-L1 negativity in TMB Intermediate/High LUAC. The impact of STK11/LKB1 alterations on clinical outcomes with PD-1/PD-L1 inhibitors extended to PD-L1-positive non-small cell lung cancer. In Kras -mutant murine LUAC models, Stk11/Lkb1 loss promoted PD-1/PD-L1 inhibitor resistance, suggesting a causal role. Our results identify STK11/LKB1 alterations as a major driver of primary resistance to PD-1 blockade in KRAS -mutant LUAC. Significance: This work identifies STK11/LKB1 alterations as the most prevalent genomic driver of primary resistance to PD-1 axis inhibitors in KRAS -mutant lung adenocarcinoma. Genomic profiling may enhance the predictive utility of PD-L1 expression and tumor mutation burden and facilitate establishment of personalized combination immunotherapy approaches for genomically defined LUAC subsets. Cancer Discov; 8(7); 822-35. ©2018 AACR. See related commentary by Etxeberria et al., p. 794 This article is highlighted in the In This Issue feature, p. 781.\n\nIndexed on Europe PMC as PubMed record 29773717 (DOI 10.1158/2159-8290.cd-18-0099). Its title names KRAS and its text names Non-small-cell lung cancer; PubMed types it as a clinical trial report (Clinical Trial, Phase III, Research Support, Non-U.S. Gov't, research-article, Randomized Controlled Trial, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural). It was matched automatically to the idea \"Turn a brake back on: drugs that reactivate the PP2A phosphatase\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer Discov 2018","url":"https://doi.org/10.1158/2159-8290.cd-18-0099"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29773717/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29773717"}],"tags":["europepmc-ingest"],"related":["stk11-keap1-loss","kras-g12c"],"cancers":["nsclc"],"sections":[],"technologies":["checkpoint-inhibitor","cgp"],"targets":["stk11","kras","keap1","pdl1","pd1"],"drugs":[],"companies":[],"institutions":[],"pathways":["t-cell-exhaustion","ras-mapk","pd1-checkpoint"],"terms":["stk11-keap1","cold-vs-hot"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-discovery"],"dependsOn":[],"notes":[],"journal":"Cancer Discovery","year":2018,"doi":"10.1158/2159-8290.cd-18-0099","pmid":"29773717","authors":"Skoulidis F, Goldberg ME, Greenawalt DM, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for KRAS in Non-small-cell lung cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by KRAS in the title and Non-small-cell lung cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-stojdl-vsv-interferon-defect-natmed-2000","kind":"paper","name":"Stojdl 2000: cancer cells that stopped answering interferon cannot stop a virus either","aka":[],"tldr":"A normal cell warned by interferon shuts a virus down; many cancer cells have broken that alarm to grow, and this paper showed a common animal virus exploits exactly that break.","summary":"Interferons bind cell-surface receptors and set off a signalling cascade that produces both an antiviral state and growth-inhibitory or apoptotic signals. Many cancers acquire mutations in that pathway, which frees them from interferon's growth control. Stojdl and colleagues in John Bell's laboratory argued that the same cells must therefore have given up their antiviral defence, and tested it with vesicular stomatitis virus, an enveloped negative-sense RNA virus that is exquisitely sensitive to interferon.\n\nVesicular stomatitis virus replicated in and killed a range of human tumour cell lines at interferon doses that completely protected normal human primary cultures. A single intratumoural injection reduced tumour burden in nude mice carrying human melanoma xenografts. This is the mechanistic argument the whole field uses in plain words: the virus is not clever, the cancer cell is defenceless.","asOf":"2026-09-25","links":[{"label":"Nat Med 2000","url":"https://doi.org/10.1038/77558"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/10888934/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/10888934"}],"tags":[],"related":[],"cancers":[],"sections":["immunotherapy"],"technologies":["oncolytic-virus"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["john-bell"],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2000,"doi":"10.1038/77558","pmid":"10888934","authors":"Stojdl DF, Lichty B, Knowles S, et al.","paperType":"basic","findings":["Vesicular stomatitis virus replicated in and killed a variety of human tumour cell lines at interferon doses that fully protected normal human primary cell cultures.","A single intratumoural injection reduced tumour burden in nude mice bearing subcutaneous human melanoma xenografts.","The selectivity came from the tumour cells' defective interferon response, not from any engineering of the virus."],"whatItMeans":"This is the reason oncolytic virotherapy is a strategy rather than an accident. Cancer cells frequently disable the interferon response because it restrains their growth, and the same break leaves them unable to mount the antiviral response a healthy neighbour mounts. Everything later in the field, including the choice of which virus to use and which gene to delete, is an attempt to widen that gap.","caveats":["Cell lines and immunodeficient mice. Nude mice lack T cells, so the model measures direct viral killing and cannot show the immune contribution that matters most in patients.","Interferon-pathway defects vary enormously between tumours and are not routinely measured before treatment, so there is still no test that says which patient's cancer is susceptible.","Wild-type vesicular stomatitis virus is neurotoxic in animals by direct routes into the nervous system, which is why the clinical versions are attenuated."]},{"id":"paper-vale-stopcap-docetaxel-bisphosphonates-lancet-oncol-2016","kind":"paper","name":"STOpCaP: docetaxel or bisphosphonates added to standard of care in hormone-sensitive prostate cancer, a systematic review and meta-analysis","aka":["STOpCaP","Vale 2016 docetaxel meta-analysis","adaptive meta-analysis prostate docetaxel"],"tldr":"Three trials of chemotherapy at the start of hormone therapy had reported, two positive and one negative. Pooling them showed the treatment does work in metastatic disease, improving four-year survival by about nine percent, and that zoledronic acid does not.","summary":"Claire Vale, Jayne Tierney and the STOpCaP steering group ran a framework for adaptive meta-analysis over every randomised trial of docetaxel or bisphosphonates added to standard care in high-risk localised or metastatic hormone-sensitive prostate cancer, taking hazard ratios from publications, presentations and directly from investigators.\n\nThis is the paper that settled the contradiction between GETUG-AFU 15, CHAARTED and STAMPEDE, and it is worth reading for its method as much as for its result: an adaptive meta-analysis is designed to be run while trials are still reporting, rather than years afterwards. It also did something rarer, which is to close a question in the negative: it found no evidence that zoledronic acid improves survival in either metastatic or non-metastatic disease.","asOf":"2026-09-25","links":[{"label":"Lancet Oncol 2016","url":"https://doi.org/10.1016/s1470-2045(15)00489-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26718929/"}],"tags":["prostate-evidence"],"related":["paper-gravis-getug-afu-15-docetaxel-lancet-oncol-2013","paper-chaarted-nejm-2015","paper-stampede-lancet-2016","prostate-roadmap"],"cancers":["prostate","prostate-mhspc"],"sections":["chemotherapy","hormonal"],"technologies":[],"targets":[],"drugs":["docetaxel","zoledronic-acid"],"companies":[],"institutions":[],"pathways":[],"terms":["adt","hazard-ratio","bone-metastases"],"trials":[],"people":["nicholas-james","karim-fizazi","christopher-sweeney"],"bottlenecks":["b-trial-design","b-negative-results","b-knowledge-diffusion"],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2016,"doi":"10.1016/s1470-2045(15)00489-1","pmid":"26718929","authors":"Vale CL, Burdett S, Rydzewska LHM, et al.","paperType":"meta-analysis","findings":["In metastatic disease, docetaxel added to standard of care improved survival: hazard ratio 0.77 (95 percent confidence interval 0.68 to 0.87; p less than 0.0001), an absolute improvement in four-year survival of 9 percent (5 to 14), from three trials covering 2,992 of 3,206 randomised men.","Failure-free survival hazard ratio 0.64 (0.58 to 0.70; p less than 0.0001), a reduction in absolute four-year failure rates of 16 percent (12 to 19).","In locally advanced (M0) disease, no evidence of a survival benefit from docetaxel: hazard ratio 0.87 (0.69 to 1.09; p equals 0.218) from three trials covering 2,121 of 3,978 men, although failure-free survival improved (0.70, 0.61 to 0.81).","No evidence that zoledronic acid improves survival in metastatic disease (hazard ratio 0.94, 0.83 to 1.07; p equals 0.323) or in M0 disease (0.98, 0.82 to 1.16; p equals 0.782).","The bisphosphonate survival signal in metastatic disease (0.88, 0.79 to 0.98; p equals 0.025) was influenced by the positive result of one trial of sodium clodronate."],"whatItMeans":"The answer to a question three individual trials could not answer on their own, and the reason docetaxel with androgen deprivation became standard for metastatic hormone-sensitive disease. It also stopped a widely used bone drug being credited with a survival effect it does not have.","caveats":["An aggregate-data meta-analysis, not individual patient data, so subgroup effects such as disease volume cannot be examined directly.","The M0 result rests on fewer than two thirds of the randomised men, because survival data were not available from every trial.","Standard of care has since changed: the comparator arms received androgen deprivation alone, while today they would usually receive an androgen receptor pathway inhibitor as well."],"changedPractice":true},{"id":"paper-storm-adjuvant-sorafenib-bruix-lancet-oncol-2015","kind":"paper","name":"STORM: adjuvant sorafenib after resection or ablation of hepatocellular carcinoma","aka":[],"tldr":"Four years of sorafenib after curative surgery or ablation for liver cancer did not delay recurrence or lengthen survival, and caused substantial toxicity, closing the door on kinase inhibitors as adjuvant therapy.","summary":"Phase 3 placebo-controlled trial of 1,114 patients with hepatocellular carcinoma after complete resection or ablation randomised to sorafenib or placebo for up to four years.\n\nMedian recurrence-free survival was 33.3 versus 33.7 months (hazard ratio 0.94) with no difference in time to recurrence or overall survival, and more than a quarter of sorafenib patients discontinued because of adverse events.","asOf":"2026-09-17","links":[{"label":"Lancet Oncol 2015","url":"https://doi.org/10.1016/S1470-2045(15)00198-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26361969/"}],"tags":[],"related":[],"cancers":["hcc-early"],"sections":[],"technologies":[],"targets":[],"drugs":["sorafenib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["jordi-bruix"],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2015,"doi":"10.1016/S1470-2045(15)00198-9","pmid":"26361969","authors":"Bruix J, Takayama T, Mazzaferro V, et al.","paperType":"rct","findings":["Median recurrence-free survival 33.3 vs 33.7 months; hazard ratio 0.94.","Discontinuation for adverse events 24 percent vs 7 percent."],"whatItMeans":"No adjuvant systemic therapy is recommended after curative treatment of hepatocellular carcinoma, a conclusion reinforced by the later failure of IMbrave050.","caveats":["Population included patients with relatively low recurrence risk."],"changedPractice":true,"participants":1114},{"id":"paper-strass-lancet-oncol-2020","kind":"paper","name":"STRASS (EORTC 62092): preoperative radiotherapy plus surgery versus surgery alone for primary retroperitoneal sarcoma","aka":[],"tldr":"Adding radiotherapy before surgery for retroperitoneal sarcoma did not improve abdominal recurrence-free survival overall, so it is no longer routine, though a possible benefit in liposarcoma keeps it under discussion.","summary":"Phase 3 trial of 266 patients with primary resectable retroperitoneal sarcoma randomised to preoperative radiotherapy (50.4 Gy) followed by surgery or surgery alone.\n\nMedian abdominal recurrence-free survival was 4.5 versus 5.0 years (hazard ratio 1.01), with more serious adverse events in the radiotherapy group; exploratory analysis suggested benefit in well-differentiated and low-grade dedifferentiated liposarcoma but not leiomyosarcoma.","asOf":"2026-09-17","links":[{"label":"Lancet Oncol 2020","url":"https://doi.org/10.1016/S1470-2045(20)30446-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32941794/"}],"tags":[],"related":[],"cancers":["retroperitoneal-sarcoma","liposarcoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["strass"],"people":["sylvie-bonvalot"],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2020,"doi":"10.1016/S1470-2045(20)30446-0","pmid":"32941794","authors":"Bonvalot S, Gronchi A, Le Péchoux C, et al.","paperType":"rct","findings":["Median abdominal recurrence-free survival 4.5 vs 5.0 years; hazard ratio 1.01.","Serious adverse events 24 percent vs 10 percent."],"whatItMeans":"Surgery alone in a reference centre is the standard for primary retroperitoneal sarcoma; preoperative radiotherapy is considered case by case in liposarcoma.","caveats":["Trial did not meet its endpoint, but the liposarcoma subgroup signal remains debated.","Surgery-alone arm had excellent outcomes at expert centres."],"changedPractice":true,"participants":266},{"id":"paper-puleo-pancreatic-tumour-microenvironment-subtypes-gastroenterology-2018","kind":"paper","name":"Stratification of pancreatic ductal adenocarcinomas based on tumor and microenvironment features","aka":[],"tldr":"Using routine formalin-fixed tissue from 309 operations, this European study confirmed the classical and basal-like tumour types, added three microenvironment-defined groups, and showed the earlier exocrine-like type was contamination by normal acinar cells.","summary":"Formalin-fixed paraffin-embedded samples from 309 consecutive resections at four European hospitals underwent gene expression, targeted sequencing and immunohistochemistry. Independent component analysis deconvoluted normal, tumour and microenvironment patterns; consensus clustering after removing normal contamination defined subtypes, associated with survival and validated in TCGA and ICGC. The basal-like and classical tumour-specific subtypes were validated and five subtypes were defined: pure basal-like, stroma activated, desmoplastic, pure classical and immune classical. An exocrine signal was associated with acinar cell contamination, and the previously reported exocrine-like (ADEX) subtype was attributed to it.","asOf":"2026-09-24","links":[{"label":"Puleo et al., Gastroenterology 2018: five tumour and microenvironment subtypes in 309 resected cancers","url":"https://doi.org/10.1053/j.gastro.2018.08.033"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30165049/"}],"tags":[],"related":[],"cancers":["pancreatic","resectable-pdac"],"sections":[],"technologies":["rna-seq"],"targets":[],"drugs":[],"companies":[],"institutions":["institut-jules-bordet"],"pathways":["tumor-microenvironment","caf-activation-desmoplasia"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["gastroenterology"],"dependsOn":[],"notes":[],"journal":"Gastroenterology","year":2018,"doi":"10.1053/j.gastro.2018.08.033","pmid":"30165049","authors":"Puleo F, Nicolle R, Blum Y, et al.","paperType":"translational","findings":["Five subtypes: pure basal-like, stroma activated, desmoplastic, pure classical, immune classical.","ADEX and exocrine-like reflect acinar contamination."],"whatItMeans":"It made subtyping possible on the archived tissue every hospital has, and it retired one of the four Bailey subtypes.","caveats":["Resected tumours only.","Subtypes are prognostic, not yet predictive."],"changedPractice":false,"participants":309},{"id":"paper-isella-stromal-contribution-colorectal-transcriptome-nat-genet-2015","kind":"paper","name":"Stromal contribution to the colorectal cancer transcriptome","aka":[],"tldr":"The gene-activity subtype with the worst prognosis turned out not to be a property of the cancer cells at all. Growing human tumours in mice showed that its defining genes are switched on in the surrounding connective tissue.","summary":"Genes upregulated in the poor-prognosis stem, serrated and mesenchymal transcriptional subtype are also prominently expressed by stromal cells, raising the possibility that the transcripts derive from stroma rather than epithelial cancer cells. Colorectal cancer expression data from patient-derived xenografts, where mouse stroma supports human cancer cells, allowed species-specific expression analysis, which showed that the subtype's messenger RNA levels were mostly due to stromal expression. Transcriptional signatures built to report the abundance of cancer-associated fibroblasts, leukocytes or endothelial cells were all significantly higher in human samples of that subtype. High fibroblast signature expression was associated with shorter survival in untreated disease, and joint high expression of the stromal signatures predicted resistance to radiotherapy in rectal cancer.","asOf":"2026-09-24","links":[{"label":"Isella et al., Nat Genet 2015: the stromal contribution to the colorectal cancer transcriptome","url":"https://doi.org/10.1038/ng.3224"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25706627/"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["rna-seq"],"targets":[],"drugs":[],"companies":[],"institutions":["candiolo"],"pathways":["caf-activation-desmoplasia","tumor-microenvironment","emt"],"terms":["cms-subtypes","desmoplasia"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":2015,"doi":"10.1038/ng.3224","pmid":"25706627","authors":"Isella C, Terrasi A, Bellomo SE, et al.","paperType":"translational","findings":["Mesenchymal subtype transcripts come mostly from stroma, shown by species-specific analysis in patient-derived xenografts.","Fibroblast signature expression associated with shorter survival in untreated disease.","Joint stromal signature expression predicted radiotherapy resistance in rectal cancer."],"whatItMeans":"It means a CMS4 call on a bulk sample partly measures how much stroma was in the block, which is both a caution for the classification and a pointer to the stroma as the thing to treat.","caveats":["Xenografts lack a human immune system, so the leukocyte component is modelled indirectly.","Retrospective prognostic associations."],"changedPractice":false},{"id":"paper-rhim-stroma-restrains-pancreatic-cancer-cell-2014","kind":"paper","name":"Stromal elements act to restrain, rather than support, pancreatic ductal adenocarcinoma","aka":[],"tldr":"Removing the hedgehog signal that builds the scar tissue around pancreatic tumours in mice gave less stroma but more aggressive, more vascular cancers, and only anti-angiogenic treatment helped them.","summary":"Sonic hedgehog, overexpressed by neoplastic cells and driving a fibroblast-rich desmoplastic stroma, was deleted in a mouse model of pancreatic ductal adenocarcinoma. Shh-deficient tumours had reduced stromal content but were more aggressive, undifferentiated, more vascular and more proliferative, effects fully recapitulated by a smoothened inhibitor in control mice. VEGFR blockade selectively improved survival of Shh-deficient tumours, indicating that hedgehog-driven stroma suppresses tumour growth partly by restraining angiogenesis.","asOf":"2026-09-24","links":[{"label":"Rhim et al., Cancer Cell 2014: stromal elements restrain pancreatic cancer","url":"https://doi.org/10.1016/j.ccr.2014.04.021"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24856585/"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["columbia-hicc"],"pathways":["hedgehog","caf-activation-desmoplasia","vegf-angiogenesis"],"terms":["desmoplasia"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-cell"],"dependsOn":[],"notes":[],"journal":"Cancer Cell","year":2014,"doi":"10.1016/j.ccr.2014.04.021","pmid":"24856585","authors":"Rhim AD, Oberstein PE, Thomas DH, et al.","paperType":"basic","findings":["Hedgehog deletion or smoothened inhibition reduced stroma but produced more aggressive, vascular tumours.","VEGFR blockade selectively helped stroma-depleted tumours."],"whatItMeans":"Published alongside Ozdemir, it explains why the hedgehog inhibitor trials in patients failed and why stromal targets are now chosen for their signalling rather than their bulk.","caveats":["Mouse genetics and models.","Does not exclude benefit from selective stromal reprogramming."],"changedPractice":false},{"id":"paper-calon-stromal-gene-expression-poor-prognosis-colorectal-nat-genet-2015","kind":"paper","name":"Stromal gene expression defines poor-prognosis subtypes in colorectal cancer","aka":[],"tldr":"Published beside the paper above and reaching the same conclusion from the other direction: the prognostic power of every published bowel cancer classification comes from the scar-forming cells, and TGF-beta is what makes them dangerous.","summary":"On evaluating recent molecular classifications of colorectal cancer, the authors found that their predictive power arises from genes expressed by stromal cells rather than epithelial tumour cells. Bioinformatic and immunohistochemical analyses identified stromal markers that associate robustly with disease relapse across the various classifications. Functional studies showed that cancer-associated fibroblasts increase the frequency of tumour-initiating cells, an effect dramatically enhanced by TGF-beta signalling, and that all poor-prognosis subtypes share a gene programme induced by TGF-beta in tumour stromal cells. In patient-derived tumour organoids and xenografts, TGF-beta signalling inhibitors blocking the cross-talk between cancer cells and the microenvironment halted disease progression.","asOf":"2026-09-24","links":[{"label":"Calon et al., Nat Genet 2015: stromal gene expression defines the poor-prognosis subtypes of colorectal cancer","url":"https://doi.org/10.1038/ng.3225"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25706628/"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["organoids","rna-seq"],"targets":["tgfb1","tgfbr2"],"drugs":[],"companies":[],"institutions":[],"pathways":["tgf-beta","caf-activation-desmoplasia","cancer-stem-cells-plasticity"],"terms":["cms-subtypes","desmoplasia"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":2015,"doi":"10.1038/ng.3225","pmid":"25706628","authors":"Calon A, Lonardo E, Berenguer-Llergo A, et al.","paperType":"translational","findings":["Predictive power of published classifications arises from stromal, not epithelial, genes.","Fibroblasts increase tumour-initiating cell frequency, dramatically enhanced by TGF-beta.","TGF-beta inhibition halted progression in organoids and xenografts."],"whatItMeans":"It made TGF-beta the central target of the microsatellite-stable half of the disease, which is the line that leads to Tauriello's immune-evasion work and to the TGF-beta plus checkpoint combinations in trials.","caveats":["Model systems; no TGF-beta inhibitor has an approval in colorectal cancer.","Stromal signatures are sensitive to sampling and to how much tumour was in the section."],"changedPractice":false},{"id":"paper-stupp-temozolomide-nejm-2005","kind":"paper","name":"Stupp 2005: temozolomide added to radiotherapy for newly diagnosed glioblastoma","aka":[],"tldr":"Adding the oral chemotherapy temozolomide during and after radiotherapy extended median survival in glioblastoma by about two and a half months and more than doubled the number of patients alive at two years; twenty years later it is still the standard.","summary":"Open-label phase 3 trial (EORTC 26981/NCIC CE.3) of 573 patients aged 18-70 with newly diagnosed glioblastoma randomised to radiotherapy alone (60 Gy) or radiotherapy with concomitant daily temozolomide followed by six cycles of adjuvant temozolomide. Primary endpoint was overall survival.\n\nMedian OS was 14.6 vs 12.1 months (HR 0.63) and 2-year OS 26.5% vs 10.4%. The companion paper by Hegi showed that MGMT promoter methylation predicted benefit. The 'Stupp protocol' became the global standard for glioblastoma and remains so, with only tumour-treating fields added since; the trial also illustrates how little progress has been made against this tumour.","asOf":"2026-09-08","links":[{"label":"NEJM 2005","url":"https://doi.org/10.1056/NEJMoa043330"},{"label":"Hegi et al. NEJM 2005 (MGMT)","url":"https://doi.org/10.1056/NEJMoa043331"}],"tags":[],"related":[],"cancers":["glioblastoma"],"sections":[],"technologies":["cytotoxic-chemotherapy","imrt-igrt","methylation-profiling","ttfields"],"targets":[],"drugs":[],"companies":["curie-nki-eortc"],"institutions":[],"pathways":[],"terms":["os","standard-of-care"],"trials":[],"people":["roger-stupp","michael-weller","denis-lacombe"],"bottlenecks":["b-brain-delivery","b-negative-results","b-undruggable-targets"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2005,"doi":"10.1056/NEJMoa043330","authors":"Stupp R, Mason WP, van den Bent MJ, et al.","paperType":"rct","findings":["Median overall survival 14.6 vs 12.1 months; HR 0.63 (95% CI 0.52-0.75).","2-year overall survival 26.5% vs 10.4%.","Five-year follow-up (Lancet Oncology 2009): 5-year OS 9.8% vs 1.9%.","MGMT promoter methylation (Hegi, NEJM 2005) identified patients with the greatest benefit: median OS 21.7 months with temozolomide in methylated tumours vs 12.7 months in unmethylated.","Grade 3-4 haematological toxicity in about 7% during concomitant treatment and 14% during adjuvant treatment."],"whatItMeans":"Patients with newly diagnosed glioblastoma who are fit and under about 70 receive six weeks of radiotherapy with daily temozolomide followed by six monthly cycles of temozolomide; this is still the backbone of treatment two decades later. Testing MGMT methylation identifies who benefits most and guides decisions in older patients. Median survival with the regimen remains only around 15-20 months, and no drug since has clearly improved on it, which is why glioblastoma is a priority for new approaches.","caveats":["Excluded patients over 70 and with poor performance status; later trials (e.g. Perry 2017) addressed short-course radiotherapy with temozolomide in the elderly.","The benefit in MGMT-unmethylated tumours is small, yet temozolomide is still usually given for lack of alternatives.","Open-label design; no quality-of-life data in the primary report.","Two decades of subsequent negative trials (bevacizumab, nivolumab, vaccines) make this the standard by default rather than by continued advance."],"changedPractice":true,"participants":573},{"id":"paper-robinson-integrative-clinical-genomics-advanced-prostate-cell-2015","kind":"paper","name":"SU2C-PCF: integrative clinical genomics of advanced prostate cancer","aka":["Robinson 2015","SU2C prostate 150 mCRPC","Stand Up To Cancer prostate dream team"],"tldr":"One hundred and fifty men with prostate cancer that had spread and stopped responding to hormones had their tumours biopsied and sequenced prospectively. Nine in ten had a genetic change that a drug could in principle be aimed at, and one in five had a broken DNA repair gene.","summary":"Dan Robinson, Arul Chinnaiyan, Charles Sawyers, Johann de Bono and the Stand Up To Cancer-Prostate Cancer Foundation Dream Team built a multi-institutional clinical sequencing infrastructure and prospectively whole-exome and transcriptome sequenced bone or soft tissue biopsies from 150 men with metastatic castration-resistant prostate cancer.\n\nThe single most consequential number is 19.3 percent: aberrations of BRCA2, BRCA1 and ATM at substantially higher frequency than in primary prostate cancer. That figure, together with Pritchard's germline result the following year, is why every man with metastatic prostate cancer should now be offered DNA repair testing. The paper also documented what castration resistance looks like at the genomic level: androgen receptor aberrations in 62.7 percent, and enrichment of TP53 and androgen receptor alterations relative to primary disease.","asOf":"2026-09-25","links":[{"label":"Cell 2015","url":"https://doi.org/10.1016/j.cell.2015.05.001"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26000489/"},{"label":"cBioPortal: SU2C/PCF prostate (2015)","url":"https://www.cbioportal.org/study/summary?id=prad_su2c_2015"}],"tags":["prostate-evidence"],"related":["paper-pritchard-inherited-dna-repair-metastatic-prostate-nejm-2016","paper-tcga-molecular-taxonomy-primary-prostate-cell-2015","paper-mateo-toparp-a-olaparib-dna-repair-nejm-2015","prostate-roadmap"],"cancers":["prostate","prostate-mcrpc"],"sections":["diagnostics","targeted-therapy"],"technologies":["wes-wgs","rna-seq","cgp"],"targets":["androgen-receptor","tp53","pten","brca","atm","pik3ca","erg","apc","zbtb16"],"drugs":[],"companies":[],"institutions":["michigan-rogel","mskcc","royal-marsden"],"pathways":["ar-signaling","homologous-recombination-repair","pi3k-akt-mtor","wnt","prostate-cancer-signalling"],"terms":["hrd","ngs","castration-resistance","germline-vs-somatic","driver-mutation","biopsy"],"trials":[],"people":["arul-chinnaiyan","charles-sawyers","johann-de-bono"],"bottlenecks":["b-biomarker-validation","b-hereditary-risk","b-data-silos"],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Cell","year":2015,"doi":"10.1016/j.cell.2015.05.001","pmid":"26000489","authors":"Robinson D, Van Allen EM, Wu YM, et al.","paperType":"basic","findings":["Aberrations of the androgen receptor, ETS genes, TP53 and PTEN were frequent, in 40 to 60 percent of cases, with TP53 and androgen receptor alterations enriched in metastatic castration-resistant disease compared with primary prostate cancer.","Aberrations of BRCA2, BRCA1 and ATM were observed at substantially higher frequencies than in primary prostate cancers, at 19.3 percent overall.","89 percent of affected individuals harboured a clinically actionable aberration, including 62.7 percent with aberrations in the androgen receptor and 65 percent in other cancer-related genes.","8 percent had actionable pathogenic germline alterations.","New genomic alterations were identified in PIK3CA and PIK3CB, R-spondin, BRAF and RAF1, APC, beta-catenin and ZBTB16/PLZF."],"whatItMeans":"The genomic definition of advanced prostate cancer, and the evidence that made molecular testing standard in it. The 19.3 percent DNA repair figure is the direct ancestor of PROfound, TRITON3, PROpel and TALAPRO-2, and the 8 percent germline figure is why a tumour result in this disease has implications for a man's relatives.","caveats":["150 men who consented to a metastatic biopsy at academic centres, which selects for fitness and for accessible disease.","Clinically actionable was defined bioinformatically in 2015; most of the 89 percent had no drug available then and many still do not.","Bone biopsies yield lower tumour content than soft tissue, which affects detection sensitivity across the cohort unevenly."],"changedPractice":true,"participants":150},{"id":"paper-nct05722015-ann-oncol-2025","kind":"paper","name":"Subcutaneous versus intravenous pembrolizumab, in combination with chemotherapy, for treatment of metastatic non-small-cell lung cancer: the phase III 3475A-D77 trial","aka":[],"tldr":"Published report from the trial registered as NCT05722015, in Annals of Oncology (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Pembrolizumab with berahyaluronidase alfa is for subcutaneous (s.c.) administration. The phase III open-label 3475A-D77 study (NCT05722015) assessed s.c. pembrolizumab versus intravenous (i.v.) pembrolizumab, plus chemotherapy, for treatment of metastatic non-small-cell lung cancer (mNSCLC).\n\nPatients and methods: Participants with newly diagnosed stage IV squamous or nonsquamous NSCLC without sensitizing EGFR, ALK, or ROS1 alterations were randomized 2: 1 to pembrolizumab s.c. 790 mg every 6 weeks (q6w) or pembrolizumab i.v. 400 mg q6w (18 cycles), each given with platinum-doublet chemotherapy. Dual primary endpoints were pharmacokinetic exposure measures of cycle 1 area under the curve (AUC 0-6 weeks) and steady-state trough concentration (C trough) of pembrolizumab. The noninferiority margin for AUC 0-6 weeks and C trough geometric mean ratios (GMRs) of pembrolizumab s.c. versus i.v. was specified as 0.8. Secondary endpoints included additional pharmacokinetic exposure measures, pembrolizumab immunogenicity, efficacy, and safety.\n\nResults: In total 377 participants were randomized to the pembrolizumab s.c. (n = 251) or i.v. (n = 126) arms. The median time from randomization to data cut-off (12 July 2024) was 9.6 months (range 6.2-16.4 months). The median injection time for pembrolizumab s.c. was 2.0 min (range 1-12 min). The GMR [96% confidence interval (CI)] for cycle 1 AUC 0-6 weeks was 1.14 (1.06-1.22); P < 0.0001. The GMR (94% CI) for steady-state C trough was 1.67 (1.52-1.84); P < 0.0001. Secondary pharmacokinetic endpoints were within established bounds for pembrolizumab. Anti-pembrolizumab antibodies were detected in 1.4% (pembrolizumab s.c. arm) and 0.9% (pembrolizumab i.v. arm) of participants. For the pembrolizumab s.c. versus i.v. arms, objective response rates (ORRs) were 45.4% versus 42.1% (ORR ratio 1.08, 95% CI 0.85-1.37). Other efficacy measures were similar and safety profiles were consistent between treatment arms.\n\nConclusions: Overall exposure and trough concentrations of pembrolizumab s.c. 790 mg q6w were noninferior to those of pembrolizumab i.v. 400 mg q6w given with chemotherapy in participants with treatment-naive mNSCLC. Results support pembrolizumab s.c. as a treatment option in all indications where pembrolizumab i.v. can be used.\n\nIndexed on Europe PMC as PubMed record 40157574 (DOI 10.1016/j.annonc.2025.03.012). Its abstract cites the registry id NCT05722015, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2025","url":"https://doi.org/10.1016/j.annonc.2025.03.012"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40157574/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40157574"},{"label":"ClinicalTrials.gov NCT05722015","url":"https://clinicaltrials.gov/study/NCT05722015"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05722015"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2025,"doi":"10.1016/j.annonc.2025.03.012","pmid":"40157574","authors":"Felip E, Rojas CI, Schenker M, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05722015 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-zhukova-tp53-medulloblastoma-jco-2013","kind":"paper","name":"Subgroup-specific prognostic implications of TP53 mutation in medulloblastoma","aka":[],"tldr":"TP53 mutations mark much shorter survival in SHH-subgroup medulloblastoma, with five-year survival around 40 percent, but have no effect in WNT tumours, so the mutation must be interpreted alongside the subgroup.","summary":"Analysis of 553 medulloblastomas for TP53 mutation by molecular subgroup in a discovery and validation cohort, finding TP53 mutations in 21 percent of SHH and 16 percent of WNT tumours but rarely in groups 3 and 4.\n\nIn SHH tumours, TP53 mutation was associated with five-year overall survival of 41 percent against 81 percent for wild-type, often with germline mutations (Li-Fraumeni syndrome) and chromothripsis, whereas WNT tumours with TP53 mutations retained excellent survival.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2013","url":"https://doi.org/10.1200/JCO.2012.48.5052"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23835706/"}],"tags":[],"related":[],"cancers":["medulloblastoma-shh"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2013,"doi":"10.1200/JCO.2012.48.5052","pmid":"23835706","authors":"Zhukova N, Ramaswamy V, Remke M, et al.","paperType":"translational","findings":["SHH TP53-mutant: five-year overall survival 41 percent vs 81 percent for wild-type.","WNT TP53-mutant: survival unaffected (90 percent)."],"whatItMeans":"SHH-activated, TP53-mutant medulloblastoma is a separate WHO entity treated as very high risk, and its diagnosis prompts germline testing of the child and family.","caveats":["Retrospective; treatment varied across cohorts."],"changedPractice":true,"participants":553},{"id":"paper-kumar-interindividual-genomic-diversity-metastatic-prostate-nat-med-2016","kind":"paper","name":"Substantial interindividual and limited intraindividual genomic diversity among tumours from men with metastatic prostate cancer","aka":[],"tldr":"Sequencing several metastases from the same man showed they are genetically much more alike than metastases from different men, so one good biopsy usually represents the rest.","summary":"Multiple tumours from men with disseminated prostate cancer were analysed by whole-exome sequencing, array comparative genomic hybridisation and RNA transcript profiling, and genomic diversity within and between individuals was compared. In contrast to the substantial heterogeneity between men, there was limited diversity among metastases within an individual: the number of somatic mutations, the burden of copy-number alterations and aberrations in known oncogenic drivers were all highly concordant, as were metrics of androgen receptor activity and cell-cycle activity. Androgen receptor activity was inversely associated with cell proliferation, while expression of Fanconi anaemia complex genes correlated with elevated cell-cycle progression, E2F1 expression and RB1 loss. Men with somatic aberrations in Fanconi anaemia complex genes or in ATM had significantly longer responses to carboplatin than men without DNA repair gene defects.","asOf":"2026-09-25","links":[{"label":"Kumar et al., Nat Med 2016: multiple metastases per man show limited within-patient and substantial between-patient genomic diversity in disseminated prostate cancer","url":"https://doi.org/10.1038/nm.4053"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26928463/"},{"label":"cBioPortal study prad_fhcrc (Fred Hutchinson, Nat Med 2016; 141 sequenced and 149 copy-number-profiled metastases from men with disseminated prostate cancer)","url":"https://www.cbioportal.org/study/summary?id=prad_fhcrc"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["wes-wgs","rna-seq"],"targets":["androgen-receptor","atm","rb1"],"drugs":[],"companies":[],"institutions":[],"pathways":["clonal-evolution","homologous-recombination-repair","ar-signaling"],"terms":["biopsy","castration-resistance","resistance"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2016,"doi":"10.1038/nm.4053","pmid":"26928463","authors":"Kumar A, Coleman I, Morrissey C, et al.","paperType":"basic","findings":["Limited genomic diversity among metastases within one man against substantial diversity between men.","Concordant mutation counts, copy-number burden, driver aberrations, androgen receptor activity and cell-cycle activity across a man's metastases.","Longer carboplatin response durations in men with Fanconi anaemia complex or ATM aberrations."],"whatItMeans":"It is the reason a single metastatic biopsy is defensible in this disease, where in lung and bowel cancer heterogeneity makes one sample a gamble. The caveat is that it applies to driver alterations and not to the polyclonal resistance events that appear under treatment.","caveats":["Rapid-autopsy and research-biopsy material, so the men are not a clinic population.","Exceptions existed and the authors said so.","The carboplatin association is retrospective and in small numbers."],"changedPractice":false},{"id":"paper-topham-subtype-discordant-pancreatic-ccr-2021","kind":"paper","name":"Subtype-discordant pancreatic ductal adenocarcinoma tumors show intermediate clinical and molecular characteristics","aka":[],"tldr":"Running six published subtype classifiers over 574 tumours, the authors found they agreed in 88% of cases, and the 12% they disagreed on were genuine hybrids with intermediate survival and intermediate KRAS allele imbalance.","summary":"Sequencing data for 574 pancreatic ductal adenocarcinomas from prospective trials and public databases were classified by six published strategies (Moffitt regression and clustering, Collisson, Bailey, Karasinska). Basal-like and classical calls were concordant in 88% and survival differed by subtype. Twelve percent of tumours were discordant and showed intermediate survival in univariate and multivariate analyses, hybrid expression profiles with classical and basal-like genes co-expressed, and intermediate mutant KRAS allelic imbalance (P < 0.001). Nearly 1 in 6 patients had tumours that failed to fall reliably into either subtype on the two regression tools aimed at clinical practice.","asOf":"2026-09-24","links":[{"label":"Topham et al., Clin Cancer Res 2021: subtype-discordant tumours in 574 cases","url":"https://doi.org/10.1158/1078-0432.CCR-20-2831"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33051307/"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":["rna-seq"],"targets":["kras"],"drugs":[],"companies":[],"institutions":["bc-cancer"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2021,"doi":"10.1158/1078-0432.CCR-20-2831","pmid":"33051307","authors":"Topham JT, Karasinska JM, Lee MKC, et al.","paperType":"translational","findings":["88% concordance between classifiers; 12% discordant hybrids.","Hybrids show intermediate survival and intermediate KRAS allelic imbalance."],"whatItMeans":"A subtype report should carry a confidence, and a trial that dichotomises subtype will misplace about one patient in eight.","caveats":["Retrospective; mixed platforms.","No treatment assignment by subtype."],"changedPractice":false,"participants":574},{"id":"paper-barretina-nat-genet","kind":"paper","name":"Subtype-specific genomic alterations define new targets for soft-tissue sarcoma therapy","aka":[],"tldr":"Paper cited by one target page, indexed on Europe PMC as PubMed record 20601955 and published in Nature Genetics; the citing page links this DOI, which is how the record was matched.","summary":"Soft-tissue sarcomas, which result in approximately 10,700 diagnoses and 3,800 deaths per year in the United States, show remarkable histologic diversity, with more than 50 recognized subtypes. However, knowledge of their genomic alterations is limited. We describe an integrative analysis of DNA sequence, copy number and mRNA expression in 207 samples encompassing seven major subtypes. Frequently mutated genes included TP53 (17% of pleomorphic liposarcomas), NF1 (10.5% of myxofibrosarcomas and 8% of pleomorphic liposarcomas) and PIK3CA (18% of myxoid/round-cell liposarcomas, or MRCs). PIK3CA mutations in MRCs were associated with Akt activation and poor clinical outcomes. In myxofibrosarcomas and pleomorphic liposarcomas, we found both point mutations and genomic deletions affecting the tumor suppressor NF1. Finally, we found that short hairpin RNA (shRNA)-based knockdown of several genes amplified in dedifferentiated liposarcoma, including CDK4 and YEATS4, decreased cell proliferation. Our study yields a detailed map of molecular alterations across diverse sarcoma subtypes and suggests potential subtype-specific targets for therapy.\n\nIndexed on Europe PMC as PubMed record 20601955 (DOI 10.1038/ng.619). Matched by DOI alone: one target page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Genet 2010","url":"https://doi.org/10.1038/ng.619"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20601955/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/20601955"}],"tags":["europepmc-ingest"],"related":["mdm2"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":2010,"doi":"10.1038/ng.619","pmid":"20601955","authors":"Barretina J, Taylor BS, Banerji S, et al.","paperType":"observational","findings":[],"whatItMeans":"One target page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-collisson-pancreatic-subtypes-nat-med-2011","kind":"paper","name":"Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy","aka":[],"tldr":"The first gene-expression subtypes of pancreatic cancer, classical, quasi-mesenchymal and exocrine-like, came from pooling tumour and cell-line profiles, and the authors showed the types differ in outcome and in how cell lines respond to drugs.","summary":"Because tumour specimens were scarce, transcriptional profiles of primary pancreatic ductal adenocarcinoma samples from several studies were combined with human and mouse cell lines. Three subtypes were defined, classical, quasi-mesenchymal and exocrine-like, with evidence for clinical outcome and therapeutic response differences between them. Gene signatures for the subtypes and preclinical model systems for finding subtype-specific therapies were presented.","asOf":"2026-09-24","links":[{"label":"Collisson et al., Nat Med 2011: classical, quasi-mesenchymal and exocrine-like subtypes","url":"https://doi.org/10.1038/nm.2344"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21460848/"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":["rna-seq"],"targets":["kras"],"drugs":[],"companies":[],"institutions":["ucsf"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2011,"doi":"10.1038/nm.2344","pmid":"21460848","authors":"Collisson EA, Sadanandam A, Olson P, et al.","paperType":"translational","findings":["Three subtypes: classical, quasi-mesenchymal, exocrine-like.","Outcome and cell-line drug response differed by subtype."],"whatItMeans":"It opened the subtype programme that Moffitt, Bailey and COMPASS refined; the classical versus mesenchymal or basal split has survived every re-analysis.","caveats":["Small, heterogeneous primary datasets and cell lines.","The exocrine-like class was later attributed to acinar contamination."],"changedPractice":false},{"id":"paper-hur-sugar-sweetened-beverages-early-onset-colorectal-gut-2021","kind":"paper","name":"Sugar-sweetened beverage intake in adulthood and adolescence and risk of early-onset colorectal cancer among women","aka":[],"tldr":"In 95,464 nurses followed for 24 years, women who drank two or more sugary drinks a day had double the risk of bowel cancer before 50, and each daily drink in adolescence raised it by a third.","summary":"Hur, Otegbeye, Joh and colleagues prospectively investigated the association between sugar-sweetened beverage intake and early-onset colorectal cancer in the Nurses' Health Study II from 1991 to 2015, among 95,464 women who reported adulthood beverage intake on validated food frequency questionnaires every four years. A subset of 41,272 participants reported beverage intake at ages 13 to 18 using a validated high-school questionnaire in 1998. Cox proportional hazards models estimated relative risks.\n\nOne hundred and nine cases of early-onset colorectal cancer were documented, which is the number that sets the limits of what the study can claim.","asOf":"2026-09-24","links":[{"label":"Gut 2021","url":"https://doi.org/10.1136/gutjnl-2020-323450"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33958435/"},{"label":"Europe PMC full text (PMC8571123)","url":"https://europepmc.org/article/MED/33958435"}],"tags":["colorectal-evidence"],"related":["paper-siegel-colorectal-incidence-birth-cohort-jnci-2017","paper-diaz-gay-colibactin-geographic-age-mutational-processes-nature-2025"],"cancers":["colorectal","early-onset-colorectal"],"sections":["prevention","nutrition-lifestyle"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-early-detection"],"keyPapers":[],"journals":["gut"],"dependsOn":[],"notes":[],"journal":"Gut","year":2021,"doi":"10.1136/gutjnl-2020-323450","pmid":"33958435","authors":"Hur J, Otegbeye E, Joh HK, et al.","paperType":"observational","findings":["109 early-onset colorectal cancer cases over 24 years of follow-up.","Two or more servings a day in adulthood against under one a week: relative risk 2.18 (95 percent CI 1.10 to 4.35, p for trend 0.02).","Each additional serving per day in adulthood: relative risk 1.16 (1.00 to 1.36).","Each additional serving per day at ages 13 to 18: relative risk 1.32 (1.00 to 1.75).","Replacing a daily sugar-sweetened drink with artificially sweetened beverages, coffee or milk was associated with 17 to 36 percent lower risk."],"whatItMeans":"One of the few modifiable exposures with a plausible adolescent window to match the birth-cohort pattern; it is the kind of hypothesis a cohort can generate but not settle.","caveats":["109 cases: confidence intervals reach 1.00 at the lower bound for two of the three main estimates.","Self-reported diet, including diet recalled from adolescence more than a decade later.","Female nurses in the United States; residual confounding by obesity, physical activity and total energy cannot be excluded."],"participants":95464},{"id":"paper-gemstone-302-lancet-oncol-2022","kind":"paper","name":"Sugemalimab versus placebo, in combination with platinum-based chemotherapy, as first-line treatment of metastatic non-small-cell lung cancer (GEMSTONE-302): interim and final analyses of a double-blind, randomised, phase 3 clinical trial","aka":[],"tldr":"Published report from the GEMSTONE-302 trial registered as NCT03789604, in The Lancet Oncology (2022), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: PD-1 inhibitor plus chemotherapy had been shown to be an effective first-line treatment for patients with metastatic non-small-cell lung cancer (NSCLC). However, there was no robust evidence showing a PD-L1 inhibitor combined with chemotherapy benefited patients with squamous and non-squamous NSCLC. GEMSTONE-302 aimed to evaluate the efficacy and safety of a PD-L1 inhibitor, sugemalimab, plus chemotherapy for patients with metastatic squamous or non-squamous NSCLC.\n\nMethods: This randomised, double-blind, phase 3 trial was done in 35 hospitals and academic research centres in China. Eligible patients were aged 18-75 years, had histologically or cytologically confirmed stage IV squamous or non-squamous NSCLC without known EGFR sensitising mutations, ALK, ROS1, or RET fusions, no previous systemic treatment for metastatic disease, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients were randomly assigned (2:1) to receive sugemalimab (1200 mg, intravenously, every 3 weeks) plus platinum-based chemotherapy (carboplatin [area under the curve (AUC) 5 mg/mL per min, intravenously] and paclitaxel [175 mg/m 2, intravenously] for squamous NSCLC, or carboplatin [AUC 5 mg/mL per min, intravenously] and pemetrexed [500 mg/m 2, intravenously] for non-squamous NSCLC; sugemalimab group) or placebo plus the same platinum-based chemotherapy regimens for squamous or non-squamous NSCLC as in the sugemalimab group; placebo group) for up to four cycles, followed by maintenance therapy with sugemalimab or placebo for squamous NSCLC, and intravenous sugemalimab 500 mg/m 2 or matching placebo plus pemetrexed for non-squamous NSCLC. Randomisation was done by an interactive voice-web-response system via permuted blocks (block size was a mixture of three and six with a random order within each stratum) and stratified by ECOG performance status, PD-L1 expression, and tumour pathology. The investigators, patients, and the sponsor were masked to treatment assignment. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population. Safety was analysed in all patients who received at least one treatment dose. Results reported are from a prespecified interim analysis (ie, when the study met the primary endpoint) and an updated analysis (prespecified final analysis for progression-free survival) with a longer follow-up. This study is registered with ClinicalTrials.gov (NCT03789604), is closed to new participants, and follow-up is ongoing.\n\nFindings: Between Dec 13, 2018, and May 15, 2020, 846 patients were assessed for eligibility; 367 were ineligible, and the remaining 479 patients were randomly assigned to the sugemalimab group (n=320) or placebo group (n=159). At the preplanned interim analysis (data cutoff June 8, 2020; median follow-up 8·6 months [IQR 6·1-11·4]), GEMSTONE-302 met its primary endpoint, with significantly longer progression-free survival in the sugemalimab group compared with the placebo group (median 7·8 months [95% CI 6·9-9·0] vs 4·9 months [4·7-5·0]; stratified hazard ratio [HR] 0·50 [95% CI 0·39-0·64], p<0·0001]). At the final analysis (March 15, 2021) with a median follow-up of 17·8 months (IQR 15·1-20·9), the improvement in progression-free survival was maintained (median 9·0 months [95% CI 7·4-10·8] vs 4·9 months [4·8-5·1]; stratified HR 0·48 [95% CI 0·39-0·60], p<0·0001). The most common grade 3 or 4 any treatment-related adverse events were neutrophil count decreased (104 [33%] of 320 with sugemalimab vs 52 [33%] of 159 with placebo), white blood cell count decreased (45 [14%] vs 27 [17%]), anaemia (43 [13%] vs 18 [11%]), platelet count decreased (33 [10%] vs 15 [9%]), and neutropenia (12 [4%] vs seven [4%]). Any treatment-related serious adverse events occurred in 73 (23%) patients in the sugemalimab group and 31 (20%) patients in the placebo group. Any treatment-related deaths were reported in ten (3%) patients in the sugemalimab group (pneumonia with respiratory failure in one patient; myelosuppression with septic shock in one patient; pneumonia in two patients; respiratory failure, abdominal pain, cardiac failure, and immune-mediated pneumonitis in one patient each; the other two deaths had an unspecified cause) and in two (1%) patients in the placebo group (pneumonia and multiple organ dysfunction syndrome).\n\nInterpretation: Sugemalimab plus chemotherapy showed a statistically significant and clinically meaningful progression-free survival improvement compared with placebo plus chemotherapy, in patients with previously untreated squamous and non-squamous metastatic NSCLC, regardless of PD-L1 expression, and could be a newfirst-line treatment option for both squamous and non-squamous metastatic NSCLC.\n\nFunding: CStone Pharmaceuticals.\n\nTranslation: For the Chinese translation of the abstract see Supplementary Materials section.\n\nIndexed on Europe PMC as PubMed record 35038432 (DOI 10.1016/s1470-2045(21)00650-1). Its abstract cites the registry id NCT03789604, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2022","url":"https://doi.org/10.1016/s1470-2045(21)00650-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35038432/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35038432"},{"label":"ClinicalTrials.gov NCT03789604","url":"https://clinicaltrials.gov/study/NCT03789604"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["gemstone-302"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2022,"doi":"10.1016/s1470-2045(21)00650-1","pmid":"35038432","authors":"Zhou C, Wang Z, Sun Y, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03789604 with the most citations, so it is the natural first reading for anyone following the GEMSTONE-302 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-sung-globocan-2020-cacancer-2021","kind":"paper","name":"Sung 2021: GLOBOCAN 2020, the year breast cancer overtook lung cancer as the most diagnosed cancer","aka":[],"tldr":"The IARC count for 2020: about 19.3 million new cancer cases worldwide, with female breast cancer overtaking lung cancer as the most commonly diagnosed cancer for the first time, and a projected rise to about 28 million cases a year by 2040.","summary":"GLOBOCAN 2020, from the International Agency for Research on Cancer, estimated incidence and mortality for 36 cancers in 185 countries. It counted an estimated 19.3 million new cases (18.1 million excluding non-melanoma skin cancer) in 2020. Female breast cancer became the most commonly diagnosed cancer, ahead of lung, colorectal, prostate and stomach cancers, while lung cancer remained the leading cause of cancer death. The authors projected 28.4 million cases in 2040, a 47% rise on 2020 driven by population growth and ageing, with the largest relative increases in countries undergoing economic transition.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.3322/caac.21660"},{"label":"IARC Global Cancer Observatory","url":"https://gco.iarc.who.int/today"}],"tags":[],"related":["paper-bray-globocan-2022-cacancer-2024"],"cancers":["breast-hr-positive","nsclc","colorectal"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["iarc"],"pathways":[],"terms":["incidence-vs-prevalence","mortality"],"trials":[],"people":["bray-freddie"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"CA: A Cancer Journal for Clinicians","year":2021,"doi":"10.3322/caac.21660","authors":"Sung H, Ferlay J, Siegel RL, et al.","paperType":"observational","findings":["About 19.3 million new cancer cases and almost 10 million cancer deaths worldwide in 2020.","Female breast cancer the most commonly diagnosed cancer (about 2.3 million cases, 11.7% of the total), overtaking lung cancer.","Lung cancer the leading cause of cancer death (about 1.8 million deaths, 18% of the total), followed by colorectal, liver, stomach and female breast cancers.","Projected 28.4 million cases in 2040, a 47% increase from 2020."],"whatItMeans":"This report marked the shift of the global cancer burden towards breast cancer and towards lower-income countries, and it is the baseline most 2020s policy documents cite. The GLOBOCAN 2022 release has since updated the totals.","caveats":["Estimates for 2020 were made before the COVID-19 pandemic's effect on diagnoses could be measured.","Many countries lack population-based registries, so their figures rest on modelling."],"changedPractice":false},{"id":"paper-demetri-sunitinib-gist-lancet-2006","kind":"paper","name":"Sunitinib in advanced gastrointestinal stromal tumour after failure of imatinib","aka":[],"tldr":"Sunitinib more than quadrupled the time to progression compared with placebo in gastrointestinal stromal tumours that had become resistant to or intolerant of imatinib, establishing the standard second-line treatment.","summary":"Phase 3 placebo-controlled trial of 312 patients with advanced gastrointestinal stromal tumour after imatinib failure randomised 2:1 to sunitinib 50 mg daily (four weeks on, two off) or placebo, unblinded early after an interim analysis.\n\nMedian time to progression was 27.3 versus 6.4 weeks (hazard ratio 0.33) with a survival benefit at interim analysis (hazard ratio 0.49); fatigue, diarrhoea, skin discolouration and hand-foot syndrome were common.","asOf":"2026-09-17","links":[{"label":"Lancet 2006","url":"https://doi.org/10.1016/S0140-6736(06)69446-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/17046465/"}],"tags":[],"related":[],"cancers":["gist-imatinib-resistant"],"sections":[],"technologies":[],"targets":[],"drugs":["imatinib","sunitinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2006,"doi":"10.1016/S0140-6736(06)69446-4","pmid":"17046465","authors":"Demetri GD, van Oosterom AT, Garrett CR, et al.","paperType":"rct","findings":["Median time to progression 27.3 vs 6.4 weeks; hazard ratio 0.33.","Interim overall survival hazard ratio 0.49."],"whatItMeans":"Sunitinib is the standard second-line kinase inhibitor for GIST, with particular activity against KIT exon 9 and exon 13/14 secondary mutations.","caveats":["Trial unblinded early; final survival analysis confounded by crossover.","Less active against exon 17/18 secondary mutations."],"changedPractice":true,"participants":312},{"id":"paper-raymond-sunitinib-pnet-nejm-2011","kind":"paper","name":"Sunitinib malate for the treatment of pancreatic neuroendocrine tumours","aka":[],"tldr":"The multikinase inhibitor sunitinib doubled the time to progression in advanced pancreatic neuroendocrine tumours and was approved at the same time as everolimus, giving the disease its first targeted therapies.","summary":"Phase 3 placebo-controlled trial of 171 patients with advanced, well-differentiated, progressive pancreatic neuroendocrine tumours randomised to sunitinib 37.5 mg daily or placebo, stopped early after an independent monitoring committee observed more deaths and serious events with placebo.\n\nMedian progression-free survival was 11.4 versus 5.5 months (hazard ratio 0.42) with response of 9.3 versus 0 percent; hypertension, hand-foot syndrome and fatigue were the main toxicities.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2011","url":"https://doi.org/10.1056/NEJMoa1003825"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21306237/"}],"tags":[],"related":[],"cancers":["pancreatic-net"],"sections":[],"technologies":[],"targets":[],"drugs":["sunitinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2011,"doi":"10.1056/NEJMoa1003825","pmid":"21306237","authors":"Raymond E, Dahan L, Raoul JL, et al.","paperType":"rct","findings":["Median progression-free survival 11.4 vs 5.5 months; hazard ratio 0.42.","Objective response 9.3 percent vs 0 percent."],"whatItMeans":"Sunitinib is a standard targeted option for progressive pancreatic neuroendocrine tumours; the choice between it and everolimus is guided by comorbidity and side-effect profile.","caveats":["Trial stopped early with 171 of a planned 340 patients, which can overestimate effect."],"changedPractice":true,"participants":171},{"id":"paper-sunrise-1-jco-2025","kind":"paper","name":"SunRISe-1: TAR-200, a gemcitabine-releasing device placed in the bladder, for BCG-unresponsive non-muscle-invasive bladder cancer","aka":[],"tldr":"A small pretzel-shaped device that slowly releases gemcitabine inside the bladder cleared carcinoma in situ in about four out of five patients whose cancer had stopped responding to BCG, offering an alternative to bladder removal.","summary":"Open-label phase 2b trial of patients with BCG-unresponsive high-risk non-muscle-invasive bladder cancer with carcinoma in situ, who declined or were unfit for radical cystectomy. Cohort 2 tested TAR-200 monotherapy, an intravesical drug-releasing system placed cystoscopically every three weeks then every twelve weeks for up to two years. Primary endpoint was complete response rate.\n\nThe complete response rate was about 84%, with most responses durable beyond a year and a low rate of serious adverse events, mostly urinary symptoms. It led to FDA approval in 2025, the first intravesical drug-releasing system and a rare new option for a group whose only curative alternative is cystectomy.","asOf":"2026-09-08","links":[{"label":"PubMed search: SunRISe-1 TAR-200","url":"https://pubmed.ncbi.nlm.nih.gov/?term=SunRISe-1+TAR-200+BCG-unresponsive"},{"label":"ClinicalTrials.gov NCT04640623","url":"https://clinicaltrials.gov/study/NCT04640623"}],"tags":[],"related":[],"cancers":["urothelial"],"sections":[],"technologies":["cytotoxic-chemotherapy"],"targets":[],"drugs":[],"companies":["johnson-johnson"],"institutions":[],"pathways":[],"terms":["orr","accelerated-approval"],"trials":[],"people":[],"bottlenecks":["b-surgery-radiation-innovation","b-toxicity-qol","b-trial-design"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2025,"doi":"10.1200/JCO-25-01651","pmid":"40737582","authors":"Jacob JM, Daneshmand S, Necchi A, et al.","paperType":"rct","findings":["Complete response in about 84% of patients with carcinoma in situ (cohort 2, TAR-200 alone).","Median duration of response over two years, with a majority of responders remaining in complete response at 12 months.","Most adverse events were low-grade urinary symptoms (frequency, dysuria, urgency); grade 3 or higher treatment-related events in a small minority and rare discontinuations.","Placement and removal are outpatient cystoscopic procedures requiring no anaesthesia.","Response rates compared favourably with pembrolizumab (about 41%) and nadofaragene firadenovec (about 51%) in similar populations, though not in a randomised comparison."],"whatItMeans":"Patients with high-risk bladder cancer confined to the lining whose disease has not responded to BCG now have a bladder-sparing option that clears the cancer in most cases, delivered through a simple outpatient procedure. It may allow many to avoid or defer cystectomy, a life-changing operation. Whether responses translate into avoided progression and cystectomy over the long term, and how it compares with cystectomy on survival, remain to be shown.","caveats":["Single-arm phase 2b; no randomised comparison with cystectomy or other bladder-sparing options.","Follow-up is still relatively short for a disease where recurrence and progression occur over years.","Complete response is a surrogate; progression to muscle-invasive disease is the outcome that matters.","Requires regular cystoscopy for device exchange and surveillance, and cost is substantial."],"changedPractice":true,"participants":85},{"id":"paper-nct05712902-lancet-respir-med-2024","kind":"paper","name":"Sunvozertinib for patients in China with platinum-pretreated locally advanced or metastatic non-small-cell lung cancer and EGFR exon 20 insertion mutation (WU-KONG6): single-arm, open-label, multicentre, phase 2 trial","aka":[],"tldr":"Published report from the WU-KONG6 trial registered as NCT05712902, in The Lancet. Respiratory medicine (2024), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Sunvozertinib is an oral, irreversible, and selective tyrosine kinase inhibitor that has a favourable safety profile and encouraging antitumour activity, as shown in phase 1 studies of patients with heavily pretreated non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutation (exon20ins). We aimed to assess the antitumour efficacy of sunvozertinib in patients with platinum-pretreated locally advanced or metastatic NSCLC with EGFR exon20ins.\n\nMethods: WU-KONG6 is a single-group, open-label, multicentre phase 2 trial of sunvozertinib monotherapy, conducted across 37 medical centres in China. We enrolled adult patients with pathologically or cytologically confirmed locally advanced or metastatic NSCLC whose tumour tissue carried an EGFR exon20ins mutation. All patients had received at least one line of previous systemic therapy, with at least one line containing platinum-based chemotherapy. The primary endpoint was objective response rate (ORR), as assessed by the independent review committee. The ORR was defined as the percentage of patients who achieved complete or partial response, confirmed by two separate assessments with at least 4-week time interval, until disease progression or initiation of any new anti-cancer therapy. Enrolled patients received sunvozertinib 300 mg once daily until meeting discontinuation criteria per the protocol. Patients who received at least one dose of treatment and were evaluable for efficacy analysis were included in the primary analysis, and all patients who received at least one dose of treatment were included in the safety analysis. This study is registered with ChinaDrugTrials.org, CTR20211009, and ClinicalTrials.gov, NCT05712902, and efficacy and safety follow-up are ongoing.\n\nFindings: Between July 19, 2021, and May 6, 2022, 104 patients were enrolled. At data cutoff (Oct 17, 2022), the last enrolled patient had been followed up for about 6 months. Among 97 patients evaluable for efficacy analysis, 59 (61%) patients achieved tumour response, with a confirmed ORR of 61% (95% CI 50-71). All tumour responses were partial responses. Tumour responses were observed irrespective of age, sex, smoking history, EGFR exon20ins subtypes, brain metastasis at baseline, previous lines of therapy, and history of onco-immunotherapy. In total, 19 death events occurred over a median follow-up period of 7·6 months (IQR 6·1-9·4). Sunvozertinib was well tolerated at 300 mg once daily. The most common grade 3 or worse treatment-related adverse events were blood creatine phosphokinase increased (18 [17%] of 104), diarrhoea (eight [8%]), and anaemia (six [6%]). The most common serious treatment-related adverse events were interstitial lung disease (five [5%] of 104), anaemia (three [3%]), vomiting (two [2%]), nausea (two [2%]) and pneumonia (two [2%]).\n\nInterpretation: In this phase 2 study, sunvozertinib demonstrated antitumour efficacy in patients with platinum-based chemotherapy pretreated NSCLC with EGFR exon20ins, with a manageable safety profile. A multinational randomised, phase 3 study of sunvozertinib versus platinum-doublet chemotherapy in EGFR exon20ins NSCLC is ongoing (NCT05668988).\n\nFunding: Dizal Pharmaceutical.\n\nIndexed on Europe PMC as PubMed record 38101437 (DOI 10.1016/s2213-2600(23)00379-x). Its abstract cites the registry id NCT05712902, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Respir Med 2024","url":"https://doi.org/10.1016/s2213-2600(23)00379-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38101437/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38101437"},{"label":"ClinicalTrials.gov NCT05712902","url":"https://clinicaltrials.gov/study/NCT05712902"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05712902"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Lancet. Respiratory medicine","year":2024,"doi":"10.1016/s2213-2600(23)00379-x","pmid":"38101437","authors":"Wang M, Fan Y, Sun M, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05712902 with the most citations, so it is the natural first reading for anyone following the WU-KONG6 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","The abstract cites more than one registry id (NCT05712902, NCT05668988); it was kept because the trial's acronym appears in the title."]},{"id":"paper-parker-j-clin-oncol","kind":"paper","name":"Supervised risk predictor of breast cancer based on intrinsic subtypes","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 19204204 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Unlabelled: PURPOSE To improve on current standards for breast cancer prognosis and prediction of chemotherapy benefit by developing a risk model that incorporates the gene expression-based \"intrinsic\" subtypes luminal A, luminal B, HER2-enriched, and basal-like. METHODS A 50-gene subtype predictor was developed using microarray and quantitative reverse transcriptase polymerase chain reaction data from 189 prototype samples. Test sets from 761 patients (no systemic therapy) were evaluated for prognosis, and 133 patients were evaluated for prediction of pathologic complete response (pCR) to a taxane and anthracycline regimen.\n\nResults: The intrinsic subtypes as discrete entities showed prognostic significance (P = 2.26E-12) and remained significant in multivariable analyses that incorporated standard parameters (estrogen receptor status, histologic grade, tumor size, and node status). A prognostic model for node-negative breast cancer was built using intrinsic subtype and clinical information. The C-index estimate for the combined model (subtype and tumor size) was a significant improvement on either the clinicopathologic model or subtype model alone. The intrinsic subtype model predicted neoadjuvant chemotherapy efficacy with a negative predictive value for pCR of 97%. CONCLUSION Diagnosis by intrinsic subtype adds significant prognostic and predictive information to standard parameters for patients with breast cancer. The prognostic properties of the continuous risk score will be of value for the management of node-negative breast cancers. The subtypes and risk score can also be used to assess the likelihood of efficacy from neoadjuvant chemotherapy.\n\nIndexed on Europe PMC as PubMed record 19204204 (DOI 10.1200/jco.2008.18.1370). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2009","url":"https://doi.org/10.1200/jco.2008.18.1370"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19204204/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/19204204"}],"tags":["europepmc-ingest"],"related":["pam50"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2009,"doi":"10.1200/jco.2008.18.1370","pmid":"19204204","authors":"Parker JS, Mullins M, Cheang MC, et al.","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-bakker-n-engl-j-med","kind":"paper","name":"Supplemental MRI Screening for Women with Extremely Dense Breast Tissue","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 31774954 and published in New England Journal of Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Background: Extremely dense breast tissue is a risk factor for breast cancer and limits the detection of cancer with mammography. Data are needed on the use of supplemental magnetic resonance imaging (MRI) to improve early detection and reduce interval breast cancers in such patients.\n\nMethods: In this multicenter, randomized, controlled trial in the Netherlands, we assigned 40,373 women between the ages of 50 and 75 years with extremely dense breast tissue and normal results on screening mammography to a group that was invited to undergo supplemental MRI or to a group that received mammography screening only. The groups were assigned in a 1:4 ratio, with 8061 in the MRI-invitation group and 32,312 in the mammography-only group. The primary outcome was the between-group difference in the incidence of interval cancers during a 2-year screening period.\n\nResults: The interval-cancer rate was 2.5 per 1000 screenings in the MRI-invitation group and 5.0 per 1000 screenings in the mammography-only group, for a difference of 2.5 per 1000 screenings (95% confidence interval [CI], 1.0 to 3.7; P<0.001). Of the women who were invited to undergo MRI, 59% accepted the invitation. Of the 20 interval cancers that were diagnosed in the MRI-invitation group, 4 were diagnosed in the women who actually underwent MRI (0.8 per 1000 screenings) and 16 in those who did not accept the invitation (4.9 per 1000 screenings). The MRI cancer-detection rate among the women who actually underwent MRI screening was 16.5 per 1000 screenings (95% CI, 13.3 to 20.5). The positive predictive value was 17.4% (95% CI, 14.2 to 21.2) for recall for additional testing and 26.3% (95% CI, 21.7 to 31.6) for biopsy. The false positive rate was 79.8 per 1000 screenings. Among the women who underwent MRI, 0.1% had either an adverse event or a serious adverse event during or immediately after the screening.\n\nConclusions: The use of supplemental MRI screening in women with extremely dense breast tissue and normal results on mammography resulted in the diagnosis of significantly fewer interval cancers than mammography alone during a 2-year screening period. (Funded by the University Medical Center Utrecht and others; DENSE ClinicalTrials.gov number, NCT01315015.).\n\nIndexed on Europe PMC as PubMed record 31774954 (DOI 10.1056/nejmoa1903986). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2019","url":"https://doi.org/10.1056/nejmoa1903986"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31774954/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31774954"}],"tags":["europepmc-ingest"],"related":["breast-mri-coils-abbreviated-mri"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2019,"doi":"10.1056/nejmoa1903986","pmid":"31774954","authors":"Bakker MF, de Lange SV, Pijnappel RM, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-mcclements-capbil-surgical-outcomes-gallbladder-cancer-hpb-2026","kind":"paper","name":"Surgical outcomes in gallbladder cancer: evidence from the UK nationwide CAPBIL study","aka":[],"tldr":"Among 516 people operated on for gallbladder cancer at 24 UK centres, how far the tumour had grown and whether nodes were involved decided survival, and chemotherapy after surgery showed no measurable benefit once like was compared with like.","summary":"UK HPB Research Collaborative Group analysis of 516 patients who underwent surgery for gallbladder cancer at 24 UK centres between January 2014 and December 2022, with a median follow-up of 25 months. T3 to T4 tumours more often presented with jaundice, were non-incidental and underwent major hepatectomy, which carried higher major morbidity and 30-day mortality. In propensity score-matched analysis, adjuvant therapy showed no significant benefit in disease-free or overall survival. On multivariable analysis T3 to T4 stage, nodal disease and perineural invasion predicted poorer disease-free survival, and T3 to T4 stage and nodal disease poorer overall survival.","asOf":"2026-09-24","links":[{"label":"HPB 2026","url":"https://doi.org/10.1016/j.hpb.2026.06.009"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42399203/"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":["capecitabine"],"companies":[],"institutions":["liverpool-hpb-centre"],"pathways":[],"terms":["neoadjuvant-adjuvant","radical-cholecystectomy"],"trials":["bilcap","acticca-1"],"people":["hassan-malik"],"bottlenecks":["b-real-world-evidence"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"HPB","year":2026,"doi":"10.1016/j.hpb.2026.06.009","pmid":"42399203","authors":"McClements J, Lee WT, Lucocq J, et al.","paperType":"real-world","findings":["516 patients operated at 24 UK centres, 2014 to 2022; median follow-up 25 months.","Propensity-matched analysis: no significant disease-free or overall survival benefit from adjuvant therapy.","T3 to T4 stage, nodal disease and perineural invasion predicted poorer disease-free survival."],"whatItMeans":"The adjuvant finding sits uneasily beside BILCAP, on which NHS adjuvant capecitabine rests; in a mostly gallbladder population the benefit is not visible. ACTICCA-1 and ARTEMIDE-Biliary01 are the trials that can settle it.","caveats":["Observational; adjuvant therapy was given selectively and matching cannot remove all confounding.","Median follow-up of 25 months is short for survival endpoints."],"changedPractice":false,"participants":516},{"id":"paper-lee-t2-gallbladder-cancer-surgical-strategy-aso-2015","kind":"paper","name":"Surgical Strategy for T2 Gallbladder Cancer According to Tumor Location","aka":[],"tldr":"A Korean series suggesting that muscle-invading gallbladder tumours on the free side may not always need part of the liver removed, while those against the liver bed do.","summary":"Single-centre Korean series of 157 T2 gallbladder cancers resected with curative intent between 2000 and 2011: 33 peritoneal-side and 124 hepatic-side (epicentre in the gallbladder bed or neck); 122 had hepatic resection and 35 did not. After a median follow-up of 40 months, peritoneal-side tumours had better survival (p=0.002). Tumour location, lymph node metastasis, hepatic resection, lymphatic invasion and perineural invasion were independent prognostic factors. The authors recommend hepatic resection for hepatic-side tumours and suggest it is not always necessary for selected peritoneal-side tumours.","asOf":"2026-09-24","links":[{"label":"Ann Surg Oncol 2015","url":"https://doi.org/10.1245/s10434-014-4300-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25519930/"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["t2a-versus-t2b","radical-cholecystectomy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-surgical-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Surgical Oncology","year":2015,"doi":"10.1245/s10434-014-4300-7","pmid":"25519930","authors":"Lee H, Choi DW, Park JY, et al.","paperType":"observational","findings":["157 T2 tumours: 33 peritoneal-side, 124 hepatic-side; peritoneal-side survival better (p=0.002).","Tumour location, nodal metastasis, hepatic resection, lymphatic and perineural invasion were independent prognostic factors."],"whatItMeans":"One of the series that raised the question of sparing the liver resection in T2a disease; only 33 peritoneal-side tumours, so it poses the question rather than settles it.","caveats":["Single centre, retrospective, small peritoneal-side group.","Location definitions differ from later studies."],"changedPractice":false,"participants":157},{"id":"paper-peter-thuss-patience-eur-j-cancer-2011","kind":"paper","name":"Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer--a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO)","aka":[],"tldr":"Paper by Peter Thuss-Patience indexed on Europe PMC as PubMed record 21742485, in European Journal of Cancer (2011), one of the most cited records naming an author with this name at Charité Universitätsmedizin Berlin.","summary":"Background: The value of second-line therapy for metastatic gastric cancer is unclear. So far there are no randomised phase III data comparing second-line chemotherapy to best supportive care (BSC). In this prospective, multicenter, open label, randomised phase III study we compared irinotecan to BSC to evaluate the impact on survival of second-line chemotherapy.\n\nMethods: Eligible patients (pts) had metastatic or locally advanced gastro-oesophageal junction or gastric adenocarcinoma, objective tumour progression during or within 6months after first-line chemotherapy and ECOG performance status 0-2. Stratification for time of progression after first-line therapy, ECOG PS and pretreatment secured even distribution of important prognostic factors.\n\nTreatment: Arm A: Irinotecan 250mg/m(2)q3w (first cycle) to be increased to 350mg/m(2), depending on toxicity. Arm B: BSC.\n\nFindings: Between 10/2002 and 12/2006 40 pts were randomised. The study was closed prematurely due to poor accrual. Responsefor arm A (19 pts evaluable): No objective responses, SD 53%, PD 47%. Improvement of tumour related symptoms: Arm A 50% of pts, arm B 7%. Overall Survival: (all events in 40 pts have occurred): The hazard ratio for death was reduced to 0.48 (95%CI 0.25-0.92) in the irinotecan-arm (p=0.012). Median survival arm A: 4.0months (95% CI 3.6-7.5), arm B: 2.4months (95% CI 1.7-4.9).\n\nInterpretation: Irinotecan as second-line chemotherapy significantly prolongs overall survival compared to BSC in the studied pts. Second-line chemotherapy can now be considered as a proven treatment option for metastatic or locally advanced gastric cancer.\n\nFunding: The study was supported by a research grant from Aventis and Pfizer.\n\nIndexed on Europe PMC as PubMed record 21742485 (DOI 10.1016/j.ejca.2011.06.002). Its author list gives \"Thuss-Patience PC\" with the affiliation \"Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Medizinische Klinik m.S. Hämatologie, Onkologie und Tumorimmunologie, Augustenburger Platz 1, 13353 Berlin, Germany. peter.thuss@charite.de\", which names Charité Universitätsmedizin Berlin; that is how the record was matched to Peter Thuss-Patience, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Eur J Cancer 2011","url":"https://doi.org/10.1016/j.ejca.2011.06.002"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21742485/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/21742485"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["peter-thuss-patience"],"bottlenecks":[],"keyPapers":[],"journals":["european-journal-of-cancer"],"dependsOn":[],"notes":[],"journal":"European Journal of Cancer","year":2011,"doi":"10.1016/j.ejca.2011.06.002","pmid":"21742485","authors":"Thuss-Patience PC, Kretzschmar A, Bichev D, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Peter Thuss-Patience at Charité Universitätsmedizin Berlin, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-loibl-geparsixto-survival-hrd-ann-oncol-2018","kind":"paper","name":"Survival analysis of carboplatin added to an anthracycline/taxane-based neoadjuvant chemotherapy and HRD score as predictor of response-final results from GeparSixto","aka":[],"tldr":"The final GeparSixto report: adding carboplatin before surgery cut relapse in triple-negative disease by 44 percent, and a DNA-repair deficiency score predicted which tumours would disappear, though it did not predict who gained from the platinum.","summary":"Loibl, Weber, Timms, Elkin and colleagues report survival and homologous recombination deficiency (HRD) analyses from GeparSixto, in which patients received paclitaxel plus non-pegylated liposomal doxorubicin with or without carboplatin; median follow-up was 47.3 months. Disease-free survival was significantly better with carboplatin in triple-negative disease (hazard ratio 0.56, 95 percent confidence interval 0.34 to 0.93, p=0.022); the overall survival improvement was not significant, and carboplatin did not help HER2-positive tumours. HRD (score 42 or more and/or tumour BRCA mutation) was measured in 193 of 315 triple-negative participants and present in 136 (70.5 percent), of whom 82 (60.3 percent) had a high score without a BRCA mutation. HRD independently predicted pathological complete response (odds ratio 2.60, p=0.008); carboplatin raised the response rate from 33.9 to 63.5 percent in HR-deficient tumours (p=0.001) and from 20.0 to 29.6 percent in non-deficient tumours (p=0.540; interaction p=0.327), and from 31.7 to 63.2 percent in high-HRD tumours without BRCA mutation. Disease-free survival improved with carboplatin in both deficient (0.49) and non-deficient (0.44) tumours.","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2018","url":"https://doi.org/10.1093/annonc/mdy460"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30335131/"},{"label":"ClinicalTrials.gov NCT01426880","url":"https://clinicaltrials.gov/study/NCT01426880"}],"tags":["tnbc-evidence"],"related":["paper-geparsixto-lancet-oncol-2014"],"cancers":["tnbc","tnbc-early"],"sections":[],"technologies":["platinum","hrd-testing"],"targets":[],"drugs":["carboplatin","mychoice-cdx"],"companies":["gbg"],"institutions":[],"pathways":[],"terms":["hrd","pcr","hazard-ratio"],"trials":["geparsixto"],"people":["sibylle-loibl","gunter-von-minckwitz","carsten-denkert"],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2018,"doi":"10.1093/annonc/mdy460","pmid":"30335131","authors":"Loibl S, Weber KE, Timms KM, et al.","paperType":"rct","findings":["Carboplatin in triple-negative disease: disease-free survival hazard ratio 0.56 (95 percent CI 0.34 to 0.93), p=0.022; overall survival gain not significant.","HRD present in 70.5 percent of 193 triple-negative tumours; HRD predicted pathological complete response (odds ratio 2.60) but not carboplatin benefit (interaction p=0.327)."],"whatItMeans":"The survival evidence behind platinum in early triple-negative disease, and the first large demonstration that most triple-negative tumours are DNA-repair deficient whether or not BRCA is mutated, which is why HRD scores have not become a platinum selection test.","caveats":["Disease-free survival was a secondary endpoint; the trial was powered for pathological complete response.","HRD measured in 61 percent of triple-negative participants."],"changedPractice":true,"participants":315},{"id":"paper-obenauf-trends-cancer","kind":"paper","name":"Surviving at a Distance: Organ-Specific Metastasis","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 28741564 and published in Trends in cancer; the citing page links this DOI, which is how the record was matched.","summary":"The clinical manifestation of metastasis in a vital organ is the final stage of cancer progression and the main culprit of cancer-related mortality. Once established, metastasis is devastating, but only a small proportion of the cancer cells that leave a tumor succeed at infiltrating, surviving, and ultimately overtaking a distant organ. The bottlenecks that challenge cancer cells in newly invaded microenvironments are organ-specific and consequently demand distinct mechanisms for metastatic colonization. We review the metastatic traits that allow cancer cells to colonize distinct organ sites.\n\nIndexed on Europe PMC as PubMed record 28741564 (DOI 10.1016/j.trecan.2015.07.009). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Trends Cancer 2015","url":"https://doi.org/10.1016/j.trecan.2015.07.009"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28741564/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28741564"}],"tags":["europepmc-ingest"],"related":["organ-tropism-seed-soil"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["trends-in-cancer"],"dependsOn":[],"notes":[],"journal":"Trends in cancer","year":2015,"doi":"10.1016/j.trecan.2015.07.009","pmid":"28741564","authors":"Obenauf AC, Massagué J","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-olympia-6-year-update-ann-oncol-2026","kind":"paper","name":"Sustained benefit of adjuvant olaparib in women with germline BRCA1- and BRCA2-associated high-risk HER2-negative early breast cancer: updated results from the OlympiA phase III trial","aka":[],"tldr":"The six-year OlympiA update: the year of olaparib still cut relapse by 35 percent and death by 28 percent, six-year survival was 87.5 versus 83.2 percent, there were fewer new BRCA-related breast and ovarian cancers, and no excess of leukaemia.","summary":"Garber, Cameron, Campbell, Yothers and colleagues report the third pre-specified interim analysis of OlympiA (NCT02032823) at a median follow-up of 6.1 years, with descriptive analyses of invasive disease-free survival, distant disease-free survival and overall survival. Olaparib benefit was maintained: invasive disease-free survival hazard ratio 0.65 (95 percent confidence interval 0.53 to 0.78), distant disease-free survival 0.65 (0.53 to 0.81) and overall survival 0.72 (0.56 to 0.93); six-year overall survival was 87.5 versus 83.2 percent (difference 4.4 percentage points, 95 percent CI 0.9 to 6.7). Benefit was consistent across key subgroups including high-risk hormone receptor-positive disease. There were fewer BRCA-associated new breast and ovarian or fallopian tube cancers and no increase in adverse events of special interest (6.3 versus 9.3 percent), including myelodysplastic syndrome or acute myeloid leukaemia (0.4 versus 0.7 percent).","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2026","url":"https://doi.org/10.1016/j.annonc.2026.08.002"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42636977/"},{"label":"ClinicalTrials.gov NCT02032823","url":"https://clinicaltrials.gov/study/NCT02032823"}],"tags":["tnbc-evidence"],"related":["paper-olympia-overall-survival-ann-oncol-2022"],"cancers":["tnbc","breast-hr-positive"],"sections":[],"technologies":["parp-inhibitor"],"targets":["brca"],"drugs":["olaparib"],"companies":["astrazeneca","merck"],"institutions":[],"pathways":[],"terms":["os","germline-testing"],"trials":["olympia","keynote-522"],"people":["judy-garber","andrew-tutt"],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2026,"doi":"10.1016/j.annonc.2026.08.002","pmid":"42636977","authors":"Garber JE, Cameron D, Campbell C, et al.","paperType":"rct","findings":["At 6.1 years: invasive disease-free survival hazard ratio 0.65 (95 percent CI 0.53 to 0.78); distant disease-free survival 0.65; overall survival 0.72 (0.56 to 0.93).","Six-year overall survival 87.5 vs 83.2 percent (difference 4.4 points, 95 percent CI 0.9 to 6.7).","Myelodysplastic syndrome or acute myeloid leukaemia 0.4 vs 0.7 percent; fewer new BRCA-associated breast and ovarian cancers."],"whatItMeans":"Answers the two questions that hung over adjuvant olaparib, durability and late leukaemia, in its favour; the remaining question is whether carriers who also received pembrolizumab or capecitabine, whom the trial did not study, get the same benefit.","caveats":["Trial predates KEYNOTE-522 and CREATE-X as standards, so the combination with pembrolizumab or capecitabine is untested.","Interim analysis, descriptive by design."],"changedPractice":true,"participants":1836},{"id":"paper-prima-final-rituximab-maintenance-follicular-jco-2019","kind":"paper","name":"Sustained progression-free survival benefit of rituximab maintenance in patients with follicular lymphoma: long-term results of the PRIMA study","aka":["PRIMA final analysis","Bachy 2019"],"tldr":"After nine years the antibody maintenance group had gone more than six years longer before their lymphoma returned, and exactly as many people in each group were alive.","summary":"The final analysis of PRIMA after nine years of follow-up, with a data cut-off of 31 December 2016. 1,018 patients had been randomised to rituximab maintenance (505) or observation (513); 607 (59.6 per cent) consented to extended follow-up.\n\nMedian progression-free survival was 10.5 years in the maintenance arm against 4.1 years in the observation arm (hazard ratio 0.61, 95 per cent confidence interval 0.52 to 0.73). Overall survival did not differ (p = 0.7948), with ten-year estimates of approximately 80 per cent in both arms. No new safety signals were observed.","asOf":"2026-10-01","links":[{"label":"Journal of Clinical Oncology 2019","url":"https://doi.org/10.1200/JCO.19.01073"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31339826/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31339826"}],"tags":["lymphoma-evidence"],"related":["paper-prima-rituximab-maintenance-follicular-lancet-2011","paper-casulo-pod24-follicular-lymphoma-jco-2015","lymphoma-roadmap"],"cancers":["follicular-lymphoma","non-hodgkin-lymphoma"],"sections":["immunotherapy"],"technologies":[],"targets":["cd20"],"drugs":["rituximab"],"companies":["lysa"],"institutions":[],"pathways":[],"terms":["maintenance-therapy","lymphoma-tx-maintenance","lymphoma-tx-pod24"],"trials":["prima-follicular"],"people":["gilles-salles"],"bottlenecks":["b-toxicity-qol","b-patient-voice"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2019,"doi":"10.1200/JCO.19.01073","pmid":"31339826","authors":"Bachy E, Seymour JF, Feugier P, et al.","paperType":"rct","findings":["Median progression-free survival was 10.5 years with rituximab maintenance against 4.1 years with observation (hazard ratio 0.61, 95 per cent confidence interval 0.52 to 0.73).","Overall survival did not differ (p = 0.7948); ten-year estimates were approximately 80 per cent in both arms.","607 of 1,018 patients (59.6 per cent) consented to the extended follow-up.","No new safety signals were observed."],"whatItMeans":"The number to give a patient deciding about maintenance: a median of six and a half extra years before the next treatment, and no difference in how long they live. Both halves belong in the conversation.","caveats":["Only 59.6 per cent of randomised patients consented to extended follow-up, which could bias the long-term estimates in either direction.","Ten-year overall survival of about 80 per cent in both arms means the trial had limited power to detect a small survival difference.","The result predates the routine availability of bispecific antibodies and CAR-T at relapse, which change what the next treatment is worth."],"changedPractice":true,"participants":1018},{"id":"paper-nct05168566-j-thorac-oncol-2026","kind":"paper","name":"Sutetinib for Patients with Non-Small Cell Lung Cancer Harboring Uncommon EGFR Mutations: A Multicenter, Open-Label, Phase IIb Trial","aka":[],"tldr":"Published report from the trial registered as NCT05168566, in Journal of Thoracic Oncology (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Purpose: Uncommon epidermal growth factor receptor (EGFR) mutations account for ∼10% of EGFR-altered non-small cell lung cancer (NSCLC) and show heterogeneous sensitivity to EGFR-tyrosine kinase inhibitors (TKIs), with limited prospective evidence to inform first-line therapy. Sutetinib is an irreversible EGFR-TKI. We assessed the safety and antitumor efficacy of sutetinib in patients with locally advanced or metastatic NSCLC with uncommon EGFR mutations.\n\nMethods: In this multicenter, open-label, single-arm phase IIb trial, adults with locally advanced or metastatic NSCLC harboring EGFR G719X, S768I, L861Q, or predefined compound mutations and no prior EGFR-TKI therapy were enrolled. Patients received sutetinib 80 mg orally once daily in 28-day cycles until radiographic progression or unacceptable toxicity. Patients who received at least one dose of treatment and evaluable for efficacy analysis were included in the primary analysis, and all patients who received at least one dose of treatment were included in the safety analysis. The primary endpoint was objective response rate (ORR), as assessed by the independent review committee (IRC). Secondary endpoints included duration of response (DoR), disease control rate (DCR), time to response (TTR), progression-free survival (PFS), overall survival (OS), and safety.\n\nResults: From December 9, 2021, to May 5, 2024, 99 patients were enrolled (efficacy-evaluable, n=96; safety, n=99). at data cut-off in October, 2024, the median follow-up was 16.6 months. The IRC-confirmed ORR was 70.8% (95% confidence interval [CI], 60.7-79.7) and the DCR was 90.6% (95% CI, 82.9-95.6). Median DoR was 12.0 months (95% CI, 9.3-15.7) and median PFS was 13.7 months (95% CI, 10.9-16.4). Median OS was not reached (95% CI, 22.2-not reached). ORR was numerically higher in patients with compound versus solitary uncommon EGFR mutations (84.4% vs 64.1%), with median PFS of 13.8 versus 11.0 months, respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 97.0% (96/99) of patients, and grade ≥3 TRAEs occurred in 42.4% (42/99). The most common grade ≥3 TRAEs were diarrhea (28.3% [28/99]), hypokalemia (8.1% [8/99]), and increased gamma-glutamyl transferase (5.1% [5/99]). TRAEs led to dose reduction in 34.3% (34/99) and treatment discontinuation in 4.0% (4/99). No treatment-related deaths occurred.\n\nConclusions: Sutetinib met the prespecified primary endpoint and demonstrated clinically meaningful antitumor activity with a manageable safety profile in advanced NSCLC harboring uncommon EGFR mutations (G719X, S768I, and L861Q). These findings support sutetinib as a potential treatment option for this molecularly heterogeneous population.\n\nTrial registration: NCT05168566.\n\nIndexed on Europe PMC as PubMed record 42637134 (DOI 10.1016/j.jtho.2026.104165). Its abstract cites the registry id NCT05168566, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Thorac Oncol 2026","url":"https://doi.org/10.1016/j.jtho.2026.104165"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42637134/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42637134"},{"label":"ClinicalTrials.gov NCT05168566","url":"https://clinicaltrials.gov/study/NCT05168566"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05168566"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-thoracic-oncology"],"dependsOn":[],"notes":[],"journal":"Journal of Thoracic Oncology","year":2026,"doi":"10.1016/j.jtho.2026.104165","pmid":"42637134","authors":"Wu F, Zhang W, Zhao Y, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05168566 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-hpv-vaccine-sweden-nejm-2020","kind":"paper","name":"Swedish registry study: HPV vaccination almost eliminates cervical cancer when given before 17","aka":[],"tldr":"Among 1.7 million Swedish girls and women, quadrivalent HPV vaccination cut invasive cervical cancer by 88% when given before age 17 and by about half when given at 17-30.","summary":"A nationwide cohort of 1,672,983 girls and women aged 10-30 was followed from 2006 to 2017 through Swedish registries, linking HPV vaccination status to invasive cervical cancer diagnoses. Analyses adjusted for age, calendar year, county and parental characteristics.\n\nCumulative incidence of cervical cancer by age 30 was 47 per 100,000 in vaccinated women and 94 per 100,000 in unvaccinated women. The adjusted incidence rate ratio was 0.12 for women vaccinated before 17 and 0.47 for those vaccinated at 17-30.\n\nThis was the first population-level demonstration that HPV vaccination prevents invasive cancer, not just precancerous lesions.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1056/NEJMoa1917338"}],"tags":[],"related":["paper-hpv-vaccine-england-lancet-2021","idea-prev-hpv-single-dose-switch-catchup","idea-moon-hpv-vaccine-confidence","idea-single-dose-hpv-self-sampling-elimination"],"cancers":["cervical","head-and-neck"],"sections":["prevention"],"technologies":["hpv-vaccine","hpv-testing"],"targets":[],"drugs":[],"companies":[],"institutions":["karolinska"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-misinformation","b-global-access"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2020,"doi":"10.1056/NEJMoa1917338","pmid":"32997908","authors":"Lei J, Ploner A, Elfström KM, et al.","paperType":"observational","findings":["Adjusted incidence rate ratio for cervical cancer 0.37 (95% CI 0.21-0.57) overall in vaccinated vs unvaccinated","Vaccinated before age 17: IRR 0.12 (95% CI 0.00-0.34), an 88% reduction","Vaccinated at 17-30: IRR 0.47 (95% CI 0.27-0.75)","Cumulative incidence by age 30: 47 vs 94 per 100,000"],"whatItMeans":"Vaccinating girls before they are exposed to HPV prevents most cervical cancers. Catch-up vaccination in young adults still helps, but less. Combined with HPV screening, elimination of cervical cancer as a public health problem is a realistic goal.","caveats":["Observational; residual confounding by health-seeking behaviour is possible despite adjustment","Follow-up ends at age 30, before most cervical cancers occur","Sweden used the quadrivalent vaccine; effects for bivalent and nonavalent vaccines are inferred","Does not address single-dose schedules or vaccination of boys"],"changedPractice":true,"participants":1672983},{"id":"paper-swog-8710-neoadjuvant-mvac-nejm-2003","kind":"paper","name":"SWOG 8710: neoadjuvant MVAC chemotherapy before cystectomy for muscle-invasive bladder cancer","aka":[],"tldr":"Giving three cycles of cisplatin-based chemotherapy before removing the bladder lengthened survival compared with surgery alone, and became the standard for fit patients with muscle-invasive bladder cancer.","summary":"Randomised trial of 317 patients with muscle-invasive urothelial bladder cancer (T2 to T4a) assigned to three cycles of methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) followed by radical cystectomy, or cystectomy alone.\n\nMedian survival was 77 months with neoadjuvant chemotherapy against 46 months with surgery alone, and 38 percent of chemotherapy patients had no residual tumour at surgery compared with 15 percent, a finding tightly linked to long-term survival. The trial anchored neoadjuvant cisplatin-based chemotherapy as the standard of care.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2003","url":"https://doi.org/10.1056/NEJMoa022148"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/12944571/"}],"tags":[],"related":[],"cancers":["muscle-invasive-bladder-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2003,"doi":"10.1056/NEJMoa022148","pmid":"12944571","authors":"Grossman HB, Natale RB, Tangen CM, et al.","paperType":"rct","findings":["Median overall survival 77 months with neoadjuvant MVAC vs 46 months with cystectomy alone.","Pathological complete response (pT0) in 38 percent vs 15 percent, with 85 percent five-year survival among pT0 patients."],"whatItMeans":"Fit patients with muscle-invasive bladder cancer should be offered cisplatin-based chemotherapy before cystectomy; a complete pathological response predicts cure. Newer regimens such as gemcitabine-cisplatin and dose-dense MVAC, and now durvalumab, build on this result.","caveats":["The survival difference reached only borderline statistical significance in the primary analysis.","Slow accrual over eleven years; MVAC has largely been replaced by better-tolerated cisplatin regimens."],"changedPractice":true,"participants":317},{"id":"paper-hussain-swog-9346-intermittent-androgen-deprivation-nejm-2013","kind":"paper","name":"SWOG 9346: intermittent versus continuous androgen deprivation in metastatic prostate cancer","aka":["SWOG 9346","S9346","Hussain 2013 intermittent androgen deprivation"],"tldr":"Hormone therapy causes hot flushes, loss of libido, loss of muscle and bone, and low mood. This trial asked whether men could take breaks from it. After ten years the answer was uncomfortable: the breaks felt better for three months, and the trial could not rule out a worse chance of survival.","summary":"Maha Hussain and the Southwest Oncology Group enrolled 3,040 men with newly diagnosed metastatic hormone-sensitive prostate cancer, gave them seven months of androgen deprivation, and randomised the 1,535 whose prostate-specific antigen fell to 4 ng per millilitre or lower to continuous or intermittent therapy. The co-primary objectives were non-inferiority of survival, with an upper boundary on the hazard ratio of 1.20, and quality of life at three months.\n\nThe result is one of the most honestly reported inconclusive trials in oncology. Median survival was 5.8 years on continuous therapy and 5.1 years on intermittent, with a hazard ratio of 1.10 and a 90 percent confidence interval running to 1.23, which crosses the non-inferiority boundary without demonstrating inferiority either. Erectile function and mental health were better on intermittent therapy at month 3 and not afterwards.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2013","url":"https://doi.org/10.1056/nejmoa1212299"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23550669/"},{"label":"ClinicalTrials.gov NCT00002651","url":"https://clinicaltrials.gov/study/NCT00002651"}],"tags":["prostate-evidence"],"related":["paper-langley-lancet","paper-denmeade-transformer-bipolar-androgen-therapy-jco-2021","prostate-roadmap"],"cancers":["prostate","prostate-mhspc"],"sections":["hormonal","supportive-care"],"technologies":[],"targets":[],"drugs":["leuprolide","bicalutamide"],"companies":[],"institutions":[],"pathways":[],"terms":["adt","psa","quality-of-life","hazard-ratio","intermittent-androgen-deprivation","other-cause-mortality"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-trial-design","b-survivorship"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2013,"doi":"10.1056/nejmoa1212299","pmid":"23550669","authors":"Hussain M, Tangen CM, Berry DL, et al.","paperType":"rct","findings":["Median survival 5.8 years in the continuous-therapy group and 5.1 years in the intermittent-therapy group; hazard ratio for death with intermittent therapy 1.10 (90 percent confidence interval 0.99 to 1.23).","The confidence interval exceeded the pre-specified upper non-inferiority boundary of 1.20, so a 20 percent greater risk of death with intermittent therapy could not be ruled out, and too few events occurred to demonstrate inferiority.","Median follow-up 9.8 years; 3,040 men enrolled and 1,535 randomised after the seven-month induction (765 continuous, 770 intermittent).","Intermittent therapy was associated with better erectile function (P less than 0.001) and mental health (P equals 0.003) at month 3 but not thereafter.","No significant differences between the groups in the number of treatment-related high-grade adverse events."],"whatItMeans":"The reason intermittent androgen deprivation is offered as a choice in metastatic disease rather than recommended, and a case study in what an inconclusive non-inferiority trial should say. For a man weighing the side effects, the honest statement is that the quality-of-life gain is real but brief and the survival question is open.","caveats":["Statistically inconclusive by the authors' own statement: neither non-inferiority nor inferiority was established.","Only men whose prostate-specific antigen fell below 4 ng per millilitre after seven months were randomised, so the result does not apply to men who do not achieve that response.","Standard of care has changed completely since enrolment: androgen deprivation alone is no longer first-line treatment for metastatic disease, so the question would have to be re-asked on top of a modern backbone."],"changedPractice":true,"participants":1535},{"id":"paper-petrylak-swog-9916-docetaxel-estramustine-nejm-2004","kind":"paper","name":"SWOG 9916: docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer","aka":["SWOG 9916","Petrylak 2004 docetaxel estramustine"],"tldr":"Published in the same issue as TAX 327 and reaching the same conclusion by a different route: docetaxel extends life in advanced prostate cancer. The extra drug it was paired with, estramustine, brought enough side effects that it was dropped from practice.","summary":"Daniel Petrylak and the Southwest Oncology Group randomised 770 men with metastatic androgen-independent prostate cancer to docetaxel with estramustine or to mitoxantrone with prednisone; 674 were eligible for analysis. Overall survival was the primary endpoint.\n\nThe pair of trials published in the New England Journal of Medicine on 7 October 2004 is the reason docetaxel became standard. TAX 327 gave the better toxicity profile and the schedule that survived; SWOG 9916 gave the independent replication. The estramustine combination produced more febrile neutropenia, more nausea and vomiting and more cardiovascular events, and did not deliver a better survival result, so the simpler regimen won.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2004","url":"https://doi.org/10.1056/nejmoa041318"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/15470214/"}],"tags":["prostate-evidence"],"related":["paper-tannock-tax-327-docetaxel-prednisone-nejm-2004","chemotherapy-roadmap","prostate-roadmap"],"cancers":["prostate","prostate-mcrpc"],"sections":["chemotherapy"],"technologies":[],"targets":[],"drugs":["docetaxel","mitoxantrone","estramustine","prednisone"],"companies":[],"institutions":[],"pathways":[],"terms":["castration-resistance","psa"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-resistance"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2004,"doi":"10.1056/nejmoa041318","pmid":"15470214","authors":"Petrylak DP, Tangen CM, Hussain MH, et al.","paperType":"rct","findings":["Median overall survival 17.5 months with docetaxel and estramustine against 15.6 months with mitoxantrone and prednisone (P equals 0.02; hazard ratio for death 0.80, 95 percent confidence interval 0.67 to 0.97).","Median time to progression 6.3 months against 3.2 months (P less than 0.001).","Declines in prostate-specific antigen of at least 50 percent in 50 percent against 27 percent (P less than 0.001).","Objective tumour responses in 17 percent against 11 percent of patients with bidimensionally measurable disease (P equals 0.30).","Grade 3 or 4 neutropenic fevers (P equals 0.01), nausea and vomiting (P less than 0.001) and cardiovascular events (P equals 0.001) were more common with docetaxel and estramustine; pain relief was similar in both groups."],"whatItMeans":"The confirmatory half of the 2004 result. Two independent trials, two different docetaxel regimens, the same direction of effect: this is why docetaxel was adopted quickly and why it survived the move into hormone-sensitive disease a decade later.","caveats":["The comparison bundles docetaxel with estramustine, so the trial cannot say how much of the benefit or the harm each drug contributed; TAX 327 answered that by omitting estramustine.","96 of 770 randomised men were ineligible, and the analysis is of the 674 eligible.","Cardiovascular events were significantly more common in the experimental arm, which is why estramustine is no longer used."],"changedPractice":true,"participants":770},{"id":"paper-swog-s0809-adjuvant-chemoradiation-jco-2015","kind":"paper","name":"SWOG S0809: A Phase II Intergroup Trial of Adjuvant Capecitabine and Gemcitabine Followed by Radiotherapy and Concurrent Capecitabine in Extrahepatic Cholangiocarcinoma and Gallbladder Carcinoma","aka":[],"tldr":"In the only prospective trial of chemotherapy then radiotherapy after surgery for gallbladder or bile duct cancer, two in three patients were alive at two years, including those whose cancer had reached the cut edge, but there was no comparison group.","summary":"S0809 enrolled patients with extrahepatic cholangiocarcinoma or gallbladder carcinoma after radical resection with pT2 to 4, node-positive or margin-positive disease. Four cycles of gemcitabine and capecitabine were followed by capecitabine with radiotherapy (45 Gy to regional lymphatics, 54 to 59.4 Gy to the tumour bed). Of 79 eligible patients (68 percent cholangiocarcinoma, 32 percent gallbladder; 54 R0, 25 R1), 86 percent completed treatment. Two-year survival was 65 percent (95 percent CI 53 to 74): 67 percent after R0 and 60 percent after R1. Median overall survival was 35 months. Relapse was local in 14, distant in 24 and both in 9 patients. Grade 3 and 4 adverse effects occurred in 52 and 11 percent; one patient died of gastrointestinal haemorrhage.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2015","url":"https://doi.org/10.1200/JCO.2014.60.2219"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25964250/"},{"label":"ClinicalTrials.gov NCT00789958","url":"https://clinicaltrials.gov/study/NCT00789958"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder","extrahepatic-cholangiocarcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":["gemcitabine","capecitabine"],"companies":["swog"],"institutions":[],"pathways":[],"terms":["chemoradiation","radiotherapy"],"trials":["swog-s0809"],"people":[],"bottlenecks":["b-surgery-radiation-innovation"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2015,"doi":"10.1200/JCO.2014.60.2219","pmid":"25964250","authors":"Ben-Josef E, Guthrie KA, El-Khoueiry AB, et al.","paperType":"observational","findings":["Two-year overall survival 65 percent (95 percent CI 53 to 74); 67 percent after R0 and 60 percent after R1 resection.","Median overall survival 35 months (R0 34, R1 35).","Grade 3 adverse effects 52 percent, grade 4 11 percent; one treatment-related death."],"whatItMeans":"This single-arm trial is why NCCN lists chemoradiation after a positive margin or involved nodes. The near-identical survival after R0 and R1 resection is suggestive but unproven; no randomised trial has followed, and the UK does not routinely offer it.","caveats":["Single-arm phase 2 with a historical benchmark, not a randomised comparison.","Only 25 gallbladder cancer patients."],"changedPractice":true,"participants":79},{"id":"paper-lung-map-j-thorac-oncol-2019","kind":"paper","name":"SWOG S1400C (NCT02154490)-A Phase II Study of Palbociclib for Previously Treated Cell Cycle Gene Alteration-Positive Patients with Stage IV Squamous Cell Lung Cancer (Lung-MAP Substudy)","aka":[],"tldr":"Published report from the Lung-MAP trial registered as NCT02154490, in Journal of Thoracic Oncology (2019), chosen as the most cited paper whose own text cites the registry id.","summary":"Objective: Lung-MAP (SWOG S1400) is a master platform trial assessing targeted therapies in squamous NSCLC. The objective of study C (S1400C) was to evaluate the response rate to palbociclib, a cyclin-dependent kinase 4 and cyclin-dependent kinase 6 inhibitor, in patients with cell cycle gene abnormalities.\n\nMethods: Patients with squamous NSCLC, a performance status of 0 to 2, and normal organ function who had progressed after at least one prior platinum-based chemotherapy with cyclin-dependent kinase 4 gene (CDK4) or cyclin D1 gene (CCND1), cyclin D2 gene (CCND2), or cyclin D3 gene (CCND3) amplifications on tumor specimens were eligible. The study was originally designed as a phase II/III trial comparing palbociclib with docetaxel, but it was modified to a single-arm phase II trial with the primary end point of response when immunotherapy was approved. If two or fewer responses were seen in the first 20 patients, then the study would cease enrollment.\n\nResults: A total of 88 patients (9% of patients screened) were assigned to S1400C, and 53 patients enrolled (including 17 to receive docetaxel). One patient who had been registered to receive docetaxel was re-registered to receive palbociclib after progression while taking docetaxel. The frequencies of cell cycle gene alterations in the eligible patients taking palbociclib (n = 32) were as follows: CCND1, 81% (n = 26); CCND2, 9% (n = 3); CCND3, 6% (n = 2); and CDK4, 3% (n = 1). In all, 32 eligible patients received palbociclib. There were two partial responses (response rate 6% [95% confidence interval (CI): 0%-15%]), both with CCND1 amplification. Twelve patients had stable disease (38% [95% CI: 21%-54%]). The median progression-free survival was 1.7 months (95% CI: 1.6-2.9 months) and the median overall survival was 7.1 months (95% CI: 4.2-12.5).\n\nConclusion: Palbociclib as monotherapy failed to demonstrate the prespecified criteria for advancement to phase III testing.\n\nIndexed on Europe PMC as PubMed record 31302234 (DOI 10.1016/j.jtho.2019.06.027). Its title cites the registry id NCT02154490, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Thorac Oncol 2019","url":"https://doi.org/10.1016/j.jtho.2019.06.027"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31302234/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31302234"},{"label":"ClinicalTrials.gov NCT02154490","url":"https://clinicaltrials.gov/study/NCT02154490"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["lung-map"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-thoracic-oncology"],"dependsOn":[],"notes":[],"journal":"Journal of Thoracic Oncology","year":2019,"doi":"10.1016/j.jtho.2019.06.027","pmid":"31302234","authors":"Edelman MJ, Redman MW, Albain KS, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02154490 with the most citations, so it is the natural first reading for anyone following the Lung-MAP trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-swog-s1826-nivolumab-avd-nejm-2024","kind":"paper","name":"SWOG S1826: nivolumab plus AVD chemotherapy versus brentuximab-AVD for advanced Hodgkin lymphoma in adolescents and adults","aka":[],"tldr":"Adding a PD-1 antibody to chemotherapy beat the brentuximab-based standard, with 92% of patients progression-free at two years and less nerve damage.","summary":"S1826 was a phase 3 trial run jointly by adult and paediatric cooperative groups, randomising 994 patients aged 12 and over with newly diagnosed stage III or IV classical Hodgkin lymphoma to nivolumab plus AVD (N-AVD) or brentuximab vedotin plus AVD (BV-AVD) for six cycles. Radiotherapy was discouraged and given to under 1%. The primary endpoint was PFS. At two years PFS was 92% versus 83% (hazard ratio 0.45), with benefit across ages including patients over 60. N-AVD caused less peripheral neuropathy and fewer treatment discontinuations, while immune-related events (mainly thyroid dysfunction and rash) were mostly low grade.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa2405888"},{"label":"ClinicalTrials.gov NCT03907488","url":"https://clinicaltrials.gov/study/NCT03907488"}],"tags":[],"related":["pd1-plus-avd-hodgkin","paper-echelon-1-brentuximab-avd-nejm-2018"],"cancers":["hodgkin-lymphoma"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["pd1","cd30"],"drugs":["nivolumab","brentuximab-vedotin","doxorubicin"],"companies":["bms","swog","childrens-oncology-group"],"institutions":[],"pathways":[],"terms":["pfs","irae"],"trials":["swog-s1826","echelon-1","hd21","ahod2131"],"people":["alex-herrera"],"bottlenecks":["b-trial-design","b-survivorship"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2024,"doi":"10.1056/NEJMoa2405888","authors":"Herrera AF, LeBlanc M, Castellino SM, et al.","paperType":"rct","findings":["994 patients aged 12 and over (about a quarter under 18) with stage III-IV classical Hodgkin lymphoma; N-AVD vs BV-AVD.","2-year PFS 92% vs 83%; hazard ratio 0.45.","Benefit consistent in adolescents, adults and patients over 60.","Less peripheral neuropathy and fewer discontinuations with N-AVD; immune-related adverse events mostly grade 1-2.","Consolidative radiotherapy used in fewer than 1% of patients."],"whatItMeans":"S1826 moved checkpoint blockade into first-line Hodgkin lymphoma and made N-AVD a preferred regimen for advanced disease in patients from adolescence to older age, while removing radiotherapy for most. It also showed the value of a single trial spanning paediatric and adult groups. Longer follow-up is needed for overall survival and late immune effects in young patients.","caveats":["Overall survival data are immature; both arms have high survival.","Follow-up is short for a disease where late relapses and second cancers matter.","Comparison is with BV-AVD, not the European BrECADD regimen.","Nivolumab cost and access limit adoption in some health systems."],"changedPractice":true,"participants":994},{"id":"paper-mikhael-j-clin-oncol","kind":"paper","name":"Sybil: A Validated Deep Learning Model to Predict Future Lung Cancer Risk From a Single Low-Dose Chest Computed Tomography","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 36634294 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: Low-dose computed tomography (LDCT) for lung cancer screening is effective, although most eligible people are not being screened. Tools that provide personalized future cancer risk assessment could focus approaches toward those most likely to benefit. We hypothesized that a deep learning model assessing the entire volumetric LDCT data could be built to predict individual risk without requiring additional demographic or clinical data.\n\nMethods: We developed a model called Sybil using LDCTs from the National Lung Screening Trial (NLST). Sybil requires only one LDCT and does not require clinical data or radiologist annotations; it can run in real time in the background on a radiology reading station. Sybil was validated on three independent data sets: a heldout set of 6,282 LDCTs from NLST participants, 8,821 LDCTs from Massachusetts General Hospital (MGH), and 12,280 LDCTs from Chang Gung Memorial Hospital (CGMH, which included people with a range of smoking history including nonsmokers).\n\nResults: Sybil achieved area under the receiver-operator curves for lung cancer prediction at 1 year of 0.92 (95% CI, 0.88 to 0.95) on NLST, 0.86 (95% CI, 0.82 to 0.90) on MGH, and 0.94 (95% CI, 0.91 to 1.00) on CGMH external validation sets. Concordance indices over 6 years were 0.75 (95% CI, 0.72 to 0.78), 0.81 (95% CI, 0.77 to 0.85), and 0.80 (95% CI, 0.75 to 0.86) for NLST, MGH, and CGMH, respectively.\n\nConclusion: Sybil can accurately predict an individual's future lung cancer risk from a single LDCT scan to further enable personalized screening. Future study is required to understand Sybil's clinical applications. Our model and annotations are publicly available.[Media: see text].\n\nIndexed on Europe PMC as PubMed record 36634294 (DOI 10.1200/jco.22.01345). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2023","url":"https://doi.org/10.1200/jco.22.01345"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36634294/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36634294"}],"tags":["europepmc-ingest"],"related":["sybil"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2023,"doi":"10.1200/jco.22.01345","pmid":"36634294","authors":"Mikhael PG, Wohlwend J, Yala A, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-di-maio-j-clin-oncol","kind":"paper","name":"Symptomatic toxicities experienced during anticancer treatment: agreement between patient and physician reporting in three randomized trials","aka":[],"tldr":"Paper cited by one bottleneck page and 15 idea pages, indexed on Europe PMC as PubMed record 25624439 and published in Journal of Clinical Oncology; the citing pages link this DOI, which is how the record was matched.","summary":"Purpose: Information about symptomatic toxicities of anticancer treatments is not based on direct report by patients, but rather on reports by clinicians in trials. Given the potential for under-reporting, our aim was to compare reporting by patients and physicians of six toxicities (anorexia, nausea, vomiting, constipation, diarrhea, and hair loss) within three randomized trials.\n\nPatients and methods: In one trial, elderly patients with breast cancer received adjuvant chemotherapy; in two trials, patients with advanced non-small-cell lung cancer received first-line treatment. Toxicity was prospectively collected by investigators (graded by National Cancer Institute Common Toxicity Criteria [version 2.0] or Common Terminology Criteria for Adverse Events [version 3]). At the end of each cycle, patients completed the European Organisation for Research and Treatment of Cancer quality-of-life questionnaires, including toxicity-related symptom items. Possible answers were \"not at all,\" \"a little,\" \"quite a bit,\" and \"very much.\" Analysis was limited to the first three cycles. For each toxicity, agreement between patients and physicians and under-reporting by physicians (ie, toxicity reported by patients but not reported by physicians) were calculated.\n\nResults: Overall, 1,090 patients (2,482 cycles) were included. Agreement between patients and physicians was low for all toxicities. Toxicity rates reported by physicians were always lower than those reported by patients. For patients who reported toxicity (any severity), under-reporting by physicians ranged from 40.7% to 74.4%. Examining only patients who reported \"very much\" toxicity, under-reporting by physicians ranged from 13.0% to 50.0%.\n\nConclusion: Subjective toxicities are at high risk of under-reporting by physicians, even when prospectively collected within randomized trials. This strongly supports the incorporation of patient-reported outcomes into toxicity reporting in clinical trials.\n\nIndexed on Europe PMC as PubMed record 25624439 (DOI 10.1200/jco.2014.57.9334). Matched by DOI alone: one bottleneck page and 15 idea pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2015","url":"https://doi.org/10.1200/jco.2014.57.9334"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25624439/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25624439"}],"tags":["europepmc-ingest"],"related":["b-toxicity-qol","idea-moon-adult-late-effects-registry","idea-moon-supportive-care-platform-trial","idea-moon-neuropathy-prevention-programme","idea-moon-cardioprotection-by-default","idea-moon-fertility-preservation-default","idea-moon-hair-preservation-for-all","idea-moon-cognitive-toxicity-programme","idea-moon-oncology-hospital-at-home","idea-moon-quality-adjusted-pricing","idea-moon-mucositis-taste-programme","idea-moon-irae-prediction-and-prevention","idea-moon-hearing-protection-cisplatin","idea-moon-quality-adjusted-survival-standard","idea-moon-sexual-health-as-toxicity-domain","idea-moon-toxicity-first-endpoints"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2015,"doi":"10.1200/jco.2014.57.9334","pmid":"25624439","authors":"Di Maio M, Gallo C, Leighl NB, et al.","paperType":"rct","findings":[],"whatItMeans":"One bottleneck page and 15 idea pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-ishiguro-dichloroacetate-ivermectin-cureus-2022","kind":"paper","name":"Synergistic anti-tumor effect of dichloroacetate and ivermectin","aka":[],"tldr":"Three patients treated at a private clinic with dichloroacetate, omeprazole, tamoxifen and ivermectin were reported to have relief of symptoms; there was no control, no measured tumour response and no follow-up study.","summary":"The authors, who had earlier proposed that dichloroacetate, omeprazole and tamoxifen block cancer progression by reducing lactic acid production, present three patients in whom adding ivermectin was said to have 'dramatically relieved' the symptoms of cancer and sarcoma progression (Ishiguro case series 2022). The report describes symptom relief rather than tumour measurements (Ishiguro case series 2022).","asOf":"2026-09-24","links":[{"label":"Ishiguro case series 2022","url":"https://doi.org/10.7759/cureus.21884"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35265417/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["ivermectin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo agent (Claude Fable 5.1)","editedOn":"2026-09-24","note":"Written from cached ClinicalTrials.gov v2, Europe PMC, DailyMed, Drugs@FDA and WHO eEML responses; no figure appears without its source link."},"journal":"Cureus","year":2022,"doi":"10.7759/cureus.21884","pmid":"35265417","authors":"Ishiguro T, Ishiguro RH, Ishiguro M, Toki A, Terunuma H.","paperType":"observational","findings":["Three patients; symptom relief reported; no objective response measured."],"whatItMeans":"An anecdote from the clinic that prescribed the regimen; it cannot show benefit and has not led to a trial.","caveats":["No control group, no tumour measurements, authors treated the patients they report on."],"changedPractice":false,"participants":3},{"id":"paper-goonetilleke-ca19-9-systematic-review-ejso-2007","kind":"paper","name":"Systematic review of carbohydrate antigen (CA 19-9) as a biochemical marker in the diagnosis of pancreatic cancer","aka":[],"tldr":"Pooling studies of 2,283 patients put the CA 19-9 blood test at about 79% sensitivity and 82% specificity for diagnosing pancreatic cancer, with blocked bile ducts causing false positives.","summary":"A MEDLINE search for pancreatic neoplasm and serum tumour marker retained studies giving original sensitivity and specificity data, with attention to diagnostic accuracy, the effect of cholestasis and the relation of stage to marker level. CA 19-9 was the most extensively evaluated, with pooled data from 2,283 patients: median sensitivity 79% (70 to 90%) and median specificity 82% (68 to 91%). CA 19-9 elevation in non-malignant jaundice reduces specificity; combination with other markers improves accuracy. The authors conclude CA 19-9 should be used in diagnostic algorithms with elevated values repeated after relief of jaundice.","asOf":"2026-09-24","links":[{"label":"Goonetilleke and Siriwardena, Eur J Surg Oncol 2007: systematic review of CA 19-9 in 2,283 patients","url":"https://doi.org/10.1016/j.ejso.2006.10.004"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/17097848/"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["manchester-royal-infirmary"],"pathways":[],"terms":["ca19-9"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"European Journal of Surgical Oncology","year":2007,"doi":"10.1016/j.ejso.2006.10.004","pmid":"17097848","authors":"Goonetilleke KS, Siriwardena AK.","paperType":"meta-analysis","findings":["Pooled median sensitivity 79% and specificity 82% across 2,283 patients.","Cholestasis raises CA 19-9 and lowers specificity; repeat after relief of jaundice."],"whatItMeans":"The numbers that keep CA 19-9 a monitoring and prognostic marker rather than a diagnostic or screening test.","caveats":["Pooled heterogeneous studies from before modern assays.","Lewis-negative non-producers are not separated out."],"changedPractice":false,"participants":2283},{"id":"paper-soreide-incidental-gallbladder-cancer-review-bjs-2019","kind":"paper","name":"Systematic review of management of incidental gallbladder cancer after cholecystectomy","aka":[],"tldr":"A British Journal of Surgery review of what to do when a gallbladder removed for stones turns out to hold cancer: about one in 200 do, tumours confined to the lining are cured by the first operation, deeper ones need a second, and cutting out the keyhole port sites does not help.","summary":"Systematic review (PubMed to May 2018) from Edinburgh identifying 12 systematic reviews and meta-analyses plus consensus reports, multi-institutional series and national audits. Incidental gallbladder cancer was found in 0.25 to 0.89 percent of cholecystectomy specimens; about half were pT2 and a third pT1. Five-year survival after cholecystectomy alone was up to 100 percent for T1a or less; re-resection is recommended from T1b, though its type, extent and timing remain controversial. Perforation at the first operation raised dissemination risk; PET is useful for residual disease; routine laparoscopic staging is not warranted for all stages; port-site metastases occur in about 10 percent and routine port-site resection does not affect survival; adjuvant chemotherapy is poorly documented and probably underused.","asOf":"2026-09-24","links":[{"label":"Br J Surg 2019","url":"https://doi.org/10.1002/bjs.11035"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30582640/"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":["pet-ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["incidental-gallbladder-cancer","radical-cholecystectomy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"British Journal of Surgery","year":2019,"doi":"10.1002/bjs.11035","pmid":"30582640","authors":"Søreide K, Guest RV, Harrison EM, et al.","paperType":"review","findings":["Incidental gallbladder cancer in 0.25 to 0.89 percent of cholecystectomy specimens; about half pT2, a third pT1.","Five-year survival up to 100 percent after cholecystectomy alone for T1a or less; re-resection recommended for T1b or above.","Port-site metastases about 10 percent; routine port-site resection has no effect on survival."],"whatItMeans":"The UK-authored summary that most NHS hepatobiliary units work from; it names the open questions (type, extent and timing of re-resection; adjuvant chemotherapy) that the trials in this roadmap are trying to answer.","caveats":["Narrative synthesis of heterogeneous retrospective data.","Predates BILCAP's publication and the immunotherapy trials."],"changedPractice":false},{"id":"paper-zadik-support-care-cancer","kind":"paper","name":"Systematic review of photobiomodulation for the management of oral mucositis in cancer patients and clinical practice guidelines","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 31286228 and published in Supportive care in cancer; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: To systematically review the literature and update the evidence-based clinical practice guidelines for the use of photobiomodulation (PBM), such as laser and other light therapies, for the prevention and/or treatment of oral mucositis (OM).\n\nMethods: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO) using PubMed and Web of Science. We followed the MASCC methods for systematic review and guidelines development. The rigorously evaluated evidence for each intervention, in each cancer treatment setting, was assigned a level-of-evidence (LoE). Based on the LoE, one of the following guidelines was determined: Recommendation, Suggestion, or No Guideline Possible.\n\nResults: Recommendations are made for the prevention of OM and related pain with PBM therapy in cancer patients treated with one of the following modalities: hematopoietic stem cell transplantation, head and neck (H&N) radiotherapy (without chemotherapy), and H&N radiotherapy with chemotherapy. For each of these modalities, we recommend 1-2 clinically effective protocols; the clinician should adhere to all parameters of the protocol selected. Due to inadequate evidence, currently, No Guideline Possible for treatment of established OM or for management of chemotherapy-related OM. The reported clinical settings were extremely variable, limiting data integration.\n\nConclusions: The evidence supports the use of specific settings of PBM therapy for the prevention of OM in specific patient populations. Under these circumstances, PBM is recommended for the prevention of OM. The guidelines are subject to continuous update based on new published data.\n\nIndexed on Europe PMC as PubMed record 31286228 (DOI 10.1007/s00520-019-04890-2). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Support Care Cancer 2019","url":"https://doi.org/10.1007/s00520-019-04890-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31286228/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31286228"}],"tags":["europepmc-ingest"],"related":["photobiomodulation-mucositis"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["supportive-care-in-cancer"],"dependsOn":[],"notes":[],"journal":"Supportive care in cancer","year":2019,"doi":"10.1007/s00520-019-04890-2","pmid":"31286228","authors":"Zadik Y, Arany PR, Fregnani ER, et al.","paperType":"review","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nagaraja-eslick-typhi-carrier-gallbladder-cancer-meta-analysis-apt-2014","kind":"paper","name":"Systematic review with meta-analysis: the relationship between chronic Salmonella typhi carrier status and gall-bladder cancer","aka":[],"tldr":"Across 17 studies, mostly from India and China, people who carried the typhoid bacterium long term were about four times as likely to have gallbladder cancer, and the authors suggest offering them gallbladder removal or ultrasound checks.","summary":"Systematic review of MEDLINE, PubMed, EMBASE, Cochrane and other databases identifying 17 studies of chronic Salmonella Typhi carriage and gallbladder carcinoma. The pooled odds ratio for chronic carrier state was 4.28 (95 percent CI 1.84 to 9.96); most studies were from South Asia, especially India and China, and the South-East Asian subgroup odds ratio was 4.13 (2.87 to 5.94). The authors conclude chronic carriage is an important risk factor and that management should include elective cholecystectomy or careful ultrasound monitoring.","asOf":"2026-09-24","links":[{"label":"Aliment Pharmacol Ther 2014","url":"https://doi.org/10.1111/apt.12655"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24612190/"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["prophylactic-cholecystectomy","screening"],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Alimentary Pharmacology and Therapeutics","year":2014,"doi":"10.1111/apt.12655","pmid":"24612190","authors":"Nagaraja V, Eslick GD.","paperType":"meta-analysis","findings":["Pooled odds ratio 4.28 (95 percent CI 1.84 to 9.96) for chronic S. Typhi carriage and gallbladder cancer across 17 studies.","South-East Asian subgroup odds ratio 4.13 (2.87 to 5.94)."],"whatItMeans":"No trial has tested cholecystectomy or surveillance for chronic carriers; the recommendation is expert inference from a fourfold risk. It is one of the prevention ideas on this page.","caveats":["Heterogeneous case-control studies with varied carrier definitions.","Publication bias likely in a literature dominated by small positive studies."],"changedPractice":false},{"id":"paper-gordan-j-clin-oncol","kind":"paper","name":"Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline","aka":[],"tldr":"Paper cited by one trial page and one treatment page, indexed on Europe PMC as PubMed record 33197225 and published in Journal of Clinical Oncology; the citing pages link this DOI, which is how the record was matched.","summary":"Purpose: To develop an evidence-based clinical practice guideline to assist in clinical decision making for patients with advanced hepatocellular carcinoma (HCC).\n\nMethods: ASCO convened an Expert Panel to conduct a systematic review of published phase III randomized controlled trials (2007-2020) on systemic therapy for advanced HCC and provide recommended care options for this patient population.\n\nResults: Nine phase III randomized controlled trials met the inclusion criteria.\n\nRecommendations: Atezolizumab + bevacizumab (atezo + bev) may be offered as first-line treatment of most patients with advanced HCC, Child-Pugh class A liver disease, Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1, and following management of esophageal varices, when present, according to institutional guidelines. Where there are contraindications to atezolizumab and/or bevacizumab, tyrosine kinase inhibitors sorafenib or lenvatinib may be offered as first-line treatment of patients with advanced HCC, Child-Pugh class A liver disease, and ECOG PS 0-1. Following first-line treatment with atezo + bev, and until better data are available, second-line therapy with a tyrosine kinase inhibitor may be recommended for appropriate candidates. Following first-line therapy with sorafenib or lenvatinib, second-line therapy options for appropriate candidates include cabozantinib, regorafenib for patients who previously tolerated sorafenib, or ramucirumab (for patients with α-fetoprotein ≥ 400 ng/mL), or atezo + bev where patients did not have access to this option as first-line therapy. Pembrolizumab or nivolumab are also reasonable options for appropriate patients following sorafenib or lenvatinib. Consideration of nivolumab + ipilimumab as an option for second-line therapy and third-line therapy is discussed. Further guidance on choosing between therapy options is included within the guideline. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.\n\nIndexed on Europe PMC as PubMed record 33197225 (DOI 10.1200/jco.20.02672). Matched by DOI alone: one trial page and one treatment page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2020","url":"https://doi.org/10.1200/jco.20.02672"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33197225/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33197225"}],"tags":["europepmc-ingest"],"related":["donafenib"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["zgdh3"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/jco.20.02672","pmid":"33197225","authors":"Gordan JD, Kennedy EB, Abou-Alfa GK, et al.","paperType":"guideline","findings":[],"whatItMeans":"One trial page and one treatment page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-laurie-licitra-salivary-systemic-jco-2006","kind":"paper","name":"Systemic therapy in the palliative management of advanced salivary gland cancers (review)","aka":[],"tldr":"This review of chemotherapy in salivary gland cancers concluded that responses are uncommon and short, that observation is reasonable for slowly progressing disease, and that trials of targeted agents based on tumour biology were needed.","summary":"Systematic review of systemic therapy studies in recurrent or metastatic salivary gland carcinoma, summarising response rates to single agents and combinations by histology, the natural history of indolent adenoid cystic carcinoma, and early experience with targeted agents.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2006","url":"https://doi.org/10.1200/JCO.2005.05.3025"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/16763282/"}],"tags":[],"related":[],"cancers":["mucoepidermoid-carcinoma","adenoid-cystic-carcinoma","salivary-duct-carcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2006,"doi":"10.1200/JCO.2005.05.3025","pmid":"16763282","authors":"Laurie SA, Licitra L.","paperType":"review","findings":[],"whatItMeans":"The observation-first approach for indolent metastases and the move to biomarker-directed therapy (HER2, androgen receptor, NTRK) on the salivary cancer pages follow this review's conclusions.","caveats":["Predates the HER2, androgen receptor and immunotherapy studies that now guide treatment."],"changedPractice":false},{"id":"paper-inmind-tafasitamab-lenalidomide-rituximab-follicular-lancet-2026","kind":"paper","name":"Tafasitamab, lenalidomide, and rituximab in relapsed or refractory follicular lymphoma (inMIND): a global, phase 3, randomised controlled trial","aka":["inMIND","Sehn 2026"],"tldr":"Adding a third antibody, directed at a different target, to the usual tablet-and-antibody pairing added about eight months before follicular lymphoma progressed again.","summary":"A phase 3, double-blind, randomised, placebo-controlled trial at 210 centres in North America, Europe and the Asia-Pacific region. Adults with relapsed or refractory follicular lymphoma after at least one previous line were randomised 1 to 1 to up to twelve 28-day cycles of tafasitamab 12 mg per kilogram intravenously, or placebo, both with lenalidomide 20 mg daily on days 1 to 21 of cycles 1 to 12 and rituximab 375 mg per square metre. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population.\n\nBetween 16 April 2021 and 10 August 2023, 548 of 817 patients assessed were enrolled and randomised, 273 to tafasitamab and 275 to placebo; 299 (55 per cent) were male and 249 (45 per cent) female. Median progression-free survival by investigator was 22.4 months (95 per cent confidence interval 19.2 to not evaluable) with tafasitamab against 13.9 months (11.5 to 16.4) with placebo, a hazard ratio of 0.43 (0.32 to 0.58).","asOf":"2026-10-01","links":[{"label":"Lancet 2026","url":"https://doi.org/10.1016/S0140-6736(25)01778-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41360064/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41360064"}],"tags":["lymphoma-evidence"],"related":["lymphoma-roadmap"],"cancers":["follicular-lymphoma","marginal-zone-lymphoma","non-hodgkin-lymphoma"],"sections":["immunotherapy"],"technologies":["monoclonal-antibody"],"targets":["cd19","cd20"],"drugs":["tafasitamab","lenalidomide","rituximab"],"companies":["incyte"],"institutions":[],"pathways":[],"terms":[],"trials":["nct04680052"],"people":["laurie-sehn"],"bottlenecks":["b-combination-space","b-resistance"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"Lancet","year":2026,"doi":"10.1016/S0140-6736(25)01778-7","pmid":"41360064","authors":"Sehn LH, Hübel K, Luminari S, et al.","paperType":"rct","findings":["Median investigator-assessed progression-free survival was 22.4 months with tafasitamab, lenalidomide and rituximab against 13.9 months with placebo, lenalidomide and rituximab (hazard ratio 0.43, 95 per cent confidence interval 0.32 to 0.58).","548 patients were randomised at 210 centres across North America, Europe and the Asia-Pacific region.","The trial was double-blind and placebo-controlled, with patients, investigators and funder masked until the primary analysis.","Eligibility required at least one previous line of systemic therapy, which is a broader population than most relapsed follicular lymphoma trials."],"whatItMeans":"A new combination for relapsed or refractory follicular lymphoma that adds a CD19-directed antibody to the established lenalidomide and rituximab pairing, with the largest progression-free survival hazard ratio reported in the setting.","caveats":["Progression-free survival is the primary endpoint; overall survival data were immature at this analysis.","The comparator, lenalidomide with rituximab, is a reasonable standard, but the trial does not compare against CAR-T or bispecific antibodies, which are the alternatives for early-progressing disease.","Adding a CD19-directed antibody before CAR-T raises a question about subsequent CD19 CAR-T efficacy that the trial does not answer."],"changedPractice":true,"participants":548},{"id":"paper-pemmaraju-n-engl-j-med","kind":"paper","name":"Tagraxofusp in Blastic Plasmacytoid Dendritic-Cell Neoplasm","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 31018069 and published in New England Journal of Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Background: Blastic plasmacytoid dendritic-cell neoplasm (BPDCN) is an aggressive hematologic cancer that is caused by transformed plasmacytoid dendritic cells that overexpress interleukin-3 receptor subunit alpha (IL3RA or CD123). Tagraxofusp (SL-401) is a CD123-directed cytotoxin consisting of human interleukin-3 fused to truncated diphtheria toxin.\n\nMethods: In this open-label, multicohort study, we assigned 47 patients with untreated or relapsed BPDCN to receive an intravenous infusion of tagraxofusp at a dose of 7 μg or 12 μg per kilogram of body weight on days 1 to 5 of each 21-day cycle. Treatment continued until disease progression or unacceptable toxic effects. The primary outcome was the combined rate of complete response and clinical complete response among patients who had not received previous treatment for BPDCN. A secondary outcome was the duration of response.\n\nResults: Of the 47 patients, 32 were receiving tagraxofusp as first-line treatment and 15 had received previous treatment. The median age of the patients was 70 years (range, 22 to 84). Among the 29 previously untreated patients who received tagraxofusp at a dose of 12 μg per kilogram, the primary outcome occurred in 21 (72%), and the overall response rate was 90%; of these patients, 45% went on to undergo stem-cell transplantation. Survival rates at 18 and 24 months were 59% and 52%, respectively. Among the 15 previously treated patients, the response rate was 67%, and the median overall survival was 8.5 months. The most common adverse events were increased levels of alanine aminotransferase (64%) and aspartate aminotransferase (60%), hypoalbuminemia (55%), peripheral edema (51%), and thrombocytopenia (49%). Capillary leak syndrome was reported in 19% of the patients and was associated with one death in each of the dose subgroups.\n\nConclusions: In adult patients with untreated or relapsed BPDCN, the use of tagraxofusp led to clinical responses. Serious adverse events included capillary leak syndrome; hepatic dysfunction and thrombocytopenia were common. (Funded by Stemline Therapeutics and the Leukemia and Lymphoma Society Therapy Acceleration Program; ClinicalTrials.gov number, NCT02113982.).\n\nIndexed on Europe PMC as PubMed record 31018069 (DOI 10.1056/nejmoa1815105). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2019","url":"https://doi.org/10.1056/nejmoa1815105"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31018069/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31018069"}],"tags":["europepmc-ingest"],"related":["bpdcn"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2019,"doi":"10.1056/nejmoa1815105","pmid":"31018069","authors":"Pemmaraju N, Lane AA, Sweet KL, et al.","paperType":"observational","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-irwin-j-clin-oncol","kind":"paper","name":"Tai Chi Chih Compared With Cognitive Behavioral Therapy for the Treatment of Insomnia in Survivors of Breast Cancer: A Randomized, Partially Blinded, Noninferiority Trial","aka":[],"tldr":"Paper cited by two technology pages, indexed on Europe PMC as PubMed record 28489508 and published in Journal of Clinical Oncology; the citing pages link this DOI, which is how the record was matched.","summary":"Purpose Cognitive behavioral therapy for insomnia (CBT-I) and Tai Chi Chih (TCC), a movement meditation, improve insomnia symptoms. Here, we evaluated whether TCC is noninferior to CBT-I for the treatment of insomnia in survivors of breast cancer. Patients and Methods This was a randomized, partially blinded, noninferiority trial that involved survivors of breast cancer with insomnia who were recruited from the Los Angeles community from April 2008 to July 2012. After a 2-month phase-in period with repeated baseline assessment, participants were randomly assigned to 3 months of CBT-I or TCC and evaluated at months 2, 3 (post-treatment), 6, and 15 (follow-up). Primary outcome was insomnia treatment response-that is, marked clinical improvement of symptoms by the Pittsburgh Sleep Quality Index-at 15 months. Secondary outcomes were clinician-assessed remission of insomnia; sleep quality; total sleep time, sleep onset latency, sleep efficiency, and awake after sleep onset, derived from sleep diaries; polysomnography; and symptoms of fatigue, sleepiness, and depression. Results Of 145 participants who were screened, 90 were randomly assigned (CBT-I: n = 45; TCC: n = 45). The proportion of participants who showed insomnia treatment response at 15 months was 43.7% and 46.7% in CBT-I and TCC, respectively. Tests of noninferiority showed that TCC was noninferior to CBT-I at 15 months ( P =.02) and at months 3 ( P =.02) and 6 ( P <.01). For secondary outcomes, insomnia remission was 46.2% and 37.9% in CBT-I and TCC, respectively. CBT-I and TCC groups showed robust improvements in sleep quality, sleep diary measures, and related symptoms (all P <.01), but not polysomnography, with similar improvements in both groups. Conclusion CBT-I and TCC produce clinically meaningful improvements in insomnia. TCC, a mindful movement meditation, was found to be statistically noninferior to CBT-I, the gold standard for behavioral treatment of insomnia.\n\nIndexed on Europe PMC as PubMed record 28489508 (DOI 10.1200/jco.2016.71.0285). Matched by DOI alone: two technology pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2017","url":"https://doi.org/10.1200/jco.2016.71.0285"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28489508/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28489508"}],"tags":["europepmc-ingest"],"related":["cbt-insomnia-cancer","tai-chi-qigong"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2017,"doi":"10.1200/jco.2016.71.0285","pmid":"28489508","authors":"Irwin MR, Olmstead R, Carrillo C, et al.","paperType":"rct","findings":[],"whatItMeans":"Two technology pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-st-gallen-2025-consensus-ann-oncol-2025","kind":"paper","name":"Tailoring treatment to cancer risk and patient preference: the 2025 St Gallen International Breast Cancer Consensus Statement on individualizing therapy for patients with early breast cancer","aka":[],"tldr":"The 2025 international consensus on early breast cancer, which recommends platinum chemotherapy and immunotherapy for triple-negative disease, updated genetic testing guidance and shorter radiotherapy schedules.","summary":"Consensus statement from the biennial St Gallen Breast Cancer Consensus conference by Burstein, Curigliano, Gnant, Loibl and colleagues. Innovations in 2025 include updated guidance on genetic testing; endorsement of hypofractionated and ultra-hypofractionated radiotherapy for more patients; a recommendation for platinum-based chemotherapy in triple-negative breast cancer and use of biological risk markers to consider anthracyclines in other subtypes; avoidance of sentinel lymph node surgery in many low-risk oestrogen receptor-positive cancers; use of immunotherapy in triple-negative and certain oestrogen receptor low-positive tumours; guidance on re-irradiation and systemic therapy at locoregional recurrence; criteria for oligometastatic disease; and survivorship recommendations on neuropathy and sexual health.","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2025","url":"https://doi.org/10.1016/j.annonc.2025.09.007"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41072918/"}],"tags":["tnbc-evidence"],"related":[],"cancers":["tnbc","breast-hr-positive","breast-her2-positive"],"sections":[],"technologies":["platinum","checkpoint-inhibitor"],"targets":[],"drugs":["carboplatin","pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":["germline-testing","de-escalation"],"trials":["keynote-522"],"people":["giuseppe-curigliano","sibylle-loibl"],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2025,"doi":"10.1016/j.annonc.2025.09.007","pmid":"41072918","authors":"Burstein HJ, Curigliano G, Gnant M, et al.","paperType":"guideline","findings":["Platinum-based chemotherapy recommended in triple-negative breast cancer.","Immunotherapy recommended in triple-negative and certain oestrogen receptor low-positive tumours.","Updated genetic testing guidance and endorsement of hypofractionated and ultra-hypofractionated radiotherapy."],"whatItMeans":"Platinum and immunotherapy are now consensus for early triple-negative disease; the open votes have moved to who can safely receive less.","caveats":["Expert consensus by vote.","Does not address the post-neoadjuvant antibody-drug conjugate trials, which had not reported."],"changedPractice":true},{"id":"paper-tailorx-nejm-2018","kind":"paper","name":"TAILORx: adjuvant chemotherapy guided by the 21-gene recurrence score in hormone receptor-positive, node-negative breast cancer","aka":[],"tldr":"Women with hormone receptor-positive, HER2-negative, node-negative breast cancer and a mid-range 21-gene recurrence score did just as well with endocrine therapy alone as with chemotherapy added, sparing most of them chemotherapy.","summary":"Prospective trial of 10,273 women with hormone receptor-positive, HER2-negative, axillary node-negative breast cancer; those with a recurrence score of 11 to 25 (6,711 women) were randomised to endocrine therapy alone or chemoendocrine therapy.\n\nNine-year invasive disease-free survival was 83.3 percent with endocrine therapy against 84.3 percent with chemoendocrine therapy, meeting non-inferiority. Some benefit from chemotherapy was seen in women aged 50 or younger with scores of 16 to 25.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2018","url":"https://doi.org/10.1056/NEJMoa1804710"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29860917/"}],"tags":[],"related":[],"cancers":["hr-positive-early-high-risk"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["tailorx"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2018,"doi":"10.1056/NEJMoa1804710","pmid":"29860917","authors":"Sparano JA, Gray RJ, Makower DF, et al.","paperType":"rct","findings":["Nine-year invasive disease-free survival 83.3 percent vs 84.3 percent for scores 11 to 25 (hazard ratio 1.08, non-inferior).","Women 50 or younger with scores 16 to 25 had some chemotherapy benefit."],"whatItMeans":"Most women with node-negative hormone receptor-positive breast cancer can safely skip chemotherapy on the basis of a genomic assay; the exception is premenopausal women with scores in the upper part of the intermediate range.","caveats":["The benefit in younger women may partly reflect chemotherapy-induced ovarian suppression.","Node-positive disease was addressed separately in RxPONDER."],"changedPractice":true,"participants":10273},{"id":"paper-embraca-n-engl-j-med-2018","kind":"paper","name":"Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation","aka":[],"tldr":"Published report from the EMBRACA trial registered as NCT01945775, in New England Journal of Medicine (2018), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: The poly(adenosine diphosphate-ribose) inhibitor talazoparib has shown antitumor activity in patients with advanced breast cancer and germline mutations in BRCA1 and BRCA2 ( BRCA1/2).\n\nMethods: We conducted a randomized, open-label, phase 3 trial in which patients with advanced breast cancer and a germline BRCA1/2 mutation were assigned, in a 2:1 ratio, to receive talazoparib (1 mg once daily) or standard single-agent therapy of the physician's choice (capecitabine, eribulin, gemcitabine, or vinorelbine in continuous 21-day cycles). The primary end point was progression-free survival, which was assessed by blinded independent central review.\n\nResults: Of the 431 patients who underwent randomization, 287 were assigned to receive talazoparib and 144 were assigned to receive standard therapy. Median progression-free survival was significantly longer in the talazoparib group than in the standard-therapy group (8.6 months vs. 5.6 months; hazard ratio for disease progression or death, 0.54; 95% confidence interval [CI], 0.41 to 0.71; P<0.001). The interim median hazard ratio for death was 0.76 (95% CI, 0.55 to 1.06; P=0.11 [57% of projected events]). The objective response rate was higher in the talazoparib group than in the standard-therapy group (62.6% vs. 27.2%; odds ratio, 5.0; 95% CI, 2.9 to 8.8; P<0.001). Hematologic grade 3-4 adverse events (primarily anemia) occurred in 55% of the patients who received talazoparib and in 38% of the patients who received standard therapy; nonhematologic grade 3 adverse events occurred in 32% and 38% of the patients, respectively. Patient-reported outcomes favored talazoparib; significant overall improvements and significant delays in the time to clinically meaningful deterioration according to both the global health status-quality-of-life and breast symptoms scales were observed.\n\nConclusions: Among patients with advanced breast cancer and a germline BRCA1/2 mutation, single-agent talazoparib provided a significant benefit over standard chemotherapy with respect to progression-free survival. Patient-reported outcomes were superior with talazoparib. (Funded by Medivation [Pfizer]; EMBRACA ClinicalTrials.gov number, NCT01945775.).\n\nIndexed on Europe PMC as PubMed record 30110579 (DOI 10.1056/nejmoa1802905). Its abstract cites the registry id NCT01945775, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2018","url":"https://doi.org/10.1056/nejmoa1802905"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30110579/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30110579"},{"label":"ClinicalTrials.gov NCT01945775","url":"https://clinicaltrials.gov/study/NCT01945775"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["embraca"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2018,"doi":"10.1056/nejmoa1802905","pmid":"30110579","authors":"Litton JK, Rugo HS, Ettl J, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT01945775 with the most citations, so it is the natural first reading for anyone following the EMBRACA trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-talapro-2-lancet-2023","kind":"paper","name":"Talazoparib plus enzalutamide in men with first-line metastatic castration-resistant prostate cancer (TALAPRO-2): a randomised, placebo-controlled, phase 3 trial","aka":[],"tldr":"Published report from the TALAPRO-2 trial registered as NCT03395197, in The Lancet (2023), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Co-inhibition of poly(ADP-ribose) polymerase (PARP) and androgen receptor activity might result in antitumour efficacy irrespective of alterations in DNA damage repair genes involved in homologous recombination repair (HRR). We aimed to compare the efficacy and safety of talazoparib (a PARP inhibitor) plus enzalutamide (an androgen receptor blocker) versus enzalutamide alone in patients with metastatic castration-resistant prostate cancer (mCRPC).\n\nMethods: TALAPRO-2 is a randomised, double-blind, phase 3 trial of talazoparib plus enzalutamide versus placebo plus enzalutamide as first-line therapy in men (age ≥18 years [≥20 years in Japan]) with asymptomatic or mildly symptomatic mCRPC receiving ongoing androgen deprivation therapy. Patients were enrolled from 223 hospitals, cancer centres, and medical centres in 26 countries in North America, Europe, Israel, South America, South Africa, and the Asia-Pacific region. Patients were prospectively assessed for HRR gene alterations in tumour tissue and randomly assigned (1:1) to talazoparib 0·5 mg or placebo, plus enzalutamide 160 mg, administered orally once daily. Randomisation was stratified by HRR gene alteration status (deficient vs non-deficient or unknown) and previous treatment with life-prolonging therapy (docetaxel or abiraterone, or both: yes vs no) in the castration-sensitive setting. The sponsor, patients, and investigators were masked to talazoparib or placebo, while enzalutamide was open-label. The primary endpoint was radiographic progression-free survival (rPFS) by blinded independent central review, evaluated in the intention-to-treat population. Safety was evaluated in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov (NCT03395197) and is ongoing.\n\nFindings: Between Jan 7, 2019, and Sept 17, 2020, 805 patients were enrolled and randomly assigned (402 to the talazoparib group and 403 to the placebo group). Median follow-up for rPFS was 24·9 months (IQR 21·9-30·2) for the talazoparib group and 24·6 months (14·4-30·2) for the placebo group. At the planned primary analysis, median rPFS was not reached (95% CI 27·5 months-not reached) for talazoparib plus enzalutamide and 21·9 months (16·6-25·1) for placebo plus enzalutamide (hazard ratio 0·63; 95% CI 0·51-0·78; p<0·0001). In the talazoparib group, the most common treatment-emergent adverse events were anaemia, neutropenia, and fatigue; the most common grade 3-4 event was anaemia (185 [46%] of 398 patients), which improved after dose reduction, and only 33 (8%) of 398 patients discontinued talazoparib due to anaemia. Treatment-related deaths occurred in no patients in the talazoparib group and two patients (<1%) in the placebo group.\n\nInterpretation: Talazoparib plus enzalutamide resulted in clinically meaningful and statistically significant improvement in rPFS versus standard of care enzalutamide as first-line treatment for patients with mCRPC. Final overall survival data and additional long-term safety follow-up will further clarify the clinical benefit of the treatment combination in patients with and without tumour HRR gene alterations.\n\nFunding: Pfizer.\n\nIndexed on Europe PMC as PubMed record 37285865 (DOI 10.1016/s0140-6736(23)01055-3). Its abstract cites the registry id NCT03395197, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet 2023","url":"https://doi.org/10.1016/s0140-6736(23)01055-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37285865/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37285865"},{"label":"ClinicalTrials.gov NCT03395197","url":"https://clinicaltrials.gov/study/NCT03395197"}],"tags":["europepmc-ingest"],"related":["prostate-roadmap","paper-fizazi-triton3-rucaparib-nejm-2023","idea-prostate-hrr-testing-at-metastatic-diagnosis"],"cancers":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["talapro-2"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2023,"doi":"10.1016/s0140-6736(23)01055-3","pmid":"37285865","authors":"Agarwal N, Azad AA, Carles J, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03395197 with the most citations, so it is the natural first reading for anyone following the TALAPRO-2 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-talapro-2-lancet-2025-update","kind":"paper","name":"Talazoparib plus enzalutamide in men with metastatic castration-resistant prostate cancer: final overall survival results from the randomised, placebo-controlled, phase 3 TALAPRO-2 trial","aka":[],"tldr":"Later report from the TALAPRO-2 trial registered as NCT03395197, in The Lancet (2025); its title describes an updated or longer-term analysis.","summary":"Background: The primary analysis of this phase 3 trial combining talazoparib with enzalutamide demonstrated significantly improved radiographic progression-free survival (rPFS) versus enzalutamide plus placebo in patients with metastatic castration-resistant prostate cancer unselected for homologous recombination repair (HRR) gene alterations. Overall survival data were immature at that time. Here we report the final prespecified overall survival analysis, an updated descriptive analysis of rPFS, and safety in the cohort unselected for HRR gene alterations.\n\nMethods: TALAPRO-2 was a randomised, double-blind, placebo-controlled, phase 3 trial. In the genetically unselected cohort, patients were randomly assigned from 200 centres, including hospitals, cancer centres, and medical centres, in 26 countries in North America, Europe, Israel, South America, South Africa, and the Asia-Pacific region. Adult men (aged ≥18 years [≥20 years in Japan]) with asymptomatic or mildly symptomatic metastatic castration-resistant prostate cancer receiving ongoing androgen deprivation therapy, and with no previous life-prolonging systemic therapy for castration-resistant prostate cancer, were randomly assigned (1:1) to talazoparib 0·5 mg plus enzalutamide 160 mg or enzalutamide plus placebo, administered orally once daily as initial treatment for metastatic castration-resistant prostate cancer, stratified by HRR gene alteration status (HRR-deficient vs HRR-non-deficient or unknown) and previous treatment for castration-sensitive disease (yes vs no). The sponsor, patients, and investigators were masked to talazoparib or placebo, and enzalutamide was open label. The primary endpoint was rPFS by blinded independent central review, and overall survival (time from randomisation to death due to any cause) was an event-based α-protected key secondary endpoint (α-threshold at final overall survival analysis was 0·022 [two-sided])-both assessed in the intention-to-treat population. Follow-up for overall survival was intended to continue until the planned final analysis. Safety was assessed in patients who received at least one dose of a study drug. This study is registered with ClinicalTrials.gov, NCT03395197, and is ongoing.\n\nFindings: Between Jan 7, 2019, and Sept 17, 2020, 993 patients were assessed for eligibility, of whom 188 (19%) patients were excluded and 805 (81%) patients were enrolled and randomly assigned (402 [50%] to talazoparib plus enzalutamide, 403 [50%] to enzalutamide plus placebo). At a median follow-up of 52·5 months (IQR 48·6-56·0), overall survival was significantly improved with talazoparib plus enzalutamide compared with enzalutamide plus placebo (hazard ratio [HR] 0·80 [95% CI 0·66-0·96]; p=0·016); median overall survival was 45·8 months (95% CI 39·4-50·8) in the talazoparib group compared with 37·0 months (34·1-40·4) in the control group. Overall survival favoured talazoparib plus enzalutamide over enzalutamide plus placebo in HRR-deficient patients (n=169; HR 0·55 [0·36-0·83]; p=0·0035) and to a lesser extent in HRR-non-deficient or unknown patients (n=636; HR 0·88 [0·71-1·08]; p=0·22). Updated rPFS also favoured talazoparib plus enzalutamide (HR 0·67 [0·55-0·81]; p<0·0001); median rPFS was 33·1 months for talazoparib plus enzalutamide versus 19·5 months for enzalutamide plus placebo. Safety was consistent with the known profile of talazoparib; common grade 3 or higher adverse events with talazoparib plus enzalutamide were anaemia (195 [49%] vs 18 [4%] patients with enzalutamide plus placebo) and neutropenia (77 [19%] vs six [1%] patients with enzalutamide plus placebo).\n\nInterpretation: Combining talazoparib with enzalutamide significantly improved overall survival in patients with metastatic castration-resistant prostate cancer, supporting this combination as a standard-of-care initial treatment option for these patients.\n\nFunding: Pfizer.\n\nIndexed on Europe PMC as PubMed record 40683290 (DOI 10.1016/s0140-6736(25)00684-1). Its abstract cites the registry id NCT03395197, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet 2025","url":"https://doi.org/10.1016/s0140-6736(25)00684-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40683290/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40683290"},{"label":"ClinicalTrials.gov NCT03395197","url":"https://clinicaltrials.gov/study/NCT03395197"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["talapro-2"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2025,"doi":"10.1016/s0140-6736(25)00684-1","pmid":"40683290","authors":"Agarwal N, Azad AA, Carles J, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the TALAPRO-2 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-jain-talicabtagene-lancet-haem-2025","kind":"paper","name":"Talicabtagene autoleucel for relapsed or refractory B-cell malignancies: an open-label, multicentre, phase 1/2 study","aka":[],"tldr":"The trial report behind India's first CAR-T therapy: about three in four heavily pretreated patients with lymphoma or leukaemia responded to cells engineered and made in Mumbai.","summary":"Open-label phase 1/2 study at six Indian tertiary centres enrolling 64 patients (14 phase 1, 50 phase 2) with relapsed or refractory B-cell lymphoma or B-ALL; phase 2 dose at least 5 x 10^6 CAR-T cells per kg (up to 2 x 10^9). Among 51 efficacy-evaluable patients (36 lymphoma, 15 B-ALL) the overall response rate was 73% (37 of 51; 95% CI 59-83). Grade 3 or worse neutropenia (96%), thrombocytopenia (65%) and anaemia (61%) were common; two deaths were treatment related. An accompanying commentary framed the approval as a model for CAR-T in lower-income countries.","asOf":"2026-09-10","links":[{"label":"Lancet Haematology 2025","url":"https://doi.org/10.1016/S2352-3026(24)00377-6"},{"label":"Commentary: CAR T-cell therapy in LMICs","url":"https://doi.org/10.1016/S2352-3026(25)00040-7"}],"tags":[],"related":[],"cancers":["dlbcl","all-leukemia"],"sections":[],"technologies":["car-t"],"targets":[],"drugs":["talicabtagene-autoleucel"],"companies":["immunoact"],"institutions":["tata-memorial","iit-bombay"],"pathways":[],"terms":[],"trials":["talicel-phase-1-2"],"people":["jain-hasmukh","narula-gaurav","purwar-rahul"],"bottlenecks":["b-manufacturing-cell-therapy","b-global-access"],"keyPapers":[],"journals":["lancet-haematology"],"dependsOn":[],"notes":[],"journal":"Lancet Haematology","year":2025,"doi":"10.1016/S2352-3026(24)00377-6","pmid":"40090352","authors":"Jain H, Karulkar A, Kalra D, et al.","paperType":"rct","findings":["Overall response rate 73% (37 of 51 evaluable patients).","Grade 3 or worse neutropenia in 96%, thrombocytopenia 65%, anaemia 61%.","Two treatment-related deaths (one with haemophagocytic lymphohistiocytosis and septic shock, one pulmonary bleed with cytokine release syndrome).","Product manufactured domestically with a humanised CD19 binder; approved by the DCGI in 2023."],"whatItMeans":"A lower-middle-income country can design, manufacture, trial and approve an autologous CAR-T therapy. Response rates are in the range of first-generation Western products in similar mixed populations, at a price an order of magnitude lower, which reopens the question of what CAR-T should cost everywhere.","caveats":["Single-arm, small, mixed histologies; durability data are short.","Response assessment and comparability to pivotal Western trials (which used disease-specific cohorts and complete response endpoints) are limited.","Haematological toxicity was very high and two deaths were treatment related; safety systems at 130-plus centres matter."],"changedPractice":true,"participants":64},{"id":"paper-nct06612151-n-engl-j-med-2026","kind":"paper","name":"Tambotatug Pelitecan in Small-Cell Lung Cancer after Platinum-Based Therapy","aka":[],"tldr":"Published report from the TAISHAN-302 trial registered as NCT06612151, in New England Journal of Medicine (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Tambotatug pelitecan (known as Tam-Peli, a new antibody-drug conjugate that targets the immune-checkpoint molecule B7-H3) showed promising clinical efficacy in patients with relapsed extensive-stage small-cell lung cancer in early-phase trials.\n\nMethods: In this phase 3, multicenter, open-label, randomized trial, we assigned eligible patients with small-cell lung cancer that had progressed after first-line platinum-based therapy in a 1:1 ratio to receive tambotatug pelitecan or topotecan. The primary end point was overall survival. The key secondary end points were progression-free survival and objective response as assessed by investigators. Here, we report the results from the prespecified interim analysis.\n\nResults: A total of 451 patients underwent randomization: 225 were assigned to receive tambotatug pelitecan and 226 to receive topotecan. Overall survival was significantly longer with tambotatug pelitecan than with topotecan - a median of 13.3 months (95% confidence interval [CI], 12.1 to could not be estimated), as compared with 9.4 months (95% CI, 7.7 to 10.5); the stratified hazard ratio for death was 0.46 (95% CI, 0.35 to 0.62; P<0.001). Treatment with tambotatug pelitecan also resulted in significantly longer progression-free survival than treatment with topotecan (median, 7.4 months [95% CI, 6.1 to 7.6] vs. 2.8 months [95% CI, 1.8 to 3.0]; stratified hazard ratio, 0.29 [95% CI, 0.23 to 0.37]; P<0.001). A confirmed objective response occurred in 59.1% of the patients in the tambotatug pelitecan group, as compared with 9.7% of those in the topotecan group (P<0.001). The overall incidence of adverse events of grade 3 or higher was lower with tambotatug pelitecan than with topotecan (55.4% vs. 77.9%).\n\nConclusions: Among patients with relapsed small-cell lung cancer after platinum-based therapy, treatment with tambotatug pelitecan resulted in longer overall survival, longer progression-free survival, and a higher percentage of patients with an objective response than treatment with topotecan, with a lower incidence of adverse events of grade 3 or higher. (Funded by the Innovative Drug Research and Development National Science and Technology Major Project and MediLink Therapeutics; TAISHAN-302 ClinicalTrials.gov number, NCT06612151.).\n\nIndexed on Europe PMC as PubMed record 42734213 (DOI 10.1056/nejmoa2610229). Its abstract cites the registry id NCT06612151, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2026","url":"https://doi.org/10.1056/nejmoa2610229"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42734213/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42734213"},{"label":"ClinicalTrials.gov NCT06612151","url":"https://clinicaltrials.gov/study/NCT06612151"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct06612151"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2026,"doi":"10.1056/nejmoa2610229","pmid":"42734213","authors":"Zhao Y, Liu H, Meng X, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT06612151 with the most citations, so it is the natural first reading for anyone following the TAISHAN-302 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-roberts-ph-like-all-nejm-2014","kind":"paper","name":"Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukaemia","aka":[],"tldr":"Sequencing showed that Ph-like acute lymphoblastic leukaemia, which behaves like Philadelphia-positive disease without the BCR-ABL1 fusion, is driven by a range of kinase-activating alterations, many of them potentially treatable with existing kinase inhibitors.","summary":"Genomic study of 1,725 patients with B-ALL identifying the Ph-like subtype in 15 percent of children and over 25 percent of young adults, with transcriptome and genome sequencing of 154 Ph-like cases revealing ABL-class fusions, CRLF2 rearrangements with JAK mutations, and other JAK-STAT and Ras pathway lesions; cell lines and patient-derived xenografts responded to matching kinase inhibitors.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2014","url":"https://doi.org/10.1056/NEJMoa1403088"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25207766/"}],"tags":[],"related":[],"cancers":["all-ph-like"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2014,"doi":"10.1056/NEJMoa1403088","pmid":"25207766","authors":"Roberts KG, Li Y, Payne-Turner D, et al.","paperType":"translational","findings":["Ph-like ALL frequency rises with age: about 10 percent of standard-risk children to over 25 percent of young adults.","Kinase-activating alterations in 91 percent of Ph-like cases; ABL-class fusions in about 13 percent."],"whatItMeans":"Screening for Ph-like ALL and its underlying kinase lesion is now part of high-risk ALL protocols, directing ABL-class cases to imatinib or dasatinib and JAK-pathway cases to ruxolitinib trials.","caveats":["Efficacy of kinase inhibitors in Ph-like ALL is still being established in trials."],"changedPractice":true,"participants":1725},{"id":"paper-nct03436485-nejm-evid-2024","kind":"paper","name":"Targeted Inhibition of CYP11A1 in Castration-Resistant Prostate Cancer","aka":[],"tldr":"Published report from the CYPIDES trial registered as NCT03436485, in NEJM Evidence (2024), chosen as the most cited paper whose own text cites the registry id.","summary":"BACKGROUND: Prostate cancer is regulated by steroid hormones, even in castration-resistant disease. ODM-208, a novel inhibitor of cytochrome P450 11A1 (which catalyzes the first step of steroid-hormone biosynthesis), was investigated in patients with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC). METHODS: CYPIDES is a first-in-human phase 1 (3 + 3 design) and phase 2 study. We administered ODM-208 twice daily with glucocorticoid/mineralocorticoid replacement and ongoing androgen deprivation therapy to adults with previously treated mCRPC, regardless of androgen receptor gene (AR) ligand-binding domain mutations (phase 1) and with activating AR ligand-binding domain mutations (ARmut; phase 2). Safety, pharmacokinetics, steroid-hormone pharmacodynamics, and preliminary efficacy were the key outcomes. RESULTS: Ninety-two patients received one or more doses of ODM-208: 47 in phase 1 (20 [42.6%] with ARmut) and 45 in phase 2 (all ARmut). A dose of ODM-208 of 5 mg twice a day with dexamethasone 1 mg/fludrocortisone 0.1 mg provided a balance between decreased steroidogenesis and toxicity. Treatment-related adrenal insufficiency was the most common toxicity in phase 1 (n=17, 36.2%; necessitating ODM-208 discontinuation in one patient); this toxicity occurred in six patients (13.3%) at 5 mg twice a day in phase 2. Median circulating testosterone levels declined from 3.0 ng/dl (interquartile range, 1.3 to 6.2 ng/dl) at baseline to undetectable levels within the first week of ODM-208 5 mg twice a day treatment in 46 of 53 (87%) patients. A decrease in prostate-specific antigen levels of 50% or more occurred in 14 of 19 (73.7%) patients with ARmut and 2 of 23 (8.7%) patients with AR wild type in phase 1 and in 24 of 45 (53.3%) patients with ARmut in phase 2. CONCLUSIONS: ODM-208 potently inhibited steroid-hormone biosynthesis with the expected toxicity of adrenal insufficiency. Evidence of antitumor activity was observed in this heavily pretreated mCRPC population, especially in those with ARmut. (Funded by Orion Pharma; ClinicalTrials.gov number, NCT03436485.)\n\nIndexed on Europe PMC as PubMed record 38320513 (DOI 10.1056/evidoa2300171). Its abstract cites the registry id NCT03436485, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"NEJM Evid 2024","url":"https://doi.org/10.1056/evidoa2300171"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38320513/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38320513"},{"label":"ClinicalTrials.gov NCT03436485","url":"https://clinicaltrials.gov/study/NCT03436485"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct03436485"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm-evidence"],"dependsOn":[],"notes":[],"journal":"NEJM Evidence","year":2024,"doi":"10.1056/evidoa2300171","pmid":"38320513","authors":"Fizazi K, Bernard-Tessier A, Roubaud G, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03436485 with the most citations, so it is the natural first reading for anyone following the CYPIDES trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-hainsworth-j-clin-oncol","kind":"paper","name":"Targeted Therapy for Advanced Solid Tumors on the Basis of Molecular Profiles: Results From MyPathway, an Open-Label, Phase IIa Multiple Basket Study","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 29320312 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose Detection of specific molecular alterations in tumors guides the selection of effective targeted treatment of patients with several types of cancer. These molecular alterations may occur in other tumor types for which the efficacy of targeted therapy remains unclear. The MyPathway study evaluates the efficacy and safety of selected targeted therapies in tumor types that harbor relevant genetic alterations but are outside of current labeling for these treatments. Methods MyPathway ( ClinicalTrials.gov identifier: NCT02091141) is a multicenter, nonrandomized, phase IIa multiple basket study. Patients with advanced refractory solid tumors harboring molecular alterations in human epidermal growth factor receptor-2, epidermal growth factor receptor, v-raf murine sarcoma viral oncogene homolog B1, or the Hedgehog pathway are treated with pertuzumab plus trastuzumab, erlotinib, vemurafenib, or vismodegib, respectively. The primary end point is investigator-assessed objective response rate within each tumor-pathway cohort. Results Between April 1, 2014 and November 1, 2016, 251 patients with 35 different tumor types received study treatment. The efficacy population contains 230 treated patients who were evaluated for response or discontinued treatment before evaluation. Fifty-two patients (23%) with 14 different tumor types had objective responses (complete, n = 4; partial, n = 48). Tumor-pathway cohorts with notable objective response rates included human epidermal growth factor receptor-2-amplified/overexpressing colorectal (38% [14 of 37]; 95% CI, 23% to 55%) and v-raf murine sarcoma viral oncogene homolog B1 V600-mutated non-small-cell lung cancer (43% [six of 14]; 95% CI, 18% to 71%). Conclusion The four currently approved targeted therapy regimens in the MyPathway study produced meaningful responses when administered without chemotherapy in several refractory solid tumor types not currently labeled for these agents.\n\nIndexed on Europe PMC as PubMed record 29320312 (DOI 10.1200/jco.2017.75.3780). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2018","url":"https://doi.org/10.1200/jco.2017.75.3780"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29320312/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29320312"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["mypathway"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2018,"doi":"10.1200/jco.2017.75.3780","pmid":"29320312","authors":"Hainsworth JD, Meric-Bernstam F, Swanton C, et al.","paperType":"basic","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-blinatumomab-all-leukemia-j-clin-oncol-2011","kind":"paper","name":"Targeted therapy with the T-cell-engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival","aka":[],"tldr":"Phase 2 or 3 results paper on Blinatumomab in Acute lymphoblastic leukaemia, in Journal of Clinical Oncology (2011), one of the most cited Europe PMC records with Blinatumomab in its title.","summary":"Purpose: Blinatumomab, a bispecific single-chain antibody targeting the CD19 antigen, is a member of a novel class of antibodies that redirect T cells for selective lysis of tumor cells. In acute lymphoblastic leukemia (ALL), persistence or relapse of minimal residual disease (MRD) after chemotherapy indicates resistance to chemotherapy and results in hematologic relapse. A phase II clinical study was conducted to determine the efficacy of blinatumomab in MRD-positive B-lineage ALL.\n\nPatients and methods: Patients with MRD persistence or relapse after induction and consolidation therapy were included. MRD was assessed by quantitative reverse transcriptase polymerase chain reaction for either rearrangements of immunoglobulin or T-cell receptor genes, or specific genetic aberrations. Blinatumomab was administered as a 4-week continuous intravenous infusion at a dose of 15 μg/m2/24 hours.\n\nResults: Twenty-one patients were treated, of whom 16 patients became MRD negative. One patient was not evaluable due to a grade 3 adverse event leading to treatment discontinuation. Among the 16 responders, 12 patients had been molecularly refractory to previous chemotherapy. Probability for relapse-free survival is 78% at a median follow-up of 405 days. The most frequent grade 3 and 4 adverse event was lymphopenia, which was completely reversible like most other adverse events.\n\nConclusion: Blinatumomab is an efficacious and well-tolerated treatment in patients with MRD-positive B-lineage ALL after intensive chemotherapy. T cells engaged by blinatumomab seem capable of eradicating chemotherapy-resistant tumor cells that otherwise cause clinical relapse.\n\nIndexed on Europe PMC as PubMed record 21576633 (DOI 10.1200/jco.2010.32.7270). Its title names Blinatumomab and its text names Acute lymphoblastic leukaemia; PubMed types it as a clinical trial report (Clinical Trial, Phase II, Research Support, Non-U.S. Gov't, Multicenter Study). It was matched automatically to the idea \"Menin inhibitors for infant KMT2A-rearranged ALL\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2011","url":"https://doi.org/10.1200/jco.2010.32.7270"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21576633/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/21576633"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2011,"doi":"10.1200/jco.2010.32.7270","pmid":"21576633","authors":"Topp MS, Kufer P, Gökbuget N, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Blinatumomab in Acute lymphoblastic leukaemia, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Blinatumomab in the title and Acute lymphoblastic leukaemia in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-lineweaver-bioessays","kind":"paper","name":"Targeting cancer's weaknesses (not its strengths): Therapeutic strategies suggested by the atavistic model","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 25043755 and published in BioEssays; the citing page links this DOI, which is how the record was matched.","summary":"In the atavistic model of cancer progression, tumor cell dedifferentiation is interpreted as a reversion to phylogenetically earlier capabilities. The more recently evolved capabilities are compromised first during cancer progression. This suggests a therapeutic strategy for targeting cancer: design challenges to cancer that can only be met by the recently evolved capabilities no longer functional in cancer cells. We describe several examples of this target-the-weakness strategy. Our most detailed example involves the immune system. The absence of adaptive immunity in immunosuppressed tumor environments is an irreversible weakness of cancer that can be exploited by creating a challenge that only the presence of adaptive immunity can meet. This leaves tumor cells more vulnerable than healthy tissue to pathogenic attack. Such a target-the-weakness therapeutic strategy has broad applications, and contrasts with current therapies that target the main strength of cancer: cell proliferation.\n\nIndexed on Europe PMC as PubMed record 25043755 (DOI 10.1002/bies.201400070). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Bioessays 2014","url":"https://doi.org/10.1002/bies.201400070"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25043755/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25043755"}],"tags":["europepmc-ingest"],"related":["atavistic-theory-of-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"BioEssays","year":2014,"doi":"10.1002/bies.201400070","pmid":"25043755","authors":"Lineweaver CH, Davies PC, Vincent MD","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-feig-cxcl12-fap-cafs-t-cell-exclusion-pnas-2013","kind":"paper","name":"Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer","aka":[],"tldr":"Mice with pancreatic cancer had tumour-specific T cells but did not respond to checkpoint drugs; the fibroblasts were coating the cancer cells with a chemical, CXCL12, that kept T cells away, and blocking it let the T cells in and made anti-PD-L1 work.","summary":"An autochthonous model of pancreatic ductal adenocarcinoma allowed analysis of why immunotherapy is ineffective. Despite cancer cell-specific CD8 T cells, mice did not respond to anti-CTLA-4 or anti-PD-L1. Depleting FAP-expressing carcinoma-associated fibroblasts achieved immune control and uncovered the antitumour effects of both checkpoint antagonists. T cells were absent from regions containing cancer cells, cancer cells were coated with CXCL12, and the FAP-positive CAF was the principal source of it. AMD3100, a CXCR4 inhibitor, induced rapid T-cell accumulation among cancer cells and acted synergistically with anti-PD-L1, leaving a residual tumour of premalignant epithelial and inflammatory cells.","asOf":"2026-09-24","links":[{"label":"Feig et al., PNAS 2013: CXCL12 from FAP-positive fibroblasts excludes T cells and blocks checkpoint therapy","url":"https://doi.org/10.1073/pnas.1320318110"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24277834/"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":["fap","cxcr4","pdl1","ctla4"],"drugs":[],"companies":[],"institutions":["cruk-cambridge-centre"],"pathways":["immune-desert-exclusion","caf-activation-desmoplasia","pd1-checkpoint"],"terms":["immune-exclusion","cold-vs-hot"],"trials":[],"people":["david-tuveson"],"bottlenecks":[],"keyPapers":[],"journals":["pnas"],"dependsOn":[],"notes":[],"journal":"PNAS","year":2013,"doi":"10.1073/pnas.1320318110","pmid":"24277834","authors":"Feig C, Jones JO, Kraman M, et al.","paperType":"basic","findings":["FAP-positive CAFs are the principal source of CXCL12, which coats cancer cells and excludes T cells.","CXCR4 inhibition let T cells in and synergised with anti-PD-L1."],"whatItMeans":"The mechanistic account of T-cell exclusion that all later combination immunotherapy trials in pancreatic cancer cite, and the origin of CXCR4 inhibitor combinations.","caveats":["Mouse model; human CXCR4 inhibitor trials have been small.","FAP depletion is not clinically available."],"changedPractice":false},{"id":"paper-ezh2-sarcoma-biochem-pharmacol-2023","kind":"paper","name":"Targeting EZH2 in SMARCB1-deficient sarcomas: Advances and opportunities to potentiate the efficacy of EZH2 inhibitors","aka":[],"tldr":"Review on EZH2 in Sarcomas, in Biochemical pharmacology (2023), one of the most cited Europe PMC records with EZH2 in its title.","summary":"Soft tissue sarcomas (STSs) are rare mesechymal malignancies characterized by distintive molecular, histological and clinical features. Many STSs are considered as predominatly epigenetic diseases due to underlying chromatin deregulation. Discovery of deregulated functional antagonism between the chromatin remodeling BRG1/BRM-associated (BAFs) and the histone modifying Polycomb repressor complexes (PRCs) has provided novel actionable targets. In epithelioid sarcoma (ES), extracranial, extrarenal malignant rhabdoid tumors (eMRTs) and synovial sarcoma (SS), the total or partial loss of the BAF core subunit SMARCB1, driven by different alterations, is associated with PRC2 deregulation and dependency on its enzymatic subunit, EZH2. In these SMARCB1-deficient STSs, aberrant EZH2 expression and/or activity emerged as a druggable vulnerability. Although preclinical investigation supported EZH2 targeting as a promising therapeutic option, clinical studies demonstrated a variable response to EZH2 inhibitors. Actually, whereas the clinical benefit recorded in ES patients prompted the FDA approval of the EZH2 inhibitor tazemetostat, the modest and sporadic responses observed in eMRT and SS patients highlighted the need to deepen mechanistic as well as pharmacological investigations to improve drug effectiveness. We summarize the current knowledge of different mechanisms driving SMARCB1 deficiency and EZH2 deregulation in ES, eMRT and SS along with preclinical and clinical studies of EZH2-targeting agents. Possible implication of the PRC2- and enzymatic-independent functions of EZH2 and of its homolog, EZH1, in the response to anti-EZH2 agents will be discussed together with combinatorial strategies under investigation to improve the efficacy of EZH2 targeting in these tumors.\n\nIndexed on Europe PMC as PubMed record 37541451 (DOI 10.1016/j.bcp.2023.115727). Its title names EZH2 and its text names Sarcomas; PubMed types it as a review (Research Support, Non-U.S. Gov't, Review). It was matched automatically to the idea \"Group trials by broken mechanism, not by organ or single mutation\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Biochem Pharmacol 2023","url":"https://doi.org/10.1016/j.bcp.2023.115727"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37541451/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37541451"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Biochemical pharmacology","year":2023,"doi":"10.1016/j.bcp.2023.115727","pmid":"37541451","authors":"Lanzi C, Arrighetti N, Pasquali S, et al.","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for EZH2 in Sarcomas, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by EZH2 in the title and Sarcomas in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-steeg-nat-rev-cancer","kind":"paper","name":"Targeting metastasis","aka":[],"tldr":"Paper cited by one bottleneck page, indexed on Europe PMC as PubMed record 27009393 and published in Nature Reviews Cancer; the citing page links this DOI, which is how the record was matched.","summary":"Tumour metastasis, the movement of tumour cells from a primary site to progressively colonize distant organs, is a major contributor to the deaths of cancer patients. Therapeutic goals are the prevention of an initial metastasis in high-risk patients, shrinkage of established lesions and prevention of additional metastases in patients with limited disease. Instead of being autonomous, tumour cells engage in bidirectional interactions with metastatic microenvironments to alter antitumour immunity, the extracellular milieu, genomic stability, survival signalling, chemotherapeutic resistance and proliferative cycles. Can targeting of these interactions significantly improve patient outcomes? In this Review preclinical research, combination therapies and clinical trial designs are re-examined.\n\nIndexed on Europe PMC as PubMed record 27009393 (DOI 10.1038/nrc.2016.25). Matched by DOI alone: one bottleneck page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Cancer 2016","url":"https://doi.org/10.1038/nrc.2016.25"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27009393/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27009393"}],"tags":["europepmc-ingest"],"related":["b-metastasis-biology"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Cancer","year":2016,"doi":"10.1038/nrc.2016.25","pmid":"27009393","authors":"Steeg PS","paperType":"review","findings":[],"whatItMeans":"One bottleneck page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-ashkenazi-j-clin-invest","kind":"paper","name":"Targeting the extrinsic apoptotic pathway in cancer: lessons learned and future directions","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 25642709 and published in Journal of Clinical Investigation; the citing page links this DOI, which is how the record was matched.","summary":"Apoptosis is a metazoan process of controlled cell elimination that plays critical roles in embryonic development and adult tissue homeostasis. Apoptosis dysregulation contributes to several important diseases, including cancer. Two distinct yet interconnected signaling pathways control apoptosis by activating a core intracellular machinery of death proteases called caspases. The intrinsic apoptotic pathway engages caspases via members of the BCL-2 protein family and the mitochondria in reaction to severe cellular damage or stress. The extrinsic pathway activates caspases via cell-surface death receptors, which respond to cognate death ligands expressed on immune-effector cells. Tumor cells can acquire various apoptosis-evasion mechanisms; nevertheless, the transformed state of these cells makes them uniquely susceptible to apoptosis reactivation if resistance is circumvented. Molecular approaches to reengage the apoptotic pathways in cancer have been underway for over two decades. Gratifyingly, BCL-2 antagonists - which drive the intrinsic pathway - are beginning to bear clinical fruit. In contrast, clinical attempts to stimulate the extrinsic pathway with proapoptotic receptor agonists (PARAs) have been disappointing, despite compelling preclinical efficacy with this class of agents. Here, I discuss some of the possible reasons for this translational discrepancy and suggest strategies to overcome it with the next generation of PARAs.\n\nIndexed on Europe PMC as PubMed record 25642709 (DOI 10.1172/jci80420). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Invest 2015","url":"https://doi.org/10.1172/jci80420"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25642709/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25642709"}],"tags":["europepmc-ingest"],"related":["extrinsic-apoptosis-death-receptors"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jci"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Investigation","year":2015,"doi":"10.1172/jci80420","pmid":"25642709","authors":"Ashkenazi A","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-tarlatamab-sclc-n-engl-j-med-2025","kind":"paper","name":"Tarlatamab in Small-Cell Lung Cancer after Platinum-Based Chemotherapy","aka":[],"tldr":"Phase 2 or 3 results paper on Tarlatamab in Small-cell lung cancer, in New England Journal of Medicine (2025), one of the most cited Europe PMC records with Tarlatamab in its title.","summary":"Background: Tarlatamab, a bispecific delta-like ligand 3-directed T-cell engager immunotherapy, received accelerated approval for the treatment of patients with previously treated small-cell lung cancer. Whether tarlatamab is more effective than chemotherapy in the treatment of patients whose small-cell lung cancer has progressed during or after initial platinum-based chemotherapy is not known.\n\nMethods: We conducted a multinational, phase 3, open-label trial to compare tarlatamab with chemotherapy as second-line treatment in patients with small-cell lung cancer whose disease had progressed during or after platinum-based chemotherapy. Patients were randomly assigned to receive tarlatamab or chemotherapy (topotecan, lurbinectedin, or amrubicin). The primary end point was overall survival. Key secondary end points were investigator-assessed progression-free survival and patient-reported outcomes. Results of the prespecified interim analysis (data-cutoff date, January 29, 2025) are reported.\n\nResults: A total of 509 patients were randomly assigned to receive tarlatamab (254 patients) or chemotherapy (255 patients). Treatment with tarlatamab resulted in significantly longer overall survival than chemotherapy (median, 13.6 months [95% confidence interval {CI}, 11.1 to not reached] vs. 8.3 months [95% CI, 7.0 to 10.2]; stratified hazard ratio for death, 0.60; 95% CI, 0.47 to 0.77; P<0.001). Tarlatamab treatment also had a significant benefit with respect to progression-free survival and cancer-related dyspnea and cough as compared with chemotherapy. The incidence of adverse events of grade 3 or higher was lower with tarlatamab than with chemotherapy (54% vs. 80%), as was the incidence of adverse events resulting in treatment discontinuation (5% vs. 12%).\n\nConclusions: Treatment with tarlatamab led to longer overall survival than chemotherapy among patients with small-cell lung cancer whose disease had progressed during or after platinum-based chemotherapy. (Funded by Amgen; DeLLphi-304 ClinicalTrials.gov number, NCT05740566.).\n\nIndexed on Europe PMC as PubMed record 40454646 (DOI 10.1056/nejmoa2502099). Its title names Tarlatamab and its text names Small-cell lung cancer; PubMed types it as a clinical trial report (Clinical Trial, Phase III, Comparative Study, Multicenter Study, Randomized Controlled Trial). It was matched automatically to the idea \"Subtype-directed therapy for SCLC (ASCL1 / NEUROD1 / POU2F3 / inflamed)\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2025","url":"https://doi.org/10.1056/nejmoa2502099"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40454646/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40454646"},{"label":"ClinicalTrials.gov NCT05740566","url":"https://clinicaltrials.gov/study/NCT05740566"}],"tags":["europepmc-ingest"],"related":["lung-cancer-evidence-roadmap","paper-dellphi-301-nejm-2023"],"cancers":["lung-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["dellphi-304"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2025,"doi":"10.1056/nejmoa2502099","pmid":"40454646","authors":"Mountzios G, Sun L, Cho BC, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Tarlatamab in Small-cell lung cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Tarlatamab in the title and Small-cell lung cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-tannock-tax-327-docetaxel-prednisone-nejm-2004","kind":"paper","name":"TAX 327: docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer","aka":["TAX 327","Tannock 2004 docetaxel prostate"],"tldr":"The first treatment ever shown to help men live longer once prostate cancer stopped responding to hormones. Docetaxel every three weeks added about two and a half months to median survival compared with the older drug, and made pain and quality of life better as well.","summary":"Ian Tannock and colleagues randomised 1,006 men with metastatic hormone-refractory prostate cancer, all taking 5 mg of prednisone twice daily, to mitoxantrone every three weeks, docetaxel every three weeks, or weekly docetaxel. The primary endpoint was overall survival, with pain, prostate-specific antigen and quality of life as secondary endpoints, each compared against mitoxantrone.\n\nMitoxantrone had been approved in 1996 on palliation alone: it relieved pain and did not extend life. TAX 327 is where prostate cancer got a drug that did both, and where the three-weekly schedule beat the weekly one, which is why the three-weekly schedule is the one still used. Twenty years later docetaxel is given much earlier, at the first diagnosis of metastatic disease, on the strength of CHAARTED and STAMPEDE.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2004","url":"https://doi.org/10.1056/nejmoa040720"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/15470213/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/15470213"}],"tags":["prostate-evidence"],"related":["paper-petrylak-swog-9916-docetaxel-estramustine-nejm-2004","paper-de-bono-tropic-cabazitaxel-lancet-2010","paper-chaarted-nejm-2015","chemotherapy-roadmap","prostate-roadmap"],"cancers":["prostate","prostate-mcrpc"],"sections":["chemotherapy"],"technologies":[],"targets":[],"drugs":["docetaxel","mitoxantrone","prednisone"],"companies":[],"institutions":[],"pathways":[],"terms":["castration-resistance","psa","quality-of-life","hazard-ratio"],"trials":[],"people":["ian-tannock","nicholas-james"],"bottlenecks":["b-resistance","b-toxicity-qol"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2004,"doi":"10.1056/nejmoa040720","pmid":"15470213","authors":"Tannock IF, de Wit R, Berry WR, et al.","paperType":"rct","findings":["Median survival 16.5 months with mitoxantrone, 18.9 months with docetaxel every three weeks and 17.4 months with weekly docetaxel.","Hazard ratio for death with three-weekly docetaxel 0.76 (95 percent confidence interval 0.62 to 0.94; P equals 0.009); with weekly docetaxel 0.91 (0.75 to 1.11; P equals 0.36).","A decrease in serum prostate-specific antigen of at least 50 percent in 32 percent, 45 percent and 48 percent of the three groups respectively (P less than 0.001 for both docetaxel comparisons).","Predefined reductions in pain in 22 percent, 35 percent (P equals 0.01) and 31 percent (P equals 0.08).","Improvements in quality of life in 13 percent, 22 percent (P equals 0.009) and 23 percent (P equals 0.005); adverse events were more common in the docetaxel groups."],"whatItMeans":"The end of therapeutic nihilism in castration-resistant prostate cancer. It is also the trial that set the field's expectation of what a positive result looks like in this disease: a hazard ratio near 0.75 and a median gain measured in months, not years.","caveats":["Median survival gain of 2.4 months against mitoxantrone, at the cost of more adverse events.","The control was mitoxantrone, a drug approved for palliation and never shown to extend survival, so the comparison is against a low bar.","The trial population was fitter than the average man with castration-resistant disease; performance status 2 patients were a minority."],"changedPractice":true,"participants":1006},{"id":"paper-gounder-lancet-oncol","kind":"paper","name":"Tazemetostat in advanced epithelioid sarcoma with loss of INI1/SMARCB1: an international, open-label, phase 2 basket study","aka":[],"tldr":"Paper cited by one cancer page and one trial page, indexed on Europe PMC as PubMed record 33035459 and published in The Lancet Oncology; the citing pages link this DOI, which is how the record was matched.","summary":"Background: Epithelioid sarcoma is a rare and aggressive soft-tissue sarcoma subtype. Over 90% of tumours have lost INI1 expression, leading to oncogenic dependence on the transcriptional repressor EZH2. In this study, we report the clinical activity and safety of tazemetostat, an oral selective EZH2 inhibitor, in patients with epithelioid sarcoma.\n\nMethods: In this open-label, phase 2 basket study, patients were enrolled from 32 hospitals and clinics in Australia, Belgium, Canada, France, Germany, Italy, Taiwan, the USA, and the UK into seven cohorts of patients with different INI1-negative solid tumours or synovial sarcoma. Patients eligible for the epithelioid sarcoma cohort (cohort 5) were aged 16 years or older with histologically confirmed, locally advanced or metastatic epithelioid sarcoma; documented loss of INI1 expression by immunohistochemical analysis or biallelic SMARCB1 (the gene that encodes INI1) alterations, or both; and an Eastern Cooperative Oncology Group performance status score of 0-2. Patients received 800 mg tazemetostat orally twice per day in continuous 28-day cycles until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was investigator-assessed objective response rate measured according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary endpoints were duration of response, disease control rate at 32 weeks, progression-free survival, overall survival, and pharmacokinetic and pharmacodynamic analyses (primary results reported elsewhere). Time to response was also assessed as an exploratory endpoint. Activity and safety were assessed in the modified intention-to-treat population (ie, patients who received one or more doses of tazemetostat). This trial is registered with ClinicalTrials.gov, NCT02601950, and is ongoing.\n\nFindings: Between Dec 22, 2015, and July 7, 2017, 62 patients with epithelioid sarcoma were enrolled in the study and deemed eligible for inclusion in this cohort. All 62 patients were included in the modified intention-to-treat analysis. Nine (15% [95% CI 7-26]) of 62 patients had an objective response at data cutoff (Sept 17, 2018). At a median follow-up of 13·8 months (IQR 7·8-19·0), median duration of response was not reached (95% CI 9·2-not estimable). 16 (26% [95% CI 16-39]) patients had disease control at 32 weeks. Median time to response was 3·9 months (IQR 1·9-7·4). Median progression-free survival was 5·5 months (95% CI 3·4-5·9), and median overall survival was 19·0 months (11·0-not estimable). Grade 3 or worse treatment-related adverse events included anaemia (four [6%]) and weight loss (two [3%]). Treatment-related serious adverse events occurred in two patients (one seizure and one haemoptysis). There were no treatment-related deaths.\n\nInterpretation: Tazemetostat was well tolerated and showed clinical activity in this cohort of patients with advanced epithelioid sarcoma characterised by loss of INI1/SMARCB1. Tazemetostat has the potential to improve outcomes in patients with advanced epithelioid sarcoma. A phase 1b/3 trial of tazemetostat plus doxorubicin in the front-line setting is currently underway (NCT04204941).\n\nFunding: Epizyme.\n\nIndexed on Europe PMC as PubMed record 33035459 (DOI 10.1016/s1470-2045(20)30451-4). Matched by DOI alone: one cancer page and one trial page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2020","url":"https://doi.org/10.1016/s1470-2045(20)30451-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33035459/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33035459"}],"tags":["europepmc-ingest"],"related":["epithelioid-sarcoma"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["tazemetostat-doxorubicin-es"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2020,"doi":"10.1016/s1470-2045(20)30451-4","pmid":"33035459","authors":"Gounder M, Schöffski P, Jones RL, et al.","paperType":"rct","findings":[],"whatItMeans":"One cancer page and one trial page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-tcga-pancancer-atlas-cell-2018","kind":"paper","name":"TCGA Pan-Cancer Atlas: 10,000 tumours across 33 cancer types, classified by molecular features","aka":[],"tldr":"The capstone of The Cancer Genome Atlas integrated DNA, RNA, protein and methylation data on about 10,000 tumours, showing that cell of origin dominates molecular classification but that some cancers regroup across organs.","summary":"The Pan-Cancer Atlas was a set of 27 papers in Cell Press journals in April 2018 summarising a decade of TCGA. The flagship classification paper (Hoadley et al.) integrated five data types on 9,759 tumours from 33 cancer types and identified 28 molecular clusters. Most clusters were dominated by tissue of origin, but squamous cancers from different organs grouped together, as did gastrointestinal adenocarcinomas and kidney cancers of different histologies.\n\nCompanion papers catalogued 299 driver genes and over 3,400 driver mutations (Bailey et al.), showed that 89% of tumours had at least one driver alteration in ten canonical signalling pathways and 57% had at least one potentially targetable alteration (Sanchez-Vega et al.), and characterised immune subtypes, oncogenic processes and cell-of-origin patterns.\n\nTCGA data, freely available through the Genomic Data Commons, became the reference against which nearly every cancer genomics study is compared.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1016/j.cell.2018.03.022"},{"label":"Driver genes (Bailey 2018)","url":"https://doi.org/10.1016/j.cell.2018.02.060"},{"label":"NCI Genomic Data Commons","url":"https://portal.gdc.cancer.gov"}],"tags":[],"related":["tcga-gdc","paper-vogelstein-cancer-genome-landscapes-science-2013"],"cancers":[],"sections":["diagnostics","drug-discovery"],"technologies":["wes-wgs","rna-seq","methylation-profiling","cgp"],"targets":[],"drugs":[],"companies":[],"institutions":["nci","broad-institute"],"pathways":[],"terms":["mutational-signature","tmb","pam50"],"trials":[],"people":["gad-getz"],"bottlenecks":["b-data-silos","b-tumor-heterogeneity","b-trial-diversity"],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Cell","year":2018,"doi":"10.1016/j.cell.2018.03.022","pmid":"29625048","authors":"Hoadley KA, Yau C, Hinoue T, et al. (The Cancer Genome Atlas Network)","paperType":"basic","findings":["9,759 tumours from 33 cancer types integrated across mRNA, miRNA, DNA methylation, copy number and protein data","28 iCluster molecular subtypes; about two-thirds dominated by tissue of origin, with cross-tissue clusters for squamous and pan-gastrointestinal cancers","Companion paper: 299 driver genes, of which about half were not previously in curated driver lists (Bailey et al.)","Companion paper: 89% of tumours had at least one alteration in ten signalling pathways; 57% had a potentially actionable alteration (Sanchez-Vega et al.)"],"whatItMeans":"Cancers are defined as much by the tissue they come from as by the mutations they carry, which is why the same drug can work in one organ and fail in another with the same mutation. TCGA is the shared public dataset behind most modern biomarkers and target discovery.","caveats":["Primary, untreated tumours only; metastatic and post-treatment biology are under-represented","Predominantly white US patients; ancestry diversity is limited","Bulk tissue profiling averages over heterogeneity later revealed by single-cell and spatial methods","Actionability estimates count alterations with any drug evidence, not proven clinical benefit"],"changedPractice":false,"participants":10000},{"id":"paper-tcga-molecular-taxonomy-primary-prostate-cell-2015","kind":"paper","name":"TCGA: the molecular taxonomy of primary prostate cancer","aka":["TCGA prostate 2015","molecular taxonomy primary prostate cancer","seven subtypes prostate"],"tldr":"The Cancer Genome Atlas classified 333 prostate cancers taken out at surgery and found that three quarters fall into one of seven groups defined by a fusion or a mutation. A quarter had a change that a drug could in principle be aimed at, and one in five had a broken DNA repair gene.","summary":"The Cancer Genome Atlas Research Network profiled 333 primary prostate carcinomas across DNA, RNA, methylation and protein, and defined a taxonomy in which 74 percent of tumours belong to one of seven subtypes: the fusions ERG, ETV1, ETV4 and FLI1, and the mutations SPOP, FOXA1 and IDH1.\n\nAndrogen receptor activity varied widely and in a subtype-specific way, with SPOP and FOXA1 mutant tumours showing the highest androgen receptor-induced transcription. Twenty-five percent had a presumed actionable lesion in the PI3K or MAPK pathways, and DNA repair genes were inactivated in 19 percent, which is the finding that seeds the PARP inhibitor and platinum work in this disease. Roughly a quarter of primary prostate cancers still fall outside all seven subtypes, which is a candid statement of how much remains unclassified.","asOf":"2026-09-25","links":[{"label":"Cell 2015","url":"https://doi.org/10.1016/j.cell.2015.10.025"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26544944/"},{"label":"TCGA PRAD at the NCI Genomic Data Commons","url":"https://portal.gdc.cancer.gov/projects/TCGA-PRAD"},{"label":"cBioPortal study prad_tcga_pub (TCGA, Cell 2015; the 333 primary tumours of the published molecular taxonomy)","url":"https://www.cbioportal.org/study/summary?id=prad_tcga_pub"},{"label":"cBioPortal study prad_tcga_pan_can_atlas_2018 (TCGA PanCancer Atlas; 494 sequenced primary prostate adenocarcinomas, 489 with copy number, 494 with structural variants)","url":"https://www.cbioportal.org/study/summary?id=prad_tcga_pan_can_atlas_2018"}],"tags":["prostate-evidence"],"related":["paper-robinson-integrative-clinical-genomics-advanced-prostate-cell-2015","paper-taylor-integrative-genomic-profiling-cancer-cell-2010","paper-capitello-281-ann-oncol-2026","prostate-roadmap"],"cancers":["prostate","prostate-high-risk"],"sections":["diagnostics","targeted-therapy"],"technologies":["wes-wgs","rna-seq"],"targets":["spop","foxa1","erg","tmprss2","pten","pik3ca","androgen-receptor","brca","etv1","idh","tp53"],"drugs":[],"companies":[],"institutions":[],"pathways":["prostate-cancer-signalling","ar-signaling","pi3k-akt-mtor","ubiquitin-proteasome-system","epigenetic-reprogramming"],"terms":["hrd","ngs","gene-fusion","driver-mutation","gleason-grade-group","somatic-mutations-wxs-wgs"],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation","b-tumor-heterogeneity","b-data-silos"],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Cell","year":2015,"doi":"10.1016/j.cell.2015.10.025","pmid":"26544944","authors":"Cancer Genome Atlas Research Network.","paperType":"basic","findings":["74 percent of 333 primary prostate carcinomas fell into one of seven subtypes defined by gene fusions (ERG, ETV1, ETV4, FLI1) or mutations (SPOP, FOXA1, IDH1).","Epigenetic profiles showed substantial heterogeneity, including an IDH1 mutant subset with a methylator phenotype.","Androgen receptor activity varied widely and in a subtype-specific manner, with SPOP and FOXA1 mutant tumours having the highest levels of androgen receptor-induced transcripts.","25 percent of the prostate cancers had a presumed actionable lesion in the PI3K or MAPK signalling pathways.","DNA repair genes were inactivated in 19 percent of tumours."],"whatItMeans":"The reference classification of prostate cancer as it presents, and the source of the two numbers that drive most molecular treatment decisions in the disease: a quarter with a PI3K or MAPK lesion, which is the rationale for capivasertib in PTEN-deficient disease, and a fifth with DNA repair inactivation, which is the rationale for PARP inhibitors.","caveats":["Primary tumours from men fit for radical prostatectomy, so it does not describe metastatic or castration-resistant disease; Robinson 2015 does that.","Presumed actionable is a bioinformatic judgement, not a demonstrated response to a drug.","26 percent of tumours fit none of the seven subtypes and remain unclassified."],"changedPractice":false,"participants":333},{"id":"paper-tebentafusp-melanoma-cancers-basel-2019","kind":"paper","name":"Tebentafusp: T Cell Redirection for the Treatment of Metastatic Uveal Melanoma","aka":[],"tldr":"Review on Tebentafusp in Melanoma, in Cancers (2019), one of the most cited Europe PMC records with Tebentafusp in its title.","summary":"Metastatic disease from uveal melanoma occurs in almost 50% of patients suffering from this ocular tumour, with median survival from development of symptoms being around 1 year. In contrast to cutaneous melanoma, kinase inhibitors and immune checkpoint inhibitors are usually ineffective in patients with metastatic uveal melanoma. Tebentafusp is a novel form of immunotherapy based on the immune-mobilising monoclonal T cell receptor against cancer (ImmTAC) platform, which comprises a soluble T cell receptor that is fused to an anti-CD3 single-chain variable fragment. The T cell receptor domain of tebentafusp targets cells present a human leukocyte antigen-A*02:01 complexed with a peptide derived from the melanoma-associated antigen gp100, which is expressed strongly by melanoma cells, weakly by normal melanocytes and minimally by other tissues. The anti-CD3 domain recruits CD3+ T cells (and, indirectly, other immune cells), redirecting these to the melanoma cells. The most common adverse events with tebentafusp are manageable and usually transient. Early survival data in patients with metastatic uveal melanoma are promising when considered alongside historical data. Based on these encouraging results, a randomised study comparing tebentafusp to investigator's choice of therapy in metastatic uveal melanoma is ongoing.\n\nIndexed on Europe PMC as PubMed record 31336704 (DOI 10.3390/cancers11070971). Its title names Tebentafusp and its text names Melanoma; PubMed types it as a review (review-article, Review). It was matched automatically to the idea \"TCR therapeutics for non-HLA-A*02 patients\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancers (Basel) 2019","url":"https://doi.org/10.3390/cancers11070971"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31336704/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31336704"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancers-mdpi"],"dependsOn":[],"notes":[],"journal":"Cancers","year":2019,"doi":"10.3390/cancers11070971","pmid":"31336704","authors":"Damato BE, Dukes J, Goodall H, et al.","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for Tebentafusp in Melanoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Tebentafusp in the title and Melanoma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-zon-jco-oncol-pract","kind":"paper","name":"Telehealth in Oncology: ASCO Standards and Practice Recommendations","aka":[],"tldr":"Paper cited by two technology pages, indexed on Europe PMC as PubMed record 34319760 and published in JCO Oncology Practice; the citing pages link this DOI, which is how the record was matched.","summary":"Purpose: To provide standards and practice recommendations specific to telehealth in oncology.\n\nMethods: A systematic review of the literature on telehealth in oncology was performed, including the use of technologies and telecommunications systems, and other electronic methods of care delivery and sharing of information with patients. The evidence base was combined with the opinion of the ASCO Telehealth Expert Panel to develop telehealth standards and guidance. Public comments were solicited and considered in preparation of the final manuscript.\n\nResults: The Expert Panel determined that general guidance on implementing telehealth across general and specialty settings has been published previously and these resources are endorsed. A systematic search for studies on topics specific to oncology resulted in the inclusion of two clinical practice guidelines, 12 systematic reviews, and six primary studies.\n\nStandards and guidance: Standards and guidance are provided for which patients in oncology can be seen via telehealth, establishment of the doctor-physician relationship, role of allied health professionals, role of advanced practice providers, multidisciplinary cancer conferences, and teletrials in oncology. Additional information is available at www.asco.org/standards.\n\nIndexed on Europe PMC as PubMed record 34319760 (DOI 10.1200/op.21.00438). Matched by DOI alone: two technology pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JCO Oncol Pract 2021","url":"https://doi.org/10.1200/op.21.00438"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34319760/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34319760"}],"tags":["europepmc-ingest"],"related":["telehealth-oncology","telemedicine-teleoncology"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco-oncology-practice"],"dependsOn":[],"notes":[],"journal":"JCO Oncology Practice","year":2021,"doi":"10.1200/op.21.00438","pmid":"34319760","authors":"Zon RT, Kennedy EB, Adelson K, et al.","paperType":"review","findings":[],"whatItMeans":"Two technology pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-greer-jama","kind":"paper","name":"Telehealth vs In-Person Early Palliative Care for Patients With Advanced Lung Cancer: A Multisite Randomized Clinical Trial","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 39259563 and published in JAMA; the citing page links this DOI, which is how the record was matched.","summary":"Importance: Numerous studies show that early palliative care improves quality of life and other key outcomes in patients with advanced cancer and their caregivers, although most lack access to this evidence-based model of care.\n\nObjective: To evaluate whether delivering early palliative care via secure video vs in-person visits has an equivalent effect on quality of life in patients with advanced non-small cell lung cancer (NSCLC).\n\nDesign, setting, and participants: Randomized, multisite, comparative effectiveness trial from June 14, 2018, to May 4, 2023, at 22 US cancer centers among 1250 patients within 12 weeks of diagnosis of advanced NSCLC and 548 caregivers.\n\nIntervention: Participants were randomized to meet with a specialty-trained palliative care clinician every 4 weeks either via video visit or in person in the outpatient clinic from the time of enrollment and throughout the course of disease. The video visit group had an initial in-person visit to establish rapport, followed by subsequent virtual visits.\n\nMain outcomes and measures: Equivalence of the effect of video visit vs in-person early palliative care on quality of life at week 24 per the Functional Assessment of Cancer Therapy-Lung questionnaire (equivalence margin of ±4 points; score range: 0-136, with higher scores indicating better quality of life). Participants completed study questionnaires at enrollment and at weeks 12, 24, 36, and 48.\n\nResults: By 24 weeks, participants (mean age, 65.5 years; 54.0% women; 82.7% White) had a mean of 4.7 (video) and 4.9 (in-person) early palliative care encounters. Patient-reported quality-of-life scores were equivalent between groups (video mean, 99.7 vs in-person mean, 97.7; difference, 2.0 [90% CI, 0.1-3.9]; P =.04 for equivalence). Rate of caregiver participation in visits was lower for video vs in-person early palliative care (36.6% vs 49.7%; P <.001). Study groups did not differ in caregiver quality of life, patient coping, or patient and caregiver satisfaction with care, mood symptoms, or prognostic perceptions.\n\nConclusions and relevance: The delivery of early palliative care virtually vs in person demonstrated equivalent effects on quality of life in patients with advanced NSCLC, underscoring the considerable potential for improving access to this evidence-based care model through telehealth delivery.\n\nTrial registration: ClinicalTrials.gov Identifier: NCT03375489.\n\nIndexed on Europe PMC as PubMed record 39259563 (DOI 10.1001/jama.2024.13964). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA 2024","url":"https://doi.org/10.1001/jama.2024.13964"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39259563/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39259563"}],"tags":["europepmc-ingest"],"related":["telehealth-oncology"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2024,"doi":"10.1001/jama.2024.13964","pmid":"39259563","authors":"Greer JA, Temel JS, El-Jawahri A, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-luminosity-jto-clin-res-rep-2026-update","kind":"paper","name":"Telisotuzumab Vedotin Monotherapy in Patients With Previously Treated c-Met Protein Overexpressing, Nonsquamous, EGFR Wild-type Advanced NSCLC: Updated Analysis of the LUMINOSITY Trial","aka":[],"tldr":"Later report from the LUMINOSITY trial registered as NCT03539536, in JTO clinical and research reports (2026); its title describes an updated or longer-term analysis.","summary":"Introduction: Telisotuzumab vedotin (Teliso-V) is a c-Met-directed antibody-drug conjugate comprising the monoclonal antibody telisotuzumab and the monomethyl auristatin E payload. Primary analysis of the phase 2 LUMINOSITY trial (NCT03539536) revealed Teliso-V monotherapy 1.9 mg/kg elicited durable responses and had generally manageable safety in patients with locally advanced or metastatic c-Met protein overexpressing, EGFR wild-type, nonsquamous NSCLC. We present updated outcomes with approximately 6 months longer follow-up and explore the impact of previous therapies.\n\nMethods: Patients (≥18 y; had previous therapy including ≤1 chemotherapy) received 1.9 mg/kg Teliso-V every 2 weeks. c-Met protein overexpression (clinical trial assay for MET [SP44] [Roche]) was defined as greater than or equal to 25% tumor cells with 3+ staining intensity (c-Met high: ≥50% 3+; c-Met intermediate: 25 to <50% 3+). Primary end point was the overall response rate by independent central review per the Response Evaluation Criteria in Solid Tumors version 1.1.\n\nResults: at February 21, 2024, 172 patients received at least one dose of Teliso-V; 168 patients (c-Met high, n = 84; c-Met intermediate, n = 84) were evaluable for efficacy. The overall response rate was 29.2% (95% confidence interval [CI]: 22.4-36.7; c-Met high, 34.5% [24.5-45.7]; c-Met intermediate, 23.8% [15.2-34.3]). Median duration of response was 7.2 months (95% CI: 5.5-11.0; c-Met high, 7.2 [95% CI: 4.2-12.0]; c-Met intermediate, 7.2 [95% CI: 4.7-11.5]). Previous therapy (platinum, immune checkpoint inhibitors, or both) did not impact efficacy outcomes. The most common treatment-related adverse event was peripheral sensory neuropathy (any-grade: 31%; grade ≥3: 7%).\n\nConclusions: Teliso-V monotherapy 1.9 mg/kg elicited durable responses, irrespective of the type of previous therapy received, and maintained a manageable safety profile in patients with c-Met protein overexpressing EGFR wild-type, nonsquamous NSCLC.\n\nClinicaltrialsgov id number: NCT03539536.\n\nIndexed on Europe PMC as PubMed record 42368479 (DOI 10.1016/j.jtocrr.2026.100988). Its abstract cites the registry id NCT03539536, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"JTO Clin Res Rep 2026","url":"https://doi.org/10.1016/j.jtocrr.2026.100988"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42368479/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42368479"},{"label":"ClinicalTrials.gov NCT03539536","url":"https://clinicaltrials.gov/study/NCT03539536"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["luminosity"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"JTO clinical and research reports","year":2026,"doi":"10.1016/j.jtocrr.2026.100988","pmid":"42368479","authors":"Girard N, Goldman J, Lu S, et al.","paperType":"observational","findings":[],"whatItMeans":"A second publication from the LUMINOSITY trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-luminosity-j-clin-oncol-2024","kind":"paper","name":"Telisotuzumab Vedotin Monotherapy in Patients With Previously Treated c-Met Protein-Overexpressing Advanced Nonsquamous EGFR -Wildtype Non-Small Cell Lung Cancer in the Phase II LUMINOSITY Trial","aka":[],"tldr":"Published report from the LUMINOSITY trial registered as NCT03539536, in Journal of Clinical Oncology (2024), chosen as the most cited paper whose own text cites the registry id.","summary":"Purpose: Telisotuzumab vedotin (Teliso-V) is a c-Met-directed antibody-drug conjugate with a monomethyl auristatin E cytotoxic payload. The phase II LUMINOSITY trial (ClinicalTrials.gov identifier: NCT03539536) aimed to identify the optimal c-Met protein-overexpressing non-small cell lung cancer (NSCLC) population for treatment with Teliso-V (stage I) and expand the selected group for efficacy evaluation (stage II). Stage II enrolled patients with nonsquamous epidermal growth factor receptor ( EGFR)-wildtype NSCLC.\n\nMethods: Eligible patients had locally advanced/metastatic c-Met protein-overexpressing NSCLC and ≤2 previous lines of therapy (including ≤1 line of systemic chemotherapy). c-Met protein overexpression in nonsquamous EGFR -wildtype NSCLC was defined as ≥25% tumor cells with 3+ staining (high [≥50% 3+]; intermediate [≥25%-<50%]). Teliso-V was administered at 1.9 mg/kg once every 2 weeks. The primary end point was overall response rate (ORR) by independent central review.\n\nResults: In total, 172 patients with nonsquamous EGFR -wildtype NSCLC received Teliso-V in stages I and II. ORR was 28.6% (95% CI, 21.7 to 36.2; c-Met high, 34.6% [95% CI, 24.2 to 46.2]; c-Met intermediate, 22.9% [95% CI, 14.4 to 33.4]). The median duration of response was 8.3 months (95% CI, 5.6 to 11.3; c-Met high, 9.0 [95% CI, 4.2 to 13.0]; c-Met intermediate: 7.2 [95% CI, 5.3 to 11.5]). The median overall survival was 14.5 months (95% CI, 9.9 to 16.6; c-Met high, 14.6 [95% CI, 9.2 to 25.6]; c-Met intermediate, 14.2 [95% CI, 9.6 to 16.6]). The median progression-free survival was 5.7 months (95% CI, 4.6 to 6.9; c-Met high, 5.5 [95% CI, 4.1 to 8.3]; c-Met intermediate: 6.0 [95% CI, 4.5 to 8.1]). Most common any-grade treatment-related adverse events (AEs) were peripheral sensory neuropathy (30%), peripheral edema (16%), and fatigue (14%); the most common grade ≥3 AE was peripheral sensory neuropathy (7%).\n\nConclusion: Teliso-V was associated with durable responses in c-Met protein-overexpressing nonsquamous EGFR -wildtype NSCLC, especially in those with high c-Met. AEs were generally manageable.\n\nIndexed on Europe PMC as PubMed record 38843488 (DOI 10.1200/jco.24.00720). Its abstract cites the registry id NCT03539536, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2024","url":"https://doi.org/10.1200/jco.24.00720"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38843488/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38843488"},{"label":"ClinicalTrials.gov NCT03539536","url":"https://clinicaltrials.gov/study/NCT03539536"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["luminosity"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2024,"doi":"10.1200/jco.24.00720","pmid":"38843488","authors":"Camidge DR, Bar J, Horinouchi H, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03539536 with the most citations, so it is the natural first reading for anyone following the LUMINOSITY trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-shay-nat-rev-genet","kind":"paper","name":"Telomeres and telomerase: three decades of progress","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 30760854 and published in Nature reviews. Genetics; the citing page links this DOI, which is how the record was matched.","summary":"Many recent advances have emerged in the telomere and telomerase fields. This Timeline article highlights the key advances that have expanded our views on the mechanistic underpinnings of telomeres and telomerase and their roles in ageing and disease. Three decades ago, the classic view was that telomeres protected the natural ends of linear chromosomes and that telomerase was a specific telomere-terminal transferase necessary for the replication of chromosome ends in single-celled organisms. While this concept is still correct, many diverse fields associated with telomeres and telomerase have substantially matured. These areas include the discovery of most of the key molecular components of telomerase, implications for limits to cellular replication, identification and characterization of human genetic disorders that result in premature telomere shortening, the concept that inhibiting telomerase might be a successful therapeutic strategy and roles for telomeres in regulating gene expression. We discuss progress in these areas and conclude with challenges and unanswered questions in the field.\n\nIndexed on Europe PMC as PubMed record 30760854 (DOI 10.1038/s41576-019-0099-1). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Genet 2019","url":"https://doi.org/10.1038/s41576-019-0099-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30760854/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30760854"}],"tags":["europepmc-ingest"],"related":["telomere-maintenance"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature reviews. Genetics","year":2019,"doi":"10.1038/s41576-019-0099-1","pmid":"30760854","authors":"Shay JW, Wright WE","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-temel-early-palliative-care-nejm-2010","kind":"paper","name":"Temel: early palliative care alongside chemotherapy improved quality of life, mood and survival in lung cancer","aka":[],"tldr":"Patients newly diagnosed with metastatic lung cancer who saw a palliative care team from diagnosis had better quality of life, less depression, less aggressive end-of-life care and lived a median 2.7 months longer than those receiving oncology care alone.","summary":"At Massachusetts General Hospital, 151 patients with newly diagnosed metastatic non-small-cell lung cancer were randomised to early palliative care integrated with standard oncology care (monthly visits with a palliative care clinician) or to standard oncology care with palliative care only on request.\n\nThe primary endpoint, change in quality of life at 12 weeks (FACT-L), favoured early palliative care (98.0 vs 91.5). Fewer patients had depressive symptoms (16% vs 38%), fewer received aggressive end-of-life care (33% vs 54%), and median survival was 11.6 versus 8.9 months.\n\nThe survival signal overturned the assumption that palliative care shortens life and led ASCO to recommend concurrent palliative care for all patients with metastatic cancer from diagnosis.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1056/NEJMoa1000678"},{"label":"ClinicalTrials.gov NCT01038271","url":"https://clinicaltrials.gov/study/NCT01038271"}],"tags":[],"related":["hospice-end-of-life","idea-moon-palliative-care-from-diagnosis-everywhere","idea-acc-automatic-early-palliative-triggers","idea-acc-tele-palliative-care-default"],"cancers":["nsclc"],"sections":["supportive-care"],"technologies":["palliative-care","epro-symptom-monitoring"],"targets":[],"drugs":[],"companies":[],"institutions":["mgh"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-palliative","b-workforce","b-toxicity-qol"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2010,"doi":"10.1056/NEJMoa1000678","pmid":"20818875","authors":"Temel JS, Greer JA, Muzikansky A, et al.","paperType":"rct","findings":["Quality of life at 12 weeks: FACT-L 98.0 vs 91.5 (p = 0.03)","Depressive symptoms 16% vs 38% (p = 0.01)","Aggressive end-of-life care 33% vs 54%; more patients documented resuscitation preferences","Median overall survival 11.6 vs 8.9 months (p = 0.02) despite less chemotherapy near death"],"whatItMeans":"Palliative care is not what happens when treatment stops; it works best alongside cancer treatment from the start. Patients feel better, are less depressed and may live longer. Access remains the constraint: most of the world's patients never see a palliative care specialist.","caveats":["Single centre, unblinded, and survival was not the primary endpoint; later trials showed mixed survival effects","Small sample; the survival difference was not confirmed in the larger 2017 Temel trial across cancers","Requires trained palliative care workforce that most health systems lack","Mechanism (symptom control, less futile chemotherapy, better decision-making) remains debated"],"changedPractice":true,"participants":151},{"id":"paper-baumert-lancet-oncol","kind":"paper","name":"Temozolomide chemotherapy versus radiotherapy in high-risk low-grade glioma (EORTC 22033-26033): a randomised, open-label, phase 3 intergroup study","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 27686946 and published in The Lancet Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background: Outcome of low-grade glioma (WHO grade II) is highly variable, reflecting molecular heterogeneity of the disease. We compared two different, single-modality treatment strategies of standard radiotherapy versus primary temozolomide chemotherapy in patients with low-grade glioma, and assessed progression-free survival outcomes and identified predictive molecular factors.\n\nMethods: For this randomised, open-label, phase 3 intergroup study (EORTC 22033-26033), undertaken in 78 clinical centres in 19 countries, we included patients aged 18 years or older who had a low-grade (WHO grade II) glioma (astrocytoma, oligoastrocytoma, or oligodendroglioma) with at least one high-risk feature (aged >40 years, progressive disease, tumour size >5 cm, tumour crossing the midline, or neurological symptoms), and without known HIV infection, chronic hepatitis B or C virus infection, or any condition that could interfere with oral drug administration. Eligible patients were randomly assigned (1:1) to receive either conformal radiotherapy (up to 50·4 Gy; 28 doses of 1·8 Gy once daily, 5 days per week for up to 6·5 weeks) or dose-dense oral temozolomide (75 mg/m 2 once daily for 21 days, repeated every 28 days [one cycle], for a maximum of 12 cycles). Random treatment allocation was done online by a minimisation technique with prospective stratification by institution, 1p deletion (absent vs present vs undetermined), contrast enhancement (yes vs no), age (<40 vs ≥40 years), and WHO performance status (0 vs ≥1). Patients, treating physicians, and researchers were aware of the assigned intervention. A planned analysis was done after 216 progression events occurred. Our primary clinical endpoint was progression-free survival, analysed by intention-to-treat; secondary outcomes were overall survival, adverse events, neurocognitive function (will be reported separately), health-related quality of life and neurological function (reported separately), and correlative analyses of progression-free survival by molecular markers (1p/19q co-deletion, MGMT promoter methylation status, and IDH1/IDH2 mutations). This trial is closed to accrual but continuing for follow-up, and is registered at the European Trials Registry, EudraCT 2004-002714-11, and at ClinicalTrials.gov, NCT00182819.\n\nFindings: Between Sept 23, 2005, and March 26, 2010, 707 patients were registered for the study. Between Dec 6, 2005, and Dec 21, 2012, we randomly assigned 477 patients to receive either radiotherapy (n=240) or temozolomide chemotherapy (n=237). At a median follow-up of 48 months (IQR 31-56), median progression-free survival was 39 months (95% CI 35-44) in the temozolomide group and 46 months (40-56) in the radiotherapy group (unadjusted hazard ratio [HR] 1·16, 95% CI 0·9-1·5, p=0·22). Median overall survival has not been reached. Exploratory analyses in 318 molecularly-defined patients confirmed the significantly different prognosis for progression-free survival in the three recently defined molecular low-grade glioma subgroups (IDHmt, with or without 1p/19q co-deletion [IDHmt/codel], or IDH wild type [IDHwt]; p=0·013). Patients with IDHmt/non-codel tumours treated with radiotherapy had a longer progression-free survival than those treated with temozolomide (HR 1·86 [95% CI 1·21-2·87], log-rank p=0·0043), whereas there were no significant treatment-dependent differences in progression-free survival for patients with IDHmt/codel and IDHwt tumours. Grade 3-4 haematological adverse events occurred in 32 (14%) of 236 patients treated with temozolomide and in one (<1%) of 228 patients treated with radiotherapy, and grade 3-4 infections occurred in eight (3%) of 236 patients treated with temozolomide and in two (1%) of 228 patients treated with radiotherapy. Moderate to severe fatigue was recorded in eight (3%) patients in the radiotherapy group (grade 2) and 16 (7%) in the temozolomide group. 119 (25%) of all 477 patients had died at database lock. Four patients died due to treatment-related causes: two in the temozolomide group and two in the radiotherapy group.\n\nInterpretation: Overall, there was no significant difference in progression-free survival in patients with low-grade glioma when treated with either radiotherapy alone or temozolomide chemotherapy alone. Further data maturation is needed for overall survival analyses and evaluation of the full predictive effects of different molecular subtypes for future individualised treatment choices.\n\nFunding: Merck Sharpe & Dohme-Merck & Co, Canadian Cancer Society, Swiss Cancer League, UK National Institutes of Health, Australian National Health and Medical Research Council, US National Cancer Institute, European Organisation for Research and Treatment of Cancer Cancer Research Fund.\n\nIndexed on Europe PMC as PubMed record 27686946 (DOI 10.1016/s1470-2045(16)30313-8). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2016","url":"https://doi.org/10.1016/s1470-2045(16)30313-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27686946/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27686946"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["eortc-22033"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2016,"doi":"10.1016/s1470-2045(16)30313-8","pmid":"27686946","authors":"Baumert BG, Hegi ME, van den Bent MJ, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-malmstrom-lancet-oncol","kind":"paper","name":"Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 22877848 and published in The Lancet Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background: Most patients with glioblastoma are older than 60 years, but treatment guidelines are based on trials in patients aged only up to 70 years. We did a randomised trial to assess the optimum palliative treatment in patients aged 60 years and older with glioblastoma.\n\nMethods: Patients with newly diagnosed glioblastoma were recruited from Austria, Denmark, France, Norway, Sweden, Switzerland, and Turkey. They were assigned by a computer-generated randomisation schedule, stratified by centre, to receive temozolomide (200 mg/m(2) on days 1-5 of every 28 days for up to six cycles), hypofractionated radiotherapy (34·0 Gy administered in 3·4 Gy fractions over 2 weeks), or standard radiotherapy (60·0 Gy administered in 2·0 Gy fractions over 6 weeks). Patients and study staff were aware of treatment assignment. The primary endpoint was overall survival. Analyses were done by intention to treat. This trial is registered, number ISRCTN81470623.\n\nFindings: 342 patients were enrolled, of whom 291 were randomised across three treatment groups (temozolomide n=93, hypofractionated radiotherapy n=98, standard radiotherapy n=100) and 51 of whom were randomised across only two groups (temozolomide n=26, hypofractionated radiotherapy n=25). In the three-group randomisation, in comparison with standard radiotherapy, median overall survival was significantly longer with temozolomide (8·3 months [95% CI 7·1-9·5; n=93] vs 6·0 months [95% CI 5·1-6·8; n=100], hazard ratio [HR] 0·70; 95% CI 0·52-0·93, p=0·01), but not with hypofractionated radiotherapy (7·5 months [6·5-8·6; n=98], HR 0·85 [0·64-1·12], p=0·24). For all patients who received temozolomide or hypofractionated radiotherapy (n=242) overall survival was similar (8·4 months [7·3-9·4; n=119] vs 7·4 months [6·4-8·4; n=123]; HR 0·82, 95% CI 0·63-1·06; p=0·12). For age older than 70 years, survival was better with temozolomide and with hypofractionated radiotherapy than with standard radiotherapy (HR for temozolomide vs standard radiotherapy 0·35 [0·21-0·56], p<0·0001; HR for hypofractionated vs standard radiotherapy 0·59 [95% CI 0·37-0·93], p=0·02). Patients treated with temozolomide who had tumour MGMT promoter methylation had significantly longer survival than those without MGMT promoter methylation (9·7 months [95% CI 8·0-11·4] vs 6·8 months [5·9-7·7]; HR 0·56 [95% CI 0·34-0·93], p=0·02), but no difference was noted between those with methylated and unmethylated MGMT promoter treated with radiotherapy (HR 0·97 [95% CI 0·69-1·38]; p=0·81). As expected, the most common grade 3-4 adverse events in the temozolomide group were neutropenia (n=12) and thrombocytopenia (n=18). Grade 3-5 infections in all randomisation groups were reported in 18 patients. Two patients had fatal infections (one in the temozolomide group and one in the standard radiotherapy group) and one in the temozolomide group with grade 2 thrombocytopenia died from complications after surgery for a gastrointestinal bleed.\n\nInterpretation: Standard radiotherapy was associated with poor outcomes, especially in patients older than 70 years. Both temozolomide and hypofractionated radiotherapy should be considered as standard treatment options in elderly patients with glioblastoma. MGMT promoter methylation status might be a useful predictive marker for benefit from temozolomide.\n\nFunding: Merck, Lion's Cancer Research Foundation, University of Umeå, and the Swedish Cancer Society.\n\nIndexed on Europe PMC as PubMed record 22877848 (DOI 10.1016/s1470-2045(12)70265-6). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2012","url":"https://doi.org/10.1016/s1470-2045(12)70265-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22877848/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/22877848"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["cctg-ce6"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2012,"doi":"10.1016/s1470-2045(12)70265-6","pmid":"22877848","authors":"Malmström A, Grønberg BH, Marosi C, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-paszek-cancer-cell","kind":"paper","name":"Tensional homeostasis and the malignant phenotype","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 16169468 and published in Cancer Cell; the citing page links this DOI, which is how the record was matched.","summary":"Tumors are stiffer than normal tissue, and tumors have altered integrins. Because integrins are mechanotransducers that regulate cell fate, we asked whether tissue stiffness could promote malignant behavior by modulating integrins. We found that tumors are rigid because they have a stiff stroma and elevated Rho-dependent cytoskeletal tension that drives focal adhesions, disrupts adherens junctions, perturbs tissue polarity, enhances growth, and hinders lumen formation. Matrix stiffness perturbs epithelial morphogenesis by clustering integrins to enhance ERK activation and increase ROCK-generated contractility and focal adhesions. Contractile, EGF-transformed epithelia with elevated ERK and Rho activity could be phenotypically reverted to tissues lacking focal adhesions if Rho-generated contractility or ERK activity was decreased. Thus, ERK and Rho constitute part of an integrated mechanoregulatory circuit linking matrix stiffness to cytoskeletal tension through integrins to regulate tissue phenotype.\n\nIndexed on Europe PMC as PubMed record 16169468 (DOI 10.1016/j.ccr.2005.08.010). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer Cell 2005","url":"https://doi.org/10.1016/j.ccr.2005.08.010"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/16169468/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/16169468"}],"tags":["europepmc-ingest"],"related":["mechanical-theory-of-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-cell"],"dependsOn":[],"notes":[],"journal":"Cancer Cell","year":2005,"doi":"10.1016/j.ccr.2005.08.010","pmid":"16169468","authors":"Paszek MJ, Zahir N, Johnson KR, et al.","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nct02864992-jama-oncol-2023-update","kind":"paper","name":"Tepotinib Treatment in Patients With MET Exon 14-Skipping Non-Small Cell Lung Cancer: Long-term Follow-up of the VISION Phase 2 Nonrandomized Clinical Trial","aka":[],"tldr":"Later report from the trial registered as NCT02864992, in JAMA Oncology (2023); its title describes an updated or longer-term analysis.","summary":"Importance: MET inhibitors have recently demonstrated clinical activity in patients with MET exon 14 (METex14)-skipping non-small cell lung cancer (NSCLC); however, data with longer follow-up and in larger populations are needed to further optimize therapeutic approaches.\n\nObjective: To assess the long-term efficacy and safety of tepotinib, a potent and highly selective MET inhibitor, in patients with METex14-skipping NSCLC in the VISION study.\n\nDesign, setting, and participants: The VISION phase 2 nonrandomized clinical trial was a multicohort, open-label, multicenter study that enrolled patients with METex14-skipping advanced/metastatic NSCLC (cohorts A and C) from September 2016 to May 2021. Cohort C (>18 months' follow-up) was an independent cohort, designed to confirm findings from cohort A (>35 months' follow-up). Data cutoff was November 20, 2022.\n\nIntervention: Patients received tepotinib, 500 mg (450 mg active moiety), once daily.\n\nMain outcomes and measures: The primary end point was objective response by independent review committee (RECIST v1.1). Secondary end points included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.\n\nResults: Cohorts A and C included 313 patients (50.8% female, 33.9% Asian; median [range] age, 72 [41-94] years). The objective response rate (ORR) was 51.4% (95% CI, 45.8%-57.1%) with a median (m)DOR of 18.0 (95% CI, 12.4-46.4) months. In cohort C (n = 161), an ORR of 55.9% (95% CI, 47.9%-63.7%) with an mDOR of 20.8 (95% CI, 12.6-not estimable [NE]) months was reported across treatment lines, comparable to cohort A (n = 152). In treatment-naive patients (cohorts A and C; n = 164), ORR was 57.3% (95% CI, 49.4%-65.0%) and mDOR was 46.4 (95% CI, 13.8-NE) months. In previously treated patients (n = 149), ORR was 45.0% (95% CI, 36.8%-53.3%) and mDOR was 12.6 (95% CI, 9.5-18.5) months. Peripheral edema, the most common treatment-related adverse event, occurred in 210 patients (67.1%) (35 [11.2%] experienced grade ≥3 events).\n\nConclusions and relevance: The findings from cohort C in this nonrandomized clinical trial supported the results from original cohort A. Overall, the long-term outcomes of VISION demonstrated robust and durable clinical activity following treatment with tepotinib, particularly in the treatment-naive setting, in the largest known clinical trial of patients with METex14-skipping NSCLC, supporting the global approvals of tepotinib and enabling clinicians to implement this therapeutic approach for such patients.\n\nTrial registration: ClinicalTrials.gov Identifier: NCT02864992.\n\nIndexed on Europe PMC as PubMed record 37270698 (DOI 10.1001/jamaoncol.2023.1962). Its abstract cites the registry id NCT02864992, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"JAMA Oncol 2023","url":"https://doi.org/10.1001/jamaoncol.2023.1962"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37270698/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37270698"},{"label":"ClinicalTrials.gov NCT02864992","url":"https://clinicaltrials.gov/study/NCT02864992"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct02864992"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2023,"doi":"10.1001/jamaoncol.2023.1962","pmid":"37270698","authors":"Mazieres J, Paik PK, Garassino MC, et al.","paperType":"observational","findings":[],"whatItMeans":"A second publication from the trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-crockett-nagtegaal-serrated-neoplasia-gastroenterology-2019","kind":"paper","name":"Terminology, molecular features, epidemiology, and management of serrated colorectal neoplasia","aka":[],"tldr":"A review that fixed the names, counted how common serrated polyps are, and explained why they are missed: they are flat, pale and proximal, and finding them depends on how carefully the endoscopist looks.","summary":"In addition to the adenoma-to-carcinoma sequence, colorectal carcinogenesis can occur through the serrated pathway. World Health Organization guidelines assign serrated polyps to hyperplastic polyps, traditional serrated adenomas and sessile serrated lesions, the latter two being precursors of colorectal cancer. The serrated pathway is characterised by mutations in RAS and RAF, disruption of WNT signalling and widespread methylation of CpG islands. The prevalence of serrated-class polyps is 20 to 40% in average-risk individuals, most of them hyperplastic; sessile serrated lesions, the most common premalignant serrated subtype, are found in up to 15% of average-risk patients by high-detecting endoscopists. Variation in endoscopic detection rates points to the need for careful examination with adequate bowel preparation and sufficient withdrawal time. Risk factors for sessile serrated lesions include white race, family history of colorectal cancer, smoking and alcohol intake, and patients with serrated polyps have an increased risk of synchronous and metachronous advanced neoplasia.","asOf":"2026-09-24","links":[{"label":"Crockett and Nagtegaal, Gastroenterology 2019: terminology, molecular features, epidemiology and management of serrated colorectal neoplasia","url":"https://doi.org/10.1053/j.gastro.2019.06.041"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31323292/"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":[],"targets":["braf","kras","rnf43"],"drugs":[],"companies":[],"institutions":["radboudumc"],"pathways":["epigenetic-reprogramming","wnt","ras-mapk"],"terms":["colonoscopy","msi"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["gastroenterology"],"dependsOn":[],"notes":[],"journal":"Gastroenterology","year":2019,"doi":"10.1053/j.gastro.2019.06.041","pmid":"31323292","authors":"Crockett SD, Nagtegaal ID.","paperType":"review","findings":["Serrated-class polyps in 20 to 40% of average-risk people; sessile serrated lesions in up to 15% with high-detecting endoscopists.","WNT disruption in the serrated pathway arrives through methylation and RNF43 rather than APC.","Serrated polyp detection varies widely between endoscopists."],"whatItMeans":"It links the molecular route to the practical failure mode: interval cancers after a clear colonoscopy are disproportionately serrated, so detection quality is a molecular problem as much as a technical one.","caveats":["A review; prevalence estimates depend heavily on the endoscopist and the pathologist.","Surveillance intervals for sessile serrated lesions differ between countries."],"changedPractice":false},{"id":"paper-tauriello-tgfbeta-immune-evasion-colorectal-nature-2018","kind":"paper","name":"TGF-beta drives immune evasion in genetically reconstituted colon cancer metastasis","aka":[],"tldr":"Mice given all four of the main bowel cancer mutations grew tumours that spread and, like most human bowel cancers, ignored immunotherapy. Blocking TGF-beta let the immune system in, stopped the spread, and made the tumours answer checkpoint drugs.","summary":"Mice bearing conditional alleles of four main colorectal cancer mutations in intestinal stem cells were crossed to analyse the interplay between genetic alterations and the tumour microenvironment. Quadruple-mutant mice developed metastatic intestinal tumours displaying key hallmarks of human microsatellite-stable colorectal cancer, including low mutational burden, T-cell exclusion and TGF-beta-activated stroma. Inhibition of the PD-1 and PD-L1 checkpoint provoked only a limited response. Inhibition of TGF-beta unleashed a potent and enduring cytotoxic T-cell response against tumour cells that prevented metastasis, and in mice with progressive liver metastatic disease, blockade of TGF-beta signalling rendered tumours susceptible to anti-PD-1 and anti-PD-L1 therapy. Increased TGF-beta in the microenvironment therefore represents a primary mechanism of immune evasion that promotes T-cell exclusion and blocks acquisition of the T-helper-1 effector phenotype.","asOf":"2026-09-24","links":[{"label":"Tauriello et al., Nature 2018: TGF-beta drives immune evasion in genetically reconstituted colon cancer metastasis","url":"https://doi.org/10.1038/nature25492"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29443964/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29443964"}],"tags":[],"related":["tgf-beta"],"cancers":["colorectal"],"sections":[],"technologies":[],"targets":["tgfb1","pd1","apc","kras","tp53","smad4"],"drugs":[],"companies":[],"institutions":[],"pathways":["tgf-beta","immune-desert-exclusion","pd1-checkpoint","metastatic-cascade"],"terms":["cold-vs-hot","immune-exclusion","mss-pmmr"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2018,"doi":"10.1038/nature25492","pmid":"29443964","authors":"Tauriello DVF, Palomo-Ponce S, Stork D, et al.","paperType":"basic","findings":["Quadruple-mutant mice reproduce microsatellite-stable human disease: low mutational burden, T-cell exclusion, TGF-beta-activated stroma.","PD-1 or PD-L1 blockade alone gave only a limited response.","TGF-beta inhibition prevented metastasis and made liver metastases susceptible to checkpoint blockade."],"whatItMeans":"It is the clearest mechanistic answer to why microsatellite-stable colorectal cancer resists immunotherapy, and the rationale for every TGF-beta plus checkpoint combination now in trials in this disease.","caveats":["Mouse genetics; no clinical trial has yet reproduced the effect in patients.","TGF-beta blockade carries cardiac and epithelial toxicity that has limited the clinical agents."],"changedPractice":false},{"id":"paper-mariathasan-nature","kind":"paper","name":"TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells","aka":[],"tldr":"Paper cited by one term page and one idea page, indexed on Europe PMC as PubMed record 29443960 and published in Nature; the citing pages link this DOI, which is how the record was matched.","summary":"Therapeutic antibodies that block the programmed death-1 (PD-1)-programmed death-ligand 1 (PD-L1) pathway can induce robust and durable responses in patients with various cancers, including metastatic urothelial cancer. However, these responses only occur in a subset of patients. Elucidating the determinants of response and resistance is key to improving outcomes and developing new treatment strategies. Here we examined tumours from a large cohort of patients with metastatic urothelial cancer who were treated with an anti-PD-L1 agent (atezolizumab) and identified major determinants of clinical outcome. Response to treatment was associated with CD8 + T-effector cell phenotype and, to an even greater extent, high neoantigen or tumour mutation burden. Lack of response was associated with a signature of transforming growth factor β (TGFβ) signalling in fibroblasts. This occurred particularly in patients with tumours, which showed exclusion of CD8 + T cells from the tumour parenchyma that were instead found in the fibroblast- and collagen-rich peritumoural stroma; a common phenotype among patients with metastatic urothelial cancer. Using a mouse model that recapitulates this immune-excluded phenotype, we found that therapeutic co-administration of TGFβ-blocking and anti-PD-L1 antibodies reduced TGFβ signalling in stromal cells, facilitated T-cell penetration into the centre of tumours, and provoked vigorous anti-tumour immunity and tumour regression. Integration of these three independent biological features provides the best basis for understanding patient outcome in this setting and suggests that TGFβ shapes the tumour microenvironment to restrain anti-tumour immunity by restricting T-cell infiltration.\n\nIndexed on Europe PMC as PubMed record 29443960 (DOI 10.1038/nature25501). Matched by DOI alone: one term page and one idea page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2018","url":"https://doi.org/10.1038/nature25501"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29443960/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29443960"}],"tags":["europepmc-ingest"],"related":["immune-exclusion","idea-immune-exclusion-drivers"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2018,"doi":"10.1038/nature25501","pmid":"29443960","authors":"Mariathasan S, Turley SJ, Nickles D, et al.","paperType":"observational","findings":[],"whatItMeans":"One term page and one idea page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-who-2019-digestive-system-tumours-nagtegaal-histopathology-2020","kind":"paper","name":"The 2019 WHO classification of tumours of the digestive system","aka":[],"tldr":"The current WHO rulebook for cancers of the gut, which among other changes renamed goblet cell carcinoid as goblet cell adenocarcinoma, adopted the LAMN terminology for appendiceal tumours and re-graded neuroendocrine neoplasms.","summary":"Overview by the WHO Classification of Tumours Editorial Board of the fifth-edition digestive system volume, summarising changes across oesophagus, stomach, small bowel, appendix, colorectum, liver, biliary tract and pancreas.\n\nFor the appendix it adopts low-grade and high-grade appendiceal mucinous neoplasm and reclassifies goblet cell carcinoid as goblet cell adenocarcinoma with a three-tier grade; it also separates neuroendocrine tumours from neuroendocrine carcinomas and introduces molecular subtypes across sites.","asOf":"2026-09-18","links":[{"label":"Histopathology 2020","url":"https://doi.org/10.1111/his.13975"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31433515/"}],"tags":[],"related":[],"cancers":["low-grade-appendiceal-mucinous-neoplasm","appendiceal-adenocarcinoma","goblet-cell-adenocarcinoma","localised-small-bowel-adenocarcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Histopathology","year":2020,"doi":"10.1111/his.13975","pmid":"31433515","authors":"Nagtegaal ID, Odze RD, Klimstra D, et al.","paperType":"review","findings":[],"whatItMeans":"The names on an appendix or small bowel pathology report, and hence which OnCo subtype page applies, follow this classification.","caveats":["The summary paper describes the changes; the full volume holds the diagnostic criteria.","Some renamings (goblet cell adenocarcinoma) are still working through registries and older literature."],"changedPractice":true},{"id":"paper-who-2021-cns-louis-neuro-oncology-2021","kind":"paper","name":"The 2021 WHO classification of tumours of the central nervous system: a summary","aka":[],"tldr":"The fifth-edition brain tumour classification makes molecular markers such as IDH mutation, 1p/19q codeletion and methylation class central to diagnosis, renaming and regrading many tumours, including separating IDH-mutant astrocytoma from glioblastoma.","summary":"Summary of the 2021 WHO classification of central nervous system tumours introducing integrated histological and molecular diagnoses, Arabic numeral grading within tumour types, new tumour types and families (paediatric-type diffuse gliomas, molecularly defined ependymomas and medulloblastoma groups), and grading of IDH-mutant astrocytoma up to grade 4 with CDKN2A/B deletion.","asOf":"2026-09-17","links":[{"label":"Neuro Oncol 2021","url":"https://doi.org/10.1093/neuonc/noab106"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34185076/"}],"tags":[],"related":[],"cancers":["idh-mutant-astrocytoma","oligodendroglioma","meningioma","paediatric-high-grade-glioma","spinal-cord-tumours","cns-germ-cell-tumours","medulloblastoma-group-3-4","medulloblastoma-shh","medulloblastoma-wnt"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["neuro-oncology"],"dependsOn":[],"notes":[],"journal":"Neuro-Oncology","year":2021,"doi":"10.1093/neuonc/noab106","pmid":"34185076","authors":"Louis DN, Perry A, Wesseling P, et al.","paperType":"guideline","findings":[],"whatItMeans":"Every brain tumour page on this site uses these names and grades; a tumour called glioblastoma before 2021 may now be an IDH-mutant astrocytoma with a different outlook and treatment.","caveats":["Requires molecular testing that is not available everywhere, leaving some diagnoses as not otherwise specified."],"changedPractice":true},{"id":"paper-who-2021-thymus-mediastinum-classification-marx-jto-2022","kind":"paper","name":"The 2021 WHO classification of tumours of the thymus and mediastinum: what is new in thymic epithelial, germ cell and mesenchymal tumours","aka":[],"tldr":"The current WHO scheme for thymic tumours, which keeps the type A to B3 thymoma letters and the separate category of thymic carcinoma while adding new molecular entities.","summary":"Summary by members of the WHO editorial board of the fifth-edition classification of thymic and mediastinal tumours: thymoma types A, AB, B1, B2 and B3 and their rarer variants, thymic carcinomas (squamous, basaloid, mucoepidermoid, lymphoepithelial, NUT carcinoma and others), thymic neuroendocrine neoplasms, and mediastinal germ cell and mesenchymal tumours.\n\nIt highlights immunohistochemical and molecular markers (such as GTF2I mutations in type A and AB thymomas and NUTM1 fusions in NUT carcinoma), the requirement to report all thymomas as malignant, and the alignment with TNM staging.","asOf":"2026-09-18","links":[{"label":"J Thorac Oncol 2022","url":"https://doi.org/10.1016/j.jtho.2021.10.010"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34695605/"}],"tags":[],"related":[],"cancers":["thymoma","thymic-carcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-thoracic-oncology"],"dependsOn":[],"notes":[],"journal":"Journal of Thoracic Oncology","year":2022,"doi":"10.1016/j.jtho.2021.10.010","pmid":"34695605","authors":"Marx A, Chan JKC, Chalabreysse L, et al.","paperType":"review","findings":[],"whatItMeans":"The names on a thymic pathology report, and the sharp line between thymoma and thymic carcinoma that drives treatment, come from this classification.","caveats":["Interobserver agreement on thymoma subtypes remains imperfect.","Molecular markers are diagnostic aids rather than treatment targets so far."],"changedPractice":true},{"id":"paper-ali-thyroid","kind":"paper","name":"The 2023 Bethesda System for Reporting Thyroid Cytopathology","aka":[],"tldr":"Paper cited by one technology page and one term page, indexed on Europe PMC as PubMed record 37427847 and published in Thyroid; the citing pages link this DOI, which is how the record was matched.","summary":"Since the publication of the first edition in 2010, The Bethesda System for Reporting Thyroid Cytopathology has allowed cytopathologists to use a standardized, category-based reporting system for thyroid fine needle aspirations. The third edition builds on the success of the 2 earlier editions and offers several key updates. The most important is the assignment of a single name for each of the 6 diagnostic categories: (i) nondiagnostic; (ii) benign; (iii) atypia of undetermined significance; (iv) follicular neoplasm; (v) suspicious for malignancy; and (vi) malignant. Each of the categories has an implied risk of malignancy (ROM), which has been updated and refined based on data reported after the second edition. The third edition offers an average ROM for each category, in addition to the expected range of cancer risk. The atypia of undetermined significance subcategorization is simplified into 2 subgroups based on the implied ROM and molecular profiling. A discussion of pediatric thyroid disease has been added, and pediatric ROMs and management algorithms are discussed in the relevant sections. Nomenclature has been updated to align with the 2022 World Health Organization Classification of Thyroid Neoplasms. Two new chapters have been added: one that addresses the significant and expanded use of molecular and ancillary testing in thyroid cytopathology, and another that summarizes clinical perspectives and imaging findings in thyroid disease.\n\nIndexed on Europe PMC as PubMed record 37427847 (DOI 10.1089/thy.2023.0141). Matched by DOI alone: one technology page and one term page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Thyroid 2023","url":"https://doi.org/10.1089/thy.2023.0141"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37427847/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37427847"}],"tags":["europepmc-ingest"],"related":["thyroid-fna-molecular","bethesda-category"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Thyroid","year":2023,"doi":"10.1089/thy.2023.0141","pmid":"37427847","authors":"Ali SZ, Baloch ZW, Cochand-Priollet B, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page and one term page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-martinez-cibrian-br-j-haematol","kind":"paper","name":"The academic point-of-care anti-CD19 chimeric antigen receptor T-cell product varnimcabtagene autoleucel (ARI-0001 cells) shows efficacy and safety in the treatment of relapsed/refractory B-cell non-Hodgkin lymphoma","aka":[],"tldr":"Paper cited by one treatment page, indexed on Europe PMC as PubMed record 37905734 and published in British journal of haematology; the citing page links this DOI, which is how the record was matched.","summary":"Varnimcabtagene autoleucel (var-cel) is an academic anti-CD19 chimeric antigen receptor (CAR) product used for the treatment of non-Hodgkin lymphoma (NHL) in the CART19-BE-01 trial. Here we report updated outcomes of patients with NHL treated with var-cel. B-cell recovery was compared with patients with acute lymphoblastic leukaemia (ALL). Forty-five patients with NHL were treated. Cytokine release syndrome (any grade) occurred in 84% of patients (4% grade ≥3) and neurotoxicity in 7% (2% grade ≥3). The objective response rate was 73% at Day +100, and the 3-year duration of response was 56%. The 3-year progression-free and overall survival were 40% and 52% respectively. High lactate dehydrogenase was the only covariate with an impact on progression-free survival. The 3-year incidence of B-cell recovery was lower in patients with NHL compared to ALL (25% vs. 60%). In conclusion, in patients with NHL, the toxicity of var-cel was manageable, while B-cell recovery was significantly prolonged compared to ALL. This trial was registered as NCT03144583.\n\nIndexed on Europe PMC as PubMed record 37905734 (DOI 10.1111/bjh.19170). Matched by DOI alone: one treatment page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Br J Haematol 2024","url":"https://doi.org/10.1111/bjh.19170"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37905734/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37905734"}],"tags":["europepmc-ingest"],"related":["varnimcabtagene-autoleucel"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"British journal of haematology","year":2024,"doi":"10.1111/bjh.19170","pmid":"37905734","authors":"Martínez-Cibrián N, Ortiz-Maldonado V, Español-Rego M, et al.","paperType":"observational","findings":[],"whatItMeans":"One treatment page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-armitage-br-j-cancer","kind":"paper","name":"The age distribution of cancer and a multi-stage theory of carcinogenesis","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 13172380 and published in British Journal of Cancer; the citing page links this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 13172380 (DOI 10.1038/bjc.1954.1). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Br J Cancer 1954","url":"https://doi.org/10.1038/bjc.1954.1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/13172380/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/13172380"}],"tags":["europepmc-ingest"],"related":["somatic-mutation-theory"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["british-journal-of-cancer"],"dependsOn":[],"notes":[],"journal":"British Journal of Cancer","year":1954,"doi":"10.1038/bjc.1954.1","pmid":"13172380","authors":"ARMITAGE P, DOLL R","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-morris-j-r-soc-med","kind":"paper","name":"The answer is 17 years, what is the question: understanding time lags in translational research","aka":[],"tldr":"Paper cited by one bottleneck page and 18 idea pages, indexed on Europe PMC as PubMed record 22179294 and published in Journal of the Royal Society of Medicine; the citing pages link this DOI, which is how the record was matched.","summary":"This study aimed to review the literature describing and quantifying time lags in the health research translation process. Papers were included in the review if they quantified time lags in the development of health interventions. The study identified 23 papers. Few were comparable as different studies use different measures, of different things, at different time points. We concluded that the current state of knowledge of time lags is of limited use to those responsible for R&D and knowledge transfer who face difficulties in knowing what they should or can do to reduce time lags. This effectively 'blindfolds' investment decisions and risks wasting effort. The study concludes that understanding lags first requires agreeing models, definitions and measures, which can be applied in practice. A second task would be to develop a process by which to gather these data.\n\nIndexed on Europe PMC as PubMed record 22179294 (DOI 10.1258/jrsm.2011.110180). Matched by DOI alone: one bottleneck page and 18 idea pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J R Soc Med 2011","url":"https://doi.org/10.1258/jrsm.2011.110180"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22179294/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/22179294"}],"tags":["europepmc-ingest"],"related":["b-knowledge-diffusion","idea-data-72-hour-second-opinion-network","idea-data-living-llm-oncology-benchmark","idea-data-patient-explainers-per-recommendation","idea-data-standard-of-care-api","idea-data-evidence-to-adoption-tracker","idea-data-tumour-board-evidence-assistant","idea-data-provenance-first-decision-support","idea-data-structured-trial-results-deposit","idea-data-full-data-with-abstract","idea-data-rapid-guideline-translation","idea-moon-living-machine-readable-guidelines","idea-data-thirty-day-practice-change-learning","idea-data-open-licensed-guidelines","idea-data-implementation-trials-programme","idea-data-guideline-concordance-dashboards","idea-data-standard-of-care-change-alerts","idea-data-toxicity-cds-for-nurses","idea-data-order-set-defaults-30-days"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of the Royal Society of Medicine","year":2011,"doi":"10.1258/jrsm.2011.110180","pmid":"22179294","authors":"Morris ZS, Wooding S, Grant J","paperType":"review","findings":[],"whatItMeans":"One bottleneck page and 18 idea pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-independent-uk-panel-on-breast-cancer-lancet","kind":"paper","name":"The benefits and harms of breast cancer screening: an independent review","aka":[],"tldr":"Paper cited by one term page and one bottleneck page, indexed on Europe PMC as PubMed record 23117178 and published in The Lancet; the citing pages link this DOI, which is how the record was matched.","summary":"Whether breast cancer screening does more harm than good has been debated extensively. The main questions are how large the benefit of screening is in terms of reduced breast cancer mortality and how substantial the harm is in terms of overdiagnosis, which is defined as cancers detected at screening that would not have otherwise become clinically apparent in the woman's lifetime. An independent Panel was convened to reach conclusions about the benefits and harms of breast screening on the basis of a review of published work and oral and written evidence presented by experts in the subject. To provide estimates of the level of benefits and harms, the Panel relied mainly on findings from randomised trials of breast cancer screening that compared women invited to screening with controls not invited, but also reviewed evidence from observational studies. The Panel focused on the UK setting, where women aged 50-70 years are invited to screening every 3 years. In this Review, we provide a summary of the full report on the Panel's findings and conclusions. In a meta-analysis of 11 randomised trials, the relative risk of breast cancer mortality for women invited to screening compared with controls was 0·80 (95% CI 0·73-0·89), which is a relative risk reduction of 20%. The Panel considered the internal biases in the trials and whether these trials, which were done a long time ago, were still relevant; they concluded that 20% was still a reasonable estimate of the relative risk reduction. The more reliable and recent observational studies generally produced larger estimates of benefit, but these studies might be biased. The best estimates of overdiagnosis are from three trials in which women in the control group were not invited to be screened at the end of the active trial period. In a meta-analysis, estimates of the excess incidence were 11% (95% CI 9-12) when expressed as a proportion of cancers diagnosed in the invited group in the long term, and 19% (15-23) when expressed as a proportion of the cancers diagnosed during the active screening period. Results from observational studies support the occurrence of overdiagnosis, but estimates of its magnitude are unreliable. The Panel concludes that screening reduces breast cancer mortality but that some overdiagnosis occurs. Since the estimates provided are from studies with many limitations and whose relevance to present-day screening programmes can be questioned, they have substantial uncertainty and should be regarded only as an approximate guide. If these figures are used directly, for every 10,000 UK women aged 50 years invited to screening for the next 20 years, 43 deaths from breast cancer would be prevented and 129 cases of breast cancer, invasive and non-invasive, would be overdiagnosed; that is one breast cancer death prevented for about every three overdiagnosed cases identified and treated. Of the roughly 307,000 women aged 50-52 years who are invited to begin screening every year, just over 1% would have an overdiagnosed cancer in the next 20 years. Evidence from a focus group organised by Cancer Research UK and attended by some members of the Panel showed that many women feel that accepting the offer of breast screening is worthwhile, which agrees with the results of previous similar studies. Information should be made available in a transparent and objective way to women invited to screening so that they can make informed decisions.\n\nIndexed on Europe PMC as PubMed record 23117178 (DOI 10.1016/s0140-6736(12)61611-0). Matched by DOI alone: one term page and one bottleneck page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet 2012","url":"https://doi.org/10.1016/s0140-6736(12)61611-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23117178/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/23117178"}],"tags":["europepmc-ingest"],"related":["overdiagnosis","b-overdiagnosis"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2012,"doi":"10.1016/s0140-6736(12)61611-0","pmid":"23117178","authors":"Independent UK Panel on Breast Cancer Screening","paperType":"meta-analysis","findings":[],"whatItMeans":"One term page and one bottleneck page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-kalluri-nat-rev-cancer","kind":"paper","name":"The biology and function of fibroblasts in cancer","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 27550820 and published in Nature Reviews Cancer; the citing page links this DOI, which is how the record was matched.","summary":"Among all cells, fibroblasts could be considered the cockroaches of the human body. They survive severe stress that is usually lethal to all other cells, and they are the only normal cell type that can be live-cultured from post-mortem and decaying tissue. Their resilient adaptation may reside in their intrinsic survival programmes and cellular plasticity. Cancer is associated with fibroblasts at all stages of disease progression, including metastasis, and they are a considerable component of the general host response to tissue damage caused by cancer cells. Cancer-associated fibroblasts (CAFs) become synthetic machines that produce many different tumour components. CAFs have a role in creating extracellular matrix (ECM) structure and metabolic and immune reprogramming of the tumour microenvironment with an impact on adaptive resistance to chemotherapy. The pleiotropic actions of CAFs on tumour cells are probably reflective of them being a heterogeneous and plastic population with context-dependent influence on cancer.\n\nIndexed on Europe PMC as PubMed record 27550820 (DOI 10.1038/nrc.2016.73). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Cancer 2016","url":"https://doi.org/10.1038/nrc.2016.73"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27550820/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27550820"}],"tags":["europepmc-ingest"],"related":["caf-activation-desmoplasia"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Cancer","year":2016,"doi":"10.1038/nrc.2016.73","pmid":"27550820","authors":"Kalluri R","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-herbst-nature","kind":"paper","name":"The biology and management of non-small cell lung cancer","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 29364287 and published in Nature; the citing page links this DOI, which is how the record was matched.","summary":"Important advancements in the treatment of non-small cell lung cancer (NSCLC) have been achieved over the past two decades, increasing our understanding of the disease biology and mechanisms of tumour progression, and advancing early detection and multimodal care. The use of small molecule tyrosine kinase inhibitors and immunotherapy has led to unprecedented survival benefits in selected patients. However, the overall cure and survival rates for NSCLC remain low, particularly in metastatic disease. Therefore, continued research into new drugs and combination therapies is required to expand the clinical benefit to a broader patient population and to improve outcomes in NSCLC.\n\nIndexed on Europe PMC as PubMed record 29364287 (DOI 10.1038/nature25183). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2018","url":"https://doi.org/10.1038/nature25183"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29364287/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29364287"}],"tags":["europepmc-ingest"],"related":["nsclc-signalling"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2018,"doi":"10.1038/nature25183","pmid":"29364287","authors":"Herbst RS, Morgensztern D, Boshoff C","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-arvanitis-nat-rev-cancer","kind":"paper","name":"The blood-brain barrier and blood-tumour barrier in brain tumours and metastases","aka":[],"tldr":"Paper cited by one bottleneck page, indexed on Europe PMC as PubMed record 31601988 and published in Nature Reviews Cancer; the citing page links this DOI, which is how the record was matched.","summary":"For a blood-borne cancer therapeutic agent to be effective, it must cross the blood vessel wall to reach cancer cells in adequate quantities, and it must overcome the resistance conferred by the local microenvironment around cancer cells. The brain microenvironment can thwart the effectiveness of drugs against primary brain tumours as well as brain metastases. In this Review, we highlight the cellular and molecular components of the blood-brain barrier (BBB), a specialized neurovascular unit evolved to maintain brain homeostasis. Tumours are known to compromise the integrity of the BBB, resulting in a vasculature known as the blood-tumour barrier (BTB), which is highly heterogeneous and characterized by numerous distinct features, including non-uniform permeability and active efflux of molecules. We discuss the challenges posed by the BBB and BTB for drug delivery, how multiple cell types dictate BBB function and the role of the BTB in disease progression and treatment. Finally, we highlight emerging molecular, cellular and physical strategies to improve drug delivery across the BBB and BTB and discuss their impact on improving conventional as well as emerging treatments, such as immune checkpoint inhibitors and engineered T cells. A deeper understanding of the BBB and BTB through the application of single-cell sequencing and imaging techniques, and the development of biomarkers of BBB integrity along with systems biology approaches, should enable new personalized treatment strategies for primary brain malignancies and brain metastases.\n\nIndexed on Europe PMC as PubMed record 31601988 (DOI 10.1038/s41568-019-0205-x). Matched by DOI alone: one bottleneck page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Cancer 2020","url":"https://doi.org/10.1038/s41568-019-0205-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31601988/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31601988"}],"tags":["europepmc-ingest"],"related":["b-brain-delivery"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Cancer","year":2020,"doi":"10.1038/s41568-019-0205-x","pmid":"31601988","authors":"Arvanitis CD, Ferraro GB, Jain RK","paperType":"review","findings":[],"whatItMeans":"One bottleneck page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-stratton-nature","kind":"paper","name":"The cancer genome","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 19360079 and published in Nature; the citing page links this DOI, which is how the record was matched.","summary":"All cancers arise as a result of changes that have occurred in the DNA sequence of the genomes of cancer cells. Over the past quarter of a century much has been learnt about these mutations and the abnormal genes that operate in human cancers. We are now, however, moving into an era in which it will be possible to obtain the complete DNA sequence of large numbers of cancer genomes. These studies will provide us with a detailed and comprehensive perspective on how individual cancers have developed.\n\nIndexed on Europe PMC as PubMed record 19360079 (DOI 10.1038/nature07943). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2009","url":"https://doi.org/10.1038/nature07943"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19360079/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/19360079"}],"tags":["europepmc-ingest"],"related":["driver-passenger-model"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2009,"doi":"10.1038/nature07943","pmid":"19360079","authors":"Stratton MR, Campbell PJ, Futreal PA","paperType":"review","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-chicago-consensus-appendiceal-neoplasms-cancer-2020","kind":"paper","name":"The Chicago Consensus on peritoneal surface malignancies: management of appendiceal neoplasms","aka":[],"tldr":"A multidisciplinary consensus laying out treatment pathways for each kind of appendix tumour, from low-grade mucinous neoplasms to adenocarcinoma and goblet cell adenocarcinoma, including when cytoreductive surgery with heated chemotherapy and when systemic chemotherapy are appropriate.","summary":"Consensus from the Chicago Consensus Working Group of surgical, medical and pathological oncologists giving management algorithms for appendiceal neoplasms: LAMN with and without peritoneal disease, high-grade mucinous neoplasm, mucinous and non-mucinous adenocarcinoma, and goblet cell adenocarcinoma.\n\nIt recommends cytoreductive surgery with HIPEC for peritoneal disease in centres with expertise, systemic chemotherapy based on colorectal regimens for high-grade and adenocarcinoma histologies, and observation for low-grade disease confined to the appendix.","asOf":"2026-09-18","links":[{"label":"Cancer 2020","url":"https://doi.org/10.1002/cncr.32881"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32282073/"}],"tags":[],"related":[],"cancers":["appendiceal-adenocarcinoma","goblet-cell-adenocarcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":["mitomycin","folfox","capox"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-wiley"],"dependsOn":[],"notes":[],"journal":"Cancer","year":2020,"doi":"10.1002/cncr.32881","pmid":"32282073","authors":"Chicago Consensus Working Group.","paperType":"guideline","findings":[],"whatItMeans":"The standard-of-care rows on the appendiceal pages, particularly who is referred for cytoreductive surgery and who receives chemotherapy, follow this consensus and the NCCN appendiceal section.","caveats":["Consensus on limited retrospective evidence; no randomised trial has tested chemotherapy in appendiceal adenocarcinoma at the time of writing.","Applies to centres with peritoneal surface malignancy expertise."],"changedPractice":false},{"id":"paper-shah-tnbc-clonal-evolution-nature-2012","kind":"paper","name":"The clonal and mutational evolution spectrum of primary triple-negative breast cancers","aka":[],"tldr":"Sequencing 104 triple-negative breast cancers at diagnosis showed they range from tumours with a handful of mutations to tumours with hundreds, that only about a third of mutations are even expressed, and that TP53, PIK3CA and PTEN are the changes present in most of the tumour's cells.","summary":"104 primary TNBCs were profiled by exome and RNA sequencing with deep re-sequencing of 2,414 somatic mutations to measure clonal frequency. The cancers showed a wide, continuous spectrum of genomic evolution; about 36% of mutations were expressed. Basal TNBC showed more variation in clonal frequencies than non-basal TNBC. TP53, PIK3CA and PTEN mutations were clonally dominant compared with other genes, though in some tumours their frequencies were incompatible with founder status; mutations in cytoskeletal, cell-shape and motility genes occurred at lower clonal frequency, suggesting later acquisition.\n\nThe cohort is deposited as brca_bccrc (British Columbia, Nature 2012) on cBioPortal.","asOf":"2026-09-24","links":[{"label":"Shah et al., Nature 2012: clonal and mutational evolution spectrum of 104 primary TNBCs","url":"https://doi.org/10.1038/nature10933"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22495314/"}],"tags":[],"related":[],"cancers":["tnbc"],"sections":[],"technologies":[],"targets":["tp53","pik3ca","pten"],"drugs":[],"companies":[],"institutions":[],"pathways":["clonal-evolution"],"terms":["ngs"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2012,"doi":"10.1038/nature10933","pmid":"22495314","authors":"Shah SP, Roth A, Goya R, et al.","paperType":"translational","findings":["Coding mutation counts ranged from a handful to hundreds per tumour; about 36% of mutations were expressed.","TP53, PIK3CA and PTEN were clonally dominant; basal TNBC showed wider clonal variation than non-basal.","Cytoskeletal and motility gene mutations were subclonal, consistent with later acquisition."],"whatItMeans":"The first TNBC-specific genome paper established that the disease has no shared driver beyond TP53 and that each tumour is a clonal mixture, the reason single-target drugs have struggled and ctDNA tracking needs patient-specific variants.","caveats":["104 tumours from one Canadian centre; exome depth of the era.","Clonal frequencies were estimated from bulk tissue without single-cell confirmation."],"changedPractice":false,"participants":104},{"id":"paper-nowell-science","kind":"paper","name":"The clonal evolution of tumor cell populations","aka":[],"tldr":"Paper cited by one technology page and one term page, indexed on Europe PMC as PubMed record 959840 and published in Science; the citing pages link this DOI, which is how the record was matched.","summary":"It is proposed that most neoplasms arise from a single cell of origin, and tumor progression results from acquired genetic variability within the original clone allowing sequential selection of more aggressive sublines. Tumor cell populations are apparently more genetically unstable than normal cells, perhaps from activation of specific gene loci in the neoplasm, continued presence of carcinogen, or even nutritional deficiencies within the tumor. The acquired genetic insta0ility and associated selection process, most readily recognized cytogenetically, results in advanced human malignancies being highly individual karyotypically and biologically. Hence, each patient's cancer may require individual specific therapy, and even this may be thwarted by emergence of a genetically variant subline resistant to the treatment. More research should be directed toward understanding and controlling the evolutionary process in tumors before it reaches the late stage usually seen in clinical cancer.\n\nIndexed on Europe PMC as PubMed record 959840 (DOI 10.1126/science.959840). Matched by DOI alone: one technology page and one term page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Science 1976","url":"https://doi.org/10.1126/science.959840"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/959840/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/959840"}],"tags":["europepmc-ingest"],"related":["clonal-evolution-models","clonal-evolution-theory"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":1976,"doi":"10.1126/science.959840","pmid":"959840","authors":"Nowell PC","paperType":"observational","findings":[],"whatItMeans":"One technology page and one term page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-burnet-prog-exp-tumor-res","kind":"paper","name":"The concept of immunological surveillance","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 4921480 and published in Progress in experimental tumor research; the citing page links this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 4921480 (DOI 10.1159/000386035). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Prog Exp Tumor Res 1970","url":"https://doi.org/10.1159/000386035"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/4921480/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/4921480"}],"tags":["europepmc-ingest"],"related":["immune-surveillance-immunoediting"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Progress in experimental tumor research","year":1970,"doi":"10.1159/000386035","pmid":"4921480","authors":"Burnet FM","paperType":"review","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-cms-guinney-nat-med-2015","kind":"paper","name":"The consensus molecular subtypes of colorectal cancer","aka":[],"tldr":"An international consortium reconciled six competing gene-expression classifications of colorectal cancer into four consensus subtypes, from immune-active microsatellite-unstable tumours to mesenchymal tumours with the worst outlook.","summary":"Analysis of gene expression data from 4,151 colorectal cancers across 18 datasets by the Colorectal Cancer Subtyping Consortium, producing four consensus molecular subtypes: CMS1 (microsatellite instability, immune), CMS2 (canonical, WNT and MYC), CMS3 (metabolic, KRAS-enriched) and CMS4 (mesenchymal, stromal, worst survival), with about 13 percent of tumours unclassified.","asOf":"2026-09-17","links":[{"label":"Nat Med 2015","url":"https://doi.org/10.1038/nm.3967"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26457759/"}],"tags":[],"related":["colorectal-roadmap","paper-tcga-colorectal-comprehensive-characterization-nature-2012"],"cancers":["braf-v600e-colorectal","early-onset-colorectal","colorectal"],"sections":[],"technologies":["rna-seq"],"targets":["braf","kras","mmr","tgfb1"],"drugs":[],"companies":[],"institutions":[],"pathways":["wnt","myc","tgf-beta","mismatch-repair-msi","caf-activation-desmoplasia"],"terms":["cms-subtypes","msi","sidedness"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2015,"doi":"10.1038/nm.3967","pmid":"26457759","authors":"Guinney J, Dienstmann R, Wang X, et al.","paperType":"translational","findings":["Four subtypes with distinct biology; CMS4 had the worst overall and relapse-free survival, CMS1 the worst survival after relapse."],"whatItMeans":"The CMS framework organises colorectal cancer biology and trial stratification; BRAF V600E tumours cluster in CMS1, and CMS4's shorter survival and stromal signalling are targets of ongoing research.","caveats":["Transcriptomic classification is not yet used to choose treatment in routine practice.","Intratumoural heterogeneity means single biopsies may misclassify."],"changedPractice":true,"participants":4151},{"id":"paper-palbociclib-breast-hr-positive-lancet-oncol-2015","kind":"paper","name":"The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study","aka":[],"tldr":"Phase 2 or 3 results paper on Palbociclib in HR-positive / HER2-negative breast cancer, in The Lancet Oncology (2015), one of the most cited Europe PMC records with Palbociclib in its title.","summary":"Background: Palbociclib (PD-0332991) is an oral, small-molecule inhibitor of cyclin-dependent kinases (CDKs) 4 and 6 with preclinical evidence of growth-inhibitory activity in oestrogen receptor-positive breast cancer cells and synergy with anti-oestrogens. We aimed to assess the safety and efficacy of palbociclib in combination with letrozole as first-line treatment of patients with advanced, oestrogen receptor-positive, HER2-negative breast cancer.\n\nMethods: In this open-label, randomised phase 2 study, postmenopausal women with advanced oestrogen receptor-positive and HER2-negative breast cancer who had not received any systemic treatment for their advanced disease were eligible to participate. Patients were enrolled in two separate cohorts that accrued sequentially: in cohort 1, patients were enrolled on the basis of their oestrogen receptor-positive and HER2-negative biomarker status alone, whereas in cohort 2 they were also required to have cancers with amplification of cyclin D1 (CCND1), loss of p16 (INK4A or CDKN2A), or both. In both cohorts, patients were randomly assigned 1:1 via an interactive web-based randomisation system, stratified by disease site and disease-free interval, to receive continuous oral letrozole 2.5 mg daily or continuous oral letrozole 2.5 mg daily plus oral palbociclib 125 mg, given once daily for 3 weeks followed by 1 week off over 28-day cycles. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population. Accrual to cohort 2 was stopped after an unplanned interim analysis of cohort 1 and the statistical analysis plan for the primary endpoint was amended to a combined analysis of cohorts 1 and 2 (instead of cohort 2 alone). The study is ongoing but closed to accrual; these are the results of the final analysis of progression-free survival. The study is registered with the ClinicalTrials.gov, number NCT00721409.\n\nFindings: Between Dec 22, 2009, and May 12, 2012, we randomly assigned 165 patients, 84 to palbociclib plus letrozole and 81 to letrozole alone. At the time of the final analysis for progression-free survival (median follow-up 29.6 months [95% CI 27.9-36.0] for the palbociclib plus letrozole group and 27.9 months [25.5-31.1] for the letrozole group), 41 progression-free survival events had occurred in the palbociclib plus letrozole group and 59 in the letrozole group. Median progression-free survival was 10.2 months (95% CI 5.7-12.6) for the letrozole group and 20.2 months (13.8-27.5) for the palbociclib plus letrozole group (HR 0.488, 95% CI 0.319-0.748; one-sided p=0.0004). In cohort 1 (n=66), median progression-free survival was 5.7 months (2.6-10.5) for the letrozole group and 26.1 months (11.2-not estimable) for the palbociclib plus letrozole group (HR 0.299, 0.156-0.572; one-sided p<0.0001); in cohort 2 (n=99), median progression-free survival was 11.1 months (7.1-16.4) for the letrozole group and 18.1 months (13.1-27.5) for the palbociclib plus letrozole group (HR 0.508, 0.303-0.853; one-sided p=0.0046). Grade 3-4 neutropenia was reported in 45 (54%) of 83 patients in the palbociclib plus letrozole group versus one (1%) of 77 patients in the letrozole group, leucopenia in 16 (19%) versus none, and fatigue in four (4%) versus one (1%). Serious adverse events that occurred in more than one patient in the palbociclib plus letrozole group were pulmonary embolism (three [4%] patients), back pain (two [2%]), and diarrhoea (two [2%]). No cases of febrile neutropenia or neutropenia-related infections were reported during the study. 11 (13%) patients in the palbociclib plus letrozole group and two (2%) in the letrozole group discontinued the study because of adverse events.\n\nInterpretation: The addition of palbociclib to letrozole in this phase 2 study significantly improved progression-free survival in women with advanced oestrogen receptor-positive and HER2-negative breast cancer. A phase 3 trial is currently underway.\n\nFunding: Pfizer.\n\nIndexed on Europe PMC as PubMed record 25524798 (DOI 10.1016/s1470-2045(14)71159-3). Its title names Palbociclib and its text names HR-positive / HER2-negative breast cancer; PubMed types it as a clinical trial report (Video-Audio Media, Clinical Trial, Phase II, Research Support, Non-U.S. Gov't, Multicenter Study, Randomized Controlled Trial, Research Support, U.S. Gov't, Non-P.H.S.). It was matched automatically to the idea \"CDK4-selective inhibitors as the new first-line backbone\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2015","url":"https://doi.org/10.1016/s1470-2045(14)71159-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25524798/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25524798"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2015,"doi":"10.1016/s1470-2045(14)71159-3","pmid":"25524798","authors":"Finn RS, Crown JP, Lang I, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Palbociclib in HR-positive / HER2-negative breast cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Palbociclib in the title and HR-positive / HER2-negative breast cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-ladanyi-aspl-tfe3-oncogene-2001","kind":"paper","name":"The der(17)t(X;17) of alveolar soft part sarcoma fuses TFE3 to ASPL","aka":[],"tldr":"This study identified the ASPL-TFE3 gene fusion created by the characteristic chromosome translocation in alveolar soft part sarcoma, giving the disease a defining molecular marker and a diagnostic test.","summary":"Molecular cloning of the unbalanced der(17)t(X;17)(p11;q25) translocation in alveolar soft part sarcoma showing fusion of the ASPL (ASPSCR1) gene on chromosome 17 to the TFE3 transcription factor gene on the X chromosome, producing a fusion transcription factor.","asOf":"2026-09-17","links":[{"label":"Oncogene 2001","url":"https://doi.org/10.1038/sj.onc.1204074"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/11244503/"}],"tags":[],"related":[],"cancers":["alveolar-soft-part-sarcoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["oncogene-journal"],"dependsOn":[],"notes":[],"journal":"Oncogene","year":2001,"doi":"10.1038/sj.onc.1204074","pmid":"11244503","authors":"Ladanyi M, Lui MY, Antonescu CR, et al.","paperType":"basic","findings":["ASPL-TFE3 fusion identified as the consistent alteration in alveolar soft part sarcoma."],"whatItMeans":"TFE3 immunostaining and ASPSCR1-TFE3 fusion testing confirm the diagnosis of alveolar soft part sarcoma and link it to a family of TFE3-rearranged tumours including a type of renal cell carcinoma.","caveats":["No direct therapeutic target has followed from the fusion itself."],"changedPractice":true},{"id":"paper-paget-cancer-metastasis-rev","kind":"paper","name":"The distribution of secondary growths in cancer of the breast. 1889","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 2673568 and published in Cancer metastasis reviews; the citing page links this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 2673568 (DOI 10.1016/s0140-6736(00)49915-0). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer Metastasis Rev 1989","url":"https://doi.org/10.1016/s0140-6736(00)49915-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/2673568/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/2673568"}],"tags":["europepmc-ingest"],"related":["seed-and-soil-hypothesis"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-metastasis-reviews"],"dependsOn":[],"notes":[],"journal":"Cancer metastasis reviews","year":1989,"doi":"10.1016/s0140-6736(00)49915-0","pmid":"2673568","authors":"Paget S","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-phan-nat-rev-cancer","kind":"paper","name":"The dormant cancer cell life cycle","aka":[],"tldr":"Paper cited by one pathway page and one bottleneck page, indexed on Europe PMC as PubMed record 32488200 and published in Nature Reviews Cancer; the citing pages link this DOI, which is how the record was matched.","summary":"The success of targeted therapies and immunotherapies has created optimism that cancers may be curable. However, not all patients respond, drug resistance is common and many patients relapse owing to dormant cancer cells. These rare and elusive cells can disseminate early and hide in specialized niches in distant organs before being reactivated to cause disease relapse after successful treatment of the primary tumour. Despite their importance, we are yet to leverage knowledge generated from experimental models and translate the potential of targeting dormant cancer cells to prevent disease relapse in the clinic. This is due, at least in part, to the lack of adherence to consensus definitions by researchers, limited models that faithfully recapitulate this stage of metastatic spread and an absence of interdisciplinary approaches. However, the application of new high-resolution, single-cell technologies is starting to revolutionize the field and transcend classical reductionist models of studying individual cell types or genes in isolation to provide a global view of the complex underlying cellular ecosystem and transcriptional landscape that controls dormancy. In this Perspective, we synthesize some of these recent advances to describe the hallmarks of cancer cell dormancy and how the dormant cancer cell life cycle offers opportunities to target not only the cancer but also its environment to achieve a durable cure for seemingly incurable cancers.\n\nIndexed on Europe PMC as PubMed record 32488200 (DOI 10.1038/s41568-020-0263-0). Matched by DOI alone: one pathway page and one bottleneck page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Cancer 2020","url":"https://doi.org/10.1038/s41568-020-0263-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32488200/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32488200"}],"tags":["europepmc-ingest"],"related":["tumor-dormancy","b-dormancy-mrd"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Cancer","year":2020,"doi":"10.1038/s41568-020-0263-0","pmid":"32488200","authors":"Phan TG, Croucher PI","paperType":"review","findings":[],"whatItMeans":"One pathway page and one bottleneck page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-freedman-plos-biol","kind":"paper","name":"The Economics of Reproducibility in Preclinical Research","aka":[],"tldr":"Paper cited by one bottleneck page, indexed on Europe PMC as PubMed record 26057340 and published in PLoS biology; the citing page links this DOI, which is how the record was matched.","summary":"Low reproducibility rates within life science research undermine cumulative knowledge production and contribute to both delays and costs of therapeutic drug development. An analysis of past studies indicates that the cumulative (total) prevalence of irreproducible preclinical research exceeds 50%, resulting in approximately US$28,000,000,000 (US$28B)/year spent on preclinical research that is not reproducible-in the United States alone. We outline a framework for solutions and a plan for long-term improvements in reproducibility rates that will help to accelerate the discovery of life-saving therapies and cures.\n\nIndexed on Europe PMC as PubMed record 26057340 (DOI 10.1371/journal.pbio.1002165). Matched by DOI alone: one bottleneck page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"PLoS Biol 2015","url":"https://doi.org/10.1371/journal.pbio.1002165"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26057340/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26057340"}],"tags":["europepmc-ingest"],"related":["b-reproducibility"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"PLoS biology","year":2015,"doi":"10.1371/journal.pbio.1002165","pmid":"26057340","authors":"Freedman LP, Cockburn IM, Simcoe TS","paperType":"basic","findings":[],"whatItMeans":"One bottleneck page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nct02107703-jama-oncol-2020-update","kind":"paper","name":"The Effect of Abemaciclib Plus Fulvestrant on Overall Survival in Hormone Receptor-Positive, ERBB2-Negative Breast Cancer That Progressed on Endocrine Therapy-MONARCH 2: A Randomized Clinical Trial","aka":[],"tldr":"Later report from the MONARCH 2 trial registered as NCT02107703, in JAMA Oncology (2020); its title describes an updated or longer-term analysis.","summary":"Importance: Statistically significant overall survival (OS) benefits of CDK4 and CDK6 inhibitors in combination with fulvestrant for hormone receptor (HR)-positive, ERBB2 (formerly HER2)-negative advanced breast cancer (ABC) in patients regardless of menopausal status after prior endocrine therapy (ET) has not yet been demonstrated.\n\nObjective: To compare the effect of abemaciclib plus fulvestrant vs placebo plus fulvestrant on OS at the prespecified interim of MONARCH 2 (338 events) in patients with HR-positive, ERBB2-negative advanced breast cancer that progressed during prior ET.\n\nDesign, setting, and participants: MONARCH 2 was a global, randomized, placebo-controlled, double-blind phase 3 trial of abemaciclib plus fulvestrant vs placebo plus fulvestrant for treatment of premenopausal or perimenopausal women (with ovarian suppression) and postmenopausal women with HR-positive, ERBB2-negative ABC that progressed during ET. Patients were enrolled between August 7, 2014, and December 29, 2015. Analyses for this report were conducted at the time of database lock on June 20, 2019.\n\nInterventions: Patients were randomized 2:1 to receive abemaciclib or placebo, 150 mg, every 12 hours on a continuous schedule plus fulvestrant, 500 mg, per label. Randomization was stratified based on site of metastasis (visceral, bone only, or other) and resistance to prior ET (primary vs secondary).\n\nMain outcomes and measures: The primary end point was investigator-assessed progression-free survival. Overall survival was a gated key secondary end point. The boundary P value for the interim analysis was.02.\n\nResults: Of 669 women enrolled, 446 (median [range] age, 59 [32-91] years) were randomized to the abemaciclib plus fulvestrant arm and 223 (median [range] age, 62 [32-87] years) were randomized to the placebo plus fulvestrant arm. At the prespecified interim, 338 deaths (77% of the planned 441 at the final analysis) were observed in the intent-to-treat population, with a median OS of 46.7 months for abemaciclib plus fulvestrant and 37.3 months for placebo plus fulvestrant (hazard ratio [HR], 0.757; 95% CI, 0.606-0.945; P =.01). Improvement in OS was consistent across all stratification factors. Among stratification factors, more pronounced effects were observed in patients with visceral disease (HR, 0.675; 95% CI, 0.511-0.891) and primary resistance to prior ET (HR, 0.686; 95% CI, 0.451-1.043). Time to second disease progression (median, 23.1 months vs 20.6 months), time to chemotherapy (median, 50.2 months vs 22.1 months), and chemotherapy-free survival (median, 25.5 months vs 18.2 months) were also statistically significantly improved in the abemaciclib arm vs placebo arm. No new safety signals were observed for abemaciclib.\n\nConclusions and relevance: Treatment with abemaciclib plus fulvestrant resulted in a statistically significant and clinically meaningful median OS improvement of 9.4 months for patients with HR-positive, ERBB2-negative ABC who progressed after prior ET regardless of menopausal status. Abemaciclib substantially delayed the receipt of subsequent chemotherapy.\n\nTrial registration: ClinicalTrials.gov identifier: NCT02107703.\n\nIndexed on Europe PMC as PubMed record 31563959 (DOI 10.1001/jamaoncol.2019.4782). Its abstract cites the registry id NCT02107703, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"JAMA Oncol 2020","url":"https://doi.org/10.1001/jamaoncol.2019.4782"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31563959/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31563959"},{"label":"ClinicalTrials.gov NCT02107703","url":"https://clinicaltrials.gov/study/NCT02107703"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct02107703"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2020,"doi":"10.1001/jamaoncol.2019.4782","pmid":"31563959","authors":"Sledge GW, Toi M, Neven P, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the MONARCH 2 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-goodwin-n-engl-j-med","kind":"paper","name":"The effect of group psychosocial support on survival in metastatic breast cancer","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 11742045 and published in New England Journal of Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Background: Supportive-expressive group therapy has been reported to prolong survival among women with metastatic breast cancer. However, in recent studies, various psychosocial interventions have not prolonged survival.\n\nMethods: In a multicenter trial, we randomly assigned 235 women with metastatic breast cancer who were expected to survive at least three months in a 2:1 ratio to an intervention group that participated in weekly supportive-expressive group therapy (158 women) or to a control group that received no such intervention (77 women). All the women received educational materials and any medical or psychosocial care that was deemed necessary. The primary outcome was survival; psychosocial function was assessed by self-reported questionnaires.\n\nResults: Women assigned to supportive-expressive therapy had greater improvement in psychological symptoms and reported less pain (P=0.04) than women in the control group. A significant interaction of treatment-group assignment with base-line psychological score was found (P</=0.003 for the comparison of mood variables; P=0.04 for the comparison of pain); women who were more distressed benefited, whereas those who were less distressed did not. The psychological intervention did not prolong survival (median survival, 17.9 months in the intervention group and 17.6 months in the control group; hazard ratio for death according to the univariate analysis, 1.06 [95 percent confidence interval, 0.78 to 1.45]; hazard ratio according to the multivariate analysis, 1.23 [95 percent confidence interval, 0.88 to 1.72]).\n\nConclusions: Supportive-expressive group therapy does not prolong survival in women with metastatic breast cancer. It improves mood and the perception of pain, particularly in women who are initially more distressed.\n\nIndexed on Europe PMC as PubMed record 11742045 (DOI 10.1056/nejmoa011871). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2001","url":"https://doi.org/10.1056/nejmoa011871"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/11742045/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/11742045"}],"tags":["europepmc-ingest"],"related":["peer-support-groups"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2001,"doi":"10.1056/nejmoa011871","pmid":"11742045","authors":"Goodwin PJ, Leszcz M, Ennis M, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-pavlova-cell-metab","kind":"paper","name":"The Emerging Hallmarks of Cancer Metabolism","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 26771115 and published in Cell metabolism; the citing page links this DOI, which is how the record was matched.","summary":"Tumorigenesis is dependent on the reprogramming of cellular metabolism as both direct and indirect consequence of oncogenic mutations. A common feature of cancer cell metabolism is the ability to acquire necessary nutrients from a frequently nutrient-poor environment and utilize these nutrients to both maintain viability and build new biomass. The alterations in intracellular and extracellular metabolites that can accompany cancer-associated metabolic reprogramming have profound effects on gene expression, cellular differentiation, and the tumor microenvironment. In this Perspective, we have organized known cancer-associated metabolic changes into six hallmarks: (1) deregulated uptake of glucose and amino acids, (2) use of opportunistic modes of nutrient acquisition, (3) use of glycolysis/TCA cycle intermediates for biosynthesis and NADPH production, (4) increased demand for nitrogen, (5) alterations in metabolite-driven gene regulation, and (6) metabolic interactions with the microenvironment. While few tumors display all six hallmarks, most display several. The specific hallmarks exhibited by an individual tumor may ultimately contribute to better tumor classification and aid in directing treatment.\n\nIndexed on Europe PMC as PubMed record 26771115 (DOI 10.1016/j.cmet.2015.12.006). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cell Metab 2016","url":"https://doi.org/10.1016/j.cmet.2015.12.006"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26771115/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26771115"}],"tags":["europepmc-ingest"],"related":["metabolic-theory-of-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Cell metabolism","year":2016,"doi":"10.1016/j.cmet.2015.12.006","pmid":"26771115","authors":"Pavlova NN, Thompson CB","paperType":"review","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-feinberg-nat-rev-genet-2006","kind":"paper","name":"The epigenetic progenitor origin of human cancer","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 16369569 and published in Nature reviews. Genetics; the citing page links this DOI, which is how the record was matched.","summary":"Cancer is widely perceived as a heterogeneous group of disorders with markedly different biological properties, which are caused by a series of clonally selected genetic changes in key tumour-suppressor genes and oncogenes. However, recent data suggest that cancer has a fundamentally common basis that is grounded in a polyclonal epigenetic disruption of stem/progenitor cells, mediated by 'tumour-progenitor genes'. Furthermore, tumour cell heterogeneity is due in part to epigenetic variation in progenitor cells, and epigenetic plasticity together with genetic lesions drives tumour progression. This crucial early role for epigenetic alterations in cancer is in addition to epigenetic alterations that can substitute for genetic variation later in tumour progression. Therefore, non-neoplastic but epigenetically disrupted stem/progenitor cells might be a crucial target for cancer risk assessment and chemoprevention.\n\nIndexed on Europe PMC as PubMed record 16369569 (DOI 10.1038/nrg1748). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Genet 2006","url":"https://doi.org/10.1038/nrg1748"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/16369569/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/16369569"}],"tags":["europepmc-ingest"],"related":["epigenetic-progenitor-theory"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature reviews. Genetics","year":2006,"doi":"10.1038/nrg1748","pmid":"16369569","authors":"Feinberg AP, Ohlsson R, Henikoff S","paperType":"review","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nelson-j-med-chem","kind":"paper","name":"The Essential Medicinal Chemistry of Curcumin","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 28074653 and published in Journal of medicinal chemistry; the citing page links this DOI, which is how the record was matched.","summary":"Curcumin is a constituent (up to ∼5%) of the traditional medicine known as turmeric. Interest in the therapeutic use of turmeric and the relative ease of isolation of curcuminoids has led to their extensive investigation. Curcumin has recently been classified as both a PAINS (pan-assay interference compounds) and an IMPS (invalid metabolic panaceas) candidate. The likely false activity of curcumin in vitro and in vivo has resulted in >120 clinical trials of curcuminoids against several diseases. No double-blinded, placebo controlled clinical trial of curcumin has been successful. This manuscript reviews the essential medicinal chemistry of curcumin and provides evidence that curcumin is an unstable, reactive, nonbioavailable compound and, therefore, a highly improbable lead. On the basis of this in-depth evaluation, potential new directions for research on curcuminoids are discussed.\n\nIndexed on Europe PMC as PubMed record 28074653 (DOI 10.1021/acs.jmedchem.6b00975). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Med Chem 2017","url":"https://doi.org/10.1021/acs.jmedchem.6b00975"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28074653/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28074653"}],"tags":["europepmc-ingest"],"related":["curcumin-turmeric"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of medicinal chemistry","year":2017,"doi":"10.1021/acs.jmedchem.6b00975","pmid":"28074653","authors":"Nelson KM, Dahlin JL, Bisson J, et al.","paperType":"review","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-gundem-evolutionary-history-lethal-metastatic-prostate-nature-2015","kind":"paper","name":"The evolutionary history of lethal metastatic prostate cancer","aka":["Gundem 2015","metastasis-to-metastasis spread prostate","polyclonal seeding prostate cancer"],"tldr":"By sequencing many separate deposits from ten men who died of prostate cancer, this study reconstructed how the cancer travelled. Metastases seeded other metastases, and often did it in groups of cells rather than one at a time.","summary":"Gunes Gundem, David Wedge, Peter Campbell, Scott Bova and the International Cancer Genome Consortium Prostate Group used whole-genome sequencing of multiple metastases from ten men with androgen-deprived metastatic prostate cancer and reconstructed the subclonal architecture across sites.\n\nThe standard model of metastasis is that each deposit descends from one cell that left the primary tumour. This work found that metastasis-to-metastasis spread is common, either by a daughter metastasis being seeded from a parent one, or, in five of the ten men, by multiple tumour clones moving between metastatic sites together. It also found a pattern in what is mutated where: tumour suppressor lesions occur as single events, whereas androgen receptor pathway mutations arise convergently and repeatedly in different metastases, which is evolution being watched under the same selective pressure in parallel.","asOf":"2026-09-25","links":[{"label":"Nature 2015","url":"https://doi.org/10.1038/nature14347"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25830880/"}],"tags":["prostate-evidence"],"related":["paper-baca-punctuated-evolution-chromoplexy-cell-2013","paper-zhang-nat-commun","paper-phillips-jama-oncol","idea-bio2-oligometastatic-signature","prostate-roadmap"],"cancers":["prostate","prostate-mcrpc"],"sections":["diagnostics"],"technologies":[],"targets":["androgen-receptor","tp53"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["oligometastatic","bone-metastases","chromoplexy"],"trials":[],"people":[],"bottlenecks":["b-metastasis-biology","b-tumor-heterogeneity","b-resistance"],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2015,"doi":"10.1038/nature14347","pmid":"25830880","authors":"Gundem G, Van Loo P, Kremeyer B, et al.","paperType":"basic","findings":["Whole-genome sequencing of multiple metastases from ten patients showed that metastasis-to-metastasis spread is common, through de novo monoclonal seeding of daughter metastases or, in five cases, through transfer of multiple tumour clones between metastatic sites.","Lesions affecting tumour suppressor genes usually occurred as single events.","Mutations in genes involved in androgen receptor signalling commonly involved multiple convergent events in different metastases.","The results provide evidence for polyclonal seeding in human malignancy, previously demonstrated mainly in mouse models."],"whatItMeans":"Metastatic prostate cancer is a communicating population, not a set of independent colonies, which is an argument for treating the whole body rather than chasing individual deposits, and an argument that resistance to androgen receptor drugs will emerge in several places at once because it emerges convergently.","caveats":["Ten men, all with androgen-deprived disease, from a research autopsy and biopsy programme; the generality of the seeding patterns is not established.","Phylogenetic reconstruction from bulk sequencing infers the history rather than observing it, and depends on the clonal deconvolution method used.","No treatment implication has yet been tested prospectively; the finding argues against, rather than disproves, metastasis-directed therapy in polymetastatic disease."],"changedPractice":false,"participants":10},{"id":"paper-de-visser-cancer-cell","kind":"paper","name":"The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 36917948 and published in Cancer Cell; the citing page links this DOI, which is how the record was matched.","summary":"Cancers represent complex ecosystems comprising tumor cells and a multitude of non-cancerous cells, embedded in an altered extracellular matrix. The tumor microenvironment (TME) includes diverse immune cell types, cancer-associated fibroblasts, endothelial cells, pericytes, and various additional tissue-resident cell types. These host cells were once considered bystanders of tumorigenesis but are now known to play critical roles in the pathogenesis of cancer. The cellular composition and functional state of the TME can differ extensively depending on the organ in which the tumor arises, the intrinsic features of cancer cells, the tumor stage, and patient characteristics. Here, we review the importance of the TME in each stage of cancer progression, from tumor initiation, progression, invasion, and intravasation to metastatic dissemination and outgrowth. Understanding the complex interplay between tumor cell-intrinsic, cell-extrinsic, and systemic mediators of disease progression is critical for the rational development of effective anti-cancer treatments.\n\nIndexed on Europe PMC as PubMed record 36917948 (DOI 10.1016/j.ccell.2023.02.016). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer Cell 2023","url":"https://doi.org/10.1016/j.ccell.2023.02.016"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36917948/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36917948"}],"tags":["europepmc-ingest"],"related":["tumor-microenvironment"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-cell"],"dependsOn":[],"notes":[],"journal":"Cancer Cell","year":2023,"doi":"10.1016/j.ccell.2023.02.016","pmid":"36917948","authors":"de Visser KE, Joyce JA","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-zafar-oncologist","kind":"paper","name":"The financial toxicity of cancer treatment: a pilot study assessing out-of-pocket expenses and the insured cancer patient's experience","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 23442307 and published in The oncologist; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: Cancer patients carry rising burdens of health care-related out-of-pocket expenses, and a growing number of patients are considered \"underinsured.\" Our objective was to describe experiences of insured cancer patients requesting copayment assistance and to describe the impact of health care expenses on well-being and treatment.\n\nMethods: We conducted baseline and follow-up surveys regarding the impact of health care costs on well-being and treatment among cancer patients who contacted a national copayment assistance foundation along with a comparison sample of patients treated at an academic medical center.\n\nResults: Among 254 participants, 75% applied for drug copayment assistance. Forty-two percent of participants reported a significant or catastrophic subjective financial burden; 68% cut back on leisure activities, 46% reduced spending on food and clothing, and 46% used savings to defray out-of-pocket expenses. To save money, 20% took less than the prescribed amount of medication, 19% partially filled prescriptions, and 24% avoided filling prescriptions altogether. Copayment assistance applicants were more likely than nonapplicants to employ at least one of these strategies to defray costs (98% vs. 78%). In an adjusted analysis, younger age, larger household size, applying for copayment assistance, and communicating with physicians about costs were associated with greater subjective financial burden.\n\nConclusion: Insured patients undergoing cancer treatment and seeking copayment assistance experience considerable subjective financial burden, and they may alter their care to defray out-of-pocket expenses. Health insurance does not eliminate financial distress or health disparities among cancer patients. Future research should investigate coverage thresholds that minimize adverse financial outcomes and identify cancer patients at greatest risk for financial toxicity.\n\nIndexed on Europe PMC as PubMed record 23442307 (DOI 10.1634/theoncologist.2012-0279). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Oncologist 2013","url":"https://doi.org/10.1634/theoncologist.2012-0279"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23442307/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/23442307"}],"tags":["europepmc-ingest"],"related":["financial-toxicity"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["the-oncologist"],"dependsOn":[],"notes":[],"journal":"The oncologist","year":2013,"doi":"10.1634/theoncologist.2012-0279","pmid":"23442307","authors":"Zafar SY, Peppercorn JM, Schrag D, et al.","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-protac-concept-sakamoto-pnas-2001","kind":"paper","name":"The first PROTAC: a chimeric molecule that tags a protein for destruction","aka":[],"tldr":"Crews and Deshaies built a two-headed molecule linking a ligand for the target protein MetAP-2 to a peptide recognised by an E3 ubiquitin ligase, and showed it induced ubiquitination and degradation of the target, founding targeted protein degradation.","summary":"The proteolysis-targeting chimera (Protac-1) joined ovalicin, which binds methionine aminopeptidase-2, to the IkappaBalpha phosphopeptide recognised by the SCF-beta-TRCP E3 ligase. In Xenopus egg extracts, Protac-1 recruited MetAP-2 to the ligase and triggered its ubiquitination and proteasomal degradation.\n\nThe paper established the principle that a bifunctional molecule can hijack the cell's own disposal machinery to eliminate a chosen protein, including proteins with no enzymatic activity to inhibit. Peptide-based PROTACs were poorly cell-permeable; the field became practical when all-small-molecule degraders using VHL and cereblon ligands appeared (Bondeson 2015; Winter 2015, dBET1 degrading BRD4 in vivo).\n\nDegraders now include vepdegestrant (oestrogen receptor), ARV-110 and other androgen-receptor degraders, and the molecular glues (lenalidomide-class drugs) reinterpreted through the same mechanism.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1073/pnas.141230798"},{"label":"In vivo small-molecule degrader dBET1 (Winter 2015)","url":"https://doi.org/10.1126/science.aab1433"}],"tags":[],"related":["molecular-glue-platforms"],"cancers":[],"sections":["drug-discovery","targeted-therapy"],"technologies":["protac-degrader","degrader-antibody-conjugate"],"targets":["estrogen-receptor","androgen-receptor"],"drugs":["vepdegestrant"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["veritac-2"],"people":[],"bottlenecks":["b-undruggable-targets","b-resistance"],"keyPapers":[],"journals":["pnas"],"dependsOn":[],"notes":[],"journal":"PNAS","year":2001,"doi":"10.1073/pnas.141230798","pmid":"11438690","authors":"Sakamoto KM, Kim KB, Kumagai A, Mercurio F, Crews CM, Deshaies RJ","paperType":"basic","findings":["Protac-1 induced ubiquitination and degradation of MetAP-2 in cell extracts by recruiting the SCF E3 ligase","Degradation required both halves of the chimera and an intact ubiquitin-proteasome pathway","Introduced the terminology and concept of proteolysis-targeting chimeras","Small-molecule successors (2015 onwards) achieved in vivo degradation of BRD4 and other targets at nanomolar potency"],"whatItMeans":"Instead of blocking a cancer protein, a drug can now remove it entirely, which works even for proteins without a druggable active site and can overcome resistance driven by target overexpression or mutation. Several degraders are in late-stage trials for breast and prostate cancer.","caveats":["The original molecule was a large peptide conjugate with no cell permeability; clinical degraders took 15 years","Degraders are large molecules with challenging oral bioavailability and pharmacokinetics","Ligase expression varies between tissues and tumours, and resistance via ligase loss has been documented","Clinical superiority over inhibitors has so far been modest in the first phase 3 readouts (for example vepdegestrant)"],"changedPractice":false},{"id":"paper-prior-cancer-res","kind":"paper","name":"The Frequency of Ras Mutations in Cancer","aka":[],"tldr":"Paper cited by one bottleneck page, indexed on Europe PMC as PubMed record 32209560 and published in Cancer Research; the citing page links this DOI, which is how the record was matched.","summary":"Ras is frequently mutated in cancer, however, there is a lack of consensus in the literature regarding the cancer mutation frequency of Ras, with quoted values varying from 10%-30%. This variability is at least in part due to the selective aggregation of data from different databases and the dominant influence of particular cancer types and particular Ras isoforms within these datasets. To provide a more definitive figure for Ras mutation frequency in cancer, we cross-referenced the data in all major publicly accessible cancer mutation databases to determine reliable mutation frequency values for each Ras isoform in all major cancer types. These percentages were then applied to current U.S. cancer incidence statistics to estimate the number of new patients each year that have Ras-mutant cancers. We find that approximately 19% of patients with cancer harbor Ras mutations, equivalent to approximately 3.4 million new cases per year worldwide. We discuss the Ras isoform and mutation-specific trends evident within the datasets that are relevant to current Ras-targeted therapies.\n\nIndexed on Europe PMC as PubMed record 32209560 (DOI 10.1158/0008-5472.can-19-3682). Matched by DOI alone: one bottleneck page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer Res 2020","url":"https://doi.org/10.1158/0008-5472.can-19-3682"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32209560/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32209560"}],"tags":["europepmc-ingest"],"related":["b-undruggable-targets"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-research"],"dependsOn":[],"notes":[],"journal":"Cancer Research","year":2020,"doi":"10.1158/0008-5472.can-19-3682","pmid":"32209560","authors":"Prior IA, Hood FE, Hartley JL","paperType":"review","findings":[],"whatItMeans":"One bottleneck page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-herschkowitz-rb1-loss-basal-like-bcr-2008","kind":"paper","name":"The functional loss of the retinoblastoma tumour suppressor is a common event in basal-like and luminal B breast carcinomas","aka":[],"tldr":"Loss of one copy of the RB1 gene was found in 72% of basal-like breast cancers, with low RB1 messenger RNA and high p16, and an RB1-loss expression signature predicted outcome and possibly chemotherapy response.","summary":"88 primary breast carcinomas and matched normal DNA were subtyped by expression and assessed for RB1 loss of heterozygosity with polymorphic markers. LOH was seen in 39% overall, 72% of basal-like and 62% of luminal B tumours, which also showed low RB1 mRNA; p16INK4a was highly expressed in basal-like tumours consistent with RB1 loss. An RB1-LOH signature was highly prognostic and a potential predictor of neoadjuvant chemotherapy response.","asOf":"2026-09-24","links":[{"label":"Herschkowitz et al., Breast Cancer Res 2008: RB1 loss in basal-like and luminal B carcinomas","url":"https://doi.org/10.1186/bcr2142"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/18782450/"}],"tags":[],"related":[],"cancers":["tnbc","breast-cancer"],"sections":[],"technologies":[],"targets":["rb1","cdk4-6"],"drugs":[],"companies":[],"institutions":[],"pathways":["p53-cell-cycle"],"terms":[],"trials":[],"people":["charles-perou"],"bottlenecks":[],"keyPapers":[],"journals":["breast-cancer-research"],"dependsOn":[],"notes":[],"journal":"Breast Cancer Research","year":2008,"doi":"10.1186/bcr2142","pmid":"18782450","authors":"Herschkowitz JI, He X, Fan C, Perou CM.","paperType":"translational","findings":["RB1 loss of heterozygosity in 72% of basal-like and 62% of luminal B tumours (39% overall).","Low RB1 mRNA and high p16 in basal-like tumours; RB1-loss signature prognostic."],"whatItMeans":"Functional RB1 loss is part of basal-like biology, which explains why CDK4/6 inhibitors have not worked in TNBC and why the cell-cycle vulnerability there lies downstream of RB.","caveats":["88 tumours; loss of heterozygosity rather than biallelic inactivation.","Later sequencing puts RB1 mutation or deep deletion nearer 15 to 20%."],"changedPractice":false,"participants":88},{"id":"paper-rieke-npj-digit-med","kind":"paper","name":"The future of digital health with federated learning","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 33015372 and published in NPJ digital medicine; the citing page links this DOI, which is how the record was matched.","summary":"Data-driven machine learning (ML) has emerged as a promising approach for building accurate and robust statistical models from medical data, which is collected in huge volumes by modern healthcare systems. Existing medical data is not fully exploited by ML primarily because it sits in data silos and privacy concerns restrict access to this data. However, without access to sufficient data, ML will be prevented from reaching its full potential and, ultimately, from making the transition from research to clinical practice. This paper considers key factors contributing to this issue, explores how federated learning (FL) may provide a solution for the future of digital health and highlights the challenges and considerations that need to be addressed.\n\nIndexed on Europe PMC as PubMed record 33015372 (DOI 10.1038/s41746-020-00323-1). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"NPJ Digit Med 2020","url":"https://doi.org/10.1038/s41746-020-00323-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33015372/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33015372"}],"tags":["europepmc-ingest"],"related":["federated-learning-medical-ai"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"NPJ digital medicine","year":2020,"doi":"10.1038/s41746-020-00323-1","pmid":"33015372","authors":"Rieke N, Hancox J, Li W, et al.","paperType":"review","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-schoenfeld-smarca4-alterations-lung-ccr-2020","kind":"paper","name":"The genomic landscape of SMARCA4 alterations and associations with outcomes in patients with lung cancer","aka":[],"tldr":"One of the most commonly mutated genes in lung cancer turns out to come in two kinds: one that destroys the protein and carries the worst prognosis, and one that leaves it intact. Both do worse than average, and both do better than average on immunotherapy.","summary":"Genomic, protein expression and clinical outcome data were analysed for patients with SMARCA4-altered lung cancer treated at one centre. Among 4,813 patients with non-small-cell lung cancer, 407, 8%, carried a SMARCA4 alteration. Two categories were described: class 1 (truncating mutations, fusions and homozygous deletion) and class 2 (missense mutations). Loss of protein expression was associated with class 1 alterations, 81% against 0%. Both classes co-occurred more frequently with KRAS, STK11 and KEAP1 mutations than in SMARCA4 wild-type tumours. In metastatic disease, SMARCA4 alterations were associated with shorter overall survival, with class 1 the shortest. Treatment with immune checkpoint inhibitors was associated with improved outcomes in SMARCA4-altered tumours, with class 1 responding best.","asOf":"2026-09-25","links":[{"label":"Schoenfeld et al., Clin Cancer Res 2020: the genomic landscape of SMARCA4 alterations in 4,813 lung cancers","url":"https://doi.org/10.1158/1078-0432.CCR-20-1825"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32709715/"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":["cgp","histopathology-ihc","checkpoint-inhibitor"],"targets":["smarca4","kras","stk11","keap1"],"drugs":[],"companies":[],"institutions":["mskcc"],"pathways":["swi-snf-chromatin","t-cell-exhaustion"],"terms":["driver-mutation","vus","ihc","stk11-keap1"],"trials":[],"people":["gregory-riely"],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2020,"doi":"10.1158/1078-0432.CCR-20-1825","pmid":"32709715","authors":"Schoenfeld AJ, Bandlamudi C, Lavery JA, et al.","paperType":"observational","findings":["SMARCA4 alterations in 407 of 4,813 lung cancers, 8%, in two genomically and clinically distinct classes.","Protein loss in 81% of class 1 alterations and none of class 2.","Both classes co-occur with KRAS, STK11 and KEAP1 and are independent predictors of shorter survival.","Checkpoint inhibitor outcomes were better in SMARCA4-altered tumours, class 1 best."],"whatItMeans":"It turned a frequently reported variant into an interpretable one: the class decides whether the stain will be negative, how poor the prognosis is, and whether immunotherapy is more rather than less likely to help.","caveats":["Single centre and retrospective.","Immunotherapy comparison is not randomised and is confounded by co-mutation.","Class 2 missense variants include variants of unknown significance."],"changedPractice":false,"participants":4813},{"id":"paper-pavlova-cell-metab-2022","kind":"paper","name":"The hallmarks of cancer metabolism: Still emerging","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 35123658 and published in Cell metabolism; the citing page links this DOI, which is how the record was matched.","summary":"Metabolism of cancer cells is geared toward biomass production and proliferation. Since the metabolic resources within the local tissue are finite, this can lead to nutrient depletion and accumulation of metabolic waste. To maintain growth in these conditions, cancer cells employ a variety of metabolic adaptations, the nature of which is collectively determined by the physiology of their cell of origin, the identity of transforming lesions, and the tissue in which cancer cells reside. Furthermore, select metabolites not only serve as substrates for energy and biomass generation, but can also regulate gene and protein expression and influence the behavior of non-transformed cells in the tumor vicinity. As they grow and metastasize, tumors can also affect and be affected by the nutrient distribution within the body. In this hallmark update, recent advances are incorporated into a conceptual framework that may help guide further research efforts in exploring cancer cell metabolism.\n\nIndexed on Europe PMC as PubMed record 35123658 (DOI 10.1016/j.cmet.2022.01.007). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cell Metab 2022","url":"https://doi.org/10.1016/j.cmet.2022.01.007"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35123658/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35123658"}],"tags":["europepmc-ingest"],"related":["cancer-metabolism"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Cell metabolism","year":2022,"doi":"10.1016/j.cmet.2022.01.007","pmid":"35123658","authors":"Pavlova NN, Zhu J, Thompson CB","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-hallmarks-of-cancer-cell-2000","kind":"paper","name":"The Hallmarks of Cancer: six capabilities every tumour must acquire","aka":[],"tldr":"Hanahan and Weinberg distilled decades of cancer biology into six acquired capabilities shared by all cancers, giving the field a common organising framework that has been cited more than any other cancer paper.","summary":"Written for the millennium issue of Cell, this review proposed that the vast catalogue of cancer genotypes is a manifestation of six essential alterations in cell physiology: self-sufficiency in growth signals, insensitivity to growth-inhibitory signals, evasion of apoptosis, limitless replicative potential, sustained angiogenesis, and tissue invasion and metastasis. Genome instability was presented as the enabling characteristic that lets cells acquire these traits.\n\nThe authors argued that tumours are not simply masses of proliferating cells but tissues composed of many cell types, anticipating the later emphasis on the microenvironment. They also predicted that cancer research would become a logical science with mechanism-based therapies targeting each hallmark.\n\nThe 2011 update added two hallmarks (reprogramming energy metabolism, evading immune destruction) and two enabling characteristics (genome instability, tumour-promoting inflammation).","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1016/S0092-8674(00)81683-9"},{"label":"Hallmarks of Cancer: The Next Generation (2011)","url":"https://doi.org/10.1016/j.cell.2011.02.013"}],"tags":[],"related":["paper-hallmarks-new-dimensions-cancer-discov-2022","sustaining-proliferative-signaling","evading-growth-suppressors","resisting-cell-death","enabling-replicative-immortality","inducing-angiogenesis","activating-invasion-metastasis","genome-instability-mutation"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["hallmarks-of-cancer","oncogene-addiction"],"trials":[],"people":[],"bottlenecks":["b-knowledge-diffusion","b-combination-space"],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Cell","year":2000,"doi":"10.1016/S0092-8674(00)81683-9","pmid":"10647931","authors":"Hanahan D, Weinberg RA","paperType":"review","findings":["Six hallmarks: sustaining proliferative signalling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis","Genome instability proposed as the enabling characteristic underlying acquisition of the hallmarks","Tumours framed as complex tissues in which stromal and immune cells are active participants","The paper became the most-cited article in Cell and one of the most-cited in biomedicine"],"whatItMeans":"The hallmarks are the mental map most oncologists and researchers use to think about what cancer is and where drugs act. A newcomer can understand nearly every therapy as an attack on one hallmark: kinase inhibitors on proliferative signalling, checkpoint blockade on immune evasion, anti-VEGF drugs on angiogenesis.","caveats":["A conceptual review rather than new data; critics argue it over-generalises across very different diseases","Some hallmarks (angiogenesis) turned out to be less universally targetable than hoped","Did not anticipate the centrality of the immune system or of epigenetic and microbial factors, later added","Provides no quantitative framework for prioritising targets"],"changedPractice":false},{"id":"paper-withers-acta-oncol","kind":"paper","name":"The hazard of accelerated tumor clonogen repopulation during radiotherapy","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 3390344 and published in Acta oncologica; the citing page links this DOI, which is how the record was matched.","summary":"When analysis of results of radiotherapy for nearly 500 patients with oropharyngeal cancer showed evidence for rapid tumor regrowth during extensions of treatment from about 5 weeks to about 8 weeks, we searched the literature on radiotherapy for head and neck cancer to determine whether it revealed similar evidence of accelerated tumor regrowth. Estimates of doses to achieve local control in 50% of cases (TCD50) were made from published local control rates, and the dependence of these doses on overall treatment duration was evaluated. In parallel, published scattergrams were analyzed to estimate the rate of tumor regrowth over the period of 4-10 weeks from initiation of therapy. Both analyses suggested that, on average, clonogen repopulation in squamous cell carcinomas of the head and neck accelerates only after a lag period of the order of 4 +/- 1 weeks after initiation of radiotherapy and that a dose increment of about 0.6 Gy per day is required to compensate for this repopulation. Such a dose increment is consistent with a 4-day clonogen doubling rate, compared with a median of about 60 days in published reports of unperturbed tumor growth rates. The values presented here are average values for a large number of patients: it is necessary, not only to verify the results of these retrospective analyses in prospective studies, but also to develop methods to predict the time of onset and rate of accelerated tumor clonogen repopulation in the individual patient.\n\nIndexed on Europe PMC as PubMed record 3390344 (DOI 10.3109/02841868809090333). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Acta Oncol 1988","url":"https://doi.org/10.3109/02841868809090333"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/3390344/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/3390344"}],"tags":["europepmc-ingest"],"related":["fractionation-repopulation-models"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["acta-oncologica"],"dependsOn":[],"notes":[],"journal":"Acta oncologica","year":1988,"doi":"10.3109/02841868809090333","pmid":"3390344","authors":"Withers HR, Taylor JM, Maciejewski B","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-prasad-nat-rev-clin-oncol","kind":"paper","name":"The high price of anticancer drugs: origins, implications, barriers, solutions","aka":[],"tldr":"Paper cited by one bottleneck page and 21 idea pages, indexed on Europe PMC as PubMed record 28290490 and published in Nature Reviews Clinical Oncology; the citing pages link this DOI, which is how the record was matched.","summary":"Globally, annual spending on anticancer drugs is around US$100 billion, and is predicted to rise to $150 billion by 2020. In the USA, a novel anticancer drug routinely costs more than $100,000 per year of treatment. When adjusted for per capita spending power, however, drugs are most unaffordable in economically developing nations, such as India and China. Not only are launch prices high and rising, but individual drug prices are often escalated during exclusivity periods. High drug prices harm patients - often directly through increased out-of-pocket expenses, which reduce levels of patient compliance and lead to unfavourable outcomes - and harms society - by imposing cumulative price burdens that are unsustainable. Moreover, high drug prices are not readily explained by rational factors, including the extent of benefit patients are likely to derive, the novelty of the agents, or spending on research and development. Herein, we summarize the available empirical evidence on the costs of anticancer drugs, probe the origins and implications of these high costs, and discuss proposed solutions.\n\nIndexed on Europe PMC as PubMed record 28290490 (DOI 10.1038/nrclinonc.2017.31). Matched by DOI alone: one bottleneck page and 21 idea pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Clin Oncol 2017","url":"https://doi.org/10.1038/nrclinonc.2017.31"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28290490/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28290490"}],"tags":["europepmc-ingest"],"related":["b-drug-pricing","idea-reg-middle-income-negotiation-bloc","idea-reg-pd1-biosimilar-advance-commitment","idea-reg-net-price-transparency-registry","idea-reg-market-expansion-repricing","idea-reg-biosimilar-first-default-switching","idea-reg-patent-buyout-prize","idea-reg-price-anchored-to-mcbs","idea-reg-rd-cost-disclosure-condition","idea-reg-tiered-pricing-for-exclusivity","idea-reg-secondary-patent-thicket-limits","idea-reg-indication-specific-pricing","idea-reg-annuity-payment-durable-therapies","idea-moon-pay-for-cure-contracts","idea-moon-neoantigen-vaccines-at-scale","idea-reg-provisional-price-until-os","idea-reg-academic-cart-at-cost-coverage","idea-reg-public-deescalation-trials-for-cost","idea-reg-weight-based-io-dosing-label","idea-reg-financial-toxicity-vital-sign","idea-reg-social-impact-bond-switching","idea-reg-io-subscription-national"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-clinical-oncology"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Clinical Oncology","year":2017,"doi":"10.1038/nrclinonc.2017.31","pmid":"28290490","authors":"Prasad V, De Jesús K, Mailankody S","paperType":"review","findings":[],"whatItMeans":"One bottleneck page and 21 idea pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-hudson-phillips-expanded-germline-testing-clin-breast-cancer-2026","kind":"paper","name":"The impact of expanded access to germline high penetrance genetic testing for women with a new diagnosis of invasive breast cancer or high-grade DCIS","aka":[],"tldr":"Offering high-penetrance gene testing to 576 newly diagnosed women regardless of the NHS criteria found an inherited variant in 3.6%, a quarter of whom would have been ineligible, and results in hand before surgery changed the operation chosen.","summary":"Women over 18 with invasive breast cancer or high-grade DCIS and no prior BRCA testing were offered high-penetrance germline testing. Of 576 patients, median turnaround was 33 days; 21 (3.6%) carried a germline pathogenic variant (11 BRCA1, 1.9%; 6 BRCA2, 1.0%; 4 PALB2, 0.7%), five of whom (23.8%) would not have been eligible on the NHS R208 pathway. 480 (83.3%) had primary surgery; 121 (25.2%) had results preoperatively, which significantly influenced the initial procedure (P .002); risk-reducing surgery uptake was 100% with a preoperative result versus 71.4% after.","asOf":"2026-09-24","links":[{"label":"Hudson-Phillips et al., Clin Breast Cancer 2026: expanded germline high-penetrance testing in 576 newly diagnosed patients","url":"https://doi.org/10.1016/j.clbc.2026.07.031"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42659730/"}],"tags":[],"related":[],"cancers":["tnbc","breast-cancer"],"sections":[],"technologies":["germline-testing"],"targets":["brca","palb2"],"drugs":[],"companies":[],"institutions":["royal-marsden"],"pathways":[],"terms":["gbrca-mutation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-breast-cancer"],"dependsOn":[],"notes":[],"journal":"Clinical Breast Cancer","year":2026,"doi":"10.1016/j.clbc.2026.07.031","pmid":"42659730","authors":"Hudson-Phillips SP, Nanda A, Attia M, et al.","paperType":"real-world","findings":["Pathogenic variant in 3.6% of 576 unselected new diagnoses: BRCA1 1.9%, BRCA2 1.0%, PALB2 0.7%.","23.8% of carriers would not have met R208 criteria.","Preoperative results changed the initial operation (P .002)."],"whatItMeans":"An argument for universal rather than criteria-based germline testing at diagnosis, with turnaround fast enough to inform surgery; for TNBC patients, who are already eligible, the lesson is timing.","caveats":["Single-centre programme at the Royal Marsden; 3.6% is an all-subtype figure, not TNBC-specific.","Uptake and cost data are outside the abstract."],"changedPractice":false,"participants":576},{"id":"paper-zhang-bmj-glob-health","kind":"paper","name":"The impacts of government reimbursement negotiation on targeted anticancer medication price, volume and spending in China","aka":[],"tldr":"Paper cited by one institution page, indexed on Europe PMC as PubMed record 34266848 and published in BMJ global health; the citing page links this DOI, which is how the record was matched.","summary":"Introduction: New targeted therapies have changed cancer treatment in the past decades. However, high prices of targeted anticancer medications have increased economic burden for both patients and health insurance systems. In July 2017, China implemented combined medication price negotiation and mandatory reimbursement policies for 15 targeted anticancer medications. This study assesses effects of the policy on hospital procurement prices, volumes and spending.\n\nMethods: Using a quasi-experimental interrupted time series design, we analysed procurement data from the Chinese Medical Economic Information of 789 public hospitals in 30 provinces between January 2016 and September 2018. The intervention group consisted of 15 targeted anticancer medications with negotiated prices in 2017. The comparison group consisted of six targeted anticancer medications without negotiated prices by 2018. The effective date of the policy was September 2017.\n\nResults: After the implementation of the 2017 medication price negotiation and reimbursement policy, cost per defined daily dose (DDD) of the 15 targeted anticancer medications dropped US$71.21 on average from an average US$169.24/DDD before (p=0.000). Compared with what would have happened without the intervention, cost/DDD of price-negotiated medications decreased by 48.9% (p=0.000), procurement volumes increased by 143.0% (p=0.000) and hospital medication spending decreased by 6.9% (p=0.146).\n\nConclusions: The 2017 medication price negotiation and reimbursement policy decreased targeted medication procurement costs per DDD, increased volumes procured and at least temporarily contained spending. These changes should result in better access to and affordability of targeted anticancer medications in China.\n\nIndexed on Europe PMC as PubMed record 34266848 (DOI 10.1136/bmjgh-2021-006196). Matched by DOI alone: one institution page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"BMJ Glob Health 2021","url":"https://doi.org/10.1136/bmjgh-2021-006196"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34266848/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34266848"}],"tags":["europepmc-ingest"],"related":["nhsa"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"BMJ global health","year":2021,"doi":"10.1136/bmjgh-2021-006196","pmid":"34266848","authors":"Zhang Y, Wushouer H, Han S, et al.","paperType":"observational","findings":[],"whatItMeans":"One institution page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-ranganathan-lancet-oncol","kind":"paper","name":"The International Collaboration for Research methods Development in Oncology (CReDO) workshops: shaping the future of global oncology research","aka":[],"tldr":"Paper cited by one institution page, indexed on Europe PMC as PubMed record 34216541 and published in The Lancet Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Low-income and middle-income countries (LMICs) have a disproportionately high burden of cancer and cancer mortality. The unique barriers to optimum cancer care in these regions necessitate context-specific research. The conduct of research in LMICs has several challenges, not least of which is a paucity of formal training in research methods. Building capacity by training early career researchers is essential to improve research output and cancer outcomes in LMICs. The International Collaboration for Research methods Development in Oncology (CReDO) workshop is an initiative by the Tata Memorial Centre and the National Cancer Grid of India to address gaps in research training and increase capacity in oncology research. Since 2015, there have been five CReDO workshops, which have trained more than 250 oncologists from India and other countries in clinical research methods and protocol development. Participants from all oncology and allied fields were represented at these workshops. Protocols developed included clinical trials, comparative effectiveness studies, health services research, and observational studies, and many of these protocols were particularly relevant to cancer management in LMICs. A follow-up of these participants in 2020 elicited an 88% response rate and showed that 42% of participants had made progress with their CReDO protocols, and 73% had initiated other research protocols and published papers. In this Policy Review, we describe the challenges to research in LMICs, as well as the evolution, structure, and impact of CReDO and other similar workshops on global oncology research.\n\nIndexed on Europe PMC as PubMed record 34216541 (DOI 10.1016/s1470-2045(21)00077-2). Matched by DOI alone: one institution page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2021","url":"https://doi.org/10.1016/s1470-2045(21)00077-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34216541/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34216541"}],"tags":["europepmc-ingest"],"related":["national-cancer-grid"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2021,"doi":"10.1016/s1470-2045(21)00077-2","pmid":"34216541","authors":"Ranganathan P, Chinnaswamy G, Sengar M, et al.","paperType":"review","findings":[],"whatItMeans":"One institution page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-inrg-cohn-jco-2009","kind":"paper","name":"The International Neuroblastoma Risk Group (INRG) classification system","aka":[],"tldr":"Analysing 8,800 patients worldwide, the INRG task force built a pretreatment classification for neuroblastoma using stage, age, histology, MYCN, chromosome 11q and ploidy that sorts children into very low, low, intermediate and high-risk groups.","summary":"Analysis of 8,800 children with neuroblastoma diagnosed between 1990 and 2002 from international cooperative groups, defining sixteen pretreatment groups by INRG stage, age, histological category, grade of differentiation, MYCN status, 11q aberration and ploidy, assigned to four risk groups by five-year event-free survival.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2009","url":"https://doi.org/10.1200/JCO.2008.16.6785"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19047291/"}],"tags":[],"related":[],"cancers":["neuroblastoma-high-risk","neuroblastoma-intermediate-risk","neuroblastoma-low-risk"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2009,"doi":"10.1200/JCO.2008.16.6785","pmid":"19047291","authors":"Cohn SL, Pearson AD, London WB, et al.","paperType":"methods","findings":["Sixteen pretreatment groups collapsed into very low (over 85 percent event-free survival), low, intermediate and high risk (under 50 percent)."],"whatItMeans":"Every neuroblastoma risk group on this site (very low, low, intermediate, high) is defined by the INRG system, which allows trials across continents to be compared.","caveats":["Based on patients treated in the 1990s; contemporary outcomes are better in most groups.","Segmental chromosome aberrations beyond 11q are being incorporated in revisions."],"changedPractice":true,"participants":8800},{"id":"paper-hu-signal-transduct-target-ther","kind":"paper","name":"The JAK/STAT signaling pathway: from bench to clinic","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 34824210 and published in Signal transduction and targeted therapy; the citing page links this DOI, which is how the record was matched.","summary":"The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway was discovered more than a quarter-century ago. As a fulcrum of many vital cellular processes, the JAK/STAT pathway constitutes a rapid membrane-to-nucleus signaling module and induces the expression of various critical mediators of cancer and inflammation. Growing evidence suggests that dysregulation of the JAK/STAT pathway is associated with various cancers and autoimmune diseases. In this review, we discuss the current knowledge about the composition, activation, and regulation of the JAK/STAT pathway. Moreover, we highlight the role of the JAK/STAT pathway and its inhibitors in various diseases.\n\nIndexed on Europe PMC as PubMed record 34824210 (DOI 10.1038/s41392-021-00791-1). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Signal Transduct Target Ther 2021","url":"https://doi.org/10.1038/s41392-021-00791-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34824210/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34824210"}],"tags":["europepmc-ingest"],"related":["jak-stat"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Signal transduction and targeted therapy","year":2021,"doi":"10.1038/s41392-021-00791-1","pmid":"34824210","authors":"Hu X, Li J, Fu M, et al.","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-lee-six-somatic-mutation-normal-colorectal-crypts-nature-2019","kind":"paper","name":"The landscape of somatic mutation in normal colorectal epithelial cells","aka":[],"tldr":"Reading the whole genome of hundreds of individual healthy bowel glands from 42 people found that about one in a hundred already carries a cancer-driving mutation by middle age. Polyps and cancers are the rare survivors of a process happening everywhere in the bowel lining.","summary":"Whole-genome sequencing was used to analyse hundreds of normal crypts from 42 individuals. Signatures of multiple mutational processes were revealed: some ubiquitous and continuous, others found only in some individuals, in some crypts or during certain periods of life. Probable driver mutations were present in around 1% of normal colorectal crypts in middle-aged individuals, indicating that adenomas and carcinomas are rare outcomes of a pervasive process of neoplastic change across morphologically normal colorectal epithelium. Colorectal cancers showed substantially increased mutational burdens relative to normal cells.","asOf":"2026-09-24","links":[{"label":"Lee-Six et al., Nature 2019: whole genomes of hundreds of normal colorectal crypts from 42 people","url":"https://doi.org/10.1038/s41586-019-1672-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31645730/"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["wes-wgs","single-cell-spatial"],"targets":["apc","kras"],"drugs":[],"companies":[],"institutions":[],"pathways":["field-cancerisation","clonal-evolution","mutagenesis-signatures"],"terms":["driver-mutation","mutational-signature","tmb"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2019,"doi":"10.1038/s41586-019-1672-7","pmid":"31645730","authors":"Lee-Six H, Olafsson S, Ellis P, et al.","paperType":"basic","findings":["Probable driver mutations in about 1% of normal colorectal crypts in middle age.","Multiple mutational processes, some universal and continuous, others individual or episodic.","Cancers carry substantially higher mutation burdens than normal crypts."],"whatItMeans":"It sets the baseline the adenoma-carcinoma sequence starts from and warns against reading a driver mutation found in tissue, or in stool or blood, as evidence of cancer.","caveats":["42 individuals, mostly from surgical specimens.","Crypt-level whole-genome sequencing is laborious, so the sample of crypts per person is small."],"changedPractice":false,"participants":42},{"id":"paper-cd19-dlbcl-cytotherapy-2020","kind":"paper","name":"The long road to the first FDA-approved gene therapy: chimeric antigen receptor T cells targeting CD19","aka":[],"tldr":"Review on CD19 in Diffuse large B-cell lymphoma, in Cytotherapy (2020), one of the most cited Europe PMC records with CD19 in its title.","summary":"Thirty years after initial publications of the concept of a chimeric antigen receptor (CAR), the U.S. Food and Drug Administration (FDA) approved the first anti-CD19 CAR T-cell therapy. Unlike other immunotherapies, such as immune checkpoint inhibitors and bispecific antibodies, CAR T cells are unique as they are \"living drugs,\" that is, gene-edited killer cells that can recognize and kill cancer. During these 30 years of development, the CAR construct, T-cell manufacturing process, and clinical patient management have gone through rounds of failures and successes that drove continuous improvement. Tisagenlecleucel was the first gene therapy to receive approval from the FDA for any indication. The initial approval was for relapsed or refractory (r/r) pediatric and young-adult B-cell acute lymphoblastic leukemia in August 2017 and in May 2018 for adult r/r diffuse large B-cell lymphoma. Here we review the preclinical and clinical development of what began as CART19 at the University of Pennsylvania and later developed into tisagenlecleucel.\n\nIndexed on Europe PMC as PubMed record 32014447 (DOI 10.1016/j.jcyt.2019.12.004). Its title names CD19 and its text names Diffuse large B-cell lymphoma; PubMed types it as a review (Research Support, Non-U.S. Gov't, research-article, Review, Research Support, N.I.H., Extramural). It was matched automatically to the idea \"In vivo CAR-T as a vial on the shelf: a cost and access trial in lymphoma\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cytotherapy 2020","url":"https://doi.org/10.1016/j.jcyt.2019.12.004"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32014447/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32014447"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Cytotherapy","year":2020,"doi":"10.1016/j.jcyt.2019.12.004","pmid":"32014447","authors":"Braendstrup P, Levine BL, Ruella M","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for CD19 in Diffuse large B-cell lymphoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by CD19 in the title and Diffuse large B-cell lymphoma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-armenia-long-tail-oncogenic-drivers-prostate-nat-genet-2018","kind":"paper","name":"The long tail of oncogenic drivers in prostate cancer","aka":[],"tldr":"Reanalysing 1,013 prostate cancers the same way found 97 genes driving the disease, 70 of them new, and almost all of them mutated in fewer than three tumours in a hundred.","summary":"Exome sequencing data from 1,013 prostate cancers were aggregated and uniformly analysed. A new class of ETS fusion-negative tumours was identified and validated, defined by mutations in epigenetic regulators, alongside alterations in pathways not previously implicated in prostate cancer such as the spliceosome pathway. The incidence of significantly mutated genes followed a long-tail distribution, with many genes mutated in less than 3% of cases. Ninety-seven significantly mutated genes were identified in total, including 70 not previously implicated in prostate cancer, among them the ubiquitin ligase CUL3 and the transcription factor SPEN. Comparing primary and metastatic prostate cancer identified genomic markers that may inform risk stratification.","asOf":"2026-09-25","links":[{"label":"Armenia et al., Nat Genet 2018: the long tail of oncogenic drivers across 1,013 uniformly analysed prostate cancer exomes","url":"https://doi.org/10.1038/s41588-018-0078-z"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29610475/"},{"label":"cBioPortal study prad_p1000 (MSK and Dana-Farber, Nat Genet 2018; 1,013 uniformly reanalysed prostate cancer exomes, primary and metastatic)","url":"https://www.cbioportal.org/study/summary?id=prad_p1000"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["wes-wgs"],"targets":["spop","foxa1","erg","kmt2c","kmt2d"],"drugs":[],"companies":[],"institutions":[],"pathways":["prostate-cancer-signalling","epigenetic-reprogramming","rna-splicing","ubiquitin-proteasome-system"],"terms":["driver-mutation","gene-fusion","somatic-mutations-wxs-wgs","vus"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":2018,"doi":"10.1038/s41588-018-0078-z","pmid":"29610475","authors":"Armenia J, Wankowicz SAM, Liu D, et al.","paperType":"basic","findings":["Ninety-seven significantly mutated genes, 70 of them new to prostate cancer.","A new ETS fusion-negative class defined by mutations in epigenetic regulators.","Alterations in the spliceosome pathway, not previously implicated.","A long-tail distribution with many drivers below 3% prevalence."],"whatItMeans":"It is the quantitative answer to why prostate cancer has so few targeted therapies. The common events are not druggable, the druggable ones are individually rare, and no trial can be powered on a driver present in 2% of men without an international basket.","caveats":["Aggregating exomes from different studies means different capture kits and different pipelines even after uniform reanalysis.","A mixture of primary and metastatic samples.","Statistical significance of a mutated gene is not the same as a demonstrated driver function."],"changedPractice":false,"participants":1013},{"id":"paper-keall-med-phys","kind":"paper","name":"The management of respiratory motion in radiation oncology report of AAPM Task Group 76","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 17089851 and published in Medical physics; the citing page links this DOI, which is how the record was matched.","summary":"This document is the report of a task group of the AAPM and has been prepared primarily to advise medical physicists involved in the external-beam radiation therapy of patients with thoracic, abdominal, and pelvic tumors affected by respiratory motion. This report describes the magnitude of respiratory motion, discusses radiotherapy specific problems caused by respiratory motion, explains techniques that explicitly manage respiratory motion during radiotherapy and gives recommendations in the application of these techniques for patient care, including quality assurance (QA) guidelines for these devices and their use with conformal and intensity modulated radiotherapy. The technologies covered by this report are motion-encompassing methods, respiratory gated techniques, breath-hold techniques, forced shallow-breathing methods, and respiration-synchronized techniques. The main outcome of this report is a clinical process guide for managing respiratory motion. Included in this guide is the recommendation that tumor motion should be measured (when possible) for each patient for whom respiratory motion is a concern. If target motion is greater than 5 mm, a method of respiratory motion management is available, and if the patient can tolerate the procedure, respiratory motion management technology is appropriate. Respiratory motion management is also appropriate when the procedure will increase normal tissue sparing. Respiratory motion management involves further resources, education and the development of and adherence to QA procedures.\n\nIndexed on Europe PMC as PubMed record 17089851 (DOI 10.1118/1.2349696). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Med Phys 2006","url":"https://doi.org/10.1118/1.2349696"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/17089851/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/17089851"}],"tags":["europepmc-ingest"],"related":["respiratory-gating-tumour-tracking-systems"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Medical physics","year":2006,"doi":"10.1118/1.2349696","pmid":"17089851","authors":"Keall PJ, Mageras GS, Balter JM, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-heald-mesorectum-rectal-cancer-surgery-br-j-surg-1982","kind":"paper","name":"The mesorectum in rectal cancer surgery: the clue to pelvic recurrence?","aka":[],"tldr":"Bill Heald noticed cancer cells hiding in the fatty envelope around the rectum, centimetres below the tumour, and started removing the whole envelope intact. Pelvic recurrence fell from a quarter of patients to almost none.","summary":"Heald, Husband and Ryall described five cases in which minute foci of adenocarcinoma were demonstrated in the mesorectum several centimetres distal to the apparent lower edge of a rectal cancer; in two of these there was no other evidence of lymphatic spread. In orthodox anterior resection much of this tissue remains in the pelvis, and the authors suggested that these foci might cause suture-line or pelvic recurrence.\n\nTotal excision of the mesorectum had therefore been carried out as part of over 100 consecutive anterior resections. Fifty of these, classified as curative or conceivably curative, had been followed for over two years with no pelvic or staple-line recurrence.","asOf":"2026-09-24","links":[{"label":"Br J Surg 1982","url":"https://doi.org/10.1002/bjs.1800691019"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/6751457/"}],"tags":["colorectal-evidence"],"related":["surgery-roadmap","paper-kapiteijn-dutch-tme-preoperative-radiotherapy-nejm-2001","paper-sebag-montefiore-cr07-preoperative-radiotherapy-lancet-2009"],"cancers":["colorectal","rectal-cancer"],"sections":["surgery"],"technologies":["robotic-surgery"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["total-mesorectal-excision"],"trials":[],"people":[],"bottlenecks":["b-surgery-radiation-innovation","b-workforce"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"British Journal of Surgery","year":1982,"doi":"10.1002/bjs.1800691019","pmid":"6751457","authors":"Heald RJ, Husband EM, Ryall RD.","paperType":"observational","findings":["Five cases with adenocarcinoma foci in the mesorectum several centimetres distal to the tumour's apparent lower edge; two had no other lymphatic spread.","Total mesorectal excision performed in over 100 consecutive anterior resections.","Fifty curative or conceivably curative operations followed for over two years with no pelvic or staple-line recurrence."],"whatItMeans":"The single largest improvement in rectal cancer outcomes came from a change in surgical technique, not a drug. Every radiotherapy trial since has had to show it adds something on top of a properly performed total mesorectal excision.","caveats":["A case series with two years of follow-up in one surgeon's practice; the randomised evidence came nearly two decades later with the Dutch TME trial.","The technique is operator-dependent, which is why quality assurance of the resected specimen became part of the trials that followed."],"changedPractice":true,"participants":100},{"id":"paper-jan-burger-blood-2009","kind":"paper","name":"The microenvironment in mature B-cell malignancies: a target for new treatment strategies","aka":[],"tldr":"Paper by Jan A. Burger indexed on Europe PMC as PubMed record 19636060, in Blood (2009), one of the most cited records naming an author with this name at MD Anderson Cancer Center.","summary":"Despite major therapeutic advances, most mature B-cell malignancies remain incurable. Compelling evidence suggests that crosstalk with accessory stromal cells in specialized tissue microenvironments, such as the bone marrow and secondary lymphoid organs, favors disease progression by promoting malignant B-cell growth and drug resistance. Therefore, disrupting the crosstalk between malignant B cells and their milieu is an attractive novel strategy for treating selected mature B-cell malignancies. Here we summarize the current knowledge about the cellular and molecular interactions between neoplastic B lymphocytes and accessory cells that shape a supportive microenvironment, and the potential therapeutic targets that are emerging, together with the new problems they raise. We discuss clinically relevant aspects and provide an outlook into future biologically oriented therapeutic strategies. We anticipate a paradigm shift in the treatment of selected B-cell malignancies, moving from targeting primarily the malignant cells toward combining cytotoxic drugs with agents that interfere with the microenvironment's proactive role. Such approaches hopefully will help eliminating residual disease, thereby improving our current therapeutic efforts.\n\nIndexed on Europe PMC as PubMed record 19636060 (DOI 10.1182/blood-2009-06-225326). Its author list gives \"Burger JA\" with the affiliation \"Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, TX 77230-1402, USA. jaburger@mdanderson.org\", which names MD Anderson Cancer Center; that is how the record was matched to Jan A. Burger, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Blood 2009","url":"https://doi.org/10.1182/blood-2009-06-225326"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19636060/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/19636060"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["jan-burger"],"bottlenecks":[],"keyPapers":[],"journals":["blood"],"dependsOn":[],"notes":[],"journal":"Blood","year":2009,"doi":"10.1182/blood-2009-06-225326","pmid":"19636060","authors":"Burger JA, Ghia P, Rosenwald A, et al.","paperType":"review","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Jan A. Burger at MD Anderson Cancer Center, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-diaz-molecular-evolution-egfr-resistance-colorectal-nature-2012","kind":"paper","name":"The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers","aka":[],"tldr":"Published beside the paper above: resistance to EGFR antibodies does not have to be invented, it is already there. Rare KRAS-mutant cells present before treatment expand under it, on a schedule a mathematical model predicts.","summary":"The hypothesis that rare cells with KRAS mutations pre-exist at low levels in tumours with ostensibly wild-type KRAS genes was tested by looking for mutant KRAS DNA in the circulation of 28 patients receiving monotherapy with panitumumab. Of 24 patients whose tumours were initially KRAS wild-type, 9 (38%) developed detectable KRAS mutations in their serum, three of them multiple different mutations. The appearance of the mutations was consistent, generally occurring between 5 and 6 months after starting treatment. Mathematical modelling indicated that the mutations were present in expanded subclones before panitumumab was begun, explaining why solid tumours develop resistance to targeted therapies in a highly reproducible fashion.","asOf":"2026-09-24","links":[{"label":"Diaz et al., Nature 2012: the molecular evolution of acquired resistance to EGFR blockade (28 panitumumab patients)","url":"https://doi.org/10.1038/nature11219"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22722843/"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["liquid-biopsy"],"targets":["kras","egfr"],"drugs":["panitumumab"],"companies":[],"institutions":["johns-hopkins"],"pathways":["clonal-evolution","ras-mapk"],"terms":["ctdna","cfdna"],"trials":[],"people":["luis-diaz","bert-vogelstein","kenneth-kinzler"],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2012,"doi":"10.1038/nature11219","pmid":"22722843","authors":"Diaz LA, Williams RT, Wu J, et al.","paperType":"translational","findings":["KRAS mutations appeared in the serum of 9 of 24 initially wild-type patients (38%), generally 5 to 6 months into treatment.","Modelling placed the resistant subclones in the tumour before treatment started."],"whatItMeans":"It reframed resistance as selection rather than mutation, which is why the field now asks how to suppress a pre-existing clone rather than how to prevent a new mutation, and why ctDNA is the natural monitoring tool.","caveats":["28 patients on monotherapy; modern practice uses combinations.","Serum rather than plasma, with the assay sensitivity of 2012.","KRAS is one of several resistance mechanisms."],"changedPractice":false,"participants":28},{"id":"paper-bolouri-paediatric-aml-genomics-nat-med-2018","kind":"paper","name":"The molecular landscape of paediatric acute myeloid leukaemia (TARGET)","aka":[],"tldr":"Sequencing nearly a thousand childhood acute myeloid leukaemias showed the disease differs sharply from adult disease, with fewer mutations, more structural rearrangements and age-specific drivers, so adult genetic risk groups cannot simply be transferred to children.","summary":"Comprehensive genomic study by the TARGET initiative of 993 children and young adults with AML, including whole-genome, exome, transcriptome and methylation profiling, identifying age-specific patterns of somatic mutations, structural variants such as KMT2A and NUP98 rearrangements, and novel focal deletions.","asOf":"2026-09-17","links":[{"label":"Nat Med 2018","url":"https://doi.org/10.1038/nm.4439"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29227476/"}],"tags":[],"related":[],"cancers":["aml-paediatric"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2018,"doi":"10.1038/nm.4439","pmid":"29227476","authors":"Bolouri H, Farrar JE, Triche T, et al.","paperType":"translational","findings":["Low mutation burden in childhood AML with structural variants and fusions predominating.","Distinct age-associated mutations, for example NPM1 and DNMT3A being rare in young children."],"whatItMeans":"Paediatric AML risk classification and targeted therapy development now rest on this landscape rather than on adult data.","caveats":["Discovery cohort; clinical translation into risk stratification is ongoing."],"changedPractice":true,"participants":993},{"id":"paper-cheasley-mucinous-ovarian-genomics-nat-commun-2019","kind":"paper","name":"The molecular origin and taxonomy of mucinous ovarian carcinoma","aka":[],"tldr":"Genomic analysis of over 200 mucinous ovarian tumours showed they arise in the ovary from benign and borderline precursors through KRAS, TP53 and CDKN2A changes, and are genuinely different from the gastrointestinal cancers they resemble.","summary":"Genomic study of 227 mucinous ovarian tumours (benign, borderline and carcinoma) identifying a progression model with KRAS mutation and CDKN2A loss early, TP53 mutation and copy-number gains including HER2 amplification in carcinomas, and a distinct profile from colorectal, gastric and pancreatic cancers.","asOf":"2026-09-17","links":[{"label":"Nat Commun 2019","url":"https://doi.org/10.1038/s41467-019-11862-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31477716/"}],"tags":[],"related":[],"cancers":["mucinous-ovarian-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-communications"],"dependsOn":[],"notes":[],"journal":"Nature Communications","year":2019,"doi":"10.1038/s41467-019-11862-x","pmid":"31477716","authors":"Cheasley D, Wakefield MJ, Ryland GL, et al.","paperType":"translational","findings":["KRAS mutation in about 65 percent, TP53 in 64 percent and CDKN2A loss in 76 percent of carcinomas.","HER2 amplification in about 26 percent of carcinomas."],"whatItMeans":"Mucinous ovarian carcinoma is confirmed as a primary ovarian disease with its own biology; HER2 amplification in about a fifth of cases is a possible treatment target.","caveats":["Treatment implications remain under investigation."],"changedPractice":true,"participants":227},{"id":"paper-doll-hill-mortality-of-doctors-smoking-bmj-1954","kind":"paper","name":"The mortality of doctors in relation to their smoking habits; a preliminary report","aka":[],"tldr":"Doll and Hill wrote to every doctor in Britain in 1951 asking how much they smoked, then waited to see who died. This first report, after two and a half years, is where the prospective evidence on smoking begins.","summary":"Richard Doll and Austin Bradford Hill's first report from the British Doctors Study, published in the British Medical Journal on 26 June 1954. The 1950 case-control paper had been attacked as an artefact of how cases and controls were chosen, so Doll and Hill built the answer the objection required: a cohort assembled before anybody was ill, its smoking habits recorded in advance, followed forward to death.\n\nEurope PMC indexes no abstract for the 1954 article, so OnCo carries no figures from it. The study ran for fifty years; the corpus holds the fifty-year report as paper-doll-peto-50-year-doctors-bmj-2004, and that record carries the figures the design eventually produced.","asOf":"2026-09-25","links":[{"label":"BMJ 1954","url":"https://doi.org/10.1136/bmj.1.4877.1451"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/13160495/"},{"label":"BMJ 2004 reprint of the 1954 report","url":"https://europepmc.org/article/MED/15217868"}],"tags":["lung-evidence"],"related":["paper-doll-hill-smoking-lung-cancer-bmj-1950","paper-doll-peto-50-year-doctors-bmj-2004","paper-wynder-graham-tobacco-bronchiogenic-carcinoma-jama-1950","prevention-roadmap"],"cancers":["lung-cancer","nsclc"],"sections":["prevention"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["richard-peto"],"bottlenecks":["b-prevention-adoption"],"keyPapers":[],"journals":["bmj"],"dependsOn":[],"notes":[],"journal":"BMJ","year":1954,"doi":"10.1136/bmj.1.4877.1451","pmid":"13160495","authors":"Doll R, Hill AB.","paperType":"observational","findings":["No abstract is indexed on Europe PMC; the design (a prospective cohort of British doctors whose smoking habits were recorded in 1951 and whose deaths were then followed) is read from the article itself."],"whatItMeans":"The methodological ancestor of modern cancer epidemiology. Cohort design, exposure recorded before outcome, and a dose-response relationship measured rather than asserted: this is the template every later study of a cancer risk factor follows.","caveats":["A preliminary report at two and a half years of follow-up; the dose-response and cessation results that mattered came from the ten, twenty, forty and fifty-year reports.","British male doctors are not the general population: they smoked, quit and died differently from the people they treated, which is a strength for internal validity and a limit on generalisation."],"changedPractice":true},{"id":"paper-dbouk-caps5-stage-survival-jco-2022","kind":"paper","name":"The Multicenter Cancer of Pancreas Screening Study: Impact on Stage and Survival","aka":[],"tldr":"The 2022 report from eight US centres: among 1,461 people at high inherited risk under regular scanning, most pancreatic cancers were caught at stage I, and across all the CAPS cohorts patients whose cancer was found by surveillance lived a median of nearly ten years against a year and a half for those found outside it.","summary":"Dbouk, Goggins and colleagues report the CAPS5 study, 1,461 high-risk individuals enrolled at eight centres between 2014 and 2021, 48.5 percent with a pathogenic variant in a susceptibility gene. Ten were diagnosed with pancreatic cancer, one metastatic four years after leaving surveillance; of the other nine, seven (77.8 percent) were stage I by surgical pathology, one stage II and one stage III, and seven of nine were alive at a median of 2.6 years. Eight more had surgery for worrisome lesions (three high-grade, five low-grade dysplasia). Across CAPS1 to CAPS5 (1,731 patients), 26 cancers were diagnosed, 19 within surveillance, 57.9 percent stage I and 5.2 percent stage IV, against six of seven (85.7 percent) stage IV among cancers found outside surveillance. Five-year survival of screen-detected cancer was 73.3 percent and median overall survival 9.8 years, against 1.5 years outside surveillance (hazard ratio 0.13, 95 percent confidence interval 0.03 to 0.50, P = 0.003).","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2022","url":"https://doi.org/10.1200/JCO.22.00298"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35704792/"}],"tags":["pancreatic-evidence"],"related":["paper-canto-caps-long-term-surveillance-gastroenterology-2018","paper-caps-consortium-surveillance-recommendations-gut-2020","paper-hu-germline-mutations-pancreatic-cancer-risk-jama-2018"],"cancers":["pancreatic","resectable-pdac"],"sections":[],"technologies":["pancreatic-surveillance","germline-testing","mri"],"targets":[],"drugs":[],"companies":[],"institutions":["johns-hopkins","penn-abramson","upmc-hillman"],"pathways":[],"terms":["os","hazard-ratio"],"trials":["precede"],"people":[],"bottlenecks":["b-hereditary-risk","b-early-detection"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2022,"doi":"10.1200/JCO.22.00298","pmid":"35704792","authors":"Dbouk M, Katona BW, Brand RE, et al.","paperType":"observational","findings":["1,461 high-risk individuals at eight centres; 7 of 9 surveillance-detected cancers were stage I.","Across CAPS1 to 5 (1,731 patients): 57.9 percent of surveillance-detected cancers stage I, 5.2 percent stage IV; 85.7 percent of cancers found outside surveillance stage IV.","Five-year survival 73.3 percent and median survival 9.8 years for screen-detected cancer versus 1.5 years outside surveillance (hazard ratio 0.13)."],"whatItMeans":"The stage shift the pancreatic cancer page quotes (about three in four surveillance-detected cancers at stage I) and the strongest argument for offering surveillance to every germline carrier found by universal testing, which the NHS does not yet do outside research.","caveats":["Observational; the comparison with cancers found outside surveillance is subject to lead-time, length-time and selection bias.","Nine surveillance-detected cancers in CAPS5; the absolute yield is low and the cost per cancer found is high."],"changedPractice":true,"participants":1461},{"id":"paper-bakhoum-cell","kind":"paper","name":"The Multifaceted Role of Chromosomal Instability in Cancer and Its Microenvironment","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 30193109 and published in Cell; the citing page links this DOI, which is how the record was matched.","summary":"Chromosomal instability (CIN) is a hallmark of human cancer, and it is associated with poor prognosis, metastasis, and therapeutic resistance. CIN results from errors in chromosome segregation during mitosis, leading to structural and numerical chromosomal abnormalities. In addition to generating genomic heterogeneity that acts as a substrate for natural selection, CIN promotes inflammatory signaling by introducing double-stranded DNA into the cytosol, engaging the cGAS-STING anti-viral pathway. These multipronged effects distinguish CIN as a central driver of tumor evolution and as a genomic source for the crosstalk between the tumor and its microenvironment, in the course of immune editing and evasion.\n\nIndexed on Europe PMC as PubMed record 30193109 (DOI 10.1016/j.cell.2018.08.027). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cell 2018","url":"https://doi.org/10.1016/j.cell.2018.08.027"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30193109/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30193109"}],"tags":["europepmc-ingest"],"related":["aneuploidy-theory-of-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Cell","year":2018,"doi":"10.1016/j.cell.2018.08.027","pmid":"30193109","authors":"Bakhoum SF, Cantley LC","paperType":"review","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-rohrig-nat-rev-cancer","kind":"paper","name":"The multifaceted roles of fatty acid synthesis in cancer","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 27658529 and published in Nature Reviews Cancer; the citing page links this DOI, which is how the record was matched.","summary":"Lipid metabolism, in particular the synthesis of fatty acids (FAs), is an essential cellular process that converts nutrients into metabolic intermediates for membrane biosynthesis, energy storage and the generation of signalling molecules. This Review explores how different aspects of FA synthesis promote tumorigenesis and tumour progression. FA synthesis has received substantial attention as a potential target for cancer therapy, but strategies to target this process have not yet translated into clinical practice. Furthermore, efforts to target this pathway must consider the influence of the tumour microenvironment.\n\nIndexed on Europe PMC as PubMed record 27658529 (DOI 10.1038/nrc.2016.89). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Cancer 2016","url":"https://doi.org/10.1038/nrc.2016.89"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27658529/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27658529"}],"tags":["europepmc-ingest"],"related":["lipid-metabolism-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Cancer","year":2016,"doi":"10.1038/nrc.2016.89","pmid":"27658529","authors":"Röhrig F, Schulze A","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-juarez-ivermectin-repositioned-cancer-drug-2018","kind":"paper","name":"The multitargeted drug ivermectin: from an antiparasitic agent to a repositioned cancer drug","aka":[],"tldr":"A 2018 review that gathered the cell-culture and animal experiments on ivermectin and argued it was ready for cancer trials; those trials began five years later and have not reported.","summary":"The review summarises in vitro and in vivo experiments in which ivermectin acted on multidrug resistance protein, Akt/mTOR and WNT-TCF signalling, purinergic receptors, PAK1, the SIN3A and SIN3B epigenetic regulators, RNA helicase and chloride channels, and on cancer stem-like cells (Juarez review 2018). It argues that the concentrations used are reachable in people on the basis of pharmacokinetic studies in healthy and parasite-infected volunteers, and that this could allow a rapid move into trials (Juarez review 2018).","asOf":"2026-09-24","links":[{"label":"Juarez review 2018","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5835698/"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29511601/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["drug-repurposing","fenbendazole-ivermectin-repurposing-claims"],"targets":[],"drugs":["ivermectin"],"companies":[],"institutions":[],"pathways":[],"terms":["in-vitro-in-vivo","preclinical"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo agent (Claude Fable 5.1)","editedOn":"2026-09-24","note":"Written from cached ClinicalTrials.gov v2, Europe PMC, DailyMed, Drugs@FDA and WHO eEML responses; no figure appears without its source link."},"journal":"American Journal of Cancer Research","year":2018,"pmid":"29511601","authors":"Juarez M, Schcolnik-Cabrera A, Dueñas-Gonzalez A.","paperType":"review","findings":["Laboratory evidence only: cell lines and animal models across several cancer types.","Argues that anticancer concentrations are clinically reachable, on pharmacokinetic grounds, not on any patient data."],"whatItMeans":"This is the paper the online claims usually trace back to. It is a call for trials, not evidence that the drug works in people, and the trials it called for are still running.","caveats":["No human efficacy data existed when it was written and none has been published since.","The concentration argument has not been tested in a cancer patient."],"changedPractice":false},{"id":"paper-erices-chilean-gallbladder-landscape-front-oncol-2025","kind":"paper","name":"The mutational landscape and actionable targets of gallbladder cancer: an ancestry-informed and comparative analysis of a Chilean population","aka":[],"tldr":"The first genomic landscape of Chilean gallbladder cancer, in 56 tumours, found TP53, TSC2 and NOTCH1 the most mutated genes, actionable changes in ATM, BRCA1/2, EGFR and ERBB2, and a hint that Mapuche ancestry goes with TP53 mutation.","summary":"118 tumour samples were collected, of which 56 passed sequencing quality control on the Oncomine Comprehensive Assay v1. Somatic variants were annotated with ANNOVAR and the Cancer Genome Interpreter, ancestry was inferred with ADMIXTURE and principal components on ancestry-informative markers, and comparisons were made with Japanese, Singaporean and United States cohorts.\n\n535 somatic mutations were detected in 43 genes, with TP53 (30%), TSC2 (29%) and NOTCH1 (27%) most frequently mutated. 121 clinically actionable variants were identified in ATM, BRCA1/2, EGFR, ERBB2 and other genes. Exploratory analysis suggested an association between higher Mapuche ancestry and TP53 mutations, and comparative analyses revealed distinct mutational patterns in the Chilean cohort relative to Asian and United States datasets.","asOf":"2026-09-24","links":[{"label":"Erices et al., Front Oncol 2025: mutational landscape of Chilean gallbladder cancer","url":"https://doi.org/10.3389/fonc.2025.1658528"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41114336/"}],"tags":[],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":["tp53","tsc2","notch1","atm","brca","egfr","her2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Frontiers in Oncology","year":2025,"doi":"10.3389/fonc.2025.1658528","pmid":"41114336","authors":"Erices JI, Gonzalez E, Salgado M, et al.","paperType":"translational","findings":["TP53 30%, TSC2 29%, NOTCH1 27% among 56 Chilean tumours.","121 actionable variants in ATM, BRCA1/2, EGFR, ERBB2 and other genes.","Exploratory association between Mapuche ancestry and TP53 mutation."],"whatItMeans":"Chile has the world's highest gallbladder cancer mortality and until this paper almost no tumour genomics; the lower TP53 rate and high TSC2 and NOTCH1 hint at a different mutational grammar, but the panel and sample size mean the figures need replication.","caveats":["Only 56 of 118 samples passed quality control; the 143-gene panel does not cover ELF3, SMAD4 or ARID1A comprehensively.","Ancestry association was exploratory."],"changedPractice":false,"participants":56},{"id":"paper-grasso-mutational-landscape-lethal-crpc-nature-2012","kind":"paper","name":"The mutational landscape of lethal castration-resistant prostate cancer","aka":["Grasso 2012","lethal CRPC exome rapid autopsy"],"tldr":"Fifty men who died of prostate cancer had their tumours sequenced within hours of death. Even after years of treatment the cancers carried few mutations, and the recurring ones were in genes that control how DNA is packaged and read rather than in classic cancer genes.","summary":"Catherine Grasso, Arul Chinnaiyan and colleagues sequenced the exomes of 50 lethal, heavily pre-treated metastatic castration-resistant prostate cancers obtained at rapid autopsy, including three separate deposits from one patient, alongside 11 treatment-naive high-grade localised cancers.\n\nThe low mutation rate, 2.00 per megabase even after years of therapy, is the number to remember: prostate cancer is a structurally rearranged genome rather than a heavily mutated one, which is why tumour mutational burden rarely qualifies it for immunotherapy. The recurrent mutations that were found sit in chromatin and histone-modifying genes and in the androgen receptor's collaborators, and the paper showed physical interaction between the MLL complex and the receptor. CHD1 disruption defined a subtype of ETS fusion-negative disease, and FOXA1 mutations were found in 5 of 147 tumours.","asOf":"2026-09-25","links":[{"label":"Nature 2012","url":"https://doi.org/10.1038/nature11125"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22722839/"},{"label":"cBioPortal study prad_mich (University of Michigan, Nature 2012; 61 samples, 50 lethal castration-resistant cancers at rapid autopsy and 11 treatment-naive primaries)","url":"https://www.cbioportal.org/study/summary?id=prad_mich"}],"tags":["prostate-evidence"],"related":["paper-baca-punctuated-evolution-chromoplexy-cell-2013","paper-robinson-integrative-clinical-genomics-advanced-prostate-cell-2015","prostate-roadmap"],"cancers":["prostate","prostate-mcrpc"],"sections":["diagnostics","epigenetics"],"technologies":["wes-wgs"],"targets":["foxa1","erg","tmprss2","androgen-receptor","kmt2d","kmt2c"],"drugs":[],"companies":[],"institutions":["michigan-rogel"],"pathways":["ar-signaling","epigenetic-reprogramming","clonal-evolution","prostate-cancer-signalling"],"terms":["tmb","ngs","chromoplexy","driver-mutation","gene-fusion","castration-resistance","somatic-mutations-wxs-wgs"],"trials":[],"people":["arul-chinnaiyan"],"bottlenecks":["b-undruggable-targets","b-immunotherapy-response","b-tumor-heterogeneity"],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2012,"doi":"10.1038/nature11125","pmid":"22722839","authors":"Grasso CS, Wu YM, Robinson DR, et al.","paperType":"basic","findings":["Low overall mutation rates even in heavily treated castration-resistant disease, at 2.00 per megabase, and confirmation of the monoclonal origin of lethal castration-resistant prostate cancer.","Disruptions of CHD1 define a subtype of ETS gene family fusion-negative prostate cancer.","Recurrent mutations in multiple chromatin- and histone-modifying genes, including MLL2 in 8.6 percent of prostate cancers, with the MLL complex shown to interact with the androgen receptor as required for androgen receptor-mediated signalling.","Novel recurrent mutations in FOXA1 in 5 of 147 prostate cancers (3.4 percent), in both untreated localised disease and castration-resistant disease; mutated FOXA1 represses androgen signalling and increases tumour growth.","ETS2, deleted in approximately one third of castration-resistant cancers, commonly through TMPRSS2-ERG fusion, is also deregulated through mutation."],"whatItMeans":"The explanation for why prostate cancer has so few targeted drugs outside the hormone axis and the DNA-repair genes: it is a quiet genome with structural rather than point-mutational damage, and the recurrent changes sit in the machinery that reads DNA rather than in kinases.","caveats":["50 rapid-autopsy cases is a small and extreme sample, selected for death from the disease and for heavy prior treatment.","Exome sequencing misses the structural rearrangements that Baca and Gundem later showed dominate this cancer.","Mutation frequencies from 61 tumours are not population estimates; TCGA and the SU2C cohort give better ones."],"changedPractice":false,"participants":61},{"id":"paper-dhanasekaran-nat-rev-clin-oncol","kind":"paper","name":"The MYC oncogene - the grand orchestrator of cancer growth and immune evasion","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 34508258 and published in Nature Reviews Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"The MYC proto-oncogenes encode a family of transcription factors that are among the most commonly activated oncoproteins in human neoplasias. Indeed, MYC aberrations or upregulation of MYC-related pathways by alternate mechanisms occur in the vast majority of cancers. MYC proteins are master regulators of cellular programmes. Thus, cancers with MYC activation elicit many of the hallmarks of cancer required for autonomous neoplastic growth. In preclinical models, MYC inactivation can result in sustained tumour regression, a phenomenon that has been attributed to oncogene addiction. Many therapeutic agents that directly target MYC are under development; however, to date, their clinical efficacy remains to be demonstrated. In the past few years, studies have demonstrated that MYC signalling can enable tumour cells to dysregulate their microenvironment and evade the host immune response. Herein, we discuss how MYC pathways not only dictate cancer cell pathophysiology but also suppress the host immune response against that cancer. We also propose that therapies targeting the MYC pathway will be key to reversing cancerous growth and restoring antitumour immune responses in patients with MYC-driven cancers.\n\nIndexed on Europe PMC as PubMed record 34508258 (DOI 10.1038/s41571-021-00549-2). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Clin Oncol 2022","url":"https://doi.org/10.1038/s41571-021-00549-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34508258/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34508258"}],"tags":["europepmc-ingest"],"related":["myc"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-clinical-oncology"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Clinical Oncology","year":2022,"doi":"10.1038/s41571-021-00549-2","pmid":"34508258","authors":"Dhanasekaran R, Deutzmann A, Mahauad-Fernandez WD, et al.","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-pramesh-indian-j-med-paediatr-oncol","kind":"paper","name":"The national cancer grid of India","aka":[],"tldr":"Paper cited by one institution page, indexed on Europe PMC as PubMed record 25336795 and published in Indian journal of medical and paediatric oncology; the citing page links this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 25336795 (DOI 10.4103/0971-5851.142040). Matched by DOI alone: one institution page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Indian J Med Paediatr Oncol 2014","url":"https://doi.org/10.4103/0971-5851.142040"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25336795/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25336795"}],"tags":["europepmc-ingest"],"related":["national-cancer-grid"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Indian journal of medical and paediatric oncology","year":2014,"doi":"10.4103/0971-5851.142040","pmid":"25336795","authors":"Pramesh CS, Badwe RA, Sinha RK","paperType":"observational","findings":[],"whatItMeans":"One institution page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-middleton-nature","kind":"paper","name":"The National Lung Matrix Trial of personalized therapy in lung cancer","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 32669708 and published in Nature; the citing page links this DOI, which is how the record was matched.","summary":"The majority of targeted therapies for non-small-cell lung cancer (NSCLC) are directed against oncogenic drivers that are more prevalent in patients with light exposure to tobacco smoke 1-3. As this group represents around 20% of all patients with lung cancer, the discovery of stratified medicine options for tobacco-associated NSCLC is a high priority. Umbrella trials seek to streamline the investigation of genotype-based treatments by screening tumours for multiple genomic alterations and triaging patients to one of several genotype-matched therapeutic agents. Here we report the current outcomes of 19 drug-biomarker cohorts from the ongoing National Lung Matrix Trial, the largest umbrella trial in NSCLC. We use next-generation sequencing to match patients to appropriate targeted therapies on the basis of their tumour genotype. The Bayesian trial design enables outcome data from open cohorts that are still recruiting to be reported alongside data from closed cohorts. Of the 5,467 patients that were screened, 2,007 were molecularly eligible for entry into the trial, and 302 entered the trial to receive genotype-matched therapy-including 14 that re-registered to the trial for a sequential trial drug. Despite pre-clinical data supporting the drug-biomarker combinations, current evidence shows that a limited number of combinations demonstrate clinically relevant benefits, which remain concentrated in patients with lung cancers that are associated with minimal exposure to tobacco smoke.\n\nIndexed on Europe PMC as PubMed record 32669708 (DOI 10.1038/s41586-020-2481-8). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2020","url":"https://doi.org/10.1038/s41586-020-2481-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32669708/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32669708"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["national-lung-matrix-trial"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2020,"doi":"10.1038/s41586-020-2481-8","pmid":"32669708","authors":"Middleton G, Fletcher P, Popat S, et al.","paperType":"observational","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-o-dwyer-nat-med","kind":"paper","name":"The NCI-MATCH trial: lessons for precision oncology","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 37322121 and published in Nature Medicine; the citing page links this DOI, which is how the record was matched.","summary":"The NCI-MATCH (Molecular Analysis for Therapy Choice) trial ( NCT02465060) was launched in 2015 as a genomically driven, signal-seeking precision medicine platform trial-largely for patients with treatment-refractory, malignant solid tumors. Having completed in 2023, it remains one of the largest tumor-agnostic, precision oncology trials undertaken to date. Nearly 6,000 patients underwent screening and molecular testing, with a total of 1,593 patients (inclusive of continued accrual from standard next-generation sequencing) being assigned to one of 38 substudies. Each substudy was a phase 2 trial of a therapy matched to a genomic alteration, with a primary endpoint of objective tumor response by RECIST criteria. In this Perspective, we summarize the outcomes of the initial 27 substudies in NCI-MATCH, which met its signal-seeking objective with 7/27 positive substudies (25.9%). We discuss key aspects of the design and operational conduct of the trial, highlighting important lessons for future precision medicine studies.\n\nIndexed on Europe PMC as PubMed record 37322121 (DOI 10.1038/s41591-023-02379-4). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Med 2023","url":"https://doi.org/10.1038/s41591-023-02379-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37322121/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37322121"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nci-match"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2023,"doi":"10.1038/s41591-023-02379-4","pmid":"37322121","authors":"O'Dwyer PJ, Gray RJ, Flaherty KT, et al.","paperType":"review","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-fidler-nat-rev-cancer","kind":"paper","name":"The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 12778135 and published in Nature Reviews Cancer; the citing page links this DOI, which is how the record was matched.","summary":"Researchers have been studying metastasis for more than 100 years, and only recently have we gained insight into the mechanisms by which metastatic cells arise from primary tumours and the reasons that certain tumour types tend to metastasize to specific organs. Stephen Paget's 1889 proposal that metastasis depends on cross-talk between selected cancer cells (the 'seeds') and specific organ microenvironments (the 'soil') still holds forth today. It is now known that the potential of a tumour cell to metastasize depends on its interactions with the homeostatic factors that promote tumour-cell growth, survival, angiogenesis, invasion and metastasis. How has this field developed over the past century, and what major breakthroughs are most likely to lead to effective therapeutic approaches?\n\nIndexed on Europe PMC as PubMed record 12778135 (DOI 10.1038/nrc1098). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Cancer 2003","url":"https://doi.org/10.1038/nrc1098"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/12778135/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/12778135"}],"tags":["europepmc-ingest"],"related":["seed-and-soil-hypothesis"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Cancer","year":2003,"doi":"10.1038/nrc1098","pmid":"12778135","authors":"Fidler IJ","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-fabbri-nat-rev-cancer","kind":"paper","name":"The plasticity of mRNA translation during cancer progression and therapy resistance","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 34341537 and published in Nature Reviews Cancer; the citing page links this DOI, which is how the record was matched.","summary":"Translational control of mRNAs during gene expression allows cells to promptly and dynamically adapt to a variety of stimuli, including in neoplasia in response to aberrant oncogenic signalling (for example, PI3K-AKT-mTOR, RAS-MAPK and MYC) and microenvironmental stress such as low oxygen and nutrient supply. Such translational rewiring allows rapid, specific changes in the cell proteome that shape specific cancer phenotypes to promote cancer onset, progression and resistance to anticancer therapies. In this Review, we illustrate the plasticity of mRNA translation. We first highlight the diverse mechanisms by which it is regulated, including by translation factors (for example, eukaryotic initiation factor 4F (eIF4F) and eIF2), RNA-binding proteins, tRNAs and ribosomal RNAs that are modulated in response to aberrant intracellular pathways or microenvironmental stress. We then describe how translational control can influence tumour behaviour by impacting on the phenotypic plasticity of cancer cells as well as on components of the tumour microenvironment. Finally, we highlight the role of mRNA translation in the cellular response to anticancer therapies and its promise as a key therapeutic target.\n\nIndexed on Europe PMC as PubMed record 34341537 (DOI 10.1038/s41568-021-00380-y). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Cancer 2021","url":"https://doi.org/10.1038/s41568-021-00380-y"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34341537/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34341537"}],"tags":["europepmc-ingest"],"related":["mrna-translation-eif4f"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Cancer","year":2021,"doi":"10.1038/s41568-021-00380-y","pmid":"34341537","authors":"Fabbri L, Chakraborty A, Robert C, et al.","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-pik3ca-colorectal-acta-oncol-2014","kind":"paper","name":"The predictive value of KRAS, NRAS, BRAF, PIK3CA and PTEN for anti-EGFR treatment in metastatic colorectal cancer: A systematic review and meta-analysis","aka":[],"tldr":"Review on PIK3CA in Colorectal cancer, in Acta oncologica (2014), one of the most cited Europe PMC records with PIK3CA in its title.","summary":"Background: In metastatic colorectal cancer, mutation testing for KRAS exon 2 is widely implemented to select patients with wild-type tumors for treatment with the monocloncal anti-EGFR antibodies cetuximab and panitumumab. The added predictive value of additional biomarkers in the RAS-RAF-MAPK and PI3K-AKT-mTOR pathways in colorectal cancer is uncertain, which led us to systematically review the impact of alterations in KRAS (outside of exon 2), NRAS, BRAF, PIK3CA and PTEN in relation to the clinical benefit from anti-EGFR treatment.\n\nMethods: In total, 22 studies that include 2395 patients formed the basis for a meta-analysis on alterations in KRAS exons 3 and 4, NRAS, BRAF, and PIK3CA and PTEN and outcome of anti-EGFR treatment. Odds ratios for objective response rate (ORR) and hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS) were calculated.\n\nResults: Mutations in KRAS exons 3 and 4, BRAF, PIK3CA and non-functional PTEN (mutations or loss of protein expression) significantly predicted poor ORR (OR = 0.26, OR = 0.29, OR = 0.39, and OR = 0.41, respectively). Significantly shorter PFS applied to mutations in KRAS exons 3 and 4 (HR = 2.19), NRAS (HR = 2.30) and BRAF (HR = 2.95) and non-functional PTEN (HR = 1.88). Significantly shorter OS applied to mutations in KRAS exons 3 and 4 (HR = 1.78), NRAS (HR = 1.85), BRAF (HR = 2.52), PIK3CA (HR = 1.43) and alterations in PTEN (HR = 2.09).\n\nConclusions: Meta-analysis suggests that mutations in KRAS exons 3 and 4, NRAS, BRAF and PIK3CA and non-functional PTEN predict resistance to anti-EGFR therapies and demonstrates that biomarker analysis beyond KRAS exon 2 should be implemented for prediction of clinical benefit from anti-EGFR antibodies in metastatic colorectal cancer.\n\nIndexed on Europe PMC as PubMed record 24666267 (DOI 10.3109/0284186x.2014.895036). Its title names PIK3CA and its text names Colorectal cancer; PubMed types it as a review (Meta-Analysis, Systematic Review). It was matched automatically to the idea \"Get biomarker-directed aspirin after colorectal surgery into labels and guidelines\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Acta Oncol 2014","url":"https://doi.org/10.3109/0284186x.2014.895036"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24666267/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/24666267"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["acta-oncologica"],"dependsOn":[],"notes":[],"journal":"Acta oncologica","year":2014,"doi":"10.3109/0284186x.2014.895036","pmid":"24666267","authors":"Therkildsen C, Bergmann TK, Henrichsen-Schnack T, et al.","paperType":"meta-analysis","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for PIK3CA in Colorectal cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by PIK3CA in the title and Colorectal cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-villarreal-garza-mexican-tnbc-brca-bcrt-2015","kind":"paper","name":"The prevalence of BRCA1 and BRCA2 mutations among young Mexican women with triple-negative breast cancer","aka":[],"tldr":"Among 190 Mexican women diagnosed with triple-negative breast cancer at 50 or under, 23% carried a BRCA mutation, nearly all in BRCA1, and a single large deletion founder mutation accounted for 41% of them.","summary":"190 women with TNBC diagnosed at age 50 or less at a single Mexico City hospital, unselected for family history, were screened for 115 recurrent BRCA mutations reported in Hispanic women including the Mexican founder large rearrangement BRCA1 ex9-12del. A mutation was detected in 44 (23%): 43 in BRCA1 and one in BRCA2. Seven mutations accounted for 39 patients (89%); the founder BRCA1 ex9-12del was found 18 times (41% of mutations).","asOf":"2026-09-24","links":[{"label":"Villarreal-Garza et al., Breast Cancer Res Treat 2015: BRCA mutations in 190 young Mexican TNBC patients","url":"https://doi.org/10.1007/s10549-015-3312-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25716084/"}],"tags":[],"related":[],"cancers":["tnbc"],"sections":[],"technologies":[],"targets":["brca"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["gbrca-mutation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["breast-cancer-research-and-treatment"],"dependsOn":[],"notes":[],"journal":"Breast Cancer Research and Treatment","year":2015,"doi":"10.1007/s10549-015-3312-8","pmid":"25716084","authors":"Villarreal-Garza C, Weitzel JN, Llacuachaqui M, et al.","paperType":"observational","findings":["BRCA mutation in 44 of 190 young Mexican TNBC patients, 23%; 43 in BRCA1.","BRCA1 ex9-12del accounted for 41% of mutations; seven recurrent mutations for 89%."],"whatItMeans":"A recurrent-mutation panel catches most carriers in Mexican TNBC at a fraction of the cost of full sequencing, and the large-rearrangement founder allele is missed by sequencing-only assays that do not test for deletions.","caveats":["Recurrent-mutation screening, so novel mutations were not sought.","Single hospital; patients aged 50 or under only."],"changedPractice":false,"participants":190},{"id":"paper-browne-clin-cancer-res","kind":"paper","name":"The Prognostic and Predictive Impact of ctDNA Levels in Patients with Advanced Breast Cancer Enrolled on the plasmaMATCH Trial","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 41159912 and published in Clinical Cancer Research; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: ctDNA dynamic levels may identify patients who will respond to therapy. We assessed ctDNA baseline levels and on-treatment dynamics in patients with advanced breast cancer on the plasmaMATCH trial with mutation-targeted therapies (cohorts A-D) and triple-negative breast cancer on olaparib and ceralasertib combination (cohort E).\n\nExperimental design: Blood samples were collected at baseline [cycle 1 day 1 (C1D1)] and before treatment on cycle 2 day 1 (C2D1). Samples were sequenced using error-corrected targeted panels (Guardant360/GuardantOMNI). Circulating DNA ratio was calculated as the ratio of C2D1/C1D1 circulating DNA ratio, and baseline ctDNA levels were associated with progression-free survival (PFS) and confirmed objective response rates (ORR).\n\nResults: A total of 167 patients had assessable C1D1-C2D1 ctDNA results. There was a strong association between baseline ctDNA levels and response in cohort E; low baseline levels were associated with longer PFS (HR, 0.33; P = 0.001) and higher ORR (40% vs. 9.7%; P = 0.02). In cohorts A to D, there was a weaker association with PFS (HR, 0.60; P = 0.03) and ORR (15.2% vs. 5.7%; P = 0.17). Associations of baseline ctDNA level and ORR were validated in the independent PEARL study. For on-treatment dynamics, suppression of ctDNA below median was predictive in cohorts A to D (HR, 0.47; P = 0.001) but not in cohort E (HR, 1.02; P = 0.94). Undetectable ctDNA levels at C2D1 were associated with good outcomes in both cohorts: in cohort E with improved PFS (HR, 0.25; P = 0.01) and improved ORR (86% vs. 11%; P = 0.01). Six of seven patients with undetectable on-treatment ctDNA were BRCA1/BRCA2/PALB2 wild type.\n\nConclusions: Baseline low ctDNA levels predict response to targeted therapy, potentially suggesting shared mechanisms between high ctDNA release and resistance to therapy. Both baseline ctDNA levels and on-treatment dynamics are a promising surrogate endpoint for drug development, with clearance of ctDNA being a robust cross-therapy surrogate for outcomes.\n\nIndexed on Europe PMC as PubMed record 41159912 (DOI 10.1158/1078-0432.ccr-24-0651). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Clin Cancer Res 2026","url":"https://doi.org/10.1158/1078-0432.ccr-24-0651"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41159912/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41159912"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["plasmamatch"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2026,"doi":"10.1158/1078-0432.ccr-24-0651","pmid":"41159912","authors":"Browne IM, Pascual J, Cutts RJ, et al.","paperType":"observational","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-alexandrov-nature","kind":"paper","name":"The repertoire of mutational signatures in human cancer","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 32025018 and published in Nature; the citing page links this DOI, which is how the record was matched.","summary":"Somatic mutations in cancer genomes are caused by multiple mutational processes, each of which generates a characteristic mutational signature 1. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium 2 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we characterized mutational signatures using 84,729,690 somatic mutations from 4,645 whole-genome and 19,184 exome sequences that encompass most types of cancer. We identified 49 single-base-substitution, 11 doublet-base-substitution, 4 clustered-base-substitution and 17 small insertion-and-deletion signatures. The substantial size of our dataset, compared with previous analyses 3-15, enabled the discovery of new signatures, the separation of overlapping signatures and the decomposition of signatures into components that may represent associated-but distinct-DNA damage, repair and/or replication mechanisms. By estimating the contribution of each signature to the mutational catalogues of individual cancer genomes, we revealed associations of signatures to exogenous or endogenous exposures, as well as to defective DNA-maintenance processes. However, many signatures are of unknown cause. This analysis provides a systematic perspective on the repertoire of mutational processes that contribute to the development of human cancer.\n\nIndexed on Europe PMC as PubMed record 32025018 (DOI 10.1038/s41586-020-1943-3). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2020","url":"https://doi.org/10.1038/s41586-020-1943-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32025018/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32025018"}],"tags":["europepmc-ingest"],"related":["mutagenesis-signatures"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2020,"doi":"10.1038/s41586-020-1943-3","pmid":"32025018","authors":"Alexandrov LB, Kim J, Haradhvala NJ, et al.","paperType":"observational","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-pantziarka-ecancermedicalscience","kind":"paper","name":"The Repurposing Drugs in Oncology (ReDO) Project","aka":[],"tldr":"Paper cited by one bottleneck page and 21 idea pages, indexed on Europe PMC as PubMed record 25075216 and published in Ecancermedicalscience; the citing pages link this DOI, which is how the record was matched.","summary":"The Repurposing Drugs in Oncology (ReDO) Project seeks to repurpose well-known and well-characterised non-cancer drugs for new uses in oncology. The rationale for this project is presented, examining current issues in oncological drug development, challenges for health systems, and existing and future patient needs. In addition to discussing the advantages of repurposing, the paper also outlines some of the characteristics used in the selection of drug candidates by this project. Challenges in moving candidate drugs into clinical trial and subsequent practice are also discussed.\n\nIndexed on Europe PMC as PubMed record 25075216 (DOI 10.3332/ecancer.2014.442). Matched by DOI alone: one bottleneck page and 21 idea pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Ecancermedicalscience 2014","url":"https://doi.org/10.3332/ecancer.2014.442"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25075216/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25075216"}],"tags":["europepmc-ingest"],"related":["b-generic-repurposing","idea-reg-repurposing-prize","idea-reg-vitamin-d-digestive-cancer-biomarker-trial","idea-reg-delinked-market-entry-reward","idea-reg-generic-targeted-therapy-drup","idea-reg-guideline-fast-track-repurposed","idea-reg-nonprofit-marketing-authorisation-holder","idea-reg-statin-hcc-prevention-trial","idea-moon-generics-for-cancer-fund","idea-reg-repurposing-social-impact-bond","idea-reg-generic-chemo-strategic-reserve","idea-reg-factorial-addon-arms-cooperative-trials","idea-reg-target-trial-emulation-pipeline","idea-reg-olanzapine-cachexia-global-confirmation","idea-reg-losartan-pancreatic-stroma","idea-reg-payer-coverage-off-label-generic-commitment","idea-reg-perioperative-propranolol-etodolac","idea-reg-preregistered-ai-repurposing-scoring","idea-reg-antihistamine-plus-io-trial","idea-reg-evidence-gate-before-repurposing-phase3","idea-reg-new-indication-exclusivity-off-patent","idea-reg-metronomic-lmic-phase3-to-label"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Ecancermedicalscience","year":2014,"doi":"10.3332/ecancer.2014.442","pmid":"25075216","authors":"Pantziarka P, Bouche G, Meheus L, et al.","paperType":"observational","findings":[],"whatItMeans":"One bottleneck page and 21 idea pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-struewing-brca-founder-mutations-ashkenazi-nejm-1997","kind":"paper","name":"The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews","aka":[],"tldr":"The 1997 study of 5,318 Ashkenazi Jewish volunteers that measured the real-world breast cancer risk of the three founder mutations carried by more than 2 percent of that population: 56 percent by age 70, lower than the 85 percent estimated from high-risk families.","summary":"Struewing, Hartge, Wacholder, Baker and colleagues collected blood from 5,318 Jewish subjects in the Washington DC area who had completed epidemiological questionnaires and identified carriers of the BRCA1 185delAG and 5382insC mutations and the BRCA2 6174delT mutation by polymerase chain reaction assays, estimating cancer risk from the cancer histories of carriers' and non-carriers' relatives. One hundred and twenty carriers were identified. By age 70 the estimated risk of breast cancer among carriers was 56 percent (95 percent confidence interval 40 to 73), of ovarian cancer 16 percent (6 to 28) and of prostate cancer 16 percent (4 to 30); breast cancer risk did not differ between BRCA1 and BRCA2 carriers, and colon cancer incidence in relatives was not raised.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 1997","url":"https://doi.org/10.1056/NEJM199705153362001"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/9145676/"}],"tags":["tnbc-evidence"],"related":[],"cancers":["tnbc","ovarian","prostate","breast-cancer"],"sections":[],"technologies":[],"targets":["brca"],"drugs":[],"companies":[],"institutions":["nci"],"pathways":[],"terms":["germline-testing","gbrca-mutation"],"trials":[],"people":["mary-claire-king"],"bottlenecks":["b-hereditary-risk"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":1997,"doi":"10.1056/NEJM199705153362001","pmid":"9145676","authors":"Struewing JP, Hartge P, Wacholder S, et al.","paperType":"observational","findings":["Over 2 percent of Ashkenazi Jews carry one of three founder mutations (BRCA1 185delAG, BRCA1 5382insC, BRCA2 6174delT).","Breast cancer risk by age 70: 56 percent (95 percent CI 40 to 73); ovarian 16 percent; prostate 16 percent."],"whatItMeans":"Founder mutations make population-level testing feasible because a three-variant panel finds most carriers; the BRCA1 founder variants in particular predispose to basal-like, triple-negative tumours, so ancestry shapes who gets this disease and who is eligible for PARP inhibitors.","caveats":["Risk estimated from relatives' histories, not from following carriers.","Volunteer sample from one metropolitan area."],"changedPractice":true,"participants":5318},{"id":"paper-elmasry-gallbladder-polyp-malignancy-systematic-review-int-j-surg-2016","kind":"paper","name":"The risk of malignancy in ultrasound detected gallbladder polyps: A systematic review","aka":[],"tldr":"A Liverpool review of twelve studies found that about one in 175 gallbladder polyps seen on ultrasound turned out to be cancer, and argued for risk-based surveillance decided in a multidisciplinary team.","summary":"Systematic review from Aintree University Hospital of 12 studies on the natural history of ultrasound-diagnosed gallbladder polyps. Of 5,482 polyps, malignant polyps had an incidence of 0.57 percent and true (neoplastic) polyps 0.60 percent; 64 patients with adenomatous or malignant polyps were reported. Risk features identified included size over 6 mm, single polyps, symptoms, age over 60, Indian ethnicity, gallstones and cholecystitis. The authors recommend risk assessment, clear surveillance planning and multidisciplinary discussion, with endoscopic ultrasound reserved for its greater sensitivity and specificity.","asOf":"2026-09-24","links":[{"label":"Int J Surg 2016","url":"https://doi.org/10.1016/j.ijsu.2016.07.061"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27465099/"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":["ultrasound"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["gallbladder-polyp","screening"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"International Journal of Surgery","year":2016,"doi":"10.1016/j.ijsu.2016.07.061","pmid":"27465099","authors":"Elmasry M, Lindop D, Dunne DF, et al.","paperType":"review","findings":["Malignant polyps 0.57 percent and true polyps 0.60 percent of 5,482 ultrasound-detected gallbladder polyps.","Risk features: size over 6 mm, single polyp, symptoms, age over 60, Indian ethnicity, gallstones, cholecystitis."],"whatItMeans":"UK evidence that the polyps found every day on NHS ultrasound lists are almost always benign; it feeds the risk factors used in the 2022 European guideline.","caveats":["Heterogeneous retrospective studies with differing follow-up.","Ultrasound size measurement is operator-dependent."],"changedPractice":false,"participants":5482},{"id":"paper-langley-int-j-cancer","kind":"paper","name":"The seed and soil hypothesis revisited--the role of tumor-stroma interactions in metastasis to different organs","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 21365651 and published in International journal of cancer; the citing page links this DOI, which is how the record was matched.","summary":"The fact that certain tumors exhibit a predilection for metastasis to specific organs has been recognized for well over a century now. An extensive body of clinical data and experimental research has confirmed Stephen Paget's original \"seed and soil\" hypothesis that proposed the organ-preference patterns of tumor metastasis are the product of favorable interactions between metastatic tumor cells (the \"seed\") and their organ microenvironment (the \"soil\"). Indeed, many of the first-line therapeutic regimens, currently in use for the treatment of human cancer are designed to target cancer cells (such as chemotherapy) and also to modulate the tumor microenvironment (such as antiangiogenic therapy). While some types of tumors are capable of forming metastases in virtually every organ in the body, the most frequent target organs of metastasis are bone, brain, liver and the lung. In this review, we discuss how tumor-stromal interactions influence metastasis in each of these organs.\n\nIndexed on Europe PMC as PubMed record 21365651 (DOI 10.1002/ijc.26031). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Int J Cancer 2011","url":"https://doi.org/10.1002/ijc.26031"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21365651/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/21365651"}],"tags":["europepmc-ingest"],"related":["seed-and-soil-hypothesis"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["international-journal-of-cancer"],"dependsOn":[],"notes":[],"journal":"International journal of cancer","year":2011,"doi":"10.1002/ijc.26031","pmid":"21365651","authors":"Langley RR, Fidler IJ","paperType":"review","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-halassy-self-experiment-ovt-vaccines-2024","kind":"paper","name":"The self-experiment: a virologist treated her own recurrent breast cancer with two viruses she made in her own laboratory","aka":[],"tldr":"A virologist whose breast cancer had come back and grown into the chest muscle injected it herself with a measles vaccine strain and then a second virus, the tumour shrank enough to be removed by simple surgery, and she was free of recurrence more than three years later.","summary":"Case report of a 50-year-old woman with locally recurrent, muscle-invasive breast cancer who was also a virologist, and who treated the tumour herself with intratumoural injections of research-grade virus preparations made in her own laboratory before having any other treatment for the recurrence.\n\nThe history: multifocal invasive ductal triple-negative breast cancer diagnosed in 2016, treated with mastectomy and adjuvant chemotherapy; a small local recurrence excised in 2018, leaving a seroma under 1 cm that was monitored; by 2020 that had become a 2 cm solid, hard, inflamed nodule. Magnetic resonance imaging, positron emission tomography with computed tomography and two independent ultrasound estimates all gave a volume of 2.47 plus or minus 0.06 cm3, with invasion into the pectoral muscle and infiltration of the skin, and no evidence of metastatic or nodal disease. A baseline core biopsy showed the tumour had changed phenotype from triple-negative to HER2 3+.\n\nThe protocol: seven injections of an Edmonston-Zagreb measles vaccine strain at three to four day intervals over three weeks, then three injections of a vesicular stomatitis virus Indiana strain separated by two weeks and one week, then surgical excision. Two months after excision, one subcutaneous dose of measles virus was given around the surgical suture. Totals were 7.89 log CCID50 of measles virus and 9.07 log CCID50 of vesicular stomatitis virus, given multifocally in 1 to 2 mL. Neither virus had been engineered to improve its oncolytic properties; the preparations were clarified cell culture supernatants grown in MRC-5 and Vero cells, not purified from host-cell nucleic acid and protein.\n\nThe outcome: the tumour transiently swelled to 4.28 cm3 by day 8 and to 2.17 cm3 on day 41 after the first vesicular stomatitis virus dose, then shrank; the excised tumour measured 0.91 cm3 pathologically. It was confined to the subcutis with no skin or muscle infiltration, in contrast to baseline. Lymphocyte infiltration rose from 10 to 45 per cent, CD20-positive B cells from 10 to 70 per cent, CD8-positive T cells from 30 to 60 per cent, macrophage infiltration increased, and PD-L1 became detectable in a tumour that had been PD-L1 negative. Neutralising antibody titres to both viruses were low but measurable at baseline and rose a hundredfold. The only systemic adverse event was fever and rigors twelve hours after the first vesicular stomatitis virus dose, resolving over three days; injections were painful at first. Because the excised tumour was HER2 3+ she completed one year of adjuvant trastuzumab, and was recurrence-free 45 months after surgery, against previous recurrence intervals of 22 and 21 months.\n\nOn ethics, the authors state that as a case of self-experimentation it does not require ethics committee review, that the patient was fully informed and consented, and that her oncologists agreed to monitor and to intervene with conventional therapy if there were adverse effects or progression. Their conclusion states plainly that self-medicating with oncolytic viruses should not be the first approach to a diagnosed cancer, and asks instead for formal clinical trials of the neoadjuvant setting. The senior author disclosed becoming a consultant to Vyriad in 2021, and a European patent application covering the subject matter.","asOf":"2026-09-25","links":[{"label":"Vaccines 2024 (open access)","url":"https://doi.org/10.3390/vaccines12090958"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39339989/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39339989"},{"label":"Europe PMC full text","url":"https://europepmc.org/articles/PMC11435696"}],"tags":[],"related":["paper-pugh-self-experimentation-publication-jme-2026","paper-bourgeois-daigneault-neoadjuvant-ovt-tnbc-scitranslmed-2018"],"cancers":["tnbc","breast-her2-positive"],"sections":["immunotherapy"],"technologies":["oncolytic-virus"],"targets":[],"drugs":["trastuzumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["beata-halassy","dubravko-forcic"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Vaccines","year":2024,"doi":"10.3390/vaccines12090958","pmid":"39339989","authors":"Forcic D, Mrsic K, Peric-Balja M, Kurtovic T, Ramic S, Silovski T, Pedisic I, Milas I, Halassy B","paperType":"observational","findings":["Seven intratumoural doses of an Edmonston-Zagreb measles vaccine strain over three weeks, then three doses of a vesicular stomatitis virus Indiana strain, totalling 7.89 log CCID50 of measles virus and 9.07 log CCID50 of vesicular stomatitis virus.","Tumour volume fell from 2.47 plus or minus 0.06 cm3 at baseline, by four independent imaging estimates, to 0.91 cm3 measured pathologically in the excised specimen, after transient swelling to 4.28 cm3 on day 8.","The excised tumour was confined to the subcutis with no skin or pectoral muscle infiltration, in contrast to the baseline imaging, so a simple non-invasive resection was possible.","Lymphocyte infiltration rose from 10 to 45 per cent; CD20-positive B cells from 10 to 70 per cent; CD8-positive T cells from 30 to 60 per cent; macrophage infiltration increased; PD-L1 became detectable in a previously PD-L1-negative tumour.","Neutralising antibody titres against both viruses were low but measurable at baseline and rose a hundredfold during treatment.","The only systemic adverse event was fever and rigors twelve hours after the first vesicular stomatitis virus dose, resolving over three days.","The tumour had changed phenotype from triple-negative at first diagnosis to HER2 3+ on the baseline biopsy, so one year of adjuvant trastuzumab was given after surgery; the patient was recurrence-free 45 months after surgery."],"whatItMeans":"One person, one tumour, one report, and it is not evidence that anyone should treat themselves. What it does contribute is unusually well documented: serial imaging through the course, a baseline biopsy and an excised specimen scored by the same pathology department, antibody titres, and a named protocol with doses. The design choices are the interesting part. Two different viruses in sequence to stay ahead of the antiviral antibody response, frequent dosing to keep infectious virus concentrated in the tumour, and the neoadjuvant setting rather than the late metastatic setting in which oncolytic viruses are normally tested. The result also cannot be attributed to the viruses alone: the tumour was surgically removed and a year of trastuzumab followed, and the phenotype change to HER2 3+ is itself a plausible reason the disease behaved differently this time.","caveats":["A single case, uncontrolled, in a patient with exceptional expertise and access; it establishes nothing about efficacy.","The tumour was excised and one year of trastuzumab followed, so the 45-month recurrence-free interval cannot be attributed to the viruses.","The tumour had converted from triple-negative to HER2 3+, a change that by itself alters both prognosis and treatment options.","The virus preparations were research grade, unpurified clarified cell-culture supernatants containing host-cell nucleic acid and protein, so the biological agent was not the virus alone.","Neither virus was engineered for tumour selectivity; wild-type vesicular stomatitis virus is considered potentially neurotoxic in humans and the authors call for neurotoxicity studies before any development.","The authors' own conclusion states that self-medication with oncolytic viruses should not be a first approach to a diagnosed cancer.","Declared interests: the senior author became a consultant to Vyriad in 2021 and the work is the subject of a European patent application."],"changedPractice":false,"participants":1},{"id":"paper-bettington-serrated-pathway-colorectal-histopathology-2013","kind":"paper","name":"The serrated pathway to colorectal carcinoma: current concepts and challenges","aka":[],"tldr":"About a third of bowel cancers do not come from the familiar polyp at all. They come from flat, saw-toothed lesions that are hard to see at colonoscopy and follow a different molecular route, driven by chemical silencing of genes rather than by chromosome loss.","summary":"Approximately 30% of colorectal carcinomas develop through a serrated neoplasia pathway, named for the pattern of crypts in the precursor polyps. Molecular abnormalities consistently involve CpG island methylation of low or high degree and activating mutations of BRAF or KRAS; microsatellite instability of high level is often present. That allows a molecular classification into BRAF-mutant CIMP-high tumours, either microsatellite-unstable or stable, and KRAS-mutant CIMP-low microsatellite-stable tumours. Precursor polyps include the sessile serrated adenoma, proximal, with crypt architectural disturbance and BRAF mutation, probably preceded by the microvesicular hyperplastic polyp, with borderline lesions between them. Cytological dysplasia in a sessile serrated adenoma indicates advanced genetic abnormality and a high risk of progression. The traditional serrated adenoma favours the left colon, has tubulovillous architecture, eosinophilic cytoplasm and frequent KRAS mutation. Serrated morphology carcinoma is a World Health Organization subtype with frequent KRAS or BRAF mutation and shorter survival.","asOf":"2026-09-24","links":[{"label":"Bettington et al., Histopathology 2013: the serrated pathway to colorectal carcinoma","url":"https://doi.org/10.1111/his.12055"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23339363/"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":[],"targets":["braf","kras","mmr"],"drugs":[],"companies":[],"institutions":["qimr-berghofer"],"pathways":["epigenetic-reprogramming","mismatch-repair-msi","ras-mapk"],"terms":["msi","sidedness","colonoscopy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"Histopathology","year":2013,"doi":"10.1111/his.12055","pmid":"23339363","authors":"Bettington M, Walker N, Clouston A, et al.","paperType":"review","findings":["About 30% of colorectal carcinomas arise through the serrated pathway.","Three molecular classes: BRAF-mutant CIMP-high MSI-high, BRAF-mutant CIMP-high microsatellite stable, KRAS-mutant CIMP-low microsatellite stable.","Cytological dysplasia in a sessile serrated adenoma marks a high risk of progression."],"whatItMeans":"It is the reason colonoscopy quality standards now count sessile serrated lesion detection separately, and the reason a right-sided, BRAF-mutant, MSI-high cancer is read as serrated in origin rather than as an odd adenoma.","caveats":["A review, so the 30% figure is a synthesis rather than a single measurement.","Terminology has since been revised: sessile serrated adenoma is now sessile serrated lesion."],"changedPractice":false},{"id":"paper-cldn18-gastric-front-oncol-2020","kind":"paper","name":"The Significance of the CLDN18-ARHGAP Fusion Gene in Gastric Cancer: A Systematic Review and Meta-Analysis","aka":[],"tldr":"Review on CLDN18 in Gastric & gastro-oesophageal junction cancer, in Frontiers in oncology (2020), one of the most cited Europe PMC records with CLDN18 in its title.","summary":"Objective: The objective of this study was to summarize the clinicopathological characteristics of the CLDN18-ARHGAP fusion gene in gastric cancer patients. Background: The CLDN18-ARHGAP26 fusion gene is one of the most frequent somatic genomic rearrangements in gastric cancer, especially in the genomically stable (GS) subtype. However, the clinical and prognostic meaning of the CLDN18-ARHGAP fusion in gastric cancer patients is unclear. Methods: Studies that investigated CLDN18-ARHGAP fusion gastric cancer patients were identified systematically from the PubMed, Cochrane, and Embase databases through the 28th of February 2020. A systematic review and meta-analysis were performed to estimate the clinical significance of CLDN18-ARHGAP fusion in patients. Results: A total of five eligible studies covering 1908 patients were selected for inclusion in the meta-analysis based on specified inclusion and exclusion criteria. Several fusion patterns were observed linking CLDN18 and ARHGAP26 or ARHGAP6, with the most common type being CLDN18/exon5 - ARHGAP26/exon12. The survival outcome meta-analysis of the CLDN18-ARHGAP fusion gene showed that it was associated with overall survival outcomes in gastric cancer (HR, 2.03, 95% CI 1.26-3.26, P < 0.01, random-effects). In addition, diffuse gastric cancer had a greater proportion of CLDN18-ARHGAP fusions than intestinal gastric cancer (13.3%, 151/1,138 vs. 1.8%, 8/442; p < 0.001). Moreover, gastric cancer patients with the CLDN18-ARHGAP fusion gene are more likely to be female or have a younger age, lymph node metastasis and advanced TNM stages. Conclusion: The CLDN18-ARHGAP fusion is one of the molecular characteristics of diffuse gastric cancer and is also an independent prognostic risk factor for gastric cancer. In addition, it is also related to multiple clinical characteristics, including age, sex, lymph node metastasis and tumor stage. However, the mechanism of the CLDN18-ARHGAP fusion gene and potential targeted therapeutic strategies need further exploration.\n\nIndexed on Europe PMC as PubMed record 32983960 (DOI 10.3389/fonc.2020.01214). Its title names CLDN18 and its text names Gastric & gastro-oesophageal junction cancer; PubMed types it as a review (Systematic Review, systematic-review). It was matched automatically to the idea \"In vivo CAR-T against solid-tumour antigens\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Front Oncol 2020","url":"https://doi.org/10.3389/fonc.2020.01214"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32983960/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32983960"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Frontiers in oncology","year":2020,"doi":"10.3389/fonc.2020.01214","pmid":"32983960","authors":"Zhang WH, Zhang SY, Hou QQ, et al.","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for CLDN18 in Gastric & gastro-oesophageal junction cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by CLDN18 in the title and Gastric & gastro-oesophageal junction cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-tcga-chromophobe-davis-cancer-cell-2014","kind":"paper","name":"The somatic genomic landscape of chromophobe renal cell carcinoma (The Cancer Genome Atlas)","aka":[],"tldr":"Genomic analysis of 66 chromophobe kidney cancers showed they arise from a different cell of origin than clear cell tumours, carry characteristic whole-chromosome losses and TP53 and PTEN mutations, and have distinctive mitochondrial DNA changes and TERT promoter rearrangements.","summary":"Integrated genomic study by The Cancer Genome Atlas of 66 chromophobe renal cell carcinomas including whole-genome sequencing, showing loss of chromosomes 1, 2, 6, 10, 13 and 17, mutations in TP53 and PTEN, recurrent structural rearrangements within the TERT promoter, mitochondrial DNA mutations, and an expression profile pointing to the distal nephron as the cell of origin.","asOf":"2026-09-17","links":[{"label":"Cancer Cell 2014","url":"https://doi.org/10.1016/j.ccr.2014.07.014"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25155756/"}],"tags":[],"related":[],"cancers":["chromophobe-rcc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-cell"],"dependsOn":[],"notes":[],"journal":"Cancer Cell","year":2014,"doi":"10.1016/j.ccr.2014.07.014","pmid":"25155756","authors":"Davis CF, Ricketts CJ, Wang M, et al.","paperType":"translational","findings":["Characteristic losses of chromosomes 1, 2, 6, 10, 13 and 17.","TP53 (32 percent) and PTEN (9 percent) mutations; TERT promoter rearrangements; distal nephron origin."],"whatItMeans":"Chromophobe renal cell carcinoma is a biologically distinct disease that should not be lumped with clear cell cancer in trials or treatment, which is why its page separates the two.","caveats":["Small cohort; therapeutic implications are still being worked out."],"changedPractice":true,"participants":66},{"id":"paper-musacchio-nat-rev-mol-cell-biol","kind":"paper","name":"The spindle-assembly checkpoint in space and time","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 17426725 and published in Nature reviews. Molecular cell biology; the citing page links this DOI, which is how the record was matched.","summary":"In eukaryotes, the spindle-assembly checkpoint (SAC) is a ubiquitous safety device that ensures the fidelity of chromosome segregation in mitosis. The SAC prevents chromosome mis-segregation and aneuploidy, and its dysfunction is implicated in tumorigenesis. Recent molecular analyses have begun to shed light on the complex interaction of the checkpoint proteins with kinetochores--structures that mediate the binding of spindle microtubules to chromosomes in mitosis. These studies are finally starting to reveal the mechanisms of checkpoint activation and silencing during mitotic progression.\n\nIndexed on Europe PMC as PubMed record 17426725 (DOI 10.1038/nrm2163). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Mol Cell Biol 2007","url":"https://doi.org/10.1038/nrm2163"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/17426725/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/17426725"}],"tags":["europepmc-ingest"],"related":["mitotic-spindle-checkpoint"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature reviews. Molecular cell biology","year":2007,"doi":"10.1038/nrm2163","pmid":"17426725","authors":"Musacchio A, Salmon ED","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-maffini-j-cell-sci","kind":"paper","name":"The stroma as a crucial target in rat mammary gland carcinogenesis","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 14996910 and published in Journal of cell science; the citing page links this DOI, which is how the record was matched.","summary":"A complex network of interactions between the stroma, the extracellular matrix and the epithelium drives mammary gland development and function. Two main assumptions in chemical carcinogenesis of the mammary gland have been that carcinogens induce neoplasia by causing mutations in the DNA of the epithelial cells and that the alterations of tissue architecture observed in neoplasms are a consequence of this primary mutational event. Here, we use a rat mammary tissue recombination model and the chemical carcinogen N-nitrosomethylurea (NMU) to determine whether the primary target of the carcinogen is the epithelium, the stroma or both tissue compartments. Mammary epithelial cells were exposed in vitro either to the carcinogen or vehicle before being transplanted into the cleared fat pads of rats exposed to carcinogen or vehicle. We observed that neoplastic transformation of these mammary epithelial cells occurred only when the stroma was exposed in vivo to NMU, regardless of whether or not the epithelial cells were exposed to the carcinogen. Mammary epithelial cells exposed in vitro to the carcinogen formed phenotypically normal ducts when injected into a non-treated stroma. Mutation in the Ha-ras-1 gene did not correlate with initiation of neoplasia. Not only was it often found in both cleared mammary fat pads of vehicle-treated animals and intact mammary glands of untreated animals, but it was also absent in some tumors. Our results suggest that the stroma is a crucial target of the carcinogen and that mutation in the Ha-ras-1 gene is neither necessary nor sufficient for tumor initiation.\n\nIndexed on Europe PMC as PubMed record 14996910 (DOI 10.1242/jcs.01000). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Cell Sci 2004","url":"https://doi.org/10.1242/jcs.01000"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/14996910/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/14996910"}],"tags":["europepmc-ingest"],"related":["tissue-organisation-field-theory"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of cell science","year":2004,"doi":"10.1242/jcs.01000","pmid":"14996910","authors":"Maffini MV, Soto AM, Calabro JM, et al.","paperType":"basic","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-tonon-crtc1-maml2-nat-genet-2003","kind":"paper","name":"The t(11;19) translocation in mucoepidermoid carcinoma creates a CRTC1-MAML2 fusion","aka":[],"tldr":"This study identified the gene fusion (CRTC1-MAML2, originally called MECT1-MAML2) created by the characteristic chromosome translocation in mucoepidermoid carcinoma, giving the tumour a defining molecular marker.","summary":"Molecular characterisation of the recurrent t(11;19)(q21;p13) translocation in mucoepidermoid carcinoma showing fusion of the CREB coactivator MECT1 (CRTC1) to the Notch coactivator MAML2, producing a fusion protein that disrupts Notch signalling and activates CREB targets.","asOf":"2026-09-17","links":[{"label":"Nat Genet 2003","url":"https://doi.org/10.1038/ng1083"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/12539049/"}],"tags":[],"related":[],"cancers":["mucoepidermoid-carcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":2003,"doi":"10.1038/ng1083","pmid":"12539049","authors":"Tonon G, Modi S, Wu L, et al.","paperType":"basic","findings":["Recurrent CRTC1-MAML2 fusion in mucoepidermoid carcinoma from the t(11;19) translocation."],"whatItMeans":"CRTC1-MAML2 fusion testing supports the diagnosis of mucoepidermoid carcinoma, particularly in difficult cases, and fusion-positive tumours tend to be lower grade with a better outlook.","caveats":["Not yet a therapeutic target."],"changedPractice":true},{"id":"paper-gilene-ivermectin-toxicity-paediatric-oncology-2025","kind":"paper","name":"The threat of medical misinformation: a case of ivermectin toxicity in a pediatric oncology patient","aka":[],"tldr":"A letter describing severe ivermectin poisoning in a young patient with bone cancer who was also taking regorafenib, a cancer drug that shares the enzyme ivermectin is cleared by.","summary":"Europe PMC indexes this letter without an abstract, so OnCo transcribes no figures from it (Gilene paediatric case 2025). The ICONIC trial's registry entry summarises it as a case of severe neurotoxicity in a patient with metastatic osteosarcoma receiving regorafenib, likely due to a pharmacokinetic interaction through CYP3A4 (ClinicalTrials.gov NCT07487805).","asOf":"2026-09-24","links":[{"label":"Gilene paediatric case 2025","url":"https://doi.org/10.1002/pbc.31876"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40556334/"},{"label":"ClinicalTrials.gov NCT07487805","url":"https://clinicaltrials.gov/study/NCT07487805"}],"tags":[],"related":[],"cancers":["osteosarcoma"],"sections":[],"technologies":[],"targets":[],"drugs":["ivermectin","regorafenib"],"companies":[],"institutions":[],"pathways":[],"terms":["pharmacokinetics"],"trials":["nct07487805"],"people":[],"bottlenecks":["b-misinformation"],"keyPapers":[],"journals":["pediatric-blood-and-cancer"],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo agent (Claude Fable 5.1)","editedOn":"2026-09-24","note":"Written from cached ClinicalTrials.gov v2, Europe PMC, DailyMed, Drugs@FDA and WHO eEML responses; no figure appears without its source link."},"journal":"Pediatric Blood & Cancer","year":2025,"doi":"10.1002/pbc.31876","pmid":"40556334","authors":"Gilene S, Haacker L, Rutan H, Pressey JG.","paperType":"observational","findings":["Severe neurotoxicity in a paediatric osteosarcoma patient on regorafenib, attributed to a CYP3A4 interaction, as summarised by the ICONIC registry entry."],"whatItMeans":"A reminder that ivermectin interacts with cancer drugs: the dose that a healthy adult tolerates can poison a patient whose liver enzymes are already occupied by a kinase inhibitor.","caveats":["Letter with no indexed abstract; details are taken from the ICONIC registry's summary of it."],"changedPractice":false,"participants":1},{"id":"paper-soto-bioessays","kind":"paper","name":"The tissue organization field theory of cancer: a testable replacement for the somatic mutation theory","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 21503935 and published in BioEssays; the citing page links this DOI, which is how the record was matched.","summary":"The somatic mutation theory (SMT) of cancer has been and remains the prevalent theory attempting to explain how neoplasms arise and progress. This theory proposes that cancer is a clonal, cell-based disease, and implicitly assumes that quiescence is the default state of cells in multicellular organisms. The SMT has not been rigorously tested, and several lines of evidence raise questions that are not addressed by this theory. Herein, we propose experimental strategies that may validate the SMT. We also call attention to an alternative theory of carcinogenesis, the tissue organization field theory (TOFT), which posits that cancer is a tissue-based disease and that proliferation is the default state of all cells. Based on epistemological and experimental evidence, we argue that the TOFT compellingly explains carcinogenesis, while placing it within an evolutionarily relevant context.\n\nIndexed on Europe PMC as PubMed record 21503935 (DOI 10.1002/bies.201100025). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Bioessays 2011","url":"https://doi.org/10.1002/bies.201100025"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21503935/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/21503935"}],"tags":["europepmc-ingest"],"related":["tissue-organisation-field-theory"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"BioEssays","year":2011,"doi":"10.1002/bies.201100025","pmid":"21503935","authors":"Soto AM, Sonnenschein C","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-pettersson-tmprss2-erg-outcome-meta-analysis-cebp-2012","kind":"paper","name":"The TMPRSS2-ERG rearrangement, ERG expression and prostate cancer outcomes: a cohort study and meta-analysis","aka":[],"tldr":"Following 1,180 men for more than twelve years, and then pooling 48 other studies, found that the commonest genetic change in prostate cancer does not predict who does badly.","summary":"Among men with prostate cancer in the prospective Physicians' Health Study and Health Professionals Follow-Up Study, rearrangement status was determined by immunohistochemical assessment of ERG protein expression, and Cox models examined associations with biochemical recurrence and lethal disease, defined as distant metastases or cancer-specific mortality. The cohort consisted of 1,180 men treated with radical prostatectomy between 1983 and 2005; during a median follow-up of 12.6 years, 266 men experienced recurrence and 85 developed lethal disease. There was no significant association between ERG overexpression and biochemical recurrence, hazard ratio 0.99, or lethal disease, hazard ratio 0.93. A meta-analysis including 47 additional studies covered 5,074 men followed for biochemical recurrence with 1,623 events and 2,049 men followed for lethal disease with 131 events; TMPRSS2-ERG was associated with stage at diagnosis, risk ratio 1.23 for T3 or above against T2, but not with biochemical recurrence, risk ratio 1.00, or lethal disease, risk ratio 0.99.","asOf":"2026-09-25","links":[{"label":"Pettersson et al., Cancer Epidemiol Biomarkers Prev 2012: TMPRSS2-ERG, ERG expression and outcome in a 1,180-man cohort and a meta-analysis of 48 studies","url":"https://doi.org/10.1158/1055-9965.EPI-12-0042"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22736790/"}],"tags":[],"related":[],"cancers":["prostate"],"sections":[],"technologies":["histopathology-ihc"],"targets":["erg","tmprss2"],"drugs":[],"companies":[],"institutions":[],"pathways":["prostate-cancer-signalling","ar-signaling"],"terms":["gene-fusion","ihc","biochemical-recurrence"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-epidemiology-biomarkers-prevention"],"dependsOn":[],"notes":[],"journal":"Cancer Epidemiology, Biomarkers and Prevention","year":2012,"doi":"10.1158/1055-9965.EPI-12-0042","pmid":"22736790","authors":"Pettersson A, Graff RE, Bauer SR, et al.","paperType":"meta-analysis","findings":["No association between ERG overexpression and biochemical recurrence, hazard ratio 0.99, in 1,180 men followed a median 12.6 years.","No association with lethal disease, hazard ratio 0.93.","Meta-analysis over 48 studies: risk ratio 1.00 for recurrence and 0.99 for lethal disease.","An association with stage at diagnosis, risk ratio 1.23."],"whatItMeans":"It is the definitive negative result for the commonest genomic alteration in this disease. A man told his tumour carries the TMPRSS2-ERG fusion should be told plainly that it does not make his cancer more dangerous.","caveats":["Surgical cohorts, so it describes men treated with prostatectomy rather than all comers.","ERG immunohistochemistry is a proxy for the rearrangement rather than the rearrangement itself.","Meta-analysis over studies with different assays and different endpoints."],"changedPractice":false,"participants":5074},{"id":"paper-ho-pancreatic-tumour-microenvironment-review-nrco-2020","kind":"paper","name":"The tumour microenvironment in pancreatic cancer: clinical challenges and opportunities","aka":[],"tldr":"A review of every attempt to attack the tissue around pancreatic cancer, explaining why deconstructing the scar tissue and blocking single immune-suppressing pathways failed and what multi-target approaches are being tried instead.","summary":"Metastatic pancreatic ductal adenocarcinoma remains one of the most lethal solid tumours despite multi-agent chemotherapy. Efforts to exploit the tumour microenvironment by deconstructing the desmoplastic stroma and targeting immunosuppressive pathways have largely failed; evidence now shows the stroma is multi-faceted, illustrating the complexity of targeting isolated features. The review describes how the microenvironment has been targeted, notes clinical outcomes that unexpectedly contradicted preclinical observations, and considers multi-modal approaches and biologically integrated targets aimed at remodelling it.","asOf":"2026-09-24","links":[{"label":"Ho, Jaffee and Zheng, Nat Rev Clin Oncol 2020: the tumour microenvironment in pancreatic cancer","url":"https://doi.org/10.1038/s41571-020-0363-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32398706/"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":["tumor-microenvironment","caf-activation-desmoplasia","myeloid-suppression-axis"],"terms":["desmoplasia","cold-vs-hot"],"trials":[],"people":["elizabeth-jaffee","lei-zheng"],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-clinical-oncology"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Clinical Oncology","year":2020,"doi":"10.1038/s41571-020-0363-5","pmid":"32398706","authors":"Ho WJ, Jaffee EM, Zheng L.","paperType":"review","findings":["Stromal deconstruction and single-pathway immunosuppression blockade have largely failed clinically.","The stroma is multi-faceted; isolated targets contradict preclinical predictions."],"whatItMeans":"The reference for why pancreatic microenvironment trials read as a list of failures and what the field now means by remodelling rather than removing the stroma.","caveats":["Narrative review.","Published before the most recent stromal and vaccine readouts."],"changedPractice":false},{"id":"paper-kilburn-nat-med","kind":"paper","name":"The type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial","aka":[],"tldr":"Paper cited by one cancer page and one trial page, indexed on Europe PMC as PubMed record 37978284 and published in Nature Medicine; the citing pages link this DOI, which is how the record was matched.","summary":"BRAF genomic alterations are the most common oncogenic drivers in pediatric low-grade glioma (pLGG). Arm 1 (n = 77) of the ongoing phase 2 FIREFLY-1 (PNOC026) trial investigated the efficacy of the oral, selective, central nervous system-penetrant, type II RAF inhibitor tovorafenib (420 mg m - 2 once weekly; 600 mg maximum) in patients with BRAF-altered, relapsed/refractory pLGG. Arm 2 (n = 60) is an extension cohort, which provided treatment access for patients with RAF-altered pLGG after arm 1 closure. Based on independent review, according to Response Assessment in Neuro-Oncology High-Grade Glioma (RANO-HGG) criteria, the overall response rate (ORR) of 67% met the arm 1 prespecified primary endpoint; median duration of response (DOR) was 16.6 months; and median time to response (TTR) was 3.0 months (secondary endpoints). Other select arm 1 secondary endpoints included ORR, DOR and TTR as assessed by Response Assessment in Pediatric Neuro-Oncology Low-Grade Glioma (RAPNO) criteria and safety (assessed in all treated patients and the primary endpoint for arm 2, n = 137). The ORR according to RAPNO criteria (including minor responses) was 51%; median DOR was 13.8 months; and median TTR was 5.3 months. The most common treatment-related adverse events (TRAEs) were hair color changes (76%), elevated creatine phosphokinase (56%) and anemia (49%). Grade ≥3 TRAEs occurred in 42% of patients. Nine (7%) patients had TRAEs leading to discontinuation of tovorafenib. These data indicate that tovorafenib could be an effective therapy for BRAF-altered, relapsed/refractory pLGG. ClinicalTrials.gov registration: NCT04775485.\n\nIndexed on Europe PMC as PubMed record 37978284 (DOI 10.1038/s41591-023-02668-y). Matched by DOI alone: one cancer page and one trial page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Med 2024","url":"https://doi.org/10.1038/s41591-023-02668-y"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37978284/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37978284"}],"tags":["europepmc-ingest"],"related":["paediatric-low-grade-glioma"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["firefly-1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2024,"doi":"10.1038/s41591-023-02668-y","pmid":"37978284","authors":"Kilburn LB, Khuong-Quang DA, Hansford JR, et al.","paperType":"observational","findings":[],"whatItMeans":"One cancer page and one trial page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-haviland-lancet-oncol","kind":"paper","name":"The UK Standardisation of Breast Radiotherapy (START) trials of radiotherapy hypofractionation for treatment of early breast cancer: 10-year follow-up results of two randomised controlled trials","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 24055415 and published in The Lancet Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background: 5-year results of the UK Standardisation of Breast Radiotherapy (START) trials suggested that lower total doses of radiotherapy delivered in fewer, larger doses (fractions) are at least as safe and effective as the historical standard regimen (50 Gy in 25 fractions) for women after primary surgery for early breast cancer. In this prespecified analysis, we report the 10-year follow-up of the START trials testing 13 fraction and 15 fraction regimens.\n\nMethods: From 1999 to 2002, women with completely excised invasive breast cancer (pT1-3a, pN0-1, M0) were enrolled from 35 UK radiotherapy centres. Patients were randomly assigned to a treatment regimen after primary surgery followed by chemotherapy and endocrine treatment (where prescribed). Randomisation was computer-generated and stratified by centre, type of primary surgery (breast-conservation surgery or mastectomy), and tumour bed boost radiotherapy. In START-A, a regimen of 50 Gy in 25 fractions over 5 weeks was compared with 41·6 Gy or 39 Gy in 13 fractions over 5 weeks. In START-B, a regimen of 50 Gy in 25 fractions over 5 weeks was compared with 40 Gy in 15 fractions over 3 weeks. Eligibility criteria included age older than 18 years and no immediate surgical reconstruction. Primary endpoints were local-regional tumour relapse and late normal tissue effects. Analysis was by intention to treat. Follow-up data are still being collected. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN59368779.\n\nFindings: START-A enrolled 2236 women. Median follow-up was 9·3 years (IQR 8·0-10·0), after which 139 local-regional relapses had occurred. 10-year rates of local-regional relapse did not differ significantly between the 41·6 Gy and 50 Gy regimen groups (6·3%, 95% CI 4·7-8·5 vs 7·4%, 5·5-10·0; hazard ratio [HR] 0·91, 95% CI 0·59-1·38; p=0·65) or the 39 Gy (8·8%, 95% CI 6·7-11·4) and 50 Gy regimen groups (HR 1·18, 95% CI 0·79-1·76; p=0·41). In START-A, moderate or marked breast induration, telangiectasia, and breast oedema were significantly less common normal tissue effects in the 39 Gy group than in the 50 Gy group. Normal tissue effects did not differ significantly between 41·6 Gy and 50 Gy groups. START-B enrolled 2215 women. Median follow-up was 9·9 years (IQR 7·5-10·1), after which 95 local-regional relapses had occurred. The proportion of patients with local-regional relapse at 10 years did not differ significantly between the 40 Gy group (4·3%, 95% CI 3·2-5·9) and the 50 Gy group (5·5%, 95% CI 4·2-7·2; HR 0·77, 95% CI 0·51-1·16; p=0·21). In START-B, breast shrinkage, telangiectasia, and breast oedema were significantly less common normal tissue effects in the 40 Gy group than in the 50 Gy group.\n\nInterpretation: Long-term follow-up confirms that appropriately dosed hypofractionated radiotherapy is safe and effective for patients with early breast cancer. The results support the continued use of 40 Gy in 15 fractions, which has already been adopted by most UK centres as the standard of care for women requiring adjuvant radiotherapy for invasive early breast cancer.\n\nFunding: Cancer Research UK, UK Medical Research Council, UK Department of Health.\n\nIndexed on Europe PMC as PubMed record 24055415 (DOI 10.1016/s1470-2045(13)70386-3). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2013","url":"https://doi.org/10.1016/s1470-2045(13)70386-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24055415/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/24055415"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["start-b"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2013,"doi":"10.1016/s1470-2045(13)70386-3","pmid":"24055415","authors":"Haviland JS, Owen JR, Dewar JA, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-rosenwald-molecular-profiling-dlbcl-nejm-2002","kind":"paper","name":"The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma","aka":["Rosenwald 2002","Lymphoma/Leukemia Molecular Profiling Project 240 biopsies","Germinal-centre, activated and type 3 diffuse large B-cell lymphoma"],"tldr":"Reading which genes were switched on in 240 lymphoma samples sorted one disease into three, and the group whose cells looked like a particular stage of normal B-cell development lived the longest.","summary":"Alizadeh and Staudt had shown in 2000 that diffuse large B-cell lymphoma is not one disease. Rosenwald and the Lymphoma/Leukemia Molecular Profiling Project turned that into a survival predictor. Biopsy samples from 240 patients were profiled on DNA microarrays and analysed for genomic abnormalities; subgroups were defined by hierarchical clustering, and a risk predictor was built on 160 patients and tested on the remaining 80.\n\nThree gene-expression subgroups came out: germinal-centre B-cell-like, activated B-cell-like, and type 3. The two commonest oncogenic events in the disease, the BCL2 translocation and c-rel amplification, were found only in the germinal-centre group, which also had the highest five-year survival. Searching for individual genes whose expression tracked survival produced four signatures, reflecting germinal-centre B cells, proliferating cells, the reactive stromal and immune cells of the lymph node, and the major histocompatibility complex class II complex. Seventeen of those genes were assembled into a predictor of overall survival after chemotherapy, which was independent of the International Prognostic Index.\n\nThe stromal and immune signatures are the part that aged best: they anticipated by a decade the idea that what surrounds the tumour predicts outcome as strongly as what is in it.","asOf":"2026-10-01","links":[{"label":"New England Journal of Medicine 2002","url":"https://doi.org/10.1056/NEJMoa012914"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/12075054/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/12075054"}],"tags":["lymphoma-evidence"],"related":["paper-alizadeh-nature","paper-hans-immunohistochemistry-cell-of-origin-dlbcl-blood-2004","paper-schmitz-genetics-pathogenesis-dlbcl-nejm-2018","lymphoma-roadmap"],"cancers":["dlbcl","non-hodgkin-lymphoma"],"sections":["diagnostics","ai-computation"],"technologies":[],"targets":["bcl2","bcl6","myc"],"drugs":[],"companies":[],"institutions":["nci"],"pathways":[],"terms":["cell-of-origin","ipi-score"],"trials":[],"people":["louis-staudt"],"bottlenecks":["b-tumor-heterogeneity","b-biomarker-validation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2002,"doi":"10.1056/NEJMoa012914","pmid":"12075054","authors":"Rosenwald A, Wright G, Chan WC, et al.","paperType":"translational","findings":["Three gene-expression subgroups were identified in diffuse large B-cell lymphoma: germinal-centre B-cell-like, activated B-cell-like, and type 3.","The BCL2 translocation and c-rel amplification were detected only in the germinal-centre B-cell-like subgroup, which had the highest five-year survival rate.","Genes whose expression correlated with survival fell into four signatures: germinal-centre B cell, proliferation, lymph-node reactive stromal and immune cells, and major histocompatibility complex class II.","A 17-gene predictor of overall survival after chemotherapy was constructed on 160 patients and validated on 80, and was prognostic independently of the International Prognostic Index."],"whatItMeans":"The reason a pathology report on diffuse large B-cell lymphoma says germinal-centre or non-germinal-centre, and the origin of every attempt since to treat the two differently. It also made the case that microarray profiling could do something the clinical index could not, which is what pulled genomics into haematology.","caveats":["The predictor was built in the era before rituximab; adding rituximab narrowed, though it did not erase, the survival gap between the subgroups.","Type 3 was a residual category rather than a biological entity and has not survived as a classification.","Microarray profiling on fresh-frozen tissue was never routinely available; the Hans immunohistochemistry algorithm was the compromise that carried the idea into clinics, at the cost of accuracy."],"changedPractice":true,"participants":240},{"id":"paper-aster-annu-rev-pathol","kind":"paper","name":"The Varied Roles of Notch in Cancer","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 27959635 and published in Annual review of pathology; the citing page links this DOI, which is how the record was matched.","summary":"Notch receptors influence cellular behavior by participating in a seemingly simple signaling pathway, but outcomes produced by Notch signaling are remarkably varied depending on signal dose and cell context. Here, after briefly reviewing new insights into physiologic mechanisms of Notch signaling in healthy tissues and defects in Notch signaling that contribute to congenital disorders and viral infection, we discuss the varied roles of Notch in cancer, focusing on cell autonomous activities that may be either oncogenic or tumor suppressive.\n\nIndexed on Europe PMC as PubMed record 27959635 (DOI 10.1146/annurev-pathol-052016-100127). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Annu Rev Pathol 2017","url":"https://doi.org/10.1146/annurev-pathol-052016-100127"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27959635/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27959635"}],"tags":["europepmc-ingest"],"related":["notch"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Annual review of pathology","year":2017,"doi":"10.1146/annurev-pathol-052016-100127","pmid":"27959635","authors":"Aster JC, Pear WS, Blacklow SC","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-sonnenschein-semin-cancer-biol","kind":"paper","name":"Theories of carcinogenesis: an emerging perspective","aka":[],"tldr":"Paper cited by one pathway page and one term page, indexed on Europe PMC as PubMed record 18472276 and published in Seminars in cancer biology; the citing pages link this DOI, which is how the record was matched.","summary":"Four decades ago Leslie Foulds remarked that \"Experimental analysis has produced an alarming mass of empirical facts without providing an adequate language for their communication or effective concepts for their synthesis\". Examining the relevance of the data avalanche we all generate and are subjected to in the context of the premises and predictions of the current cancer theories may help resolve this paradox. This goal is becoming increasingly relevant given the looming attempts to rigorously model and parameterize crucial events in carcinogenesis (microenvironmental conditions, cellular proliferation and motility), which will require the adoption of reliable premises on which to base those efforts. This choice must be made a priori, as premises are not testable, and data are not free of the theoretical frame used to gather them. In this review we provide a critical analysis of the two main currents in cancer research, one centered at the cellular level of biological organization, the somatic mutation theory, which conceptualizes carcinogenesis as a problem of cell proliferation control, and the other centered at the tissue level, the tissue organization filed theory, which considers carcinogenesis a process akin to organogenesis gone awry.\n\nIndexed on Europe PMC as PubMed record 18472276 (DOI 10.1016/j.semcancer.2008.03.012). Matched by DOI alone: one pathway page and one term page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Semin Cancer Biol 2008","url":"https://doi.org/10.1016/j.semcancer.2008.03.012"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/18472276/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/18472276"}],"tags":["europepmc-ingest"],"related":["theories-of-cancer","tissue-organisation-field-theory"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["seminars-in-cancer-biology"],"dependsOn":[],"notes":[],"journal":"Seminars in cancer biology","year":2008,"doi":"10.1016/j.semcancer.2008.03.012","pmid":"18472276","authors":"Sonnenschein C, Soto AM","paperType":"review","findings":[],"whatItMeans":"One pathway page and one term page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-therasse-recist-jnci-2000","kind":"paper","name":"Therasse 2000: RECIST, the standard rules for measuring whether a tumour responds","aka":[],"tldr":"The guideline that defined how trials decide a tumour has shrunk, stayed stable or grown, using the longest diameter of a few measured lesions, so results from different trials can be compared.","summary":"RECIST (Response Evaluation Criteria in Solid Tumours) was drawn up by the EORTC, the US National Cancer Institute and the National Cancer Institute of Canada to replace the older WHO criteria, which used two perpendicular diameters. RECIST measures only the longest diameter of each target lesion and sums them: a partial response is a decrease of at least 30% in the sum, progressive disease an increase of at least 20%, and stable disease anything between. It set rules for which lesions are measurable, how many to follow and how to confirm responses, and its revision as RECIST 1.1 in 2009 reduced the number of target lesions and added rules for lymph nodes.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1093/jnci/92.3.205"},{"label":"RECIST 1.1 (Eisenhauer 2009)","url":"https://doi.org/10.1016/j.ejca.2008.10.026"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["recist","partial-response","progressive-disease","complete-response","orr"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"JNCI: Journal of the National Cancer Institute","year":2000,"doi":"10.1093/jnci/92.3.205","authors":"Therasse P, Arbuck SG, Eisenhauer EA, et al.","paperType":"guideline","findings":["Response is judged on the sum of the longest diameters of selected target lesions rather than the products of two diameters.","Partial response: at least a 30% decrease in the sum; progressive disease: at least a 20% increase or new lesions; stable disease in between.","Revised in 2009 as RECIST 1.1: a maximum of five target lesions, two per organ, and lymph node criteria based on the short axis."],"whatItMeans":"Almost every response rate and progression-free survival figure quoted on this site rests on RECIST. Knowing that a partial response means a 30% shrinkage of a few measured lesions, not a cure, helps read trial results honestly, and the criteria's limits with immunotherapy led to iRECIST for delayed and mixed responses.","caveats":["Anatomical size does not capture necrosis or metabolic change, so RECIST can misjudge drugs that act without shrinking tumours.","Immunotherapy pseudoprogression prompted modified criteria (irRC, iRECIST).","Measurement variability between readers is real and affects small changes."],"changedPractice":true},{"id":"paper-thiery-emt-tumour-progression-nrc-2002","kind":"paper","name":"Thiery 2002: epithelial-mesenchymal transitions in tumour progression","aka":[],"tldr":"The review that brought the developmental idea of epithelial-mesenchymal transition into cancer biology, proposing it as the mechanism by which carcinoma cells detach, invade and travel to distant sites.","summary":"Thiery reviewed the evidence that carcinomas use an epithelial-mesenchymal transition to progress: loss of E-cadherin-based junctions, cytoskeletal remodelling and gain of migratory behaviour, driven by signals including TGF-beta, receptor tyrosine kinases, Wnt and the transcription factors Snail and Twist. He drew the parallel with gastrulation and neural crest migration in embryos and argued that EMT, and its reversal at secondary sites, could account for how metastases arise and why they often look epithelial again.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1038/nrc822"}],"tags":[],"related":["paper-kalluri-weinberg-emt-basics-jci-2009"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["emt","metastatic-cascade"],"terms":["metastasis","activating-invasion-metastasis"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature Reviews Cancer","year":2002,"doi":"10.1038/nrc822","authors":"Thiery JP.","paperType":"review","findings":["Carcinoma progression involves loss of E-cadherin and epithelial polarity with gain of mesenchymal, migratory features.","The same signalling pathways and transcription factors drive EMT in embryos and in tumours.","Proposed EMT and its reversal as the basis of invasion and distant metastasis."],"whatItMeans":"This is the paper that made EMT a cancer concept, cited by almost every metastasis study since. It set the research agenda that later produced the EMT stem cell link and current work on partial EMT states.","caveats":["Largely based on cell culture and developmental analogies at the time.","Direct evidence for EMT in human metastasis has remained harder to obtain than the model predicts."],"changedPractice":false},{"id":"paper-thorsson-immune-landscape-of-cancer-immunity-2018","kind":"paper","name":"Thorsson 2018: the immune landscape of cancer across 10,000 tumours","aka":[],"tldr":"An analysis of more than 10,000 tumours from 33 cancer types in The Cancer Genome Atlas that sorted cancers into six immune subtypes, showing that the immune environment of a tumour cuts across its tissue of origin and affects prognosis.","summary":"As part of the TCGA PanCancer Atlas, Thorsson and colleagues integrated gene expression, immune cell estimates, neoantigen predictions, T and B cell receptor repertoires and other data for over 10,000 tumours across 33 cancer types. They defined six immune subtypes, named wound healing, interferon-gamma dominant, inflammatory, lymphocyte depleted, immunologically quiet and TGF-beta dominant, each found in many cancer types and associated with different outcomes. They also linked immune features to tumour genetics, such as copy number changes and specific driver mutations.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1016/j.immuni.2018.03.023"}],"tags":[],"related":["paper-galon-immune-contexture-colorectal-science-2006","paper-schreiber-cancer-immunoediting-science-2011"],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["immune-system","tils","neoantigen"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Immunity","year":2018,"doi":"10.1016/j.immuni.2018.03.023","authors":"Thorsson V, Gibbs DL, Brown SD, et al.","paperType":"translational","findings":["Immunogenomic analysis of more than 10,000 TCGA tumours across 33 cancer types.","Six immune subtypes spanning tumour types: wound healing, IFN-gamma dominant, inflammatory, lymphocyte depleted, immunologically quiet and TGF-beta dominant.","Immune subtype was associated with prognosis, and immune features correlated with tumour genomic features such as copy number burden."],"whatItMeans":"This atlas is the reference for how immune the different cancers are and is widely used to choose which tumours to test immunotherapies in and to interpret immune gene signatures. It shows why immunotherapy responses depend on the tumour's immune context as much as on its tissue.","caveats":["Bulk tumour data; cell types are inferred computationally rather than observed.","TCGA samples are mostly untreated primary tumours, not the metastatic disease treated with immunotherapy."],"changedPractice":false},{"id":"paper-jan-burger-blood-2015","kind":"paper","name":"Three-year follow-up of treatment-naïve and previously treated patients with CLL and SLL receiving single-agent ibrutinib","aka":[],"tldr":"Paper by Jan A. Burger indexed on Europe PMC as PubMed record 25700432, in Blood (2015), one of the most cited records naming an author with this name at MD Anderson Cancer Center.","summary":"Ibrutinib is an orally administered inhibitor of Bruton tyrosine kinase that antagonizes B-cell receptor, chemokine, and integrin-mediated signaling. In early-phase studies, ibrutinib demonstrated high response rates and prolonged progression-free survival (PFS) in chronic lymphocytic leukemia (CLL). The durable responses observed with ibrutinib relate in part to a modest toxicity profile that allows the majority of patients to receive continuous therapy for an extended period. We report on median 3-year follow-up of 132 patients with symptomatic treatment-naïve and relapsed/refractory CLL or small lymphocytic lymphoma. Longer treatment with ibrutinib was associated with improvement in response quality over time and durable remissions. Toxicity with longer follow-up diminished with respect to occurrence of grade 3 or greater cytopenias, fatigue, and infections. Progression remains uncommon, occurring primarily in some patients with relapsed del(17)(p13.1) and/or del(11)(q22.3) disease. Treatment-related lymphocytosis remains largely asymptomatic even when persisting >1 year and does not appear to alter longer-term PFS and overall survival compared with patients with partial response or better. Collectively, these data provide evidence that ibrutinib controls CLL disease manifestations and is well tolerated for an extended period; this information can help direct potential treatment options for different subgroups to diminish the long-term risk of relapse.\n\nIndexed on Europe PMC as PubMed record 25700432 (DOI 10.1182/blood-2014-10-606038). Its author list gives \"Burger JA\" with the affiliation \"The University of Texas MD Anderson Cancer Center, Houston, TX; and\", which names MD Anderson Cancer Center; that is how the record was matched to Jan A. Burger, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Blood 2015","url":"https://doi.org/10.1182/blood-2014-10-606038"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25700432/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/25700432"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["jan-burger"],"bottlenecks":[],"keyPapers":[],"journals":["blood"],"dependsOn":[],"notes":[],"journal":"Blood","year":2015,"doi":"10.1182/blood-2014-10-606038","pmid":"25700432","authors":"Byrd JC, Furman RR, Coutre SE, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Jan A. Burger at MD Anderson Cancer Center, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-imcgp100-202-n-engl-j-med-2023-update","kind":"paper","name":"Three-Year Overall Survival with Tebentafusp in Metastatic Uveal Melanoma","aka":[],"tldr":"Later report from the IMCgp100-202 trial registered as NCT03070392, in New England Journal of Medicine (2023); its title describes an updated or longer-term analysis.","summary":"Background: Tebentafusp, a T-cell receptor-bispecific molecule that targets glycoprotein 100 and CD3, is approved for adult patients who are positive for HLA-A*02:01 and have unresectable or metastatic uveal melanoma. The primary analysis in the present phase 3 trial supported a long-term survival benefit associated with the drug.\n\nMethods: We report the 3-year efficacy and safety results from our open-label, phase 3 trial in which HLA-A*02:01-positive patients with previously untreated metastatic uveal melanoma were randomly assigned in a 2:1 ratio to receive tebentafusp (tebentafusp group) or the investigator's choice of therapy with pembrolizumab, ipilimumab, or dacarbazine (control group), with randomization stratified according to the lactate dehydrogenase level. The primary end point was overall survival.\n\nResults: At a minimum follow-up of 36 months, median overall survival was 21.6 months in the tebentafusp group and 16.9 months in the control group (hazard ratio for death, 0.68; 95% confidence interval, 0.54 to 0.87). The estimated percentage of patients surviving at 3 years was 27% in the tebentafusp group and 18% in the control group. The most common treatment-related adverse events of any grade in the tebentafusp group were rash (83%), pyrexia (76%), pruritus (70%), and hypotension (38%). Most tebentafusp-related adverse events occurred early during treatment, and no new adverse events were observed with long-term administration. The percentage of patients who discontinued treatment because of adverse events continued to be low in both treatment groups (2% in the tebentafusp group and 5% in the control group). No treatment-related deaths occurred.\n\nConclusions: This 3-year analysis supported a continued long-term benefit of tebentafusp for overall survival among adult HLA-A*02:01-positive patients with previously untreated metastatic uveal melanoma. (Funded by Immunocore; IMCgp100-202 ClinicalTrials.gov number, NCT03070392; EudraCT number, 2015-003153-18.).\n\nIndexed on Europe PMC as PubMed record 37870955 (DOI 10.1056/nejmoa2304753). Its abstract cites the registry id NCT03070392, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2023","url":"https://doi.org/10.1056/nejmoa2304753"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37870955/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37870955"},{"label":"ClinicalTrials.gov NCT03070392","url":"https://clinicaltrials.gov/study/NCT03070392"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["imcgp100-202"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/nejmoa2304753","pmid":"37870955","authors":"Hassel JC, Piperno-Neumann S, Rutkowski P, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the IMCgp100-202 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-keynote-017-j-immunother-cancer-2021-update","kind":"paper","name":"Three-year survival, correlates and salvage therapies in patients receiving first-line pembrolizumab for advanced Merkel cell carcinoma","aka":[],"tldr":"Later report from the KEYNOTE-017 trial registered as NCT02267603, in Journal for ImmunoTherapy of Cancer (2021); its title describes an updated or longer-term analysis.","summary":"Background: Merkel cell carcinoma (MCC) is an aggressive skin cancer associated with poor survival. Programmed cell death-1 (PD-1) pathway inhibitors have shown high rates of durable tumor regression compared with chemotherapy for MCC. The current study was undertaken to assess baseline and on-treatment factors associated with MCC regression and 3-year survival, and to explore the effects of salvage therapies in patients experiencing initial non-response or tumor progression after response or stable disease following first-line pembrolizumab therapy on Cancer Immunotherapy Trials Network-09/KEYNOTE-017.\n\nMethods: In this multicenter phase II trial, 50 patients with advanced unresectable MCC received pembrolizumab 2 mg/kg every 3 weeks for ≤2 years. Patients were followed for a median of 31.8 months.\n\nResults: Overall response rate to pembrolizumab was 58% (complete response 30%+partial response 28%; 95% CI 43.2 to 71.8). Among 29 responders, the median response duration was not reached (NR) at 3 years (range 1.0+ to 51.8+ months). Median progression-free survival (PFS) was 16.8 months (95% CI 4.6 to 43.4) and the 3-year PFS was 39.1%. Median OS was NR; the 3-year OS was 59.4% for all patients and 89.5% for responders. Baseline Eastern Cooperative Oncology Group performance status of 0, greater per cent tumor reduction, completion of 2 years of treatment and low neutrophil-to-lymphocyte ratio were associated with response and longer survival. Among patients with initial disease progression or those who developed progression after response or stable disease, some had extended survival with subsequent treatments including chemotherapies and immunotherapies.\n\nConclusions: This study represents the longest available follow-up from any first-line anti-programmed death-(ligand) 1 (anti-PD-(L)1) therapy in MCC, confirming durable PFS and OS in a proportion of patients. After initial tumor progression or relapse following response, some patients receiving salvage therapies survived. Improving the management of anti-PD-(L)1-refractory MCC remains a challenge and a high priority.\n\nTrial registration number: NCT02267603.\n\nIndexed on Europe PMC as PubMed record 33879601 (DOI 10.1136/jitc-2021-002478). Its abstract cites the registry id NCT02267603, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Immunother Cancer 2021","url":"https://doi.org/10.1136/jitc-2021-002478"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33879601/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33879601"},{"label":"ClinicalTrials.gov NCT02267603","url":"https://clinicaltrials.gov/study/NCT02267603"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-017"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jitc"],"dependsOn":[],"notes":[],"journal":"Journal for ImmunoTherapy of Cancer","year":2021,"doi":"10.1136/jitc-2021-002478","pmid":"33879601","authors":"Nghiem P, Bhatia S, Lipson EJ, et al.","paperType":"observational","findings":[],"whatItMeans":"A second publication from the KEYNOTE-017 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-esmo-thymic-epithelial-tumours-guideline-ann-oncol-2015","kind":"paper","name":"Thymic epithelial tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","aka":[],"tldr":"The European guideline for thymoma and thymic carcinoma, built on the French RYTHMIC network's experience: complete surgery where possible, radiotherapy for invasive tumours and platinum chemotherapy for disease that cannot be removed.","summary":"ESMO guideline covering the diagnosis, WHO histological typing, Masaoka-Koga and TNM staging, surgery, postoperative radiotherapy, induction chemotherapy for locally advanced tumours, chemotherapy and targeted agents for advanced disease, and follow-up of thymic epithelial tumours, with treatment recommended through multidisciplinary tumour boards such as RYTHMIC.\n\nIt recommends complete resection as the cornerstone, postoperative radiotherapy for stage III and incompletely resected tumours and for thymic carcinoma, cisplatin-based combinations for unresectable disease, and lists octreotide, sunitinib and everolimus as options after chemotherapy.","asOf":"2026-09-18","links":[{"label":"Ann Oncol 2015","url":"https://doi.org/10.1093/annonc/mdv277"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26314779/"}],"tags":[],"related":[],"cancers":["thymoma","thymic-carcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":["cisplatin","sunitinib","everolimus"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2015,"doi":"10.1093/annonc/mdv277","pmid":"26314779","authors":"Girard N, Ruffini E, Marx A, et al.","paperType":"guideline","findings":[],"whatItMeans":"The thymoma and thymic carcinoma pages follow this guideline for who gets surgery, radiotherapy and chemotherapy; its central message is that these rare tumours should be discussed in an expert network.","caveats":["Most recommendations rest on retrospective series; no randomised trial has compared surgery with or without radiotherapy.","Predates the lenvatinib and pembrolizumab studies in thymic carcinoma."],"changedPractice":true},{"id":"paper-cabanillas-lancet","kind":"paper","name":"Thyroid cancer","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 27240885 and published in The Lancet; the citing page links this DOI, which is how the record was matched.","summary":"Thyroid cancer is the fifth most common cancer in women in the USA, and an estimated over 62 000 new cases occurred in men and women in 2015. The incidence continues to rise worldwide. Differentiated thyroid cancer is the most frequent subtype of thyroid cancer and in most patients the standard treatment (surgery followed by either radioactive iodine or observation) is effective. Patients with other, more rare subtypes of thyroid cancer-medullary and anaplastic-are ideally treated by physicians with experience managing these malignancies. Targeted treatments that are approved for differentiated and medullary thyroid cancers have prolonged progression-free survival, but these drugs are not curative and therefore are reserved for patients with progressive or symptomatic disease.\n\nIndexed on Europe PMC as PubMed record 27240885 (DOI 10.1016/s0140-6736(16)30172-6). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet 2016","url":"https://doi.org/10.1016/s0140-6736(16)30172-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27240885/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27240885"}],"tags":["europepmc-ingest"],"related":["thyroid-cancer-signalling"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2016,"doi":"10.1016/s0140-6736(16)30172-6","pmid":"27240885","authors":"Cabanillas ME, McFadden DG, Durante C","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-selvakumar-revision-surgery-timing-ipd-meta-analysis-hpb-2026","kind":"paper","name":"Timing of revision surgery for incidental gallbladder cancer: a systematic review and individual patient data meta-analysis","aka":[],"tldr":"Pooling individual records from more than 2,000 patients, the timing of the second operation for chance-found gallbladder cancer made no measurable difference to survival, and studies did not even agree on what early or late meant.","summary":"Systematic review (four databases to 10 October 2025; PROSPERO CRD42023453990) of 12 retrospective studies with 2,067 patients (566 men, 1,346 women) reporting outcomes by timing of revision surgery. There was no consensus on definitions of early, intermediate and delayed surgery. Successful revision, perioperative morbidity and R0 rates were similar across timing groups. Individual patient data meta-analysis found no difference in overall survival by timing (hazard ratio 1.29, 95 percent CI 0.79 to 2.10 for the comparison reported). Most studies scored 7 to 8 of 10 on the JBI tool.","asOf":"2026-09-24","links":[{"label":"HPB 2026","url":"https://doi.org/10.1016/j.hpb.2025.12.017"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41436297/"}],"tags":["gallbladder-evidence"],"related":["paper-ethun-re-resection-timing-incidental-gallbladder-cancer-jama-surg-2017"],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["tata-memorial"],"pathways":[],"terms":["incidental-gallbladder-cancer","radical-cholecystectomy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"HPB","year":2026,"doi":"10.1016/j.hpb.2025.12.017","pmid":"41436297","authors":"Selvakumar B, Patkar S, Nekarakanti PK, et al.","paperType":"meta-analysis","findings":["12 retrospective studies, 2,067 patients; no consensus definition of early, intermediate or delayed revision surgery.","No difference in overall survival by timing: hazard ratio 1.29 (95 percent CI 0.79 to 2.10)."],"whatItMeans":"It softens the Ethun four-to-eight-week rule: timing within the range that services can deliver probably matters less than completing the operation at all and doing it with the liver bed and nodes cleared.","caveats":["All included studies retrospective.","Timing categories differed across studies, limiting the pooled comparison."],"changedPractice":false,"participants":2067},{"id":"paper-cho-lancet-oncol","kind":"paper","name":"Tiragolumab plus atezolizumab versus placebo plus atezolizumab as a first-line treatment for PD-L1-selected non-small-cell lung cancer (CITYSCAPE): primary and follow-up analyses of a randomised, double-blind, phase 2 study","aka":[],"tldr":"Paper cited by one pairing page, indexed on Europe PMC as PubMed record 35576957 and published in The Lancet Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background: Targeted inhibition of the PD-L1-PD-1 pathway might be further amplified through combination of PD-1 or PD-L1 inhibitors with novel anti-TIGIT inhibitory immune checkpoint agents, such as tiragolumab. In the CITYSCAPE trial, we aimed to assess the preliminary efficacy and safety of tiragolumab plus atezolizumab (anti-PD-L1) therapy as first-line treatment for non-small-cell lung cancer (NSCLC).\n\nMethods: CITYSCAPE is a phase 2, randomised, double-blind, placebo-controlled trial. Patients with chemotherapy-naive, PD-L1-positive (defined as a tumour proportion score of ≥1% by 22C3 immunohistochemistry pharmDx assay; Dako, Agilent Technologies, Santa Clara, CA, USA) recurrent or metastatic NSCLC with measurable disease, Eastern Cooperative Oncology Group performance status of 0 or 1, and no EGFR or ALK alterations were enrolled from 41 clinics in Europe, Asia, and the USA. Patients were randomly assigned (1:1), via an interactive voice or web-based response system, to receive tiragolumab (600 mg) plus atezolizumab (1200 mg) or placebo plus atezolizumab intravenously once every 3 weeks. Investigators and patients were masked to treatment assignment. The co-primary endpoints were investigator-assessed objective response rate and progression-free survival as per Response Evaluation Criteria in Solid Tumors version 1.1 in the intention-to-treat population, analysed after approximately 80 progression-free survival events had been observed in the primary population. Safety was assessed in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT03563716, and is ongoing.\n\nFindings: Patients were enrolled between Aug 10, 2018, and March 20, 2019. At data cutoff for the primary analysis (June 30, 2019), 135 of 275 patients assessed for eligibility were randomly assigned to receive tiragolumab plus atezolizumab (67 [50%]) or placebo plus atezolizumab (68 [50%]). In this primary analysis, after a median follow-up of 5·9 months (4·6-7·6, in the intention-to-treat population, 21 patients (31·3% [95% CI 19·5-43·2]) in the tiragolumab plus atezolizumab group versus 11 patients (16·2% [6·7-25·7]) in the placebo plus atezolizumab group had an objective response (p=0·031). Median progression-free survival was 5·4 months (95% CI 4·2-not estimable) in the tiragolumab plus atezolizumab group versus 3·6 months (2·7-4·4) in the placebo plus atezolizumab group (stratified hazard ratio 0·57 [95% CI 0·37-0·90], p=0·015). 14 (21%) patients receiving tiragolumab plus atezolizumab and 12 (18%) patients receiving placebo plus atezolizumab had serious treatment-related adverse events. The most frequently reported grade 3 or worse treatment-related adverse event was lipase increase (in six [9%] patients in the tiragolumab plus atezolizumab group vs two [3%] in the placebo plus atezolizumab group). Two treatment-related deaths (of pyrexia and infection) occurred in the tiragolumab plus atezolizumab group.\n\nInterpretation: Tiragolumab plus atezolizumab showed a clinically meaningful improvement in objective response rate and progression-free survival compared with placebo plus atezolizumab in patients with chemotherapy-naive, PD-L1-positive, recurrent or metastatic NSCLC. Tiragolumab plus atezolizumab was well tolerated, with a safety profile generally similar to that of atezolizumab alone. These findings demonstrate that tiragolumab plus atezolizumab is a promising immunotherapy combination for the treatment of previously untreated, locally advanced unresectable or metastatic NSCLC.\n\nFunding: F Hoffmann-La Roche and Genentech.\n\nIndexed on Europe PMC as PubMed record 35576957 (DOI 10.1016/s1470-2045(22)00226-1). Matched by DOI alone: one pairing page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2022","url":"https://doi.org/10.1016/s1470-2045(22)00226-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35576957/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35576957"}],"tags":["europepmc-ingest"],"related":["tigit-plus-pd1-caution"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2022,"doi":"10.1016/s1470-2045(22)00226-1","pmid":"35576957","authors":"Cho BC, Abreu DR, Hussein M, et al.","paperType":"rct","findings":[],"whatItMeans":"One pairing page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-elara-tisagenlecleucel-follicular-nat-med-2022","kind":"paper","name":"Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: the phase 2 ELARA trial","aka":["ELARA","Fowler 2022"],"tldr":"A single infusion of reprogrammed immune cells cleared follicular lymphoma completely in about seven of ten heavily pretreated people, with no severe cytokine release syndrome at all.","summary":"The primary prespecified interim analysis of a multinational phase 2 trial of tisagenlecleucel in adults with relapsed or refractory follicular lymphoma after two or more treatment lines, or relapsing after autologous stem-cell transplantation. The primary endpoint was the complete response rate.\n\nAt the 29 March 2021 data cut-off, 97 of 98 enrolled patients had received tisagenlecleucel, at a median follow-up of 16.59 months (interquartile range 13.8 to 20.21). The primary endpoint was met: in the 94-patient efficacy set the complete response rate was 69.1 per cent (95 per cent confidence interval 58.8 to 78.3) and the overall response rate 86.2 per cent (77.5 to 92.4). Within eight weeks of infusion, in the 97-patient safety set, cytokine release syndrome occurred in 48.5 per cent with no grade 3 or worse case, neurological events in 37.1 per cent with 3 per cent grade 3 or worse, and immune effector cell-associated neurotoxicity syndrome in 4.1 per cent with 1 per cent grade 3 or worse. There were no treatment-related deaths.","asOf":"2026-10-01","links":[{"label":"Nature Medicine 2022","url":"https://doi.org/10.1038/s41591-021-01622-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34921238/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34921238"}],"tags":["lymphoma-evidence"],"related":["lymphoma-roadmap"],"cancers":["follicular-lymphoma","non-hodgkin-lymphoma"],"sections":["cell-therapy"],"technologies":["car-t"],"targets":["cd19"],"drugs":["tisagenlecleucel"],"companies":["novartis"],"institutions":[],"pathways":[],"terms":["crs","icans","complete-response","lymphoma-tx-pod24"],"trials":["elara","zuma-5"],"people":["catherine-thieblemont","martin-dreyling"],"bottlenecks":["b-manufacturing-cell-therapy","b-global-access"],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2022,"doi":"10.1038/s41591-021-01622-0","pmid":"34921238","authors":"Fowler NH, Dickinson M, Dreyling M, et al.","paperType":"rct","findings":["The complete response rate was 69.1 per cent (95 per cent confidence interval 58.8 to 78.3) and the overall response rate 86.2 per cent (77.5 to 92.4) in the 94-patient efficacy set.","Cytokine release syndrome occurred in 48.5 per cent within eight weeks of infusion, with no grade 3 or worse case.","Neurological events occurred in 37.1 per cent, grade 3 or worse in 3 per cent; immune effector cell-associated neurotoxicity syndrome in 4.1 per cent.","There were no treatment-related deaths.","A previous pilot study of tisagenlecleucel in relapsed or refractory follicular lymphoma had reported a complete response in 71 per cent of patients."],"whatItMeans":"Chemotherapy-free cellular therapy for follicular lymphoma that has stopped responding, with a toxicity profile mild enough that the treatment is deliverable outside the largest centres.","caveats":["Single-arm phase 2 with no comparator; the natural history of this population on other treatments is not measured here.","A primary interim analysis at a median follow-up of 16.6 months, which is short for a disease measured in decades; the durability question is answered by later updates.","97 patients, so subgroup estimates including the early-progression group are imprecise."],"changedPractice":true,"participants":97},{"id":"paper-shen-j-clin-oncol","kind":"paper","name":"Tislelizumab Versus Chemotherapy as Second-Line Treatment for Advanced or Metastatic Esophageal Squamous Cell Carcinoma (RATIONALE-302): A Randomized Phase III Study","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 35442766 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: Patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) have poor prognosis. For these patients, treatment options are limited after first-line systemic therapy.\n\nPatients and methods: In this open-label phase III clinical study, patients with advanced or metastatic ESCC, whose tumor progressed after first-line systemic treatment, were randomly assigned (1:1) to receive intravenous tislelizumab, an anti-programmed cell death protein 1 antibody, 200 mg every 3 weeks or chemotherapy (investigator's choice of paclitaxel, docetaxel, or irinotecan). The primary end point was overall survival (OS) in all patients. The key secondary end point was OS in patients with programmed death-ligand 1 tumor area positivity (TAP) score ≥ 10%.\n\nResults: In total, 512 patients across 11 countries/regions were randomly assigned. At final analysis, conducted after 410 death events occurred, OS was significantly longer with tislelizumab versus chemotherapy in all patients (median, 8.6 v 6.3 months; hazard ratio [HR], 0.70 [95% CI, 0.57 to 0.85]; one-sided P =.0001), and in patients with TAP ≥ 10% (median, 10.3 months v 6.8 months; HR, 0.54 [95% CI, 0.36 to 0.79]; one-sided P =.0006). Survival benefit was consistently observed across all predefined subgroups, including those defined by baseline TAP score, region, and race. Treatment with tislelizumab was associated with higher objective response rate (20.3% v 9.8%) and a more durable antitumor response (median, 7.1 months v 4.0 months) versus chemotherapy in all patients. Fewer patients experienced ≥ grade 3 treatment-related adverse events (18.8% v 55.8%) with tislelizumab versus chemotherapy.\n\nConclusion: Tislelizumab significantly improved OS compared with chemotherapy as second-line therapy in patients with advanced or metastatic ESCC, with a tolerable safety profile. Patients with programmed death-ligand 1 TAP ≥ 10% also demonstrated statistically significant survival benefit with tislelizumab versus chemotherapy.\n\nIndexed on Europe PMC as PubMed record 35442766 (DOI 10.1200/jco.21.01926). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2022","url":"https://doi.org/10.1200/jco.21.01926"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35442766/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35442766"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["rationale-302"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2022,"doi":"10.1200/jco.21.01926","pmid":"35442766","authors":"Shen L, Kato K, Kim SB, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-tracc-clin-cancer-res-2024","kind":"paper","name":"Tissue-Free Liquid Biopsies Combining Genomic and Methylation Signals for Minimal Residual Disease Detection in Patients with Early Colorectal Cancer from the UK TRACC Part B Study","aka":[],"tldr":"Published report from the TRACC trial registered as NCT04050345, in Clinical Cancer Research (2024), chosen as the most cited paper whose own text cites the registry id.","summary":"Purpose: The absence of postoperative circulating tumor DNA (ctDNA) identifies patients with resected colorectal cancer (CRC) with low recurrence risk for adjuvant chemotherapy (ACT) de-escalation. Our study presents the largest resected CRC cohort to date with tissue-free minimal residual disease (MRD) detection.\n\nExperimental design: TRACC (tracking mutations in cell-free tumor DNA to predict relapse in early colorectal cancer) included patients with stage I to III resectable CRC. Prospective longitudinal plasma collection for ctDNA occurred pre- and postsurgery, post-ACT, every 3 months for year 1 and every 6 months in years 2 and 3 with imaging annually. The Guardant Reveal assay evaluated genomic and methylation signals. The primary endpoint was 2-year recurrence-free survival (RFS) by postoperative ctDNA detection (NCT04050345).\n\nResults: Between December 2016 and August 2022, 1,203 were patients enrolled. Plasma samples (n = 997) from 214 patients were analyzed. One hundred forty-three patients were evaluable for the primary endpoint; 92 (64.3%) colon, 51 (35.7%) rectal; two (1.4%) stage I, 64 (44.8%) stage II, and 77 (53.8%) stage III. Median follow-up was 30.3 months (95% CI, 29.5-31.3). Two-year RFS was 91.1% in patients with ctDNA not detected postoperatively and 50.4% in those with ctDNA detected [HR, 6.5 (2.96-14.5); P < 0.0001]. Landmark negative predictive value (NPV) was 91.2% (95% CI, 83.9-95.9). Longitudinal sensitivity and specificity were 62.1% (95% CI, 42.2-79.3) and 85.9% (95% CI, 78.9-91.3), respectively. The median lead time from ctDNA detection to radiological recurrence was 7.3 months (IQR, 3.3-12.5; n = 9).\n\nConclusions: Tissue-free MRD detection with longitudinal sampling predicts recurrence in patients with stage I to III CRC without the need for tissue sequencing. The UK TRACC Part C study is currently investigating the potential for ACT de-escalation in patients with undetectable postoperative ctDNA, given the high NPV indicating a low likelihood of residual disease.\n\nIndexed on Europe PMC as PubMed record 38864835 (DOI 10.1158/1078-0432.ccr-24-0226). Its abstract cites the registry id NCT04050345, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Clin Cancer Res 2024","url":"https://doi.org/10.1158/1078-0432.ccr-24-0226"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38864835/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38864835"},{"label":"ClinicalTrials.gov NCT04050345","url":"https://clinicaltrials.gov/study/NCT04050345"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["tracc"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2024,"doi":"10.1158/1078-0432.ccr-24-0226","pmid":"38864835","authors":"Slater S, Bryant A, Aresu M, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04050345 with the most citations, so it is the natural first reading for anyone following the TRACC trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-yoshida-nature","kind":"paper","name":"Tobacco smoking and somatic mutations in human bronchial epithelium","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 31996850 and published in Nature; the citing page links this DOI, which is how the record was matched.","summary":"Tobacco smoking causes lung cancer 1-3, a process that is driven by more than 60 carcinogens in cigarette smoke that directly damage and mutate DNA 4,5. The profound effects of tobacco on the genome of lung cancer cells are well-documented 6-10, but equivalent data for normal bronchial cells are lacking. Here we sequenced whole genomes of 632 colonies derived from single bronchial epithelial cells across 16 subjects. Tobacco smoking was the major influence on mutational burden, typically adding from 1,000 to 10,000 mutations per cell; massively increasing the variance both within and between subjects; and generating several distinct mutational signatures of substitutions and of insertions and deletions. A population of cells in individuals with a history of smoking had mutational burdens that were equivalent to those expected for people who had never smoked: these cells had less damage from tobacco-specific mutational processes, were fourfold more frequent in ex-smokers than current smokers and had considerably longer telomeres than their more-mutated counterparts. Driver mutations increased in frequency with age, affecting 4-14% of cells in middle-aged subjects who had never smoked. In current smokers, at least 25% of cells carried driver mutations and 0-6% of cells had two or even three drivers. Thus, tobacco smoking increases mutational burden, cell-to-cell heterogeneity and driver mutations, but quitting promotes replenishment of the bronchial epithelium from mitotically quiescent cells that have avoided tobacco mutagenesis.\n\nIndexed on Europe PMC as PubMed record 31996850 (DOI 10.1038/s41586-020-1961-1). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2020","url":"https://doi.org/10.1038/s41586-020-1961-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31996850/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31996850"}],"tags":["europepmc-ingest"],"related":["ageing-tissue-field-theory"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2020,"doi":"10.1038/s41586-020-1961-1","pmid":"31996850","authors":"Yoshida K, Gowers KHC, Lee-Six H, et al.","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-wynder-graham-tobacco-bronchiogenic-carcinoma-jama-1950","kind":"paper","name":"Tobacco smoking as a possible etiologic factor in bronchiogenic carcinoma; a study of 684 proved cases","aka":[],"tldr":"One of the two 1950 studies that first tied cigarettes to lung cancer. Wynder and Graham compared the smoking histories of 684 people with proven lung cancer against people without it, and found heavy smoking almost everywhere in the cancer group.","summary":"Ernest Wynder and Evarts Graham's case-control study of 684 proven cases of bronchiogenic carcinoma, published in the Journal of the American Medical Association on 27 May 1950. It appeared four months before Doll and Hill's British paper (paper-doll-hill-smoking-lung-cancer-bmj-1950), and the two studies were designed and run independently on two continents; their agreement is the reason the finding was believed.\n\nEurope PMC indexes no abstract for the 1950 article, so OnCo carries no figures from it. Graham, a thoracic surgeon who had performed the first successful pneumonectomy for lung cancer in 1933 and who was himself a heavy smoker, is the reason the paper is remembered as much as cited: he died of lung cancer in 1957. JAMA reprinted the article as a landmark in 1985 (PMID 3889389) and the World Health Organization's Bulletin republished it in 2005.","asOf":"2026-09-25","links":[{"label":"JAMA 1950","url":"https://doi.org/10.1001/jama.1950.02910390001001"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/15415260/"},{"label":"JAMA landmark reprint (1985)","url":"https://pubmed.ncbi.nlm.nih.gov/3889389/"},{"label":"WHO Bulletin republication (2005)","url":"https://europepmc.org/article/MED/15744408"}],"tags":["lung-evidence"],"related":["paper-doll-hill-smoking-lung-cancer-bmj-1950","prevention-roadmap"],"cancers":["lung-cancer","nsclc"],"sections":["prevention","early-detection"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["histology"],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-early-detection"],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"Journal of the American Medical Association","year":1950,"doi":"10.1001/jama.1950.02910390001001","pmid":"15415260","authors":"Wynder EL, Graham EA.","paperType":"observational","findings":["No abstract is indexed on Europe PMC; the design (684 proven cases of bronchiogenic carcinoma with smoking histories, compared against controls) is read from the article itself."],"whatItMeans":"Half of the evidence base on which every tobacco control policy in the world rests. Lung cancer was a rare disease at the start of the twentieth century and the commonest cause of cancer death by its end; this paper and Doll and Hill's are where the cause was named.","caveats":["Retrospective interview study of hospital patients, with the recall and selection problems that go with that design; the prospective British Doctors Study was built to answer those objections.","Association, not mechanism: the carcinogens in tobacco smoke and the mutational signature they leave were worked out over the following half-century."],"changedPractice":true,"participants":684},{"id":"paper-cloughesy-toca5-glioma-jamaoncol-2020","kind":"paper","name":"Toca 5: a virus plus a prodrug in recurrent brain cancer, tested properly, and it did not work","aka":[],"tldr":"Four hundred people with a brain tumour that had come back were randomly given either a virus-delivered enzyme plus a pill it converts into chemotherapy, or standard treatment; survival was the same.","summary":"Randomised, open-label phase 2/3 trial at 58 centres in the United States, Canada, Israel and South Korea. 403 patients having resection for a first or second recurrence of glioblastoma or anaplastic astrocytoma were randomised 1:1 to vocimagene amiretrorepvec, a retroviral replicating vector injected into the resection cavity wall, followed by cycles of oral flucytosine starting six weeks after surgery, or to investigator's choice of lomustine, temozolomide or bevacizumab.\n\nMedian overall survival was 11.10 months with the virus and prodrug and 12.22 months with standard of care, hazard ratio 1.06 (95% CI 0.83 to 1.35), p = 0.62. No secondary endpoint showed a significant difference. Adverse event rates were similar.\n\nThe design was the best case for the approach: the virus is injected under direct vision into the cavity where the tumour was, the prodrug converts to fluorouracil only where the virus has spread, and the trial was properly randomised and adequately sized. It still failed.","asOf":"2026-09-25","links":[{"label":"JAMA Oncol 2020","url":"https://doi.org/10.1001/jamaoncol.2020.3161"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33119048/"},{"label":"ClinicalTrials.gov NCT02414165","url":"https://clinicaltrials.gov/study/NCT02414165"}],"tags":[],"related":[],"cancers":["glioblastoma"],"sections":["immunotherapy"],"technologies":["oncolytic-virus"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["timothy-cloughesy"],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2020,"doi":"10.1001/jamaoncol.2020.3161","pmid":"33119048","authors":"Cloughesy TF, Petrecca K, Walbert T, et al.","paperType":"rct","findings":["Median overall survival 11.10 months with vocimagene amiretrorepvec and flucytosine versus 12.22 months with standard of care; hazard ratio 1.06 (95% CI 0.83 to 1.35), p = 0.62.","No secondary endpoint, including durable response rate and 12-month overall survival, showed a significant difference.","Adverse event rates were similar between the arms.","271 deaths among 403 randomised patients at a median follow-up of 22.8 months."],"whatItMeans":"The clearest randomised refutation in the field. Phase 1 data had looked encouraging, the delivery problem was solved by surgical access, and the killing mechanism was a well-understood chemotherapy released in place. None of it translated. Any claim that oncolytic virotherapy works in glioma has to be read against this trial.","caveats":["Open-label, and the control arm was a choice of three agents, none of them strong in recurrent high-grade glioma.","Vocimagene amiretrorepvec is a replicating retroviral vector delivering a prodrug-converting enzyme rather than a directly lytic virus, so the result does not transfer straightforwardly to lytic platforms.","Phase 1 results that prompted the trial came from a selected population."],"changedPractice":false,"participants":403},{"id":"paper-todo-g47delta-glioblastoma-natmed-2022","kind":"paper","name":"Todo 2022: the triple-mutated herpes virus that became Japan's first approved oncolytic virus","aka":[],"tldr":"Nineteen people with a brain tumour that had come back after radiotherapy and chemotherapy were given repeated injections of an engineered herpes virus, and more of them were alive at one year than expected.","summary":"Investigator-initiated, single-arm phase 2 trial of G47 delta, a triple-mutated third-generation oncolytic herpes simplex virus type 1, in 19 adults with residual or recurrent supratentorial glioblastoma after radiotherapy and temozolomide. The virus was given into the tumour, repeatedly, for up to six doses.\n\nThe primary endpoint, one-year survival after starting G47 delta, was 84.2 per cent (95% CI 60.4 to 96.6; 16 of 19). The prespecified endpoint was met and the trial stopped early. Median overall survival was 20.2 months from starting G47 delta and 28.8 months from the initial surgery. Fever was the commonest related adverse event, in 17 of 19. Imaging repeatedly showed the target lesion enlarging with clearing of contrast enhancement after each dose, a pattern characteristic of this therapy, so the best overall response over two years was partial response in one patient and stable disease in 18. Biopsies showed increasing tumour-infiltrating CD4-positive and CD8-positive lymphocytes with persistently low Foxp3-positive cells. The result led to approval of G47 delta in Japan.","asOf":"2026-09-25","links":[{"label":"Nat Med 2022","url":"https://doi.org/10.1038/s41591-022-01897-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35864254/"}],"tags":[],"related":[],"cancers":["glioblastoma"],"sections":["immunotherapy"],"technologies":["oncolytic-virus"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["tomoki-todo"],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2022,"doi":"10.1038/s41591-022-01897-x","pmid":"35864254","authors":"Todo T, Ito H, Ino Y, et al.","paperType":"rct","findings":["One-year survival after starting G47 delta was 84.2 per cent (95% CI 60.4 to 96.6), 16 of 19 patients; the prespecified endpoint was met and the trial ended early.","Median overall survival 20.2 months from starting treatment and 28.8 months from the initial surgery.","Best overall response over two years was partial response in one patient and stable disease in 18; the tumour typically enlarged on imaging after each dose while contrast enhancement cleared.","Fever was the commonest related adverse event, in 17 of 19 patients, followed by vomiting, nausea, lymphocytopenia and leukopenia.","Biopsies showed increasing CD4-positive and CD8-positive tumour-infiltrating lymphocytes with persistently low numbers of Foxp3-positive cells."],"whatItMeans":"This is the evidence behind a national approval, and it is 19 patients in a single arm. The survival figure is genuinely higher than historical expectation in recurrent glioblastoma, and the biopsy findings support the immune mechanism. It is not a randomised comparison, and the imaging pattern means the usual response criteria cannot be used, which makes an uncontrolled result harder rather than easier to interpret.","caveats":["Single-arm, 19 patients; the comparison is with historical expectation, not a control group.","The characteristic enlargement with contrast clearing means standard response criteria do not describe what the treatment does, so almost every patient is recorded as stable disease.","Approval in Japan was conditional and time-limited under the country's scheme for regenerative and gene therapies, so confirmation is still required."],"changedPractice":true,"participants":19},{"id":"paper-toga-trastuzumab-gastric-lancet-2010","kind":"paper","name":"ToGA (Bang 2010): trastuzumab with chemotherapy for HER2-positive advanced gastric cancer","aka":[],"tldr":"The trial that brought HER2 testing and trastuzumab to stomach cancer: adding the antibody to chemotherapy prolonged survival in patients whose gastric or junction cancers overexpressed HER2, about a fifth of those screened.","summary":"ToGA screened 3,665 patients with advanced gastric or gastro-oesophageal junction cancer and found HER2 positivity in 22.1%. It randomised 594 HER2-positive patients to trastuzumab plus cisplatin and a fluoropyrimidine or to chemotherapy alone. Trastuzumab improved overall survival, progression-free survival and response rate, with the largest benefit in tumours with high HER2 expression (immunohistochemistry 3+ or 2+ with amplification), which became the definition of HER2 positivity used for gastric cancer.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1016/S0140-6736(10)61121-X"},{"label":"ClinicalTrials.gov NCT01041404","url":"https://clinicaltrials.gov/study/NCT01041404"}],"tags":[],"related":["paper-slamon-trastuzumab-nejm-2001"],"cancers":["gastric"],"sections":[],"technologies":[],"targets":["her2"],"drugs":["trastuzumab","cisplatin","capecitabine","fluorouracil"],"companies":["roche-genentech"],"institutions":[],"pathways":[],"terms":["her2-positive","ihc","os"],"trials":["toga"],"people":["bang-yung-jue"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2010,"doi":"10.1016/S0140-6736(10)61121-X","authors":"Bang YJ, Van Cutsem E, Feyereislova A, et al.","paperType":"rct","findings":["HER2 positivity in 22.1% of 3,665 screened patients; 594 randomised to trastuzumab plus chemotherapy or chemotherapy alone.","Median overall survival 13.8 vs 11.1 months, hazard ratio 0.74.","In tumours with IHC 3+ or IHC 2+ and FISH-positive HER2: median overall survival 16.0 vs 11.8 months.","Response rate 47% vs 35%; no increase in cardiac events of note."],"whatItMeans":"ToGA made gastric cancer the second disease treated by HER2 status and introduced gastric-specific HER2 scoring. It is the base on which trastuzumab deruxtecan and pembrolizumab combinations in HER2-positive gastric cancer have built.","caveats":["Open-label design.","Benefit was concentrated in high HER2 expressers; IHC 2+ FISH-negative and IHC 0 or 1+ FISH-positive tumours gained little.","Chemotherapy backbone was cisplatin with capecitabine or fluorouracil."],"changedPractice":true,"participants":594},{"id":"paper-miften-med-phys","kind":"paper","name":"Tolerance limits and methodologies for IMRT measurement-based verification QA: Recommendations of AAPM Task Group No. 218","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 29443390 and published in Medical physics; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: Patient-specific IMRT QA measurements are important components of processes designed to identify discrepancies between calculated and delivered radiation doses. Discrepancy tolerance limits are neither well defined nor consistently applied across centers. The AAPM TG-218 report provides a comprehensive review aimed at improving the understanding and consistency of these processes as well as recommendations for methodologies and tolerance limits in patient-specific IMRT QA.\n\nMethods: The performance of the dose difference/distance-to-agreement (DTA) and γ dose distribution comparison metrics are investigated. Measurement methods are reviewed and followed by a discussion of the pros and cons of each. Methodologies for absolute dose verification are discussed and new IMRT QA verification tools are presented. Literature on the expected or achievable agreement between measurements and calculations for different types of planning and delivery systems are reviewed and analyzed. Tests of vendor implementations of the γ verification algorithm employing benchmark cases are presented.\n\nResults: Operational shortcomings that can reduce the γ tool accuracy and subsequent effectiveness for IMRT QA are described. Practical considerations including spatial resolution, normalization, dose threshold, and data interpretation are discussed. Published data on IMRT QA and the clinical experience of the group members are used to develop guidelines and recommendations on tolerance and action limits for IMRT QA. Steps to check failed IMRT QA plans are outlined.\n\nConclusion: Recommendations on delivery methods, data interpretation, dose normalization, the use of γ analysis routines and choice of tolerance limits for IMRT QA are made with focus on detecting differences between calculated and measured doses via the use of robust analysis methods and an in-depth understanding of IMRT verification metrics. The recommendations are intended to improve the IMRT QA process and establish consistent, and comparable IMRT QA criteria among institutions.\n\nIndexed on Europe PMC as PubMed record 29443390 (DOI 10.1002/mp.12810). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Med Phys 2018","url":"https://doi.org/10.1002/mp.12810"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29443390/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29443390"}],"tags":["europepmc-ingest"],"related":["radiotherapy-qa-phantoms-dosimeters"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Medical physics","year":2018,"doi":"10.1002/mp.12810","pmid":"29443390","authors":"Miften M, Olch A, Mihailidis D, et al.","paperType":"review","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-topalian-anti-pd1-nejm-2012","kind":"paper","name":"Topalian 2012: the first large trial of a PD-1 antibody shows durable responses across melanoma, lung and kidney cancer","aka":[],"tldr":"Nivolumab shrank tumours in roughly a fifth to a quarter of patients with three different advanced cancers, with responses that lasted more than a year and a hint that PD-L1 on the tumour predicted benefit.","summary":"This phase 1 dose-escalation and expansion study treated 296 patients with advanced melanoma, non-small-cell lung cancer, renal cell carcinoma, castration-resistant prostate cancer or colorectal cancer with the anti-PD-1 antibody BMS-936558 (nivolumab) at 0.1 to 10 mg/kg every two weeks. Objective responses occurred in 28% of melanoma, 18% of NSCLC and 27% of renal cancer patients, but none in prostate or colorectal cancer; of 31 responders followed for a year or more, 20 had responses lasting at least a year. Grade 3-4 drug-related adverse events occurred in 14%, and there were three deaths from pneumonitis. In 42 patients with tumour PD-L1 staining, 9 of 25 PD-L1-positive tumours responded versus none of 17 PD-L1-negative tumours. A companion paper (Brahmer et al.) reported similar activity for an anti-PD-L1 antibody.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa1200690"},{"label":"Companion anti-PD-L1 paper (Brahmer 2012)","url":"https://doi.org/10.1056/NEJMoa1200694"}],"tags":[],"related":["paper-hodi-ipilimumab-melanoma-nejm-2010","pd1-checkpoint","lung-cancer-evidence-roadmap","paper-herbst-impower110-atezolizumab-pd-l1-nejm-2020"],"cancers":["melanoma","nsclc","lung-cancer"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["pd1"],"drugs":["nivolumab","pembrolizumab","atezolizumab"],"companies":["bms"],"institutions":[],"pathways":[],"terms":["irae","orr"],"trials":[],"people":["suzanne-topalian","julie-brahmer","drew-pardoll","f-stephen-hodi"],"bottlenecks":["b-biomarker-validation","b-immunotherapy-response"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2012,"doi":"10.1056/NEJMoa1200690","authors":"Topalian SL, Hodi FS, Brahmer JR, et al.","paperType":"translational","findings":["296 patients across five tumour types; nivolumab 0.1-10 mg/kg every 2 weeks.","Objective response: melanoma 28%, NSCLC 18% (including squamous and non-squamous), renal cell carcinoma 27%; none in prostate or colorectal cancer.","Responses durable: 20 of 31 responders with a year or more of follow-up had responses lasting at least 1 year.","Grade 3-4 drug-related adverse events 14%; 3 deaths from pneumonitis.","PD-L1 expression: 9 of 25 PD-L1-positive tumours responded vs 0 of 17 PD-L1-negative."],"whatItMeans":"This study is why PD-1 inhibitors were developed across cancers rather than in melanoma alone: unexpected activity in lung cancer, historically thought immune-resistant, changed drug development priorities industry-wide. It also introduced PD-L1 immunohistochemistry as a candidate biomarker and pneumonitis as a signature toxicity. Within five years PD-1 blockade was approved in more than ten cancers.","caveats":["Phase 1 with heterogeneous doses and small tumour cohorts; response rates are imprecise.","PD-L1 analysis was on 42 patients with archival tissue; the biomarker later proved imperfect.","No colorectal responses masked the later dMMR story (the one responder in an earlier study was dMMR).","Survival was not assessed."],"changedPractice":true,"participants":296},{"id":"paper-mateo-toparp-a-olaparib-dna-repair-nejm-2015","kind":"paper","name":"TOPARP-A: DNA-repair defects and olaparib in metastatic prostate cancer","aka":["TOPARP-A","Mateo 2015 olaparib prostate"],"tldr":"Fifty men whose prostate cancer had exhausted every standard treatment were given a PARP inhibitor and biopsied. A third responded, and almost all the responders were the ones with a broken DNA repair gene, including every man who had lost BRCA2.","summary":"Joaquin Mateo, Johann de Bono and colleagues at the Institute of Cancer Research and the Royal Marsden ran a phase 2 trial of olaparib 400 mg twice daily in 50 heavily pre-treated men with metastatic castration-resistant prostate cancer, with a mandated tumour biopsy and targeted next-generation sequencing, exome and transcriptome analysis in every patient.\n\nThe design is why it matters. The trial was not restricted to men with known mutations; it treated everyone and then asked which ones responded. Sixteen of 49 evaluable men responded, and 14 of the 16 men with DNA repair defects did, with a biomarker specificity of 94 percent. That is a prospectively defined predictive biomarker read out of an unselected cohort, which is a stronger form of evidence than a biomarker-selected trial, and it is the trial PROfound was built from.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2015","url":"https://doi.org/10.1056/nejmoa1506859"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26510020/"},{"label":"ClinicalTrials.gov NCT01682772","url":"https://clinicaltrials.gov/study/NCT01682772"}],"tags":["prostate-evidence"],"related":["paper-profound-nejm-2020","paper-abida-triton2-rucaparib-brca-jco-2020","paper-pritchard-inherited-dna-repair-metastatic-prostate-nejm-2016","prostate-roadmap"],"cancers":["prostate","prostate-mcrpc"],"sections":["targeted-therapy"],"technologies":[],"targets":["brca","atm"],"drugs":["olaparib"],"companies":[],"institutions":["icr-london","royal-marsden"],"pathways":[],"terms":["hrd","synthetic-lethality","ngs"],"trials":[],"people":["johann-de-bono"],"bottlenecks":["b-biomarker-validation","b-resistance","b-rare-cancers"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2015,"doi":"10.1056/nejmoa1506859","pmid":"26510020","authors":"Mateo J, Carreira S, Sandhu S, et al.","paperType":"rct","findings":["16 of 49 evaluable patients responded (33 percent; 95 percent confidence interval 20 to 48), with 12 receiving the study treatment for more than 6 months.","Next-generation sequencing identified homozygous deletions, deleterious mutations or both in DNA repair genes, including BRCA1 and BRCA2, ATM, Fanconi anaemia genes and CHEK2, in 16 of 49 evaluable patients (33 percent).","Of those 16, 14 (88 percent) responded to olaparib, including all 7 patients with BRCA2 loss (4 biallelic somatic, 3 germline) and 4 of 5 with ATM aberrations.","The specificity of the biomarker suite was 94 percent.","All patients had received docetaxel, 49 of 50 (98 percent) abiraterone or enzalutamide and 29 (58 percent) cabazitaxel; anaemia in 10 of 50 (20 percent) and fatigue in 6 (12 percent) were the most common grade 3 or 4 adverse events."],"whatItMeans":"The first molecularly stratified treatment in prostate cancer, and the proof that the synthetic lethality that works in ovarian and breast cancer works here too. Every PARP inhibitor now licensed in prostate cancer traces back to this trial.","caveats":["50 patients, single-arm, in a heavily pre-treated population; the response rate is not a survival benefit.","The composite response definition allowed objective response, a 50 percent prostate-specific antigen fall or circulating tumour cell conversion, which is broader than RECIST alone.","The ATM signal here (4 of 5 responding) was not confirmed in the larger randomised trials: TRITON3 found no benefit in the ATM subgroup."],"changedPractice":true,"participants":50},{"id":"paper-topaz-1-nejm-evidence-2022","kind":"paper","name":"TOPAZ-1: durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer","aka":[],"tldr":"Adding durvalumab to gemcitabine-cisplatin lengthened survival in advanced bile duct and gallbladder cancer, the first improvement on chemotherapy alone in more than a decade, with about a quarter of patients alive at two years.","summary":"Phase 3 placebo-controlled trial of 685 patients with previously untreated unresectable or metastatic biliary tract cancer randomised to durvalumab or placebo with gemcitabine and cisplatin for up to eight cycles followed by durvalumab or placebo maintenance.\n\nMedian overall survival was 12.8 versus 11.5 months (hazard ratio 0.80) with 24-month survival 24.9 versus 10.4 percent, progression-free survival 7.2 versus 5.7 months, and no meaningful increase in toxicity.","asOf":"2026-09-17","links":[{"label":"NEJM Evid 2022","url":"https://doi.org/10.1056/EVIDoa2200015"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38319896/"}],"tags":[],"related":[],"cancers":["extrahepatic-cholangiocarcinoma","intrahepatic-cholangiocarcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":["cisplatin","durvalumab","gemcitabine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["topaz-1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm-evidence"],"dependsOn":[],"notes":[],"journal":"NEJM Evidence","year":2022,"doi":"10.1056/EVIDoa2200015","pmid":"38319896","authors":"Oh DY, Ruth He A, Qin S, et al.","paperType":"rct","findings":["Median overall survival 12.8 vs 11.5 months; hazard ratio 0.80.","24-month overall survival 24.9 percent vs 10.4 percent."],"whatItMeans":"Durvalumab with gemcitabine-cisplatin is a first-line standard for advanced biliary tract cancer, with pembrolizumab (KEYNOTE-966) as the alternative.","caveats":["Modest median gain; benefit concentrated in a minority of long-term survivors.","No validated biomarker to select patients."],"changedPractice":true,"participants":685},{"id":"paper-study-201-jama-dermatol-2013","kind":"paper","name":"Topical chemotherapy in cutaneous T-cell lymphoma: positive results of a randomized, controlled, multicenter trial testing the efficacy and safety of a novel mechlorethamine, 0.02%, gel in mycosis fungoides","aka":[],"tldr":"The primary report of Study 201: a ready-made mechlorethamine gel cleared index lesions in 58.5 percent of early mycosis fungoides patients against 47.7 percent with the traditional compounded ointment, meeting the noninferiority bar.","summary":"Randomised, controlled, observer-blinded, multicentre trial at academic medical and cancer centres comparing mechlorethamine hydrochloride 0.02% gel with mechlorethamine 0.02% compounded ointment, applied once daily for up to 12 months, in 260 patients with stage IA to IIA mycosis fungoides who had not used topical mechlorethamine within 2 years and were naive to topical carmustine. The primary endpoint was response by the Composite Assessment of Index Lesion Severity (CAILS); secondary endpoints were the Modified Severity-Weighted Assessment Tool and time-to-response analyses.\n\nResponse rates for gel versus ointment were 58.5 versus 47.7 percent by CAILS and 46.9 versus 46.2 percent by the Modified Severity-Weighted Assessment Tool. The ratio of gel to ointment CAILS response rates was 1.23 (95% CI 0.97 to 1.55), which met the prespecified criterion for noninferiority. Time-to-response analyses demonstrated superiority of the gel.","asOf":"2026-09-24","links":[{"label":"JAMA Dermatology 2013","url":"https://doi.org/10.1001/2013.jamadermatol.541"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23069814/"},{"label":"ClinicalTrials.gov NCT00168064","url":"https://clinicaltrials.gov/study/NCT00168064"}],"tags":[],"related":[],"cancers":["cutaneous-t-cell-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["mechlorethamine"],"companies":["helsinn"],"institutions":[],"pathways":[],"terms":[],"trials":["study-201"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"JAMA Dermatology","year":2013,"doi":"10.1001/2013.jamadermatol.541","pmid":"23069814","authors":"Lessin SR, Duvic M, Guitart J, et al.","paperType":"rct","findings":["CAILS response 58.5% with mechlorethamine 0.02% gel vs 47.7% with compounded ointment; ratio 1.23 (95% CI 0.97 to 1.55), noninferiority met.","Modified Severity-Weighted Assessment Tool response 46.9% vs 46.2%.","Time-to-response analyses favoured the gel."],"whatItMeans":"This trial gave mechlorethamine, the first chemotherapy drug ever used, a modern licensed form: the FDA approved Valchlor gel in 2013 for early mycosis fungoides-type cutaneous T-cell lymphoma after skin-directed therapy, replacing pharmacy-compounded preparations of uncertain stability.","caveats":["Active-controlled noninferiority design against a compounded ointment; no placebo or untreated arm.","Observer-blinded rather than double-blinded for the applied product.","The label's efficacy table excludes 18 patients with randomisation protocol violations and reports 60% vs 48%."],"changedPractice":true,"participants":260},{"id":"paper-mai-jama","kind":"paper","name":"Toripalimab Plus Chemotherapy for Recurrent or Metastatic Nasopharyngeal Carcinoma: The JUPITER-02 Randomized Clinical Trial","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 38015220 and published in JAMA; the citing page links this DOI, which is how the record was matched.","summary":"Importance: There are currently no therapies approved by the US Food and Drug Administration for nasopharyngeal carcinoma (NPC). Gemcitabine-cisplatin is the current standard of care for the first-line treatment of recurrent or metastatic NPC (RM-NPC).\n\nObjective: To determine whether toripalimab in combination with gemcitabine-cisplatin will significantly improve progression-free survival and overall survival as first-line treatment for RM-NPC, compared with gemcitabine-cisplatin alone.\n\nDesign, setting, and participants: JUPITER-02 is an international, multicenter, randomized, double-blind phase 3 study conducted in NPC-endemic regions, including mainland China, Taiwan, and Singapore. From November 10, 2018, to October 20, 2019, 289 patients with RM-NPC with no prior systemic chemotherapy in the RM setting were enrolled from 35 participating centers.\n\nInterventions: Patients were randomized (1:1) to receive toripalimab (240 mg [n = 146]) or placebo (n = 143) in combination with gemcitabine-cisplatin for up to 6 cycles, followed by maintenance with toripalimab or placebo until disease progression, intolerable toxicity, or completion of 2 years of treatment.\n\nMain outcome: Progression-free survival as assessed by a blinded independent central review. Secondary end points included objective response rate, overall survival, progression-free survival assessed by investigator, duration of response, and safety.\n\nResults: Among the 289 patients enrolled (median age, 46 [IQR, 38-53 years; 17% female), at the final progression-free survival analysis, toripalimab treatment had a significantly longer progression-free survival than placebo (median, 21.4 vs 8.2 months; HR, 0.52 [95% CI, 0.37-0.73]). With a median survival follow-up of 36.0 months, a significant improvement in overall survival was identified with toripalimab over placebo (hazard ratio [HR], 0.63 [95% CI, 0.45-0.89]; 2-sided P =.008). The median overall survival was not reached in the toripalimab group, while it was 33.7 months in the placebo group. A consistent effect on overall survival, favoring toripalimab, was found in subgroups with high and low PD-L1 (programmed death-ligand 1) expression. The incidence of all adverse events, grade 3 or greater adverse events, and fatal adverse events were similar between the 2 groups. However, adverse events leading to discontinuation of toripalimab or placebo (11.6% vs 4.9%), immune-related adverse events (54.1% vs 21.7%), and grade 3 or greater immune-related adverse events (9.6% vs 1.4%) were more frequent in the toripalimab group.\n\nConclusions and relevance: The addition of toripalimab to chemotherapy as first-line treatment for RM-NPC provided statistically significant and clinically meaningful progression-free survival and overall survival benefits compared with chemotherapy alone, with a manageable safety profile. These findings support the use of toripalimab plus gemcitabine-cisplatin as the new standard of care for this patient population.\n\nTrial registration: ClinicalTrials.gov Identifier: NCT03581786.\n\nIndexed on Europe PMC as PubMed record 38015220 (DOI 10.1001/jama.2023.20181). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA 2023","url":"https://doi.org/10.1001/jama.2023.20181"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38015220/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38015220"}],"tags":["europepmc-ingest"],"related":["recurrent-metastatic-nasopharyngeal-carcinoma"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2023,"doi":"10.1001/jama.2023.20181","pmid":"38015220","authors":"Mai HQ, Chen QY, Chen D, et al.","paperType":"rct","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-wang-cancer-cell","kind":"paper","name":"Toripalimab plus chemotherapy in treatment-naïve, advanced esophageal squamous cell carcinoma (JUPITER-06): A multi-center phase 3 trial","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 35245446 and published in Cancer Cell; the citing page links this DOI, which is how the record was matched.","summary":"Platinum-based chemotherapy is the standard first-line treatment for advanced esophageal squamous cell carcinoma (ESCC). In this phase 3 study (ClinicalTrial.gov: NCT03829969), 514 patients with treatment-naïve advanced ESCC were randomized (1:1) to receive toripalimab or placebo in combination with paclitaxel plus cisplatin (TP) every 3 weeks for up to 6 cycles, followed by toripalimab or placebo maintenance. At the prespecified final analysis of progression-free survival (PFS), a significant improvement in PFS is observed for the toripalimab arm over the placebo arm (hazard ratio [HR] = 0.58; 95% CI, 0.46-0.74; p < 0.0001). The prespecified interim analysis of overall survival (OS) also reveals a significant OS improvement for patients treated with toripalimab plus TP over placebo plus TP (HR = 0.58; 95% CI, 0.43-0.78; p = 0.0004). The incidences of grade ≥3 treatment-emergent adverse events are similar between the two arms. Toripalimab plus TP significantly improves PFS and OS in patients with treatment-naïve, advanced ESCC, with a manageable safety profile.\n\nIndexed on Europe PMC as PubMed record 35245446 (DOI 10.1016/j.ccell.2022.02.007). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cancer Cell 2022","url":"https://doi.org/10.1016/j.ccell.2022.02.007"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35245446/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35245446"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["jupiter-06"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-cell"],"dependsOn":[],"notes":[],"journal":"Cancer Cell","year":2022,"doi":"10.1016/j.ccell.2022.02.007","pmid":"35245446","authors":"Wang ZX, Cui C, Yao J, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-torre-global-cancer-statistics-2012-cacancer-2015","kind":"paper","name":"Torre 2015: Global cancer statistics, 2012","aka":[],"tldr":"The GLOBOCAN-based world count for 2012: about 14.1 million new cancer cases, with more than half of cases and almost two thirds of deaths occurring in less developed regions, and lung cancer leading in men while breast cancer led in women.","summary":"Torre, Bray, Siegel and colleagues summarised the GLOBOCAN 2012 estimates for the American Cancer Society. They reported about 14.1 million new cases and 8.2 million deaths in 2012, with 57% of cases and 65% of deaths in less developed regions. Lung cancer was the leading cancer in men for both incidence and mortality; breast cancer led in women. The paper highlighted the rising share of the burden in transitioning countries and the potential of prevention, early detection and treatment to reduce it.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.3322/caac.21262"}],"tags":[],"related":["paper-bray-globocan-2018-cacancer-2018"],"cancers":["nsclc","breast-hr-positive"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["iarc"],"pathways":[],"terms":["incidence-vs-prevalence","mortality"],"trials":[],"people":["bray-freddie"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"CA: A Cancer Journal for Clinicians","year":2015,"doi":"10.3322/caac.21262","authors":"Torre LA, Bray F, Siegel RL, et al.","paperType":"observational","findings":["About 14.1 million new cancer cases and 8.2 million cancer deaths worldwide in 2012.","57% of cases and 65% of deaths occurred in less developed regions.","Lung cancer the leading cause of cancer incidence and death in men; breast cancer the leading cancer in women."],"whatItMeans":"One of the most cited descriptions of the global cancer burden of the 2010s, it framed the shift of cancer towards lower-income countries that later GLOBOCAN releases have confirmed.","caveats":["Superseded by the 2018, 2020 and 2022 GLOBOCAN releases.","Estimates for many countries were modelled from limited registry data."],"changedPractice":false},{"id":"paper-hernandez-jama-oncol","kind":"paper","name":"Total Costs of Chimeric Antigen Receptor T-Cell Immunotherapy","aka":[],"tldr":"Paper cited by one bottleneck page and 22 idea pages, indexed on Europe PMC as PubMed record 29710129 and published in JAMA Oncology; the citing pages link this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 29710129 (DOI 10.1001/jamaoncol.2018.0977). Matched by DOI alone: one bottleneck page and 22 idea pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA Oncol 2018","url":"https://doi.org/10.1001/jamaoncol.2018.0977"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29710129/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29710129"}],"tags":["europepmc-ingest"],"related":["b-manufacturing-cell-therapy","idea-reg-isotope-supply-observatory","idea-reg-manufacturing-slot-exchange","idea-reg-closed-manufacturing-interop-standard","idea-reg-yb176-enrichment-capacity","idea-reg-early-apheresis-banking","idea-reg-comparability-by-design-digital-twin","idea-reg-hpapi-continuous-flow","idea-reg-ai-process-control-cell-manufacturing","idea-reg-alpha-emitter-portfolio","idea-reg-hospital-exemption-harmonised","idea-reg-in-vivo-cart-off-the-shelf-vial","idea-moon-in-vivo-cart-generic-price","idea-reg-vein-to-vein-public-benchmark","idea-reg-open-source-lentiviral-vectors","idea-reg-non-viral-cart-manufacturing","idea-reg-public-cell-therapy-foundries","idea-reg-cart-potency-reference-standards","idea-reg-lmic-public-cart-manufacturing","idea-reg-ipsc-master-bank-qualified-once","idea-reg-ac225-accelerator-pharmacopoeia","idea-reg-regional-radiopharmacy-hubs","idea-reg-two-day-cart-rapid-release"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2018,"doi":"10.1001/jamaoncol.2018.0977","pmid":"29710129","authors":"Hernandez I, Prasad V, Gellad WF","paperType":"observational","findings":[],"whatItMeans":"One bottleneck page and 22 idea pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-murphy-jama-oncol","kind":"paper","name":"Total Neoadjuvant Therapy With FOLFIRINOX in Combination With Losartan Followed by Chemoradiotherapy for Locally Advanced Pancreatic Cancer: A Phase 2 Clinical Trial","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 31145418 and published in JAMA Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Importance: Patients with locally advanced pancreatic cancer have historically poor outcomes. Evaluation of a total neoadjuvant approach is warranted.\n\nObjective: To evaluate the margin-negative (R0) resection rate of neoadjuvant FOLFIRINOX (fluorouracil, leucovorin, oxaliplatin, and irinotecan) and losartan followed by chemoradiotherapy for locally advanced pancreatic cancer.\n\nDesign, setting, and participants: A single-arm phase 2 clinical trial was conducted at a large academic hospital from August 22, 2013, to May 22, 2018, among 49 patients with previously untreated locally advanced unresectable pancreatic cancer as determined by multidisciplinary review. Patients had Eastern Cooperative Oncology Group performance status 0 or 1 and adequate hematologic, renal, and hepatic function. Median follow-up for the analysis was 17.1 months (range, 5.0-53.7) among 27 patients still alive at study completion.\n\nInterventions: Patients received FOLFIRINOX and losartan for 8 cycles. Patients with radiographically resectable tumor after chemotherapy received short-course chemoradiotherapy (5 GyE × 5 with protons) with capecitabine. Patients with persistent vascular involvement received long-course chemoradiotherapy (50.4 Gy with a vascular boost to 58.8 Gy) with fluorouracil or capecitabine.\n\nMain outcomes and measures: R0 resection rate.\n\nResults: Of the 49 patients (26 women and 23 men; median age 63 years [range, 42-78 years]), 39 completed 8 cycles of FOLFIRINOX and losartan; 10 patients had fewer than 8 cycles due to progression (5 patients), losartan intolerance (3 patients), and toxicity (2 patients). Seven patients (16%) had short-course chemoradiotherapy while 38 (84%) had long-course chemoradiotherapy. Forty-two (86%) patients underwent attempted surgery, with R0 resection achieved in 34 of 49 patients (69%; 95% CI, 55%-82%). Overall median progression-free survival was 17.5 months (95% CI: 13.9-22.7) and median overall survival was 31.4 months (95% CI, 18.1-38.5). Among patients who underwent resection, median progression-free survival was 21.3 months (95% CI, 16.6-28.2), and median overall survival was 33.0 months (95% CI, 31.4 to not reached).\n\nConclusions and relevance: Total neoadjuvant therapy with FOLFIRINOX, losartan, and chemoradiotherapy provides downstaging of locally advanced pancreatic ductal adenocarcinoma and is associated with an R0 resection rate of 61%.\n\nTrial registration: ClinicalTrials.gov identifier: NCT01821729.\n\nIndexed on Europe PMC as PubMed record 31145418 (DOI 10.1001/jamaoncol.2019.0892). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA Oncol 2019","url":"https://doi.org/10.1001/jamaoncol.2019.0892"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31145418/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31145418"}],"tags":["europepmc-ingest"],"related":["mechanical-theory-of-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2019,"doi":"10.1001/jamaoncol.2019.0892","pmid":"31145418","authors":"Murphy JE, Wo JY, Ryan DP, et al.","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-rozhok-proc-natl-acad-sci-u-s-a","kind":"paper","name":"Toward an evolutionary model of cancer: Considering the mechanisms that govern the fate of somatic mutations","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 26195756 and published in Proceedings of the National Academy of Sciences; the citing page links this DOI, which is how the record was matched.","summary":"Our understanding of cancer has greatly advanced since Nordling [Nordling CO (1953) Br J Cancer 7(1):68-72] and Armitage and Doll [Armitage P, Doll R (1954) Br J Cancer 8(1):1-12] put forth the multistage model of carcinogenesis. However, a number of observations remain poorly understood from the standpoint of this paradigm in its contemporary state. These observations include the similar age-dependent exponential rise in incidence of cancers originating from stem/progenitor pools differing drastically in size, age-dependent cell division profiles, and compartmentalization. This common incidence pattern is characteristic of cancers requiring different numbers of oncogenic mutations, and it scales to very divergent life spans of mammalian species. Also, bigger mammals with larger underlying stem cell pools are not proportionally more prone to cancer, an observation known as Peto's paradox. Here, we present a number of factors beyond the occurrence of oncogenic mutations that are unaccounted for in the current model of cancer development but should have significant impacts on cancer incidence. Furthermore, we propose a revision of the current understanding for how oncogenic and other functional somatic mutations affect cellular fitness. We present evidence, substantiated by evolutionary theory, demonstrating that fitness is a dynamic environment-dependent property of a phenotype and that oncogenic mutations should have vastly different fitness effects on somatic cells dependent on the tissue microenvironment in an age-dependent manner. Combined, this evidence provides a firm basis for understanding the age-dependent incidence of cancers as driven by age-altered systemic processes regulated above the cell level.\n\nIndexed on Europe PMC as PubMed record 26195756 (DOI 10.1073/pnas.1501713112). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Proc Natl Acad Sci U S A 2015","url":"https://doi.org/10.1073/pnas.1501713112"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26195756/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26195756"}],"tags":["europepmc-ingest"],"related":["ageing-tissue-field-theory"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["pnas"],"dependsOn":[],"notes":[],"journal":"Proceedings of the National Academy of Sciences","year":2015,"doi":"10.1073/pnas.1501713112","pmid":"26195756","authors":"Rozhok AI, DeGregori J","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-yala-sci-transl-med","kind":"paper","name":"Toward robust mammography-based models for breast cancer risk","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 33504648 and published in Science Translational Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Improved breast cancer risk models enable targeted screening strategies that achieve earlier detection and less screening harm than existing guidelines. To bring deep learning risk models to clinical practice, we need to further refine their accuracy, validate them across diverse populations, and demonstrate their potential to improve clinical workflows. We developed Mirai, a mammography-based deep learning model designed to predict risk at multiple timepoints, leverage potentially missing risk factor information, and produce predictions that are consistent across mammography machines. Mirai was trained on a large dataset from Massachusetts General Hospital (MGH) in the United States and tested on held-out test sets from MGH, Karolinska University Hospital in Sweden, and Chang Gung Memorial Hospital (CGMH) in Taiwan, obtaining C-indices of 0.76 (95% confidence interval, 0.74 to 0.80), 0.81 (0.79 to 0.82), and 0.79 (0.79 to 0.83), respectively. Mirai obtained significantly higher 5-year ROC AUCs than the Tyrer-Cuzick model ( P < 0.001) and prior deep learning models Hybrid DL ( P < 0.001) and Image-Only DL ( P < 0.001), trained on the same dataset. Mirai more accurately identified high-risk patients than prior methods across all datasets. On the MGH test set, 41.5% (34.4 to 48.5) of patients who would develop cancer within 5 years were identified as high risk, compared with 36.1% (29.1 to 42.9) by Hybrid DL ( P = 0.02) and 22.9% (15.9 to 29.6) by the Tyrer-Cuzick model ( P < 0.001).\n\nIndexed on Europe PMC as PubMed record 33504648 (DOI 10.1126/scitranslmed.aba4373). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Sci Transl Med 2021","url":"https://doi.org/10.1126/scitranslmed.aba4373"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33504648/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33504648"}],"tags":["europepmc-ingest"],"related":["mirai"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["science-translational-medicine"],"dependsOn":[],"notes":[],"journal":"Science Translational Medicine","year":2021,"doi":"10.1126/scitranslmed.aba4373","pmid":"33504648","authors":"Yala A, Mikhael PG, Strand F, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-chen-nat-med","kind":"paper","name":"Towards a general-purpose foundation model for computational pathology","aka":[],"tldr":"Paper cited by two technology pages and one idea page, indexed on Europe PMC as PubMed record 38504018 and published in Nature Medicine; the citing pages link this DOI, which is how the record was matched.","summary":"Quantitative evaluation of tissue images is crucial for computational pathology (CPath) tasks, requiring the objective characterization of histopathological entities from whole-slide images (WSIs). The high resolution of WSIs and the variability of morphological features present significant challenges, complicating the large-scale annotation of data for high-performance applications. To address this challenge, current efforts have proposed the use of pretrained image encoders through transfer learning from natural image datasets or self-supervised learning on publicly available histopathology datasets, but have not been extensively developed and evaluated across diverse tissue types at scale. We introduce UNI, a general-purpose self-supervised model for pathology, pretrained using more than 100 million images from over 100,000 diagnostic H&E-stained WSIs (>77 TB of data) across 20 major tissue types. The model was evaluated on 34 representative CPath tasks of varying diagnostic difficulty. In addition to outperforming previous state-of-the-art models, we demonstrate new modeling capabilities in CPath such as resolution-agnostic tissue classification, slide classification using few-shot class prototypes, and disease subtyping generalization in classifying up to 108 cancer types in the OncoTree classification system. UNI advances unsupervised representation learning at scale in CPath in terms of both pretraining data and downstream evaluation, enabling data-efficient artificial intelligence models that can generalize and transfer to a wide range of diagnostically challenging tasks and clinical workflows in anatomic pathology.\n\nIndexed on Europe PMC as PubMed record 38504018 (DOI 10.1038/s41591-024-02857-3). Matched by DOI alone: two technology pages and one idea page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Med 2024","url":"https://doi.org/10.1038/s41591-024-02857-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38504018/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38504018"}],"tags":["europepmc-ingest"],"related":["pathology-foundation-model","uni-conch","idea-multimodal-foundation-model"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2024,"doi":"10.1038/s41591-024-02857-3","pmid":"38504018","authors":"Chen RJ, Ding T, Lu MY, et al.","paperType":"observational","findings":[],"whatItMeans":"Two technology pages and one idea page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-tpextreme-lancet-oncol-2021","kind":"paper","name":"TPExtreme (GORTEC 2014-01): docetaxel, cisplatin and cetuximab versus the EXTREME regimen in recurrent or metastatic head and neck cancer","aka":[],"tldr":"Replacing fluorouracil with docetaxel in the cetuximab-platinum regimen for advanced head and neck cancer did not lengthen survival but was less toxic and much easier to give, so TPEx is an accepted alternative.","summary":"Randomised phase 2 trial of 541 patients with recurrent or metastatic head and neck squamous cell carcinoma randomised to TPEx (docetaxel, cisplatin and cetuximab for four cycles then cetuximab maintenance) or the EXTREME regimen.\n\nMedian overall survival was 14.5 versus 13.4 months (not significant), with fewer grade 4 or higher adverse events (34 versus 50 percent) and shorter treatment duration in the TPEx arm.","asOf":"2026-09-17","links":[{"label":"Lancet Oncol 2021","url":"https://doi.org/10.1016/S1470-2045(20)30755-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33684370/"}],"tags":[],"related":[],"cancers":["recurrent-metastatic-hnscc"],"sections":[],"technologies":[],"targets":[],"drugs":["cetuximab","cisplatin","docetaxel"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["tpextreme"],"people":["joel-guigay"],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2021,"doi":"10.1016/S1470-2045(20)30755-5","pmid":"33684370","authors":"Guigay J, Aupérin A, Fayette J, et al.","paperType":"rct","findings":["Median overall survival 14.5 vs 13.4 months (not significantly different).","Grade 4 or higher adverse events 34 percent vs 50 percent."],"whatItMeans":"TPEx is a less toxic, more convenient chemotherapy backbone for patients who need cetuximab-based first-line therapy, for instance when immunotherapy is unsuitable.","caveats":["Did not meet its superiority endpoint.","Both arms performed better than historical EXTREME data, reflecting later-line immunotherapy."],"changedPractice":true,"participants":541},{"id":"paper-trabectedin-vs-dacarbazine-demetri-jco-2016","kind":"paper","name":"Trabectedin versus dacarbazine for metastatic liposarcoma or leiomyosarcoma after anthracycline failure","aka":[],"tldr":"Trabectedin reduced the risk of progression by 45 percent compared with dacarbazine in previously treated liposarcoma and leiomyosarcoma, leading to its approval in the United States, though survival was not improved.","summary":"Phase 3 trial of 518 patients with advanced liposarcoma or leiomyosarcoma after an anthracycline and at least one other regimen randomised 2:1 to trabectedin or dacarbazine.\n\nMedian progression-free survival was 4.2 versus 1.5 months (hazard ratio 0.55) with benefit in both histologies and particularly in myxoid liposarcoma; median overall survival was 12.4 versus 12.9 months (not significant). Transaminase elevation and myelosuppression were the main toxicities.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2016","url":"https://doi.org/10.1200/JCO.2015.62.4734"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26371143/"}],"tags":[],"related":[],"cancers":["liposarcoma","leiomyosarcoma"],"sections":[],"technologies":[],"targets":[],"drugs":["dacarbazine","trabectedin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2016,"doi":"10.1200/JCO.2015.62.4734","pmid":"26371143","authors":"Demetri GD, von Mehren M, Jones RL, et al.","paperType":"rct","findings":["Median progression-free survival 4.2 vs 1.5 months; hazard ratio 0.55.","No overall survival difference (12.4 vs 12.9 months)."],"whatItMeans":"Trabectedin is a standard later-line option for liposarcoma and leiomyosarcoma and is especially active in myxoid liposarcoma.","caveats":["Open-label; dacarbazine control performed poorly on progression-free survival."],"changedPractice":true,"participants":518},{"id":"paper-tracerx-evolution-nature-2023","kind":"paper","name":"TRACERx 421: the full-cohort picture of how lung cancer evolves and which subclones drive relapse","aka":[],"tldr":"Analysis of 1,644 tumour regions from 421 patients confirmed that subclonal expansions and whole-genome doubling predict relapse, mapped which drivers are selected late, and showed that the metastasising subclone is often a minor population in the primary.","summary":"The full TRACERx 421 cohort report was published as a set of Nature papers in April 2023. Frankell and colleagues analysed 1,644 regions from 421 early-stage NSCLC tumours with whole-exome sequencing and phylogenetic reconstruction.\n\nSubclonal selection was pervasive, with evidence of positive selection acting on late-arising drivers such as those in the PI3K pathway and chromatin modifiers; subclonal expansions (a large subclone dominating a region) and whole-genome doubling were associated with worse disease-free survival. Companion papers showed that the metastasis-seeding clone was frequently a minor subclone in the primary (Al Bakir), that ctDNA at surgery and subclonal copy-number alterations predicted outcome (Abbosh), and that a mutation-independent mechanism by which air pollution promotes EGFR-mutant lung cancer (Hill) operates through inflammation acting on pre-existing mutant cells.\n\nTRACERx is the largest longitudinal tumour-evolution dataset and the model for evolutionary studies in other cancers.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1038/s41586-023-05783-5"},{"label":"TRACERx Nature collection 2023","url":"https://www.nature.com/collections/tracerx"}],"tags":[],"related":["paper-tracerx-100-nejm-2017","whole-genome-doubling","idea-prev-clean-air-never-smoker-endpoints","idea-bio1-clonal-clearance-endpoint"],"cancers":["nsclc"],"sections":["diagnostics"],"technologies":["wes-wgs","liquid-biopsy","mrd-testing"],"targets":[],"drugs":[],"companies":[],"institutions":["francis-crick","cruk"],"pathways":["clonal-evolution","chromosomal-instability","inflammation-nfkb"],"terms":["ctdna","mrd"],"trials":[],"people":["charles-swanton"],"bottlenecks":["b-tumor-heterogeneity","b-metastasis-biology","b-dormancy-mrd"],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2023,"doi":"10.1038/s41586-023-05783-5","pmid":"37046096","authors":"Frankell AM, Dietzen M, Al Bakir M, et al. (TRACERx Consortium)","paperType":"translational","findings":["1,644 regions from 421 tumours; subclonal expansions and recent whole-genome doubling associated with shorter disease-free survival","Positive selection detected on subclonal drivers, including in the PI3K pathway and chromatin regulators, meaning late drivers are not merely passengers","Companion paper: metastases frequently seeded by minor subclones of the primary, and by polyclonal seeding in a substantial fraction","Companion paper: air pollutant PM2.5 promotes lung cancer in EGFR-mutant cells via IL-1beta-driven inflammation without new mutations","Companion paper: preoperative ctDNA detection and its dynamics predicted relapse"],"whatItMeans":"Relapse after surgery is driven by particular subclones that can be identified in the primary tumour and tracked in blood, which argues for evolution-aware adjuvant strategies. The pollution finding reframes carcinogenesis: some agents promote already-mutant cells rather than causing mutations.","caveats":["Observational and correlative; interventions based on evolutionary metrics have not been tested","Whole-exome data limits detection of structural and non-coding events","Predominantly UK patients with resectable disease; evolutionary dynamics in advanced and treated disease differ","Cost and complexity of multi-region sequencing preclude routine clinical use"],"changedPractice":false,"participants":421},{"id":"paper-tracerx-100-nejm-2017","kind":"paper","name":"TRACERx first 100: tracking how lung cancers evolve, and how chromosomal chaos predicts relapse","aka":[],"tldr":"Multi-region sequencing of 327 regions from the first 100 TRACERx lung cancers showed that most driver mutations are early and shared while copy-number chaos continues to evolve, and that tumours with high copy-number heterogeneity were nearly five times more likely to relapse or kill the patient.","summary":"TRACERx (TRAcking Cancer Evolution through therapy) is a Cancer Research UK prospective study following patients with resected stage I-IIIA non-small-cell lung cancer from surgery to relapse or death. This first report analysed 327 tumour regions from 100 patients with whole-exome sequencing.\n\nIntratumour heterogeneity was pervasive: a median of 30% of mutations were subclonal, and 48% of tumours had subclonal driver alterations. Driver mutations in EGFR, MET, BRAF and TP53 were almost always clonal (early), whereas alterations in PIK3CA, NF1 and chromatin modifiers were often late. Ongoing chromosomal instability (subclonal copy-number alterations) rather than mutational heterogeneity predicted recurrence-free survival: patients whose tumours had elevated copy-number heterogeneity had a hazard ratio of 4.9 for recurrence or death.\n\nA companion paper (Abbosh, Nature 2017) showed phylogenetic ctDNA tracking could detect relapse a median 70 days before imaging.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1056/NEJMoa1616288"},{"label":"Phylogenetic ctDNA analysis (Abbosh 2017)","url":"https://doi.org/10.1038/nature22364"},{"label":"ClinicalTrials.gov NCT01888601","url":"https://clinicaltrials.gov/study/NCT01888601"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28445112/"}],"tags":[],"related":["paper-gerlinger-intratumour-heterogeneity-nejm-2012","paper-tracerx-evolution-nature-2023","whole-genome-doubling","idea-bio1-clonal-neoantigen-vaccines","paper-abbosh-phylogenetic-ctdna-lung-cancer-nature-2017","paper-hill-lung-adenocarcinoma-air-pollutants-nature-2023","paper-sequist-genotypic-histological-evolution-egfr-resistance-sci-transl-med-2011"],"cancers":["nsclc","lung-cancer","resectable-nsclc"],"sections":["diagnostics"],"technologies":["wes-wgs","liquid-biopsy","mrd-testing","ngs"],"targets":["egfr","kras","tp53","met","braf"],"drugs":[],"companies":[],"institutions":["francis-crick","cruk"],"pathways":["clonal-evolution","chromosomal-instability"],"terms":["ctdna","mrd","neoantigen","driver-mutation","biopsy","clonal-evolution"],"trials":[],"people":["charles-swanton"],"bottlenecks":["b-tumor-heterogeneity","b-dormancy-mrd","b-resistance","b-biomarker-validation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2017,"doi":"10.1056/NEJMoa1616288","pmid":"28445112","authors":"Jamal-Hanjani M, Wilson GA, McGranahan N, et al. (TRACERx Consortium)","paperType":"translational","findings":["327 regions from 100 tumours; median 30% of mutations subclonal, 48% of tumours with subclonal drivers","Elevated copy-number intratumour heterogeneity associated with recurrence or death: HR 4.9 (95% CI 1.8-13.1)","EGFR, MET, BRAF and TP53 mutations almost always clonal; PIK3CA, NF1 and chromatin-modifier mutations often subclonal","Whole-genome doubling occurred in most tumours and preceded much of the copy-number diversification","Companion ctDNA paper: relapse detected a median 70 days before CT in tracked patients"],"whatItMeans":"Lung cancers keep evolving after they form, and it is ongoing chromosomal instability rather than the number of mutations that best predicts who will relapse. This gives a rationale for targeting the earliest (clonal) drivers and neoantigens and for tracking evolution in blood after surgery.","caveats":["Early-stage, surgically resected tumours only; the interim cohort of 100 was later expanded to 421","Exome sequencing does not capture non-coding or structural events fully","The prognostic value of copy-number heterogeneity needed validation in the full cohort and other cancers","Clinical utility of clonal-neoantigen targeting remained hypothetical at the time"],"changedPractice":false,"participants":100},{"id":"paper-train-2-lancet-oncol-2018","kind":"paper","name":"TRAIN-2: neoadjuvant chemotherapy with or without anthracyclines alongside dual HER2 blockade","aka":[],"tldr":"Leaving out anthracyclines from neoadjuvant chemotherapy made no difference to how many HER2-positive breast cancers disappeared completely when trastuzumab and pertuzumab were given, so the heart-toxic drugs can be dropped.","summary":"Phase 3 trial of 438 patients with stage II to III HER2-positive breast cancer randomised to nine cycles of carboplatin-paclitaxel with trastuzumab and pertuzumab, with or without three initial cycles of an anthracycline-containing regimen.\n\nPathological complete response was 67 percent with anthracyclines and 68 percent without; three-year event-free survival was similar, while febrile neutropenia and cardiac events were more common with anthracyclines.","asOf":"2026-09-17","links":[{"label":"Lancet Oncol 2018","url":"https://doi.org/10.1016/S1470-2045(18)30570-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30413379/"}],"tags":[],"related":[],"cancers":["her2-positive-early-breast-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["train-2"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2018,"doi":"10.1016/S1470-2045(18)30570-9","pmid":"30413379","authors":"van Ramshorst MS, van der Voort A, van Werkhoven ED, et al.","paperType":"rct","findings":["Pathological complete response 67 percent with vs 68 percent without anthracyclines.","Three-year event-free survival 92.7 percent vs 93.6 percent."],"whatItMeans":"Anthracycline-free carboplatin-taxane chemotherapy with dual HER2 blockade is a standard neoadjuvant regimen, sparing patients cardiac risk without losing efficacy.","caveats":["Not powered for long-term survival differences.","Both arms used nine cycles of chemotherapy, longer than some current regimens."],"changedPractice":true,"participants":438},{"id":"paper-conti-trans-ancestry-gwas-prostate-nat-genet-2021","kind":"paper","name":"Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction","aka":["Conti 2021","prostate polygenic risk score 269 variants","trans-ancestry prostate GWAS"],"tldr":"The largest genetic study of prostate cancer pooled 107,247 men with the disease and 127,006 without, across ancestries. It brought the number of known risk variants to 269 and showed that men of African ancestry carry, on average, more than twice the genetic risk score of men of European ancestry.","summary":"David Conti, Christopher Haiman, Rosalind Eeles and a very large consortium ran a multi-ancestry meta-analysis of prostate cancer genome-wide association studies and combined the resulting variants into a genetic risk score, then compared the distribution of that score across ancestry groups.\n\nThe finding that matters for policy is the last one. Prostate cancer incidence and mortality differ sharply by ancestry, and the argument about why has run for decades between biology and access to care. This paper supplies a measured component of the biological side: the mean genetic risk score is 2.18 times higher in men of African ancestry and 0.73 times that of European ancestry in men of East Asian ancestry. It does not settle the mortality question, which Dess and colleagues addressed by adjusting for access, but it does say that a screening programme whose entry criterion is age alone is using the wrong variable.","asOf":"2026-09-25","links":[{"label":"Nat Genet 2021","url":"https://doi.org/10.1038/s41588-020-00748-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33398198/"}],"tags":["prostate-evidence"],"related":["paper-dess-black-race-prostate-mortality-jama-oncol-2019","paper-pritchard-inherited-dna-repair-metastatic-prostate-nejm-2016","idea-prev-prs-screening-start-age","idea-prev-mri-first-prostate-screening-prs","prostate-roadmap"],"cancers":["prostate"],"sections":["prevention","early-detection","diagnostics"],"technologies":["germline-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["screening","polygenic-risk-score","other-cause-mortality"],"trials":[],"people":[],"bottlenecks":["b-hereditary-risk","b-early-detection","b-trial-diversity","b-global-access"],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":2021,"doi":"10.1038/s41588-020-00748-0","pmid":"33398198","authors":"Conti DV, Darst BF, Moss LC, et al.","paperType":"observational","findings":["A multi-ancestry meta-analysis of 107,247 cases and 127,006 controls identified 86 new risk variants, bringing the total to 269 known prostate cancer risk variants.","The top genetic risk score decile was associated with odds ratios from 5.06 (95 percent confidence interval 4.84 to 5.29) in men of European ancestry to 3.74 (3.36 to 4.17) in men of African ancestry.","Men of African ancestry were estimated to have a mean genetic risk score 2.18 times higher than men of European ancestry (95 percent confidence interval 2.14 to 2.22).","Men of East Asian ancestry were estimated to have a mean genetic risk score 0.73 times that of men of European ancestry (0.71 to 0.76).","The authors concluded that germline variation contributes to population differences in prostate cancer risk and that the genetic risk score offers an approach to personalised risk prediction."],"whatItMeans":"The evidence base for setting the age at which screening starts by risk rather than by birthday. It is also a warning: the same score performs differently across ancestries, so a risk model built and validated in European cohorts will under-serve the men at highest risk.","caveats":["A risk score built largely from European-ancestry discovery data, which is why its odds ratio is lower in men of African ancestry despite their higher mean score.","Association study design: the variants are markers of risk, not causes with known mechanisms.","A higher mean genetic risk score explains part of the difference in incidence and says nothing directly about differences in mortality, which are strongly influenced by access to care."],"changedPractice":false,"participants":234253},{"id":"paper-nct05081609-j-immunother-cancer-2022","kind":"paper","name":"TransCon IL-2 β/γ: a novel long-acting prodrug with sustained release of an IL-2Rβ/γ-selective IL-2 variant with improved pharmacokinetics and potent activation of cytotoxic immune cells for the treatment of cancer","aka":[],"tldr":"Published report from the trial registered as NCT05081609, in Journal for ImmunoTherapy of Cancer (2022), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Recombinant interleukin-2 (IL-2, aldesleukin) is an approved cancer immunotherapy but causes severe toxicities including cytokine storm and vascular leak syndrome (VLS). IL-2 promotes antitumor function of IL-2Rβ/γ + natural killer (NK) cells and CD8 +, CD4 + and gamma delta (γδ) T cells. However, IL-2 also potently activates immunosuppressive IL-2Rα + regulatory T cells (Tregs) and IL-2Rα + eosinophils and endothelial cells, which may promote VLS. Aldesleukin is rapidly cleared requiring frequent dosing, resulting in high C max likely potentiating toxicity. Thus, IL-2 cancer immunotherapy has two critical drawbacks: potent activation of undesired IL-2Rα + cells and suboptimal pharmacokinetics with high C max and short half-life.\n\nMethods: TransCon IL-2 β/γ was designed to optimally address these drawbacks. To abolish IL-2Rα binding yet retain strong IL-2Rβ/γ activity, IL-2 β/γ was created by permanently attaching a small methoxy polyethylene glycol (mPEG) moiety in the IL-2Rα binding site. To improve pharmacokinetics, IL-2 β/γ was transiently attached to a 40 kDa mPEG carrier via a TransCon (transient conjugation) linker creating a prodrug, TransCon IL-2 β/γ, with sustained release of IL-2 β/γ. IL-2 β/γ was characterized in binding and primary cell assays while TransCon IL-2 β/γ was studied in tumor-bearing mice and cynomolgus monkeys.\n\nResults: IL-2 β/γ demonstrated selective and potent human IL-2Rβ/γ binding and activation without IL-2Rα interactions. TransCon IL-2 β/γ showed slow-release pharmacokinetics with a low C max and a long (>30 hours) effective half-life for IL-2 β/γ in monkeys. In mouse tumor models, TransCon IL-2 β/γ promoted CD8 + T cell and NK cell activation and antitumor activity. In monkeys, TransCon IL-2 β/γ induced robust activation and expansion of CD8 + T cells, NK cells and γδ T cells, relative to CD4 + T cells, Tregs and eosinophils, with no evidence of cytokine storm or VLS. Similarly, IL-2 β/γ enhanced proliferation and cytotoxicity of primary human CD8 + T cells, NK cells and γδ T cells.\n\nSummary: TransCon IL-2 β/γ is a novel long-acting prodrug with sustained release of an IL-2Rβ/γ-selective IL-2. It has remarkable and durable pharmacodynamic effects in monkeys and potential for improved clinical efficacy and tolerability compared with aldesleukin. TransCon IL-2 β/γ is currently being evaluated in a Phase 1/2 clinical trial (NCT05081609).\n\nIndexed on Europe PMC as PubMed record 35817480 (DOI 10.1136/jitc-2022-004991). Its abstract cites the registry id NCT05081609, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Immunother Cancer 2022","url":"https://doi.org/10.1136/jitc-2022-004991"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35817480/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35817480"},{"label":"ClinicalTrials.gov NCT05081609","url":"https://clinicaltrials.gov/study/NCT05081609"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05081609"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jitc"],"dependsOn":[],"notes":[],"journal":"Journal for ImmunoTherapy of Cancer","year":2022,"doi":"10.1136/jitc-2022-004991","pmid":"35817480","authors":"Rosen DB, Kvarnhammar AM, Laufer B, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05081609 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-chan-seng-yue-pancreatic-transcription-phenotypes-nat-genet-2020","kind":"paper","name":"Transcription phenotypes of pancreatic cancer are driven by genomic events during tumor evolution","aka":[],"tldr":"Whole genomes and transcriptomes from purified tumour cells showed that the classical and basal-like types are not two boxes but a continuum of mixed cell populations, set by how many copies of mutant KRAS and GATA6 a tumour has gained, often after its genome doubled.","summary":"A dataset of whole genomes and transcriptomes was generated from purified epithelium of primary and metastatic pancreatic adenocarcinomas. Transcriptome analysis demonstrated that molecular subtypes are a product of a gene expression continuum driven by a mixture of intratumoural subpopulations, confirmed by single-cell analysis. Integrated whole-genome analysis linked subtypes to specific copy-number aberrations in genes such as mutant KRAS and GATA6. Mapping tumour genetic histories identified tetraploidisation as a key mutational process behind these events.","asOf":"2026-09-24","links":[{"label":"Chan-Seng-Yue et al., Nat Genet 2020: transcription phenotypes driven by genomic events (purified whole genomes)","url":"https://doi.org/10.1038/s41588-019-0566-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31932696/"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":["wes-wgs","rna-seq","single-cell-spatial"],"targets":["kras"],"drugs":[],"companies":[],"institutions":["oicr","princess-margaret","cold-spring-harbor"],"pathways":["chromosomal-instability","clonal-evolution"],"terms":["whole-genome-doubling","copy-number-variation-term"],"trials":[],"people":["david-tuveson"],"bottlenecks":[],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":2020,"doi":"10.1038/s41588-019-0566-9","pmid":"31932696","authors":"Chan-Seng-Yue M, Kim JC, Wilson GW, et al.","paperType":"translational","findings":["Subtypes are a continuum of intratumoural subpopulations, confirmed by single-cell analysis.","Mutant KRAS and GATA6 copy number drive the phenotype; tetraploidisation underlies the events."],"whatItMeans":"It explains why single-sample classifiers disagree on about one tumour in eight and why KRAS allelic imbalance and GATA6 copy number are being read alongside expression.","caveats":["Purified-epithelium cohort from one programme.","Clinical value of allele-dosage readouts is untested."],"changedPractice":false},{"id":"paper-bradner-cell","kind":"paper","name":"Transcriptional Addiction in Cancer","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 28187285 and published in Cell; the citing page links this DOI, which is how the record was matched.","summary":"Cancer arises from genetic alterations that invariably lead to dysregulated transcriptional programs. These dysregulated programs can cause cancer cells to become highly dependent on certain regulators of gene expression. Here, we discuss how transcriptional control is disrupted by genetic alterations in cancer cells, why transcriptional dependencies can develop as a consequence of dysregulated programs, and how these dependencies provide opportunities for novel therapeutic interventions in cancer.\n\nIndexed on Europe PMC as PubMed record 28187285 (DOI 10.1016/j.cell.2016.12.013). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cell 2017","url":"https://doi.org/10.1016/j.cell.2016.12.013"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28187285/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28187285"}],"tags":["europepmc-ingest"],"related":["transcription-addiction"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Cell","year":2017,"doi":"10.1016/j.cell.2016.12.013","pmid":"28187285","authors":"Bradner JE, Hnisz D, Young RA","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-langley-lancet","kind":"paper","name":"Transdermal oestradiol for androgen suppression in prostate cancer: long-term cardiovascular outcomes from the randomised Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 33581820 and published in The Lancet; the citing page links this DOI, which is how the record was matched.","summary":"Background: Androgen suppression is a central component of prostate cancer management but causes substantial long-term toxicity. Transdermal administration of oestradiol (tE2) circumvents first-pass hepatic metabolism and, therefore, should avoid the cardiovascular toxicity seen with oral oestrogen and the oestrogen-depletion effects seen with luteinising hormone releasing hormone agonists (LHRHa). We present long-term cardiovascular follow-up data from the Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme.\n\nMethods: PATCH is a seamless phase 2/3, randomised, multicentre trial programme at 52 study sites in the UK. Men with locally advanced or metastatic prostate cancer were randomly allocated (1:2 from August, 2007 then 1:1 from February, 2011) to either LHRHa according to local practice or tE2 patches (four 100 μg patches per 24 h, changed twice weekly, reducing to three patches twice weekly if castrate at 4 weeks [defined as testosterone ≤1·7 nmol/L]). Randomisation was done using a computer-based minimisation algorithm and was stratified by several factors, including disease stage, age, smoking status, and family history of cardiac disease. The primary outcome of this analysis was cardiovascular morbidity and mortality. Cardiovascular events, including heart failure, acute coronary syndrome, thromboembolic stroke, and other thromboembolic events, were confirmed using predefined criteria and source data. Sudden or unexpected deaths were attributed to a cardiovascular category if a confirmatory post-mortem report was available and as other relevant events if no post-mortem report was available. PATCH is registered with the ISRCTN registry, ISRCTN70406718; the study is ongoing and adaptive.\n\nFindings: Between Aug 14, 2007, and July 30, 2019, 1694 men were randomly allocated either LHRHa (n=790) or tE2 patches (n=904). Overall, median follow-up was 3·9 (IQR 2·4-7·0) years. Respective castration rates at 1 month and 3 months were 65% and 93% among patients assigned LHRHa and 83% and 93% among those allocated tE2. 157 events from 145 men met predefined cardiovascular criteria, with a further ten sudden deaths with no post-mortem report (total 167 events in 153 men). 26 (2%) of 1694 patients had fatal cardiovascular events, 15 (2%) of 790 assigned LHRHa and 11 (1%) of 904 allocated tE2. The time to first cardiovascular event did not differ between treatments (hazard ratio 1·11, 95% CI 0·80-1·53; p=0·54 [including sudden deaths without post-mortem report]; 1·20, 0·86-1·68; p=0·29 [confirmed group only]). 30 (34%) of 89 cardiovascular events in patients assigned tE2 occurred more than 3 months after tE2 was stopped or changed to LHRHa. The most frequent adverse events were gynaecomastia (all grades), with 279 (38%) events in 730 patients who received LHRHa versus 690 (86%) in 807 patients who received tE2 (p<0·0001) and hot flushes (all grades) in 628 (86%) of those who received LHRHa versus 280 (35%) who received tE2 (p<0·0001).\n\nInterpretation: Long-term data comparing tE2 patches with LHRHa show no evidence of a difference between treatments in cardiovascular mortality or morbidity. Oestrogens administered transdermally should be reconsidered for androgen suppression in the management of prostate cancer.\n\nFunding: Cancer Research UK, and Medical Research Council Clinical Trials Unit at University College London.\n\nIndexed on Europe PMC as PubMed record 33581820 (DOI 10.1016/s0140-6736(21)00100-8). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet 2021","url":"https://doi.org/10.1016/s0140-6736(21)00100-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33581820/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33581820"}],"tags":["europepmc-ingest"],"related":["prostate-roadmap","paper-huggins-hodges-castration-serum-phosphatases-prostate-1941","idea-prostate-other-cause-mortality-as-a-reported-service-outcome"],"cancers":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["stampede"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2021,"doi":"10.1016/s0140-6736(21)00100-8","pmid":"33581820","authors":"Langley RE, Gilbert DC, Duong T, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-theodoris-nature","kind":"paper","name":"Transfer learning enables predictions in network biology","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 37258680 and published in Nature; the citing page links this DOI, which is how the record was matched.","summary":"Mapping gene networks requires large amounts of transcriptomic data to learn the connections between genes, which impedes discoveries in settings with limited data, including rare diseases and diseases affecting clinically inaccessible tissues. Recently, transfer learning has revolutionized fields such as natural language understanding 1,2 and computer vision 3 by leveraging deep learning models pretrained on large-scale general datasets that can then be fine-tuned towards a vast array of downstream tasks with limited task-specific data. Here, we developed a context-aware, attention-based deep learning model, Geneformer, pretrained on a large-scale corpus of about 30 million single-cell transcriptomes to enable context-specific predictions in settings with limited data in network biology. During pretraining, Geneformer gained a fundamental understanding of network dynamics, encoding network hierarchy in the attention weights of the model in a completely self-supervised manner. Fine-tuning towards a diverse panel of downstream tasks relevant to chromatin and network dynamics using limited task-specific data demonstrated that Geneformer consistently boosted predictive accuracy. Applied to disease modelling with limited patient data, Geneformer identified candidate therapeutic targets for cardiomyopathy. Overall, Geneformer represents a pretrained deep learning model from which fine-tuning towards a broad range of downstream applications can be pursued to accelerate discovery of key network regulators and candidate therapeutic targets.\n\nIndexed on Europe PMC as PubMed record 37258680 (DOI 10.1038/s41586-023-06139-9). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2023","url":"https://doi.org/10.1038/s41586-023-06139-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37258680/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37258680"}],"tags":["europepmc-ingest"],"related":["geneformer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2023,"doi":"10.1038/s41586-023-06139-9","pmid":"37258680","authors":"Theodoris CV, Xiao L, Chopra A, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-transform-liso-cel-lancet-2022","kind":"paper","name":"TRANSFORM: liso-cel CAR-T versus salvage chemotherapy and transplant in early-relapsing large B-cell lymphoma","aka":[],"tldr":"In TRANSFORM, a second CD19 CAR-T, lisocabtagene maraleucel, also beat chemotherapy-plus-transplant as second-line treatment, with a low rate of severe side effects.","summary":"TRANSFORM randomised 184 patients with large B-cell lymphoma refractory to or relapsed within 12 months of first-line therapy to lisocabtagene maraleucel (liso-cel) or standard salvage chemotherapy with autologous transplant for responders. Bridging chemotherapy was allowed and crossover to liso-cel was permitted for standard-arm failures. The primary endpoint was event-free survival. At the interim analysis median EFS was 10.1 versus 2.3 months (hazard ratio 0.35) with complete response 66% versus 39%; in the primary analysis median EFS was not reached versus 2.4 months (hazard ratio 0.36). Grade 3 CRS occurred in 1% and grade 3 neurological events in 4%. Overall survival was not significantly different, in part because of crossover.","asOf":"2026-09-08","links":[{"label":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=TRANSFORM%20lisocabtagene%20maraleucel%20second-line%20Kamdar%20Lancet%202022"},{"label":"ClinicalTrials.gov NCT03575351","url":"https://clinicaltrials.gov/study/NCT03575351"}],"tags":[],"related":["car-t-before-transplant-lbcl","paper-zuma-7-axi-cel-second-line-nejm-2022","lymphoma-roadmap","paper-belinda-tisagenlecleucel-second-line-nejm-2022","paper-transcend-nhl-001-liso-cel-lancet-2020"],"cancers":["dlbcl"],"sections":[],"technologies":["car-t","autologous-stem-cell-transplant"],"targets":["cd19"],"drugs":["lisocabtagene-maraleucel"],"companies":["bms"],"institutions":[],"pathways":[],"terms":["efs","crs","icans"],"trials":["transform","zuma-7","belinda"],"people":[],"bottlenecks":["b-manufacturing-cell-therapy","b-toxicity-qol"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2022,"doi":"10.1016/S0140-6736(22)00662-6","pmid":"35717989","authors":"Kamdar M, Solomon SR, Arnason J, et al.","paperType":"rct","findings":["184 patients with primary refractory or early-relapsing LBCL; liso-cel vs salvage chemotherapy and transplant.","Interim: median EFS 10.1 vs 2.3 months; hazard ratio 0.35; complete response 66% vs 39%.","Primary analysis: median EFS not reached vs 2.4 months; hazard ratio 0.36.","Grade 3 CRS 1%; grade 3 neurological events 4%; no grade 4-5 CRS or neurotoxicity.","Crossover to liso-cel allowed; OS not significantly different."],"whatItMeans":"TRANSFORM confirmed ZUMA-7's conclusion with a different CD19 CAR-T and a more permissive design that allowed bridging chemotherapy, making the results closer to real-world practice. Liso-cel's low toxicity makes it attractive for older or frailer patients and for outpatient delivery. Together the two trials made CAR-T the standard second-line therapy for early-relapsing aggressive lymphoma.","caveats":["Smaller than ZUMA-7 and reported at interim analysis; EFS rather than OS was the endpoint.","Crossover blunted any survival comparison.","Excludes late relapse.","Liso-cel manufacturing involves separate CD4 and CD8 components, adding complexity."],"changedPractice":true,"participants":184},{"id":"paper-denmeade-transformer-bipolar-androgen-therapy-jco-2021","kind":"paper","name":"TRANSFORMER: bipolar androgen therapy versus enzalutamide in asymptomatic metastatic castration-resistant prostate cancer","aka":["TRANSFORMER","Denmeade 2021 bipolar androgen therapy randomised"],"tldr":"A randomised comparison of high-dose testosterone against a standard hormone-blocking drug. Neither delayed progression better than the other, but men who had the testosterone first and the drug second lived nearly nine months longer before their second progression, and felt better throughout.","summary":"Samuel Denmeade and colleagues randomised 195 asymptomatic men with castration-resistant metastatic prostate cancer to monthly bipolar androgen therapy (94) or enzalutamide (101), with crossover permitted at progression. The primary endpoint was clinical or radiographic progression-free survival; the secondary endpoints included progression-free survival from randomisation through crossover, which the authors call PFS2.\n\nOn the primary endpoint the trial is flat: 5.7 months in both arms. The interesting result is the sequence effect. Prostate-specific antigen progression-free survival on enzalutamide was 3.8 months when it followed abiraterone and 10.9 months when it followed bipolar androgen therapy, and PFS2 was 28.2 months for the bipolar-then-enzalutamide sequence against 19.6 months for the reverse. Quality of life consistently favoured bipolar androgen therapy. The trial is the reason the approach is worth a phase 3, and PFS2 is the endpoint that phase 3 would need.","asOf":"2026-09-25","links":[{"label":"J Clin Oncol 2021","url":"https://doi.org/10.1200/jco.20.02759"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33617303/"},{"label":"ClinicalTrials.gov NCT02286921","url":"https://clinicaltrials.gov/study/NCT02286921"}],"tags":["prostate-evidence"],"related":["paper-teply-restore-bipolar-androgen-therapy-lancet-oncol-2018","paper-hussain-swog-9346-intermittent-androgen-deprivation-nejm-2013","idea-tr1-adaptive-therapy-randomised-phase-2","prostate-roadmap"],"cancers":["prostate","prostate-mcrpc"],"sections":["hormonal"],"technologies":[],"targets":["androgen-receptor"],"drugs":["enzalutamide","abiraterone"],"companies":[],"institutions":["johns-hopkins"],"pathways":[],"terms":["castration-resistance","psa","quality-of-life","bipolar-androgen-therapy","radiographic-progression-free-survival"],"trials":[],"people":[],"bottlenecks":["b-resistance","b-trial-design","b-toxicity-qol"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2021,"doi":"10.1200/jco.20.02759","pmid":"33617303","authors":"Denmeade SR, Wang H, Agarwal N, et al.","paperType":"rct","findings":["Progression-free survival 5.7 months in both arms (hazard ratio 1.14; 95 percent confidence interval 0.83 to 1.55; P equals 0.42).","A 50 percent decline in prostate-specific antigen in 28.2 percent on bipolar androgen therapy against 25.3 percent on enzalutamide.","At crossover, a 50 percent prostate-specific antigen decline occurred in 77.8 percent of patients crossing to enzalutamide and 23.4 percent of those crossing to bipolar androgen therapy.","Prostate-specific antigen progression-free survival on enzalutamide was 3.8 months when given after abiraterone and 10.9 months when given after bipolar androgen therapy.","Progression-free survival through crossover was 28.2 months for bipolar androgen therapy followed by enzalutamide against 19.6 months for the reverse sequence (hazard ratio 0.44; 0.22 to 0.88; P equals 0.02); overall survival 32.9 against 29.0 months (hazard ratio 0.95; P equals 0.80). Adverse events on bipolar androgen therapy were primarily grade 1 to 2 and patient-reported quality of life consistently favoured it."],"whatItMeans":"The first randomised evidence that the order in which prostate cancer treatments are given changes how long they work, independently of which treatments they are. It is also a rare trial in which quality of life pointed one way and the primary endpoint pointed nowhere.","caveats":["The primary endpoint was negative; PFS2 and the resensitisation effect are secondary and hypothesis-generating.","195 patients, asymptomatic and without high-risk sites for tumour flare, so the population is selected.","Overall survival did not differ significantly (32.9 against 29.0 months, P equals 0.80), and the crossover design makes survival hard to interpret."],"changedPractice":false,"participants":195},{"id":"paper-contopoulos-ioannidis-am-j-med","kind":"paper","name":"Translation of highly promising basic science research into clinical applications","aka":[],"tldr":"Paper cited by one bottleneck page, indexed on Europe PMC as PubMed record 12731504 and published in The American journal of medicine; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: To evaluate the predictors of and time taken for the translation of highly promising basic research into clinical experimentation and use.\n\nMethods: We identified 101 articles, published between 1979 and 1983 in six major basic science journals, which clearly stated that the technology studied had novel therapeutic or preventive promises. Each case was evaluated for whether the promising finding resulted in relevant randomized controlled trials and clinical use. Main outcomes included the time to published trials, time to published trials with favorable results (\"positive\" trials), and licensed clinical use.\n\nResults: By October 2002, 27 of the promising technologies had resulted in at least one published randomized trial, 19 of which had led to the publication of at least one positive randomized trial. Five basic science findings are currently licensed for clinical use, but only has been used extensively for the licensed indications. Promising technologies that did not lead to a published human study within 10 to 12 years were unlikely to be tested in humans subsequently. Some form of industry involvement in the basic science publication was the strongest predictor of clinical experimentation, accelerating the process by about eightfold (95% confidence interval: 3 to 19) when an author had industry affiliations.\n\nConclusion: Even the most promising findings of basic research take a long time to translate into clinical experimentation, and adoption in clinical practice is rare.\n\nIndexed on Europe PMC as PubMed record 12731504 (DOI 10.1016/s0002-9343(03)00013-5). Matched by DOI alone: one bottleneck page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Am J Med 2003","url":"https://doi.org/10.1016/s0002-9343(03)00013-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/12731504/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/12731504"}],"tags":["europepmc-ingest"],"related":["b-translational-valley"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The American journal of medicine","year":2003,"doi":"10.1016/s0002-9343(03)00013-5","pmid":"12731504","authors":"Contopoulos-Ioannidis DG, Ntzani E, Ioannidis JP","paperType":"rct","findings":[],"whatItMeans":"One bottleneck page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-zhu-clin-transl-sci","kind":"paper","name":"Translational findings support regimen selection for first-in-human study of ubamatamab (MUC16 × CD3 bispecific antibody) in patients with recurrent ovarian cancer","aka":[],"tldr":"Paper cited by one treatment page and one target page, indexed on Europe PMC as PubMed record 39652449 and published in Clinical and translational science; the citing pages link this DOI, which is how the record was matched.","summary":"Ubamatamab, a Mucin 16 (MUC16) × cluster of differentiation 3 (CD3) bispecific antibody that promotes T-cell-mediated cytotoxicity of MUC16-expressing cells, is being investigated for the treatment of ovarian cancer. Intravenous administration of ubamatamab, with or without the anti-programmed cell death-1 inhibitor cemiplimab, is being evaluated in a first-in-human study in patients with recurrent ovarian cancer. In vitro cytotoxicity and cytokine data and projected ubamatamab human pharmacokinetic (PK) profiles scaled with monkey PK parameters enabled starting-dose selection in humans. Mouse tumor regression studies identified ubamatamab effective concentrations. Preclinical and clinical PK, cytokine, safety, and efficacy data from dose escalation were integrated to determine expansion regimens. A starting dose of 0.1 mg was selected, which showed acceptable safety in patients. A step-up dosing approach was used to effectively manage cytokine release syndrome. Mouse tumor regression models suggested an ubamatamab efficacious concentration range of 0.4-50 mg/L, consistent with clinical activity observed at ubamatamab trough concentrations ≥5 mg/L. Integrating preclinical and clinical data determined a target trough concentration range of 5-30 mg/L, which supports evaluation of ubamatamab 250 mg with or without cemiplimab and 800 mg monotherapy once every 3 weeks in expansion cohorts. Preclinical data (cytokine release, tumor regression, monkey PK) had translational value in supporting regimen selection in dose escalation and subsequently in dose expansion after integration with patient data from dose escalation.\n\nIndexed on Europe PMC as PubMed record 39652449 (DOI 10.1111/cts.70082). Matched by DOI alone: one treatment page and one target page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Clin Transl Sci 2024","url":"https://doi.org/10.1111/cts.70082"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39652449/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39652449"}],"tags":["europepmc-ingest"],"related":["ubamatamab","muc16"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Clinical and translational science","year":2024,"doi":"10.1111/cts.70082","pmid":"39652449","authors":"Zhu M, Madia P, Crawford A, et al.","paperType":"basic","findings":[],"whatItMeans":"One treatment page and one target page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-butler-nature","kind":"paper","name":"Translational research: crossing the valley of death","aka":[],"tldr":"Paper cited by one bottleneck page and twelve idea pages, indexed on Europe PMC as PubMed record 18548043 and published in Nature; the citing pages link this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 18548043 (DOI 10.1038/453840a). Matched by DOI alone: one bottleneck page and twelve idea pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2008","url":"https://doi.org/10.1038/453840a"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/18548043/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/18548043"}],"tags":["europepmc-ingest"],"related":["b-translational-valley","idea-fund-royalty-pool-academic-assets","idea-fund-biomarker-validation-fund","idea-fund-global-academic-phase-one-network","idea-fund-public-nonprofit-cro","idea-fund-phase-zero-fund","idea-fund-academic-sponsor-indemnity-pool","idea-moon-public-phase1-factory","idea-fund-device-and-technique-translation-fund","idea-fund-academic-radiopharma-pipeline","idea-fund-hospital-exemption-registry","idea-fund-protected-time-physician-scientists","idea-fund-translational-fellowships"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2008,"doi":"10.1038/453840a","pmid":"18548043","authors":"Butler D","paperType":"observational","findings":[],"whatItMeans":"One bottleneck page and twelve idea pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-chernet-dis-model-mech","kind":"paper","name":"Transmembrane voltage potential is an essential cellular parameter for the detection and control of tumor development in a Xenopus model","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 23471912 and published in Disease models & mechanisms; the citing page links this DOI, which is how the record was matched.","summary":"Understanding mechanisms that orchestrate cell behavior into appropriately patterned tissues and organs within the organism is an essential element of preventing, detecting and treating cancer. Bioelectric signals (resting transmembrane voltage potential gradients in all cells) underlie an important and broadly conserved set of control mechanisms that regulate pattern formation. We tested the role of transmembrane potential in tumorigenesis mediated by canonical oncogenes in Xenopus laevis. Depolarized membrane potential (Vmem) was a characteristic of induced tumor-like structures (ITLSs) generated by overexpression of Gli1, Kras(G12D), Xrel3 or p53(Trp248). This bioelectric signature was also present in precursor ITLS sites. Vmem is a bioelectric marker that reveals ITLSs before they become histologically and morphologically apparent. Moreover, voltage was functionally important: overexpression of hyperpolarizing ion transporters caused a return to normal Vmem and significantly reduced ITLS formation in vivo. To characterize the molecular mechanism by which Vmem change regulates ITLS phenotypes, we performed a suppression screen. Vmem hyperpolarization was transduced into downstream events via Vmem-regulated activity of SLC5A8, a sodium-butyrate exchanger previously implicated in human cancer. These data indicate that butyrate, a histone deacetylase (HDAC) inhibitor, might be responsible for transcriptional events that mediate suppression of ITLSs by hyperpolarization. Vmem is a convenient cellular parameter by which tumors induced by human oncogenes can be detected in vivo and represents a new diagnostic modality. Moreover, control of resting membrane potential is functionally involved in the process by which oncogene-bearing cells depart from normal morphogenesis programs to form tumors. Modulation of Vmem levels is a novel and promising strategy for tumor normalization.\n\nIndexed on Europe PMC as PubMed record 23471912 (DOI 10.1242/dmm.010835). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Dis Model Mech 2013","url":"https://doi.org/10.1242/dmm.010835"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23471912/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/23471912"}],"tags":["europepmc-ingest"],"related":["bioelectric-theory-of-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Disease models & mechanisms","year":2013,"doi":"10.1242/dmm.010835","pmid":"23471912","authors":"Chernet BT, Levin M","paperType":"basic","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-hera-b31-n9831-n-engl-j-med-2005","kind":"paper","name":"Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer","aka":[],"tldr":"Published report from the HERA trial registered as NCT00045032, in New England Journal of Medicine (2005), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Trastuzumab, a recombinant monoclonal antibody against HER2, has clinical activity in advanced breast cancer that overexpresses HER2. We investigated its efficacy and safety after excision of early-stage breast cancer and completion of chemotherapy.\n\nMethods: This international, multicenter, randomized trial compared one or two years of trastuzumab given every three weeks with observation in patients with HER2-positive and either node-negative or node-positive breast cancer who had completed locoregional therapy and at least four cycles of neoadjuvant or adjuvant chemotherapy.\n\nResults: Data were available for 1694 women randomly assigned to two years of treatment with trastuzumab, 1694 women assigned to one year of trastuzumab, and 1693 women assigned to observation. We report here the results only of treatment with trastuzumab for one year or observation. At the first planned interim analysis (median follow-up of one year), 347 events (recurrence of breast cancer, contralateral breast cancer, second nonbreast malignant disease, or death) were observed: 127 events in the trastuzumab group and 220 in the observation group. The unadjusted hazard ratio for an event in the trastuzumab group, as compared with the observation group, was 0.54 (95 percent confidence interval, 0.43 to 0.67; P<0.0001 by the log-rank test, crossing the interim analysis boundary), representing an absolute benefit in terms of disease-free survival at two years of 8.4 percentage points. Overall survival in the two groups was not significantly different (29 deaths with trastuzumab vs. 37 with observation). Severe cardiotoxicity developed in 0.5 percent of the women who were treated with trastuzumab.\n\nConclusions: One year of treatment with trastuzumab after adjuvant chemotherapy significantly improves disease-free survival among women with HER2-positive breast cancer. (ClinicalTrials.gov number, NCT00045032.)\n\nIndexed on Europe PMC as PubMed record 16236737 (DOI 10.1056/nejmoa052306). Its abstract cites the registry id NCT00045032, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2005","url":"https://doi.org/10.1056/nejmoa052306"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/16236737/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/16236737"},{"label":"ClinicalTrials.gov NCT00045032","url":"https://clinicaltrials.gov/study/NCT00045032"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["hera-b31-n9831"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2005,"doi":"10.1056/nejmoa052306","pmid":"16236737","authors":"Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT00045032 with the most citations, so it is the natural first reading for anyone following the HERA trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-nct06968585-j-clin-oncol-2026","kind":"paper","name":"Trastuzumab Botidotin Versus Trastuzumab Emtansine in Human Epidermal Growth Factor Receptor 2-Positive Advanced Breast Cancer: A Phase III, Open-Label, Randomized Controlled Trial","aka":[],"tldr":"Published report from the trial registered as NCT06968585, in Journal of Clinical Oncology (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Purpose: To evaluate the safety and efficacy of the novel human epidermal growth factor receptor 2 (HER2)-directed antibody-drug conjugate, trastuzumab botidotin, for the treatment of HER2-positive unresectable/metastatic breast cancer (BC).\n\nMethods: In this phase III, open-label, multicenter trial (ClinicalTrials.gov identifier: NCT06968585), conducted at 57 centers in China, adult patients with HER2-positive, unresectable/metastatic BC who had received prior trastuzumab and a taxane were randomly assigned (1:1) to receive trastuzumab botidotin or trastuzumab emtansine. The primary end point was progression-free survival (PFS), assessed by blinded independent central review (BICR), using an intention-to-treat analysis. In a prespecified interim analysis of PFS per BICR, trastuzumab botidotin met the prespecified superiority boundary ( P <.0001). We report here the prespecified final analysis of PFS.\n\nResults: Between July 18, 2023, and April 26, 2024, 365 patients were randomly assigned to trastuzumab botidotin (n = 182) or trastuzumab emtansine (n = 183). At data cutoff (median follow-up, 14.9 months), trastuzumab botidotin resulted in longer PFS than trastuzumab emtansine (median, 11.1 v 4.4 months; hazard ratio [HR], 0.39 [95% CI, 0.30 to 0.51]; nominal P <.0001). Benefit was consistent across subgroups, including those defined by prior lines of anti-HER2 therapy, prior pertuzumab or anti-HER2 tyrosine kinase inhibitors, and visceral metastases. The objective response rate was 76.9% (95% CI, 70.1 to 82.8) with trastuzumab botidotin and 53.0% (95% CI, 45.5 to 60.4) with trastuzumab emtansine. Overall survival data were immature (medians not reached in either group; HR, 0.62 [95% CI, 0.38 to 1.03]). Grade ≥3 treatment-emergent adverse events occurred in 127 (69.8%) and 116 (63.7%) patients in each group, respectively. Ocular treatment-related adverse events had a high incidence with trastuzumab botidotin; however, with a protocol-defined algorithm, most events generally recovered or resolved. Trastuzumab botidotin treatment had low incidences of pulmonary, hematologic, hepatic, and GI toxicities.\n\nConclusion: Among patients with HER2-positive advanced BC previously treated with trastuzumab and a taxane, trastuzumab botidotin resulted in significantly longer PFS than trastuzumab emtansine, with a distinct safety profile.\n\nIndexed on Europe PMC as PubMed record 42727044 (DOI 10.1200/jco-26-00602). Its abstract cites the registry id NCT06968585, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2026","url":"https://doi.org/10.1200/jco-26-00602"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42727044/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42727044"},{"label":"ClinicalTrials.gov NCT06968585","url":"https://clinicaltrials.gov/study/NCT06968585"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct06968585"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2026,"doi":"10.1200/jco-26-00602","pmid":"42727044","authors":"Zhang J, Ouyang Q, Zhang Q, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT06968585 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-siena-destiny-crc01-trastuzumab-deruxtecan-lancet-oncol-2021","kind":"paper","name":"Trastuzumab deruxtecan (DS-8201) in patients with HER2-expressing metastatic colorectal cancer (DESTINY-CRC01)","aka":[],"tldr":"An antibody carrying a chemotherapy payload shrank 45 percent of HER2-positive bowel cancers that had already failed two or more treatments, including tumours that had progressed on other HER2 drugs.","summary":"Siena, Di Bartolomeo, Raghav and colleagues recruited patients from 25 clinics and hospitals in Italy, Japan, Spain, the United Kingdom and the United States with centrally confirmed HER2-expressing metastatic colorectal cancer that had progressed on two or more previous regimens, RAS and BRAF V600E wild-type tumours and ECOG score 0 or 1; previous HER2-targeted therapy other than trastuzumab deruxtecan was permitted. Patients were enrolled into three cohorts by HER2 expression level and received 6.4 mg/kg trastuzumab deruxtecan intravenously every three weeks. The primary endpoint was confirmed objective response in cohort A by independent central review.\n\nBetween February 2018 and July 2019, 78 patients were enrolled: 53 in cohort A (HER2-positive), seven in cohort B and 18 in cohort C.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2021","url":"https://doi.org/10.1016/S1470-2045(21)00086-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33961795/"}],"tags":["colorectal-evidence"],"related":["paper-strickler-mountaineer-tucatinib-trastuzumab-lancet-oncol-2023","paper-sartore-bianchi-heracles-trastuzumab-lapatinib-lancet-oncol-2016"],"cancers":["colorectal","her2-amplified-colorectal"],"sections":["adcs","targeted-therapy"],"technologies":["adc"],"targets":["her2"],"drugs":["trastuzumab-deruxtecan","crc01","trastuzumab"],"companies":["daiichi-sankyo"],"institutions":[],"pathways":[],"terms":[],"trials":["destiny-crc02"],"people":["salvatore-siena","yoshino-takayuki"],"bottlenecks":["b-rare-cancers","b-toxicity-qol"],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2021,"doi":"10.1016/S1470-2045(21)00086-3","pmid":"33961795","authors":"Siena S, Di Bartolomeo M, Raghav K, et al.","paperType":"rct","findings":["Confirmed objective response in 24 of 53 (45.3 percent, 95 percent CI 31.6 to 59.6) in the HER2-positive cohort, after a median 27.1 weeks of follow-up.","Grade 3 or worse treatment-emergent events occurring in at least 10 percent: decreased neutrophil count 17 of 78 (22 percent) and anaemia 11 (14 percent).","Five patients (6 percent) had adjudicated interstitial lung disease or pneumonitis, including two grade 5 events, the only treatment-related deaths."],"whatItMeans":"The antibody-drug conjugate route into HER2-positive colorectal cancer, extended by DESTINY-CRC02 at a lower dose; interstitial lung disease is the class risk that defines how the drug is monitored.","caveats":["Single-arm phase 2 in 53 evaluable patients at the registration dose.","Two treatment-related deaths from interstitial lung disease at 6.4 mg/kg; DESTINY-CRC02 tested 5.4 mg/kg partly for this reason.","Cohorts B and C, with lower HER2 expression, showed little activity."],"changedPractice":true,"participants":78},{"id":"paper-destiny-breast04-nat-med-2025-update","kind":"paper","name":"Trastuzumab deruxtecan in HER2-low metastatic breast cancer: long-term survival analysis of the randomized, phase 3 DESTINY-Breast04 trial","aka":[],"tldr":"Later report from the DESTINY-Breast04 trial registered as NCT03734029, in Nature Medicine (2025); its title describes an updated or longer-term analysis.","summary":"In DESTINY-Breast04 ( NCT03734029), trastuzumab deruxtecan (T-DXd) significantly improved overall survival (OS) and progression-free survival compared with treatment of physician's choice of chemotherapy (TPC) for patients with human epidermal growth factor receptor 2-low (HER2-low) (immunohistochemistry (IHC) 1+ or IHC 2+/in situ hybridization-negative) metastatic breast cancer. After an extended median follow-up of 32.0 months, median OS in the overall cohort was 22.9 months for T-DXd and 16.8 months for TPC (hazard ratio 0.69; 95% confidence interval 0.55-0.86). For the hormone receptor-positive cohort, median OS was 23.9 and 17.6 months for T-DXd and TPC, respectively (hazard ratio 0.69; 95% confidence interval 0.55-0.87). Median OS also favored T-DXd in exploratory analyses of hormone receptor-negative, estrogen receptor IHC 1%-10% and estrogen receptor IHC >10% cohorts. The overall safety profile of T-DXd was acceptable and generally manageable. Results confirm T-DXd as standard of care after prior chemotherapy in patients with HER2-low metastatic breast cancer. ClinicalTrials.gov identifier: NCT03734029.\n\nIndexed on Europe PMC as PubMed record 41062831 (DOI 10.1038/s41591-025-03981-4). Its abstract cites the registry id NCT03734029, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Nat Med 2025","url":"https://doi.org/10.1038/s41591-025-03981-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41062831/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41062831"},{"label":"ClinicalTrials.gov NCT03734029","url":"https://clinicaltrials.gov/study/NCT03734029"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["destiny-breast04"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2025,"doi":"10.1038/s41591-025-03981-4","pmid":"41062831","authors":"Modi S, Jacot W, Iwata H, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the DESTINY-Breast04 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-destiny-breast12-nat-med-2024","kind":"paper","name":"Trastuzumab deruxtecan in HER2-positive advanced breast cancer with or without brain metastases: a phase 3b/4 trial","aka":[],"tldr":"Published report from the DESTINY-Breast12 trial registered as NCT04739761, in Nature Medicine (2024), chosen as the most cited paper whose own text cites the registry id.","summary":"Trastuzumab deruxtecan (T-DXd) intracranial activity has been observed in small or retrospective patient cohorts with human epidermal growth factor receptor 2-positive (HER2 +) advanced/metastatic breast cancer (mBC) and stable or active (untreated/previously treated and progressing) brain metastases (BMs). The phase 3b/4 DESTINY-Breast12 study investigated T-DXd in patients with HER2 + mBC and is, to our knowledge, the largest prospective study of T-DXd in patients with BMs in this setting. Patients (stable/active BMs (n = 263) and no BMs (n = 241)) treated with one or more prior anti-HER2-based regimens received T-DXd (5.4 mg per kg). Primary endpoints were progression-free survival (PFS; BMs cohort) and objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (non-BMs cohort). Additional endpoints included central nervous system (CNS) PFS, ORR, time to second progression, CNS ORR (BMs cohort), incidence of new symptomatic CNS metastases (non-BMs cohort), time to progression, duration of response, overall survival and safety (both cohorts). No formal hypothesis testing was conducted for this single-arm, open-label study. In the BMs cohort, 12-month PFS was 61.6% (95% confidence interval (CI): 54.9-67.6), and 12-month CNS PFS was 58.9% (95% CI: 51.9-65.3). In the non-BMs cohort, ORR was 62.7% (95% CI: 56.5-68.8). Grade 3 or higher adverse events occurred in 51% (BMs cohort) and 49% (non-BMs cohort) of patients. Investigator-reported interstitial lung disease/pneumonitis occurred in 16% (grade ≥3: 3%) of patients with BMs and 13% (grade ≥3: 1%) of patients without BMs. These data show substantial and durable overall and intracranial activity for T-DXd, supporting its use in previously treated patients with HER2 + mBC irrespective of stable/active baseline BMs. ClinicalTrials.gov identifier: NCT04739761.\n\nIndexed on Europe PMC as PubMed record 39271844 (DOI 10.1038/s41591-024-03261-7). Its abstract cites the registry id NCT04739761, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Nat Med 2024","url":"https://doi.org/10.1038/s41591-024-03261-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39271844/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39271844"},{"label":"ClinicalTrials.gov NCT04739761","url":"https://clinicaltrials.gov/study/NCT04739761"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["destiny-breast12"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2024,"doi":"10.1038/s41591-024-03261-7","pmid":"39271844","authors":"Harbeck N, Ciruelos E, Jerusalem G, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04739761 with the most citations, so it is the natural first reading for anyone following the DESTINY-Breast12 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-ohba-herb-trastuzumab-deruxtecan-biliary-jco-2024","kind":"paper","name":"Trastuzumab deruxtecan in human epidermal growth factor receptor 2-expressing biliary tract cancer (HERB; NCCH1805): a multicenter, single-arm, phase II trial","aka":[],"tldr":"The antibody-drug conjugate trastuzumab deruxtecan shrank tumours in about a third of Japanese patients with HER2-positive bile duct or gallbladder cancer after chemotherapy, and in one in eight with low HER2, but a quarter developed lung inflammation and two died of it.","summary":"Patients from five Japanese institutions with pathologically confirmed unresectable or recurrent biliary tract cancer, centrally confirmed HER2-positive (IHC 3+, or IHC 2+ and ISH-positive) or HER2-low (IHC 2+ and ISH-negative, IHC 1+, or IHC 0 and ISH-positive), refractory or intolerant to a gemcitabine-containing regimen, received trastuzumab deruxtecan 5.4 mg/kg every 3 weeks. The primary endpoint was confirmed objective response rate in HER2-positive disease by independent central review (threshold 15%, expected 40%).\n\n32 patients were enrolled and treated. The 22 with HER2-positive disease had a confirmed objective response rate of 36.4% (90% CI 19.6 to 56.1; P = 0.01), meeting the primary endpoint; the 8 with HER2-low disease had a confirmed response rate of 12.5%. The most common grade 3 or worse treatment-related adverse events were anaemia (53.1%) and neutropenia (31.3%). Eight patients (25.0%) had interstitial lung disease, including two grade 5 events.","asOf":"2026-09-24","links":[{"label":"Ohba et al., J Clin Oncol 2024: trastuzumab deruxtecan in HER2-expressing biliary tract cancer (HERB)","url":"https://doi.org/10.1200/jco.23.02010"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39102634/"}],"tags":[],"related":[],"cancers":["gallbladder","biliary-tract-cancer","cholangiocarcinoma"],"sections":[],"technologies":[],"targets":["her2"],"drugs":["trastuzumab-deruxtecan"],"companies":["daiichi-sankyo","astrazeneca"],"institutions":["ncc-japan"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2024,"doi":"10.1200/jco.23.02010","pmid":"39102634","authors":"Ohba A, Morizane C, Kawamoto Y, et al.","paperType":"observational","findings":["Confirmed objective response rate 36.4% (8 of 22) in HER2-positive and 12.5% (1 of 8) in HER2-low biliary tract cancer.","Grade 3 or worse anaemia 53.1% and neutropenia 31.3%.","Interstitial lung disease in 25.0% (8 of 32), two fatal."],"whatItMeans":"Together with the DESTINY-PanTumor02 biliary cohort this is the evidence behind trastuzumab deruxtecan's tumour-agnostic IHC 3+ label being used in gallbladder cancer; the lung toxicity rate, higher than in breast cancer, is the caution for a population with pre-existing lung and liver compromise.","caveats":["32 patients, single arm, Japanese centres only.","Two treatment-related deaths from interstitial lung disease in a small cohort."],"changedPractice":false,"participants":32},{"id":"paper-nct05246514-clin-lung-cancer-2026","kind":"paper","name":"Trastuzumab Deruxtecan in Patients From China With Pretreated HER2-Mutant Non-Small Cell Lung Cancer: Final Analysis of the Phase 2, Single-Arm DESTINY-Lung05 Trial","aka":[],"tldr":"Published report from the DESTINY-Lung05 trial registered as NCT05246514, in Clinical lung cancer (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Introduction: Trastuzumab deruxtecan (T-DXd) was approved in China in October 2024 for previously treated human epidermal growth factor receptor 2 (HER2)-mutant (HER2m) unresectable/metastatic non-small cell lung cancer (NSCLC), based on DESTINY-Lung02 and DESTINY-Lung05 primary results. Here, we report the DESTINY-Lung05 final analysis.\n\nMethods: DESTINY-Lung05 (NCT05246514), an open-label, single-arm, multicenter, phase 2 study, investigated T-DXd (5.4 mg/kg once every 3 weeks) in patients from China with HER2m (locally or centrally confirmed activating HER2 exon 19/20 mutation) metastatic NSCLC with disease progression on/after ≥ 1 prior anticancer therapy. The primary endpoint was confirmed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors 1.1 by independent central review (ICR). Secondary endpoints included progression-free survival (PFS) by ICR, overall survival (OS), and safety.\n\nResults: at November 4, 2024, 72 patients with HER2m NSCLC had received T-DXd 5.4 mg/kg; the median duration of follow-up was 20.2 months (range, 2-27). Confirmed ORR (ICR) was 56.9% (95% confidence interval [CI] 44.7-68.6). Median PFS (ICR) and OS were 9.9 months (95% CI 7.1-16.5) and 21.0 months (95% CI 17.5-not calculable), respectively. Grade ≥ 3 drug-related adverse events occurred in 40 (55.6%) patients. Adjudicated drug-related interstitial lung disease/pneumonitis events were observed in 9 (12.5%) patients (n = 8 grade 1/2; n = 1 grade 3).\n\nConclusions: With extended follow-up, T-DXd continued to demonstrate clinically meaningful and durable antitumor activity in patients from China with pretreated HER2m metastatic NSCLC, with no new safety signals. Results affirm the use of T-DXd as a treatment option in China for this patient population.\n\nIndexed on Europe PMC as PubMed record 42480250 (DOI 10.1016/j.cllc.2026.06.003). Its abstract cites the registry id NCT05246514, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Clin Lung Cancer 2026","url":"https://doi.org/10.1016/j.cllc.2026.06.003"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42480250/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42480250"},{"label":"ClinicalTrials.gov NCT05246514","url":"https://clinicaltrials.gov/study/NCT05246514"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05246514"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-lung-cancer"],"dependsOn":[],"notes":[],"journal":"Clinical lung cancer","year":2026,"doi":"10.1016/j.cllc.2026.06.003","pmid":"42480250","authors":"Liu Y, Li D, Wu L, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05246514 with the most citations, so it is the natural first reading for anyone following the DESTINY-Lung05 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-destiny-crc02-lancet-oncol-2024","kind":"paper","name":"Trastuzumab deruxtecan in patients with HER2-positive advanced colorectal cancer (DESTINY-CRC02): primary results from a multicentre, randomised, phase 2 trial","aka":[],"tldr":"Published report from the DESTINY-CRC02 trial registered as NCT04744831, in The Lancet Oncology (2024), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Trastuzumab deruxtecan has shown encouraging activity in patients with treatment-refractory HER2-positive, RAS wild-type and BRAF wild-type metastatic colorectal cancer. Dose optimisation and further antitumour assessments in patients with RAS mutations and those with previous anti-HER2 therapy are warranted. We aimed to evaluate two doses of trastuzumab deruxtecan (5·4 mg/kg and 6·4 mg/kg) to establish the recommended dose in patients with pretreated HER2-positive, RAS wild-type or mutant metastatic colorectal cancer.\n\nMethods: DESTINY-CRC02 was a multicentre, randomised, two-stage, two-arm, phase 2 study done in 53 research hospitals and medical centres in Australia, Belgium, France, Italy, Japan, South Korea, Spain, Taiwan, the UK, and the USA. Eligible patients were aged 18 years and older or 20 years and older (depending on region) with pretreated pathologically documented, unresectable, recurrent, or metastatic HER2-positive, and RAS wild-type or mutant colorectal cancer. Patients were required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and have received previous chemotherapy, and anti-EGFR, anti-VEGF, or anti-PD-L1 therapy, if clinically indicated. In stage 1, patients were randomly assigned (1:1), via a secure interactive response technology system, to receive 5·4 mg/kg or 6·4 mg/kg trastuzumab deruxtecan administered intravenously every 21 days. Stratification factors were ECOG performance status, HER2 status, and RAS status. In stage 2, patients were assigned into the 5·4 mg/kg treatment group only. The primary endpoint was confirmed objective response rate by blinded independent central review, assessed in all patients for whom treatment was assigned (full analysis set). Safety was assessed in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT04744831, and is ongoing (not recruiting).\n\nFindings: Between March 5, 2021, and March 29, 2022, 135 patients were centrally screened, 122 of whom were enrolled. In stage 1, 40 patients each were randomly assigned to receive trastuzumab deruxtecan 5·4 mg/kg and 6·4 mg/kg. In stage 2, an additional 42 patients were enrolled in the 5·4 mg/kg group. 64 (52%) participants were male and 58 (48%) were female. The median duration of follow-up was 8·9 months (IQR 6·7-10·5) in the 5·4 mg/kg group and 10·3 months (5·9-12·7) in the 6·4 mg/kg group. The confirmed objective response rate by blinded independent central review was 37·8% (31/82 [95% CI 27·3-49·2]) in the 5·4 mg/kg group and 27·5% (11/40 [14·6-43·9]) in the 6·4 mg/kg group. 34 (41%) of 83 patients in the 5·4 mg/kg group and 19 (49%) of 39 in the 6·4 mg/kg group had grade 3 or worse drug-related treatment-emergent adverse events. The most common grade 3 or worse drug-related treatment-emergent adverse events were neutrophil count decreased (13 [16%] of 83 patients), anaemia (six [7%]), nausea (six [7%]), and white blood cell count decreased (five [6%]) in the 5·4 mg/kg group; and were neutrophil count decreased (10 [26%] of 39 patients), anaemia (eight [21%]), platelet count decreased (four [10%]), and white blood cell count decreased (four [10%]) in the 6·4 mg/kg group. Drug-related serious adverse events occurred in 11 (13%) of 83 patients in the 5·4 mg/kg group and six (15%) of 39 patients in the 6·4 mg/kg group; the most common in the 5·4 mg/kg group was nausea (three [4%] patients) and the most common in the 6·4 mg/kg group were fatigue (two [5%] patients), neutropenia (two [5%]), and thrombocytopenia (two [5%]). A drug-related treatment-emergent adverse event related to death occurred in one (1%) patient in the 5·4 mg/kg group (due to hepatic failure). Adjudicated drug-related interstitial lung disease or pneumonitis events were observed in seven (8%) patients in the 5·4 mg/kg group (all grade 1 or 2) and in five (13%) patients in the 6·4 mg/kg group (four grade 1 or 2; one grade 5).\n\nInterpretation: The promising antitumour activity and favourable safety profile support trastuzumab deruxtecan 5·4 mg/kg as the optimal single-agent dose for patients with pretreated HER2-positive metastatic colorectal cancer, including those with RAS mutations, previous anti-HER2 therapy, or both.\n\nFunding: Daiichi Sankyo and AstraZeneca.\n\nIndexed on Europe PMC as PubMed record 39116902 (DOI 10.1016/s1470-2045(24)00380-2). Its abstract cites the registry id NCT04744831, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2024","url":"https://doi.org/10.1016/s1470-2045(24)00380-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39116902/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/39116902"},{"label":"ClinicalTrials.gov NCT04744831","url":"https://clinicaltrials.gov/study/NCT04744831"}],"tags":["europepmc-ingest"],"related":["her2-ish-amplified","her2-ihc-3-plus"],"cancers":[],"sections":[],"technologies":[],"targets":["her2"],"drugs":[],"companies":[],"institutions":[],"pathways":["rtk-activation"],"terms":["gene-amplification"],"trials":["destiny-crc02"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2024,"doi":"10.1016/s1470-2045(24)00380-2","pmid":"39116902","authors":"Raghav K, Siena S, Takashima A, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04744831 with the most citations, so it is the natural first reading for anyone following the DESTINY-CRC02 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-nct04639219-lancet-oncol-2024","kind":"paper","name":"Trastuzumab deruxtecan in patients with solid tumours harbouring specific activating HER2 mutations (DESTINY-PanTumor01): an international, phase 2 study","aka":[],"tldr":"Published report from the trial registered as NCT04639219, in The Lancet Oncology (2024), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Trastuzumab deruxtecan is a HER2-directed antibody-drug conjugate approved by the US Food and Drug Administration and the European Medicines Agency for HER2-mutant non-small-cell lung cancer. Few treatment options exist for patients with HER2-mutant solid tumours beyond lung cancers. We investigated trastuzumab deruxtecan in metastatic solid tumours with specific activating HER2 mutations.\n\nMethods: In this open-label, phase 2, basket study done in 29 centres in Asia, Europe, and North America, we investigated trastuzumab deruxtecan (5·4 mg/kg every 3 weeks by intravenous infusion) in patients aged 18 years or older with unresectable or metastatic solid tumours with specific activating HER2 mutations, an Eastern Cooperative Oncology Group performance status of 0 or 1, and disease progression following previous treatment (previous HER2-targeted therapy was permitted) or with no satisfactory alternative treatment options. The primary endpoint was confirmed objective response rate by independent central review. Anti-tumour activity and safety were analysed in all patients who received at least one dose of trastuzumab deruxtecan. This trial is registered with ClinicalTrials.gov, NCT04639219, and is active but no longer recruiting.\n\nFindings: Between Dec 30, 2020, and Jan 25, 2023, 102 patients (62 [61%] female and 40 [39%] male; median age 66·5 years [IQR 58-72]; 51 [50%] White, two [2%] Black or African American, 38 [37%] Asian, and 11 [11%] did not have race information reported) with solid tumours with activating HER2 mutations received trastuzumab deruxtecan and were included in the anti-tumour activity and safety analyses sets. Patients had a median of three (IQR 2-4) previous treatment regimens. The median duration of follow-up was 8·61 months (IQR 3·71-12·68). The objective response rate by independent central review was 29·4% (95% CI 20·8-39·3; 30 of 102 patients). 52 (51%) patients had a treatment-emergent adverse event of grade 3 or worse; the most common events (in ≥5% of patients) were anaemia (16 [16%]) and neutrophil count decreased (eight [8%]). Drug-related treatment-emergent serious adverse events occurred in ten (10%) patients. Adjudicated drug-related interstitial lung disease or pneumonitis of any grade occurred in 11 patients (11%; three grade 1, five grade 2, one grade 3, and two grade 5); there were two (2%) cases of fatal adjudicated drug-related interstitial lung disease or pneumonitis.\n\nInterpretation: Trastuzumab deruxtecan showed anti-tumour activity and durable responses in heavily pretreated patients across multiple tumour types with activating HER2 mutations, with no new safety signals. Prespecified HER2 mutations might be targeted by HER2-directed antibody-drug conjugates and our findings support further investigation of trastuzumab deruxtecan in the pan-tumour setting.\n\nFunding: AstraZeneca and Daiichi Sankyo.\n\nIndexed on Europe PMC as PubMed record 38710187 (DOI 10.1016/s1470-2045(24)00140-2). Its abstract cites the registry id NCT04639219, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2024","url":"https://doi.org/10.1016/s1470-2045(24)00140-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38710187/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38710187"},{"label":"ClinicalTrials.gov NCT04639219","url":"https://clinicaltrials.gov/study/NCT04639219"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04639219"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2024,"doi":"10.1016/s1470-2045(24)00140-2","pmid":"38710187","authors":"Li BT, Meric-Bernstam F, Bardia A, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04639219 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-trastuzumab-deruxtecan-breast-her2-positive-n-engl-j-med-2020","kind":"paper","name":"Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer","aka":[],"tldr":"Phase 2 or 3 results paper on Trastuzumab deruxtecan in HER2-positive breast cancer, in New England Journal of Medicine (2020), one of the most cited Europe PMC records with Trastuzumab deruxtecan in its title.","summary":"Background: Trastuzumab deruxtecan (DS-8201) is an antibody-drug conjugate composed of an anti-HER2 (human epidermal growth factor receptor 2) antibody, a cleavable tetrapeptide-based linker, and a cytotoxic topoisomerase I inhibitor. In a phase 1 dose-finding study, a majority of the patients with advanced HER2-positive breast cancer had a response to trastuzumab deruxtecan (median response duration, 20.7 months). The efficacy of trastuzumab deruxtecan in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab emtansine requires confirmation.\n\nMethods: In this two-part, open-label, single-group, multicenter, phase 2 study, we evaluated trastuzumab deruxtecan in adults with pathologically documented HER2-positive metastatic breast cancer who had received previous treatment with trastuzumab emtansine. In the first part of the study, we evaluated three different doses of trastuzumab deruxtecan to establish a recommended dose; in the second part, we evaluated the efficacy and safety of the recommended dose. The primary end point was the objective response, according to independent central review. Key secondary end points were the disease-control rate, clinical-benefit rate, duration of response and progression-free survival, and safety.\n\nResults: Overall, 184 patients who had undergone a median of six previous treatments received the recommended dose of trastuzumab deruxtecan (5.4 mg per kilogram of body weight). In the intention-to-treat analysis, a response to therapy was reported in 112 patients (60.9%; 95% confidence interval [CI], 53.4 to 68.0). The median duration of follow-up was 11.1 months (range, 0.7 to 19.9). The median response duration was 14.8 months (95% CI, 13.8 to 16.9), and the median duration of progression-free survival was 16.4 months (95% CI, 12.7 to not reached). During the study, the most common adverse events of grade 3 or higher were a decreased neutrophil count (in 20.7% of the patients), anemia (in 8.7%), and nausea (in 7.6%). On independent adjudication, the trial drug was associated with interstitial lung disease in 13.6% of the patients (grade 1 or 2, 10.9%; grade 3 or 4, 0.5%; and grade 5, 2.2%).\n\nConclusions: Trastuzumab deruxtecan showed durable antitumor activity in a pretreated patient population with HER2-positive metastatic breast cancer. In addition to nausea and myelosuppression, interstitial lung disease was observed in a subgroup of patients and requires attention to pulmonary symptoms and careful monitoring. (Funded by Daiichi Sankyo and AstraZeneca; DESTINY-Breast01 ClinicalTrials.gov number, NCT03248492.).\n\nIndexed on Europe PMC as PubMed record 31825192 (DOI 10.1056/nejmoa1914510). Its title names Trastuzumab deruxtecan and its text names HER2-positive breast cancer; PubMed types it as a clinical trial report (Clinical Trial, Phase II, Research Support, Non-U.S. Gov't, research-article, Multicenter Study, Randomized Controlled Trial). It was matched automatically to the idea \"Systemic-first management of HER2-positive brain metastases\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2020","url":"https://doi.org/10.1056/nejmoa1914510"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31825192/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31825192"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2020,"doi":"10.1056/nejmoa1914510","pmid":"31825192","authors":"Modi S, Saura C, Yamashita T, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Trastuzumab deruxtecan in HER2-positive breast cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Trastuzumab deruxtecan in the title and HER2-positive breast cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-destiny-breast05-n-engl-j-med-2026","kind":"paper","name":"Trastuzumab Deruxtecan in Residual HER2-Positive Early Breast Cancer","aka":[],"tldr":"Published report from the DESTINY-Breast05 trial registered as NCT04622319, in New England Journal of Medicine (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer and residual disease after neoadjuvant therapy are at high risk for recurrence.\n\nMethods: In a phase 3, open-label, international, randomized trial, we investigated postneoadjuvant trastuzumab deruxtecan (T-DXd; 5.4 mg per kilogram of body weight) as compared with trastuzumab emtansine (T-DM1; 3.6 mg per kilogram), the current standard treatment, in patients with HER2-positive breast cancer with residual invasive disease and node-positive disease at surgery or inoperable disease at diagnosis. The primary end point was invasive disease-free survival, and the key secondary end point was disease-free survival (including survival free from noninvasive breast cancers and second primary nonbreast cancers). Other end points included overall survival, distant recurrence-free interval, brain metastasis-free interval, and safety.\n\nResults: A total of 1635 patients were randomly assigned (in a 1:1 ratio) to receive T-DXd (818 patients) or T-DM1 (817 patients). At the data-cutoff date, the median duration of follow-up was approximately 30 months in each group. Invasive-disease events or deaths were reported in 51 patients (6.2%) in the T-DXd group and 102 patients (12.5%) in the T-DM1 group (hazard ratio, 0.47; 95% confidence interval [CI], 0.34 to 0.66; P<0.001); 3-year invasive disease-free survival was 92.4% and 83.7%, respectively. Invasive-disease events, noninvasive-disease events, or deaths were reported in 52 patients (6.4%) in the T-DXd group and 103 patients (12.6%) in the T-DM1 group (hazard ratio, 0.47; 95% CI, 0.34 to 0.66; P<0.001); 3-year disease-free survival was 92.3% and 83.5%, respectively. The most common adverse events were nausea (71.3% of patients), constipation (32.0%), decreased neutrophil count (31.6%), and vomiting (31.0%) with T-DXd and increased liver-enzyme levels (aspartate aminotransferase [50.2%] and alanine aminotransferase [45.3%]) and decreased platelet count (49.8%) with T-DM1. The incidence of adjudicated drug-related interstitial lung disease was higher with T-DXd than with T-DM1 (9.6% vs. 1.6%). Two patients with interstitial lung disease in the T-DXd group died.\n\nConclusions: In patients with high-risk, residual invasive HER2-positive breast cancer, postneoadjuvant T-DXd resulted in a significantly higher likelihood of invasive disease-free survival than T-DM1; toxic effects were mainly gastrointestinal and hematologic. An important identified risk of T-DXd is interstitial lung disease, which requires appropriate monitoring and management. (Funded by Daiichi Sankyo and AstraZeneca; DESTINY-Breast05 ClinicalTrials.gov number, NCT04622319.).\n\nIndexed on Europe PMC as PubMed record 41370739 (DOI 10.1056/nejmoa2514661). Its abstract cites the registry id NCT04622319, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2026","url":"https://doi.org/10.1056/nejmoa2514661"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41370739/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41370739"},{"label":"ClinicalTrials.gov NCT04622319","url":"https://clinicaltrials.gov/study/NCT04622319"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["destiny-breast05"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2026,"doi":"10.1056/nejmoa2514661","pmid":"41370739","authors":"Loibl S, Park YH, Shao Z, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04622319 with the most citations, so it is the natural first reading for anyone following the DESTINY-Breast05 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-destiny-breast09-n-engl-j-med-2026","kind":"paper","name":"Trastuzumab Deruxtecan plus Pertuzumab for HER2-Positive Metastatic Breast Cancer","aka":[],"tldr":"Published report from the DESTINY-Breast09 trial registered as NCT04784715, in New England Journal of Medicine (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Trastuzumab deruxtecan has shown efficacy in patients with previously treated human epidermal growth factor receptor 2 (HER2)-positive advanced or metastatic breast cancer. The efficacy and safety of trastuzumab deruxtecan in patients with no previous therapy for HER2-positive advanced or metastatic breast cancer are unclear.\n\nMethods: We conducted a phase 3 trial involving patients with HER2-positive advanced or metastatic breast cancer and no previous chemotherapy or HER2-directed therapy for metastatic disease. Patients were randomly assigned in a 1:1:1 ratio to receive trastuzumab deruxtecan plus pertuzumab; trastuzumab deruxtecan plus placebo; or a taxane, trastuzumab, and pertuzumab (THP). The primary end point was progression-free survival as assessed by blinded independent central review. Secondary end points included objective response, duration of response, and safety.\n\nResults: For this prespecified interim analysis, data for trastuzumab deruxtecan plus pertuzumab and for THP are reported; data for trastuzumab deruxtecan plus placebo remain blinded until the final analysis of progression-free survival. At the data-cutoff date (February 26, 2025), the median progression-free survival was 40.7 months with trastuzumab deruxtecan plus pertuzumab (383 patients) and 26.9 months with THP (387 patients) (hazard ratio for progression or death, 0.56; 95% confidence interval [CI], 0.44 to 0.71; P<0.00001 [P-value boundary for superiority, 0.00043]). The incidence of a confirmed response was 85.1% with trastuzumab deruxtecan plus pertuzumab and 78.6% with THP (complete responses in 15.1% and 8.5%, respectively), with a median duration of response of 39.2 months and 26.4 months. Safety was consistent with the known profiles of the individual treatments. The incidence of grade 3 or higher adverse events was 63.5% with trastuzumab deruxtecan plus pertuzumab and 62.3% with THP; the most common were neutropenia, hypokalemia, and anemia with trastuzumab deruxtecan plus pertuzumab and neutropenia, leukopenia, and diarrhea with THP. Adjudicated drug-related interstitial lung disease or pneumonitis occurred in 12.1% of patients receiving trastuzumab deruxtecan plus pertuzumab (grade 1 or 2 in 44 patients and grade 5 [death] in 2 patients) and in 1.0% of those receiving THP (all grade 1 or 2).\n\nConclusions: Trastuzumab deruxtecan plus pertuzumab led to a significantly lower risk of progression or death than THP when used as first-line treatment for HER2-positive advanced or metastatic breast cancer, with no new safety signals. (Funded by AstraZeneca and Daiichi Sankyo; DESTINY-Breast09 ClinicalTrials.gov number, NCT04784715.).\n\nIndexed on Europe PMC as PubMed record 41160818 (DOI 10.1056/nejmoa2508668). Its abstract cites the registry id NCT04784715, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2026","url":"https://doi.org/10.1056/nejmoa2508668"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41160818/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41160818"},{"label":"ClinicalTrials.gov NCT04784715","url":"https://clinicaltrials.gov/study/NCT04784715"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["destiny-breast09"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2026,"doi":"10.1056/nejmoa2508668","pmid":"41160818","authors":"Tolaney SM, Jiang Z, Zhang Q, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04784715 with the most citations, so it is the natural first reading for anyone following the DESTINY-Breast09 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-destiny-breast03-lancet-2023-update","kind":"paper","name":"Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial","aka":[],"tldr":"Later report from the DESTINY-Breast03 trial registered as NCT03529110, in The Lancet (2023); its title describes an updated or longer-term analysis.","summary":"Background: An improvement in progression-free survival was shown with trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer in the progression-free survival interim analysis of the DESTINY-Breast03 trial. The aim of DESTINY-Breast03 was to compare the efficacy and safety of trastuzumab deruxtecan versus trastuzumab emtansine.\n\nMethods: This open-label, randomised, multicentre, phase 3 trial was done in 169 study centres in North America, Asia, Europe, Australia, and South America. Eligible patients were aged 18 or older, had HER2-positive unresectable or metastatic breast cancer previously treated with trastuzumab and a taxane, had an Eastern Cooperative Oncology Group performance status 0-1, and at least one measurable lesion per Response Evaluation Criteria in Solid Tumours version 1.1. Patients were randomly assigned (1:1) to receive trastuzumab deruxtecan 5·4 mg/kg or trastuzumab emtansine 3·6 mg/kg, both administered by intravenous infusion every 3 weeks. Randomisation was stratified by hormone receptor status, previous treatment with pertuzumab, and history of visceral disease, and was managed through an interactive web-based system. Within each stratum, balanced block randomisation was used with a block size of four. Patients and investigators were not masked to the treatment received. The primary endpoint was progression-free survival by blinded independent central review. The key secondary endpoint was overall survival and this prespecified second overall survival interim analysis reports updated overall survival, efficacy, and safety results. Efficacy analyses were performed using the full analysis set. Safety analyses included all randomly assigned patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT03529110.\n\nFindings: Between July 20, 2018, and June 23, 2020, 699 patients were screened for eligibility, 524 of whom were enrolled and randomly assigned to receive trastuzumab deruxtecan (n=261) or trastuzumab emtansine (n=263). Median duration of study follow-up was 28·4 months (IQR 22·1-32·9) with trastuzumab deruxtecan and 26·5 months (14·5-31·3) with trastuzumab emtansine. Median progression-free survival by blinded independent central review was 28·8 months (95% CI 22·4-37·9) with trastuzumab deruxtecan and 6·8 months (5·6-8·2) with trastuzumab emtansine (hazard ratio [HR] 0·33 [95% CI 0·26-0·43]; nominal p<0·0001). Median overall survival was not reached (95% CI 40·5 months-not estimable), with 72 (28%) overall survival events, in the trastuzumab deruxtecan group and was not reached (34·0 months-not estimable), with 97 (37%) overall survival events, in the trastuzumab emtansine group (HR 0·64; 95% CI 0·47-0·87]; p=0·0037). The number of grade 3 or worse treatment-emergent adverse events was similar in patients who received trastuzumab deruxtecan versus trastuzumab emtansine (145 [56%] patients versus 135 [52%] patients). Adjudicated drug-related interstitial lung disease or pneumonitis occurred in 39 (15%) patients treated with trastuzumab deruxtecan and eight (3%) patients treated with trastuzumab emtansine, with no grade 4 or 5 events in either group.\n\nInterpretation: Trastuzumab deruxtecan showed a significant improvement in overall survival versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer, as well as the longest reported median progression-free survival, reaffirming trastuzumab deruxtecan as the standard of care in the second-line setting. A manageable safety profile of trastuzumab deruxtecan was confirmed with longer treatment duration.\n\nFunding: Daiichi Sankyo and AstraZeneca.\n\nIndexed on Europe PMC as PubMed record 36495879 (DOI 10.1016/s0140-6736(22)02420-5). Its abstract cites the registry id NCT03529110, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet 2023","url":"https://doi.org/10.1016/s0140-6736(22)02420-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36495879/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36495879"},{"label":"ClinicalTrials.gov NCT03529110","url":"https://clinicaltrials.gov/study/NCT03529110"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["destiny-breast03"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2023,"doi":"10.1016/s0140-6736(22)02420-5","pmid":"36495879","authors":"Hurvitz SA, Hegg R, Chung WP, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the DESTINY-Breast03 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-luca-gianni-j-clin-oncol-2022","kind":"paper","name":"Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study","aka":[],"tldr":"Paper by Luca Gianni indexed on Europe PMC as PubMed record 34890214, in Journal of Clinical Oncology (2022), one of the most cited records naming an author with this name at Fondazione Michelangelo.","summary":"Purpose: We aimed to improve efficacy and reduce toxicity of high-risk human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC) treatment by replacing taxanes and trastuzumab with trastuzumab emtansine (T-DM1).\n\nMethods: The phase III KAITLIN study (NCT01966471) included adults with excised HER2-positive EBC (node-positive or node-negative, hormone receptor-negative, and tumor > 2.0 cm). Postsurgery, patients were randomly assigned 1:1 to anthracycline-based chemotherapy (three-four cycles) and then 18 cycles of T-DM1 plus pertuzumab (AC-KP) or taxane (three-four cycles) plus trastuzumab plus pertuzumab (AC-THP). Adjuvant radiotherapy/endocrine therapy was permitted. Coprimary end points were invasive disease-free survival (IDFS) in the intention-to-treat node-positive and overall populations with hierarchical testing.\n\nResults: The median follow-up was 57.1 months (interquartile range, 52.1-60.1 months) for AC-THP (n = 918) and 57.0 months (interquartile range, 52.1-59.8 months) for AC-KP (n = 928). There was no significant IDFS difference between arms in the node-positive (n = 1,658; stratified hazard ratio [HR], 0.97; 95% CI, 0.71 to 1.32) or overall population (n = 1846; stratified HR, 0.98; 95% CI, 0.72 to 1.32). In the overall population, the three-year IDFS was 94.2% (95% CI, 92.7 to 95.8) for AC-THP and 93.1% (95% CI, 91.4 to 94.7) for AC-KP. Treatment completion rates (ie, 18 cycles) were 88.4% for AC-THP and 65.0% for AC-KP (difference driven by T-DM1 discontinuation because of laboratory abnormalities [12.5%]). Similar rates of grade ≥ 3 (55.4% v 51.8%) and serious adverse events (23.3% v 21.4%) occurred with AC-THP and AC-KP, respectively. KP decreased clinically meaningful deterioration in global health status versus THP (stratified HR, 0.71; 95% CI, 0.62 to 0.80).\n\nConclusion: The primary end point was not met. Both arms achieved favorable IDFS. Trastuzumab plus pertuzumab plus chemotherapy remains the standard of care for high-risk HER2-positive EBC.\n\nIndexed on Europe PMC as PubMed record 34890214 (DOI 10.1200/jco.21.00896). Its author list gives \"Gianni L\" with the affiliation \"Michelangelo Foundation, Milan, Italy\", which names Fondazione Michelangelo; that is how the record was matched to Luca Gianni, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2022","url":"https://doi.org/10.1200/jco.21.00896"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34890214/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34890214"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["luca-gianni"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2022,"doi":"10.1200/jco.21.00896","pmid":"34890214","authors":"Krop IE, Im SA, Barrios C, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Luca Gianni at Fondazione Michelangelo, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-trastuzumab-breast-her2-positive-n-engl-j-med-2005","kind":"paper","name":"Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer","aka":[],"tldr":"Phase 2 or 3 results paper on Trastuzumab in HER2-positive breast cancer, in New England Journal of Medicine (2005), one of the most cited Europe PMC records with Trastuzumab in its title.","summary":"Background: We present the combined results of two trials that compared adjuvant chemotherapy with or without concurrent trastuzumab in women with surgically removed HER2-positive breast cancer.\n\nMethods: The National Surgical Adjuvant Breast and Bowel Project trial B-31 compared doxorubicin and cyclophosphamide followed by paclitaxel every 3 weeks (group 1) with the same regimen plus 52 weeks of trastuzumab beginning with the first dose of paclitaxel (group 2). The North Central Cancer Treatment Group trial N9831 compared three regimens: doxorubicin and cyclophosphamide followed by weekly paclitaxel (group A), the same regimen followed by 52 weeks of trastuzumab after paclitaxel (group B), and the same regimen plus 52 weeks of trastuzumab initiated concomitantly with paclitaxel (group C). The studies were amended to include a joint analysis comparing groups 1 and A (the control group) with groups 2 and C (the trastuzumab group). Group B was excluded because trastuzumab was not given concurrently with paclitaxel.\n\nResults: By March 15, 2005, 394 events (recurrent, second primary cancer, or death before recurrence) had been reported, triggering the first scheduled interim analysis. Of these, 133 were in the trastuzumab group and 261 in the control group (hazard ratio, 0.48; P<0.0001). This result crossed the early stopping boundary. The absolute difference in disease-free survival between the trastuzumab group and the control group was 12 percent at three years. Trastuzumab therapy was associated with a 33 percent reduction in the risk of death (P=0.015). The three-year cumulative incidence of class III or IV congestive heart failure or death from cardiac causes in the trastuzumab group was 4.1 percent in trial B-31 and 2.9 percent in trial N9831.\n\nConclusions: Trastuzumab combined with paclitaxel after doxorubicin and cyclophosphamide improves outcomes among women with surgically removed HER2-positive breast cancer. (ClinicalTrials.gov numbers, NCT00004067 and NCT00005970.)\n\nIndexed on Europe PMC as PubMed record 16236738 (DOI 10.1056/nejmoa052122). Its title names Trastuzumab and its text names HER2-positive breast cancer; PubMed types it as a clinical trial report (Comparative Study, Clinical Trial, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural). It was matched automatically to the idea \"Can T-DXd alone cure early HER2-positive disease?\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2005","url":"https://doi.org/10.1056/nejmoa052122"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/16236738/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/16236738"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2005,"doi":"10.1056/nejmoa052122","pmid":"16236738","authors":"Romond EH, Perez EA, Bryant J, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Trastuzumab in HER2-positive breast cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Trastuzumab in the title and HER2-positive breast cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-horizon-breast01-lancet-oncol-2026","kind":"paper","name":"Trastuzumab rezetecan versus pyrotinib plus capecitabine for patients with HER2-positive metastatic breast cancer (HORIZON-Breast01): interim analysis of a multicentre, open-label, randomised, controlled, phase 3 trial","aka":[],"tldr":"Published report from the HORIZON-Breast01 trial registered as NCT05424835, in The Lancet Oncology (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Trastuzumab rezetecan has shown antitumour activity in a phase 1 trial. Pyrotinib plus capecitabine is the current standard treatment for patients with HER2-positive advanced or metastatic breast cancer after trastuzumab and chemotherapy (taxane or anthracycline). We aimed to evaluate the efficacy and safety of trastuzumab rezetecan versus pyrotinib plus capecitabine in this patient population.\n\nMethods: This interim analysis of a multicentre, open-label, randomised, controlled, phase 3 trial was conducted at 50 hospitals in China. Eligible patients were aged 18-75 years with histologically confirmed HER2-positive unresectable or metastatic breast cancer; previously received a taxane and trastuzumab at the advanced stage or had disease progression within 12 months after (neo)adjuvant treatment with an anti-HER2 monoclonal antibody and taxane-based regimen; had measurable lesions; and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1; stratified by hormone receptor status and previous lines of chemotherapy for metastatic disease), using permuted blocks to intravenous trastuzumab rezetecan (4·8 mg/kg) on day 1 of each 21-day cycle or oral pyrotinib 400 mg once per day continuously plus oral capecitabine 1000 mg/m 2 twice per day on days 1-14 of each 21-day cycle. Protocol amendments led to a temporary modification (between Nov 29, 2022, and July 12, 2023) of trastuzumab rezetecan dose to 6·4 mg/kg; primary evaluation focuses on the 4·8 mg/kg group. The primary endpoint was progression-free survival per blinded independent central review in the modified intention-to-treat population 1 (defined as all patients randomly assigned to the trastuzumab rezetecan 4·8 mg/kg or control groups). Results presented here are from a prespecified interim analysis. This study was registered with ClinicalTrials.gov, NCT05424835 (active, not recruiting).\n\nFindings: From Aug 4, 2022, to Aug 9, 2024, 414 patients with HER2-positive metastatic breast cancer were assessed for eligibility, 127 were ineligible and 287 were randomly assigned to trastuzumab rezetecan (n=142) or pyrotinib plus capecitabine (control group; n=145) in the modified intention-to-treat population 1. All 287 patients were female and the median age was 55·0 years (IQR 49·0-60·0). 268 (93%) patients self-reported as Han Chinese and 19 (7%) as other Chinese ethnicity. At data cutoff of the interim analysis on June 30, 2025, after a median follow-up of 15·0 months (IQR 12·9-18·5) for the trastuzumab rezetecan group versus 13·9 months (11·4-17·8) for the control group, 124 progression-free survival events had occurred (37 [26%] vs 87 [60%]). The median progression-free survival was 30·6 months (95% CI 16·8-not reached [NR]) with trastuzumab rezetecan and 8·3 months (6·9-11·0) with pyrotinib plus capecitabine (HR 0·22 [0·15-0·34]; p<0·0001). The 12-month progression-free survival rate was 84·7% (77·0-90·0) in the trastuzumab rezetecan group versus 35·5% (26·8-44·2) in the control group. The most common (grade ≥3) treatment-related adverse events were decreased neutrophil count (77 [54%] with trastuzumab rezetecan vs 13 [9%] with the control), decreased white blood cell count (29 [20%] vs four [3%]), and decreased platelet count (15 [11%] vs two [1%]); whereas treatment-related serious adverse events occurred in 19 (13%) versus 17 (12%). Two adverse events led to death (one [1%] septic shock unrelated to trastuzumab rezetecan treatment and one [1%] unknown reason related to pyrotinib plus capecitabine treatment). Interstitial lung disease occurred in four (3%) patients in the trastuzumab rezetecan group.\n\nInterpretation: Trastuzumab rezetecan improved progression-free survival versus pyrotinib plus capecitabine and showed a distinct safety profile in patients with HER2-positive breast cancer, presenting as a potential new treatment option.\n\nFunding: Jiangsu Hengrui Pharmaceuticals.\n\nTranslation: For the Chinese translation of the abstract see Supplementary Materials section.\n\nIndexed on Europe PMC as PubMed record 42385760 (DOI 10.1016/s1470-2045(26)00193-2). Its abstract cites the registry id NCT05424835, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2026","url":"https://doi.org/10.1016/s1470-2045(26)00193-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42385760/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/42385760"},{"label":"ClinicalTrials.gov NCT05424835","url":"https://clinicaltrials.gov/study/NCT05424835"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["horizon-breast01"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2026,"doi":"10.1016/s1470-2045(26)00193-2","pmid":"42385760","authors":"Yao H, Zhang Q, Li H, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05424835 with the most citations, so it is the natural first reading for anyone following the HORIZON-Breast01 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-kelley-j-cell-biol","kind":"paper","name":"Traversing the basement membrane in vivo: a diversity of strategies","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 24493586 and published in The Journal of cell biology; the citing page links this DOI, which is how the record was matched.","summary":"The basement membrane is a dense, highly cross-linked, sheet-like extracellular matrix that underlies all epithelia and endothelia in multicellular animals. During development, leukocyte trafficking, and metastatic disease, cells cross the basement membrane to disperse and enter new tissues. Based largely on in vitro studies, cells have been thought to use proteases to dissolve and traverse this formidable obstacle. Surprisingly, recent in vivo studies have uncovered a remarkably diverse range of cellular- and tissue-level strategies beyond proteolysis that cells use to navigate through the basement membrane. These fascinating and unexpected mechanisms have increased our understanding of how cells cross this matrix barrier in physiological and disease settings.\n\nIndexed on Europe PMC as PubMed record 24493586 (DOI 10.1083/jcb.201311112). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Cell Biol 2014","url":"https://doi.org/10.1083/jcb.201311112"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24493586/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/24493586"}],"tags":["europepmc-ingest"],"related":["basement-membrane-tissue-barriers"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Journal of cell biology","year":2014,"doi":"10.1083/jcb.201311112","pmid":"24493586","authors":"Kelley LC, Lohmer LL, Hagedorn EJ, et al.","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-andrew-lassman-j-clin-oncol-2022","kind":"paper","name":"Treatment for Brain Metastases: ASCO-SNO-ASTRO Guideline","aka":[],"tldr":"Paper by Andrew B. Lassman indexed on Europe PMC as PubMed record 34932393, in Journal of Clinical Oncology (2022), one of the most cited records naming an author with this name at Herbert Irving Comprehensive Cancer Center, Columbia University.","summary":"Purpose: To provide guidance to clinicians regarding therapy for patients with brain metastases from solid tumors.\n\nMethods: ASCO convened an Expert Panel and conducted a systematic review of the literature.\n\nResults: Thirty-two randomized trials published in 2008 or later met eligibility criteria and form the primary evidentiary base.\n\nRecommendations: Surgery is a reasonable option for patients with brain metastases. Patients with large tumors with mass effect are more likely to benefit than those with multiple brain metastases and/or uncontrolled systemic disease. Patients with symptomatic brain metastases should receive local therapy regardless of the systemic therapy used. For patients with asymptomatic brain metastases, local therapy should not be deferred unless deferral is specifically recommended in this guideline. The decision to defer local therapy should be based on a multidisciplinary discussion of the potential benefits and harms that the patient may experience. Several regimens were recommended for non-small-cell lung cancer, breast cancer, and melanoma. For patients with asymptomatic brain metastases and no systemic therapy options, stereotactic radiosurgery (SRS) alone should be offered to patients with one to four unresected brain metastases, excluding small-cell lung carcinoma. SRS alone to the surgical cavity should be offered to patients with one to two resected brain metastases. SRS, whole brain radiation therapy, or their combination are reasonable options for other patients. Memantine and hippocampal avoidance should be offered to patients who receive whole brain radiation therapy and have no hippocampal lesions and 4 months or more expected survival. Patients with asymptomatic brain metastases with either Karnofsky Performance Status ≤ 50 or Karnofsky Performance Status < 70 with no systemic therapy options do not derive benefit from radiation therapy.Additional information is available at www.asco.org/neurooncology-guidelines.\n\nIndexed on Europe PMC as PubMed record 34932393 (DOI 10.1200/jco.21.02314). Its author list gives \"Lassman AB\" with the affiliation \"Columbia University Irving Medical Center, New York, NY\", which names Herbert Irving Comprehensive Cancer Center, Columbia University; that is how the record was matched to Andrew B. Lassman, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2022","url":"https://doi.org/10.1200/jco.21.02314"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34932393/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34932393"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["andrew-lassman"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2022,"doi":"10.1200/jco.21.02314","pmid":"34932393","authors":"Vogelbaum MA, Brown PD, Messersmith H, et al.","paperType":"review","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Andrew B. Lassman at Herbert Irving Comprehensive Cancer Center, Columbia University, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-bourhis-radiother-oncol","kind":"paper","name":"Treatment of a first patient with FLASH-radiotherapy","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 31303340 and published in Radiotherapy and Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background: When compared to conventional radiotherapy (RT) in pre-clinical studies, FLASH-RT was shown to reproducibly spare normal tissues, while preserving the anti-tumor activity. This marked increase of the differential effect between normal tissues and tumors prompted its clinical translation. In this context, we present here the treatment of a first patient with FLASH-RT.\n\nMaterial & methods: A 75-year-old patient presented with a multiresistant CD30+ T-cell cutaneous lymphoma disseminated throughout the whole skin surface. Localized skin RT has been previously used over 110 times for various ulcerative and/or painful cutaneous lesions progressing despite systemic treatments. However, the tolerance of these RT was generally poor, and it was hypothesized that FLASH-RT could offer an equivalent tumor control probability, while being less toxic for the skin. This treatment was given to a 3.5-cm diameter skin tumor with a 5.6-MeV linac specifically designed for FLASH-RT. The prescribed dose to the PTV was 15 Gy, in 90 ms. Redundant dosimetric measurements were performed with GafChromic films and alanine, to check the consistency between the prescribed and the delivered doses.\n\nResults: At 3 weeks, i.e. at the peak of the reactions, a grade 1 epithelitis (CTCAE v 5.0) along with a transient grade 1 oedema (CTCAE v5.0) in soft tissues surrounding the tumor were observed. Clinical examination was consistent with the optical coherence tomography showing no decrease of the thickness of the epidermis and no disruption at the basal membrane with limited increase of the vascularization. In parallel, the tumor response was rapid, complete, and durable with a short follow-up of 5 months. These observations, both on normal skin and on the tumor, were promising and prompt to further clinical evaluation of FLASH-RT.\n\nConclusion: This first FLASH-RT treatment was feasible and safe with a favorable outcome both on normal skin and the tumor.\n\nIndexed on Europe PMC as PubMed record 31303340 (DOI 10.1016/j.radonc.2019.06.019). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Radiother Oncol 2019","url":"https://doi.org/10.1016/j.radonc.2019.06.019"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31303340/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31303340"}],"tags":["europepmc-ingest"],"related":["flash-research-accelerators"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["radiotherapy-and-oncology"],"dependsOn":[],"notes":[],"journal":"Radiotherapy and Oncology","year":2019,"doi":"10.1016/j.radonc.2019.06.019","pmid":"31303340","authors":"Bourhis J, Sozzi WJ, Jorge PG, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-whipple-carcinoma-ampulla-of-vater-ann-surg-1935","kind":"paper","name":"Treatment of carcinoma of the ampulla of Vater","aka":[],"tldr":"The 1935 report in which Allen Whipple and two colleagues described removing the head of the pancreas and the duodenum for cancer at the junction of the bile duct and bowel, the operation that still carries his name and remains the only route to cure.","summary":"Whipple, Parsons and Mullins, Annals of Surgery, October 1935, pages 763 to 779. Europe PMC indexes no abstract for this article, so OnCo carries no figures from it; the paper is the origin of the two-stage, then one-stage, pancreaticoduodenectomy. Nine decades later the operation, refined by Traverso and Longmire's pylorus-preserving variant (1978) and by centralisation into high-volume centres, is still the only treatment that cures pancreatic cancer, and about one patient in five presents with disease that can be removed.","asOf":"2026-09-24","links":[{"label":"Ann Surg 1935","url":"https://doi.org/10.1097/00000658-193510000-00023"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/17856666/"},{"label":"Europe PMC full text (PMC1391173)","url":"https://europepmc.org/article/MED/17856666"}],"tags":["pancreatic-evidence"],"related":["surgery-roadmap","paper-traverso-longmire-pylorus-preservation-pancreaticoduodenectomy-sgo-1978"],"cancers":["pancreatic","resectable-pdac"],"sections":["surgery"],"technologies":["robotic-surgery"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["whipple","resectability"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Annals of Surgery","year":1935,"doi":"10.1097/00000658-193510000-00023","pmid":"17856666","authors":"Whipple AO, Parsons WB, Mullins CR.","paperType":"observational","findings":["No abstract is indexed on Europe PMC; the paper describes the operation and the first patients."],"whatItMeans":"Every treatment on this roadmap is either a way to reach this operation, a way to make it work better, or a substitute for patients who cannot have it.","caveats":["A case series from the 1930s, before antibiotics, blood banking and modern anaesthesia; operative mortality was high for decades.","The paper concerns ampullary cancer; the operation was extended to cancers of the pancreatic head."],"changedPractice":true},{"id":"paper-williams-bep-vs-pvb-nejm-1987","kind":"paper","name":"Treatment of disseminated germ cell tumours with cisplatin, bleomycin and either vinblastine or etoposide","aka":[],"tldr":"Replacing vinblastine with etoposide in cisplatin-based chemotherapy for testicular cancer cured as many men with far less nerve and muscle toxicity and improved survival in advanced disease, establishing the BEP regimen used ever since.","summary":"Phase 3 trial of 261 men with disseminated germ cell tumours randomised to cisplatin, bleomycin and vinblastine (PVB) or cisplatin, bleomycin and etoposide (BEP).\n\nComplete response rates were similar (74 versus 83 percent), but BEP caused less neuromuscular toxicity, and in patients with advanced disease it gave higher disease-free and overall survival.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 1987","url":"https://doi.org/10.1056/NEJM198706043162302"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/2437455/"}],"tags":[],"related":[],"cancers":["non-seminoma"],"sections":[],"technologies":[],"targets":[],"drugs":["bleomycin","cisplatin","etoposide","vinblastine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":1987,"doi":"10.1056/NEJM198706043162302","pmid":"2437455","authors":"Williams SD, Birch R, Einhorn LH, et al.","paperType":"rct","findings":["Disease-free status in 61 percent (PVB) vs 60 percent (BEP) overall; superior survival with BEP in advanced disease.","Substantially less neuromuscular toxicity with BEP."],"whatItMeans":"BEP has been the backbone of curative chemotherapy for testicular cancer for nearly forty years.","caveats":["Small trial by modern standards; later trials defined cycle number by risk group."],"changedPractice":true,"participants":261},{"id":"paper-dix-j-clin-oncol-2018","kind":"paper","name":"Treatment of Stage IV Favorable Histology Wilms Tumor With Lung Metastases: A Report From the Children's Oncology Group AREN0533 Study","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 29659330 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose The National Wilms Tumor Study (NWTS) treatment of favorable histology Wilms tumor with lung metastases was vincristine/dactinomycin/doxorubicin (DD4A) and lung radiation therapy (RT). The AREN0533 study applied a new risk stratification and treatment strategy to improve event-free survival (EFS) while reducing exposure to lung RT. Methods Patients with favorable histology Wilms tumor and isolated lung metastases showing complete lung nodule response (CR) after 6 weeks of DD4A continued receiving chemotherapy without lung RT. Patients with incomplete response (IR) or loss of heterozygosity at chromosomes 1p/16q received lung RT and four cycles of cyclophosphamide/etoposide in addition to DD4A drugs (Regimen M). AREN0533 was designed to preserve a 4-year EFS of 85% for lung nodule CR and improve 4-year EFS from 75% to 85% for lung nodule IR. Results Among 292 assessable patients, 133 had CR and 159 had IR. For patients with CR, 4-year EFS and overall survival (OS) estimates were 79.5% (95% CI, 71.2% to 87.8%) and 96.1% (95% CI, 92.1% to 100%), respectively. Expected versus observed event rates were 15% and 20.2% ( P =.052), respectively. For patients with IR, 4-year EFS and OS estimates were 88.5% (95% CI, 81.8% to 95.3%) and 95.4% (95% CI, 90.9% to 99.8%), respectively. Expected versus observed event rates were 25% and 12.2% ( P <.001), respectively. Overall, 4-year EFS and OS were 85.4% (95% CI, 80.5% to 90.2%) and 95.6% (95% CI, 92.8% to 98.4%) compared with 72.5% (95% CI, 66.9% to 78.1%; P <.001) and 84.0% (95% CI, 79.4% to 88.6%; P <.001), respectively, in the predecessor NWTS-5 study. Conclusion Excellent OS was achieved after omission of primary lung RT in patients with lung nodule CR, although there were more events than expected. EFS was significantly improved, with excellent OS, in patients with lung nodule IR using four cycles of cyclophosphamide/etoposide in addition to DD4A drugs. The overall AREN0533 treatment strategy yielded EFS and OS estimates that were superior to previous studies.\n\nIndexed on Europe PMC as PubMed record 29659330 (DOI 10.1200/jco.2017.77.1931). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2018","url":"https://doi.org/10.1200/jco.2017.77.1931"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29659330/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29659330"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["aren0533"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2018,"doi":"10.1200/jco.2017.77.1931","pmid":"29659330","authors":"Dix DB, Seibel NL, Chi YY, et al.","paperType":"observational","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nct02716116-jama-oncol-2021","kind":"paper","name":"Treatment Outcomes and Safety of Mobocertinib in Platinum-Pretreated Patients With EGFR Exon 20 Insertion-Positive Metastatic Non-Small Cell Lung Cancer: A Phase 1/2 Open-label Nonrandomized Clinical Trial","aka":[],"tldr":"Published report from the trial registered as NCT02716116, in JAMA Oncology (2021), chosen as the most cited paper whose own text cites the registry id.","summary":"Importance: Metastatic non-small cell lung cancer (mNSCLC) with EGFR exon 20 insertion (EGFRex20ins) mutations is associated with a poor prognosis. Mobocertinib is an oral tyrosine kinase inhibitor designed to selectively target EGFRex20ins mutations.\n\nObjective: To evaluate treatment outcomes and safety of mobocertinib in patients with previously treated EGFRex20ins-positive mNSCLC.\n\nDesign, setting, and participants: This 3-part, open-label, phase 1/2 nonrandomized clinical trial with dose-escalation/dose-expansion cohorts (28 sites in the US) and a single-arm extension cohort (EXCLAIM; 40 sites in Asia, Europe, and North America) was conducted between June 2016 and November 2020 (data cutoff date). The primary analysis populations were the platinum-pretreated patients (PPP) cohort and the EXCLAIM cohort. The PPP cohort included 114 patients with platinum-pretreated EGFRex20ins-positive mNSCLC who received mobocertinib 160 mg once daily from the dose-escalation (n = 6), dose-expansion (n = 22), and EXCLAIM (n = 86) cohorts. The EXCLAIM cohort included 96 patients with previously treated EGFRex20ins-positive mNSCLC (10 were not platinum pretreated and thus were excluded from the PPP cohort).\n\nInterventions: Mobocertinib 160 mg once daily.\n\nMain outcomes and measures: The primary end point of the PPP and EXCLAIM cohorts was confirmed objective response rate (ORR) assessed by independent review committee (IRC). Secondary end points included confirmed ORR by investigator, duration of response, progression-free survival, overall survival, and safety.\n\nResults: Among the PPP (n = 114) and EXCLAIM (n = 96) cohorts, the median (range) age was 60 (27-84) and 59 (27-80) years, respectively; most patients were women (75 [66%] and 62 [65%], respectively) and of Asian race (68 [60%] and 66 [69%], respectively). At data cutoff, median follow-up was 14.2 months in the PPP cohort (median 2 prior anticancer regimens; 40 [35%] had baseline brain metastases), with confirmed ORR of 28% (95% CI, 20%-37%) by IRC assessment and 35% (95% CI, 26%-45%) by investigator assessment; median duration of response by IRC assessment was 17.5 months (95% CI, 7.4-20.3). Median progression-free survival by IRC assessment was 7.3 months (95% CI, 5.5-9.2). Median overall survival was 24.0 months (95% CI, 14.6-28.8). In the EXCLAIM cohort, median follow-up was 13.0 months, with confirmed ORR by IRC assessment of 25% (95% CI, 17%-35%) and by investigator assessment of 32% (95% CI, 23%-43%). The most common treatment-related adverse events were diarrhea and rash.\n\nConclusions and relevance: In this open-label, phase 1/2 nonrandomized clinical trial, mobocertinib was associated with clinically meaningful benefit in patients with previously treated EGFRex20ins-positive mNSCLC, with a manageable safety profile.\n\nTrial registration: ClinicalTrials.gov Identifier: NCT02716116.\n\nIndexed on Europe PMC as PubMed record 34647988 (DOI 10.1001/jamaoncol.2021.4761). Its abstract cites the registry id NCT02716116, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"JAMA Oncol 2021","url":"https://doi.org/10.1001/jamaoncol.2021.4761"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34647988/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34647988"},{"label":"ClinicalTrials.gov NCT02716116","url":"https://clinicaltrials.gov/study/NCT02716116"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct02716116"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2021,"doi":"10.1001/jamaoncol.2021.4761","pmid":"34647988","authors":"Zhou C, Ramalingam SS, Kim TM, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02716116 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-metter-jama-netw-open","kind":"paper","name":"Trends in the US and Canadian Pathologist Workforces From 2007 to 2017","aka":[],"tldr":"Paper cited by one bottleneck page, indexed on Europe PMC as PubMed record 31150073 and published in JAMA network open; the citing page links this DOI, which is how the record was matched.","summary":"Importance: The current state of the US pathologist workforce is uncertain, with deficits forecast over the next 2 decades.\n\nObjective: To examine the trends in the US pathology workforce from 2007 to 2017.\n\nDesign, setting, and participants: A cross-sectional study was conducted comparing the number of US and Canadian physicians from 2007 to 2017 with a focus on pathologists, radiologists, and anesthesiologists. For the United States, the number of physicians was examined at the state population level with a focus on pathologists. New cancer diagnoses per pathologist were compared between the United States and Canada. These data from the American Association of Medical Colleges Center for Workforce Studies' Physician Specialty Data Books and the Canadian Medical Association Masterfile were analyzed from January 4, 2019, through March 26, 2019.\n\nMain outcomes and measures: Numbers of pathologists were compared with overall physician numbers as well as numbers of radiologists and anesthesiologists in the United States and Canada.\n\nResults: Between 2007 and 2017, the number of active pathologists in the United States decreased from 15 568 to 12 839 (-17.53%). In contrast, Canadian data showed an increase from 1467 to 1767 pathologists during the same period (+20.45%). When adjusted for each country's population, the number of pathologists per 100 000 population showed a decline from 5.16 to 3.94 in the United States and an increase from 4.46 to 4.81 in Canada. As a percentage of total US physicians, pathologists have decreased from 2.03% in 2007 to 1.43% in 2017. The distribution of US pathologists varied widely by state; per 100 000 population, Idaho had the fewest (1.37) and the District of Columbia had the most (15.71). When adjusted by new cancer cases per year, the diagnostic workload per US pathologist has risen by 41.73%; during the same period, the Canadian diagnostic workload increased by 7.06%.\n\nConclusions and relevance: The US pathologist workforce decreased in both absolute and population-adjusted numbers from 2007 to 2017. The current trends suggest a shortage of US pathologists.\n\nIndexed on Europe PMC as PubMed record 31150073 (DOI 10.1001/jamanetworkopen.2019.4337). Matched by DOI alone: one bottleneck page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA Netw Open 2019","url":"https://doi.org/10.1001/jamanetworkopen.2019.4337"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31150073/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31150073"}],"tags":["europepmc-ingest"],"related":["b-workforce"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"JAMA network open","year":2019,"doi":"10.1001/jamanetworkopen.2019.4337","pmid":"31150073","authors":"Metter DM, Colgan TJ, Leung ST, et al.","paperType":"observational","findings":[],"whatItMeans":"One bottleneck page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-scher-j-clin-oncol","kind":"paper","name":"Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 26903579 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: Evolving treatments, disease phenotypes, and biology, together with a changing drug development environment, have created the need to revise castration-resistant prostate cancer (CRPC) clinical trial recommendations to succeed those from prior Prostate Cancer Clinical Trials Working Groups.\n\nMethods: An international expert committee of prostate cancer clinical investigators (the Prostate Cancer Clinical Trials Working Group 3 [PCWG3]) was reconvened and expanded and met in 2012-2015 to formulate updated criteria on the basis of emerging trial data and validation studies of the Prostate Cancer Clinical Trials Working Group 2 recommendations.\n\nResults: PCWG3 recommends that baseline patient assessment include tumor histology, detailed records of prior systemic treatments and responses, and a detailed reporting of disease subtypes based on an anatomic pattern of metastatic spread. New recommendations for trial outcome measures include the time to event end point of symptomatic skeletal events, as well as time to first metastasis and time to progression for trials in the nonmetastatic CRPC state. PCWG3 introduces the concept of no longer clinically benefiting to underscore the distinction between first evidence of progression and the clinical need to terminate or change treatment, and the importance of documenting progression in existing lesions as distinct from the development of new lesions. Serial biologic profiling using tumor samples from biopsies, blood-based diagnostics, and/or imaging is also recommended to gain insight into mechanisms of resistance and to identify predictive biomarkers of sensitivity for use in prospective trials.\n\nConclusion: PCWG3 moves drug development closer to unmet needs in clinical practice by focusing on disease manifestations most likely to affect prognosis adversely for therapeutics tested in both nonmetastatic and metastatic CRPC populations. Consultation with regulatory authorities is recommended if a trial is intended to seek support for drug approval.\n\nIndexed on Europe PMC as PubMed record 26903579 (DOI 10.1200/jco.2015.64.2702). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2016","url":"https://doi.org/10.1200/jco.2015.64.2702"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26903579/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26903579"}],"tags":["europepmc-ingest"],"related":["psa50"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2016,"doi":"10.1200/jco.2015.64.2702","pmid":"26903579","authors":"Scher HI, Morris MJ, Stadler WM, et al.","paperType":"guideline","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-triangle-ibrutinib-mantle-cell-lymphoma-dreyling-lancet-2024","kind":"paper","name":"TRIANGLE: ibrutinib with immunochemotherapy with or without autologous transplant versus immunochemotherapy and transplant in untreated mantle cell lymphoma","aka":[],"tldr":"Adding ibrutinib to first-line treatment for younger people with mantle cell lymphoma kept more of them free of treatment failure at three years, and the stem cell transplant that was standard was not shown to add benefit once ibrutinib was used.","summary":"Three-arm open-label phase 3 trial of the European Mantle Cell Lymphoma Network: 870 patients aged 18 to 65 with untreated mantle cell lymphoma were randomised to R-CHOP/R-DHAP and autologous transplant (arm A, 288), the same with ibrutinib in induction and maintenance (arm A+I, 292), or ibrutinib-containing induction and maintenance without transplant (arm I, 290).\n\nAfter 31 months median follow-up three-year failure-free survival was 88 percent in arm A+I against 72 percent in arm A (hazard ratio 0.52, one-sided p 0.0008); superiority of arm A over arm I (72 against 86 percent) was not shown. Grade 3 to 5 haematological adverse events and infections during maintenance were most frequent after transplant plus ibrutinib.","asOf":"2026-09-22","links":[{"label":"Lancet 2024","url":"https://doi.org/10.1016/S0140-6736(24)00184-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38705160/"}],"tags":[],"related":["lymphoma-roadmap","paper-lyma-rituximab-maintenance-after-transplant-mantle-cell-nejm-2017","paper-enrich-ibrutinib-rituximab-mantle-cell-lancet-2025"],"cancers":["mantle-cell-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["ibrutinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["triangle"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2024,"doi":"10.1016/S0140-6736(24)00184-3","pmid":"38705160","authors":"Dreyling M, Doorduijn J, Giné E, et al.","paperType":"rct","findings":["Three-year failure-free survival 88 percent (95% CI 84 to 92) in arm A+I versus 72 percent (67 to 79) in arm A; hazard ratio 0.52, one-sided p 0.0008.","Arm A versus arm I: 72 versus 86 percent (82 to 91); hazard ratio 1.77, superiority of transplant not shown.","Grade 3 to 5 haematological events during maintenance or follow-up in 50 percent (A+I), 28 percent (I) and 21 percent (A)."],"whatItMeans":"Ibrutinib during induction and as maintenance should be part of first-line treatment for younger patients with mantle cell lymphoma; whether transplant adds anything to an ibrutinib-containing regimen is still being followed.","caveats":["The A+I against I comparison was not mature at publication.","Open-label; failure-free survival rather than overall survival was the primary endpoint."],"changedPractice":true,"participants":870},{"id":"paper-trident-1-repotrectinib-nejm-2024","kind":"paper","name":"TRIDENT-1: repotrectinib in ROS1 fusion-positive non-small-cell lung cancer","aka":[],"tldr":"The next-generation ROS1 and TRK inhibitor repotrectinib shrank tumours in almost four in five untreated patients with ROS1-positive lung cancer, kept the disease under control for nearly three years, and worked in about four in ten patients after crizotinib including those with the resistant G2032R mutation.","summary":"Phase 1/2 study of 171 patients with ROS1 fusion-positive non-small-cell lung cancer treated with repotrectinib, including 71 who had not received a ROS1 inhibitor and 56 previously treated with one.\n\nIn ROS1 inhibitor-naive patients, objective response was 79 percent with median progression-free survival 35.7 months; in patients after one prior ROS1 inhibitor without chemotherapy, response was 38 percent with median progression-free survival 9.0 months, and 59 percent of G2032R-mutant tumours responded. Dizziness was the most frequent side effect.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2024","url":"https://doi.org/10.1056/NEJMoa2302299"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38197815/"}],"tags":[],"related":[],"cancers":["ntrk-fusion-nsclc","ros1-positive-nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":["repotrectinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2024,"doi":"10.1056/NEJMoa2302299","pmid":"38197815","authors":"Drilon A, Camidge DR, Lin JJ, et al.","paperType":"observational","findings":["ROS1 inhibitor-naive: objective response 79 percent; median progression-free survival 35.7 months.","After one prior ROS1 inhibitor: objective response 38 percent; 59 percent in G2032R-mutant tumours."],"whatItMeans":"Repotrectinib is a preferred first-line ROS1 inhibitor because of its durability and coverage of resistance mutations, and it is also approved for NTRK fusion-positive tumours after prior TRK inhibitors.","caveats":["Single-arm; dizziness in about 60 percent and dysgeusia in half.","No randomised comparison with crizotinib or entrectinib."],"changedPractice":true,"participants":171},{"id":"paper-prager-sunlight-trifluridine-tipiracil-bevacizumab-nejm-2023","kind":"paper","name":"Trifluridine-tipiracil and bevacizumab in refractory metastatic colorectal cancer (SUNLIGHT)","aka":[],"tldr":"Adding a cheap old antibody to the refractory-line tablet took median survival from 7.5 to 10.8 months, the largest gain in this setting since the setting existed.","summary":"Prager, Taieb, Fakih and colleagues randomly assigned, 1:1, adult patients who had received no more than two previous chemotherapy regimens for advanced colorectal cancer to trifluridine-tipiracil plus bevacizumab or trifluridine-tipiracil alone, with overall survival as the primary end point and progression-free survival and safety, including time to worsening of ECOG performance status from 0 or 1 to 2 or more, as secondary end points. A total of 246 patients were assigned to each group.\n\nThe commonest adverse events in both groups were neutropenia, nausea and anaemia; no treatment-related deaths were reported.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2023","url":"https://doi.org/10.1056/NEJMoa2214963"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37133585/"}],"tags":["colorectal-evidence"],"related":["paper-mayer-recourse-tas-102-nejm-2015","paper-dasari-fresco-2-fruquintinib-lancet-2023"],"cancers":["colorectal","kras-g12c-colorectal"],"sections":["chemotherapy"],"technologies":["antiangiogenic","cytotoxic-chemotherapy"],"targets":["vegf"],"drugs":["trifluridine-tipiracil","bevacizumab"],"companies":["servier","taiho"],"institutions":[],"pathways":[],"terms":["performance-status"],"trials":["sunlight"],"people":["gerald-prager","eric-van-cutsem","josep-tabernero"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/NEJMoa2214963","pmid":"37133585","authors":"Prager GW, Taieb J, Fakih M, et al.","paperType":"rct","findings":["Median overall survival 10.8 months with the combination against 7.5 months with trifluridine-tipiracil alone: hazard ratio 0.61 (95 percent CI 0.49 to 0.77, p<0.001).","Median progression-free survival 5.6 against 2.4 months: hazard ratio 0.44 (0.36 to 0.54, p<0.001).","Median time to worsening performance status 9.3 against 6.3 months (hazard ratio 0.54, 0.43 to 0.67).","No treatment-related deaths."],"whatItMeans":"Trifluridine-tipiracil with bevacizumab is the refractory-line standard, and a reminder that combining two drugs already on the shelf can beat anything new in the same line.","caveats":["The comparator is trifluridine-tipiracil alone rather than the physician's best choice, which in many countries would have included regorafenib.","Patients had received no more than two previous regimens, so this is an earlier population than RECOURSE or CORRECT.","Funded by the two manufacturers."],"changedPractice":true,"participants":492},{"id":"paper-shimelis-tnbc-risk-genes-jnci-2018","kind":"paper","name":"Triple-negative breast cancer risk genes identified by multigene hereditary cancer panel testing","aka":[],"tldr":"Panel testing of 10,901 women with triple-negative breast cancer pinned down which inherited genes raise the risk of this particular subtype: BARD1, BRCA1, BRCA2, PALB2 and RAD51D carry high risk, and BRIP1, RAD51C and TP53 moderate risk.","summary":"Multigene panel testing for 21 genes in 8,753 TNBC patients by a clinical laboratory and 17 genes in 2,148 patients from the Triple Negative Breast Cancer Consortium was compared with reference controls. Germline pathogenic variants in BARD1, BRCA1, BRCA2, PALB2 and RAD51D were associated with high risk of TNBC (odds ratio above 5.0) and more than 20% lifetime breast cancer risk among Caucasians; BRIP1, RAD51C and TP53 with moderate risk (odds ratio above 2). Similar trends were observed in the African American population. Pathogenic variants in these genes were detected in 12.0% of participants (3.7% outside BRCA1/2).","asOf":"2026-09-24","links":[{"label":"Shimelis et al., JNCI 2018: TNBC risk genes from panel testing of 10,901 patients","url":"https://doi.org/10.1093/jnci/djy106"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30099541/"}],"tags":[],"related":[],"cancers":["tnbc"],"sections":[],"technologies":["germline-testing"],"targets":["brca","palb2","bard1","rad51c","rad51d","tp53"],"drugs":[],"companies":[],"institutions":["mayo-clinic"],"pathways":[],"terms":["gbrca-mutation","vus"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jnci"],"dependsOn":[],"notes":[],"journal":"JNCI: Journal of the National Cancer Institute","year":2018,"doi":"10.1093/jnci/djy106","pmid":"30099541","authors":"Shimelis H, LaDuca H, Hu C, et al.","paperType":"observational","findings":["High-risk TNBC genes: BARD1, BRCA1, BRCA2, PALB2, RAD51D (OR above 5).","Moderate-risk: BRIP1, RAD51C, TP53 (OR above 2).","12.0% of TNBC patients carried a pathogenic variant in these genes, 3.7% outside BRCA1/2."],"whatItMeans":"It defines the gene list a TNBC germline panel should report on and shows the same genes apply in African American women, the population with the highest TNBC incidence.","caveats":["Clinical laboratory referrals are enriched for family history.","Risk estimates outside BRCA1/2 rest on small carrier counts."],"changedPractice":false,"participants":10901},{"id":"paper-dent-tnbc-clinical-features-recurrence-ccr-2007","kind":"paper","name":"Triple-negative breast cancer: clinical features and patterns of recurrence","aka":[],"tldr":"The 2007 Toronto study that gave triple-negative breast cancer its clinical portrait: 11 percent of cases, a risk of distant relapse 2.6 times higher than other breast cancers, a peak at three years and then a fall, so that women who reach five years without relapse are largely safe.","summary":"Dent, Trudeau, Pritchard, Hanna and colleagues studied 1,601 women diagnosed with breast cancer at Women's College Hospital, Toronto, between 1987 and 1997, with median follow-up of 8.1 years; 180 (11.2 percent) had triple-negative tumours (oestrogen receptor-, progesterone receptor- and HER2-negative). Compared with other breast cancers, triple-negative disease carried an increased likelihood of distant recurrence (hazard ratio 2.6, 95 percent confidence interval 2.0 to 3.5) and death (hazard ratio 3.2, 2.3 to 4.5) within five years of diagnosis but not thereafter; the risk of distant recurrence peaked at about three years and declined rapidly, whereas in other cancers it was constant over follow-up.","asOf":"2026-09-24","links":[{"label":"Clin Cancer Res 2007","url":"https://doi.org/10.1158/1078-0432.CCR-06-3045"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/17671126/"}],"tags":["tnbc-evidence"],"related":["paper-bauer-triple-negative-california-registry-cancer-2007"],"cancers":["tnbc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["hazard-ratio"],"trials":[],"people":["rebecca-dent"],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2007,"doi":"10.1158/1078-0432.CCR-06-3045","pmid":"17671126","authors":"Dent R, Trudeau M, Pritchard KI, et al.","paperType":"observational","findings":["180 of 1,601 patients (11.2 percent) were triple-negative.","Distant recurrence hazard ratio 2.6 (95 percent CI 2.0 to 3.5) and death hazard ratio 3.2 (2.3 to 4.5) within five years, not thereafter.","Recurrence risk peaked at about three years and then declined rapidly."],"whatItMeans":"Explains why triple-negative trials can use three-year event-free survival, why follow-up is front-loaded, and why survivors past five years are told their risk has largely passed.","caveats":["Single-institution cohort from the pre-taxane era.","HER2 testing methods of 1987 to 1997 differ from current standards."],"changedPractice":true,"participants":1601},{"id":"paper-abida-triton2-rucaparib-brca-jco-2020","kind":"paper","name":"TRITON2: rucaparib in men with metastatic castration-resistant prostate cancer harbouring a BRCA1 or BRCA2 alteration","aka":["TRITON2","Abida 2020 rucaparib"],"tldr":"The trial that got rucaparib approved for prostate cancer. In 115 men with a BRCA fault whose cancer had already been through hormone drugs and chemotherapy, around half had their tumours shrink or their PSA halve.","summary":"Wassim Abida and the TRITON2 investigators treated men with metastatic castration-resistant prostate cancer and a deleterious BRCA1 or BRCA2 alteration with rucaparib 600 mg twice daily, after progression on one or two androgen receptor-directed therapies and one taxane. The efficacy and safety populations comprised 115 men.\n\nThe result supported accelerated approval in the United States in May 2020, on a single-arm response rate, three years before TRITON3 provided the randomised confirmation. Response rates were similar whether the BRCA alteration was germline or somatic and whether it was BRCA1 or BRCA2, although prostate-specific antigen responses were higher with BRCA2. That germline and somatic alterations behave the same is the practical reason tumour sequencing, not just a blood test for inherited faults, belongs in this disease.","asOf":"2026-09-25","links":[{"label":"J Clin Oncol 2020","url":"https://doi.org/10.1200/jco.20.01035"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32795228/"},{"label":"ClinicalTrials.gov NCT02952534","url":"https://clinicaltrials.gov/study/NCT02952534"},{"label":"Abida et al., J Clin Oncol 2020: TRITON2, rucaparib in 115 men with BRCA-altered metastatic castration-resistant prostate cancer","url":"https://doi.org/10.1200/JCO.20.01035"},{"label":"RUBRACA prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0295d202-1cfe-7659-e063-6294a90a476e"}],"tags":["prostate-evidence"],"related":["paper-fizazi-triton3-rucaparib-nejm-2023","paper-mateo-toparp-a-olaparib-dna-repair-nejm-2015","paper-profound-nejm-2020","prostate-roadmap"],"cancers":["prostate","prostate-mcrpc"],"sections":["targeted-therapy"],"technologies":["parp-inhibitor","cgp"],"targets":["brca","parp"],"drugs":["rucaparib"],"companies":["clovis-oncology"],"institutions":[],"pathways":["homologous-recombination-repair","base-excision-repair-parp","synthetic-lethality-map"],"terms":["hrd","synthetic-lethality","psa","genome-wide-loss-of-heterozygosity","germline-vs-somatic","gbrca-mutation","psa50"],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation","b-regulatory-fragmentation"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/jco.20.01035","pmid":"32795228","authors":"Abida W, Patnaik A, Campbell D, et al.","paperType":"rct","findings":["Confirmed objective response rate by independent radiology review 43.5 percent (95 percent confidence interval 31.0 to 56.7; 27 of 62 patients with measurable disease) and by investigator assessment 50.8 percent (38.1 to 63.4; 33 of 65).","Confirmed prostate-specific antigen response rate, a decrease of 50 percent or more, 54.8 percent (45.2 to 64.1; 63 of 115 patients).","Objective response rates were similar for germline and somatic BRCA alterations and for BRCA1 and BRCA2 alterations; a higher prostate-specific antigen response rate was observed with BRCA2.","The most frequent grade 3 or higher treatment-emergent adverse event was anaemia, in 29 of 115 patients (25.2 percent).","Patients had progressed after one to two lines of next-generation androgen receptor-directed therapy and one taxane-based chemotherapy."],"whatItMeans":"The trial behind the second PARP inhibitor licensed in prostate cancer, and the evidence that a somatic BRCA alteration predicts response as well as an inherited one. Together with TOPARP-A it is why tumour as well as germline sequencing is recommended in metastatic disease.","caveats":["Single-arm with a response endpoint, which supported accelerated rather than full approval; the randomised confirmation came from TRITON3 in 2023.","Restricted to BRCA1 and BRCA2; the wider homologous recombination repair gene set behaves differently and mostly worse.","Anaemia of grade 3 or higher in a quarter of patients is a meaningful burden in a population that is often already anaemic from bone disease and androgen deprivation."],"changedPractice":true,"participants":115},{"id":"paper-fizazi-triton3-rucaparib-nejm-2023","kind":"paper","name":"TRITON3: rucaparib or physician's choice in metastatic castration-resistant prostate cancer","aka":["TRITON3","Fizazi 2023 rucaparib randomised"],"tldr":"The randomised confirmation that a PARP inhibitor beats the alternatives in men with a BRCA fault, nearly doubling the time before the cancer grew on scans. In men with an ATM fault instead, it did nothing.","summary":"Karim Fizazi and the TRITON3 investigators randomised 405 men with metastatic castration-resistant prostate cancer and a BRCA1, BRCA2 or ATM alteration, after progression on a second-generation androgen receptor pathway inhibitor, in a 2 to 1 ratio to rucaparib or a physician's choice control of docetaxel, abiraterone or enzalutamide.\n\nThe trial answers two questions. In the BRCA subgroup, imaging-based progression-free survival was 11.2 against 6.4 months, hazard ratio 0.50. In the exploratory ATM subgroup it was 8.1 against 6.8 months with a hazard ratio of 0.95, which is to say no effect. The lesson is that homologous recombination repair is not one biomarker: grouping ATM with BRCA in a single test result and treating on it will produce treatment that does not work. The screening figure is also worth noting: 4,855 men were prescreened or screened to randomise 405.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2023","url":"https://doi.org/10.1056/nejmoa2214676"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36795891/"},{"label":"ClinicalTrials.gov NCT02975934","url":"https://clinicaltrials.gov/study/NCT02975934"}],"tags":["prostate-evidence"],"related":["paper-abida-triton2-rucaparib-brca-jco-2020","paper-profound-nejm-2020","paper-pritchard-inherited-dna-repair-metastatic-prostate-nejm-2016","prostate-roadmap"],"cancers":["prostate","prostate-mcrpc"],"sections":["targeted-therapy"],"technologies":[],"targets":["brca","atm"],"drugs":["rucaparib","docetaxel","abiraterone","enzalutamide"],"companies":["clovis-oncology"],"institutions":[],"pathways":[],"terms":["hrd","synthetic-lethality","genome-wide-loss-of-heterozygosity","radiographic-progression-free-survival"],"trials":[],"people":["karim-fizazi"],"bottlenecks":["b-biomarker-validation","b-trial-enrolment","b-resistance"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/nejmoa2214676","pmid":"36795891","authors":"Fizazi K, Piulats JM, Reaume MN, et al.","paperType":"rct","findings":["Of 4,855 men who underwent prescreening or screening, 270 were assigned to rucaparib and 135 to a control medication; 201 and 101 respectively had a BRCA alteration.","At 62 months, imaging-based progression-free survival in the BRCA subgroup was 11.2 months with rucaparib against 6.4 months with control (hazard ratio 0.50; 95 percent confidence interval 0.36 to 0.69).","In the intention-to-treat population it was 10.2 against 6.4 months (hazard ratio 0.61; 0.47 to 0.80; P less than 0.001 for both comparisons).","In the exploratory ATM subgroup, imaging-based progression-free survival was 8.1 months with rucaparib against 6.8 months with control (hazard ratio 0.95; 0.59 to 1.52).","The most frequent adverse events with rucaparib were fatigue and nausea."],"whatItMeans":"The randomised proof for PARP inhibition in BRCA-altered prostate cancer, and the clearest evidence that the homologous recombination repair gene list should not be used as a single yes-or-no test. ATM-altered disease needs a different answer, and does not yet have one.","caveats":["The primary endpoint is imaging-based progression-free survival, not overall survival; the control arm allowed another androgen receptor pathway inhibitor, which is a weak comparator after progression on one.","4,855 men screened for 405 randomised shows how much testing capacity a biomarker-selected trial in this disease consumes.","The ATM result is exploratory and the subgroup is small, but it points the same way as every other dataset in the field."],"changedPractice":true,"participants":405},{"id":"paper-trophimmun-avelumab-chemoresistant-gtn-you-jco-2020","kind":"paper","name":"TROPHIMMUN cohort A: avelumab in gestational trophoblastic tumours resistant to single-agent chemotherapy","aka":[],"tldr":"The PD-L1 antibody avelumab cured about half of women whose gestational trophoblastic tumour had stopped responding to single-drug chemotherapy, with mild side effects.","summary":"Single-arm phase 2 trial at the Hospices Civils de Lyon: 15 women with gestational trophoblastic tumours resistant to methotrexate (all) or actinomycin D received avelumab 10 mg/kg every two weeks until hCG normalised and for three further cycles.\n\nEight women (53.3 percent) reached normal hCG after a median of nine cycles and none relapsed at a median follow-up of 25 months; one later had a healthy pregnancy. Grade 1 to 2 treatment-related adverse events occurred in 93 percent (fatigue, nausea or vomiting, infusion reactions); the seven non-responders were cured with actinomycin D or combination chemotherapy and surgery.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2020","url":"https://doi.org/10.1200/JCO.20.00803"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32716740/"}],"tags":[],"related":[],"cancers":["low-risk-gtn","gestational-trophoblastic"],"sections":[],"technologies":[],"targets":[],"drugs":["avelumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["trophimmun"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/JCO.20.00803","pmid":"32716740","authors":"You B, Bolze PA, Lotz JP, et al.","paperType":"observational","findings":["hCG normalisation in 8 of 15 women (53.3 percent) after a median of 9 cycles; no subsequent relapse.","Grade 1 to 2 treatment-related adverse events in 93 percent; one unrelated grade 3 uterine bleed."],"whatItMeans":"Avelumab is a chemotherapy-sparing option for single-agent-resistant gestational trophoblastic neoplasia, particularly where the alternative is combination chemotherapy.","caveats":["Fifteen patients; cohort B later showed little activity after combination chemotherapy failure."],"changedPractice":true,"participants":15},{"id":"paper-de-bono-tropic-cabazitaxel-lancet-2010","kind":"paper","name":"TROPIC: prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel","aka":["TROPIC","de Bono 2010 cabazitaxel"],"tldr":"The first drug shown to extend life after docetaxel has stopped working. Cabazitaxel, a taxane designed to get past the pumps that expel docetaxel from resistant cells, added about two and a half months, at the cost of a high rate of low white cell counts.","summary":"Johann de Bono and the TROPIC investigators randomised 755 men whose metastatic castration-resistant prostate cancer had progressed during or after docetaxel to cabazitaxel or mitoxantrone, each with 10 mg of oral prednisone daily. It was an open-label phase 3 trial with overall survival as the primary endpoint.\n\nBefore TROPIC there was nothing after docetaxel. The trial opened the second line and, in the same period as abiraterone and enzalutamide, turned castration-resistant prostate cancer from a single-treatment disease into a sequencing problem. The toxicity is the reason cabazitaxel is used carefully: 82 percent of patients had grade 3 or higher neutropenia and 8 percent had febrile neutropenia, which is why growth factor support became routine.","asOf":"2026-09-25","links":[{"label":"Lancet 2010","url":"https://doi.org/10.1016/s0140-6736(10)61389-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20888992/"},{"label":"ClinicalTrials.gov NCT00417079","url":"https://clinicaltrials.gov/study/NCT00417079"}],"tags":["prostate-evidence"],"related":["paper-tannock-tax-327-docetaxel-prednisone-nejm-2004","paper-scher-affirm-enzalutamide-nejm-2012","chemotherapy-roadmap","prostate-roadmap"],"cancers":["prostate","prostate-mcrpc"],"sections":["chemotherapy"],"technologies":[],"targets":[],"drugs":["cabazitaxel","docetaxel","mitoxantrone","prednisone"],"companies":["sanofi"],"institutions":[],"pathways":[],"terms":["castration-resistance","hazard-ratio"],"trials":[],"people":["johann-de-bono"],"bottlenecks":["b-resistance","b-toxicity-qol"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2010,"doi":"10.1016/s0140-6736(10)61389-x","pmid":"20888992","authors":"de Bono JS, Oudard S, Ozguroglu M, et al.","paperType":"rct","findings":["Median survival 15.1 months (95 percent confidence interval 14.1 to 16.3) with cabazitaxel against 12.7 months (11.6 to 13.7) with mitoxantrone.","Hazard ratio for death 0.70 (95 percent confidence interval 0.59 to 0.83; p less than 0.0001).","Median progression-free survival 2.8 months against 1.4 months (hazard ratio 0.74, 0.64 to 0.86; p less than 0.0001).","Grade 3 or higher neutropenia in 303 of 377 cabazitaxel patients (82 percent) against 215 (58 percent) on mitoxantrone; febrile neutropenia in 28 (8 percent) against 5 (1 percent).","Grade 3 or higher diarrhoea in 23 patients (6 percent) against 1 (less than 1 percent)."],"whatItMeans":"Proof that a cancer resistant to one taxane is not resistant to all of them, and the beginning of treatment sequencing in castration-resistant disease. The CARD trial later showed that after an androgen receptor drug has failed, cabazitaxel beats switching to the other androgen receptor drug.","caveats":["Open-label, so the quality-of-life and adverse event reporting are not blinded.","The comparator, mitoxantrone, had never been shown to extend survival, so the control arm represents palliation rather than an active alternative.","Haematological toxicity is substantial and the trial predates routine primary granulocyte colony-stimulating factor prophylaxis; the 25 mg per square metre dose was later shown to be reducible to 20 mg with similar efficacy."],"changedPractice":true,"participants":755},{"id":"paper-tropion-breast01-china-cohort-esmo-open-2026","kind":"paper","name":"TROPION-Breast01 China cohort: datopotamab deruxtecan versus chemotherapy in previously treated HR-positive, HER2-negative breast cancer","aka":[],"tldr":"Among the 83 patients enrolled in mainland China, datopotamab deruxtecan roughly doubled the time before the cancer grew compared with chemotherapy, with fewer severe side effects, in line with the global trial.","summary":"Prespecified analysis of the 83 patients enrolled in mainland China in TROPION-Breast01, the global phase 3 trial of datopotamab deruxtecan (6 mg/kg every three weeks) against investigator's choice of chemotherapy (eribulin, capecitabine, vinorelbine or gemcitabine) in inoperable or metastatic hormone receptor-positive, HER2-negative breast cancer after progression on endocrine therapy and one or two lines of chemotherapy. Dual primary endpoints were progression-free survival by blinded independent central review and overall survival.\n\nIn the China cohort (44 on datopotamab deruxtecan, 39 on chemotherapy) median progression-free survival was 8.1 against 4.2 months (hazard ratio 0.54, 95 percent CI 0.30 to 0.96, nominal p 0.0329). Overall survival numerically favoured datopotamab deruxtecan (hazard ratio 0.83, 95 percent CI 0.49 to 1.43, nominal p 0.5028). Grade 3 or worse treatment-related adverse events occurred in 29.5 percent against 58.3 percent; nausea (47.7 percent) and raised aspartate aminotransferase (40.9 percent) were the commonest with datopotamab deruxtecan, and oral mucositis or stomatitis and ocular surface events affected 43.2 and 47.7 percent.","asOf":"2026-09-21","links":[{"label":"ESMO Open 2026","url":"https://doi.org/10.1016/j.esmoop.2026.108538"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/42727418/"},{"label":"ClinicalTrials.gov NCT05104866","url":"https://clinicaltrials.gov/study/NCT05104866"}],"tags":[],"related":[],"cancers":["breast-hr-positive"],"sections":[],"technologies":[],"targets":[],"drugs":["datopotamab-deruxtecan"],"companies":["astrazeneca","daiichi-sankyo"],"institutions":[],"pathways":[],"terms":["pfs","os"],"trials":["tropion-breast01"],"people":["xu-binghe","aditya-bardia"],"bottlenecks":[],"keyPapers":[],"journals":["esmo-open"],"dependsOn":[],"notes":[],"journal":"ESMO Open","year":2026,"doi":"10.1016/j.esmoop.2026.108538","pmid":"42727418","authors":"Wang S, Zhang Q, Jiang Z, et al.","paperType":"rct","findings":["Median progression-free survival by blinded review 8.1 vs 4.2 months; hazard ratio 0.54 (95 percent CI 0.30 to 0.96, nominal p 0.0329).","Overall survival hazard ratio 0.83 (95 percent CI 0.49 to 1.43, nominal p 0.5028), not significant.","Grade 3 or worse treatment-related adverse events 29.5 percent vs 58.3 percent; oral mucositis or stomatitis in 43.2 percent and ocular surface events in 47.7 percent with datopotamab deruxtecan."],"whatItMeans":"Chinese patients in the trial saw the same pattern as the global population: a clear progression-free survival gain, no proven survival gain, and a different rather than heavier side-effect burden, with mouth and eye toxicity in nearly half. It supports use of datopotamab deruxtecan in this setting in China but does not resolve the global trial's missing survival benefit.","caveats":["Small cohort of 83 patients; p-values are nominal and the trial was not powered for this subgroup.","Overall survival was not significantly different, as in the global analysis."],"changedPractice":false,"participants":83},{"id":"paper-tropion-breast01-jco-2024","kind":"paper","name":"TROPION-Breast01: datopotamab deruxtecan versus chemotherapy in pretreated hormone-receptor-positive breast cancer, and why a PFS win did not translate to survival","aka":[],"tldr":"The TROP2-directed antibody-drug conjugate Dato-DXd delayed progression by about two months compared with chemotherapy, but patients did not live longer, which stalled its approval in breast cancer.","summary":"Open-label phase 3 trial of 732 patients with hormone-receptor-positive, HER2-negative metastatic breast cancer after one or two lines of chemotherapy, randomised to datopotamab deruxtecan (Dato-DXd, 6 mg/kg) or investigator's choice chemotherapy (eribulin, vinorelbine, capecitabine or gemcitabine). Dual primary endpoints were PFS by blinded review and overall survival.\n\nPFS was improved (6.9 vs 4.9 months, HR 0.63) with fewer high-grade adverse events, but the final overall survival analysis showed no difference. The trial is a cautionary example that a TROP2 ADC can beat chemotherapy on PFS in an unselected population without changing survival.","asOf":"2026-09-08","links":[{"label":"PubMed search: TROPION-Breast01","url":"https://pubmed.ncbi.nlm.nih.gov/?term=TROPION-Breast01+datopotamab+deruxtecan+Bardia"},{"label":"ClinicalTrials.gov NCT05104866","url":"https://clinicaltrials.gov/study/NCT05104866"}],"tags":[],"related":["idea-trop2-pet-selection","idea-payload-switching"],"cancers":["breast-hr-positive"],"sections":[],"technologies":["adc","topoisomerase-inhibitors"],"targets":["trop2"],"drugs":["datopotamab-deruxtecan"],"companies":["daiichi-sankyo","astrazeneca"],"institutions":[],"pathways":[],"terms":["pfs","os","adc-sequencing","ihc"],"trials":["tropion-breast01","tropion-breast02"],"people":["im-seock-ah","xu-binghe","barrios-carlos"],"bottlenecks":["b-biomarker-validation","b-trial-design","b-negative-results"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2024,"doi":"10.1200/JCO.24.00920","pmid":"39265124","authors":"Bardia A, Jhaveri K, Im SA, et al.","paperType":"rct","findings":["Median PFS by blinded central review 6.9 vs 4.9 months; HR 0.63 (95% CI 0.52-0.76).","Objective response rate 36.4% vs 22.9%.","Grade 3 or higher treatment-related adverse events about 21% vs 45%; stomatitis and ocular surface events were the characteristic Dato-DXd toxicities.","Final overall survival analysis (2024): no significant difference (HR close to 1.0).","TROP2 expression by immunohistochemistry did not select responders."],"whatItMeans":"For hormone-receptor-positive metastatic breast cancer that has already had chemotherapy, Dato-DXd controls the disease for longer with fewer severe side effects than chemotherapy, but does not help patients live longer, so it is not a standard option here. The result is a reminder that progression-free survival is a surrogate; regulators and clinicians should wait for survival data before adopting an ADC in a setting where later therapies are effective.","caveats":["Open-label; PFS assessed by blinded review but subsequent therapy was at physician discretion.","Post-progression therapy, including other ADCs, likely diluted any survival effect.","The population was chemotherapy-pretreated and heterogeneous; a first-line or biomarker-selected trial might behave differently.","Immunohistochemistry for TROP2 was not predictive, leaving no validated way to choose patients."],"changedPractice":false,"participants":732},{"id":"paper-hammel-j-clin-oncol","kind":"paper","name":"TRYBECA-1: A Randomized Phase III Study of Eryaspase Combined With Chemotherapy Versus Chemotherapy as Second-Line Treatment in Patients With Advanced Pancreatic Adenocarcinoma","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 41187298 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: This phase III (ClinicalTrials.gov identifier: NCT03665441) study evaluated eryaspase in combination with chemotherapy as second-line treatment in advanced pancreatic ductal adenocarcinoma (PDAC).\n\nPatients and methods: TRYBECA-1 enrolled patients 18 years and older whose disease progressed on or after 1L chemotherapy. Patients were randomly assigned to eryaspase plus chemotherapy (gemcitabine/nab-paclitaxel or fluorouracil [5-FU], leucovorin [LV], and irinotecan/nanoliposomal irinotecan) or chemotherapy. Treatment was administered in a 4-week cycle for each of the following drugs until disease progression or unacceptable toxicity: eryaspase 100 U/kg intravenously on days 1 and 15; gemcitabine 1,000 mg/m 2 and nab-paclitaxel 125 mg/m 2 intravenously on days 1, 8 and 15; irinotecan 180 mg/m 2 (or nanoliposomal irinotecan 70 mg/m 2) intravenously on days 1 and 15; 5-FU 2,400 mg/m 2 as one 46-hour infusion (with a bolus of 400 mg/m 2); and LV 400 mg/m 2 intravenously on days 1 and 15. The primary end point was overall survival (OS); secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety.\n\nResults: A total of 512 patients were randomly assigned (n = 255 for eryaspase and n = 257 for chemotherapy alone). Baseline characteristics were balanced between the two groups. There were 420 deaths, with a median OS of 7.5 months for eryaspase and chemotherapy versus 6.7 months for chemotherapy (hazard ratio [HR], 0.92 [95% CI, 0.76 to 1.11]; P =.374); the median PFS was 3.7 months versus 3.4 months (HR, 0.88 [95% CI, 0.73 to 1.07]; P =.196), and the ORR was 16.1% versus 12.5% (odds ratio, 1.35; [95% CI, 0.81 to 2.24]), respectively. Grade ≥3 adverse events (AEs) included neutropenia (25.4% v 20.3%), asthenia (16.9% v 13.8%), and anemia (17.3% v 12.2%) in the experimental versus control arms, respectively.\n\nConclusion: The addition of eryaspase to chemotherapy did not improve OS, PFS, or ORR. AEs were generally consistent with previous reports of chemotherapy. These results do not support additional development of eryaspase in PDAC.\n\nIndexed on Europe PMC as PubMed record 41187298 (DOI 10.1200/jco-25-00872). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2025","url":"https://doi.org/10.1200/jco-25-00872"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41187298/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41187298"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["trybeca-1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2025,"doi":"10.1200/jco-25-00872","pmid":"41187298","authors":"Hammel P, Metges JP, Macarulla Mercade T, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-her2climb-02-ann-oncol-2026","kind":"paper","name":"Tucatinib and trastuzumab emtansine for patients with previously treated HER2-positive locally advanced and metastatic breast cancer: primary analysis of the randomized phase III trial HER2CLIMB-02","aka":[],"tldr":"Published report from the HER2CLIMB-02 trial registered as NCT03975647, in Annals of Oncology (2026), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Trastuzumab emtansine (T-DM1) is a standard treatment option in patients with previously treated human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancer (LA/MBC). Here, we report the efficacy and safety of tucatinib in combination with T-DM1 compared with T-DM1 alone from the phase III HER2CLIMB-02 study (NCT03975647).\n\nPatients and methods: Eligible patients had HER2-positive LA/MBC that had been previously treated with trastuzumab and a taxane in any setting; these included patients with brain metastases (BMs). Patients were randomly assigned 1: 1 to receive T-DM1 (3.6 mg/kg intravenously every 21 days) combined with either tucatinib (300 mg orally twice daily) in the tucatinib arm or placebo (orally twice daily) in the control arm.\n\nResults: In total, 463 patients were randomly assigned. After a median follow-up duration of 24.4 months, the median progression-free survival (PFS) was 9.5 months in the tucatinib arm and 7.4 months in the control arm [hazard ratio (HR) 0.76, 95% confidence interval (CI) 0.61-0.95, P = 0.0163]. A PFS benefit was observed across all prespecified subgroups, including in patients with BMs. Interim overall survival analysis results were immature. The median OS was not reached in the tucatinib arm and was 38.0 months in the control arm (HR 1.23, 95% CI 0.87-1.74). The incidences of treatment-emergent adverse events (TEAEs) associated with any treatment discontinuation and of grade ≥3 TEAEs were higher in the tucatinib arm than in the control arm (22.1% versus 11.6% and 68.8% versus 41.2%, respectively). The most common grade ≥3 TEAEs in the tucatinib arm were elevated alanine aminotransferase (16.5%) and aspartate aminotransferase levels (16.5%) (versus 2.6% for both in the control arm).\n\nConclusion: The addition of tucatinib to T-DM1 improved PFS in patients with previously treated HER2-positive LA/MBC, including patients with BMs, and exhibited a manageable safety profile.\n\nIndexed on Europe PMC as PubMed record 41260264 (DOI 10.1016/j.annonc.2025.11.005). Its abstract cites the registry id NCT03975647, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2026","url":"https://doi.org/10.1016/j.annonc.2025.11.005"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41260264/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41260264"},{"label":"ClinicalTrials.gov NCT03975647","url":"https://clinicaltrials.gov/study/NCT03975647"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["her2climb-02"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2026,"doi":"10.1016/j.annonc.2025.11.005","pmid":"41260264","authors":"Hurvitz SA, Loi S, O'Shaughnessy J, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03975647 with the most citations, so it is the natural first reading for anyone following the HER2CLIMB-02 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-nct04579380-j-clin-oncol-2023","kind":"paper","name":"Tucatinib and Trastuzumab for Previously Treated Human Epidermal Growth Factor Receptor 2-Positive Metastatic Biliary Tract Cancer (SGNTUC-019): A Phase II Basket Study","aka":[],"tldr":"Published report from the trial registered as NCT04579380, in Journal of Clinical Oncology (2023), chosen as the most cited paper whose own text cites the registry id.","summary":"Purpose: To evaluate the efficacy and safety of tucatinib and trastuzumab in patients with previously treated human epidermal growth factor receptor 2-positive (HER2+) metastatic biliary tract cancer (mBTC).\n\nMethods: SGNTUC-019 (ClinicalTrials.gov identifier: NCT04579380) is an open-label phase II basket study evaluating the efficacy and safety of tucatinib and trastuzumab in patients with HER2-altered solid tumors. In the biliary tract cancer cohort, patients had previously treated HER2 overexpressing or amplified (HER2+) tumors (identified with local testing) with no prior HER2-directed therapy. The primary end point was confirmed objective response rate (cORR) per investigator assessment. Patients were treated on a 21-day cycle with tucatinib (300 mg orally twice daily) and trastuzumab (8 mg/kg intravenously followed by 6 mg/kg every 3 weeks).\n\nResults: Thirty patients were enrolled. at data cutoff (January 30, 2023), the median duration of follow-up was 10.8 months. The cORR was 46.7% (90% CI, 30.8 to 63.0), with a disease control rate of 76.7% (90% CI, 60.6 to 88.5). The median duration of response and progression-free survival were 6.0 months (90% CI, 5.5 to 6.9) and 5.5 months (90% CI, 3.9 to 8.1), respectively. At data cutoff, 15 patients (50.0%) had died, and the estimated 12-month overall survival rate was 53.6% (90% CI, 36.8 to 67.8). The two most common treatment-emergent adverse events (TEAEs) were pyrexia (43.3%) and diarrhea (40.0%). Grade ≥3 TEAEs were reported in 18 patients (60.0%), with the most common being cholangitis, decreased appetite, and nausea (all 10.0%), which were generally not treatment related. TEAEs led to treatment regimen discontinuation in one patient, and there were no deaths due to TEAEs.\n\nConclusion: Tucatinib combined with trastuzumab had clinically significant antitumor activity and was well tolerated in patients with previously treated HER2+ mBTC.\n\nIndexed on Europe PMC as PubMed record 37751561 (DOI 10.1200/jco.23.00606). Its abstract cites the registry id NCT04579380, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2023","url":"https://doi.org/10.1200/jco.23.00606"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37751561/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37751561"},{"label":"ClinicalTrials.gov NCT04579380","url":"https://clinicaltrials.gov/study/NCT04579380"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04579380"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2023,"doi":"10.1200/jco.23.00606","pmid":"37751561","authors":"Nakamura Y, Mizuno N, Sunakawa Y, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04579380 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-mountaineer-nat-commun-2026-update","kind":"paper","name":"Tucatinib plus trastuzumab for chemotherapy-refractory, HER2 +, RAS wild-type metastatic colorectal cancer (MOUNTAINEER): final analysis","aka":[],"tldr":"Later report from the MOUNTAINEER trial registered as NCT03043313, in Nature Communications (2026); its title describes an updated or longer-term analysis.","summary":"MOUNTAINEER was a multicenter, open-label, phase 2 trial (NCT03043313) that evaluated the efficacy and safety of tucatinib plus trastuzumab, a dual HER2-targeted chemotherapy-free regimen. Patients were included if they had chemotherapy-refractory, HER2+, RAS wild-type unresectable or metastatic colorectal cancer. This final analysis reports updated efficacy and safety after a median follow-up of 32.4 months. Of the 84 patients who received tucatinib plus trastuzumab, the confirmed objective response rate was 39.3%; median duration of response was 15.2 months. Median progression-free survival was 8.1 months and overall survival was 23.9 months. Efficacy was relatively similar across central HER2+ testing methods. No clear association of treatment response with co-occurring biomarker alterations was seen. Few patients discontinued treatment due to adverse events; no treatment-emergent deaths occurred. Tucatinib plus trastuzumab showed clinically meaningful efficacy and favorable safety. Efficacy was observed irrespective of central HER2+ testing methods and in patients with heterogeneous tumor biomarker profiles.\n\nIndexed on Europe PMC as PubMed record 41526345 (DOI 10.1038/s41467-025-67824-z). Its abstract cites the registry id NCT03043313, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Nat Commun 2026","url":"https://doi.org/10.1038/s41467-025-67824-z"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41526345/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41526345"},{"label":"ClinicalTrials.gov NCT03043313","url":"https://clinicaltrials.gov/study/NCT03043313"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["mountaineer"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-communications"],"dependsOn":[],"notes":[],"journal":"Nature Communications","year":2026,"doi":"10.1038/s41467-025-67824-z","pmid":"41526345","authors":"Strickler JH, Cercek A, Siena S, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the MOUNTAINEER trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-strickler-mountaineer-tucatinib-trastuzumab-lancet-oncol-2023","kind":"paper","name":"Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER)","aka":[],"tldr":"A HER2 pill with an antibody gave a 38 percent response rate in chemotherapy-refractory HER2-positive bowel cancer, and became the first HER2-directed regimen approved for the disease.","summary":"Strickler, Cercek, Siena and colleagues enrolled patients aged 18 and older with chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer at 34 sites in Belgium, France, Italy, Spain and the United States. The study began as a single cohort of tucatinib 300 mg orally twice daily plus intravenous trastuzumab, and after an interim analysis expanded with randomisation 4:3 to the combination or to tucatinib alone. The primary endpoint was confirmed objective response by blinded independent central review in the two combination cohorts together.\n\nBetween August 2017 and September 2021, 117 patients were enrolled; 114 had locally assessed HER2-positive disease and received treatment, with a median age of 56.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2023","url":"https://doi.org/10.1016/S1470-2045(23)00150-X"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37142372/"}],"tags":["colorectal-evidence"],"related":["paper-sartore-bianchi-heracles-trastuzumab-lapatinib-lancet-oncol-2016","paper-siena-destiny-crc01-trastuzumab-deruxtecan-lancet-oncol-2021","her2-ish-amplified","her2-ihc-3-plus"],"cancers":["colorectal","her2-amplified-colorectal"],"sections":["targeted-therapy"],"technologies":["kinase-inhibitors","monoclonal-antibody"],"targets":["her2"],"drugs":["tucatinib","trastuzumab"],"companies":["pfizer","merck"],"institutions":[],"pathways":["rtk-activation"],"terms":["gene-amplification"],"trials":["mountaineer"],"people":["john-strickler","andrea-cercek","salvatore-siena","thierry-andre","eric-van-cutsem","tanios-bekaii-saab"],"bottlenecks":["b-rare-cancers"],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2023,"doi":"10.1016/S1470-2045(23)00150-X","pmid":"37142372","authors":"Strickler JH, Cercek A, Siena S, et al.","paperType":"rct","findings":["Confirmed objective response by central review in the combination cohorts 38.1 percent (95 percent CI 27.7 to 49.3) of 84 patients: three complete and 29 partial responses.","Commonest adverse event in the combination cohorts was diarrhoea (55 of 86, 64 percent); commonest grade 3 or worse event was hypertension (six of 86, 7 percent).","Tucatinib-related serious adverse events in three of 86 patients; no deaths were attributed to adverse events."],"whatItMeans":"The first United States approval of a HER2-directed regimen in colorectal cancer, and the basis for MOUNTAINEER-03, which is testing the combination with chemotherapy in the first line.","caveats":["Single-arm for the primary endpoint; the randomised monotherapy cohort was small and not the registration basis.","Response rate rather than survival, in a rare biomarker group.","Funded by the manufacturers."],"changedPractice":true,"participants":117},{"id":"paper-jiang-lancet-oncol","kind":"paper","name":"Tucidinostat plus exemestane for postmenopausal patients with advanced, hormone receptor-positive breast cancer (ACE): a randomised, double-blind, placebo-controlled, phase 3 trial","aka":[],"tldr":"Paper cited by one treatment page, indexed on Europe PMC as PubMed record 31036468 and published in The Lancet Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background: Tucidinostat (formerly known as chidamide) is an oral subtype-selective histone deacetylase inhibitor. In an exploratory study, the combination of tucidinostat with exemestane showed preliminary signs of encouraging anti-tumour activity in patients with advanced hormone receptor-positive breast cancer. To build on these findings, we aimed to assess the efficacy and safety of this combination in a randomised trial in a larger population of postmenopausal patients with advanced, hormone receptor-positive breast cancer.\n\nMethods: We did the randomised, double-blind, placebo-controlled, phase 3 ACE trial at 22 specialist cancer centres in China. Eligible patients were postmenopausal women (aged ≥60 years or aged <60 years if their serum follicle-stimulating hormone and oestradiol concentrations were within postmenopausal ranges) with hormone receptor-positive, HER2-negative breast cancer, whose disease had relapsed or progressed after at least one endocrine therapy (either in advanced or metastatic or adjuvant setting), and who had at least one measurable lesion, adequate organ function, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and adequate haematological and biochemical parameters. Endocrine therapy did not have to be the most recent therapy before randomisation, but recurrence or progression after the most recent therapy was a prerequisite. Patients were randomly assigned (2:1) by a dynamic randomisation scheme via an interactive web-response system to receive 30 mg oral tucidinostat or placebo twice weekly. All patients in both groups also received 25 mg oral exemestane daily. Randomisation was stratified according to the presence of visceral metastases (yes vs no). Patients, investigators, study site staff, and the sponsor were masked to treatment assignment. The primary endpoint was investigator-assessed progression-free survival. Efficacy analyses were done in the full analysis set population, comprising all patients who received at least one dose of any study treatment, and safety analyses were done in all patients who received at least one dose of any study treatment and for whom at least one safety case report form was available. This study is registered with ClinicalTrials.gov, number NCT02482753. The study has reached the required number of events for final analysis of the primary endpoint. The trial is no longer enrolling patients, but follow-up for investigation of overall survival is ongoing.\n\nFindings: Between July 20, 2015, and June 26, 2017, 365 patients were enrolled and randomly assigned, 244 to the tucidinostat group and 121 to the placebo group. The median duration of follow-up was 13·9 months (IQR 9·8-17·5). Investigator-assessed median progression-free survival was 7·4 months (95% CI 5·5-9·2) in the tucidinostat group and 3·8 months (3·7-5·5) in the placebo group (HR 0·75 [95% CI 0·58-0·98]; p=0·033). The most common grade 3 or 4 adverse events in either group were neutropenia (124 [51%] of 244 patients in the tucidinostat group vs three [2%] of 121 patients in the placebo group), thrombocytopenia (67 [27%] vs three [2%]), and leucopenia (46 [19%] vs three [2%]). Serious adverse events of any cause occurred in 51 (21%) of 244 patients in the tucidinostat group and seven (6%) of 121 patients in the placebo group. No treatment-related deaths were reported.\n\nInterpretation: Tucidinostat plus exemestane improved progression-free survival compared with placebo plus exemestane in patients with advanced, hormone receptor-positive, HER2-negative breast cancer that progressed after previous endocrine therapy. Grade 3-4 haematological adverse events were more common in the tucidinostat plus exemestane group than in the placebo plus exemestane group. Tucidinostat plus exemestane could represent a new treatment option for these patients.\n\nFunding: Chipscreen Biosciences.\n\nIndexed on Europe PMC as PubMed record 31036468 (DOI 10.1016/s1470-2045(19)30164-0). Matched by DOI alone: one treatment page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2019","url":"https://doi.org/10.1016/s1470-2045(19)30164-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31036468/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31036468"}],"tags":["europepmc-ingest"],"related":["tucidinostat"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2019,"doi":"10.1016/s1470-2045(19)30164-0","pmid":"31036468","authors":"Jiang Z, Li W, Hu X, et al.","paperType":"rct","findings":[],"whatItMeans":"One treatment page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-tumeh-pd1-adaptive-immune-resistance-nature-2014","kind":"paper","name":"Tumeh 2014: PD-1 blockade works by releasing T cells already present at the tumour edge","aka":[],"tldr":"Melanomas that responded to pembrolizumab already contained killer T cells pressed up against tumour cells expressing PD-L1, showing that the drug works by releasing an immune attack that is already there rather than creating a new one.","summary":"Tumeh, Ribas and colleagues at UCLA studied tumour biopsies from 46 patients with metastatic melanoma before and during pembrolizumab. Responding tumours had higher densities of CD8 T cells, PD-1 and PD-L1 at the invasive margin and in the tumour before treatment, with T cells and PD-L1 in close proximity, and their T cell receptor repertoires were more clonal and expanded further on treatment. The authors proposed that PD-L1 is induced as an adaptive resistance mechanism in response to interferon from attacking T cells and that pembrolizumab reverses it.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1038/nature13954"}],"tags":[],"related":["paper-rizvi-mutational-landscape-pd1-science-2015"],"cancers":["melanoma"],"sections":[],"technologies":[],"targets":["pd1","pdl1"],"drugs":["pembrolizumab"],"companies":[],"institutions":["ucla-jonsson"],"pathways":[],"terms":["tils","immune-checkpoint"],"trials":[],"people":["antoni-ribas"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature","year":2014,"doi":"10.1038/nature13954","authors":"Tumeh PC, Harview CL, Yearley JH, et al.","paperType":"translational","findings":["Serial biopsies from 46 melanoma patients treated with pembrolizumab.","Pre-treatment CD8 T cell density and PD-1 and PD-L1 expression at the invasive margin and in the tumour were higher in responders.","Responders showed more clonal T cell receptor repertoires that expanded during treatment.","A predictive model based on these features identified most responders in a validation set."],"whatItMeans":"This paper explained why PD-1 antibodies work in some patients and not others and introduced the idea of inflamed versus non-inflamed tumours that now guides combination strategies designed to bring T cells into cold tumours.","caveats":["Small cohort from a single centre.","Biopsies sample one site and may not represent all metastases."],"changedPractice":false,"participants":46},{"id":"paper-shailender-bhatia-cell-2017","kind":"paper","name":"Tumor and Microenvironment Evolution during Immunotherapy with Nivolumab","aka":[],"tldr":"Paper by Shailender Bhatia indexed on Europe PMC as PubMed record 29033130, in Cell (2017), one of the most cited records naming an author with this name at Fred Hutchinson Cancer Center.","summary":"The mechanisms by which immune checkpoint blockade modulates tumor evolution during therapy are unclear. We assessed genomic changes in tumors from 68 patients with advanced melanoma, who progressed on ipilimumab or were ipilimumab-naive, before and after nivolumab initiation (CA209-038 study). Tumors were analyzed by whole-exome, transcriptome, and/or T cell receptor (TCR) sequencing. In responding patients, mutation and neoantigen load were reduced from baseline, and analysis of intratumoral heterogeneity during therapy demonstrated differential clonal evolution within tumors and putative selection against neoantigenic mutations on-therapy. Transcriptome analyses before and during nivolumab therapy revealed increases in distinct immune cell subsets, activation of specific transcriptional networks, and upregulation of immune checkpoint genes that were more pronounced in patients with response. Temporal changes in intratumoral TCR repertoire revealed expansion of T cell clones in the setting of neoantigen loss. Comprehensive genomic profiling data in this study provide insight into nivolumab's mechanism of action.\n\nIndexed on Europe PMC as PubMed record 29033130 (DOI 10.1016/j.cell.2017.09.028). Its author list gives \"Bhatia S\" with the affiliation \"Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA 98105, USA\", which names Fred Hutchinson Cancer Center; that is how the record was matched to Shailender Bhatia, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cell 2017","url":"https://doi.org/10.1016/j.cell.2017.09.028"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29033130/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29033130"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["shailender-bhatia"],"bottlenecks":[],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Cell","year":2017,"doi":"10.1016/j.cell.2017.09.028","pmid":"29033130","authors":"Riaz N, Havel JJ, Makarov V, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Shailender Bhatia at Fred Hutchinson Cancer Center, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-stutman-science","kind":"paper","name":"Tumor development after 3-methylcholanthrene in immunologically deficient athymic-nude mice","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 4588620 and published in Science; the citing page links this DOI, which is how the record was matched.","summary":"Athymic-nude (nu/nu) mice and normal (nu/+) mice showed no differences in either latent period or incidence of local sarcomas or lung adenomas within 120 days after administration of 3-methylcholanthrene at birth. However, nu/nu mice were incapable of rejecting allogeneic skin grafts for the duration of the experiment. These results argue against an active role of thymus-dependent immunity as a surveillance mechanism preventing tumor development.\n\nIndexed on Europe PMC as PubMed record 4588620 (DOI 10.1126/science.183.4124.534). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Science 1974","url":"https://doi.org/10.1126/science.183.4124.534"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/4588620/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/4588620"}],"tags":["europepmc-ingest"],"related":["immune-surveillance-immunoediting"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":1974,"doi":"10.1126/science.183.4124.534","pmid":"4588620","authors":"Stutman O","paperType":"basic","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-khan-t2-gallbladder-cancer-liver-resection-meta-analysis-updates-surg-2021","kind":"paper","name":"Tumor location and concurrent liver resection, impact survival in T2 gallbladder cancer: a meta-analysis of the literature","aka":[],"tldr":"A second pooled analysis of muscle-invading gallbladder cancer found tumours on the liver side about three times as deadly, found removing part of the liver helped only that group, and found chemotherapy after surgery did not change the risk of death.","summary":"Meta-analysis of nine retrospective studies (2014 to 2020, 2,345 patients) reporting hazard ratios for survival in T2 gallbladder cancer. Hepatic-side (T2b) tumours had higher mortality (hazard ratio 3.16, 95 percent CI 2.11 to 4.74; I2 0 percent). Liver resection was associated with better five-year overall survival only in T2b (odds ratio 2.20, 1.33 to 3.63; I2 67 percent). Adjuvant chemotherapy was not associated with lower mortality (hazard ratio 0.98, 0.83 to 1.16). The authors propose that T2a tumours can be managed without hepatic resection and offer a mortality risk score.","asOf":"2026-09-24","links":[{"label":"Updates Surg 2021","url":"https://doi.org/10.1007/s13304-021-01150-z"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34426958/"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["t2a-versus-t2b","radical-cholecystectomy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Updates in Surgery","year":2021,"doi":"10.1007/s13304-021-01150-z","pmid":"34426958","authors":"Khan SM, Emile SH, Choudhry MS, Sumbal R.","paperType":"meta-analysis","findings":["T2b mortality hazard ratio 3.16 (95 percent CI 2.11 to 4.74).","Liver resection improved five-year survival only in T2b: odds ratio 2.20 (1.33 to 3.63).","Adjuvant chemotherapy: hazard ratio 0.98 (0.83 to 1.16), no association with mortality."],"whatItMeans":"Consistent with Kang and colleagues on prognosis, and more optimistic about liver resection for T2b. The adjuvant chemotherapy finding is retrospective and predates gallbladder-specific analysis of BILCAP, but it is a warning that the adjuvant benefit in this disease is not established.","caveats":["Retrospective data with selection into liver resection.","Heterogeneity was high for the liver resection comparison (I2 67 percent)."],"changedPractice":false,"participants":2345},{"id":"paper-shindoh-t2-gallbladder-cancer-tumour-location-ann-surg-2015","kind":"paper","name":"Tumor location is a strong predictor of tumor progression and survival in T2 gallbladder cancer: an international multicenter study","aka":[],"tldr":"Where a muscle-invading gallbladder tumour sits matters: those on the side against the liver spread more and killed more, with five-year survival of 43 in 100 against 65 in 100 for tumours on the free side.","summary":"Four institutions analysed 437 resected gallbladder cancers, defining tumour location as hepatic side or peritoneal side. Among 252 T2 tumours, hepatic-side tumours (99) had more vascular invasion (51 versus 19 percent), neural invasion (33 versus 8 percent) and nodal metastasis (40 versus 17 percent) than peritoneal-side tumours (153). After a median follow-up of 58.9 months, three- and five-year survival was 52.1 and 42.6 percent for hepatic-side and 73.7 and 64.7 percent for peritoneal-side T2 tumours (p=0.0006); no such difference was seen for T1 or T3. Hepatic-side location was independently associated with survival (hazard ratio 2.7, 95 percent CI 1.7 to 4.2) and predicted liver recurrence (23 versus 3 percent) and distant nodal recurrence (16 versus 3 percent) even after radical resection.","asOf":"2026-09-24","links":[{"label":"Ann Surg 2015","url":"https://doi.org/10.1097/SLA.0000000000000728"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24854451/"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["md-anderson"],"pathways":[],"terms":["t2a-versus-t2b","tnm-staging"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Annals of Surgery","year":2015,"doi":"10.1097/SLA.0000000000000728","pmid":"24854451","authors":"Shindoh J, de Aretxabala X, Aloia TA, et al.","paperType":"observational","findings":["Five-year survival 42.6 percent for hepatic-side vs 64.7 percent for peritoneal-side T2 tumours (p=0.0006).","Hepatic-side location: hazard ratio 2.7 (95 percent CI 1.7 to 4.2) for death; nodal metastasis 40 vs 17 percent.","Liver recurrence 23 vs 3 percent and distant nodal recurrence 16 vs 3 percent after radical resection."],"whatItMeans":"The study behind the T2a/T2b split adopted by the AJCC eighth edition in 2017, the one staging change in gallbladder cancer that grew from the disease's own anatomy rather than from bile duct cancer.","caveats":["Retrospective, four referral centres.","Location was assigned on pathology review; reproducibility between pathologists is a known difficulty."],"changedPractice":true,"participants":437},{"id":"paper-barroso-sousa-tmb-pten-ici-mtnbc-ccr-2020","kind":"paper","name":"Tumor mutational burden and PTEN alterations as molecular correlates of response to PD-1/L1 blockade in metastatic triple-negative breast cancer","aka":[],"tldr":"In 62 women with metastatic triple-negative cancer treated with immunotherapy, high mutation burden (18%) went with a year of progression-free time versus under four months, while PTEN loss (29%) went with almost no responses.","summary":"62 patients with metastatic TNBC who consented to targeted DNA sequencing and were treated with anti-PD-1/L1 therapy on trials at Dana-Farber (2014 to 2019) alone (23%), with targeted therapy (19%) or chemotherapy (58%). High TMB (10 or more nonsynonymous mutations/Mb; 18%) was associated with longer progression-free survival (12.5 versus 3.7 months; P 0.04); PTEN alterations (nonsynonymous mutation or one- or two-copy deletion; 29%) with lower objective response (6% versus 48%), shorter PFS (2.3 versus 6.1 months) and shorter overall survival (9.7 versus 20.5 months), independent of performance status, prior lines, regimen, visceral disease and PD-L1, and not seen in chemotherapy-treated (90) or non-immunotherapy (169) cohorts.","asOf":"2026-09-24","links":[{"label":"Barroso-Sousa et al., Clin Cancer Res 2020: TMB and PTEN alterations and checkpoint response in 62 metastatic TNBC patients","url":"https://doi.org/10.1158/1078-0432.CCR-19-3507"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32019858/"}],"tags":[],"related":["tmb-high","pten-alteration"],"cancers":["tnbc","tnbc-metastatic"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["pten","pdl1","pd1"],"drugs":[],"companies":[],"institutions":["dana-farber"],"pathways":[],"terms":["tmb"],"trials":[],"people":["sara-tolaney","nancy-lin"],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2020,"doi":"10.1158/1078-0432.CCR-19-3507","pmid":"32019858","authors":"Barroso-Sousa R, Keenan TE, Pernas S, et al.","paperType":"observational","findings":["High TMB in 18%: PFS 12.5 versus 3.7 months.","PTEN alterations in 29%: response 6% versus 48%, overall survival 9.7 versus 20.5 months.","Associations independent of PD-L1 and absent in non-immunotherapy cohorts."],"whatItMeans":"PTEN loss, the most common PI3K-pathway lesion in TNBC, may mark primary immunotherapy resistance, and TMB may add to PD-L1 in choosing who gets checkpoint blockade.","caveats":["62 patients across heterogeneous trials; hypothesis-generating.","Panel-derived TMB."],"changedPractice":false,"participants":62},{"id":"paper-panova-3-ttfields-locally-advanced-pancreatic-jco-2025","kind":"paper","name":"Tumor Treating Fields With Gemcitabine and Nab-Paclitaxel for Locally Advanced Pancreatic Adenocarcinoma: Randomized, Open-Label, Pivotal Phase III PANOVA-3 Study","aka":[],"tldr":"The 2025 trial in which a wearable device delivering alternating electric fields to the abdomen, added to chemotherapy, lengthened survival in locally advanced pancreatic cancer from about 14 to 16 months and delayed the onset of pain.","summary":"PANOVA-3 randomised 571 patients with newly diagnosed unresectable locally advanced pancreatic adenocarcinoma to gemcitabine 1,000 mg/m2 and nab-paclitaxel 125 mg/m2 on days 1, 8 and 15 of 28-day cycles with or without tumour treating fields. Overall survival, the primary endpoint, was 16.2 months (95 percent confidence interval 15.0 to 18.0) with the device against 14.2 months (12.8 to 15.4) without (hazard ratio 0.82, 0.68 to 0.99, P = 0.039). Progression-free survival, local progression-free survival and response rate were not improved. Pain-free survival was 15.2 versus 9.1 months (hazard ratio 0.74, P = 0.027) and distant progression-free survival, analysed post hoc, 13.9 versus 11.5 months (hazard ratio 0.74). Device-related skin adverse events occurred in 76.3 percent of patients, mostly mild to moderate, grade 3 in 7.7 percent, with no additive systemic toxicity.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2025","url":"https://doi.org/10.1200/JCO-25-00746"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40448572/"},{"label":"ClinicalTrials.gov NCT03377491","url":"https://clinicaltrials.gov/study/NCT03377491"},{"label":"J Clin Oncol 2025","url":"https://doi.org/10.1200/jco-25-00746"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40448572"}],"tags":["pancreatic-evidence"],"related":["devices-roadmap","paper-lap07-chemoradiotherapy-locally-advanced-pancreatic-jama-2016"],"cancers":["pancreatic"],"sections":["devices"],"technologies":["ttfields"],"targets":[],"drugs":["optune","gemcitabine-nab-paclitaxel"],"companies":["novocure"],"institutions":[],"pathways":[],"terms":["os","pfs"],"trials":["panova-3"],"people":["eric-van-cutsem"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2025,"doi":"10.1200/JCO-25-00746","pmid":"40448572","authors":"Babiker HM, Picozzi V, Chandana SR, et al.","paperType":"rct","findings":["571 patients with unresectable locally advanced disease.","Overall survival 16.2 versus 14.2 months (hazard ratio 0.82, P = 0.039).","Progression-free survival, local control and response rate not improved; pain-free survival 15.2 versus 9.1 months.","Device-related skin events in 76.3 percent, grade 3 in 7.7 percent."],"whatItMeans":"The evidence behind the 2026 approval of Optune Pax for locally advanced disease, the first new approval in that setting in decades, and an unusual case of a survival gain without a progression-free survival gain.","caveats":["Open-label with no sham device; the survival gain is two months and progression endpoints did not move.","Wearing the device for most of the day is a burden not captured by adverse event counts."],"changedPractice":true,"participants":571},{"id":"paper-loi-tils-pooled-early-tnbc-jco-2019","kind":"paper","name":"Tumor-infiltrating lymphocytes and prognosis: a pooled individual patient analysis of early-stage triple-negative breast cancers","aka":[],"tldr":"Pooling 2,148 women from nine studies showed that every extra 10% of immune cells in the tumour stroma cut the risk of relapse by about 13%, and node-negative patients with 30% or more had a 97% chance of being free of distant relapse at three years.","summary":"Individual data from 2,148 early TNBC patients in nine studies treated with anthracycline-based chemotherapy with or without taxanes were pooled; stromal TILs were scored the same way in each. Average sTILs were 23% (SD 20%) and 77% had 1% or more; sTILs were lower with older age, larger tumours, nodal involvement and lower grade. In multivariable models sTILs added independent prognostic information for invasive disease-free, distant disease-free and overall survival; each 10% increment gave hazard ratios of 0.87, 0.83 and 0.84. In node-negative patients with sTILs 30% or more, three-year iDFS was 92%, D-DFS 97% and OS 99%.","asOf":"2026-09-24","links":[{"label":"Loi et al., J Clin Oncol 2019: pooled analysis of stromal TILs in 2,148 early TNBC patients","url":"https://doi.org/10.1200/JCO.18.01010"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30650045/"},{"label":"TILs in breast cancer prognostic model","url":"https://www.tilsinbreastcancer.org"}],"tags":[],"related":[],"cancers":["tnbc","tnbc-early"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tils"],"trials":[],"people":["loi-sherene","martine-piccart"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2019,"doi":"10.1200/JCO.18.01010","pmid":"30650045","authors":"Loi S, Drubay D, Adams S, et al.","paperType":"meta-analysis","findings":["Mean sTILs 23%; 77% of patients at 1% or more.","Each 10% sTIL increment: iDFS HR 0.87, D-DFS 0.83, OS 0.84.","Node-negative, sTILs 30% or more: three-year D-DFS 97%, OS 99%."],"whatItMeans":"TILs are the strongest cheap prognostic biomarker in early TNBC, scored on a standard slide, and the basis of the de-escalation trials that omit chemotherapy in small, lymphocyte-rich tumours.","caveats":["Retrospective pooling of chemotherapy-treated trial patients.","Scoring reproducibility depends on the International TIL Working Group method."],"changedPractice":true,"participants":2148},{"id":"paper-leon-ferre-tils-tnbc-no-chemotherapy-jama-2024","kind":"paper","name":"Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer","aka":[],"tldr":"A pooled study of 1,966 women with early triple-negative breast cancer treated with surgery and radiotherapy but no chemotherapy, in which those whose tumours were half or more immune cells had 94 percent five-year freedom from distant relapse in stage I disease against 78 percent for immune-poor tumours.","summary":"Leon-Ferre, Jonas, Salgado, Loi and colleagues pooled individual patient data from 13 centres in North America, Europe and Asia for 1,966 patients diagnosed with triple-negative breast cancer between 1979 and 2017 who received surgery with or without radiotherapy but no adjuvant or neoadjuvant chemotherapy (median age 56; 55 percent stage I). Median tumour-infiltrating lymphocyte level was 15 percent; 417 (21 percent) had 50 percent or more (median age 41) and 1,300 (66 percent) less than 30 percent. In stage I disease five-year distant recurrence-free survival was 94 percent (95 percent confidence interval 91 to 96) with lymphocytes of 50 percent or more versus 78 percent (75 to 80) below 30 percent, and five-year overall survival 95 versus 82 percent. At a median follow-up of 18 years each 10 percent increment in lymphocytes was independently associated with better invasive disease-free survival (hazard ratio 0.92), recurrence-free survival (0.90), distant recurrence-free survival (0.87) and overall survival (0.88).","asOf":"2026-09-24","links":[{"label":"JAMA 2024","url":"https://doi.org/10.1001/jama.2024.3056"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38563834/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38563834"}],"tags":["tnbc-evidence"],"related":["idea-til-guided-deescalation"],"cancers":["tnbc","tnbc-early"],"sections":[],"technologies":["digital-pathology-ai"],"targets":[],"drugs":[],"companies":[],"institutions":["mayo-clinic"],"pathways":[],"terms":["tils","de-escalation","hazard-ratio"],"trials":[],"people":["loi-sherene","giuseppe-curigliano"],"bottlenecks":["b-toxicity-qol","b-biomarker-validation"],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2024,"doi":"10.1001/jama.2024.3056","pmid":"38563834","authors":"Leon-Ferre RA, Jonas SF, Salgado R, et al.","paperType":"observational","findings":["Stage I, lymphocytes 50 percent or more vs under 30 percent: five-year distant recurrence-free survival 94 vs 78 percent; five-year overall survival 95 vs 82 percent.","Each 10 percent increase in lymphocytes: hazard ratios 0.92 (invasive disease-free), 0.90 (recurrence-free), 0.87 (distant recurrence-free), 0.88 (overall survival), adjusted for age, size, nodes, grade and radiotherapy."],"whatItMeans":"The evidence behind the stage I de-escalation statement on the triple-negative page: an ordinary haematoxylin and eosin slide identifies a fifth of patients whose outcome without chemotherapy matches treated cohorts. A prospective trial of chemotherapy omission is the missing step.","caveats":["Retrospective; patients were untreated for historical or clinical reasons that may confound.","Lymphocyte scoring reproducibility between pathologists is imperfect; digital scoring is under evaluation."],"changedPractice":false,"participants":1966},{"id":"paper-zhou-clin-cancer-res","kind":"paper","name":"Tumor-Specific Activity of Precision Medicines in the NCI-MATCH Trial","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 38109210 and published in Clinical Cancer Research; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) is a precision medicine basket trial designed to test the effectiveness of treating cancers based on specific genetic changes in patients' tumors, regardless of cancer type. Multiple subprotocols have each tested different targeted therapies matched to specific genetic aberrations. Most subprotocols exhibited low rates of tumor shrinkage as evaluated across all tumor types enrolled. We hypothesized that these results may arise because these precision cancer therapies have tumor type-specific efficacy, as is common among other cancer therapies.\n\nExperimental design: To test the hypothesis that certain tumor types are more sensitive to specific therapies than other tumor types, we applied permutation testing to tumor volume change and progression-free survival data from 10 published NCI-MATCH subprotocols (together n = 435 patients). FDR was controlled by the Benjamini-Hochberg procedure.\n\nResults: Six of ten subprotocols exhibited statistically significant evidence of tumor-specific drug sensitivity, four of which were previously considered negative based on response rate across all tumors. This signal-finding analysis highlights potential uses of FGFR tyrosine kinase inhibition in urothelial carcinomas with actionable FGFR aberrations and MEK inhibition in lung cancers with BRAF non-V600E mutations. In addition, it identifies low-grade serious ovarian carcinoma with BRAF v600E mutation as especially sensitive to BRAF and MEK co-inhibition (dabrafenib plus trametinib), a treatment that received accelerated FDA approval for advanced solid tumors with BRAF v600E mutation.\n\nConclusions: These findings support the value of basket trials because even when precision medicines do not have tumor-agnostic activity, basket trials can identify tumor-specific activity for future study.\n\nIndexed on Europe PMC as PubMed record 38109210 (DOI 10.1158/1078-0432.ccr-23-0983). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Clin Cancer Res 2024","url":"https://doi.org/10.1158/1078-0432.ccr-23-0983"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38109210/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38109210"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nci-match"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2024,"doi":"10.1158/1078-0432.ccr-23-0983","pmid":"38109210","authors":"Zhou I, Plana D, Palmer AC","paperType":"observational","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-bergers-nat-rev-cancer","kind":"paper","name":"Tumorigenesis and the angiogenic switch","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 12778130 and published in Nature Reviews Cancer; the citing page links this DOI, which is how the record was matched.","summary":"It has become evident that we cannot understand tumour growth without considering components of the stromal microenvironment, such as the vasculature. At the same time, the tumour phenotype determines the nature of the tumour vasculature. Much research is now devoted to determining the impact of angiogenesis on tumour development and progression, and the reciprocal influences of tumour products on the microvasculature. A more detailed understanding of the complex parameters that govern the interactions between the tumour and vascular compartments will help to improve anti-angiogenic strategies-- not only for cancer treatment, but also for preventing recurrence.\n\nIndexed on Europe PMC as PubMed record 12778130 (DOI 10.1038/nrc1093). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Cancer 2003","url":"https://doi.org/10.1038/nrc1093"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/12778130/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/12778130"}],"tags":["europepmc-ingest"],"related":["angiogenic-switch"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Cancer","year":2003,"doi":"10.1038/nrc1093","pmid":"12778130","authors":"Bergers G, Benjamin LE","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-dvorak-n-engl-j-med","kind":"paper","name":"Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 3537791 and published in New England Journal of Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 3537791 (DOI 10.1056/nejm198612253152606). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 1986","url":"https://doi.org/10.1056/nejm198612253152606"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/3537791/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/3537791"}],"tags":["europepmc-ingest"],"related":["microenvironment-inflammation-theory"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":1986,"doi":"10.1056/nejm198612253152606","pmid":"3537791","authors":"Dvorak HF","paperType":"review","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-oreilly-hechtman-ntrk-fusion-pancreatic-larotrectinib-ann-oncol-2019","kind":"paper","name":"Tumour response to TRK inhibition in a patient with pancreatic adenocarcinoma harbouring an NTRK gene fusion","aka":[],"tldr":"A woman whose pancreatic cancer carried a CTRC-NTRK1 fusion responded to larotrectinib for six months after chemotherapy failed, then developed resistance, showing both the promise and the limits of TRK inhibitors in this disease.","summary":"A 61-year-old with metastatic pancreatic ductal adenocarcinoma received gemcitabine, nab-paclitaxel and ADI-PEG 20 for 12 months (partial response), then modified FOLFIRINOX, before somatic profiling revealed a CTRC-NTRK1 fusion. Larotrectinib 100 mg twice daily gave a partial response at 2 months; progression at 6 months led to re-biopsy and the next-generation TRK inhibitor selitrectinib, then dabrafenib and trametinib for a BRAF V600E mutation; the patient died two months later.","asOf":"2026-09-24","links":[{"label":"O'Reilly and Hechtman, Ann Oncol 2019: CTRC-NTRK1 fusion pancreatic cancer treated with larotrectinib","url":"https://doi.org/10.1093/annonc/mdz385"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31605106/"}],"tags":[],"related":["ntrk-fusion"],"cancers":["pancreatic","kras-wild-type-pdac"],"sections":[],"technologies":[],"targets":["ntrk"],"drugs":["larotrectinib"],"companies":[],"institutions":["mskcc"],"pathways":[],"terms":["tumour-agnostic"],"trials":[],"people":["eileen-oreilly"],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2019,"doi":"10.1093/annonc/mdz385","pmid":"31605106","authors":"O'Reilly EM, Hechtman JF.","paperType":"observational","findings":["CTRC-NTRK1 fusion pancreatic cancer: partial response to larotrectinib, progression at 6 months.","Acquired resistance and a BRAF V600E clone followed."],"whatItMeans":"NTRK fusions are under 0.5% of pancreatic cancers but carry a tumour-agnostic approval; this case is the published proof that the label applies here.","caveats":["Single case.","Resistance mechanisms were not fully characterised in the abstract."],"changedPractice":false,"participants":1},{"id":"paper-denkert-tils-neoadjuvant-pooled-lancet-oncol-2018","kind":"paper","name":"Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy","aka":[],"tldr":"In 906 triple-negative patients from six German trials, half of the tumours with dense lymphocytes disappeared completely on chemotherapy before surgery against under a third of those with few, and more lymphocytes meant longer survival.","summary":"Pre-treatment core biopsies from 3,771 patients in six German Breast Group neoadjuvant trials were scored for stromal TILs by International TIL Working Group methods in three groups: low (0 to 10%), intermediate (11 to 59%) and high (60% or more). In TNBC, pCR was 31% (80 of 260) with low, 31% (117 of 373) with intermediate and 50% (136 of 273) with high TILs (P less than 0.0001); a 10% TIL increase was associated with longer disease-free survival (HR 0.93) and overall survival (HR 0.92). TILs predicted response in all subtypes but were an adverse survival factor in luminal-HER2-negative disease.","asOf":"2026-09-24","links":[{"label":"Denkert et al., Lancet Oncol 2018: TILs in 3,771 neoadjuvant patients from six German Breast Group trials","url":"https://doi.org/10.1016/S1470-2045(17)30904-X"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29233559/"}],"tags":[],"related":[],"cancers":["tnbc","tnbc-early","breast-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["gbg"],"institutions":[],"pathways":[],"terms":["tils","pcr"],"trials":[],"people":["carsten-denkert","sibylle-loibl"],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2018,"doi":"10.1016/S1470-2045(17)30904-X","pmid":"29233559","authors":"Denkert C, von Minckwitz G, Darb-Esfahani S, et al.","paperType":"meta-analysis","findings":["TNBC (906 patients): high TILs (60% or more) in 273, 30%; pCR 50% with high versus 31% with low TILs.","10% TIL increase: TNBC disease-free survival HR 0.93, overall survival HR 0.92.","TILs were adverse for survival in luminal-HER2-negative disease."],"whatItMeans":"It fixes the lymphocyte-predominant share of TNBC at about 30% and shows TILs predict chemotherapy response before immunotherapy enters the picture.","caveats":["Trial populations; non-standard regimens in some trials.","Three-band grouping; continuous scoring is now preferred."],"changedPractice":false,"participants":3771},{"id":"paper-korolev-nat-rev-cancer","kind":"paper","name":"Turning ecology and evolution against cancer","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 24739582 and published in Nature Reviews Cancer; the citing page links this DOI, which is how the record was matched.","summary":"The fight against cancer has drawn researchers from a wide variety of disciplines, ranging from molecular biology to physics, but the perspective of an ecological theorist has been mostly overlooked. By thinking about the cells that make up a tumour as an endangered species, cancer vulnerabilities become more apparent. Studies in conservation biology and microbial experiments indicate that extinction is a complex phenomenon, which is often driven by the interaction of ecological and evolutionary processes. Recent advances in cancer research have shown that tumours, like species striving for survival, harbour intricate population dynamics, which suggests the possibility to exploit the ecology of tumours for treatment.\n\nIndexed on Europe PMC as PubMed record 24739582 (DOI 10.1038/nrc3712). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Cancer 2014","url":"https://doi.org/10.1038/nrc3712"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24739582/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/24739582"}],"tags":["europepmc-ingest"],"related":["evolutionary-game-theory-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Cancer","year":2014,"doi":"10.1038/nrc3712","pmid":"24739582","authors":"Korolev KS, Xavier JB, Gore J","paperType":"review","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-tuxedo-1-trastuzumab-deruxtecan-brain-metastases-nat-med-2022","kind":"paper","name":"TUXEDO-1: trastuzumab deruxtecan in HER2-positive breast cancer with active brain metastases","aka":[],"tldr":"In a small trial, the antibody-drug conjugate trastuzumab deruxtecan shrank brain metastases in almost three quarters of women with HER2-positive breast cancer, showing that a large antibody-based drug can work inside the brain.","summary":"Single-arm phase 2 trial of 15 patients with HER2-positive breast cancer and newly diagnosed or progressing brain metastases not needing immediate local therapy, treated with trastuzumab deruxtecan 5.4 mg/kg.\n\nIntracranial response by RANO-BM criteria was 73.3 percent in the intention-to-treat population, with a median progression-free survival of 14 months and preserved quality of life. The larger DESTINY-Breast12 study later confirmed intracranial activity in a broader population.","asOf":"2026-09-17","links":[{"label":"Nat Med 2022","url":"https://doi.org/10.1038/s41591-022-01935-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35941372/"}],"tags":[],"related":[],"cancers":["her2-positive-breast-brain-metastases"],"sections":[],"technologies":[],"targets":[],"drugs":["trastuzumab","trastuzumab-deruxtecan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["tuxedo-1"],"people":["rupert-bartsch"],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2022,"doi":"10.1038/s41591-022-01935-8","pmid":"35941372","authors":"Bartsch R, Berghoff AS, Furtner J, et al.","paperType":"observational","findings":["Intracranial objective response 73.3 percent.","Median progression-free survival 14 months."],"whatItMeans":"Trastuzumab deruxtecan is an option for active HER2-positive brain metastases, complementing tucatinib-based therapy, and challenges the assumption that antibody-drug conjugates cannot reach the brain.","caveats":["Very small single-centre study.","Patients with lesions needing urgent local treatment were excluded."],"changedPractice":true,"participants":15},{"id":"paper-turrisi-twice-daily-thoracic-radiotherapy-limited-sclc-nejm-1999","kind":"paper","name":"Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide","aka":[],"tldr":"Giving the same total radiation dose twice a day over three weeks instead of once a day over five raised five-year survival from 16 to 26 percent, at the cost of a much sorer gullet.","summary":"Turrisi, Kim, Blum and colleagues randomised 417 patients with limited small-cell lung cancer, all receiving four 21-day cycles of cisplatin and etoposide, to 45 Gy of concurrent thoracic radiotherapy given either twice daily over three weeks or once daily over five, starting with cycle 1 of chemotherapy.\n\nIt is the trial that defined limited-stage small-cell treatment for twenty-five years, and it is also a study in why a proven regimen can fail to be adopted: twice-daily radiotherapy needs two hospital visits a day for three weeks and causes grade 3 oesophagitis in more than a quarter of patients, so many centres continued once-daily treatment regardless.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 1999","url":"https://doi.org/10.1056/NEJM199901283400403"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/9920950/"}],"tags":["lung-evidence"],"related":["paper-auperin-prophylactic-cranial-irradiation-sclc-nejm-1999","paper-adriatic-nejm-2024","radiation-roadmap"],"cancers":["lung-cancer","sclc","limited-stage-sclc"],"sections":["radiation"],"technologies":["radiotherapy","imrt-igrt"],"targets":[],"drugs":["cisplatin","etoposide"],"companies":[],"institutions":[],"pathways":[],"terms":["chemoradiation"],"trials":[],"people":[],"bottlenecks":["b-surgery-radiation-innovation","b-toxicity-qol","b-knowledge-diffusion"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":1999,"doi":"10.1056/NEJM199901283400403","pmid":"9920950","authors":"Turrisi AT, Kim K, Blum R, et al.","paperType":"rct","findings":["Median survival 23 months with twice-daily radiotherapy against 19 months with once-daily, after a median follow-up of almost 8 years (P equals 0.04 by log-rank).","Survival with twice-daily radiotherapy 47 percent at two years and 26 percent at five years; with once-daily, 41 percent and 16 percent.","Grade 3 oesophagitis in 27 percent of the twice-daily group against 11 percent of the once-daily group.","Overall two- and five-year survival across both arms 44 percent and 23 percent, a considerable improvement over previous results in limited small-cell lung cancer."],"whatItMeans":"The standard of care in limited-stage small-cell lung cancer from 1999 until ADRIATIC added immunotherapy in 2024, and a rare example of a curative gain in a disease that has had almost none.","caveats":["45 Gy twice daily is not the only accelerated schedule, and the later CONVERT and higher-dose once-daily trials did not settle the question.","Grade 3 oesophagitis in 27 percent is a substantial cost, and toxicity is part of why adoption has been patchy.","Chemotherapy, staging and supportive care of the 1990s; patients today also receive prophylactic cranial irradiation and, since ADRIATIC, consolidation durvalumab."],"changedPractice":true,"participants":417},{"id":"paper-ucart19-allogeneic-car-t-lancet-2020","kind":"paper","name":"UCART19: the first gene-edited, donor-derived CAR-T cells in children and adults with relapsed B-cell ALL","aka":[],"tldr":"Off-the-shelf CAR-T cells made from a healthy donor, gene-edited to avoid rejection and graft-versus-host disease, produced remission in 14 of 21 patients with relapsed ALL.","summary":"This report pooled two phase 1 studies (PALL in 7 children and CALM in 14 adults) of UCART19, allogeneic CD19 CAR-T cells from healthy donors in which TALEN gene editing disrupted the T-cell receptor alpha constant gene (to prevent graft-versus-host disease) and CD52 (to allow alemtuzumab in lymphodepletion). Patients with relapsed or refractory CD19-positive B-cell ALL received fludarabine and cyclophosphamide with or without alemtuzumab followed by UCART19. Complete remission or remission with incomplete count recovery occurred in 14 of 21 patients (67%) at day 28; UCART19 expansion was only seen in patients who received alemtuzumab. Cytokine release syndrome occurred in 91% (grade 3-4 in 3 patients), neurotoxicity in 38% (all grade 1-2), and grade 1 skin graft-versus-host disease in two patients. Most responders proceeded to allogeneic transplant, and durability without transplant was limited.","asOf":"2026-09-08","links":[{"label":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=UCART19%20genome-edited%20donor-derived%20allogeneic%20anti-CD19%20CAR%20T%20Benjamin%20Lancet%202020"},{"label":"ClinicalTrials.gov NCT02746952","url":"https://clinicaltrials.gov/study/NCT02746952"},{"label":"ClinicalTrials.gov NCT02808442","url":"https://clinicaltrials.gov/study/NCT02808442"}],"tags":[],"related":["allogeneic-cell-banking","point-of-care-cell-manufacturing","paper-eliana-tisagenlecleucel-nejm-2018"],"cancers":["all-leukemia"],"sections":[],"technologies":["allogeneic-cell-therapy","car-t","in-vivo-car-t"],"targets":["cd19"],"drugs":[],"companies":["servier","allogene"],"institutions":[],"pathways":[],"terms":["crs"],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy","b-resistance"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2020,"doi":"10.1016/S0140-6736(20)32334-5","pmid":"33308471","authors":"Benjamin R, Graham C, Yallop D, et al.","paperType":"translational","findings":["21 patients (7 children, 14 adults) with relapsed/refractory B-ALL treated with donor-derived, TALEN-edited CD19 CAR-T cells.","Complete remission or CRi in 14 of 21 (67%) at day 28.","CAR-T expansion required alemtuzumab-containing lymphodepletion; no expansion without it.","CRS 91% (3 grade 3-4); neurotoxicity 38%, all grade 1-2; grade 1 skin GvHD in 2 patients.","10 responders proceeded to allogeneic transplant; persistence of UCART19 was short (weeks), limiting durability."],"whatItMeans":"The UCART19 report was the first clinical evidence that a universal, pre-manufactured CAR-T made from a donor can work, avoiding the weeks of autologous manufacturing and the problem of patients whose own T cells are too damaged. It set the template for later allogeneic programmes (including cemacabtagene autoleucel in the ALPHA studies) and for in vivo CAR generation. Short persistence and the need for deep lymphodepletion remain the central weaknesses.","caveats":["Very small phase 1 with heterogeneous dosing.","Remissions were mostly a bridge to transplant; few durable responses without further therapy.","Alemtuzumab-based lymphodepletion causes profound, prolonged immunosuppression and infection risk.","Gene editing raises questions about off-target effects and chromosomal rearrangements."],"changedPractice":false,"participants":21},{"id":"paper-widmark-lancet","kind":"paper","name":"Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer: 5-year outcomes of the HYPO-RT-PC randomised, non-inferiority, phase 3 trial","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 31227373 and published in The Lancet; the citing page links this DOI, which is how the record was matched.","summary":"Background: Hypofractionated radiotherapy for prostate cancer has gained increased attention due to its proposed high radiation-fraction sensitivity. Recent reports from studies comparing moderately hypofractionated and conventionally fractionated radiotherapy support the clinical use of moderate hypofractionation. To date, there are no published randomised studies on ultra-hypofractionated radiotherapy. Here, we report the outcomes of the Scandinavian HYPO-RT-PC phase 3 trial with the aim to show non-inferiority of ultra-hypofractionation compared with conventional fractionation.\n\nMethods: In this open-label, randomised, phase 3 non-inferiority trial done in 12 centres in Sweden and Denmark, we recruited men up to 75 years of age with intermediate-to-high-risk prostate cancer and a WHO performance status between 0 and 2. Patients were randomly assigned to ultra-hypofractionation (42·7 Gy in seven fractions, 3 days per week for 2·5 weeks) or conventional fractionated radiotherapy (78·0 Gy in 39 fractions, 5 days per week for 8 weeks). No androgen deprivation therapy was allowed. The primary endpoint was time to biochemical or clinical failure, analysed in the per-protocol population. The prespecified non-inferiority margin was 4% at 5 years, corresponding to a critical hazard ratio (HR) limit of 1·338. Physician-recorded toxicity was measured according to the Radiation Therapy Oncology Group (RTOG) morbidity scale and patient-reported outcome measurements with the Prostate Cancer Symptom Scale (PCSS) questionnaire. This trial is registered with the ISRCTN registry, number ISRCTN45905321.\n\nFindings: Between July 1, 2005, and Nov 4, 2015, 1200 patients were randomly assigned to conventional fractionation (n=602) or ultra-hypofractionation (n=598), of whom 1180 (591 conventional fractionation and 589 ultra-hypofractionation) constituted the per-protocol population. 1054 (89%) participants were intermediate risk and 126 (11%) were high risk. Median follow-up time was 5·0 years (IQR 3·1-7·0). The estimated failure-free survival at 5 years was 84% (95% CI 80-87) in both treatment groups, with an adjusted HR of 1·002 (95% CI 0·758-1·325; log-rank p=0·99). There was weak evidence of an increased frequency of acute physician-reported RTOG grade 2 or worse urinary toxicity in the ultra-hypofractionation group at end of radiotherapy (158 [28%] of 569 patients vs 132 [23%] of 578 patients; p=0·057). There were no significant differences in grade 2 or worse urinary or bowel late toxicity between the two treatment groups at any point after radiotherapy, except for an increase in urinary toxicity in the ultra-hypofractionation group compared to the conventional fractionation group at 1-year follow-up (32 [6%] of 528 patients vs 13 [2%] of 529 patients; (p=0·0037). We observed no differences between groups in frequencies at 5 years of RTOG grade 2 or worse urinary toxicity (11 [5%] of 243 patients for the ultra-hypofractionation group vs 12 [5%] of 249 for the conventional fractionation group; p=1·00) and bowel toxicity (three [1%] of 244 patients vs nine [4%] of 249 patients; p=0·14). Patient-reported outcomes revealed significantly higher levels of acute urinary and bowel symptoms in the ultra-hypofractionation group compared with the conventional fractionation group but no significant increases in late symptoms were found, except for increased urinary symptoms at 1-year follow-up, consistent with the physician-evaluated toxicity.\n\nInterpretation: Ultra-hypofractionated radiotherapy is non-inferior to conventionally fractionated radiotherapy for intermediate-to-high risk prostate cancer regarding failure-free survival. Early side-effects are more pronounced with ultra-hypofractionation compared with conventional fractionation whereas late toxicity is similar in both treatment groups. The results support the use of ultra-hypofractionation for radiotherapy of prostate cancer.\n\nFunding: The Nordic Cancer Union, the Swedish Cancer Society, and the Swedish Research Council.\n\nIndexed on Europe PMC as PubMed record 31227373 (DOI 10.1016/s0140-6736(19)31131-6). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet 2019","url":"https://doi.org/10.1016/s0140-6736(19)31131-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31227373/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31227373"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["hypo-rt-pc"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2019,"doi":"10.1016/s0140-6736(19)31131-6","pmid":"31227373","authors":"Widmark A, Gunnlaugsson A, Beckman L, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-lane-bmj","kind":"paper","name":"Ultra-processed food exposure and adverse health outcomes: umbrella review of epidemiological meta-analyses","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 38418082 and published in BMJ; the citing page links this DOI, which is how the record was matched.","summary":"Objective: To evaluate the existing meta-analytic evidence of associations between exposure to ultra-processed foods, as defined by the Nova food classification system, and adverse health outcomes.\n\nDesign: Systematic umbrella review of existing meta-analyses.\n\nData sources: MEDLINE, PsycINFO, Embase, and the Cochrane Database of Systematic Reviews, as well as manual searches of reference lists from 2009 to June 2023.\n\nEligibility criteria for selecting studies: Systematic reviews and meta-analyses of cohort, case-control, and/or cross sectional study designs. To evaluate the credibility of evidence, pre-specified evidence classification criteria were applied, graded as convincing (\"class I\"), highly suggestive (\"class II\"), suggestive (\"class III\"), weak (\"class IV\"), or no evidence (\"class V\"). The quality of evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) framework, categorised as \"high,\" \"moderate,\" \"low,\" or \"very low\" quality.\n\nResults: The search identified 45 unique pooled analyses, including 13 dose-response associations and 32 non-dose-response associations (n=9 888 373). Overall, direct associations were found between exposure to ultra-processed foods and 32 (71%) health parameters spanning mortality, cancer, and mental, respiratory, cardiovascular, gastrointestinal, and metabolic health outcomes. Based on the pre-specified evidence classification criteria, convincing evidence (class I) supported direct associations between greater ultra-processed food exposure and higher risks of incident cardiovascular disease related mortality (risk ratio 1.50, 95% confidence interval 1.37 to 1.63; GRADE=very low) and type 2 diabetes (dose-response risk ratio 1.12, 1.11 to 1.13; moderate), as well as higher risks of prevalent anxiety outcomes (odds ratio 1.48, 1.37 to 1.59; low) and combined common mental disorder outcomes (odds ratio 1.53, 1.43 to 1.63; low). Highly suggestive (class II) evidence indicated that greater exposure to ultra-processed foods was directly associated with higher risks of incident all cause mortality (risk ratio 1.21, 1.15 to 1.27; low), heart disease related mortality (hazard ratio 1.66, 1.51 to 1.84; low), type 2 diabetes (odds ratio 1.40, 1.23 to 1.59; very low), and depressive outcomes (hazard ratio 1.22, 1.16 to 1.28; low), together with higher risks of prevalent adverse sleep related outcomes (odds ratio 1.41, 1.24 to 1.61; low), wheezing (risk ratio 1.40, 1.27 to 1.55; low), and obesity (odds ratio 1.55, 1.36 to 1.77; low). Of the remaining 34 pooled analyses, 21 were graded as suggestive or weak strength (class III-IV) and 13 were graded as no evidence (class V). Overall, using the GRADE framework, 22 pooled analyses were rated as low quality, with 19 rated as very low quality and four rated as moderate quality.\n\nConclusions: Greater exposure to ultra-processed food was associated with a higher risk of adverse health outcomes, especially cardiometabolic, common mental disorder, and mortality outcomes. These findings provide a rationale to develop and evaluate the effectiveness of using population based and public health measures to target and reduce dietary exposure to ultra-processed foods for improved human health. They also inform and provide support for urgent mechanistic research.\n\nSystematic review registration: PROSPERO CRD42023412732.\n\nIndexed on Europe PMC as PubMed record 38418082 (DOI 10.1136/bmj-2023-077310). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"BMJ 2024","url":"https://doi.org/10.1136/bmj-2023-077310"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38418082/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38418082"}],"tags":["europepmc-ingest"],"related":["ultra-processed-food-ssb"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["bmj"],"dependsOn":[],"notes":[],"journal":"BMJ","year":2024,"doi":"10.1136/bmj-2023-077310","pmid":"38418082","authors":"Lane MM, Gamage E, Du S, et al.","paperType":"review","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-hutchins-n-engl-j-med","kind":"paper","name":"Underrepresentation of patients 65 years of age or older in cancer-treatment trials","aka":[],"tldr":"Paper cited by one bottleneck page, indexed on Europe PMC as PubMed record 10615079 and published in New England Journal of Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Background: Studies have documented the underrepresentation of women and blacks in clinical trials, and their recruitment is now federally mandated. However, little is known about the level of participation of elderly patients. We determined the rates of enrollment of patients 65 years of age or older in trials of treatment for cancer.\n\nMethods: We analyzed data on 16,396 patients consecutively enrolled in 164 Southwest Oncology Group treatment trials between 1993 and 1996 according to sex, race (black or white), and age under 65 years or 65 or older. These rates were compared with the corresponding rates in the general population of patients with cancer, derived from the 1990 U.S. Census and from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program for the period from 1992 through 1994. Fifteen types of cancer were included in the analysis.\n\nResults: The overall proportions of women and blacks enrolled in Southwest Oncology Group trials were similar to or the same as the estimated proportions in the U.S. population of patients with cancer (women, 41 percent and 43 percent; blacks, 10 percent and 10 percent, respectively). In contrast, patients 65 years of age or older were underrepresented overall (25 percent vs. 63 percent, P<0.001) and in trials involving all 15 types of cancer except lymphoma. The underrepresentation was particularly notable in trials of treatment for breast cancer (9 percent vs. 49 percent, P<0.001). The findings were similar when data on patients who were 70 years of age or older were analyzed, when 15 trials that excluded older patients were eliminated from the analysis, and when community-based enrollment was analyzed separately from enrollment at academic centers.\n\nConclusions: There is substantial underrepresentation of patients 65 years of age or older in studies of treatment for cancer. The reasons should be clarified, and policies adopted to correct this underrepresentation.\n\nIndexed on Europe PMC as PubMed record 10615079 (DOI 10.1056/nejm199912303412706). Matched by DOI alone: one bottleneck page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 1999","url":"https://doi.org/10.1056/nejm199912303412706"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/10615079/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/10615079"}],"tags":["europepmc-ingest"],"related":["b-trial-diversity"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":1999,"doi":"10.1056/nejm199912303412706","pmid":"10615079","authors":"Hutchins LF, Unger JM, Crowley JJ, et al.","paperType":"observational","findings":[],"whatItMeans":"One bottleneck page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-st-gallen-2023-consensus-ann-oncol-2023","kind":"paper","name":"Understanding breast cancer complexity to improve patient outcomes: The St Gallen International Consensus Conference for the Primary Therapy of Individuals with Early Breast Cancer 2023","aka":[],"tldr":"The 2023 report of the international expert panel that meets every two years to vote on how early breast cancer should be treated, this time stressing multidisciplinary decisions and the right intensity and duration of treatment.","summary":"Report of the 18th St Gallen International Breast Cancer Conference, held in March 2023 in Vienna, by Curigliano, Burstein, Gnant, Loibl and colleagues. The panel assessed new findings for local and systemic therapy of early breast cancer with a focus on multimodal options, emphasised multidisciplinary discussion of the clinical benefit of interventions as integral to a plan with the right degree of intensity and duration, concentrated on ductal (no special type) and lobular histologies, and framed its opinions as interpretations of data shaped by practice environments, patient factors and reimbursement and access constraints worldwide, while advocating participation in well-designed clinical studies.","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2023","url":"https://doi.org/10.1016/j.annonc.2023.08.017"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37683978/"}],"tags":["tnbc-evidence"],"related":[],"cancers":["tnbc","breast-hr-positive","breast-her2-positive"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["de-escalation"],"trials":[],"people":["giuseppe-curigliano","sibylle-loibl"],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2023,"doi":"10.1016/j.annonc.2023.08.017","pmid":"37683978","authors":"Curigliano G, Burstein HJ, Gnant M, et al.","paperType":"guideline","findings":["Consensus emphasises multidisciplinary treatment planning with the right degree of intensity and duration.","Panel opinions explicitly account for reimbursement and accessibility constraints around the world."],"whatItMeans":"St Gallen is where de-escalation questions in triple-negative disease (who needs the full KEYNOTE-522 regimen, who can skip adjuvant pembrolizumab) are first put to a vote; the 2023 panel framed intensity and duration as the central problem.","caveats":["Expert consensus by vote, not a systematic review.","Recommendations are for early disease and largely for common histologies."],"changedPractice":true},{"id":"paper-cd30-hodgkin-lymphoma-blood-cancer-j-2017","kind":"paper","name":"Understanding CD30 biology and therapeutic targeting: a historical perspective providing insight into future directions","aka":[],"tldr":"Review on CD30 in Hodgkin lymphoma, in Blood cancer journal (2017), one of the most cited Europe PMC records with CD30 in its title.","summary":"CD30 is a member of the tumor necrosis factor receptor superfamily. It is characteristically expressed in certain hematopoietic malignancies, including anaplastic large cell lymphoma and Hodgkin lymphoma, among others. The variable expression of CD30 on both normal and malignant lymphoid cells has focused research efforts on understanding the pathogenesis of CD30 upregulation, its contribution to lymphomagenesis through anti-apoptotic mechanisms, and its effect on cell survival. Given the restriction of CD30 to certain tumor types, the logical extension of this has been to attempt to exploit it as a therapeutic target. The efficacy of naked anti-CD30 antibodies in practice was, however, modest. Moreover, combinations with bacterial toxins and radioimmunoconjugates have also had limited success. The development of the antibody-drug compound brentuximab vedotin (BV), however, has rejuvenated interest in CD30 as a tumor target. Phase I and II clinical trials in Hodgkin lymphoma, peripheral T-cell lymphoma, cutaneous T cell lymphoma, and even CD30-expressing B-cell lymphomas, have shown the compound is well tolerated, but more importantly, able to deliver meaningful disease control even in patients with multiply relapsed or refractory disease. FDA approval has been granted for its use in relapsed Hodgkin lymphoma and systemic anaplastic large cell lymphoma. A recent phase III trial of BV in cutaneous T-cell lymphoma has confirmed its superiority to standard of care therapies. In this manuscript, we explore the history of CD30 as a tumor marker and as a therapeutic target, both in the laboratory and in the clinic, with a view to understanding future avenues for further study.\n\nIndexed on Europe PMC as PubMed record 28885612 (DOI 10.1038/bcj.2017.85). Its title names CD30 and its text names Hodgkin lymphoma; PubMed types it as a review (review-article, Review). It was matched automatically to the idea \"CD30 CAR-T for multiply relapsed Hodgkin lymphoma\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Blood Cancer J 2017","url":"https://doi.org/10.1038/bcj.2017.85"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28885612/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28885612"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["blood-cancer-journal"],"dependsOn":[],"notes":[],"journal":"Blood cancer journal","year":2017,"doi":"10.1038/bcj.2017.85","pmid":"28885612","authors":"van der Weyden CA, Pileri SA, Feldman AL, et al.","paperType":"review","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for CD30 in Hodgkin lymphoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by CD30 in the title and Hodgkin lymphoma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},{"id":"paper-vander-heiden-science","kind":"paper","name":"Understanding the Warburg effect: the metabolic requirements of cell proliferation","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 19460998 and published in Science; the citing page links this DOI, which is how the record was matched.","summary":"In contrast to normal differentiated cells, which rely primarily on mitochondrial oxidative phosphorylation to generate the energy needed for cellular processes, most cancer cells instead rely on aerobic glycolysis, a phenomenon termed \"the Warburg effect.\" Aerobic glycolysis is an inefficient way to generate adenosine 5'-triphosphate (ATP), however, and the advantage it confers to cancer cells has been unclear. Here we propose that the metabolism of cancer cells, and indeed all proliferating cells, is adapted to facilitate the uptake and incorporation of nutrients into the biomass (e.g., nucleotides, amino acids, and lipids) needed to produce a new cell. Supporting this idea are recent studies showing that (i) several signaling pathways implicated in cell proliferation also regulate metabolic pathways that incorporate nutrients into biomass; and that (ii) certain cancer-associated mutations enable cancer cells to acquire and metabolize nutrients in a manner conducive to proliferation rather than efficient ATP production. A better understanding of the mechanistic links between cellular metabolism and growth control may ultimately lead to better treatments for human cancer.\n\nIndexed on Europe PMC as PubMed record 19460998 (DOI 10.1126/science.1160809). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Science 2009","url":"https://doi.org/10.1126/science.1160809"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19460998/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/19460998"}],"tags":["europepmc-ingest"],"related":["metabolic-theory-of-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2009,"doi":"10.1126/science.1160809","pmid":"19460998","authors":"Vander Heiden MG, Cantley LC, Thompson CB","paperType":"review","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-rueth-inflammatory-breast-trimodality-jco-2014","kind":"paper","name":"Underuse of trimodality treatment and survival in inflammatory breast cancer (National Cancer Data Base)","aka":[],"tldr":"In a national registry, only about a third of women with inflammatory breast cancer received all three recommended treatments, chemotherapy, mastectomy and radiotherapy, and those who did lived substantially longer.","summary":"Analysis of 10,197 women with non-metastatic inflammatory breast cancer in the National Cancer Data Base between 1998 and 2010 examining receipt of chemotherapy, surgery and radiotherapy and its association with survival.\n\nOnly 58.4 percent received all three modalities in recent years, with wide variation by facility and region; median survival was longest with trimodality therapy, and its use was an independent predictor of survival.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2014","url":"https://doi.org/10.1200/JCO.2014.55.1978"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24888808/"}],"tags":[],"related":[],"cancers":["inflammatory-breast-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2014,"doi":"10.1200/JCO.2014.55.1978","pmid":"24888808","authors":"Rueth NM, Lin HY, Bedrosian I, et al.","paperType":"observational","findings":["Trimodality therapy associated with improved overall survival compared with any lesser combination.","Use of trimodality therapy varied substantially by treatment facility type."],"whatItMeans":"The gap between guideline and practice in inflammatory breast cancer is large; this paper is the reason guidelines insist on referral to centres that deliver the full sequence.","caveats":["Registry data with selection bias; healthier patients are more likely to complete all treatments."],"changedPractice":true,"participants":10197},{"id":"paper-unger-trial-participation-barriers-jnci-2019","kind":"paper","name":"Unger: most patients never get the chance to join a cancer trial, and when offered, half say yes","aka":[],"tldr":"Pooling 13 studies of 8,883 patients, 56% had no trial available at their site and a further 22% were ineligible for the trials that existed; among patients actually offered a trial, roughly half enrolled, so overall participation was about 8%.","summary":"Unger and colleagues systematically reviewed studies that tracked consecutive cancer patients through the decision pathway to trial enrolment, quantifying structural, clinical and physician-or-patient barriers at each step. Thirteen studies (nine academic, four community) with 8,883 patients were pooled.\n\nStructural barriers dominated: 55.6% of patients had no trial available for their cancer type and stage at their institution. Of the remainder, 21.5% were ineligible for the available trial. Physician and patient factors (not offered, or declined) accounted for 14.8%. Overall trial participation was 8.1%; but among patients who had an available trial and were eligible, about half enrolled. Participation was lower in community settings.\n\nThe analysis reframed low enrolment from a problem of patient reluctance to one of trial availability and eligibility criteria, shaping ASCO and FDA initiatives to broaden eligibility and decentralise trials.","asOf":"2026-09-08","links":[{"label":"DOI","url":"https://doi.org/10.1093/jnci/djy221"}],"tags":[],"related":["idea-tr1-remote-consent-tele-screening","idea-tr1-protected-physician-time-for-enrolment","idea-tr1-incidence-weighted-enrolment-targets"],"cancers":[],"sections":["drug-discovery"],"technologies":["decentralised-clinical-trials","community-oncology-networks","ai-trial-matching"],"targets":[],"drugs":[],"companies":[],"institutions":["fred-hutch"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment","b-trial-diversity","b-care-fragmentation"],"keyPapers":[],"journals":["jnci"],"dependsOn":[],"notes":[],"journal":"JNCI: Journal of the National Cancer Institute","year":2019,"doi":"10.1093/jnci/djy221","pmid":"30783627","authors":"Unger JM, Vaidya R, Hershman DL, Minasian LM, Fleury ME","paperType":"meta-analysis","findings":["55.6% of patients had no trial available at their site (95% CI 43.7-67.3)","21.5% were ineligible for available trials (95% CI 10.9-33.9)","14.8% did not enrol for physician or patient reasons (not offered, declined)","Overall participation 8.1%; about 55% of eligible patients offered a trial enrolled","Academic centres had higher participation (15.9%) than community sites (7.0%)"],"whatItMeans":"Patients are not the bottleneck; trial access is. Bringing trials to community practices, loosening restrictive eligibility criteria and reducing site burden would do more for enrolment than patient education. Trials today reflect the minority of patients who happen to be treated where trials exist.","caveats":["Included studies were heterogeneous and mostly US-based; barriers differ in single-payer and low-resource systems","Studies varied in how they recorded reasons for non-enrolment, so barrier categories overlap","Academic centres are over-represented in the source studies","Does not capture racial, ethnic or socioeconomic disparities within each barrier category"],"changedPractice":false,"participants":8883},{"id":"paper-martincorena-cell","kind":"paper","name":"Universal Patterns of Selection in Cancer and Somatic Tissues","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 29056346 and published in Cell; the citing page links this DOI, which is how the record was matched.","summary":"Cancer develops as a result of somatic mutation and clonal selection, but quantitative measures of selection in cancer evolution are lacking. We adapted methods from molecular evolution and applied them to 7,664 tumors across 29 cancer types. Unlike species evolution, positive selection outweighs negative selection during cancer development. On average, <1 coding base substitution/tumor is lost through negative selection, with purifying selection almost absent outside homozygous loss of essential genes. This allows exome-wide enumeration of all driver coding mutations, including outside known cancer genes. On average, tumors carry ∼4 coding substitutions under positive selection, ranging from <1/tumor in thyroid and testicular cancers to >10/tumor in endometrial and colorectal cancers. Half of driver substitutions occur in yet-to-be-discovered cancer genes. With increasing mutation burden, numbers of driver mutations increase, but not linearly. We systematically catalog cancer genes and show that genes vary extensively in what proportion of mutations are drivers versus passengers.\n\nIndexed on Europe PMC as PubMed record 29056346 (DOI 10.1016/j.cell.2017.09.042). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cell 2017","url":"https://doi.org/10.1016/j.cell.2017.09.042"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29056346/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29056346"}],"tags":["europepmc-ingest"],"related":["driver-passenger-model"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Cell","year":2017,"doi":"10.1016/j.cell.2017.09.042","pmid":"29056346","authors":"Martincorena I, Raine KM, Gerstung M, et al.","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-bareche-tnbc-microenvironment-jnci-2020","kind":"paper","name":"Unraveling triple-negative breast cancer tumor microenvironment heterogeneity: towards an optimized treatment approach","aka":[],"tldr":"Across 1,512 triple-negative tumours each molecular subtype had its own immune landscape: the immunomodulatory type is fully inflamed and suited to checkpoint drugs, while basal-like, LAR and mesenchymal tumours are immune-cold with the T cells kept at the margin.","summary":"Tumour microenvironment heterogeneity was investigated within each TNBC molecular subtype, including immune infiltrate localisation and composition and expression of targetable immune pathways, in public transcriptomic and genomic datasets totalling 1,512 samples. Each subtype exhibited distinct profiles of immune, vascularisation, stroma and metabolism processes. The immunomodulatory subtype had the highest adaptive immune signatures and a fully inflamed spatial pattern; most mesenchymal stem-like and LAR tumours were immunosuppressive with high stromal signatures; basal-like, LAR and mesenchymal subtypes showed an immune-cold, margin-restricted phenotype. Tumours with high chromosomal instability and copy-number loss on 5q and 15q, including MHC-related genes, showed reduced cytotoxic activity as a plausible immune escape mechanism.","asOf":"2026-09-24","links":[{"label":"Bareche et al., JNCI 2020: tumour microenvironment heterogeneity across 1,512 TNBC samples","url":"https://doi.org/10.1093/jnci/djz208"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31665482/"}],"tags":[],"related":[],"cancers":["tnbc"],"sections":[],"technologies":[],"targets":["pdl1"],"drugs":[],"companies":[],"institutions":["institut-jules-bordet"],"pathways":["immune-desert-exclusion","antigen-presentation-immunoediting","tumor-microenvironment"],"terms":["tils"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jnci"],"dependsOn":[],"notes":[],"journal":"JNCI: Journal of the National Cancer Institute","year":2020,"doi":"10.1093/jnci/djz208","pmid":"31665482","authors":"Bareche Y, Buisseret L, Gruosso T, et al.","paperType":"translational","findings":["Immunomodulatory subtype: highest adaptive immune signatures, fully inflamed pattern.","Basal-like, LAR and mesenchymal: immune-cold, margin-restricted; MSL and LAR immunosuppressive stroma.","5q and 15q loss including MHC genes reduces cytotoxic activity."],"whatItMeans":"It links the Lehmann subtypes to the spatial immune classes of Gruosso and gives a rationale for pairing checkpoint inhibitors with the immunomodulatory subtype and stromal or metabolic agents with the cold ones.","caveats":["In silico deconvolution of public datasets; no prospective immunotherapy outcome data.","Spatial patterns were inferred, not measured, in most samples."],"changedPractice":false,"participants":1512},{"id":"paper-bareche-tnbc-multiomic-heterogeneity-ann-oncol-2018","kind":"paper","name":"Unravelling triple-negative breast cancer molecular heterogeneity using an integrative multiomic analysis","aka":[],"tldr":"Applying the Lehmann subtypes to 550 triple-negative tumours from the two biggest breast cancer genome projects showed each subtype has its own mutations: BL1 is TP53-mutant and unstable, LAR carries PIK3CA in more than half, the immunomodulatory type does best and LAR worst.","summary":"Copy-number, somatic mutation and gene expression data from METABRIC (355) and TCGA (195) gave 550 TNBC samples classified with the TNBCtype tool; 485 were stably classified (BL1 25%, IM 25%, M 21%, LAR 16%, MSL 13%) and 447 had sequencing. TP53 (81%), MUC16 (21%) and PIK3CA (20%) were the most mutated genes. IM was associated with better prognosis (HR 0.68, 95% CI 0.46 to 0.99) and LAR with worse (HR 1.47, 1.0 to 2.14). BL1 was the most genomically unstable subtype with TP53 mutation in 92% and copy-number deletion of BRCA2, MDM2, PTEN, RB1 and TP53. LAR carried a higher mutational burden with PIK3CA (55%), KMT2C (19%), CDH1 (13%), NF1 (13%) and AKT1 (13%) mutations and was 75% HER2-enriched by PAM50. MYC (64%), PIK3CA (51%) and CDK6 (39%) were the most gained or amplified genes. IM showed high expression of PD1, PDL1 and CTLA4. By PAM50, 76% of TNBCs were basal-like, 15% HER2-enriched, 5% normal-like and 2% luminal.","asOf":"2026-09-24","links":[{"label":"Bareche et al., Ann Oncol 2018: integrative multiomic analysis of 550 TNBCs from METABRIC and TCGA","url":"https://doi.org/10.1093/annonc/mdy024"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29365031/"},{"label":"cBioPortal study brca_metabric (METABRIC, Nature 2012 and Nat Commun 2016; 320 triple-negative samples, 299 on the 173-gene panel)","url":"https://www.cbioportal.org/study/summary?id=brca_metabric"},{"label":"cBioPortal study brca_tcga_pub (TCGA, Nature 2012; 825 samples, 123 recorded ER-, PR- and HER2-negative, 84 of them exome-sequenced)","url":"https://www.cbioportal.org/study/summary?id=brca_tcga_pub"}],"tags":[],"related":[],"cancers":["tnbc"],"sections":[],"technologies":[],"targets":["tp53","pik3ca","akt","pten","rb1","androgen-receptor","kmt2c","nf1"],"drugs":[],"companies":[],"institutions":["institut-jules-bordet"],"pathways":["myc","pi3k-akt-mtor","pd1-checkpoint"],"terms":["pam50"],"trials":[],"people":["martine-piccart"],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2018,"doi":"10.1093/annonc/mdy024","pmid":"29365031","authors":"Bareche Y, Venet D, Ignatiadis M, et al.","paperType":"translational","findings":["Stable subtypes among 485: BL1 25%, IM 25%, M 21%, LAR 16%, MSL 13%; BL2 did not reproduce.","TP53 81%, MUC16 21%, PIK3CA 20% overall; TP53 92% in BL1; PIK3CA 55%, AKT1 13%, CDH1 13%, KMT2C 19%, NF1 13% in LAR.","IM better (HR 0.68) and LAR worse (HR 1.47) prognosis; MYC gained or amplified in 64%; PAM50 basal-like 76%."],"whatItMeans":"This is the sourced bridge between expression subtype and mutation: it tells a clinician that a LAR tumour is the one to sequence for PIK3CA and AKT1, and that immunomodulatory biology is a favourable prognostic group before any immunotherapy.","caveats":["Retrospective re-analysis of METABRIC (173-gene panel) and TCGA; sequencing depth and gene coverage differ.","Subtype assignment used the online TNBCtype tool; 65 samples were unclassifiable."],"changedPractice":false,"participants":550},{"id":"paper-scott-tnbc-disparities-uscs-cancer-2019","kind":"paper","name":"Update on triple-negative breast cancer disparities for the United States: A population-based study from the United States Cancer Statistics database, 2010 through 2014","aka":[],"tldr":"A count of 1.15 million US breast cancers from 2010 to 2014 in which Black women had 2.27 times the odds of a triple-negative diagnosis and women under 40 nearly twice the odds, confirming the disparity at national scale.","summary":"Scott, Mobley, Kuo and Il'yasova examined differences between triple-negative and other breast cancers by age, race and ethnicity and stage in the United States Cancer Statistics database. Of 1,151,724 breast cancers identified from 2010 through 2014, the triple-negative phenotype accounted for about 8.4 percent. In unadjusted analyses non-Hispanic Black women (odds ratio 2.27, 95 percent confidence interval 2.23 to 2.31) and Hispanic women (1.22, 1.19 to 1.25) had higher odds of a triple-negative diagnosis than non-Hispanic white women; women under 40 had the highest odds compared with women aged 50 to 64 (1.95, 1.90 to 2.01); stage III (1.69) and stage IV (1.47) at diagnosis conferred higher odds. Results varied slightly after adjustment.","asOf":"2026-09-24","links":[{"label":"Cancer 2019","url":"https://doi.org/10.1002/cncr.32207"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31282032/"}],"tags":["tnbc-evidence"],"related":["paper-howlader-us-incidence-breast-subtypes-jnci-2014","paper-bauer-triple-negative-california-registry-cancer-2007"],"cancers":["tnbc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-diversity","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Cancer","year":2019,"doi":"10.1002/cncr.32207","pmid":"31282032","authors":"Scott LC, Mobley LR, Kuo TM, et al.","paperType":"observational","findings":["Triple-negative phenotype in about 8.4 percent of 1,151,724 US breast cancers, 2010 to 2014.","Odds of triple-negative diagnosis: non-Hispanic Black 2.27 (95 percent CI 2.23 to 2.31); Hispanic 1.22; age under 40 1.95; stage III 1.69; stage IV 1.47."],"whatItMeans":"The most recent national figure behind the statement that Black women in the United States have about twice the incidence of triple-negative breast cancer; trial enrolment has not matched it.","caveats":["Unadjusted odds ratios are the headline figures; adjusted results differed slightly.","The 8.4 percent share is lower than SEER's 12.2 percent, reflecting unknown-status coding across registries."],"changedPractice":false,"participants":1151724},{"id":"paper-atezolizumab-hcc-j-hepatol-2022","kind":"paper","name":"Updated efficacy and safety data from IMbrave150: Atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma","aka":[],"tldr":"Phase 2 or 3 results paper on Atezolizumab in Hepatocellular carcinoma, in Journal of hepatology (2022), one of the most cited Europe PMC records with Atezolizumab in its title.","summary":"Background & aims: IMbrave150 demonstrated that atezolizumab plus bevacizumab led to significantly improved overall survival (OS) and progression-free survival (PFS) compared with sorafenib in patients with unresectable hepatocellular carcinoma at the primary analysis (after a median 8.6 months of follow-up). We present updated data after 12 months of additional follow-up.\n\nMethods: Patients with systemic treatment-naive, unresectable hepatocellular carcinoma were randomized 2:1 to receive 1,200 mg atezolizumab plus 15 mg/kg bevacizumab intravenously every 3 weeks or 400 mg sorafenib orally twice daily in this open-label, phase III study. Co-primary endpoints were OS and PFS by independently assessed RECIST 1.1 in the intention-to-treat population. Secondary efficacy endpoints included objective response rates and exploratory subgroup efficacy analyses. This is a post hoc updated analysis of efficacy and safety.\n\nResults: From March 15, 2018, to January 30, 2019, 501 patients (intention-to-treat population) were randomly allocated to receive atezolizumab plus bevacizumab (n = 336) or sorafenib (n = 165). On August 31, 2020, after a median 15.6 (range, 0-28.6) months of follow-up, the median OS was 19.2 months (95% CI 17.0-23.7) with atezolizumab plus bevacizumab and 13.4 months (95% CI 11.4-16.9) with sorafenib (hazard ratio [HR] 0.66; 95% CI 0.52-0.85; descriptive p <0.001). The median PFS was 6.9 (95% CI 5.7-8.6) and 4.3 (95% CI 4.0-5.6) months in the respective treatment groups (HR 0.65; 95% CI 0.53-0.81; descriptive p < 0.001). Treatment-related grade 3/4 adverse events occurred in 143 (43%) of 329 and 72 (46%) of 156 safety-evaluable patients in the respective groups, and treatment-related grade 5 events occurred in 6 (2%) and 1 (<1%) patients.\n\nConclusion: After longer follow-up, atezolizumab plus bevacizumab maintained clinically meaningful survival benefits over sorafenib and had a safety profile consistent with the primary analysis.\n\nGov identifier: NCT03434379.\n\nLay summary: The primary analysis of IMbrave150 showed that atezolizumab plus bevacizumab had significantly greater benefits than sorafenib in patients with advanced hepatocellular carcinoma, but survival data were not yet mature. At this updated analysis done 12 months later, median overall survival was 5.8 months longer with atezolizumab plus bevacizumab than sorafenib, and the severity profile of treatment-related side effects remained similar. These updated results confirm atezolizumab plus bevacizumab as the first-line standard of care for advanced hepatocellular carcinoma.\n\nIndexed on Europe PMC as PubMed record 34902530 (DOI 10.1016/j.jhep.2021.11.030). Its title names Atezolizumab and its text names Hepatocellular carcinoma; PubMed types it as a clinical trial report (Research Support, Non-U.S. Gov't, Randomized Controlled Trial). It was matched automatically to the idea \"Immunotherapy downstaging to transplant with a safe washout\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Hepatol 2022","url":"https://doi.org/10.1016/j.jhep.2021.11.030"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34902530/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34902530"},{"label":"ClinicalTrials.gov NCT03434379","url":"https://clinicaltrials.gov/study/NCT03434379"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["imbrave150"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of hepatology","year":2022,"doi":"10.1016/j.jhep.2021.11.030","pmid":"34902530","authors":"Cheng AL, Qin S, Ikeda M, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Atezolizumab in Hepatocellular carcinoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Atezolizumab in the title and Hepatocellular carcinoma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-pharos-j-thorac-oncol-2025","kind":"paper","name":"Updated Efficacy and Safety From the Phase 2 PHAROS Study of Encorafenib Plus Binimetinib in Patients With BRAF V600E-Mutant Metastatic NSCLC-A Brief Report","aka":[],"tldr":"Published report from the PHAROS trial registered as NCT03915951, in Journal of Thoracic Oncology (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Introduction: The PHAROS primary analysis revealed robust antitumor activity and acceptable safety with encorafenib plus binimetinib in patients with BRAF V600E-mutant metastatic NSCLC (mNSCLC). We report results after 18 months of additional follow-up.\n\nMethods: In this ongoing open-label, single-arm, phase 2 study, patients with BRAF V600E-mutant mNSCLC (59 treatment-naive and 39 previously treated) received encorafenib 450 mg once daily and binimetinib 45 mg twice daily. Primary end point was objective response rate (ORR). Secondary end points included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.\n\nResults: At this data cutoff, median treatment duration with encorafenib plus binimetinib was 16.3 months in treatment-naive and 5.5 months in previously treated patients; minimum follow-up was approximately 32 and 22 months, respectively. In treatment-naive patients, the ORR was 75%, median DOR was 40.0 months, median PFS was 30.2 months, median OS was not estimable (95% confidence interval: 31.3-not estimable), and the 3-year OS probability was 53%. In previously treated patients, the ORR was 46%, median DOR was 16.7 months, median PFS was 9.3 months, median OS was 22.7 months, and the 3-year OS probability was 29%. Overall, the most frequent treatment-related adverse events were nausea (52%), diarrhea (44%), fatigue (33%), and vomiting (30%). Treatment-related adverse events led to dose reductions and permanent treatment discontinuations in 25 (26%) and 16 (16%) patients, respectively.\n\nConclusions: With longer follow-up, encorafenib plus binimetinib showed durable and clinically meaningful antitumor activity, especially in treatment-naive patients, with a manageable safety profile in patients with BRAF V600E-mutant mNSCLC.\n\nClinical trial information: ClinicalTrials.gov Identifier: NCT03915951.\n\nIndexed on Europe PMC as PubMed record 40480428 (DOI 10.1016/j.jtho.2025.05.023). Its abstract cites the registry id NCT03915951, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Thorac Oncol 2025","url":"https://doi.org/10.1016/j.jtho.2025.05.023"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40480428/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40480428"},{"label":"ClinicalTrials.gov NCT03915951","url":"https://clinicaltrials.gov/study/NCT03915951"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["pharos"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-thoracic-oncology"],"dependsOn":[],"notes":[],"journal":"Journal of Thoracic Oncology","year":2025,"doi":"10.1016/j.jtho.2025.05.023","pmid":"40480428","authors":"Riely GJ, Ahn MJ, Clarke JM, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03915951 with the most citations, so it is the natural first reading for anyone following the PHAROS trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-javelin-merkel-200-j-immunother-cancer-2018-update","kind":"paper","name":"Updated efficacy of avelumab in patients with previously treated metastatic Merkel cell carcinoma after ≥1 year of follow-up: JAVELIN Merkel 200, a phase 2 clinical trial","aka":[],"tldr":"Later report from the JAVELIN Merkel 200 trial registered as NCT02155647, in Journal for ImmunoTherapy of Cancer (2018); its title describes an updated or longer-term analysis.","summary":"Background: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer associated with poor survival outcomes in patients with distant metastatic disease (mMCC). In an initial analysis from JAVELIN Merkel 200, a phase 2, prospective, open-label, single-arm trial in mMCC, avelumab-a human anti-programmed death-ligand 1 (PD-L1) monoclonal antibody-showed promising efficacy and a safety profile that was generally manageable and tolerable. Here, we report the efficacy of avelumab after ≥1 year of follow-up in patients with distant mMCC that had progressed following prior chemotherapy for metastatic disease.\n\nPatients and methods: Patients received avelumab 10 mg/kg by 1-h intravenous infusion every 2 weeks until confirmed disease progression, unacceptable toxicity, or withdrawal. The primary endpoint was best overall response. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), and overall survival (OS).\n\nResults: Patients (N = 88) were followed for a minimum of 12 months. The confirmed objective response rate was 33.0% (95% CI, 23.3%-43.8%; complete response: 11.4%). An estimated 74% of responses lasted ≥1 year, and 72.4% of responses were ongoing at data cutoff. Responses were durable, with the median DOR not yet reached (95% CI, 18.0 months-not estimable), and PFS was prolonged; 1-year PFS and OS rates were 30% (95% CI, 21%-41%) and 52% (95% CI, 41%-62%), respectively. Median OS was 12.9 months (95% CI, 7.5-not estimable). Subgroup analyses suggested a higher probability of response in patients receiving fewer prior lines of systemic therapy, with a lower baseline disease burden, and with PD-L1-positive tumors; however, durable responses occurred irrespective of baseline factors, including tumor Merkel cell polyomavirus status.\n\nConclusions: With longer follow-up, avelumab continues to show durable responses and promising survival outcomes in patients with distant mMCC whose disease had progressed after chemotherapy.\n\nTrial registration: Clinicaltrials.gov identifier: NCT02155647.\n\nIndexed on Europe PMC as PubMed record 29347993 (DOI 10.1186/s40425-017-0310-x). Its abstract cites the registry id NCT02155647, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Immunother Cancer 2018","url":"https://doi.org/10.1186/s40425-017-0310-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29347993/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29347993"},{"label":"ClinicalTrials.gov NCT02155647","url":"https://clinicaltrials.gov/study/NCT02155647"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["javelin-merkel-200"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jitc"],"dependsOn":[],"notes":[],"journal":"Journal for ImmunoTherapy of Cancer","year":2018,"doi":"10.1186/s40425-017-0310-x","pmid":"29347993","authors":"Kaufman HL, Russell JS, Hamid O, et al.","paperType":"observational","findings":[],"whatItMeans":"A second publication from the JAVELIN Merkel 200 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-lindeman-lung-molecular-testing-guideline-jto-2018","kind":"paper","name":"Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors","aka":[],"tldr":"Three professional bodies set out what every laboratory must test for in lung cancer, which sample types are acceptable, and when a blood test may stand in for a piece of tumour.","summary":"An expert panel convened by the College of American Pathologists, the International Association for the Study of Lung Cancer and the Association for Molecular Pathology systematically reviewed the evidence since the 2013 guideline and drafted 18 new recommendations while updating three. The 2013 guideline was largely reaffirmed, with updates allowing testing of cytology samples, requiring improved assay sensitivity and recommending against immunohistochemistry for EGFR testing. Key new recommendations include ROS1 testing for all patients with adenocarcinoma; the inclusion of ERBB2, MET, BRAF, KRAS and RET for laboratories that perform next-generation sequencing panels; immunohistochemistry as an alternative to fluorescence in situ hybridisation for ALK and ROS1 testing; assays with 5% sensitivity for EGFR T790M in patients with secondary resistance to EGFR inhibitors; and the use of cell-free DNA to rule in targetable mutations when tissue is limited or hard to obtain.","asOf":"2026-09-25","links":[{"label":"Lindeman et al., J Thorac Oncol 2018: the CAP, IASLC and AMP molecular testing guideline for lung cancer","url":"https://doi.org/10.1016/j.jtho.2017.12.001"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29396253/"}],"tags":[],"related":["egfr-t790m","alk-fusion","ros1-fusion","met-ex14"],"cancers":["nsclc"],"sections":[],"technologies":["cgp","liquid-biopsy","histopathology-ihc","cytogenetics-fish","rna-seq"],"targets":["egfr","alk","ros1","ret","met","braf","kras","her2"],"drugs":[],"companies":[],"institutions":[],"pathways":["rtk-activation","nsclc-signalling"],"terms":["ngs","ihc","fish","ctdna","cfdna","biopsy","gene-fusion"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-thoracic-oncology"],"dependsOn":[],"notes":[],"journal":"Journal of Thoracic Oncology","year":2018,"doi":"10.1016/j.jtho.2017.12.001","pmid":"29396253","authors":"Lindeman NI, Cagle PT, Aisner DL, et al.","paperType":"guideline","findings":["ROS1 testing recommended for every patient with lung adenocarcinoma.","Cell-free DNA may rule a mutation in but not out when tissue is limited.","Assays for EGFR T790M in acquired resistance must reach 5% sensitivity.","Immunohistochemistry is acceptable for ALK and ROS1 screening and not for EGFR."],"whatItMeans":"It is the document that defines what a complete lung cancer molecular report looks like, and its asymmetry about plasma, rule in but never rule out, is the single most useful sentence in it.","caveats":["Published before MET exon 14, RET fusion, KRAS G12C, HER2 exon 20 insertion and NTRK fusion indications became routine, so practice now exceeds the text.","It sets minimum standards rather than describing what laboratories actually do.","Recommendations on tissue stewardship are general rather than prescriptive."],"changedPractice":true},{"id":"paper-alex-ann-oncol-2020-update","kind":"paper","name":"Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study","aka":[],"tldr":"Later report from the ALEX trial registered as NCT02075840, in Annals of Oncology (2020); its title describes an updated or longer-term analysis.","summary":"Background: The ALEX study demonstrated significantly improved progression-free survival (PFS) with alectinib versus crizotinib in treatment-naive ALK-positive non-small-cell lung cancer (NSCLC) at the primary data cut-off (9 February 2017). We report mature PFS (cut-off: 30 November 2018) and overall survival (OS) data up to 5 years (cut-off: 29 November 2019).\n\nPatients and methods: Patients with stage III/IV ALK-positive NSCLC were randomized to receive twice-daily alectinib 600 mg (n = 152) or crizotinib 250 mg (n = 151) until disease progression, toxicity, withdrawal or death. Primary end point: investigator-assessed PFS. Secondary end points included objective response rate, OS and safety.\n\nResults: Mature PFS data showed significantly prolonged investigator-assessed PFS with alectinib [hazard ratio (HR) 0.43, 95% confidence interval (CI) 0.32-0.58; median PFS 34.8 versus 10.9 months crizotinib]. Median duration of OS follow-up: 48.2 months alectinib, 23.3 months crizotinib. OS data remain immature (37% of events). Median OS was not reached with alectinib versus 57.4 months with crizotinib (stratified HR 0.67, 95% CI 0.46-0.98). The 5-year OS rate was 62.5% (95% CI 54.3-70.8) with alectinib and 45.5% (95% CI 33.6-57.4) with crizotinib, with 34.9% and 8.6% of patients still on study treatment, respectively. The OS benefit of alectinib was seen in patients with central nervous system metastases at baseline [HR 0.58 (95% CI 0.34-1.00)] and those without [HR 0.76 (95% CI 0.45-1.26)]. Median treatment duration was longer with alectinib (28.1 versus 10.8 months), and no new safety signals were observed.\n\nConclusions: Mature PFS data from ALEX confirmed significant improvement in PFS for alectinib over crizotinib in ALK-positive NSCLC. OS data remain immature, with a higher 5-year OS rate with alectinib versus crizotinib. This is the first global randomized study to show clinically meaningful improvement in OS for a next-generation tyrosine kinase inhibitor versus crizotinib in treatment-naive ALK-positive NSCLC.\n\nClinical trials number: NCT02075840.\n\nIndexed on Europe PMC as PubMed record 32418886 (DOI 10.1016/j.annonc.2020.04.478). Its abstract cites the registry id NCT02075840, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2020","url":"https://doi.org/10.1016/j.annonc.2020.04.478"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32418886/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32418886"},{"label":"ClinicalTrials.gov NCT02075840","url":"https://clinicaltrials.gov/study/NCT02075840"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["alex"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2020,"doi":"10.1016/j.annonc.2020.04.478","pmid":"32418886","authors":"Mok T, Camidge DR, Gadgeel SM, et al.","paperType":"rct","findings":[],"whatItMeans":"A second publication from the ALEX trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper."]},{"id":"paper-gehl-acta-oncol","kind":"paper","name":"Updated standard operating procedures for electrochemotherapy of cutaneous tumours and skin metastases","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 29577784 and published in Acta oncologica; the citing page links this DOI, which is how the record was matched.","summary":"Electrochemotherapy is now in routine clinical use to treat cutaneous metastases of any histology, and is listed in national and international guidelines for cutaneous metastases and primary skin cancer. Electrochemotherapy is used by dermatologists, surgeons, and oncologists, and for different degrees and manifestations of metastases to skin and primary skin tumours not amenable to surgery. This treatment utilises electric pulses to permeabilize cell membranes in tumours, thus allowing a dramatic increase of the cytotoxicity of anti-cancer agents. Response rates, often after only one treatment, are very high across all tumour types. The most frequent indications are cutaneous metastases from malignant melanoma and breast cancer. In 2006, standard operating procedures (SOPs) were written for this novel technology, greatly facilitating introduction and dissemination of the therapy. Since then considerable experience has been obtained treating a wider range of tumour histologies and increasing size of tumours which was not originally thought possible. A pan-European expert panel drawn from a range of disciplines from dermatology, general surgery, head and neck surgery, plastic surgery, and oncology met to form a consensus opinion to update the SOPs based on the experience obtained. This paper contains these updated recommendations for indications for electrochemotherapy, pre-treatment information and evaluation, treatment choices, as well as follow-up.\n\nIndexed on Europe PMC as PubMed record 29577784 (DOI 10.1080/0284186x.2018.1454602). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Acta Oncol 2018","url":"https://doi.org/10.1080/0284186x.2018.1454602"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29577784/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29577784"}],"tags":["europepmc-ingest"],"related":["electrochemotherapy-devices"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["acta-oncologica"],"dependsOn":[],"notes":[],"journal":"Acta oncologica","year":2018,"doi":"10.1080/0284186x.2018.1454602","pmid":"29577784","authors":"Gehl J, Sersa G, Matthiessen LW, et al.","paperType":"review","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-esmo-mbc-living-guideline-update-ann-oncol-2025","kind":"paper","name":"Updated treatment recommendations for systemic treatment: from the ESMO Metastatic Breast Cancer Living Guideline","aka":[],"tldr":"A 2025 letter recording the latest changes to Europe's continuously updated guideline for metastatic breast cancer, the mechanism through which first-line antibody-drug conjugate results enter European practice.","summary":"Letter in Annals of Oncology (2025) by Trapani, Martins-Branco, Curigliano, Gennari and colleagues announcing updated systemic treatment recommendations from the ESMO Metastatic Breast Cancer Living Guideline. Europe PMC indexes no abstract, so OnCo carries no figures from it; the current recommendations are read from the living guideline on the ESMO website, which for triple-negative disease incorporates the first-line antibody-drug conjugate trials as they are published.","asOf":"2026-09-24","links":[{"label":"Ann Oncol 2025","url":"https://doi.org/10.1016/j.annonc.2025.07.017"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40930896/"},{"label":"ESMO Metastatic Breast Cancer Living Guideline","url":"https://www.esmo.org/living-guidelines"}],"tags":["tnbc-evidence"],"related":["paper-esmo-metastatic-breast-cancer-guideline-ann-oncol-2021"],"cancers":["tnbc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["esmo"],"pathways":[],"terms":[],"trials":[],"people":["giuseppe-curigliano"],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2025,"doi":"10.1016/j.annonc.2025.07.017","pmid":"40930896","authors":"Trapani D, Martins-Branco D, Curigliano G, et al.","paperType":"guideline","findings":["No abstract is indexed on Europe PMC; the living guideline itself carries the recommendations."],"whatItMeans":"For a fast-moving disease the living guideline, not the 2021 paper, is where European recommendations for triple-negative breast cancer now change; readers should check the website rather than the journal.","caveats":["A letter announcing updates, not a full guideline text.","No abstract indexed."],"changedPractice":true},{"id":"paper-schnipper-j-clin-oncol","kind":"paper","name":"Updating the American Society of Clinical Oncology Value Framework: Revisions and Reflections in Response to Comments Received","aka":[],"tldr":"Paper cited by one idea page, indexed on Europe PMC as PubMed record 27247218 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Europe PMC indexes no abstract for this record; the title is the only text available.\n\nIndexed on Europe PMC as PubMed record 27247218 (DOI 10.1200/jco.2016.68.2518). Matched by DOI alone: one idea page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2016","url":"https://doi.org/10.1200/jco.2016.68.2518"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27247218/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/27247218"}],"tags":["europepmc-ingest"],"related":["idea-cost-indication-based-pricing"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2016,"doi":"10.1200/jco.2016.68.2518","pmid":"27247218","authors":"Schnipper LE, Davidson NE, Wollins DS, et al.","paperType":"observational","findings":[],"whatItMeans":"One idea page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-howlader-us-incidence-breast-subtypes-jnci-2014","kind":"paper","name":"US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status","aka":[],"tldr":"The first US national count of breast cancer by receptor subtype, from 2010 when cancer registries began recording HER2: 12.2 percent of cases were triple-negative, and Black women had the highest rate of that subtype.","summary":"Howlader, Altekruse, Li, Chen and colleagues assessed breast cancer subtypes defined by joint hormone receptor and HER2 status across the 28 percent of the US population covered by SEER registries, which began collecting HER2 in 2010, with age-specific rates for non-Hispanic white, non-Hispanic Black, non-Hispanic Asian Pacific Islander and Hispanic women and polytomous logistic regression on age, ethnicity, county poverty, registry, stage, grade, size and nodes. Among cases with known status, 36,810 (72.7 percent) were hormone receptor-positive/HER2-negative, 6,193 (12.2 percent) triple-negative, 5,240 (10.3 percent) hormone receptor-positive/HER2-positive and 2,328 (4.6 percent) hormone receptor-negative/HER2-positive; 6,912 (12 percent) were unknown. Non-Hispanic Black women had the highest triple-negative incidence; triple-negative patients were more likely to be non-Hispanic Black and Hispanic, 10 to 30 percent less likely to be diagnosed at older ages, and 6.4- to 20-fold more likely to present with high-grade disease.","asOf":"2026-09-24","links":[{"label":"J Natl Cancer Inst 2014","url":"https://doi.org/10.1093/jnci/dju055"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24777111/"}],"tags":["tnbc-evidence"],"related":[],"cancers":["tnbc","breast-hr-positive","breast-her2-positive"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nci"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-diversity"],"keyPapers":[],"journals":["jnci"],"dependsOn":[],"notes":[],"journal":"Journal of the National Cancer Institute","year":2014,"doi":"10.1093/jnci/dju055","pmid":"24777111","authors":"Howlader N, Altekruse SF, Li CI, et al.","paperType":"observational","findings":["Triple-negative: 6,193 of cases with known status (12.2 percent); 12 percent of cases had unknown receptor status.","Highest triple-negative incidence in non-Hispanic Black women; triple-negative tumours 6.4- to 20-fold more likely to be high grade."],"whatItMeans":"The denominator for US triple-negative disparity statistics and the origin of the 10 to 15 percent figure quoted for the subtype's share of breast cancer.","caveats":["First year of HER2 registry collection; 12 percent unknown status.","US population only; UK registries did not record HER2 comprehensively until later."],"changedPractice":false,"participants":57483},{"id":"paper-uspstf-crc-screening-45-jama-2021","kind":"paper","name":"US Preventive Services Task Force recommendation: colorectal cancer screening from age 45","aka":[],"tldr":"In 2021 the US Preventive Services Task Force lowered the recommended age to start colorectal cancer screening from 50 to 45 for average-risk adults, in response to rising rates in younger people.","summary":"Recommendation statement based on systematic review and modelling concluding with moderate certainty that screening adults aged 45 to 49 has moderate net benefit (B recommendation), continuing the A recommendation for ages 50 to 75, with a range of acceptable tests including colonoscopy, faecal immunochemical testing, stool DNA testing and CT colonography.","asOf":"2026-09-17","links":[{"label":"JAMA 2021","url":"https://doi.org/10.1001/jama.2021.6238"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34003218/"}],"tags":[],"related":[],"cancers":["early-onset-colorectal"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2021,"doi":"10.1001/jama.2021.6238","pmid":"34003218","authors":"US Preventive Services Task Force, Davidson KW, Barry MJ, et al.","paperType":"guideline","findings":[],"whatItMeans":"Screening from 45 is now standard in the United States and has been adopted or debated elsewhere; it is the main policy response to early-onset colorectal cancer.","caveats":["Modelling-based; uptake in the 45 to 49 group has been slow.","Benefit for those under 45 remains unaddressed."],"changedPractice":true},{"id":"paper-johnson-alternative-medicine-jnci-2018","kind":"paper","name":"Use of alternative medicine for cancer and its impact on survival","aka":[],"tldr":"People with curable breast, lung or bowel cancer who chose alternative medicine instead of conventional treatment were two and a half times as likely to die during follow-up as matched patients who had standard treatment.","summary":"Using the US National Cancer Database (2004 to 2013), the authors identified 281 patients with non-metastatic breast, prostate, lung or colorectal cancer whose only recorded treatment was 'other-unproven: cancer treatments administered by non-medical personnel', and matched each to two patients (560) who received conventional treatment on cancer type, age, stage, comorbidity, insurance, race, year and clinical group.\n\nAlternative medicine users were more likely to be younger, female, wealthier and better educated, and more likely to have breast or lung cancer and stage II or III disease. Five-year survival was lower with alternative medicine overall, and the adjusted hazard ratio for death was 2.50 across cancers, 5.68 in breast cancer, 4.57 in colorectal cancer and 2.17 in lung cancer; in prostate cancer, where observation is often reasonable, there was no significant difference. The companion JAMA Oncology paper showed that complementary medicine users were more likely to refuse surgery, chemotherapy, radiotherapy or hormone therapy and that this refusal explained their worse survival.","asOf":"2026-09-10","links":[{"label":"Johnson et al., Use of alternative medicine for cancer and its impact on survival (JNCI 2018)","url":"https://doi.org/10.1093/jnci/djx145"},{"label":"Companion analysis: complementary medicine, refusal of conventional therapy and survival (JAMA Oncol 2018)","url":"https://doi.org/10.1001/jamaoncol.2018.2487"}],"tags":["complementary"],"related":[],"cancers":["breast-hr-positive","tnbc","colorectal","nsclc","prostate"],"sections":[],"technologies":["alternative-medicine-instead-of-treatment","integrative-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-misinformation"],"keyPapers":[],"journals":["jnci"],"dependsOn":[],"notes":[],"journal":"JNCI: Journal of the National Cancer Institute","year":2018,"doi":"10.1093/jnci/djx145","authors":"Johnson SB, Park HS, Gross CP, Yu JB","paperType":"observational","findings":["281 alternative-medicine-only patients matched to 560 conventionally treated patients from the National Cancer Database, 2004 to 2013.","Hazard ratio for death with alternative medicine: 2.50 overall (95% CI 1.88 to 3.27).","By cancer: breast 5.68, colorectal 4.57, lung 2.17; prostate not significantly different.","Users were younger, more often female, with higher income and education, and more often had stage II or III disease."],"whatItMeans":"Complementary approaches used alongside treatment are one thing; substituting an alternative therapy for surgery, chemotherapy, radiotherapy or hormone therapy in a curable cancer is associated with a large increase in the risk of dying. The finding is the evidence base for offering complementary therapies inside cancer centres and for asking every patient, without judgement, what else they are using.","caveats":["Observational and reliant on a single coded field; the specific alternative therapies are unknown.","Patients who choose alternative medicine may differ in unmeasured ways, although matching and adjustment reduced the imbalance.","Follow-up ended at a median of around five years; the absolute survival difference varies by cancer and stage."],"changedPractice":false,"participants":841},{"id":"paper-liu-n-engl-j-med","kind":"paper","name":"Use of CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 32023374 and published in New England Journal of Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Background: Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has shown remarkable clinical efficacy in B-cell cancers. However, CAR T cells can induce substantial toxic effects, and the manufacture of the cells is complex. Natural killer (NK) cells that have been modified to express an anti-CD19 CAR have the potential to overcome these limitations.\n\nMethods: In this phase 1 and 2 trial, we administered HLA-mismatched anti-CD19 CAR-NK cells derived from cord blood to 11 patients with relapsed or refractory CD19-positive cancers (non-Hodgkin's lymphoma or chronic lymphocytic leukemia [CLL]). NK cells were transduced with a retroviral vector expressing genes that encode anti-CD19 CAR, interleukin-15, and inducible caspase 9 as a safety switch. The cells were expanded ex vivo and administered in a single infusion at one of three doses (1×10 5, 1×10 6, or 1×10 7 CAR-NK cells per kilogram of body weight) after lymphodepleting chemotherapy.\n\nResults: The administration of CAR-NK cells was not associated with the development of cytokine release syndrome, neurotoxicity, or graft-versus-host disease, and there was no increase in the levels of inflammatory cytokines, including interleukin-6, over baseline. The maximum tolerated dose was not reached. Of the 11 patients who were treated, 8 (73%) had a response; of these patients, 7 (4 with lymphoma and 3 with CLL) had a complete remission, and 1 had remission of the Richter's transformation component but had persistent CLL. Responses were rapid and seen within 30 days after infusion at all dose levels. The infused CAR-NK cells expanded and persisted at low levels for at least 12 months.\n\nConclusions: Among 11 patients with relapsed or refractory CD19-positive cancers, a majority had a response to treatment with CAR-NK cells without the development of major toxic effects. (Funded by the M.D. Anderson Cancer Center CLL and Lymphoma Moonshot and the National Institutes of Health; ClinicalTrials.gov number, NCT03056339.).\n\nIndexed on Europe PMC as PubMed record 32023374 (DOI 10.1056/nejmoa1910607). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2020","url":"https://doi.org/10.1056/nejmoa1910607"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32023374/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/32023374"}],"tags":["europepmc-ingest"],"related":["car-nk-macrophage"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2020,"doi":"10.1056/nejmoa1910607","pmid":"32023374","authors":"Liu E, Marin D, Banerjee P, et al.","paperType":"observational","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-andrea-decensi-j-clin-oncol-2019","kind":"paper","name":"Use of Endocrine Therapy for Breast Cancer Risk Reduction: ASCO Clinical Practice Guideline Update","aka":[],"tldr":"Paper by Andrea DeCensi indexed on Europe PMC as PubMed record 31479306, in Journal of Clinical Oncology (2019), one of the most cited records naming an author with this name at E.O. Ospedali Galliera.","summary":"Purpose: To update the ASCO guideline on pharmacologic interventions for breast cancer risk reduction and provide guidance on clinical issues that arise when deciding to use endocrine therapy for breast cancer risk reduction.\n\nMethods: An Expert Panel conducted targeted systematic literature reviews to identify new studies.\n\nResults: A randomized clinical trial that evaluated the use of anastrozole for reduction of estrogen receptor-positive breast cancers in postmenopausal women at increased risk of developing breast cancer provided the predominant basis for the update.\n\nUpdated recommendations: In postmenopausal women at increased risk, the choice of endocrine therapy now includes anastrozole (1 mg/day) in addition to exemestane (25 mg/day), raloxifene (60 mg/day), or tamoxifen (20 mg/day). The decision regarding choice of endocrine therapy should take into consideration age, baseline comorbidities, and adverse effect profiles. Clinicians should not prescribe anastrozole, exemestane, or raloxifene for breast cancer risk reduction to premenopausal women. Tamoxifen 20 mg/day for 5 years is still considered standard of care for risk reduction in premenopausal women who are at least 35 years old and have completed childbearing. Data on low-dose tamoxifen as an alternative to the standard dose for both pre- and postmenopausal women with intraepithelial neoplasia are discussed in the Clinical Considerations section of this article. Additional information is available at www.asco.org/breast-cancer-guidelines.\n\nIndexed on Europe PMC as PubMed record 31479306 (DOI 10.1200/jco.19.01472). Its author list gives \"DeCensi A\" with the affiliation \"National Hospital E.O. Ospedali Galliera S.C. Oncologia Medica, Genoa, Italy; and Queen Mary University of London, United Kingdom\", which names E.O. Ospedali Galliera; that is how the record was matched to Andrea DeCensi, and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2019","url":"https://doi.org/10.1200/jco.19.01472"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31479306/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31479306"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["andrea-decensi"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2019,"doi":"10.1200/jco.19.01472","pmid":"31479306","authors":"Visvanathan K, Fabian CJ, Bantug E, et al.","paperType":"guideline","findings":[],"whatItMeans":"One of the most cited papers Europe PMC returns for Andrea DeCensi at E.O. Ospedali Galliera, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship."]},{"id":"paper-chernet-oncotarget","kind":"paper","name":"Use of genetically encoded, light-gated ion translocators to control tumorigenesis","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 26988909 and published in Oncotarget; the citing page links this DOI, which is how the record was matched.","summary":"It has long been known that the resting potential of tumor cells is depolarized relative to their normal counterparts. More recent work has provided evidence that resting potential is not just a readout of cell state: it regulates cell behavior as well. Thus, the ability to control resting potential in vivo would provide a powerful new tool for the study and treatment of tumors, a tool capable of revealing living-state physiological information impossible to obtain using molecular tools applied to isolated cell components. Here we describe the first use of optogenetics to manipulate ion-flux mediated regulation of membrane potential specifically to prevent and cause regression of oncogene-induced tumors. Injection of mutant-KRAS mRNA induces tumor-like structures with many documented similarities to tumors, in Xenopus tadpoles. We show that expression and activation of either ChR2D156A, a blue-light activated cation channel, or Arch, a green-light activated proton pump, both of which hyperpolarize cells, significantly lowers the incidence of KRAS tumor formation. Excitingly, we also demonstrate that activation of co-expressed light-activated ion translocators after tumor formation significantly increases the frequency with which the tumors regress in a process called normalization. These data demonstrate an optogenetic approach to dissect the biophysics of cancer. Moreover, they provide proof-of-principle for a novel class of interventions, directed at regulating cell state by targeting physiological regulators that can over-ride the presence of mutations.\n\nIndexed on Europe PMC as PubMed record 26988909 (DOI 10.18632/oncotarget.8036). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Oncotarget 2016","url":"https://doi.org/10.18632/oncotarget.8036"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26988909/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26988909"}],"tags":["europepmc-ingest"],"related":["bioelectric-theory-of-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["oncotarget"],"dependsOn":[],"notes":[],"journal":"Oncotarget","year":2016,"doi":"10.18632/oncotarget.8036","pmid":"26988909","authors":"Chernet BT, Adams DS, Lobikin M, et al.","paperType":"basic","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-asco-pembrolizumab-early-tnbc-rapid-update-jco-2022","kind":"paper","name":"Use of Immune Checkpoint Inhibitor Pembrolizumab in the Treatment of High-Risk, Early-Stage Triple-Negative Breast Cancer: ASCO Guideline Rapid Recommendation Update","aka":[],"tldr":"The 2022 fast-track amendment in which the US oncology society added pembrolizumab before and after surgery for high-risk early triple-negative breast cancer, a year after its main guideline had said the evidence was insufficient.","summary":"ASCO Rapid Recommendation Update by Korde, Somerfield, Hershman and the neoadjuvant therapy guideline expert panel. Rapid updates highlight revisions to selected ASCO guideline recommendations in response to new, practice-changing data, are supported by an evidence review and follow the ASCO Guideline Methodology Manual; their goal is to disseminate updated recommendations quickly. This update responded to the KEYNOTE-522 event-free survival result and the July 2021 US approval of pembrolizumab with chemotherapy as neoadjuvant treatment, continued as a single agent after surgery, for high-risk early-stage triple-negative breast cancer.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2022","url":"https://doi.org/10.1200/JCO.22.00503"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35417251/"}],"tags":["tnbc-evidence"],"related":["paper-asco-neoadjuvant-therapy-breast-guideline-jco-2021"],"cancers":["tnbc"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["pembrolizumab"],"companies":[],"institutions":["asco"],"pathways":[],"terms":[],"trials":["keynote-522","optimice-pcr"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2022,"doi":"10.1200/JCO.22.00503","pmid":"35417251","authors":"Korde LA, Somerfield MR, Hershman DL, et al.","paperType":"guideline","findings":["Rapid update mechanism: an evidence review and the ASCO methodology manual applied to a single practice-changing result.","Adds pembrolizumab with neoadjuvant chemotherapy, continued after surgery, for high-risk early-stage triple-negative breast cancer."],"whatItMeans":"Shows how quickly the standard moved: the 2021 guideline and its reversal are 15 months apart.","caveats":["Abstract on Europe PMC describes the rapid update process rather than the recommendation wording; the recommendation is read from the article.","Does not address pembrolizumab omission after pathological complete response, now under test in OptimICE-pCR."],"changedPractice":true},{"id":"paper-kris-lung-cancer-mutation-consortium-jama-2014","kind":"paper","name":"Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs","aka":[],"tldr":"Fourteen American centres tested a thousand lung adenocarcinomas for ten genes at once and found a driver in about two thirds. The patients whose treatment was chosen to match their driver lived about a year longer.","summary":"From 2009 to 2012, 14 sites enrolled patients with metastatic lung adenocarcinoma and tested their tumours for ten oncogenic drivers. Tumours from 1,007 patients were tested for at least one gene and 733 for all ten. An oncogenic driver was found in 466 of 733, 64%. Among those 733 tumours, 182 had KRAS (25%), 122 sensitising EGFR (17%), 57 ALK rearrangement (8%), 29 other EGFR (4%), 24 two or more genes (3%), 19 ERBB2 (3%), 16 BRAF (2%), 6 PIK3CA, 5 MET amplification, 5 NRAS and 1 MEK1, with no AKT1. Results were used to select a targeted therapy or trial in 275 of 1,007 patients, 28%. Median survival was 3.5 years for the 260 patients with an oncogenic driver who received genotype-directed therapy against 2.4 years for the 318 with a driver who did not, with a propensity-adjusted hazard ratio of 0.69.","asOf":"2026-09-25","links":[{"label":"Kris et al., JAMA 2014: multiplexed driver testing in 1,007 lung adenocarcinomas (Lung Cancer Mutation Consortium)","url":"https://doi.org/10.1001/jama.2014.3741"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24846037/"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":["cgp","cytogenetics-fish"],"targets":["kras","egfr","alk","her2","braf","pik3ca","met","nras"],"drugs":[],"companies":[],"institutions":["mskcc","vanderbilt-ingram","md-anderson"],"pathways":["nsclc-signalling","rtk-activation","ras-mapk"],"terms":["driver-mutation","ngs","wild-type"],"trials":[],"people":["lecia-sequist"],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2014,"doi":"10.1001/jama.2014.3741","pmid":"24846037","authors":"Kris MG, Johnson BE, Berry LD, et al.","paperType":"observational","findings":["An oncogenic driver in 466 of 733 fully genotyped lung adenocarcinomas, 64%.","KRAS 25%, sensitising EGFR 17%, ALK rearrangement 8%, ERBB2 3%, BRAF 2%.","Multiplexed testing guided treatment in 28% of all patients tested.","Median survival 3.5 against 2.4 years with matched therapy, adjusted hazard ratio 0.69."],"whatItMeans":"It is the study that made multiplex testing standard practice in lung adenocarcinoma, by showing both that most tumours have a driver and that finding it changes what patients receive.","caveats":["Not randomised: patients who received matched therapy differed from those who did not in ways propensity adjustment cannot fully remove.","Ten genes only, so ROS1, RET, NTRK and MET exon 14 were not counted.","Conducted before immunotherapy, so the comparator has changed."],"changedPractice":true,"participants":1007},{"id":"paper-moyer-uspstf-prostate-screening-ann-intern-med-2012","kind":"paper","name":"USPSTF 2012: screening for prostate cancer, recommendation statement (grade D)","aka":["USPSTF 2012 prostate","Moyer 2012","grade D prostate screening"],"tldr":"In 2012 the American preventive services body recommended against PSA screening for every man at every age. It is the most consequential negative screening recommendation ever made, and it was reversed six years later.","summary":"The United States Preventive Services Task Force, reporting through Virginia Moyer, updated its 2008 statement after reviewing the evidence on the benefits and harms of prostate-specific antigen screening and of treating screen-detected localised disease. The recommendation was grade D: recommend against, for men in the general United States population regardless of age.\n\nThe statement was made in the light of PLCO, which had found no mortality benefit, and ERSPC, which had found a small one at a high cost in overdiagnosis. Prostate-specific antigen testing and prostate biopsy rates fell in the United States afterwards, and so, over the following years, did the proportion of cancers diagnosed at a localised stage. The 2018 update (paper-uspstf-prostate-screening-jama-2018) moved men aged 55 to 69 to grade C, shared decision-making, and left men aged 70 and over at grade D.","asOf":"2026-09-25","links":[{"label":"Ann Intern Med 2012","url":"https://doi.org/10.7326/0003-4819-157-2-201207170-00459"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22801674/"},{"label":"USPSTF: prostate cancer screening","url":"https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/prostate-cancer-screening"}],"tags":["prostate-evidence"],"related":["paper-uspstf-prostate-screening-jama-2018","paper-andriole-plco-prostate-screening-nejm-2009","paper-schroder-erspc-screening-mortality-nejm-2009","prostate-roadmap"],"cancers":["prostate","prostate-low-risk"],"sections":["early-detection","prevention"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["psa","screening","overdiagnosis","overtreatment","lead-time-bias"],"trials":[],"people":[],"bottlenecks":["b-overdiagnosis","b-early-detection","b-prevention-adoption","b-knowledge-diffusion"],"keyPapers":[],"journals":["annals-internal-medicine"],"dependsOn":[],"notes":[],"journal":"Annals of Internal Medicine","year":2012,"doi":"10.7326/0003-4819-157-2-201207170-00459","pmid":"22801674","authors":"Moyer VA, U.S. Preventive Services Task Force.","paperType":"guideline","findings":["Grade D recommendation: the task force recommends against prostate-specific antigen-based screening for prostate cancer.","The recommendation applied to men in the general United States population regardless of age.","It did not cover use of the prostate-specific antigen test for surveillance after diagnosis or treatment, which was outside the task force's scope.","It updated the 2008 statement after review of new evidence on the benefits and harms of screening and of treating localised screen-detected disease."],"whatItMeans":"The clearest case in cancer screening of a national body acting on the harms rather than the headline. Whether it was right is still argued: testing and localised-stage diagnosis fell, and the long-term effect on metastatic presentation and mortality is the subject of the studies that followed.","caveats":["A recommendation statement, not new evidence; it rests on the screening trials and the lead-time models, which are recorded separately.","A blanket recommendation across all ages and risk groups, including men at high familial or ancestral risk, which is the criticism that drove the 2018 revision.","United States practice; other countries reached different conclusions from the same trials."],"changedPractice":true},{"id":"paper-uspstf-prostate-screening-jama-2018","kind":"paper","name":"USPSTF 2018: screening for prostate cancer, recommendation statement (grade C at 55 to 69, grade D at 70 and over)","aka":["USPSTF 2018 prostate","grade C prostate screening","shared decision making prostate screening"],"tldr":"Six years after recommending against PSA testing for everyone, the same body changed its mind for men aged 55 to 69 and said the decision should be theirs. The statement puts the numbers on both sides: about 1.3 deaths prevented per 1,000 men screened, and one in five who have surgery left with long-term incontinence.","summary":"The United States Preventive Services Task Force updated the 2012 grade D statement after reviewing the trials, commissioning a review of decision-analysis models and commissioning a separate review of the overdiagnosis rate, including in subgroups at higher risk: older men, African American men and men with a family history.\n\nThe 2018 statement is unusually useful to read as a patient because it states the benefit and the harm in the same units. Screening men aged 55 to 69 may prevent about 1.3 prostate cancer deaths and about 3 cases of metastatic disease per 1,000 men screened over about 13 years. Against that: about 1 in 5 men who have radical prostatectomy develop long-term urinary incontinence and 2 in 3 experience long-term erectile dysfunction. The task force concluded the net benefit is small for some men and that clinicians should not screen men who do not express a preference for it.","asOf":"2026-09-25","links":[{"label":"JAMA 2018","url":"https://doi.org/10.1001/jama.2018.3710"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29801017/"},{"label":"USPSTF: prostate cancer screening","url":"https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/prostate-cancer-screening"}],"tags":["prostate-evidence"],"related":["paper-moyer-uspstf-prostate-screening-ann-intern-med-2012","paper-loeb-overdiagnosis-overtreatment-prostate-eur-urol-2014","paper-protect-15-year-nejm-2023","idea-acc-embedded-decision-aids","prostate-roadmap"],"cancers":["prostate","prostate-low-risk","prostate-intermediate-risk"],"sections":["early-detection","prevention"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["psa","screening","overdiagnosis","quality-of-life","overtreatment","number-needed-to-screen","other-cause-mortality"],"trials":[],"people":[],"bottlenecks":["b-overdiagnosis","b-early-detection","b-patient-voice","b-trial-diversity"],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2018,"doi":"10.1001/jama.2018.3710","pmid":"29801017","authors":"US Preventive Services Task Force, Grossman DC, Curry SJ, et al.","paperType":"guideline","findings":["Screening programmes in men aged 55 to 69 may prevent approximately 1.3 deaths from prostate cancer over approximately 13 years per 1,000 men screened.","Screening programmes may also prevent approximately 3 cases of metastatic prostate cancer per 1,000 men screened.","About 1 in 5 men who undergo radical prostatectomy develop long-term urinary incontinence, and 2 in 3 will experience long-term erectile dysfunction.","Grade C for men aged 55 to 69: the decision should be an individual one after discussion of benefits and harms, and clinicians should not screen men who do not express a preference for screening.","Grade D for men aged 70 and over: the potential benefits do not outweigh the expected harms, because of increased risk of false-positive results and diagnostic and treatment harms.","The statement records a lifetime risk of being diagnosed with prostate cancer of approximately 13 percent and of dying of it of 2.5 percent, with a median age at death from prostate cancer of 80 years."],"whatItMeans":"The current shape of the screening question in the United States, and the best short statement of the trade-off in numbers a man can weigh. The three-to-one ratio between metastatic cases prevented and deaths prevented is also the argument for using metastatic presentation, not mortality, to judge a screening programme sooner.","caveats":["A recommendation on prostate-specific antigen-based screening as practised in the trials, which did not include magnetic resonance imaging triage or modern active surveillance.","The harms quoted are the harms of treatment, so they fall on the men who are treated rather than on everyone screened; the size of the harm therefore depends on how many screen-detected cancers are managed conservatively.","Evidence in African American men and men with a family history was reviewed but is thinner than in the general population, and the recommendation does not set separate thresholds for them."],"changedPractice":true},{"id":"paper-rothwell-nat-med","kind":"paper","name":"Utility of ctDNA to support patient selection for early phase clinical trials: the TARGET study","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 31011204 and published in Nature Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) supports blood-based genomic profiling but is not yet routinely implemented in the setting of a phase I trials clinic. TARGET is a molecular profiling program with the primary aim to match patients with a broad range of advanced cancers to early phase clinical trials on the basis of analysis of both somatic mutations and copy number alterations (CNA) across a 641 cancer-associated-gene panel in a single ctDNA assay. For the first 100 TARGET patients, ctDNA data showed good concordance with matched tumor and results were turned round within a clinically acceptable timeframe for Molecular Tumor Board (MTB) review. When a 2.5% variant allele frequency (VAF) threshold was applied, actionable mutations were identified in 41 of 100 patients, and 11 of these patients received a matched therapy. These data support the application of ctDNA in this early phase trial setting where broad genomic profiling of contemporaneous tumor material enhances patient stratification to novel therapies and provides a practical template for bringing routinely applied blood-based analyses to the clinic.\n\nIndexed on Europe PMC as PubMed record 31011204 (DOI 10.1038/s41591-019-0380-z). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Med 2019","url":"https://doi.org/10.1038/s41591-019-0380-z"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31011204/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31011204"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["target-national"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2019,"doi":"10.1038/s41591-019-0380-z","pmid":"31011204","authors":"Rothwell DG, Ayub M, Cook N, et al.","paperType":"observational","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-basu-single-dose-hpv-lancet-oncol-2021","kind":"paper","name":"Vaccine efficacy against persistent HPV 16/18 infection at 10 years after one, two and three doses of quadrivalent HPV vaccine in girls in India","aka":[],"tldr":"Ten years after vaccination, Indian girls who had received a single dose of HPV vaccine were as well protected against the cancer-causing HPV types as those who had two or three doses, which let the world switch to one-dose programmes.","summary":"Multicentre prospective cohort study arising from an IARC trial at nine Indian centres whose recruitment was suspended in 2010, leaving cohorts of girls aged 10 to 18 who had received one (4,949), two (4,980) or three (4,348) doses of quadrivalent HPV vaccine. At a median follow-up of 9.0 years (IQR 8.2-9.6), vaccine efficacy against persistent HPV 16/18 infection was 95.4% (95% CI 85.0-99.9) after one dose, 93.1% (77.3-99.8) after two and 93.3% (77.5-99.7) after three, compared with unvaccinated married women of similar age.","asOf":"2026-09-10","links":[{"label":"Lancet Oncology 2021","url":"https://doi.org/10.1016/S1470-2045(21)00453-8"}],"tags":[],"related":[],"cancers":["cervical"],"sections":[],"technologies":["hpv-vaccine"],"targets":[],"drugs":["gardasil-9","cervavac"],"companies":[],"institutions":["iarc"],"pathways":[],"terms":[],"trials":["iarc-india-hpv-dose-study","ken-she"],"people":["basu-partha","sankaranarayanan-rengaswamy"],"bottlenecks":["b-prevention-adoption","b-dose-optimisation"],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"Lancet Oncology","year":2021,"doi":"10.1016/S1470-2045(21)00453-8","authors":"Basu P, Malvi SG, Joshi S, et al.","paperType":"observational","findings":["Single-dose efficacy against persistent HPV 16/18 infection 95.4% at a median of 9 years.","Two-dose 93.1% and three-dose 93.3%: no meaningful difference between schedules.","Antibody levels after one dose were lower but stable over time.","Cohorts were defined by default after the 2010 suspension, not by randomisation to one dose."],"whatItMeans":"One dose protects. WHO endorsed one- or two-dose schedules in 2022, halving the cost and the logistics of vaccinating girls, which is decisive for India (about 127,500 cervical cancers a year) and for the global elimination target. It also removed the main barrier to India's national programme with its home-made vaccine.","caveats":["Non-randomised comparison of dose groups; confounding by who happened to receive fewer doses cannot be fully excluded.","Endpoint is persistent infection, not cervical cancer, although the link is well established.","Quadrivalent vaccine; nonavalent and bivalent products rely on separate evidence (KEN SHE, Costa Rica)."],"changedPractice":true,"participants":17729},{"id":"paper-chalasani-clin-gastroenterol-hepatol","kind":"paper","name":"Validation of a Novel Multitarget Blood Test Shows High Sensitivity to Detect Early Stage Hepatocellular Carcinoma","aka":[],"tldr":"Paper cited by one idea page, indexed on Europe PMC as PubMed record 34391922 and published in Clinical gastroenterology and hepatology; the citing page links this DOI, which is how the record was matched.","summary":"Background & aims: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Although biannual ultrasound surveillance with or without α-fetoprotein (AFP) testing is recommended for at-risk patients, sensitivity for early stage HCC, for which potentially curative treatments exist, is suboptimal. We conducted studies to establish the multitarget HCC blood test (mt-HBT) algorithm and cut-off values and to validate test performance in patients with chronic liver disease.\n\nMethods: Algorithm development and clinical validation studies were conducted with participants in an international, multicenter, case-control study. Study subjects had underlying cirrhosis or chronic hepatitis B virus; HCC cases were diagnosed per the American Association for the Study of Liver Diseases criteria and controls were matched for age and liver disease etiology. Whole blood and serum were shipped to a central laboratory and processed while blinded to case/control status. An algorithm was developed for the mt-HBT, which incorporates methylation biomarkers (HOXA1, TSPYL5, and B3GALT6), AFP, and sex.\n\nResults: In algorithm development, with 136 HCC cases (60% early stage) and 404 controls, the mt-HBT showed 72% sensitivity for early stage HCC at 88% specificity. Test performance was validated in an independent cohort of 156 HCC cases (50% early stage) and 245 controls, showing 88% overall sensitivity, 82% early stage sensitivity, and 87% specificity. Early stage sensitivity in clinical validation was significantly higher than AFP at 20 ng/mL or greater (40%; P <.0001) and GALAD (gender, age, Lens culinaris agglutinin-reactive AFP, AFP, and des-γ-carboxy-prothrombin score) of -0.63 or greater (71%; P =.03), although AFP and GALAD at these cut-off values had higher specificities (100% and 93%, respectively).\n\nConclusions: The mt-HBT may significantly improve early stage HCC detection for patients undergoing HCC surveillance, a critical step to increasing curative treatment opportunities and reducing mortality. ClinicalTrials.gov number NCT03628651.\n\nIndexed on Europe PMC as PubMed record 34391922 (DOI 10.1016/j.cgh.2021.08.010). Matched by DOI alone: one idea page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Clin Gastroenterol Hepatol 2022","url":"https://doi.org/10.1016/j.cgh.2021.08.010"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34391922/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34391922"}],"tags":["europepmc-ingest"],"related":["idea-hcc-blood-surveillance"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Clinical gastroenterology and hepatology","year":2022,"doi":"10.1016/j.cgh.2021.08.010","pmid":"34391922","authors":"Chalasani NP, Porter K, Bhattacharya A, et al.","paperType":"observational","findings":[],"whatItMeans":"One idea page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-giannis-ajcc8-gallbladder-staging-validation-cancers-2021","kind":"paper","name":"Validation of the 8th Edition American Joint Commission on Cancer (AJCC) Gallbladder Cancer Staging System: Prognostic Discrimination and Identification of Key Predictive Factors","aka":[],"tldr":"Tested on 7,743 US patients, the 2017 gallbladder cancer staging system predicted survival no better than the 2010 one it replaced.","summary":"National Cancer Database analysis of 7,743 gallbladder carcinoma patients diagnosed 2005 to 2015 comparing AJCC seventh and eighth editions; 202 patients were reclassified. Overall survival concordance indices were 0.665 (eighth) and 0.663 (seventh). Within T1, T2 and T3, N2 carried higher mortality than N1. In stage IIIB or higher with known grade, higher stage, Charlson-Deyo score of 2 or more, higher grade and unknown nodal status raised the risk of death, while diagnosis after 2013, treatment at an academic centre, chemotherapy and radiotherapy lowered it; chemotherapy was associated with lower mortality in T3 to T4 and radiotherapy in T2 to T4. The authors call for prospective validation of the T2 subclassification.","asOf":"2026-09-24","links":[{"label":"Cancers 2021","url":"https://doi.org/10.3390/cancers13030547"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33535552/"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tnm-staging","t2a-versus-t2b","radiotherapy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Cancers","year":2021,"doi":"10.3390/cancers13030547","pmid":"33535552","authors":"Giannis D, Cerullo M, Moris D, et al.","paperType":"observational","findings":["Concordance index for overall survival 0.665 (AJCC 8th) vs 0.663 (AJCC 7th).","Radiotherapy associated with lower risk of death in T2 to T4 and chemotherapy in T3 to T4 disease (univariate, registry data)."],"whatItMeans":"Anatomy alone explains only about two thirds of the ranking of who lives longer; the 2026 staging review makes the same point and argues for molecular and nodal-burden modifiers alongside TNM.","caveats":["Registry data with missing grade and nodal information.","Treatment associations are confounded by selection."],"changedPractice":false,"participants":7743},{"id":"paper-tarpswg-retroperitoneal-sarcoma-gronchi-ann-surg-2016","kind":"paper","name":"Variability in patterns of recurrence after resection of primary retroperitoneal sarcoma (TARPSWG)","aka":[],"tldr":"Pooling over a thousand patients from eight expert centres showed that recurrence after retroperitoneal sarcoma surgery depends on histology: liposarcoma recurs locally, leiomyosarcoma spreads distantly, which shapes follow-up and the case for radiotherapy or chemotherapy by subtype.","summary":"Retrospective analysis of 1,007 patients with primary retroperitoneal sarcoma treated with curative-intent surgery at eight Trans-Atlantic Retroperitoneal Sarcoma Working Group centres, describing patterns of local and distant recurrence and survival by histology.\n\nFive-year overall survival was 67 percent; well-differentiated liposarcoma recurred locally with almost no metastases, dedifferentiated liposarcoma recurred both ways, and leiomyosarcoma had a high distant recurrence rate with low local recurrence.","asOf":"2026-09-17","links":[{"label":"Ann Surg 2016","url":"https://doi.org/10.1097/SLA.0000000000001447"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26727100/"}],"tags":[],"related":[],"cancers":["retroperitoneal-sarcoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Annals of Surgery","year":2016,"doi":"10.1097/SLA.0000000000001447","pmid":"26727100","authors":"Gronchi A, Strauss DC, Miceli R, et al.","paperType":"observational","findings":["Five-year overall survival 67 percent after complete resection.","Local recurrence dominant in liposarcoma; distant recurrence dominant in leiomyosarcoma."],"whatItMeans":"Histology-specific strategies, such as considering neoadjuvant chemotherapy for leiomyosarcoma and high-grade dedifferentiated liposarcoma in STRASS2, follow from these patterns.","caveats":["Retrospective data from expert centres; results may not generalise to non-specialist surgery."],"changedPractice":true,"participants":1007},{"id":"paper-jcog9801-vcap-amp-vecp-adult-t-cell-leukaemia-jco-2007","kind":"paper","name":"VCAP-AMP-VECP compared with biweekly CHOP for adult T-cell leukemia-lymphoma: Japan Clinical Oncology Group Study JCOG9801","aka":["JCOG9801","Tsukasaki 2007","LSG15"],"tldr":"The only randomised trial run exclusively in the virus-driven adult T-cell leukaemia found an intensive Japanese regimen produced more complete remissions than standard chemotherapy, at considerable cost in toxicity.","summary":"A randomised controlled trial conducted exclusively in human T-lymphotropic virus type 1-associated adult T-cell leukaemia-lymphoma. Previously untreated patients with aggressive disease were assigned to six courses of VCAP-AMP-VECP every four weeks or eight courses of biweekly CHOP, both with granulocyte colony-stimulating factor support and intrathecal prophylaxis. 118 patients were enrolled.\n\nThe complete response rate was 40 per cent with VCAP-AMP-VECP against 25 per cent with biweekly CHOP (p = 0.020). One-year progression-free survival was 28 against 16 per cent (p = 0.100, two-sided p = 0.200) and three-year overall survival 24 against 13 per cent (p = 0.085, two-sided p = 0.169). Grade 4 neutropenia occurred in 98 against 83 per cent, grade 4 thrombocytopenia in 74 against 17 per cent and grade 3 or 4 infection in 32 against 15 per cent, with three toxic deaths in the VCAP-AMP-VECP arm.","asOf":"2026-10-01","links":[{"label":"Journal of Clinical Oncology 2007","url":"https://doi.org/10.1200/JCO.2007.11.9958"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/17968021/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/17968021"}],"tags":["lymphoma-evidence"],"related":["paper-poiesz-htlv-retrovirus-cutaneous-t-cell-lymphoma-pnas-1980","paper-hinuma-adult-t-cell-leukaemia-antigen-pnas-1981","lymphoma-roadmap"],"cancers":["peripheral-t-cell-lymphoma","non-hodgkin-lymphoma"],"sections":["chemotherapy"],"technologies":[],"targets":[],"drugs":["vincristine","cyclophosphamide","doxorubicin","prednisone","etoposide","carboplatin"],"companies":[],"institutions":[],"pathways":[],"terms":["complete-response","intrathecal-therapy"],"trials":["jcog9801"],"people":[],"bottlenecks":["b-rare-cancers","b-global-access"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2007,"doi":"10.1200/JCO.2007.11.9958","pmid":"17968021","authors":"Tsukasaki K, Utsunomiya A, Fukuda H, et al.","paperType":"rct","findings":["The complete response rate was 40 per cent with VCAP-AMP-VECP against 25 per cent with biweekly CHOP (p = 0.020).","One-year progression-free survival was 28 per cent against 16 per cent (p = 0.100, two-sided p = 0.200).","Three-year overall survival was 24 per cent against 13 per cent (p = 0.085, two-sided p = 0.169).","Grade 4 thrombocytopenia occurred in 74 per cent against 17 per cent, and grade 3 or 4 infection in 32 against 15 per cent.","Three toxic deaths occurred in the VCAP-AMP-VECP arm."],"whatItMeans":"The Japanese standard regimen for aggressive adult T-cell leukaemia/lymphoma rests on this trial. Three-year overall survival of 24 per cent with the better arm is the plainest statement of how much room remains, and is why allogeneic transplantation, mogamulizumab and antiviral approaches have all been pursued since.","caveats":["The survival and progression-free survival differences did not reach statistical significance on two-sided testing; the significant endpoint was complete response rate.","118 patients is small, and the trial has never been repeated.","Conducted entirely in Japan, where the virus is endemic and supportive care is intensive; the regimen has not been adopted widely elsewhere.","OnCo has no cancer record for adult T-cell leukaemia/lymphoma yet, so this record is attached to peripheral T-cell lymphoma."],"changedPractice":true,"participants":118},{"id":"paper-ve-basket-vemurafenib-erdheim-chester-lch-jama-oncol-2018","kind":"paper","name":"VE-BASKET: vemurafenib for BRAF V600-mutant Erdheim-Chester disease and Langerhans cell histiocytosis","aka":[],"tldr":"The BRAF inhibitor vemurafenib shrank disease in most adults with BRAF-mutant Erdheim-Chester disease, and the responses lasted, leading to the first drug approval for this histiocytosis.","summary":"Analysis of the histiocytosis cohort of the histology-independent phase 2 VE-BASKET study: 26 patients (22 with Erdheim-Chester disease, 4 with Langerhans cell histiocytosis) with BRAF V600 mutations treated with vemurafenib.\n\nThe objective response rate was 61.5 percent, no patient progressed on treatment and median progression-free survival was not reached after about two years of follow-up; skin toxicity, arthralgia and secondary skin cancers were common. The FDA approved vemurafenib for Erdheim-Chester disease in 2017 on these data.","asOf":"2026-09-18","links":[{"label":"JAMA Oncol 2018","url":"https://doi.org/10.1001/jamaoncol.2017.5029"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29188284/"}],"tags":[],"related":[],"cancers":["erdheim-chester-disease"],"sections":[],"technologies":[],"targets":[],"drugs":["vemurafenib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2018,"doi":"10.1001/jamaoncol.2017.5029","pmid":"29188284","authors":"Diamond EL, Subbiah V, Lockhart AC, et al.","paperType":"observational","findings":["Objective response 61.5 percent; no progression on treatment at a median follow-up of about two years.","Frequent skin toxicity and secondary cutaneous squamous cell carcinomas."],"whatItMeans":"Erdheim-Chester disease with a BRAF V600E mutation is treated first with a BRAF inhibitor; the first targeted approval in any histiocytosis.","caveats":["26 patients, single-arm.","Disease usually returns when the drug is stopped, so treatment is long term."],"changedPractice":true,"participants":26},{"id":"paper-veber-oral-bioavailability-jmedchem-2002","kind":"paper","name":"Veber 2002: molecular properties that influence the oral bioavailability of drug candidates","aka":[],"tldr":"An analysis of over a thousand experimental drug candidates that found molecules with few rotatable bonds and a modest polar surface area were far more likely to be absorbed when swallowed, giving medicinal chemists two simple rules that shaped the design of oral cancer drugs.","summary":"Veber and colleagues at GlaxoSmithKline analysed rat oral bioavailability data for about 1,100 drug candidates and related it to calculated molecular properties. Compounds with ten or fewer rotatable bonds and a polar surface area of 140 square angstroms or less (or twelve or fewer hydrogen bond donors and acceptors) had a high probability of good oral bioavailability, largely independent of molecular weight, which had been the emphasis of earlier rules. The paper argued that reduced molecular flexibility and polar surface area, not size alone, are what predict oral absorption.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1021/jm020017n"}],"tags":[],"related":[],"cancers":[],"sections":["drug-discovery"],"technologies":["protac-degrader"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["pharmacokinetics"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of Medicinal Chemistry","year":2002,"doi":"10.1021/jm020017n","authors":"Veber DF, Johnson SR, Cheng HY, Smith BR, Ward KW, Kopple KD.","paperType":"methods","findings":["Analysis of oral bioavailability in rats for about 1,100 drug candidates.","Ten or fewer rotatable bonds and polar surface area of 140 square angstroms or less predicted good oral bioavailability.","Molecular weight was a weaker predictor than flexibility and polarity."],"whatItMeans":"Veber's rules, alongside Lipinski's rule of five, are used across the industry to decide whether a molecule can become a pill. They set the boundaries within which most oral kinase inhibitors and other targeted cancer drugs were designed, and the current push into larger molecules such as PROTACs and macrocycles is partly an effort to work beyond them.","caveats":["Based on rat data from one company's compounds.","Later oral drugs, including many beyond these limits, show the rules are guides rather than laws."],"changedPractice":true},{"id":"paper-kaplan-nature","kind":"paper","name":"VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 16341007 and published in Nature; the citing page links this DOI, which is how the record was matched.","summary":"The cellular and molecular mechanisms by which a tumour cell undergoes metastasis to a predetermined location are largely unknown. Here we demonstrate that bone marrow-derived haematopoietic progenitor cells that express vascular endothelial growth factor receptor 1 (VEGFR1; also known as Flt1) home to tumour-specific pre-metastatic sites and form cellular clusters before the arrival of tumour cells. Preventing VEGFR1 function using antibodies or by the removal of VEGFR1(+) cells from the bone marrow of wild-type mice abrogates the formation of these pre-metastatic clusters and prevents tumour metastasis, whereas reconstitution with selected Id3 (inhibitor of differentiation 3)-competent VEGFR1+ cells establishes cluster formation and tumour metastasis in Id3 knockout mice. We also show that VEGFR1+ cells express VLA-4 (also known as integrin alpha4beta1), and that tumour-specific growth factors upregulate fibronectin--a VLA-4 ligand--in resident fibroblasts, providing a permissive niche for incoming tumour cells. Conditioned media obtained from distinct tumour types with unique patterns of metastatic spread redirected fibronectin expression and cluster formation, thereby transforming the metastatic profile. These findings demonstrate a requirement for VEGFR1+ haematopoietic progenitors in the regulation of metastasis, and suggest that expression patterns of fibronectin and VEGFR1+VLA-4+ clusters dictate organ-specific tumour spread.\n\nIndexed on Europe PMC as PubMed record 16341007 (DOI 10.1038/nature04186). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2005","url":"https://doi.org/10.1038/nature04186"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/16341007/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/16341007"}],"tags":["europepmc-ingest"],"related":["seed-and-soil-hypothesis"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2005,"doi":"10.1038/nature04186","pmid":"16341007","authors":"Kaplan RN, Riba RD, Zacharoulis S, et al.","paperType":"basic","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-donadieu-vemurafenib-refractory-multisystem-lch-jco-2019","kind":"paper","name":"Vemurafenib for refractory multisystem Langerhans cell histiocytosis in children: an international observational study","aka":[],"tldr":"In children with life-threatening Langerhans cell histiocytosis that had not responded to chemotherapy, the BRAF inhibitor vemurafenib brought the disease under control in nearly all of them, though it usually returned when the drug was stopped.","summary":"International observational study of 54 children with BRAF V600E-mutant multisystem LCH refractory to chemotherapy, most with risk-organ involvement, treated with vemurafenib.\n\nAll children responded and 38 (70 percent) had a complete response at eight weeks; no deaths occurred on treatment. Among those who stopped vemurafenib, about 80 percent relapsed, so most resumed treatment. Skin toxicity was common.","asOf":"2026-09-18","links":[{"label":"J Clin Oncol 2019","url":"https://doi.org/10.1200/JCO.19.00456"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31513482/"}],"tags":[],"related":[],"cancers":["lch-multisystem"],"sections":[],"technologies":[],"targets":[],"drugs":["vemurafenib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2019,"doi":"10.1200/JCO.19.00456","pmid":"31513482","authors":"Donadieu J, Larabi IA, Tardieu M, et al.","paperType":"observational","findings":["Complete response at eight weeks in 38 of 54 children (70 percent) with no on-treatment deaths.","Relapse in about 80 percent of children after stopping vemurafenib."],"whatItMeans":"Vemurafenib rescues children with refractory BRAF-mutant multisystem LCH, but it controls rather than cures, and how to stop it safely is an open question.","caveats":["Observational compassionate-use series without a comparator.","Long-term effects of BRAF inhibition in children are unknown."],"changedPractice":true,"participants":54},{"id":"paper-braf-thyroid-n-engl-j-med-2015","kind":"paper","name":"Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations","aka":[],"tldr":"Phase 2 or 3 results paper on BRAF in Thyroid cancer, in New England Journal of Medicine (2015), one of the most cited Europe PMC records with BRAF in its title.","summary":"Background: BRAF V600 mutations occur in various nonmelanoma cancers. We undertook a histology-independent phase 2 \"basket\" study of vemurafenib in BRAF V600 mutation-positive nonmelanoma cancers.\n\nMethods: We enrolled patients in six prespecified cancer cohorts; patients with all other tumor types were enrolled in a seventh cohort. A total of 122 patients with BRAF V600 mutation-positive cancer were treated, including 27 patients with colorectal cancer who received vemurafenib and cetuximab. The primary end point was the response rate; secondary end points included progression-free and overall survival.\n\nResults: In the cohort with non-small-cell lung cancer, the response rate was 42% (95% confidence interval [CI], 20 to 67) and median progression-free survival was 7.3 months (95% CI, 3.5 to 10.8). In the cohort with Erdheim-Chester disease or Langerhans'-cell histiocytosis, the response rate was 43% (95% CI, 18 to 71); the median treatment duration was 5.9 months (range, 0.6 to 18.6), and no patients had disease progression during therapy. There were anecdotal responses among patients with pleomorphic xanthoastrocytoma, anaplastic thyroid cancer, cholangiocarcinoma, salivary-duct cancer, ovarian cancer, and clear-cell sarcoma and among patients with colorectal cancer who received vemurafenib and cetuximab. Safety was similar to that in prior studies of vemurafenib for melanoma.\n\nConclusions: BRAF V600 appears to be a targetable oncogene in some, but not all, nonmelanoma cancers. Preliminary vemurafenib activity was observed in non-small-cell lung cancer and in Erdheim-Chester disease and Langerhans'-cell histiocytosis. The histologic context is an important determinant of response in BRAF V600-mutated cancers. (Funded by F. Hoffmann-La Roche/Genentech; ClinicalTrials.gov number, NCT01524978.).\n\nIndexed on Europe PMC as PubMed record 26287849 (DOI 10.1056/nejmoa1502309). Its title names BRAF and its text names Thyroid cancer; PubMed types it as a clinical trial report (Clinical Trial, Phase II, Research Support, Non-U.S. Gov't, research-article, Multicenter Study). It was matched automatically to the idea \"BRAF/MEK plus PD-1 blockade as standard for BRAF-mutant anaplastic thyroid cancer\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2015","url":"https://doi.org/10.1056/nejmoa1502309"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26287849/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26287849"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2015,"doi":"10.1056/nejmoa1502309","pmid":"26287849","authors":"Hyman DM, Puzanov I, Subbiah V, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for BRAF in Thyroid cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by BRAF in the title and Thyroid cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-key-j-clin-oncol","kind":"paper","name":"Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Guideline Update","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 37075273 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Purpose: To conduct an update of the ASCO venous thromboembolism (VTE) guideline.\n\nMethods: After publication of potentially practice-changing clinical trials, identified through ASCO's signals approach to updating, an updated systematic review was performed for two guideline questions: perioperative thromboprophylaxis and treatment of VTE. PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) published between November 1, 2018, and June 6, 2022.\n\nResults: Five RCTs provided information that contributed to changes to the 2019 recommendations. Two RCTs addressed direct factor Xa inhibitors (either rivaroxaban or apixaban) for extended thromboprophylaxis after surgery. Each of these postoperative trials had important limitations but suggested that these two oral anticoagulants are safe and effective in the settings studied. An additional three RCTs addressed apixaban in the setting of VTE treatment. Apixaban was effective in reducing the risk of recurrent VTE, with a low risk of major bleeding.\n\nRecommendations: Apixaban and rivaroxaban were added as options for extended pharmacologic thromboprophylaxis after cancer surgery, with a weak strength of recommendation. Apixaban was also added as an option for the treatment of VTE, with high quality of evidence and a strong recommendation.Additional information is available at www.asco.org/supportive-care-guidelines.\n\nIndexed on Europe PMC as PubMed record 37075273 (DOI 10.1200/jco.23.00294). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2023","url":"https://doi.org/10.1200/jco.23.00294"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37075273/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37075273"}],"tags":["europepmc-ingest"],"related":["cancer-associated-thrombosis"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2023,"doi":"10.1200/jco.23.00294","pmid":"37075273","authors":"Key NS, Khorana AA, Kuderer NM, et al.","paperType":"review","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-carlson-link-vestibular-schwannomas-nejm-2021","kind":"paper","name":"Vestibular schwannomas (review)","aka":[],"tldr":"A clinical review of acoustic neuromas covering how they present, why observation is now the first choice for most small tumours, and how microsurgery and radiosurgery compare for tumours that grow.","summary":"Review article summarising the epidemiology, natural history, imaging, hearing outcomes and management of sporadic vestibular schwannoma, including the shift towards observation with serial MRI, indications and outcomes for stereotactic radiosurgery and microsurgery, quality-of-life considerations and NF2-related disease.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2021","url":"https://doi.org/10.1056/NEJMra2020394"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33826821/"}],"tags":[],"related":[],"cancers":["vestibular-schwannoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2021,"doi":"10.1056/NEJMra2020394","pmid":"33826821","authors":"Carlson ML, Link MJ.","paperType":"review","findings":[],"whatItMeans":"The observation-first approach and the framing of treatment as a trade between facial nerve function, hearing and tumour control on the vestibular schwannoma page reflect this review.","caveats":["No randomised trials compare the three main strategies; recommendations rest on observational data."],"changedPractice":false},{"id":"paper-viale-a-venetoclax-azacitidine-nejm-2020","kind":"paper","name":"VIALE-A: venetoclax plus azacitidine for older adults with acute myeloid leukaemia who cannot have intensive chemotherapy","aka":[],"tldr":"Adding the BCL-2 inhibitor venetoclax to azacitidine more than doubled remission rates and extended median survival from 9.6 to 14.7 months in unfit AML patients.","summary":"VIALE-A randomised 431 patients with newly diagnosed AML who were ineligible for intensive induction (median age 76) in a 2:1 ratio to azacitidine plus venetoclax or azacitidine plus placebo. Primary endpoints were overall survival and composite complete remission. Median OS was 14.7 versus 9.6 months (hazard ratio 0.66); complete remission was 36.7% versus 17.9% and complete remission with incomplete count recovery 66.4% versus 28.3%, with responses achieved faster and more often MRD-negative. Febrile neutropenia (42% versus 19%) and infections were more frequent with venetoclax. The regimen became the global standard for unfit AML.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa2012971"},{"label":"ClinicalTrials.gov NCT02993523","url":"https://clinicaltrials.gov/study/NCT02993523"}],"tags":[],"related":["venetoclax-plus-hma","menin-plus-venetoclax-hma"],"cancers":["aml"],"sections":[],"technologies":[],"targets":["bcl2"],"drugs":["venetoclax","azacitidine"],"companies":["abbvie"],"institutions":["md-anderson"],"pathways":[],"terms":["os","mrd-negative-cr"],"trials":["viale-a"],"people":[],"bottlenecks":["b-aging-comorbidity","b-resistance"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2020,"doi":"10.1056/NEJMoa2012971","authors":"DiNardo CD, Jonas BA, Pullarkat V, et al.","paperType":"rct","findings":["431 patients unfit for intensive chemotherapy, median age 76; azacitidine + venetoclax vs azacitidine + placebo (2:1).","Median OS 14.7 vs 9.6 months; hazard ratio 0.66.","Complete remission 36.7% vs 17.9%; CR + CRi 66.4% vs 28.3%.","Responses were faster (median 1.3 months to first response) and more often MRD-negative.","Febrile neutropenia 42% vs 19%; grade 3 or higher infections more frequent."],"whatItMeans":"VIALE-A turned a palliative regimen into one that produces remission in two-thirds of older AML patients and is now the reference treatment for anyone not fit for intensive chemotherapy. It shifted the field towards lower-intensity targeted combinations and opened the door to adding FLT3, IDH and menin inhibitors to the backbone. Cure remains uncommon and most patients relapse within two years.","caveats":["Median survival gain was about five months; long-term survival is still poor.","Benefit was smaller in TP53-mutated and adverse-karyotype disease.","Prolonged cytopenias require dose interruptions and expertise; real-world outcomes are worse than trial results.","No comparison against intensive chemotherapy in fit patients."],"changedPractice":true,"participants":431},{"id":"paper-gelderblom-lancet","kind":"paper","name":"Vimseltinib versus placebo for tenosynovial giant cell tumour (MOTION): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 38843860 and published in The Lancet; the citing page links this DOI, which is how the record was matched.","summary":"Background: Tenosynovial giant cell tumour (TGCT) is a locally aggressive neoplasm for which few systemic treatment options exist. This study evaluated the efficacy and safety of vimseltinib, an oral, switch-control, CSF1R inhibitor, in patients with symptomatic TGCT not amenable to surgery.\n\nMethods: MOTION is a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial done in 35 specialised hospitals in 13 countries. Eligible patients were adults (aged ≥18 years) with a histologically confirmed diagnosis of TGCT for which surgical resection could potentially worsen functional limitation or cause severe morbidity. Patients were randomly assigned (2:1) with interactive response technology to vimseltinib (30 mg orally twice weekly) or placebo, administrated in 28-day cycles for 24 weeks. Patients and site personnel were masked to treatment assignment until week 25, unless progressive disease was confirmed earlier. The primary endpoint was objective response rate by independent radiological review using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST) at week 25 in the intention-to-treat population. Safety was assessed in all patients who received the study drug. The trial is registered with ClinicalTrials.gov, NCT05059262, and enrolment is complete.\n\nFindings: Between Jan 21, 2022, and Feb 21, 2023, 123 patients were randomly assigned (83 to vimseltinib and 40 to placebo). 73 (59%) patients were female and 50 (41%) were male. Nine (11%) of 83 patients assigned to vimseltinib and five (13%) of 40 patients assigned to placebo discontinued treatment before week 25; one patient in the placebo group did not receive any study drug. Objective response rate per RECIST was 40% (33 of 83 patients) in the vimseltinib group vs 0% (none of 40) in the placebo group (difference 40% [95% CI 29-51]; p<0·0001). Most treatment-emergent adverse events (TEAEs) were grade 1 or 2; the only grade 3 or 4 TEAE that occurred in more than 5% of patients receiving vimseltinib was increased blood creatine phosphokinase (eight [10%] of 83). One patient in the vimseltinib group had a treatment-related serious TEAE of subcutaneous abscess. No evidence of cholestatic hepatotoxicity or drug-induced liver injury was noted.\n\nInterpretation: Vimseltinib produced a significant objective response rate and clinically meaningful functional and symptomatic improvement in patients with TGCT, providing an effective treatment option for these patients.\n\nFunding: Deciphera Pharmaceuticals.\n\nIndexed on Europe PMC as PubMed record 38843860 (DOI 10.1016/s0140-6736(24)00885-7). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet 2024","url":"https://doi.org/10.1016/s0140-6736(24)00885-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38843860/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38843860"}],"tags":["europepmc-ingest"],"related":["tenosynovial-giant-cell-tumour"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2024,"doi":"10.1016/s0140-6736(24)00885-7","pmid":"38843860","authors":"Gelderblom H, Bhadri V, Stacchiotti S, et al.","paperType":"rct","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-bisogno-lancet-oncol","kind":"paper","name":"Vinorelbine and continuous low-dose cyclophosphamide as maintenance chemotherapy in patients with high-risk rhabdomyosarcoma (RMS 2005): a multicentre, open-label, randomised, phase 3 trial","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 31562043 and published in The Lancet Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background: For more than three decades, standard treatment for rhabdomyosarcoma in Europe has included 6 months of chemotherapy. The European paediatric Soft tissue sarcoma Study Group (EpSSG) aimed to investigate whether prolonging treatment with maintenance chemotherapy would improve survival in patients with high-risk rhabdomyosarcoma.\n\nMethods: RMS 2005 was a multicentre, open-label, randomised, controlled, phase 3 trial done at 102 hospitals in 14 countries. We included patients aged 6 months to 21 years with rhabdomyosarcoma who were considered to be at high risk of relapse: those with non-metastatic incompletely resected embryonal rhabdomyosarcoma occurring at unfavourable sites with unfavourable age (≥10 years) or tumour size (>5 cm), or both; those with any non-metastatic rhabdomyosarcoma with nodal involvement; and those with non-metastatic alveolar rhabdomyosarcoma but without nodal involvement. Patients in remission after standard treatment (nine cycles of ifosfamide, vincristine, dactinomycin with or without doxorubicin, and surgery or radiotherapy, or both) were randomly assigned (1:1) to stop treatment or continue maintenance chemotherapy (six cycles of intravenous vinorelbine 25 mg/m 2 on days 1, 8, and 15, and daily oral cyclophosphamide 25 mg/m 2, on days 1-28). Randomisation was done by use of a web-based system and was stratified (block size of four) by enrolling country and risk subgroup. Neither investigators nor patients were masked to treatment allocation. The primary outcome was disease-free survival in the intention-to-treat population. Secondary outcomes were overall survival and toxicity. This trial is registered with EudraCT, number 2005-000217-35, and ClinicalTrials.gov, number NCT00339118, and follow-up is ongoing.\n\nFindings: Between April 20, 2006, and Dec 21, 2016, 371 patients were enrolled and randomly assigned to the two groups: 186 to stop treatment and 185 to receive maintenance chemotherapy. Median follow-up was 60·3 months (IQR 32·4-89·4). In the intention-to-treat population, 5-year disease-free survival was 77·6% (95% CI 70·6-83·2) with maintenance chemotherapy versus 69·8% (62·2-76·2) without maintenance chemotherapy (hazard ratio [HR] 0·68 [95% CI 0·45-1·02]; p=0·061), and 5-year overall survival was 86·5% (95% CI 80·2-90·9) with maintenance chemotherapy versus 73·7% (65·8-80·1) without (HR 0·52 [95% CI 0·32-0·86]; p=0·0097). Toxicity was manageable in patients who received maintenance chemotherapy: 136 (75%) of 181 patients had grade 3-4 leucopenia, 148 (82%) had grade 3-4 neutropenia, 19 (10%) had anaemia, two (1%) had thrombocytopenia, and 56 (31%) had an infection. One (1%) patient had a grade 4 non-haematological toxicity (neurotoxicity). Two treatment-related serious adverse events occurred: one case of inappropriate antidiuretic hormone secretion and one of a severe steppage gait with limb pain, both of which resolved.\n\nInterpretation: Adding maintenance chemotherapy seems to improve survival for patients with high-risk rhabdomyosarcoma. This approach will be the new standard of care for patients with high-risk rhabdomyosarcoma in future EpSSG trials.\n\nFunding: Fondazione Città della Speranza, Association Léon Berard Enfant Cancéreux, Clinical Research Hospital Program (French Ministry of Health), and Cancer Research UK.\n\nIndexed on Europe PMC as PubMed record 31562043 (DOI 10.1016/s1470-2045(19)30617-5). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2019","url":"https://doi.org/10.1016/s1470-2045(19)30617-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31562043/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31562043"}],"tags":["europepmc-ingest"],"related":["rhabdomyosarcoma"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2019,"doi":"10.1016/s1470-2045(19)30617-5","pmid":"31562043","authors":"Bisogno G, De Salvo GL, Bergeron C, et al.","paperType":"rct","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-moffitt-virtual-microdissection-subtypes-nat-genet-2015","kind":"paper","name":"Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma","aka":[],"tldr":"The 2015 study that computationally separated cancer cells from the surrounding scar tissue in gene expression data and found two tumour types, classical and basal-like, and two kinds of stroma, each of which predicts survival.","summary":"Moffitt and colleagues at the University of North Carolina applied blind source separation to a diverse collection of pancreatic ductal adenocarcinoma gene expression microarray data, including primary tumour, metastatic and normal samples, to digitally separate tumour, stromal and normal expression. They identified and validated two tumour subtypes, including a basal-like subtype with worse outcome that is molecularly similar to basal tumours of bladder and breast cancer, and defined normal and activated stromal subtypes that are independently prognostic. The abstract records the five-year survival of the disease as 4 percent.","asOf":"2026-09-24","links":[{"label":"Nat Genet 2015","url":"https://doi.org/10.1038/ng.3398"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26343385/"}],"tags":["pancreatic-evidence"],"related":["paper-bailey-molecular-subtypes-pancreatic-nature-2016"],"cancers":["pancreatic"],"sections":[],"technologies":["rna-seq"],"targets":[],"drugs":[],"companies":[],"institutions":["unc-lineberger"],"pathways":["tumor-microenvironment","caf-activation-desmoplasia"],"terms":["desmoplasia","desmoplastic-stroma-rich","cancer-associated-fibroblasts"],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity"],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":2015,"doi":"10.1038/ng.3398","pmid":"26343385","authors":"Moffitt RA, Marayati R, Flate EL, et al.","paperType":"basic","findings":["Two tumour subtypes, classical and basal-like; basal-like has worse outcome and resembles basal bladder and breast tumours.","Normal and activated stromal subtypes, independently prognostic.","Five-year survival 4 percent at the time of writing."],"whatItMeans":"The classical versus basal-like split, later tied to GATA6 expression and to chemotherapy response, is the subtype scheme most likely to reach the clinic; the stromal subtypes are why the desmoplastic stroma is treated as a partner in the disease rather than inert scar.","caveats":["Microarray data from mixed sources; the subtype is a continuum and tumours can shift under treatment.","No subtype-directed treatment has yet been proven in a randomised trial."]},{"id":"paper-epstein-virus-particles-burkitt-lymphoblasts-lancet-1964","kind":"paper","name":"Virus particles in cultured lymphoblasts from Burkitt's lymphoma","aka":["Epstein 1964","Epstein, Achong and Barr","Discovery of Epstein-Barr virus"],"tldr":"Looking at cells grown from an African child's jaw tumour under an electron microscope, three researchers in London saw virus particles, the first virus ever linked to a human cancer.","summary":"Michael Anthony Epstein, Bert Achong and Yvonne Barr reported virus particles in lymphoblasts cultured from a Burkitt lymphoma biopsy. Europe PMC indexes no abstract for the Lancet report, so no figure from it is quoted here.\n\nIts importance is categorical rather than numerical: it was the first demonstration of a virus in a human tumour, and it opened the field that now includes human papillomavirus and cervical cancer, hepatitis B and C and liver cancer, Helicobacter pylori and gastric MALT lymphoma, human herpesvirus 8 and Kaposi sarcoma and primary effusion lymphoma, and human T-lymphotropic virus type 1 and adult T-cell leukaemia/lymphoma.\n\nEpstein-Barr virus is now known to infect most of the world's adult population harmlessly and to be associated with endemic Burkitt lymphoma, a subset of Hodgkin lymphoma, Epstein-Barr virus-positive diffuse large B-cell lymphoma, extranodal NK/T-cell lymphoma, post-transplant lymphoproliferative disorder and nasopharyngeal carcinoma. Two companion papers from the same group appeared in the same year, on the cultivation of the lymphoblasts (PubMed 14090852) and on a second virus-carrying strain (PubMed 14255814).","asOf":"2026-10-01","links":[{"label":"Lancet 1964","url":"https://doi.org/10.1016/S0140-6736(64)91524-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/14107961/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/14107961"}],"tags":["lymphoma-evidence"],"related":["paper-burkitt-sarcoma-involving-jaws-african-children-br-j-surg-1958","idea-prev-ebv-vaccine","lymphoma-roadmap"],"cancers":["burkitt-lymphoma","non-hodgkin-lymphoma","hodgkin-lymphoma","post-transplant-lymphoproliferative-disorder"],"sections":["prevention","diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-global-access"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"Lancet","year":1964,"doi":"10.1016/S0140-6736(64)91524-7","pmid":"14107961","authors":"Epstein MA, Achong BG, Barr YM.","paperType":"basic","findings":["Reported virus particles in lymphoblasts cultured from Burkitt's lymphoma, the first virus observed in a human tumour.","Europe PMC indexes no abstract for this record, so no figure from the paper is quoted here.","Two companion reports from the same group appeared in 1964: on the cultivation in vitro of human lymphoblasts from Burkitt's malignant lymphoma (PubMed 14090852) and on a second virus-carrying tissue culture strain (PubMed 14255814)."],"whatItMeans":"The start of viral oncology. Everything in cancer prevention that works by preventing or treating an infection, from hepatitis B vaccination to Helicobacter eradication for gastric MALT lymphoma, descends from the idea this paper established.","caveats":["No abstract is indexed, and the 1964 report establishes the presence of virus particles rather than causation; the causal argument was built over the following decades.","Epstein-Barr virus infects most adults worldwide without causing cancer, so its presence in a tumour is necessary rather than sufficient and the cofactors in endemic Burkitt lymphoma, including malaria, remain the subject of research."],"changedPractice":true},{"id":"paper-vision-nejm-2021","kind":"paper","name":"VISION: lutetium-177 PSMA-617 radioligand therapy extends survival in advanced prostate cancer","aka":[],"tldr":"A radioactive drug that homes to the PSMA protein on prostate cancer cells helped men with heavily pretreated metastatic prostate cancer live about four months longer, launching radioligand therapy as a mainstream treatment.","summary":"Open-label phase 3 trial of 831 men with PSMA-PET-positive metastatic castration-resistant prostate cancer previously treated with at least one androgen-receptor pathway inhibitor and one or two taxanes, randomised 2:1 to 177Lu-PSMA-617 (7.4 GBq every six weeks for up to six cycles) plus protocol-permitted standard care, or standard care alone. Primary endpoints were radiographic PFS and OS.\n\nMedian OS was 15.3 vs 11.3 months (HR 0.62) and median rPFS 8.7 vs 3.4 months (HR 0.40). It led to FDA and EMA approval of Pluvicto in 2022, the first radioligand therapy to show a survival benefit in a common cancer, and made PSMA PET a theranostic gatekeeper.","asOf":"2026-09-08","links":[{"label":"NEJM 2021","url":"https://doi.org/10.1056/NEJMoa2107322"},{"label":"ClinicalTrials.gov NCT03511664","url":"https://clinicaltrials.gov/study/NCT03511664"}],"tags":[],"related":["psma-pet-to-rlt","prostate-roadmap","paper-therap-lancet-2021","idea-prostate-randomise-the-sequence-not-only-the-drugs"],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["radioligand-therapy","psma-pet","pet-ct"],"targets":["psma"],"drugs":["pluvicto"],"companies":["novartis"],"institutions":[],"pathways":[],"terms":["theranostics","alpha-vs-beta","dosimetry","os","pfs"],"trials":["vision","psmafore"],"people":["johann-de-bono","karim-fizazi","michael-morris"],"bottlenecks":["b-global-access","b-workforce","b-trial-design"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2021,"doi":"10.1056/NEJMoa2107322","authors":"Sartor O, de Bono J, Chi KN, et al.","paperType":"rct","findings":["Median overall survival 15.3 vs 11.3 months; HR 0.62 (95% CI 0.52-0.74).","Median radiographic PFS 8.7 vs 3.4 months; HR 0.40 (99.2% CI 0.29-0.57).","PSA decline of 50% or more in 46% vs 7%; objective response in measurable disease 30% vs 2%.","Grade 3 or higher adverse events 53% vs 38%, mainly anaemia, thrombocytopenia and fatigue; dry mouth was common but rarely severe.","About 13% of screened patients were excluded by PSMA PET (PSMA-negative lesions), and early dropout in the control arm required protocol changes."],"whatItMeans":"Men with metastatic castration-resistant prostate cancer that has progressed after hormonal therapy and chemotherapy, and whose tumours show PSMA on a PET scan, can now receive lutetium-PSMA, which extends life, controls pain and is usually better tolerated than further chemotherapy. It has established a new treatment class in which a scan decides who gets the matching radioactive drug, and it is now being tested earlier in the disease (PSMAfore, PSMAddition).","caveats":["Standard care in the control arm excluded chemotherapy, radium-223 and other active drugs, and about 56% of control patients withdrew early, weakening the comparison.","Open-label; the OS benefit is nonetheless robust to sensitivity analyses.","Requires nuclear medicine infrastructure, isotope supply and PSMA PET access, which are unequally distributed.","PSMAfore in the pre-chemotherapy setting improved rPFS but not OS, because most control patients crossed over."],"changedPractice":true,"participants":831},{"id":"paper-vision-tepotinib-paik-nejm-2020","kind":"paper","name":"VISION: tepotinib in non-small-cell lung cancer with MET exon 14 skipping mutations","aka":[],"tldr":"The once-daily MET inhibitor tepotinib shrank tumours in about half of patients with MET exon 14-skipping lung cancer, detected either in tissue or in a blood test, supporting approval and the use of liquid biopsy to find the alteration.","summary":"Phase 2 study of 152 patients with advanced non-small-cell lung cancer with MET exon 14 skipping detected by liquid or tissue biopsy treated with tepotinib 500 mg daily.\n\nObjective response by independent review was 46 percent overall (48 percent in liquid-biopsy and 50 percent in tissue-biopsy groups) with a median duration of response of 11.1 months; peripheral oedema was the main toxicity.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2020","url":"https://doi.org/10.1056/NEJMoa2004407"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32469185/"}],"tags":[],"related":[],"cancers":["met-altered-nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":["tepotinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["paul-paik"],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2020,"doi":"10.1056/NEJMoa2004407","pmid":"32469185","authors":"Paik PK, Felip E, Veillon R, et al.","paperType":"observational","findings":["Objective response 46 percent; median duration of response 11.1 months.","Similar responses whether detected by liquid or tissue biopsy."],"whatItMeans":"Tepotinib is an approved alternative to capmatinib for MET exon 14 lung cancer, and the trial validated circulating tumour DNA as a way to find the alteration.","caveats":["Single-arm; grade 3 or higher peripheral oedema in 7 percent."],"changedPractice":true,"participants":152},{"id":"paper-robinson-vismodegib-shh-medulloblastoma-jco-2015","kind":"paper","name":"Vismodegib in recurrent sonic hedgehog-subgroup medulloblastoma (PBTC-025B and PBTC-032)","aka":[],"tldr":"The hedgehog pathway inhibitor vismodegib produced responses in recurrent SHH-subgroup medulloblastoma but not in other subgroups, and only in tumours whose mutation lay upstream of the drug's target, showing that molecular subgrouping must guide its use.","summary":"Two phase 2 studies of vismodegib in 43 patients (adults and children) with recurrent medulloblastoma, analysed by molecular subgroup and mutation.\n\nResponses occurred in 3 of 12 adults and 1 of 8 children with SHH-subgroup tumours and in none of the 20 non-SHH patients; responders had PTCH1 or SMO alterations, while tumours with downstream SUFU or GLI2 alterations did not respond, and growth plate fusion occurred in children.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2015","url":"https://doi.org/10.1200/JCO.2014.60.1591"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26169613/"}],"tags":[],"related":[],"cancers":["medulloblastoma-shh"],"sections":[],"technologies":[],"targets":[],"drugs":["vismodegib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["giles-robinson"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2015,"doi":"10.1200/JCO.2014.60.1591","pmid":"26169613","authors":"Robinson GW, Orr BA, Wu G, et al.","paperType":"observational","findings":["Responses only in SHH-subgroup tumours with upstream (PTCH1, SMO) alterations.","No responses in non-SHH medulloblastoma."],"whatItMeans":"Vismodegib or sonidegib is reserved for skeletally mature patients with relapsed SHH medulloblastoma and upstream pathway mutations, a niche defined by this trial.","caveats":["Small numbers; responses were transient.","Irreversible growth plate closure in growing children."],"changedPractice":true,"participants":43},{"id":"paper-johnston-nature","kind":"paper","name":"VISTA is an acidic pH-selective ligand for PSGL-1","aka":[],"tldr":"Paper cited by one target page, indexed on Europe PMC as PubMed record 31645726 and published in Nature; the citing page links this DOI, which is how the record was matched.","summary":"Co-inhibitory immune receptors can contribute to T cell dysfunction in patients with cancer 1,2. Blocking antibodies against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1) partially reverse this effect and are becoming standard of care in an increasing number of malignancies 3. However, many of the other axes by which tumours become inhospitable to T cells are not fully understood. Here we report that V-domain immunoglobulin suppressor of T cell activation (VISTA) engages and suppresses T cells selectively at acidic pH such as that found in tumour microenvironments. Multiple histidine residues along the rim of the VISTA extracellular domain mediate binding to the adhesion and co-inhibitory receptor P-selectin glycoprotein ligand-1 (PSGL-1). Antibodies engineered to selectively bind and block this interaction in acidic environments were sufficient to reverse VISTA-mediated immune suppression in vivo. These findings identify a mechanism by which VISTA may engender resistance to anti-tumour immune responses, as well as an unexpectedly determinative role for pH in immune co-receptor engagement.\n\nIndexed on Europe PMC as PubMed record 31645726 (DOI 10.1038/s41586-019-1674-5). Matched by DOI alone: one target page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2019","url":"https://doi.org/10.1038/s41586-019-1674-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31645726/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31645726"}],"tags":["europepmc-ingest"],"related":["vista"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2019,"doi":"10.1038/s41586-019-1674-5","pmid":"31645726","authors":"Johnston RJ, Su LJ, Pinckney J, et al.","paperType":"basic","findings":[],"whatItMeans":"One target page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-manson-n-engl-j-med","kind":"paper","name":"Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease","aka":[],"tldr":"Paper cited by one trial page and one technology page, indexed on Europe PMC as PubMed record 30415629 and published in New England Journal of Medicine; the citing pages link this DOI, which is how the record was matched.","summary":"Background: It is unclear whether supplementation with vitamin D reduces the risk of cancer or cardiovascular disease, and data from randomized trials are limited.\n\nMethods: We conducted a nationwide, randomized, placebo-controlled trial, with a two-by-two factorial design, of vitamin D 3 (cholecalciferol) at a dose of 2000 IU per day and marine n-3 (also called omega-3) fatty acids at a dose of 1 g per day for the prevention of cancer and cardiovascular disease among men 50 years of age or older and women 55 years of age or older in the United States. Primary end points were invasive cancer of any type and major cardiovascular events (a composite of myocardial infarction, stroke, or death from cardiovascular causes). Secondary end points included site-specific cancers, death from cancer, and additional cardiovascular events. This article reports the results of the comparison of vitamin D with placebo.\n\nResults: A total of 25,871 participants, including 5106 black participants, underwent randomization. Supplementation with vitamin D was not associated with a lower risk of either of the primary end points. During a median follow-up of 5.3 years, cancer was diagnosed in 1617 participants (793 in the vitamin D group and 824 in the placebo group; hazard ratio, 0.96; 95% confidence interval [CI], 0.88 to 1.06; P=0.47). A major cardiovascular event occurred in 805 participants (396 in the vitamin D group and 409 in the placebo group; hazard ratio, 0.97; 95% CI, 0.85 to 1.12; P=0.69). In the analyses of secondary end points, the hazard ratios were as follows: for death from cancer (341 deaths), 0.83 (95% CI, 0.67 to 1.02); for breast cancer, 1.02 (95% CI, 0.79 to 1.31); for prostate cancer, 0.88 (95% CI, 0.72 to 1.07); for colorectal cancer, 1.09 (95% CI, 0.73 to 1.62); for the expanded composite end point of major cardiovascular events plus coronary revascularization, 0.96 (95% CI, 0.86 to 1.08); for myocardial infarction, 0.96 (95% CI, 0.78 to 1.19); for stroke, 0.95 (95% CI, 0.76 to 1.20); and for death from cardiovascular causes, 1.11 (95% CI, 0.88 to 1.40). In the analysis of death from any cause (978 deaths), the hazard ratio was 0.99 (95% CI, 0.87 to 1.12). No excess risks of hypercalcemia or other adverse events were identified.\n\nConclusions: Supplementation with vitamin D did not result in a lower incidence of invasive cancer or cardiovascular events than placebo. (Funded by the National Institutes of Health and others; VITAL ClinicalTrials.gov number, NCT01169259.).\n\nIndexed on Europe PMC as PubMed record 30415629 (DOI 10.1056/nejmoa1809944). Matched by DOI alone: one trial page and one technology page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2019","url":"https://doi.org/10.1056/nejmoa1809944"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30415629/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30415629"}],"tags":["europepmc-ingest"],"related":["vitamin-d-omega3-supplementation"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["vital"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2019,"doi":"10.1056/nejmoa1809944","pmid":"30415629","authors":"Manson JE, Cook NR, Lee IM, et al.","paperType":"rct","findings":[],"whatItMeans":"One trial page and one technology page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-vogelstein-surfing-p53-network-nature-2000","kind":"paper","name":"Vogelstein, Lane and Levine 2000: surfing the p53 network","aka":[],"tldr":"A concise map of the p53 system as a network: the stresses that activate it, the many genes it controls, and the feedback loops that keep it in check, explaining why a single gene sits at the centre of so much of cancer biology.","summary":"Written by three of the field's founders, this review presented p53 as a signalling network rather than a single switch. Upstream, DNA damage, oncogene activation, hypoxia and nucleotide depletion converge on p53 through kinases and the MDM2 and ARF regulators; downstream, p53 activates genes for cell cycle arrest, apoptosis, DNA repair and inhibition of angiogenesis. The authors emphasised the MDM2 negative feedback loop, the effects of viral oncoproteins and the fact that most cancers disable the network at one point or another, whether by mutating p53 itself or by altering its regulators.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1038/35042675"}],"tags":[],"related":["paper-levine-p53-gatekeeper-cell-1997","paper-hollstein-p53-mutations-science-1991"],"cancers":[],"sections":[],"technologies":[],"targets":["tp53","mdm2"],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":["p53-cell-cycle","p53-mdm2-axis"],"terms":["tp53-mutated","tumour-suppressor-gene"],"trials":[],"people":["bert-vogelstein"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature","year":2000,"doi":"10.1038/35042675","authors":"Vogelstein B, Lane D, Levine AJ.","paperType":"review","findings":["p53 integrates signals from DNA damage, oncogene activation and hypoxia through MDM2, ARF and stress kinases.","Its outputs include cell cycle arrest, apoptosis, DNA repair and anti-angiogenic genes.","Most cancers disable the network, either by TP53 mutation or by altering upstream regulators such as MDM2 amplification or ARF loss."],"whatItMeans":"This paper is the reason TP53 status, MDM2 amplification and CDKN2A loss are read together in tumour genomes. It frames the current drug development around MDM2 inhibitors and mutant p53 reactivators as attempts to restore a network rather than a single protein.","caveats":["A review from 2000; many network components and p53 isoforms were identified later.","Concise by design, so it omits much mechanistic detail."],"changedPractice":false},{"id":"paper-ramsey-health-aff-millwood","kind":"paper","name":"Washington State cancer patients found to be at greater risk for bankruptcy than people without a cancer diagnosis","aka":[],"tldr":"Paper cited by one bottleneck page and one idea page, indexed on Europe PMC as PubMed record 23676531 and published in Health affairs (Project Hope); the citing pages link this DOI, which is how the record was matched.","summary":"Much has been written about the relationship between high medical expenses and the likelihood of filing for bankruptcy, but the relationship between receiving a cancer diagnosis and filing for bankruptcy is less well understood. We estimated the incidence and relative risk of bankruptcy for people age twenty-one or older diagnosed with cancer compared to people the same age without cancer by conducting a retrospective cohort analysis that used a variety of medical, personal, legal, and bankruptcy sources covering the Western District of Washington State in US Bankruptcy Court for the period 1995-2009. We found that cancer patients were 2.65 times more likely to go bankrupt than people without cancer. Younger cancer patients had 2-5 times higher rates of bankruptcy than cancer patients age sixty-five or older, which indicates that Medicare and Social Security may mitigate bankruptcy risk for the older group. The findings suggest that employers and governments may have a policy role to play in creating programs and incentives that could help people cover expenses in the first year following a cancer diagnosis.\n\nIndexed on Europe PMC as PubMed record 23676531 (DOI 10.1377/hlthaff.2012.1263). Matched by DOI alone: one bottleneck page and one idea page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Health Aff (Millwood) 2013","url":"https://doi.org/10.1377/hlthaff.2012.1263"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23676531/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/23676531"}],"tags":["europepmc-ingest"],"related":["b-drug-pricing","idea-cost-financial-toxicity-screening"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Health affairs (Project Hope)","year":2013,"doi":"10.1377/hlthaff.2012.1263","pmid":"23676531","authors":"Ramsey S, Blough D, Kirchhoff A, et al.","paperType":"observational","findings":[],"whatItMeans":"One bottleneck page and one idea page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-schmitz-n-engl-j-med","kind":"paper","name":"Weight lifting in women with breast-cancer-related lymphedema","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 19675330 and published in New England Journal of Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Background: Weight lifting has generally been proscribed for women with breast-cancer-related lymphedema, preventing them from obtaining the well-established health benefits of weight lifting, including increases in bone density.\n\nMethods: We performed a randomized, controlled trial of twice-weekly progressive weight lifting involving 141 breast-cancer survivors with stable lymphedema of the arm. The primary outcome was the change in arm and hand swelling at 1 year, as measured through displaced water volume of the affected and unaffected limbs. Secondary outcomes included the incidence of exacerbations of lymphedema, number and severity of lymphedema symptoms, and muscle strength. Participants were required to wear a well-fitted compression garment while weight lifting.\n\nResults: The proportion of women who had an increase of 5% or more in limb swelling was similar in the weight-lifting group (11%) and the control group (12%) (cumulative incidence ratio, 1.00; 95% confidence interval, 0.88 to 1.13). As compared with the control group, the weight-lifting group had greater improvements in self-reported severity of lymphedema symptoms (P=0.03) and upper- and lower-body strength (P<0.001 for both comparisons) and a lower incidence of lymphedema exacerbations as assessed by a certified lymphedema specialist (14% vs. 29%, P=0.04). There were no serious adverse events related to the intervention.\n\nConclusions: In breast-cancer survivors with lymphedema, slowly progressive weight lifting had no significant effect on limb swelling and resulted in a decreased incidence of exacerbations of lymphedema, reduced symptoms, and increased strength. (ClinicalTrials.gov number, NCT00194363.)\n\nIndexed on Europe PMC as PubMed record 19675330 (DOI 10.1056/nejmoa0810118). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2009","url":"https://doi.org/10.1056/nejmoa0810118"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/19675330/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/19675330"}],"tags":["europepmc-ingest"],"related":["lymphoedema-decongestive-therapy"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2009,"doi":"10.1056/nejmoa0810118","pmid":"19675330","authors":"Schmitz KH, Ahmed RL, Troxel A, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-lazebnik-nat-rev-cancer","kind":"paper","name":"What are the hallmarks of cancer?","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 20355252 and published in Nature Reviews Cancer; the citing page links this DOI, which is how the record was matched.","summary":"The seminal article by Douglas Hanahan and Robert Weinberg on the hallmarks of cancer is 10 years old this year and its contribution to how we see cancer has been substantial. But, in embracing this view, have we lost sight of what makes cancer cancer?\n\nIndexed on Europe PMC as PubMed record 20355252 (DOI 10.1038/nrc2827). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Cancer 2010","url":"https://doi.org/10.1038/nrc2827"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/20355252/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/20355252"}],"tags":["europepmc-ingest"],"related":["hallmarks-synthesis"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-cancer"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Cancer","year":2010,"doi":"10.1038/nrc2827","pmid":"20355252","authors":"Lazebnik Y","paperType":"observational","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-who-2022-lymphoid-alaggio-leukemia-2022","kind":"paper","name":"WHO classification of haematolymphoid tumours, fifth edition: lymphoid neoplasms","aka":[],"tldr":"The 2022 World Health Organization classification of lymphomas and lymphoid leukaemias, the reference for how these diseases are named, defined and separated.","summary":"Summary of the fifth-edition WHO classification of lymphoid neoplasms, reorganising B-cell and T-cell lymphomas, plasma cell neoplasms and lymphoid leukaemias with updated entities, new genetically defined subtypes and revised terminology.","asOf":"2026-09-17","links":[{"label":"Leukemia 2022","url":"https://doi.org/10.1038/s41375-022-01620-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35732829/"}],"tags":[],"related":[],"cancers":["richter-transformation-cll","primary-mediastinal-b-cell-lymphoma","marginal-zone-lymphoma","cutaneous-t-cell-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["leukemia"],"dependsOn":[],"notes":[],"journal":"Leukemia","year":2022,"doi":"10.1038/s41375-022-01620-2","pmid":"35732829","authors":"Alaggio R, Amador C, Anagnostopoulos I, et al.","paperType":"guideline","findings":[],"whatItMeans":"Every lymphoma diagnosis on this site refers to an entity in this classification or the parallel International Consensus Classification.","caveats":["Coexists with the 2022 International Consensus Classification, which differs in some entity names."],"changedPractice":true},{"id":"paper-who-2022-myeloid-khoury-leukemia-2022","kind":"paper","name":"WHO classification of haematolymphoid tumours, fifth edition: myeloid and histiocytic neoplasms","aka":[],"tldr":"The 2022 World Health Organization classification redefines myeloid cancers, including myelodysplastic neoplasms, acute myeloid leukaemia by genetic type, and the boundaries between them.","summary":"Summary of the fifth-edition WHO classification of myeloid and histiocytic neoplasms, renaming myelodysplastic syndromes as myelodysplastic neoplasms, removing the 20 percent blast threshold for AML with defining genetic abnormalities, and reorganising AML, myeloproliferative neoplasms and secondary myeloid neoplasms around genetics.","asOf":"2026-09-17","links":[{"label":"Leukemia 2022","url":"https://doi.org/10.1038/s41375-022-01613-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35732831/"}],"tags":[],"related":[],"cancers":["mds-higher-risk","aml-secondary","cml-advanced-phase"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["leukemia"],"dependsOn":[],"notes":[],"journal":"Leukemia","year":2022,"doi":"10.1038/s41375-022-01613-1","pmid":"35732831","authors":"Khoury JD, Solary E, Abla O, et al.","paperType":"guideline","findings":[],"whatItMeans":"The names and definitions on a marrow report (for example MDS with biallelic TP53 inactivation, or AML myelodysplasia-related) come from this document or from the parallel International Consensus Classification.","caveats":["Differs in places from the International Consensus Classification published the same year, which can complicate trial eligibility."],"changedPractice":true},{"id":"paper-who-2022-gu-moch-eur-urol-2022","kind":"paper","name":"WHO classification of tumours of the urinary system and male genital organs, 2022: renal, penile and testicular tumours","aka":[],"tldr":"The 2022 World Health Organization classification of kidney tumours reorganises renal cell carcinoma into morphologically and molecularly defined types, including new molecularly defined entities, and clarifies chromophobe, papillary and clear cell subtypes.","summary":"Summary of the fifth-edition WHO classification for renal, penile and testicular tumours, introducing molecularly defined renal cell carcinomas (TFE3-rearranged, TFEB-altered, ELOC-mutated, fumarate hydratase-deficient, SDH-deficient, ALK-rearranged, SMARCB1-deficient medullary), abolishing type 1 and type 2 papillary subdivision, and refining eosinophilic and oncocytic tumours.","asOf":"2026-09-17","links":[{"label":"Eur Urol 2022","url":"https://doi.org/10.1016/j.eururo.2022.06.016"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35853783/"}],"tags":[],"related":[],"cancers":["chromophobe-rcc","papillary-rcc","clear-cell-rcc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["european-urology"],"dependsOn":[],"notes":[],"journal":"European Urology","year":2022,"doi":"10.1016/j.eururo.2022.06.016","pmid":"35853783","authors":"Moch H, Amin MB, Berney DM, et al.","paperType":"guideline","findings":[],"whatItMeans":"Kidney cancer subtype pages use these definitions; several rare entities are now diagnosed by molecular testing rather than appearance alone.","caveats":["Many new entities lack subtype-specific treatment evidence."],"changedPractice":true},{"id":"paper-roberts-familial-pancreatic-whole-genome-cancer-discov-2016","kind":"paper","name":"Whole genome sequencing defines the genetic heterogeneity of familial pancreatic cancer","aka":[],"tldr":"Reading the inherited genomes of 638 people from pancreatic cancer families confirmed BRCA2, CDKN2A and ATM as causes but found that most families' risk is spread across many rare genes rather than one.","summary":"Germline genomes of 638 familial pancreatic cancer patients and tumour exomes of 39 familial adenocarcinomas were sequenced. The analyses supported previously identified susceptibility genes BRCA2, CDKN2A and ATM and identified novel candidate genes harbouring rare deleterious germline variants. Somatic mutations arising during haematopoiesis were shown to affect interpretation of genome-wide hereditary studies. The genetic basis of susceptibility in most familial patients remained unexplained and highly heterogeneous.","asOf":"2026-09-24","links":[{"label":"Roberts et al., Cancer Discov 2016: whole genomes of 638 familial pancreatic cancer patients","url":"https://doi.org/10.1158/2159-8290.CD-15-0402"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26658419/"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":["wes-wgs","germline-testing","pancreatic-surveillance"],"targets":["brca","cdkn2a","atm"],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":[],"terms":["hereditary-cancer-syndromes"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-discovery"],"dependsOn":[],"notes":[],"journal":"Cancer Discovery","year":2016,"doi":"10.1158/2159-8290.CD-15-0402","pmid":"26658419","authors":"Roberts NJ, Norris AL, Petersen GM, et al.","paperType":"translational","findings":["BRCA2, CDKN2A and ATM confirmed; many rare candidate genes.","Clonal haematopoiesis can confound germline genome studies."],"whatItMeans":"Familial risk is mostly unexplained by the panel genes, which is why surveillance programmes enrol on family history as well as on a named variant.","caveats":["Candidate genes unvalidated.","Familial cohort, not population-based."],"changedPractice":false,"participants":638},{"id":"paper-waddell-whole-genomes-pancreatic-nature-2015","kind":"paper","name":"Whole genomes redefine the mutational landscape of pancreatic cancer","aka":[],"tldr":"The 2015 whole-genome study of 100 pancreatic cancers that sorted them by how broken their chromosomes were and noticed that the most unstable tumours, often with BRCA-type defects, responded to platinum chemotherapy.","summary":"Waddell and colleagues of the Australian Pancreatic Cancer Genome Initiative performed whole-genome sequencing and copy number analysis of 100 pancreatic ductal adenocarcinomas. Chromosomal rearrangements disrupting known genes (TP53, SMAD4, CDKN2A, ARID1A, ROBO2) and new candidates (KDM6A, PREX2) were prevalent. Patterns of structural variation classified the tumours into four subtypes: stable, locally rearranged, scattered and unstable. Focal amplifications containing druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3, PIK3CA) were found at low individual prevalence. Genomic instability co-segregated with inactivation of BRCA1, BRCA2 or PALB2 and a DNA damage repair deficiency signature; of eight patients who received platinum, four of five with these measures of defective DNA maintenance responded.","asOf":"2026-09-24","links":[{"label":"Nature 2015","url":"https://doi.org/10.1038/nature14169"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25719666/"}],"tags":["pancreatic-evidence"],"related":["paper-bailey-molecular-subtypes-pancreatic-nature-2016","paper-polo-olaparib-maintenance-gbrca-pancreatic-nejm-2019"],"cancers":["pancreatic","brca-palb2-pdac"],"sections":[],"technologies":["wes-wgs","platinum","hrd-testing"],"targets":["brca","palb2","kdm6a","tp53","smad4","cdkn2a","her2"],"drugs":[],"companies":[],"institutions":["garvan-institute"],"pathways":["ddr","homologous-recombination-repair","chromosomal-instability","mutagenesis-signatures"],"terms":["platinum-sensitivity","gbrca-mutation","hrd","mutational-signature"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2015,"doi":"10.1038/nature14169","pmid":"25719666","authors":"Waddell N, Pajic M, Patch AM, et al.","paperType":"basic","findings":["100 whole genomes; four structural subtypes: stable, locally rearranged, scattered, unstable.","Druggable focal amplifications (ERBB2, MET, FGFR1, CDK6, PIK3R3, PIK3CA) at low individual prevalence.","Unstable genomes co-segregated with BRCA1, BRCA2 or PALB2 inactivation; 4 of 5 such patients responded to platinum."],"whatItMeans":"The genomic case for platinum in BRCA-type pancreatic cancer, four years before POLO built a maintenance strategy on top of it.","caveats":["Eight platinum-treated patients; the response observation is a hint, not a trial.","Whole-genome sequencing was not routine clinical practice in 2015 and is not routine in the NHS pathway now."],"participants":100},{"id":"paper-li-gallbladder-exome-erbb-nat-genet-2014","kind":"paper","name":"Whole-exome and targeted gene sequencing of gallbladder carcinoma identifies recurrent mutations in the ErbB pathway","aka":[],"tldr":"The first exome study of gallbladder cancer, in 57 Chinese patients, found TP53 mutated in about half and showed that the ErbB family of growth receptors (EGFR, HER2, HER3 and their partners) is the most commonly hit pathway, with a worse outlook when it is.","summary":"Somatic mutations were identified in 57 tumour-normal pairs of gallbladder carcinoma through a combination of exome sequencing and ultra-deep sequencing of cancer-related genes. The mutation pattern was defined by a dominant prevalence of C>T mutations at TCN sites. Genes with a significant frequency (false discovery rate below 0.05) of non-silent mutations were TP53 (47.1%), KRAS (7.8%) and ERBB3 (11.8%).\n\nErbB signalling (including EGFR, ERBB2, ERBB3, ERBB4 and their downstream genes) was the most extensively mutated pathway, affecting 36.8% (21 of 57) of the samples, and multivariate analysis showed that cases with ErbB pathway mutations had a worse outcome (P = 0.001).","asOf":"2026-09-24","links":[{"label":"Li et al., Nat Genet 2014: exome and targeted sequencing of 57 gallbladder carcinomas","url":"https://doi.org/10.1038/ng.3030"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24997986/"},{"label":"cBioPortal study gbc_shanghai_2014 (Gallbladder Carcinoma, Shanghai, Nat Genet 2014; 32 exomes)","url":"https://www.cbioportal.org/study/summary?id=gbc_shanghai_2014"}],"tags":[],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":["tp53","kras","her3","her2","egfr"],"drugs":[],"companies":[],"institutions":[],"pathways":["rtk-activation"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":2014,"doi":"10.1038/ng.3030","pmid":"24997986","authors":"Li M, Zhang Z, Li X, et al.","paperType":"translational","findings":["TP53 mutated in 47.1%, ERBB3 in 11.8% and KRAS in 7.8% of 57 gallbladder carcinomas.","The ErbB pathway was mutated in 36.8% (21 of 57) and carried a worse outcome (P = 0.001).","C>T mutations at TCN sites dominated the mutation spectrum."],"whatItMeans":"This paper put HER-family signalling at the centre of gallbladder cancer biology a decade before HER2-directed drugs were approved for it, and it is why ERBB2 and ERBB3 sit near the top of every later panel study.","caveats":["57 patients from one Chinese centre; frequencies in Chile, India and the West differ.","Exome depth of the era; copy-number calls were limited."],"changedPractice":false,"participants":57},{"id":"paper-wu-pancreatic-cyst-exomes-rnf43-pnas-2011","kind":"paper","name":"Whole-exome sequencing of neoplastic cysts of the pancreas reveals recurrent mutations in components of ubiquitin-dependent pathways","aka":[],"tldr":"Sequencing the four main kinds of pancreatic cyst found that the two that can turn into cancer, IPMN and mucinous cystic neoplasm, share inactivating mutations in a previously unknown suppressor gene, RNF43.","summary":"Exomic sequences were determined from the neoplastic epithelium of eight surgically resected cysts of each major type: serous cystadenoma, IPMN, mucinous cystic neoplasm and solid pseudopapillary neoplasm. They contained 10, 27, 16 and 2.9 somatic mutations per tumour respectively. Four of eight serous cystadenomas carried VHL mutations. Six of eight IPMNs and three of eight mucinous cystic neoplasms harboured mutations of RNF43, a gene encoding a protein with intrinsic E3 ubiquitin ligase activity not previously found altered in any human cancer; the preponderance of inactivating mutations establishes it as a suppressor of both. Solid pseudopapillary neoplasms always contained CTNNB1 mutations.","asOf":"2026-09-24","links":[{"label":"Wu et al., PNAS 2011: exomes of neoplastic pancreatic cysts, RNF43 in IPMN and MCN","url":"https://doi.org/10.1073/pnas.1118046108"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22158988/"}],"tags":[],"related":[],"cancers":["pancreatic","ipmn-cystic-precursors"],"sections":[],"technologies":[],"targets":["rnf43","ctnnb1"],"drugs":[],"companies":[],"institutions":["johns-hopkins"],"pathways":["wnt","ubiquitin-proteasome-system"],"terms":[],"trials":[],"people":["bert-vogelstein","kenneth-kinzler"],"bottlenecks":[],"keyPapers":[],"journals":["pnas"],"dependsOn":[],"notes":[],"journal":"PNAS","year":2011,"doi":"10.1073/pnas.1118046108","pmid":"22158988","authors":"Wu J, Jiao Y, Dal Molin M, et al.","paperType":"translational","findings":["RNF43 inactivating mutations in 6 of 8 IPMNs and 3 of 8 mucinous cystic neoplasms.","VHL in serous cystadenomas; CTNNB1 in every solid pseudopapillary neoplasm."],"whatItMeans":"It put RNF43 on the pancreatic driver list and gave cyst fluid testing a way to separate the harmless serous cyst from the mucinous ones that need watching.","caveats":["Eight cysts of each type.","Mutation profiles do not by themselves grade dysplasia."],"changedPractice":false,"participants":32},{"id":"paper-witkiewicz-pancreatic-exomes-utsw-nat-commun-2015","kind":"paper","name":"Whole-exome sequencing of pancreatic cancer defines genetic diversity and therapeutic targets","aka":[],"tldr":"By cutting the cancer cells out from the surrounding scar tissue before sequencing 109 tumours, this study got cleaner mutation calls and found that MYC gain marks the worst outcomes, that codon-61 KRAS and RBM10 changes go with longer survival, and that BRAF-mutant tumours lack KRAS and respond to BRAF drugs in models.","summary":"109 microdissected pancreatic ductal adenocarcinomas underwent whole-exome sequencing; microdissection enriched cellularity and mutation calling. Environmental stress and DNA repair gene alterations associated with distinct mutation spectra. Amplification of MYC was uniquely associated with poor outcome and the adenosquamous subtype. RBM10 mutations associated with longer survival despite aggressive histology. KRAS mutations were observed in more than 90%, but codon Q61 alleles were selectively associated with improved survival. Oncogenic BRAF mutations were mutually exclusive with KRAS and defined sensitivity to vemurafenib in models. High-frequency alterations in Wnt, chromatin remodelling, Hedgehog, DNA repair and cell cycle processes were observed.\n\nDeposited as paad_utsw_2015 on cBioPortal (KRAS 100 of 109; MYC amplified in 13; BRAF V600E in 3).","asOf":"2026-09-24","links":[{"label":"Witkiewicz et al., Nat Commun 2015: exomes of 109 microdissected pancreatic cancers (UTSW)","url":"https://doi.org/10.1038/ncomms7744"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25855536/"},{"label":"cBioPortal study paad_utsw_2015 (UTSW, Nat Commun 2015; 109 microdissected exomes with copy number)","url":"https://www.cbioportal.org/study/summary?id=paad_utsw_2015"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":["wes-wgs"],"targets":["kras","myc-gene","braf","rnf43"],"drugs":[],"companies":[],"institutions":["utsw-simmons"],"pathways":["myc","ras-mapk","wnt"],"terms":["kras-mutation-subtypes"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-communications"],"dependsOn":[],"notes":[],"journal":"Nature Communications","year":2015,"doi":"10.1038/ncomms7744","pmid":"25855536","authors":"Witkiewicz AK, McMillan EA, Balaji U, et al.","paperType":"translational","findings":["KRAS in more than 90%; Q61 alleles associated with better survival.","MYC amplification associated with poor outcome and adenosquamous histology.","BRAF mutations mutually exclusive with KRAS and vemurafenib-sensitive in models."],"whatItMeans":"The microdissected cohort is the cleanest exome reference for allele-level KRAS and copy-number calls, and it first tied MYC amplification to the squamous, chemotherapy-resistant end of the disease.","caveats":["Single-centre resected cohort.","Survival associations are retrospective."],"changedPractice":false,"participants":109},{"id":"paper-ren-chinese-prostate-whole-genome-eur-urol-2018","kind":"paper","name":"Whole-genome and transcriptome sequencing of prostate cancer identifies new genetic alterations driving disease progression","aka":[],"tldr":"The first large genomic study of prostate cancer in Chinese men found the signature fusion that dominates Western series is uncommon, and a different deletion takes its place.","summary":"Whole-genome and transcriptome sequencing was performed on tumour and matched benign tissue from 65 treatment-naive Chinese prostate cancer patients, with targeted deep sequencing of 293 prostate cancer-relevant genes in a further 145 tumours. A high frequency of CHD1 deletion was associated with a low rate of TMPRSS2-ERG fusion and a relatively high proportion of mutations in genes upstream of the androgen receptor. Five putative clustered deleted tumour suppressor genes were identified, with experimental and clinical evidence that PCDH9, deleted or lost in about 23% of tumours, functions as a tumour suppressor with prognostic value. Axon guidance pathway genes were frequently deregulated, including gain or amplification of PLXNA1 in about 17% of tumours, and increased PLXNA1 expression promoted tumour growth and independently predicted biochemical recurrence, metastasis and shorter survival in multi-institutional cohorts.","asOf":"2026-09-25","links":[{"label":"Ren et al., Eur Urol 2018: whole-genome and transcriptome sequencing of 65 treatment-naive Chinese prostate cancers with a 145-tumour targeted validation cohort","url":"https://doi.org/10.1016/j.eururo.2017.08.027"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28927585/"},{"label":"cBioPortal study prad_eururol_2017 (Second Military Medical University, Eur Urol 2018; 65 treatment-naive Chinese prostate cancers)","url":"https://www.cbioportal.org/study/summary?id=prad_eururol_2017"}],"tags":[],"related":[],"cancers":["prostate"],"sections":[],"technologies":["wes-wgs","rna-seq"],"targets":["erg","tmprss2","androgen-receptor"],"drugs":[],"companies":[],"institutions":[],"pathways":["prostate-cancer-signalling","ar-signaling","chromosomal-instability"],"terms":["gene-fusion","copy-number-variation-term","driver-mutation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["european-urology"],"dependsOn":[],"notes":[],"journal":"European Urology","year":2018,"doi":"10.1016/j.eururo.2017.08.027","pmid":"28927585","authors":"Ren S, Wei GH, Liu D, et al.","paperType":"basic","findings":["High CHD1 deletion frequency with a low TMPRSS2-ERG fusion rate in Chinese patients.","PCDH9 deleted or lost in about 23% of tumours and shown to be a tumour suppressor with prognostic value.","PLXNA1 gained or amplified in about 17%, predicting recurrence, metastasis and shorter survival."],"whatItMeans":"It is the reason a prostate cancer fusion frequency quoted without an ancestry is unsafe. In this cohort the founder event that defines almost half of Western tumours is uncommon, and the fusion-negative, CHD1-deleted route dominates instead.","caveats":["Sixty-five whole genomes with a 145-tumour targeted validation set.","Treatment-naive disease, so it describes the primary tumour.","PCDH9 and PLXNA1 have no therapy and have not been widely replicated."],"changedPractice":false,"participants":210},{"id":"paper-hayward-melanoma-whole-genome-nature-2017","kind":"paper","name":"Whole-genome landscapes of major melanoma subtypes","aka":[],"tldr":"Whole-genome sequencing of 183 melanomas showed that acral and mucosal melanomas have far fewer mutations than sun-exposed skin melanomas but many more structural rearrangements, confirming they are biologically different diseases.","summary":"Whole-genome sequencing of 183 melanomas including cutaneous, acral and mucosal subtypes, characterising mutation burden, ultraviolet signatures, structural variants, telomerase promoter alterations and driver genes.\n\nCutaneous melanomas carried a high ultraviolet-signature mutation load, whereas acral and mucosal melanomas had low point-mutation burden, frequent structural variants and amplifications (including KIT, CDK4 and CCND1), and different driver patterns.","asOf":"2026-09-17","links":[{"label":"Nature 2017","url":"https://doi.org/10.1038/nature22071"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28467829/"}],"tags":[],"related":[],"cancers":["acral-melanoma","mucosal-melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2017,"doi":"10.1038/nature22071","pmid":"28467829","authors":"Hayward NK, Wilmott JS, Waddell N, et al.","paperType":"translational","findings":["Acral and mucosal melanomas: low mutation burden, high structural variant load.","Frequent amplifications of KIT, CDK4 and CCND1 in non-sun-exposed subtypes."],"whatItMeans":"The lower response of acral and mucosal melanoma to immunotherapy and the interest in KIT and CDK4/6 inhibitors for these subtypes follow from this genomic picture.","caveats":["Relatively small numbers of acral and mucosal tumours."],"changedPractice":true,"participants":183},{"id":"paper-staaf-tnbc-whole-genome-scan-b-nat-med-2019","kind":"paper","name":"Whole-genome sequencing of triple-negative breast cancers in a population-based clinical study","aka":[],"tldr":"Reading the whole genome of 254 Swedish triple-negative cancers showed that 59% carry the signature of broken BRCA-type DNA repair, two-thirds of them explained by BRCA1 or BRCA2 mutation, BRCA1 or RAD51C promoter methylation or PALB2 loss, and that these patients did best on standard chemotherapy.","summary":"254 TNBCs from the population-based SCAN-B project (NCT02306096; TNBC was 9% of the cohort) were whole-genome sequenced; 237 (93%) gave sufficient data, with 3% failure at 30-fold depth and 11% at 15-fold. HRDetect classified 58.6% as HRDetect-high, 5.5% intermediate and 35.9% low; 88.5% of women under 50 were HRDetect-high. Of 139 high cases, 29 (21%) had biallelic BRCA1/2 loss (20 germline, 9 somatic), 55 (40%) BRCA1 promoter hypermethylation with loss of the other allele, five pathogenic germline PALB2 variants and five RAD51C hypermethylations; 33% were unexplained. A germline SINE-VNTR-Alu retrotransposition abrogating BRCA1 was discovered. HRDetect-high patients had better invasive disease-free survival (HR 0.42) and distant relapse-free interval (HR 0.31) on adjuvant chemotherapy; intermediate had the poorest outcome; about 4.7% of HRDetect-low tumours were mismatch-repair deficient and the low group was enriched for PIK3CA/AKT1 pathway abnormalities. The copy-number-based HRD assay had a 13% false-negative rate against HRDetect.","asOf":"2026-09-24","links":[{"label":"Staaf et al., Nat Med 2019: whole-genome sequencing of 254 population-based TNBCs (SCAN-B)","url":"https://doi.org/10.1038/s41591-019-0582-4"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31570822/"}],"tags":[],"related":[],"cancers":["tnbc","tnbc-early"],"sections":[],"technologies":["wes-wgs","hrd-testing"],"targets":["brca","palb2","rad51c","mmr"],"drugs":[],"companies":[],"institutions":["lund-skane"],"pathways":["homologous-recombination-repair","mutagenesis-signatures"],"terms":["hrd","mutational-signature"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2019,"doi":"10.1038/s41591-019-0582-4","pmid":"31570822","authors":"Staaf J, Glodzik D, Bosch A, et al.","paperType":"translational","findings":["HRDetect-high 58.6%, intermediate 5.5%, low 35.9% of 237 TNBC genomes.","Causes of high scores: BRCA1/2 biallelic loss 21%, BRCA1 promoter hypermethylation 40%, PALB2 and RAD51C 6.5%, unexplained 33%.","HRDetect-high: invasive disease-free survival HR 0.42 and distant relapse-free HR 0.31 on adjuvant chemotherapy; 4.7% of HRDetect-low tumours mismatch-repair deficient."],"whatItMeans":"It is the best population-based estimate of how much TNBC is homologous recombination deficient, shows that most of it is not germline BRCA, and argues that whole-genome sequencing at diagnosis could stratify trials and pick out the low group that needs something other than DNA-damaging chemotherapy.","caveats":["Prognostic, not predictive: the outcome benefit was on chemotherapy, with no untreated comparison.","Swedish population; ancestry-specific founder effects are absent."],"changedPractice":false,"participants":254},{"id":"paper-bissell-nat-med","kind":"paper","name":"Why don't we get more cancer? A proposed role of the microenvironment in restraining cancer progression","aka":[],"tldr":"Paper cited by one term page, indexed on Europe PMC as PubMed record 21383745 and published in Nature Medicine; the citing page links this DOI, which is how the record was matched.","summary":"Tumors are like new organs and are made of multiple cell types and components. The tumor competes with the normal microenvironment to overcome antitumorigenic pressures. Before that battle is won, the tumor may exist within the organ unnoticed by the host, referred to as 'occult cancer'. We review how normal tissue homeostasis and architecture inhibit progression of cancer and how changes in the microenvironment can shift the balance of these signals to the procancerous state. We also include a discussion of how this information is being tailored for clinical use.\n\nIndexed on Europe PMC as PubMed record 21383745 (DOI 10.1038/nm.2328). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Med 2011","url":"https://doi.org/10.1038/nm.2328"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/21383745/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/21383745"}],"tags":["europepmc-ingest"],"related":["tissue-organisation-field-theory"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2011,"doi":"10.1038/nm.2328","pmid":"21383745","authors":"Bissell MJ, Hines WC","paperType":"review","findings":[],"whatItMeans":"One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-kras-colorectal-j-clin-oncol-2008","kind":"paper","name":"Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer","aka":[],"tldr":"Phase 2 or 3 results paper on KRAS in Colorectal cancer, in Journal of Clinical Oncology (2008), one of the most cited Europe PMC records with KRAS in its title.","summary":"Purpose: Panitumumab, a fully human antibody against the epidermal growth factor receptor (EGFR), has activity in a subset of patients with metastatic colorectal cancer (mCRC). Although activating mutations in KRAS, a small G-protein downstream of EGFR, correlate with poor response to anti-EGFR antibodies in mCRC, their role as a selection marker has not been established in randomized trials.\n\nPatients and methods: KRAS mutations were detected using polymerase chain reaction on DNA from tumor sections collected in a phase III mCRC trial comparing panitumumab monotherapy to best supportive care (BSC). We tested whether the effect of panitumumab on progression-free survival (PFS) differed by KRAS status.\n\nResults: KRAS status was ascertained in 427 (92%) of 463 patients (208 panitumumab, 219 BSC). KRAS mutations were found in 43% of patients. The treatment effect on PFS in the wild-type (WT) KRAS group (hazard ratio [HR], 0.45; 95% CI: 0.34 to 0.59) was significantly greater (P <.0001) than in the mutant group (HR, 0.99; 95% CI, 0.73 to 1.36). Median PFS in the WT KRAS group was 12.3 weeks for panitumumab and 7.3 weeks for BSC. Response rates to panitumumab were 17% and 0%, for the WT and mutant groups, respectively. WT KRAS patients had longer overall survival (HR, 0.67; 95% CI, 0.55 to 0.82; treatment arms combined). Consistent with longer exposure, more grade III treatment-related toxicities occurred in the WT KRAS group. No significant differences in toxicity were observed between the WT KRAS group and the overall population.\n\nConclusion: Panitumumab monotherapy efficacy in mCRC is confined to patients with WT KRAS tumors. KRAS status should be considered in selecting patients with mCRC as candidates for panitumumab monotherapy.\n\nIndexed on Europe PMC as PubMed record 18316791 (DOI 10.1200/jco.2007.14.7116). Its title names KRAS and its text names Colorectal cancer; PubMed types it as a clinical trial report (Clinical Trial, Phase III, Multicenter Study, Randomized Controlled Trial). It was matched automatically to the idea \"Covalent chemistry for the RAS mutations that still have no drug\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Clin Oncol 2008","url":"https://doi.org/10.1200/jco.2007.14.7116"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/18316791/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/18316791"}],"tags":["europepmc-ingest"],"related":["paper-douillard-prime-panitumumab-ras-nejm-2013"],"cancers":["colorectal"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2008,"doi":"10.1200/jco.2007.14.7116","pmid":"18316791","authors":"Amado RG, Wolf M, Peeters M, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for KRAS in Colorectal cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by KRAS in the title and Colorectal cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-barton-j-natl-cancer-inst","kind":"paper","name":"Wisconsin Ginseng (Panax quinquefolius) to improve cancer-related fatigue: a randomized, double-blind trial, N07C2","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 23853057 and published in JNCI: Journal of the National Cancer Institute; the citing page links this DOI, which is how the record was matched.","summary":"Background: Safe, effective interventions to improve cancer-related fatigue (CRF) are needed because it remains a prevalent, distressing, and activity-limiting symptom. Based on pilot data, a phase III trial was developed to evaluate the efficacy of American ginseng on CRF.\n\nMethods: A multisite, double-blind trial randomized fatigued cancer survivors to 2000mg of American ginseng vs a placebo for 8 weeks. The primary endpoint was the general subscale of the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) at 4 weeks. Changes from baseline at 4 and 8 weeks were evaluated between arms by a two-sided, two-sample t test. Toxicities were evaluated by self-report and the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) provider grading.\n\nResults: Three hundred sixty-four participants were enrolled from 40 institutions. Changes from baseline in the general subscale of the MFSI-SF were 14.4 (standard deviation [SD] = 27.1) in the ginseng arm vs 8.2 (SD = 24.8) in the placebo arm at 4 weeks (P =.07). A statistically significant difference was seen at 8 weeks with a change score of 20 (SD = 27) for the ginseng group and 10.3 (SD = 26.1) for the placebo group (P =.003). Greater benefit was reported in patients receiving active cancer treatment vs those who had completed treatment. Toxicities per self-report and CTCAE grading did not differ statistically significantly between arms.\n\nConclusions: Data support the benefit of American ginseng, 2000mg daily, on CRF over an 8-week period. There were no discernible toxicities associated with the treatment. Studies to increase knowledge to guide the role of ginseng to improve CRF are needed.\n\nIndexed on Europe PMC as PubMed record 23853057 (DOI 10.1093/jnci/djt181). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Natl Cancer Inst 2013","url":"https://doi.org/10.1093/jnci/djt181"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23853057/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/23853057"}],"tags":["europepmc-ingest"],"related":["american-ginseng-fatigue"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jnci"],"dependsOn":[],"notes":[],"journal":"JNCI: Journal of the National Cancer Institute","year":2013,"doi":"10.1093/jnci/djt181","pmid":"23853057","authors":"Barton DL, Liu H, Dakhil SR, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-wisnoski-acinar-cell-carcinoma-672-patients-seer-surgery-2008","kind":"paper","name":"Wisnoski 2008: 672 patients with acinar cell carcinoma of the pancreas, a population-based comparison to pancreatic adenocarcinoma","aka":[],"tldr":"Using the US cancer registry, this study showed that people with acinar cell carcinoma live far longer than those with ordinary pancreatic cancer at every stage, and that surgery gives a large fraction of them a chance of long-term survival.","summary":"Analysis of the SEER registry from 1988 to 2003 comparing 672 patients with pancreatic acinar cell carcinoma to more than 40,000 with pancreatic ductal adenocarcinoma. Acinar cell carcinoma patients were more often men and presented with larger tumours but were more likely to undergo resection.\n\nSurvival was markedly better for acinar cell carcinoma: median survival of several years against a few months for adenocarcinoma, five-year survival many times higher, and resected patients doing best. The survival advantage held after adjustment for stage and resection.","asOf":"2026-09-21","links":[{"label":"Surgery 2008","url":"https://doi.org/10.1016/j.surg.2008.03.006"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/18656619/"}],"tags":[],"related":[],"cancers":["pancreatic-acinar-cell-carcinoma","pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Surgery","year":2008,"doi":"10.1016/j.surg.2008.03.006","pmid":"18656619","authors":"Wisnoski NC, Townsend CM, Nealon WH, Freeman JL, Riall TS.","paperType":"observational","findings":["Acinar cell carcinoma survival was several times longer than ductal adenocarcinoma at every stage in SEER data.","Resection was associated with the best outcomes and was performed more often than in adenocarcinoma."],"whatItMeans":"Acinar cell carcinoma justifies an aggressive surgical approach, including for larger tumours and selected metastatic disease, because the natural history is far better than ductal adenocarcinoma.","caveats":["Registry data with no information on chemotherapy or molecular features.","Histological misclassification is possible in registry coding."],"participants":672},{"id":"paper-chan-nature","kind":"paper","name":"WRN helicase is a synthetic lethal target in microsatellite unstable cancers","aka":[],"tldr":"Paper cited by one target page, indexed on Europe PMC as PubMed record 30971823 and published in Nature; the citing page links this DOI, which is how the record was matched.","summary":"Synthetic lethality-an interaction between two genetic events through which the co-occurrence of these two genetic events leads to cell death, but each event alone does not-can be exploited for cancer therapeutics 1. DNA repair processes represent attractive synthetic lethal targets, because many cancers exhibit an impairment of a DNA repair pathway, which can lead to dependence on specific repair proteins 2. The success of poly(ADP-ribose) polymerase 1 (PARP-1) inhibitors in cancers with deficiencies in homologous recombination highlights the potential of this approach 3. Hypothesizing that other DNA repair defects would give rise to synthetic lethal relationships, we queried dependencies in cancers with microsatellite instability (MSI), which results from deficient DNA mismatch repair. Here we analysed data from large-scale silencing screens using CRISPR-Cas9-mediated knockout and RNA interference, and found that the RecQ DNA helicase WRN was selectively essential in MSI models in vitro and in vivo, yet dispensable in models of cancers that are microsatellite stable. Depletion of WRN induced double-stranded DNA breaks and promoted apoptosis and cell cycle arrest selectively in MSI models. MSI cancer models required the helicase activity of WRN, but not its exonuclease activity. These findings show that WRN is a synthetic lethal vulnerability and promising drug target for MSI cancers.\n\nIndexed on Europe PMC as PubMed record 30971823 (DOI 10.1038/s41586-019-1102-x). Matched by DOI alone: one target page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nature 2019","url":"https://doi.org/10.1038/s41586-019-1102-x"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30971823/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30971823"}],"tags":["europepmc-ingest"],"related":["wrn"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2019,"doi":"10.1038/s41586-019-1102-x","pmid":"30971823","authors":"Chan EM, Shibue T, McFarland JM, et al.","paperType":"basic","findings":[],"whatItMeans":"One target page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-xia-h101-head-neck-aizheng-2004","kind":"paper","name":"Xia 2004: the randomised trial behind China's approval of the oncolytic adenovirus H101","aka":[],"tldr":"Adding injections of an engineered adenovirus to chemotherapy roughly doubled the proportion of head and neck or oesophageal cancers that shrank, but the trial reported no survival figures.","summary":"Phase 3 randomised trial of intratumoural H101, an E1B-55 kilodalton gene-deleted replication-selective adenovirus of essentially the same design as ONYX-015, added to cisplatin-based chemotherapy in squamous cell cancer of the head and neck or oesophagus. 160 patients were recruited. Patients with no history of, or sensitivity to, cisplatin and fluorouracil received that regimen; those who had not responded to it received doxorubicin and fluorouracil. Each group was randomised to receive intratumoural H101, at 5.0 x 10^11 to 1.5 x 10^12 viral particles per day for five consecutive days every three weeks, or not.\n\nAmong 123 evaluable patients, overall response rate with cisplatin and fluorouracil plus H101 was 78.8 per cent (41 of 52) against 39.6 per cent (21 of 53) for that chemotherapy alone. The differences between the combined virus arms and the chemotherapy-alone arms were significant. The main side effects were fever in 45.7 per cent, injection-site reaction in 28.3 per cent and influenza-like symptoms in 9.8 per cent. H101 was approved in China in 2005 and marketed as Oncorine, making it the first oncolytic virus approved anywhere.","asOf":"2026-09-25","links":[{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/15601557/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/15601557"}],"tags":[],"related":[],"cancers":[],"sections":["immunotherapy"],"technologies":["oncolytic-virus"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Ai Zheng (Chinese Journal of Cancer)","year":2004,"pmid":"15601557","authors":"Xia ZJ, Chang JH, Zhang L, et al.","paperType":"rct","findings":["Overall response rate 78.8 per cent (41 of 52) with cisplatin, fluorouracil and H101 versus 39.6 per cent (21 of 53) with cisplatin and fluorouracil alone (p = 0.000 as reported).","In the doxorubicin and fluorouracil groups, response was 50.0 per cent (7 of 14) with H101 and 50.0 per cent (2 of 4) without, on numbers too small to compare.","Commonest side effects were fever (45.7 per cent), injection-site reaction (28.3 per cent) and influenza-like symptoms (9.8 per cent).","The report gives response rates only; no overall or progression-free survival result is presented."],"whatItMeans":"The world's first approval of an oncolytic virus rests on a response-rate trial of 160 patients with no survival endpoint, an uneven randomisation across two chemotherapy backbones, and 37 patients excluded from the efficacy analysis. Tumour shrinkage after injecting something into a tumour is the easiest result to obtain in this field and the least informative. H101 has never been approved outside China.","caveats":["No survival data. Response rate in an open-label trial with injected lesions is a weak endpoint.","123 of 160 recruited patients were analysed, without a described intention-to-treat analysis.","The doxorubicin and fluorouracil comparison has four patients in the control arm.","Published in Chinese in a national journal, with no DOI, and never replicated in a registrational trial outside China."],"changedPractice":true,"participants":160},{"id":"paper-yarden-sliwkowski-erbb-network-nrmcb-2001","kind":"paper","name":"Yarden and Sliwkowski 2001: untangling the ErbB signalling network","aka":[],"tldr":"The classic account of the HER family of receptors, explaining why HER2 is such a powerful cancer driver: it is the preferred partner for the other three receptors and turns their signals up, which is what trastuzumab and later HER2 drugs exploit.","summary":"Yarden and Sliwkowski described the four ErbB receptors (EGFR, HER2, HER3 and HER4) as a layered signalling network in which ligands select receptor pairs, the pairs determine which intracellular pathways are engaged, and the network's outputs control proliferation, survival and differentiation. They emphasised that HER2 has no ligand of its own but is the preferred dimerisation partner, that HER3 lacks kinase activity but couples strongly to PI3K, and that HER2 overexpression or EGFR mutation deregulates the whole network, which explains the activity of antibodies and kinase inhibitors against these receptors.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1038/35052073"}],"tags":[],"related":["paper-lemmon-schlessinger-rtk-signalling-cell-2010","paper-slamon-her2-amplification-science-1987"],"cancers":[],"sections":[],"technologies":[],"targets":["egfr","her2","her3","erbb4"],"drugs":[],"companies":["roche-genentech"],"institutions":[],"pathways":["rtk-activation"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature Reviews Molecular Cell Biology","year":2001,"doi":"10.1038/35052073","authors":"Yarden Y, Sliwkowski MX.","paperType":"review","findings":["The four ErbB receptors form a network of homo- and heterodimers whose composition determines signalling output.","HER2 is ligand-less but the preferred and most potent dimerisation partner; HER3 is kinase-impaired but a strong activator of PI3K.","Deregulation by HER2 amplification or EGFR mutation underlies many cancers and is targetable with antibodies and small molecules."],"whatItMeans":"This review is the conceptual basis for trastuzumab, pertuzumab, HER2 antibody-drug conjugates and EGFR inhibitors, and for the HER3-mediated resistance that later drugs try to overcome.","caveats":["A review; structural details of the receptor dimers were resolved later.","Written before most HER2 and EGFR drugs reached the clinic."],"changedPractice":false},{"id":"paper-cramer-cochrane-database-syst-rev","kind":"paper","name":"Yoga for improving health-related quality of life, mental health and cancer-related symptoms in women diagnosed with breast cancer","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 28045199 and published in The Cochrane database of systematic reviews; the citing page links this DOI, which is how the record was matched.","summary":"Background: Breast cancer is the cancer most frequently diagnosed in women worldwide. Even though survival rates are continually increasing, breast cancer is often associated with long-term psychological distress, chronic pain, fatigue and impaired quality of life. Yoga comprises advice for an ethical lifestyle, spiritual practice, physical activity, breathing exercises and meditation. It is a complementary therapy that is commonly recommended for breast cancer-related impairments and has been shown to improve physical and mental health in people with different cancer types.\n\nObjectives: To assess effects of yoga on health-related quality of life, mental health and cancer-related symptoms among women with a diagnosis of breast cancer who are receiving active treatment or have completed treatment.\n\nSearch methods: We searched the Cochrane Breast Cancer Specialised Register, MEDLINE (via PubMed), Embase, the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 1), Indexing of Indian Medical Journals (IndMED), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal and Clinicaltrials.gov on 29 January 2016. We also searched reference lists of identified relevant trials or reviews, as well as conference proceedings of the International Congress on Complementary Medicine Research (ICCMR), the European Congress for Integrative Medicine (ECIM) and the American Society of Clinical Oncology (ASCO). We applied no language restrictions.\n\nSelection criteria: Randomised controlled trials were eligible when they (1) compared yoga interventions versus no therapy or versus any other active therapy in women with a diagnosis of non-metastatic or metastatic breast cancer, and (2) assessed at least one of the primary outcomes on patient-reported instruments, including health-related quality of life, depression, anxiety, fatigue or sleep disturbances.\n\nData collection and analysis: Two review authors independently collected data on methods and results. We expressed outcomes as standardised mean differences (SMDs) with 95% confidence intervals (CIs) and conducted random-effects model meta-analyses. We assessed potential risk of publication bias through visual analysis of funnel plot symmetry and heterogeneity between studies by using the Chi 2 test and the I 2 statistic. We conducted subgroup analyses for current treatment status, time since diagnosis, stage of cancer and type of yoga intervention.\n\nMain results: We included 24 studies with a total of 2166 participants, 23 of which provided data for meta-analysis. Thirteen studies had low risk of selection bias, five studies reported adequate blinding of outcome assessment and 15 studies had low risk of attrition bias.Seventeen studies that compared yoga versus no therapy provided moderate-quality evidence showing that yoga improved health-related quality of life (pooled SMD 0.22, 95% CI 0.04 to 0.40; 10 studies, 675 participants), reduced fatigue (pooled SMD -0.48, 95% CI -0.75 to -0.20; 11 studies, 883 participants) and reduced sleep disturbances in the short term (pooled SMD -0.25, 95% CI -0.40 to -0.09; six studies, 657 participants). The funnel plot for health-related quality of life was asymmetrical, favouring no therapy, and the funnel plot for fatigue was roughly symmetrical. This hints at overall low risk of publication bias. Yoga did not appear to reduce depression (pooled SMD -0.13, 95% CI -0.31 to 0.05; seven studies, 496 participants; low-quality evidence) or anxiety (pooled SMD -0.53, 95% CI -1.10 to 0.04; six studies, 346 participants; very low-quality evidence) in the short term and had no medium-term effects on health-related quality of life (pooled SMD 0.10, 95% CI -0.23 to 0.42; two studies, 146 participants; low-quality evidence) or fatigue (pooled SMD -0.04, 95% CI -0.36 to 0.29; two studies, 146 participants; low-quality evidence). Investigators reported no serious adverse events.Four studies that compared yoga versus psychosocial/educational interventions provided moderate-quality evidence indicating that yoga can reduce depression (pooled SMD -2.29, 95% CI -3.97 to -0.61; four studies, 226 participants), anxiety (pooled SMD -2.21, 95% CI -3.90 to -0.52; three studies, 195 participants) and fatigue (pooled SMD -0.90, 95% CI -1.31 to -0.50; two studies, 106 participants) in the short term. Very low-quality evidence showed no short-term effects on health-related quality of life (pooled SMD 0.81, 95% CI -0.50 to 2.12; two studies, 153 participants) or sleep disturbances (pooled SMD -0.21, 95% CI -0.76 to 0.34; two studies, 119 participants). No trial adequately reported safety-related data.Three studies that compared yoga versus exercise presented very low-quality evidence showing no short-term effects on health-related quality of life (pooled SMD -0.04, 95% CI -0.30 to 0.23; three studies, 233 participants) or fatigue (pooled SMD -0.21, 95% CI -0.66 to 0.25; three studies, 233 participants); no trial provided safety-related data.\n\nAuthors' conclusions: Moderate-quality evidence supports the recommendation of yoga as a supportive intervention for improving health-related quality of life and reducing fatigue and sleep disturbances when compared with no therapy, as well as for reducing depression, anxiety and fatigue, when compared with psychosocial/educational interventions. Very low-quality evidence suggests that yoga might be as effective as other exercise interventions and might be used as an alternative to other exercise programmes.\n\nIndexed on Europe PMC as PubMed record 28045199 (DOI 10.1002/14651858.cd010802.pub2). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Cochrane Database Syst Rev 2017","url":"https://doi.org/10.1002/14651858.cd010802.pub2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28045199/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28045199"}],"tags":["europepmc-ingest"],"related":["yoga-cancer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Cochrane database of systematic reviews","year":2017,"doi":"10.1002/14651858.cd010802.pub2","pmid":"28045199","authors":"Cramer H, Lauche R, Klose P, et al.","paperType":"meta-analysis","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-harding-lancet-oncol","kind":"paper","name":"Zanidatamab for HER2-amplified, unresectable, locally advanced or metastatic biliary tract cancer (HERIZON-BTC-01): a multicentre, single-arm, phase 2b study","aka":[],"tldr":"Paper cited by one cancer page, indexed on Europe PMC as PubMed record 37276871 and published in The Lancet Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background: HER2 is overexpressed or amplified in a subset of biliary tract cancer. Zanidatamab, a bispecific antibody targeting two distinct HER2 epitopes, exhibited tolerability and preliminary anti-tumour activity in HER2-expressing or HER2 (also known as ERBB2)-amplified treatment-refractory biliary tract cancer.\n\nMethods: HERIZON-BTC-01 is a global, multicentre, single-arm, phase 2b trial of zanidatamab in patients with HER2-amplified, unresectable, locally advanced, or metastatic biliary tract cancer with disease progression on previous gemcitabine-based therapy, recruited at 32 clinical trial sites in nine countries in North America, South America, Asia, and Europe. Eligible patients were aged 18 years or older with HER2-amplified biliary tract cancer confirmed by in-situ hybridisation per central testing, at least one measurable target lesion per Response Evaluation Criteria in Solid Tumours (version 1.1), and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were assigned into cohorts based on HER2 immunohistochemistry (IHC) score: cohort 1 (IHC 2+ or 3+; HER2-positive) and cohort 2 (IHC 0 or 1+). Patients received zanidatamab 20 mg/kg intravenously every 2 weeks. The primary endpoint was confirmed objective response rate in cohort 1 as assessed by independent central review. Anti-tumour activity and safety were assessed in all participants who received any dose of zanidatamab. This trial is registered with ClinicalTrials.gov, NCT04466891, is ongoing, and is closed to recruitment.\n\nFindings: Between Sept 15, 2020, and March 16, 2022, 87 patients were enrolled in HERIZON-BTC-01: 80 in cohort 1 (45 [56%] were female and 35 [44%] were male; 52 [65%] were Asian; median age was 64 years [IQR 58-70]) and seven in cohort 2 (five [71%] were male and two [29%] were female; five [71%] were Asian; median age was 62 years [IQR 58-77]). At the time of the data cutoff (Oct 10, 2022), 18 (21%) patients (17 in cohort 1 and one in cohort 2) were continuing to receive zanidatamab; 69 (79%) discontinued treatment (radiographic progression in 64 [74%] patients). The median duration of follow-up was 12·4 months (IQR 9·4-17·2). Confirmed objective responses by independent central review were observed in 33 patients in cohort 1 (41·3% [95% CI 30·4-52·8]). 16 (18%) patients had grade 3 treatment-related adverse events; the most common were diarrhoea (four [5%] patients) and decreased ejection fraction (three [3%] patients). There were no grade 4 treatment-related adverse events and no treatment-related deaths.\n\nInterpretation: Zanidatamab demonstrated meaningful clinical benefit with a manageable safety profile in patients with treatment-refractory, HER2-positive biliary tract cancer. These results support the potential of zanidatamab as a future treatment option in HER2-positive biliary tract cancer.\n\nFunding: Zymeworks, Jazz, and BeiGene.\n\nIndexed on Europe PMC as PubMed record 37276871 (DOI 10.1016/s1470-2045(23)00242-5). Matched by DOI alone: one cancer page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2023","url":"https://doi.org/10.1016/s1470-2045(23)00242-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37276871/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37276871"}],"tags":["europepmc-ingest"],"related":["gallbladder","her2-ihc-3-plus","her2-ish-amplified","her2-testing-in-biliary-cancer"],"cancers":["gallbladder","biliary-tract-cancer"],"sections":[],"technologies":[],"targets":["her2"],"drugs":["zanidatamab"],"companies":["zymeworks","jazz","beone"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["oh-do-youn"],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2023,"doi":"10.1016/s1470-2045(23)00242-5","pmid":"37276871","authors":"Harding JJ, Fan J, Oh DY, et al.","paperType":"observational","findings":[],"whatItMeans":"One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-zanubrutinib-cll-n-engl-j-med-2023","kind":"paper","name":"Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia","aka":[],"tldr":"Phase 2 or 3 results paper on Zanubrutinib in Chronic lymphocytic leukaemia, in New England Journal of Medicine (2023), one of the most cited Europe PMC records with Zanubrutinib in its title.","summary":"Background: In a multinational, phase 3, head-to-head trial, ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, was compared with zanubrutinib, a BTK inhibitor with greater specificity, as treatment for relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). In prespecified interim analyses, zanubrutinib was superior to ibrutinib with respect to overall response (the primary end point). Data from the final analysis of progression-free survival are now available.\n\nMethods: We randomly assigned, in a 1:1 ratio, patients with relapsed or refractory CLL or SLL who had received at least one previous course of therapy to receive zanubrutinib or ibrutinib until the occurrence of disease progression or unacceptable toxic effects. In this final analysis, progression-free survival (a key secondary end point) was assessed with the use of a hierarchical testing strategy to determine whether zanubrutinib was noninferior to ibrutinib. If noninferiority was established, the superiority of zanubrutinib was assessed and claimed if the two-sided P value was less than 0.05.\n\nResults: At a median follow-up of 29.6 months, zanubrutinib was found to be superior to ibrutinib with respect to progression-free survival among 652 patients (hazard ratio for disease progression or death, 0.65; 95% confidence interval, [CI], 0.49 to 0.86; P = 0.002), as assessed by the investigators; the results were similar to those as assessed by an independent-review committee. At 24 months, the investigator-assessed rates of progression-free survival were 78.4% in the zanubrutinib group and 65.9% in the ibrutinib group. Among patients with a 17p deletion, a TP53 mutation, or both, those who received zanubrutinib had longer progression-free survival than those who received ibrutinib (hazard ratio for disease progression or death, 0.53; 95% CI, 0.31 to 0.88); progression-free survival across other major subgroups consistently favored zanubrutinib. The percentage of patients with an overall response was higher in the zanubrutinib group than in the ibrutinib group. The safety profile of zanubrutinib was better than that of ibrutinib, with fewer adverse events leading to treatment discontinuation and fewer cardiac events, including fewer cardiac events leading to treatment discontinuation or death.\n\nConclusions: In patients with relapsed or refractory CLL or SLL, progression-free survival was significantly longer among patients who received zanubrutinib than among those who received ibrutinib, and zanubrutinib was associated with fewer cardiac adverse events. (Funded by BeiGene; ALPINE ClinicalTrials.gov number, NCT03734016.).\n\nIndexed on Europe PMC as PubMed record 36511784 (DOI 10.1056/nejmoa2211582). Its title names Zanubrutinib and its text names Chronic lymphocytic leukaemia; PubMed types it as a clinical trial report (Clinical Trial, Phase III, Research Support, Non-U.S. Gov't, Multicenter Study, Randomized Controlled Trial). It was matched automatically to the idea \"MRD-guided treatment duration in CLL\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2023","url":"https://doi.org/10.1056/nejmoa2211582"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/36511784/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/36511784"},{"label":"ClinicalTrials.gov NCT03734016","url":"https://clinicaltrials.gov/study/NCT03734016"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["alpine"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/nejmoa2211582","pmid":"36511784","authors":"Brown JR, Eichhorst B, Hillmen P, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Zanubrutinib in Chronic lymphocytic leukaemia, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Zanubrutinib in the title and Chronic lymphocytic leukaemia in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-zanubrutinib-cll-lancet-oncol-2022","kind":"paper","name":"Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial","aka":[],"tldr":"Phase 2 or 3 results paper on Zanubrutinib in Chronic lymphocytic leukaemia, in The Lancet Oncology (2022), one of the most cited Europe PMC records with Zanubrutinib in its title.","summary":"Background: Zanubrutinib is a next-generation, selective Bruton tyrosine kinase inhibitor with efficacy in relapsed chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). We compared zanubrutinib with bendamustine-rituximab to determine its effectiveness as frontline therapy in patients with CLL or SLL.\n\nMethods: We conducted an open-label, multicentre, phase 3 study at 153 academic or community hospitals in 14 countries and regions. Eligible patients had untreated CLL or SLL requiring treatment as per International Workshop on CLL criteria; were aged 65 years or older, or 18 years or older and had comorbidities; and had an Eastern Cooperative Oncology Group performance status score of 0-2. A central interactive web response system randomly assigned patients without del(17)(p13·1) to zanubrutinib (group A) or bendamustine-rituximab (group B) by sequential block method (permutated blocks with a random block size of four). Patients with del(17)(p13·1) were enrolled in group C and received zanubrutinib. Zanubrutinib was administered orally at 160 mg twice per day (28-day cycles); bendamustine at 90 mg/m 2 of body surface area on days 1 and 2 for six cycles plus rituximab at 375 mg/m 2 of body surface area the day before or on day 1 of cycle 1, and 500 mg/m 2 of body surface area on day 1 of cycles 2-6, were administered intravenously. The primary endpoint was progression-free survival per independent review committee in the intention-to-treat population in groups A and B, with minimum two-sided α of 0·05 for superiority. Safety was analysed in all patients who received at least one dose of study treatment. The study is registered with ClinicalTrials.gov, NCT03336333, and is closed to recruitment.\n\nFindings: Between Oct 31, 2017, and July 22, 2019, 590 patients were enrolled; patients without del(17)(p13·1) were randomly assigned to zanubrutinib (group A; n=241) or bendamustine-rituximab (group B; n=238). At median follow-up of 26·2 months (IQR 23·7-29·6), median progression-free survival per independent review committee was not reached in either group (group A 95% CI not estimable [NE] to NE; group B 28·1 months to NE). Progression-free survival was significantly improved in group A versus group B (HR 0·42 [95% CI 0·28 to 0·63]; two-sided p<0·0001). The most common grade 3 or worse adverse event was neutropenia (27 [11%] of 240 patients in group A, 116 [51%] of 227 in group B, and 17 [15%] of 111 patients in group C). Serious adverse events occurred in 88 (37%) of 240 patients in group A, 113 (50%) of 227 patients in group B, and 45 (41%) of 111 patients in group C. Adverse events leading to death occurred in 11 (5%) of 240 patients in group A, 12 (5%) of 227 patients in group B, and three (3%) of 111 patients in group C, most commonly due to COVID-19 (four [2%] of 240 patients in group A), diarrhoea, and aspiration pneumonia (two each [1%] of 227 patients in group B).\n\nInterpretation: Zanubrutinib significantly improved progression-free survival versus bendamustine-rituximab, with an acceptable safety profile consistent with previous studies. These data support zanubrutinib as a potential new treatment option for untreated CLL and SLL.\n\nFunding: BeiGene.\n\nIndexed on Europe PMC as PubMed record 35810754 (DOI 10.1016/s1470-2045(22)00293-5). Its title names Zanubrutinib and its text names Chronic lymphocytic leukaemia; PubMed types it as a clinical trial report (Clinical Trial, Phase III, Research Support, Non-U.S. Gov't, Randomized Controlled Trial). It was matched automatically to the idea \"MRD-guided treatment duration in CLL\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2022","url":"https://doi.org/10.1016/s1470-2045(22)00293-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35810754/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35810754"},{"label":"ClinicalTrials.gov NCT03336333","url":"https://clinicaltrials.gov/study/NCT03336333"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["sequoia"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2022,"doi":"10.1016/s1470-2045(22)00293-5","pmid":"35810754","authors":"Tam CS, Brown JR, Kahl BS, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Zanubrutinib in Chronic lymphocytic leukaemia, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Zanubrutinib in the title and Chronic lymphocytic leukaemia in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-zanubrutinib-cll-lancet-haematol-2021","kind":"paper","name":"Zanubrutinib, obinutuzumab, and venetoclax with minimal residual disease-driven discontinuation in previously untreated patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: a multicentre, single-arm, phase 2 trial","aka":[],"tldr":"Phase 2 or 3 results paper on Zanubrutinib in Chronic lymphocytic leukaemia, in The Lancet Haematology (2021), one of the most cited Europe PMC records with Zanubrutinib in its title.","summary":"Background: We hypothesised that combining zanubrutinib with obinutuzumab and venetoclax (BOVen) as an initial therapy for chronic lymphocytic leukaemia and small lymphocytic lymphoma would lead to high rates of undetectable minimal residual disease (MRD), and we explored MRD as a biomarker for directing treatment duration.\n\nMethods: This multicenter, investigator-initiated, single-arm, phase 2 trial took place at two two academic medical centres in the USA. Patients were eligible for the primary cohort if they had treatment-naive chronic lymphocytic leukaemia or small lymphocytic lymphoma, required therapy, and were at least 18 years of age with an Eastern Cooperative Oncology Group performance status up to 2. BOVen was administered in 28 day cycles (oral zanubrutinib at 160 mg twice per day starting in cycle 1 on day 1; intravenous obinutuzumab at 1000 mg on day 1 [split over day 1 with 100 mg and day 2 with 900 mg for an absolute lymphocyte count >25 000 cells per μL or lymph nodes >5 cm in diameter], day 8, and day 15 of cycle 1, and day 1 of cycles 2-8; and oral venetoclax ramp up to 400 mg per day starting in cycle 3 on day 1) and discontinued after 8-24 cycles when prespecified undetectable MRD criteria were met in the peripheral blood and bone marrow. The primary endpoint was the proportion of patients that reached undetectable MRD in both the peripheral blood and bone marrow (flow cytometry cutoff less than one chronic lymphocytic leukaemia cell per 10 000 leukocytes [<10 -4 ]) assessed per protocol. This trial is registered at clinicaltrials.gov (NCT03824483). The primary cohort is closed to recruitment, and recruitment continues in the TP53-mutated mantle cell lymphoma cohort.\n\nFindings: Between March 14, 2019, and Oct 10, 2019, 47 patients were screened for eligibility, and 39 patients were enrolled and treated. Median age was 62 years (IQR 52-70) with 30 (77%) of 39 male participants and nine (23%) of 39 female participants. 28 (72%) of 39 patients had unmutated immunoglobulin heavy-chain variable-region and five (13%) of 39 had 17p deletion or TP53 mutation. After a median follow-up of 25·8 months (IQR 24·0-27·3), 33 (89%) of 37 patients (95% CI 75-97) had undetectable MRD in both blood and bone marrow, meeting the prespecified undetectable MRD criteria to stop therapy after a median of ten cycles (IQR 8-12), which includes two cycles of zanubrutinib and obinutuzumab before starting venetoclax. After median surveillance after treatment of 15·8 months (IQR 13·0-18·6), 31 (94%) of 33 patients had undetectable MRD. The most common adverse events were thrombocytopenia (23 [59%] of 39), fatigue (21 [54%]), neutropenia (20 [51%]), and bruising (20 [51%]), and the most common adverse event at grade 3 or worse was neutropenia (seven [18%]) in the intention-to-treat population. One death occurred in a patient with intracranial haemorrhage on day 1 of cycle 1 after initiating intravenous heparin for pulmonary emboli.\n\nInterpretation: BOVen was well tolerated and met its primary endpoint, with 33 (89%) of 37 previously untreated patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma reaching undetectable MRD in both peripheral blood and bone marrow despite a median treatment duration of only 10 months, owing to our undetectable MRD-driven treatment discontinuation design. These data support further evaluation of the BOVen regimen in chronic lymphocytic leukaemia and small lymphocytic lymphoma with treatment duration guided by early MRD response kinetics.\n\nFunding: Beigene, Genentech (Roche), Grais-Cutler Fund, Lymphoma Research Fund, Lymphoma Research Foundation, American Cancer Society, Farmer Family Foundation, and the National Instititutes of Health and National Cancer Institute.\n\nIndexed on Europe PMC as PubMed record 34826411 (DOI 10.1016/s2352-3026(21)00307-0). Its title names Zanubrutinib and its text names Chronic lymphocytic leukaemia; PubMed types it as a clinical trial report (Clinical Trial, Phase II, research-article, Multicenter Study). It was matched automatically to the idea \"MRD-guided treatment duration in CLL\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Haematol 2021","url":"https://doi.org/10.1016/s2352-3026(21)00307-0"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34826411/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34826411"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-haematology"],"dependsOn":[],"notes":[],"journal":"The Lancet Haematology","year":2021,"doi":"10.1016/s2352-3026(21)00307-0","pmid":"34826411","authors":"Soumerai JD, Mato AR, Dogan A, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Zanubrutinib in Chronic lymphocytic leukaemia, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Zanubrutinib in the title and Chronic lymphocytic leukaemia in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},{"id":"paper-nct05425940-lancet-2025","kind":"paper","name":"Zanzalintinib plus atezolizumab versus regorafenib in refractory colorectal cancer (STELLAR-303): a randomised, open-label, phase 3 trial","aka":[],"tldr":"Published report from the STELLAR-303 trial registered as NCT05425940, in The Lancet (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Zanzalintinib is a multitargeted tyrosine-kinase inhibitor that, when combined with atezolizumab, showed promising antitumour activity and manageable toxicity in a phase 1 study. We aimed to compare the efficacy and safety of zanzalintinib-atezolizumab versus regorafenib in patients with previously treated metastatic colorectal cancer.\n\nMethods: STELLAR-303 is a global, randomised, open-label, phase 3 trial done at 121 centres (including hospitals, academic medical centres, and specialised cancer research facilities) in 16 countries. Patients aged 18 years and older with confirmed metastatic adenocarcinoma of the colon or rectum, who had previously received standard-of-care therapy, and did not have microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumours were randomly assigned (1:1) in blocks of four to oral zanzalintinib (100 mg daily) plus intravenous atezolizumab (1200 mg every 3 weeks) or oral regorafenib (160 mg daily on days 1-21 of each 28-day cycle) using an interactive response technology system, stratified by geographical region, RAS status, and presence of liver metastases. Dual primary endpoints were overall survival in the intention-to-treat (ITT) population and in the subset of patients without liver metastases. Safety was assessed in all patients who received at least one dose of study drug. This report is based on a planned overall survival analysis (data cutoff April 30, 2025); the trial is active but not recruiting, and continues to the final overall survival analysis in the subset of patients without liver metastases. This trial is registered with ClinicalTrials.gov (NCT05425940).\n\nFindings: 1325 patients were screened for eligibility; between Sept 7, 2022, and July 15, 2024, 901 patients were randomly assigned to zanzalintinib-atezolizumab (n=451) or regorafenib (n=450). 528 (59%) patients were male and 373 (41%) were female; 485 (54%) were White, 338 (38%) were Asian, 18 (2%) were Black, 24 (3%) were other races, and 36 (4%) had race not reported. At a median follow-up of 18·0 months (IQR 14·6-21·5), zanzalintinib-atezolizumab showed a significant overall survival benefit versus regorafenib in the ITT population (stratified hazard ratio [HR] 0·80 [95% CI 0·69-0·93]; p=0·0045) with a median overall survival of 10·9 months (95% CI 9·9-12·1) versus 9·4 months (8·5-10·2). At the interim analysis of overall survival in the subset of patients without liver metastases, the stratified HR for zanzalintinib-atezolizumab versus regorafenib was 0·79 (95% CI 0·61-1·03); p=0·087 (median overall survival 15·9 months [95% CI 13·5-17·6] vs 12·7 months [10·9-15·5]). Grade 3 or worse treatment-related adverse events occurred in 268 (60%) of 446 patients receiving zanzalintinib-atezolizumab and 161 (37%) of 434 patients receiving regorafenib. There were five (1%) treatment-related deaths in the zanzalintinib-atezolizumab group and one (<1%) in the regorafenib group.\n\nInterpretation: STELLAR-303 is the first phase 3 trial to show a significant improvement in overall survival with an immunotherapy-based regimen, zanzalintinib-atezolizumab, in patients with relapsed or refractory metastatic colorectal cancer that is not MSI-H or dMMR. This combination represents a chemotherapy-free treatment option with a novel mechanism of action for heavily pretreated patients in need of improved therapies.\n\nFunding: Exelixis.\n\nIndexed on Europe PMC as PubMed record 41130252 (DOI 10.1016/s0140-6736(25)02025-2). Its abstract cites the registry id NCT05425940, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"Lancet 2025","url":"https://doi.org/10.1016/s0140-6736(25)02025-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/41130252/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/41130252"},{"label":"ClinicalTrials.gov NCT05425940","url":"https://clinicaltrials.gov/study/NCT05425940"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct05425940"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2025,"doi":"10.1016/s0140-6736(25)02025-2","pmid":"41130252","authors":"Hecht JR, Park YS, Tabernero J, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT05425940 with the most citations, so it is the natural first reading for anyone following the STELLAR-303 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-zebra-pembrolizumab-small-bowel-adenocarcinoma-ccr-2021","kind":"paper","name":"ZEBRA: pembrolizumab in advanced small bowel adenocarcinoma","aka":[],"tldr":"Immunotherapy on its own helped only a few patients with advanced small bowel adenocarcinoma, mainly those whose tumours had mismatch repair deficiency, so the drug is reserved for that group.","summary":"Multicentre single-arm phase 2 study of 40 patients with previously treated advanced small bowel adenocarcinoma given pembrolizumab every three weeks.\n\nThe objective response rate was 8 percent and the study did not meet its primary endpoint; responses clustered in patients with mismatch repair deficient or microsatellite instability high tumours, while microsatellite stable disease rarely responded.","asOf":"2026-09-18","links":[{"label":"Clin Cancer Res 2021","url":"https://doi.org/10.1158/1078-0432.CCR-21-0159"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33883178/"}],"tags":[],"related":[],"cancers":["advanced-small-bowel-adenocarcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2021,"doi":"10.1158/1078-0432.CCR-21-0159","pmid":"33883178","authors":"Pedersen KS, Foster NR, Overman MJ, et al.","paperType":"observational","findings":["Objective response 8 percent overall; the primary endpoint was not met.","Responses were seen in mismatch repair deficient tumours and rarely in microsatellite stable disease."],"whatItMeans":"Every small bowel adenocarcinoma should be tested for mismatch repair deficiency, because immunotherapy is worthwhile for those patients and of little use to the rest.","caveats":["Small single-arm study.","Few dMMR patients were included, so the estimate of benefit in that group is imprecise."],"changedPractice":false,"participants":40},{"id":"paper-zeta-vandetanib-mtc-wells-jco-2012","kind":"paper","name":"ZETA: vandetanib in locally advanced or metastatic medullary thyroid cancer","aka":[],"tldr":"Vandetanib was the first drug shown to delay progression in medullary thyroid cancer, roughly doubling progression-free survival compared with placebo, and became the first approved therapy for the disease.","summary":"Phase 3 placebo-controlled trial of 331 patients with unresectable locally advanced or metastatic medullary thyroid cancer randomised 2:1 to vandetanib 300 mg daily or placebo.\n\nMedian progression-free survival was predicted at 30.5 versus 19.3 months (hazard ratio 0.46) with response 45 versus 13 percent (placebo responses reflecting slow disease and crossover); QT prolongation, diarrhoea and rash were the main toxicities.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2012","url":"https://doi.org/10.1200/JCO.2011.35.5040"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22025146/"}],"tags":[],"related":[],"cancers":["medullary-thyroid-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["vandetanib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["zeta"],"people":["samuel-wells"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2012,"doi":"10.1200/JCO.2011.35.5040","pmid":"22025146","authors":"Wells SA, Robinson BG, Gagel RF, et al.","paperType":"rct","findings":["Progression-free survival hazard ratio 0.46; predicted median 30.5 vs 19.3 months.","Objective response 45 percent vs 13 percent."],"whatItMeans":"Vandetanib is an approved option for progressive medullary thyroid cancer, used less since selpercatinib for RET-mutant disease.","caveats":["Enrolled patients with indolent disease, some not progressing; QT monitoring required."],"changedPractice":true,"participants":331},{"id":"paper-dhillon-mol-diagn-ther","kind":"paper","name":"Zevorcabtagene Autoleucel: First Approval","aka":[],"tldr":"Paper cited by one treatment page, indexed on Europe PMC as PubMed record 38888762 and published in Molecular diagnosis & therapy; the citing page links this DOI, which is how the record was matched.","summary":"Zevorcabtagene autoleucel () is a fully humanised B cell maturation antigen (BCMA)-targeting specific chimeric antigen receptor (CAR) T-cell therapy being developed by CARsgen for the treatment of multiple myeloma. Zevorcabtagene autoleucel is an autologous CAR T cell comprising a fully human BCMA-specific scFv (25C2), a CD8α hinge region and transmembrane domain, a 4-1BB costimulatory domain and a CD3-ζ T cell activation domain. Zevorcabtagene autoleucel recognizes and induces selective toxicity against BCMA-expressing tumour cells leading to their elimination. In February 2024, zevorcabtagene autoleucel received its first approval in China for the treatment of adults with relapsed or refractory multiple myeloma who have progressed after ≥ 3 prior lines of therapy (including ≥ 1 proteasome inhibitor and an immunomodulatory agent). Clinical studies of zevorcabtagene autoleucel are underway in Canada and the US. This article summarizes the milestones in the development of zevorcabtagene autoleucel leading to this first approval for relapsed or refractory multiple myeloma.\n\nIndexed on Europe PMC as PubMed record 38888762 (DOI 10.1007/s40291-024-00723-z). Matched by DOI alone: one treatment page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Mol Diagn Ther 2024","url":"https://doi.org/10.1007/s40291-024-00723-z"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38888762/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/38888762"}],"tags":["europepmc-ingest"],"related":["zevorcabtagene-autoleucel"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Molecular diagnosis & therapy","year":2024,"doi":"10.1007/s40291-024-00723-z","pmid":"38888762","authors":"Dhillon S","paperType":"review","findings":[],"whatItMeans":"One treatment page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},{"id":"paper-nct04036682-j-clin-oncol-2025","kind":"paper","name":"Zipalertinib in Patients With Epidermal Growth Factor Receptor Exon 20 Insertion-Positive Non-Small Cell Lung Cancer Previously Treated With Platinum-Based Chemotherapy With or Without Amivantamab","aka":[],"tldr":"Published report from the REZILIENT1 trial registered as NCT04036682, in Journal of Clinical Oncology (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Purpose: To evaluate the safety and efficacy of zipalertinib, an irreversible epidermal growth factor receptor (EGFR) inhibitor, in pretreated patients with non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion (ex20ins) mutations.\n\nMethods: REZILIENT1 (ClinicalTrials.gov identifier: NCT04036682) is a phase I/II open-label trial enrolling patients with locally advanced or metastatic EGFR ex20ins-mutant NSCLC previously treated with platinum-based chemotherapy with/without ex20ins-targeted therapies. Asymptomatic, treated and untreated stable CNS metastases are permitted. We report data from patients treated with zipalertinib 100 mg twice daily. The primary end points are objective response rate (ORR) and duration of response (DOR) by independent central review.\n\nResults: At data cutoff (December 10, 2024), 244 patients had received treatment with zipalertinib 100 mg twice daily. The primary efficacy population (8 months' follow-up) comprised patients who had received prior platinum-based chemotherapy without ex20ins-targeted therapy (125 patients), with amivantamab only (30 patients), or with amivantamab and other ex20ins-targeted therapy (21 patients). The confirmed ORR was 35.2% (95% CI, 28.2 to 42.8); median DOR was 8.8 months (95% CI, 8.3 to 12.7). Among patients who received prior platinum-based chemotherapy without ex20ins-targeted therapy, amivantamab only, or amivantamab and other ex20ins-targeted therapy, the confirmed ORR was 40%, 30%, and 14.3%, and median DOR was 8.8, 14.7, and 4.2 months, respectively. Among 68 patients with CNS metastases, the ORR was 30.9%. The most common grade ≥3 treatment-related adverse events were anemia (7%), pneumonitis and rash (2.5% each), and diarrhea, ALT increased, and platelet count decreased (2% each).\n\nConclusion: Zipalertinib demonstrated clinically meaningful efficacy with a manageable safety profile in patients with EGFR ex20ins-mutant NSCLC who received prior platinum-based chemotherapy with or without amivantamab.\n\nIndexed on Europe PMC as PubMed record 40450572 (DOI 10.1200/jco-25-00763). Its abstract cites the registry id NCT04036682, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-24","links":[{"label":"J Clin Oncol 2025","url":"https://doi.org/10.1200/jco-25-00763"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40450572/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40450572"},{"label":"ClinicalTrials.gov NCT04036682","url":"https://clinicaltrials.gov/study/NCT04036682"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04036682"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2025,"doi":"10.1200/jco-25-00763","pmid":"40450572","authors":"Piotrowska Z, Passaro A, Nguyen D, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT04036682 with the most citations, so it is the natural first reading for anyone following the REZILIENT1 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},{"id":"paper-zuma-1-axi-cel-nejm-2017","kind":"paper","name":"ZUMA-1: axicabtagene ciloleucel for refractory large B-cell lymphoma, the first CAR-T approved for lymphoma","aka":[],"tldr":"In lymphoma refractory to chemotherapy, where expected survival was around six months, a single CAR-T infusion produced responses in 82% of patients and long-term remission in about 40%.","summary":"ZUMA-1 was a multicentre single-arm phase 2 trial of axicabtagene ciloleucel (axi-cel), a CD19 CAR-T with a CD28 costimulatory domain, in 111 enrolled and 101 treated patients with refractory diffuse large B-cell, primary mediastinal or transformed follicular lymphoma. Manufacturing succeeded in 99% and the median time from apheresis to delivery was 17 days. The objective response rate was 82% with complete response in 54%; at a median follow-up of 15.4 months 42% remained in response (40% in complete response), and 18-month overall survival was 52%. Grade 3 or higher cytokine release syndrome occurred in 13% and neurological events in 28%. Five-year follow-up showed overall survival of about 43% with a plateau, consistent with cure in a substantial minority. It supported FDA approval in October 2017.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa1707447"},{"label":"ClinicalTrials.gov NCT02348216","url":"https://clinicaltrials.gov/study/NCT02348216"}],"tags":[],"related":["paper-zuma-7-axi-cel-second-line-nejm-2022","paper-juliet-tisagenlecleucel-dlbcl-nejm-2019","lymphoma-roadmap","paper-transcend-nhl-001-liso-cel-lancet-2020"],"cancers":["dlbcl","follicular-lymphoma"],"sections":[],"technologies":["car-t"],"targets":["cd19"],"drugs":["axicabtagene-ciloleucel"],"companies":["gilead"],"institutions":["md-anderson","moffitt"],"pathways":[],"terms":["crs","icans","orr"],"trials":["zuma-7"],"people":["frederick-locke"],"bottlenecks":["b-manufacturing-cell-therapy","b-toxicity-qol"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2017,"doi":"10.1056/NEJMoa1707447","authors":"Neelapu SS, Locke FL, Bartlett NL, et al.","paperType":"translational","findings":["111 enrolled, 101 treated patients with chemotherapy-refractory large B-cell lymphoma; 22 centres.","Manufacturing success 99%; median 17 days from apheresis to delivery; no bridging chemotherapy allowed.","Objective response 82%; complete response 54%; 42% still responding at 15.4 months median follow-up.","18-month overall survival 52%; 5-year overall survival about 43% with a plateau.","Grade 3 or higher CRS 13%; grade 3 or higher neurological events 28%; 3 deaths during treatment."],"whatItMeans":"ZUMA-1 showed that CAR-T can cure a meaningful fraction of adults whose aggressive lymphoma no longer responds to chemotherapy, a group with a historical median survival of about six months (SCHOLAR-1). Axi-cel became the first CAR-T approved for lymphoma and later the first to beat standard second-line therapy in ZUMA-7. The comparatively high neurotoxicity of CD28-costimulated products was also first characterised here.","caveats":["Single-arm with a historical comparator (SCHOLAR-1).","No bridging therapy was allowed, selecting patients with slower-growing disease.","Roughly 60% of patients eventually relapsed or died; long-term survivors are a minority.","Toxicity required intensive-care-capable centres; real-world use has since expanded with prophylactic steroids."],"changedPractice":true,"participants":101},{"id":"paper-zuma-2-brexu-cel-mantle-cell-nejm-2020","kind":"paper","name":"ZUMA-2: brexu-cel CAR-T for mantle cell lymphoma that has failed BTK inhibitors","aka":[],"tldr":"In mantle cell lymphoma that had stopped responding to BTK inhibitors, a single CAR-T infusion produced responses in 93% of patients and complete remissions in two-thirds.","summary":"ZUMA-2 was a single-arm phase 2 study of KTE-X19 (brexucabtagene autoleucel), a CD19 CAR-T manufactured with removal of circulating tumour cells, in relapsed or refractory mantle cell lymphoma after up to five prior lines including a BTK inhibitor. Of 74 patients enrolled, 68 received the product. In the primary efficacy analysis of the first 60 treated patients the overall response rate was 93% and complete response 67%; estimated 12-month PFS was 61% and OS 83%. Grade 3 or higher CRS occurred in 15% and neurological events in 31%. It led to FDA approval in 2020, the first CAR-T for mantle cell lymphoma.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa1914347"},{"label":"ClinicalTrials.gov NCT02601313","url":"https://clinicaltrials.gov/study/NCT02601313"}],"tags":[],"related":["paper-zuma-1-axi-cel-nejm-2017"],"cancers":["mantle-cell-lymphoma"],"sections":[],"technologies":["car-t"],"targets":["cd19","btk"],"drugs":["brexucabtagene-autoleucel","ibrutinib","pirtobrutinib"],"companies":["gilead"],"institutions":["md-anderson"],"pathways":[],"terms":["crs","icans","orr"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-resistance"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2020,"doi":"10.1056/NEJMoa1914347","authors":"Wang M, Munoz J, Goy A, et al.","paperType":"translational","findings":["74 enrolled, 68 treated; all had prior BTK inhibitor; 60 in primary efficacy analysis.","Overall response 93%; complete response 67%.","Estimated 12-month PFS 61%; 12-month OS 83%.","Grade 3 or higher CRS 15%; grade 3 or higher neurological events 31%.","Responses seen in high-risk features including TP53 mutation and blastoid morphology."],"whatItMeans":"ZUMA-2 gave patients with BTK-inhibitor-refractory mantle cell lymphoma, who previously had a median survival under a year, a therapy with durable remissions in a substantial fraction. Brexu-cel is now standard after BTK inhibitor failure and CAR-T is being tested earlier in the disease. Neurotoxicity rates are higher than in other lymphoma CAR-T trials.","caveats":["Single-arm; no randomised comparison.","High rates of neurological toxicity, and a treatment-related death rate that requires experienced centres.","Later real-world data showed lower complete response rates than the trial.","Long-term durability is limited by late relapses in roughly half of responders."],"changedPractice":true,"participants":68},{"id":"paper-zuma-7-axi-cel-second-line-nejm-2022","kind":"paper","name":"ZUMA-7: axi-cel CAR-T instead of salvage chemotherapy and transplant for large B-cell lymphoma that relapses early","aka":[],"tldr":"For lymphoma that came back within a year, going straight to CAR-T beat the decades-old chemotherapy-then-transplant approach, and later improved survival.","summary":"ZUMA-7 randomised 359 patients with large B-cell lymphoma that was refractory to, or relapsed within 12 months of, first-line chemo-immunotherapy to axicabtagene ciloleucel (axi-cel) or standard second-line salvage chemotherapy followed by high-dose therapy and autologous transplant in responders. The primary endpoint was event-free survival. Median EFS was 8.3 versus 2.0 months (hazard ratio 0.40) and 24-month EFS 41% versus 16%; complete response was 65% versus 32%. Only about a third of standard-arm patients reached transplant, and 56% went on to receive CAR-T off protocol. Despite that crossover, the later analysis (Westin et al., NEJM 2023) showed improved overall survival with axi-cel (4-year OS 54.6% versus 46.0%; hazard ratio 0.73).","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa2116133"},{"label":"Overall survival analysis (Westin 2023)","url":"https://doi.org/10.1056/NEJMoa2301665"},{"label":"ClinicalTrials.gov NCT03391466","url":"https://clinicaltrials.gov/study/NCT03391466"}],"tags":[],"related":["car-t-before-transplant-lbcl","paper-transform-liso-cel-lancet-2022","lymphoma-roadmap","paper-belinda-tisagenlecleucel-second-line-nejm-2022","lymphoma-ev-manufacturing-time-as-a-trial-endpoint"],"cancers":["dlbcl"],"sections":[],"technologies":["car-t","autologous-stem-cell-transplant"],"targets":["cd19"],"drugs":["axicabtagene-ciloleucel"],"companies":["gilead"],"institutions":["moffitt"],"pathways":[],"terms":["efs","os","crs","icans"],"trials":["zuma-7","transform","belinda"],"people":["frederick-locke"],"bottlenecks":["b-manufacturing-cell-therapy","b-global-access"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/NEJMoa2116133","authors":"Locke FL, Miklos DB, Jacobson CA, et al.","paperType":"rct","findings":["359 patients with primary refractory or early-relapsing (within 12 months) LBCL; axi-cel vs salvage chemotherapy plus autologous transplant.","Median EFS 8.3 vs 2.0 months; hazard ratio 0.40; 24-month EFS 41% vs 16%.","Overall response 83% vs 50%; complete response 65% vs 32%.","Only 36% of standard-arm patients proceeded to transplant; 56% later received cellular therapy off protocol.","Overall survival improved (4-year OS 54.6% vs 46.0%; HR 0.73), the first survival gain in this setting in decades.","Grade 3 or higher CRS 6%; grade 3 or higher neurological events 21%; no bridging chemotherapy allowed (steroids only)."],"whatItMeans":"ZUMA-7 rewrote second-line treatment for aggressive lymphoma: patients whose disease returns within a year of R-CHOP should be offered CAR-T rather than salvage chemotherapy and transplant. It is also one of the few cell-therapy trials to show an overall survival benefit despite crossover. Patients relapsing later than 12 months were not studied and transplant remains standard for them if chemosensitive.","caveats":["Applies only to early relapse or primary refractory disease; late relapse was excluded.","No bridging chemotherapy was permitted, so patients with rapidly progressive disease may not have been enrolled.","The parallel BELINDA trial of tisagenlecleucel in the same setting was negative, showing the result depends on product and logistics.","Costs and centre capacity limit uptake outside high-income countries."],"changedPractice":true,"participants":359},{"id":"paper-cowan-lancet-oncol","kind":"paper","name":"γ-Secretase inhibitor in combination with BCMA chimeric antigen receptor T-cell immunotherapy for individuals with relapsed or refractory multiple myeloma: a phase 1, first-in-human trial","aka":[],"tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 37414012 and published in The Lancet Oncology; the citing page links this DOI, which is how the record was matched.","summary":"Background: γ-Secretase inhibitors (GSIs) increase B cell maturation antigen (BCMA) density on malignant plasma cells and enhance antitumour activity of BCMA chimeric antigen receptor (CAR) T cells in preclinical models. We aimed to evaluate the safety and identify the recommended phase 2 dose of BCMA CAR T cells in combination with crenigacestat (LY3039478) for individuals with relapsed or refractory multiple myeloma.\n\nMethods: We conducted a phase 1, first-in-human trial combining crenigacestat with BCMA CAR T-cells at a single cancer centre in Seattle, WA, USA. We included individuals aged 21 years or older with relapsed or refractory multiple myeloma, previous autologous stem-cell transplant or persistent disease after more than four cycles of induction therapy, and Eastern Cooperative Oncology Group performance status of 0-2, regardless of previous BCMA-targeted therapy. To assess the effect of the GSI on BCMA surface density on bone marrow plasma cells, participants received GSI during a pretreatment run-in, consisting of three doses administered 48 h apart. BCMA CAR T cells were infused at doses of 50 × 10 6 CAR T cells, 150 × 10 6 CAR T cells, 300 × 10 6 CAR T cells, and 450 × 10 6 CAR T cells (total cell dose), in combination with the 25 mg crenigacestat dosed three times a week for up to nine doses. The primary endpoints were the safety and recommended phase 2 dose of BCMA CAR T cells in combination with crenigacestat, an oral GSI. This study is registered with ClinicalTrials.gov, NCT03502577, and has met accrual goals.\n\nFindings: 19 participants were enrolled between June 1, 2018, and March 1, 2021, and one participant did not proceed with BCMA CAR T-cell infusion. 18 participants (eight [44%] men and ten [56%] women) with multiple myeloma received treatment between July 11, 2018, and April 14, 2021, with a median follow up of 36 months (95% CI 26 to not reached). The most common non-haematological adverse events of grade 3 or higher were hypophosphataemia in 14 (78%) participants, fatigue in 11 (61%), hypocalcaemia in nine (50%), and hypertension in seven (39%). Two deaths reported outside of the 28-day adverse event collection window were related to treatment. Participants were treated at doses up to 450 × 10 6 CAR + cells, and the recommended phase 2 dose was not reached.\n\nInterpretations: Combining a GSI with BCMA CAR T cells appears to be well tolerated, and crenigacestat increases target antigen density. Deep responses were observed among heavily pretreated participants with multiple myeloma who had previously received BCMA-targeted therapy and those who were naive to previous BCMA-targeted therapy. Further study of GSIs given with BCMA-targeted therapeutics is warranted in clinical trials.\n\nFunding: Juno Therapeutics-a Bristol Myers Squibb company and the National Institutes of Health.\n\nIndexed on Europe PMC as PubMed record 37414012 (DOI 10.1016/s1470-2045(23)00246-2). Matched by DOI alone: one trial page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2023","url":"https://doi.org/10.1016/s1470-2045(23)00246-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37414012/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37414012"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["lumina"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2023,"doi":"10.1016/s1470-2045(23)00246-2","pmid":"37414012","authors":"Cowan AJ, Pont MJ, Sather BD, et al.","paperType":"observational","findings":[],"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]}]